No Effect of Selenium Supplementation on Serum Glucose Levels in Men with Prostate Cancer

Background

Literature indicates a relationship between selenium supplementation and risk of diabetes. However, because these data are inconclusive, we investigated the effect of selenium supplementation on serum glucose levels in men with prostate cancer enrolled in a clinical trial testing of the effect of selenium on prostate cancer progression.

Methods

Subjects were randomized to receive placebo (n = 46), selenium 200 μg/day (n = 47), and selenium 800 μg/day (n = 47). Serum glucose levels were obtained every 6 months for up to 5 years. Longitudinal analysis was carried out to assess whether rate of change of serum glucose levels was significantly different in the selenium-supplemented groups as compared with placebo. Sensitivity analyses were performed to assess the robustness of findings.

Results

Changes in serum glucose levels during the course of the trial were not statistically significantly different as compared with placebo for the selenium 200 μg/day (P = .56) or selenium 800 μg/day (P = .91) treatment groups.

Conclusion

These results do not support a relationship between selenium supplementation and changes in serum glucose levels. Recommendations about selenium supplementation and risk of diabetes will require more definitive studies.     

Predictive value of brachial–ankle pulse wave velocity for long-term clinical outcomes after percutaneous coronary intervention in a Korean cohort

Objective

The aim of this study was to determine the associations of brachial–ankle pulse wave velocity (baPWV), high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-B type natriuretic peptide (NT-proBNP) with the development of adverse outcomes after percutaneous coronary intervention (PCI).

Methods

The baPWV, hs-cTnT and NT-proBNP were analyzed in 372 patients who underwent PCI. The primary endpoint was cardiac death.

Results

There were 21 events of cardiac death during a mean of 25.8 months of follow-up. When the baPWV cut-off level was set to 1672 cm/s using the receiver operating characteristic curve, the sensitivity was 85.7% and the specificity was 60.1% for differentiating between the group with cardiac death and the group without cardiac death. Kaplan–Meier analysis revealed that the higher baPWV group (≥ 1672 cm/s) had a significantly higher cardiac death rate than the lower baPWV group (< 1672 cm/s) (11.4% vs. 1.4%, log-rank: P < 0.0001). This value was more useful in patients with myocardial injury (hs-cTnT ≥ 0.1 ng/mL) or heart failure (NT-proBNP ≥ 450 pg/mL).

Conclusions

The results of this study show that high baPWV is a predictive marker for cardiac death after PCI.     

Associations between N-terminal pro-B-type natriuretic peptide and cardiac function in adults with corrected tetralogy of Fallot

Background

Amino-terminal B-type natriuretic peptide (NT-proBNP) may detect early cardiac dysfunction in adults with tetralogy of Fallot (ToF) late after corrective surgery. We aimed to determine the value of NT-proBNP in adults with ToF and establish its relationship with echocardiography and exercise capacity.

Methods and results

NT-proBNP measurement, electrocardiography and detailed 2D-echocardiography were performed on the same day in 177 consecutive adults with ToF (mean age 34.6 ± 11.8 years, 58% male, 89% NYHA I, 29.3 ± 8.5 years after surgical correction). Thirty-eight percent of the patients also underwent a cardiopulmonary-exercise test. Median NT-proBNP was 16 [IQR 6.7–33.6] pmol/L, and was elevated in 55%. NT-proBNP correlated with right ventricular (RV) dilatation (r = 0.271, p < 0.001) and RV systolic dysfunction (r = − 0.195, p = 0.022), but more strongly with LV systolic dysfunction (r = − 0.367, p < 0.001), which was present in 69 patients (39%). Moderate or severe pulmonary regurgitation was not associated with higher NT-proBNP. Tricuspid and pulmonary regurgitation peak velocities correlated with NT-proBNP (r = 0.305, p < 0.001 and r = 0.186, p = 0.045, respectively). LV twist was measured with speckle-tracking echocardiography in 71 patients. An abnormal LV twist (20 patients, 28%) was associated with elevated NT-proBNP (p = 0.030). No relationship between NT-proBNP and exercise capacity was found.

Conclusions

NT-proBNP levels are elevated in more than 50% of adults with corrected ToF, while they are in stable clinical condition. Higher NT-proBNP is most strongly associated with elevated pulmonary pressures, and with LV dysfunction rather than RV dysfunction. NT-proBNP has the potential to become routine examination in patients with ToF to monitor ventricular function and may be used for timely detection of clinical deterioration.     

Changes of plasma norepinephrine and serum N-terminal pro-brain natriuretic peptide after exercise training predict survival in patients with heart failure

Background

Short-term changes of neurohormones can give important prognostic information in heart failure (HF) patients. In this study, we evaluate whether changes in plasma Norepinephrine (NE) and serum N-terminal pro-brain natriuretic peptide (NT-proBNP) after exercise training predict cardiac mortality in HF patients.

Methods and results

We enrolled 221 HF patients (mean age 72.5 ± 10.2 year) followed-up for a mean period of 27.64 ± 10.7 months. All pts underwent a 3-month exercise training. Before training, clinical examination, echocardiography, peak VO2 determination, and blood draw for NT-proBNP and NE measurements were performed. Primary end-point was cardiac related mortality. Eighty-six-nine percent of patients were in NYHA class III, mean left ventricular ejection fraction (LVEF) was 32.5 ± 10.4%, and mean peak VO2 was 12.36 ± 1.45 ml/kg/min. At baseline, mean NT-proBNP was 2111.4 ± 1145.6 pg/ml and mean NE was 641.8 ± 215.3 pg/ml. One hundred-one subjects died for cardiac causes. Training was associated with a significant increase of peak VO2 and LVEF, whereas NE, NT-proBNP, and heart rate decreased. Multiple Cox proportional hazards regression analysis was performed using delta% values (post vs pre-training) of LVEF, heart rate, NE, and NT-proBNP along with baseline covariates, revealing delta value of NE as the strongest predictor of cardiac mortality. Noteworthy, training reduced NT-proBNP in both survivor and non-survivor patients, while a lack of reduction of NE was observed in non survivors.

Conclusions

In our HF population, short-term changes of NE after exercise training independently predicted long-term cardiac mortality.     

¿Cuándo remitir al cardiólogo al paciente con síndrome de apneas-hipopneas durante el sueño? Utilidad del NT-proBNP

Introduction and objective

When sleep apnea-hypopnea syndrome (SAHS) and cardiovascular disease occur concurrently, prognosis is affected. Echocardiography can detect structural cardiac abnormalities but using this technique in all patients would place a heavy burden on resources. The objective of this study was to investigate whether the N-terminal fraction of brain natriuretic peptide (NT-proBNP) can be used as a marker for silent heart disease.

Patients and methods

NT-proBNP concentration was measured in the 114 consecutive patients with SAHS who underwent echocardiography before starting treatment. Left and right ventricular systolic and diastolic function, as well as structural abnormalities, were studied. Correlations between NT-proBNP concentration and the abnormalities detected were investigated. A receiver operating characteristics (ROC) curve was plotted for NT-proBNP concentration and cardiac abnormalities.

Results

Data for 98 patients were finally analyzed. NT-proBNP concentration was significantly correlated with ventricular septal thickness (r=0.63), posterior wall thickness (r=0.45), and left ventricular end-diastolic diameter (r=0.51) (P<.0001 for all correlations). The area under the ROC curve was significant (0.870; 95% confidence interval, 0.801–0.939; P<.0001). Assuming that specificity would be more useful for clinical practice, we calculated that NT-proBNP concentrations below 100 and 200 pg/mL could rule out structural abnormalities with a reliability of 90% and 100%, respectively.

Conclusions

NT-proBNP concentration was strongly correlated with echocardiographic abnormalities and so could be a useful tool for identifying patients who should be referred to the cardiologist.     

Does residual aortic regurgitation after transcatheter aortic valve implantation increase mortality in all patients? The importance of baseline natriuretic peptides

Background

Aortic regurgitation (AR) is an important complication of transcatheter aortic valve implantation (TAVI) and even moderate AR is associated with increased mortality after TAVI. The association with decreased survival is unclear. We aimed to analyse the impact of AR after TAVI as a function of baseline NT-proBNP.

Methods

We included 236 consecutive patients implanted in our centre with the SAPIEN and SAPIEN XT valves, via the transfemoral route. AR was evaluated by transthoracic echocardiography. NT-proBNP was measured 24 h before implantation and patients were divided according to the median value.

Results

Median age was 85 years (80–89) and 137 (58.1%) were women. Patients with high NT-proBNP had lower left ventricular ejection fraction: 52% (35–65) vs. 63% (55–70), p < 0.001, larger telediastolic diameters: 56 mm (49–61) vs. 52 mm (46–56), p = 0.01, and more severe aortic stenosis: 0.62 ± 0.15 cm² vs. 0.70 ± 0.2 cm², p < 0.001. Pre-procedural moderate or severe AR (42% vs. 26%, p = 0.013) and mitral regurgitation (56% vs. 36%, p = 0.004) were more common in the high NT-proBNP group. After TAVI, moderate or severe AR occurred in 26% of patients and was associated with increased 2-year mortality only in the low NT-proBNP group, while patients in the high NT-proBNP group were not affected.

Conclusions

Moderate or severe AR after TAVI was not associated with increased 2-year mortality in patients with high baseline NT-proBNP. Our data suggest that the impact of AR after TAVI is absent in patients with significant pre-procedural AR or mitral regurgitation and more severe aortic stenosis.     

Tandospirone reduces wasting and improves cardiac function in experimental cancer cachexia

Background

Cancer cachexia is thought to be the cause of > 20% of cancer related deaths. Symptoms of cancer cachexia patients include depression and anorexia significantly worsening their quality of life. Moreover, in rodent models of cancer cachexia atrophy of the heart has been shown to impair cardiac function. Here, we characterize the effects of the antidepressant and anxiolytic drug tandospirone on wasting, cardiac function and survival in experimental cancer cachexia.

Methods

The well-established Yoshida hepatoma rat model was used and tumor-bearing rats were treated with 1 mg/kg/d (LD), 10 mg/kg/d (HD) tandospirone or placebo. Weight, body composition (NMR), cardiac function (echocardiography), activity and food intake were assessed. Noradrenalin and cortisol were measured in plasma and caspase activity in skeletal muscle.

Results

Ten mg/kg/d tandospirone decreased the loss of body weight (p = 0.0003) compared to placebo animals, mainly due to preservation of muscle mass (p < 0.001), while 1 mg/kg/d tandospirone was not effective. Locomotor activity (p = 0.0007) and food intake (p = 0.0001) were increased by HD tandospirone. The weight (p = 0.0277) and function of heart (left ventricular mass, fractional shortening, stroke volume, ejection fraction, all p < 0.05) were significantly improved. In the HD tandospirone group, plasma levels of noradrenalin and cortisol were significantly reduced by 49% and 52%, respectively, which may have contributed to the lower caspase activity in the gastrocnemius muscle. Most importantly, HD tandospirone significantly improved survival compared to placebo rats (HR: 0.34; 95% CI: 0.13–0.86; p = 0.0495).

Conclusion

Tandospirone showed significant beneficial effects in the Yoshida hepatoma cancer cachexia model and should be further examined as a prospective drug for this syndrome.     

Beneficio clínico de la terapia de resincronización cardiaca con desfibrilador para pacientes con fracción de eyección > 35% por resonancia magnética

Introduction and objectives

Cardiac resynchronization therapy with a defibrillator prolongs survival and improves quality of life in advanced heart failure. Traditionally, patients with ejection fraction > 35% estimated by echocardiography have been excluded. We assessed the prognostic impact of this therapy in a group of patients with severely depressed systolic function as assessed by echocardiography but with an ejection fraction > 35% as assessed by cardiac magnetic resonance.

Methods

We analyzed consecutive patients admitted for decompensated heart failure between 2004 and 2011. The patients were in functional class II-IV, with a QRS ≥ 120 ms, ejection fraction ≤ 35% estimated by echocardiography, and a cardiac magnetic resonance study. We included all patients (n = 103) who underwent device implantation for primary prevention. Ventricular arrhythmia, all-cause mortality and readmission for heart failure were considered major cardiac events. The patients were divided into 2 groups according to systolic function assessed by magnetic resonance.

Results

The 2 groups showed similar improvements in functional class and ejection fraction at 6 months. We found a nonsignificant trend toward a higher risk of all-cause mortality in patients with systolic function ≤ 35% at long-term follow-up. The presence of a pattern of necrosis identified patients with a worse prognosis for ventricular arrhythmias and mortality in both groups.

Conclusions

We conclude that cardiac resynchronization therapy with a defibrillator leads to a similar clinical benefit in patients with an ejection fraction ≤ 35% or > 35% estimated by cardiac magnetic resonance. Analysis of the pattern of late gadolinium enhancement provides additional information on arrhythmic risk and long-term prognosis.Full English text available from:www.revespcardiol.org/en     

Echocardiographic screening for rheumatic heart disease: Age matters

Background

Echocardiography is emerging as a screening tool for rheumatic heart disease (RHD) in endemic regions. The vast majority of surveys have been limited to children. We ought to appreciate the interest of including adolescents in their late teens in such school screening programmes.

Methods

School-based echocardiography cross-sectional survey conducted in Dakar, Senegal (March 2010). A total of 2004 school attendees were randomly selected and enrolled in the study, among which 1116 were aged 5–15 years old (group 1), and 888 were 16–18 years old (group 2). Case detection rates and phenotype of RHD were compared according to age groups.

Results

A total of 22 youngsters were suspected by on-site echocardiography, 12 in group 1 and 10 in group 2. Among the 12 RHD cases suspected on-site in group 1, 6 (50%) were eventually considered as confirmed RHD, compared to 9 out of 10 (90%) in group 2, giving prevalence rates of 5.4 (CI 95% 2.0–11.7) and 10.1 (CI 95% 4.6–19.2) per 1000 in group 1 and group 2, respectively. The proportion of marked/advanced lesions was 33% in group 1, and 89% in group 2 (p = 0.08). Mean concordance rates between the 3 reviewers were 40% for group 1, compared to 93% in group 2 (p = 0.05).

Conclusions

Extension of screening to adolescents in their late teens should be considered with interest in the light of the higher prevalence of the disease and relative clarity of subclinical cardiac lesions that could be more easily detected in the field.     

Prevalence of acute cardiac disorders in patients with suspected ST-segment elevation myocardial infarction and non-significant coronary artery disease

Background and purpose

We aimed to study the prevalence of acute cardiac disorders in patients with suspected ST-segment elevation myocardial infarction (STEMI) and non-significant coronary artery disease (CAD).

Methods

From January to October 2012 we consecutively included patients admitted with suspected STEMI and non-significant CAD (coronary artery stenosis diameter < 50%). Patients were diagnosed with acute cardiac disorder in the presence of elevated cardiac biomarkers (troponin T > 50 ng/l or creatine kinase MB > 4 μg/l) or dynamic ECG changes (ST-segment changes or T-wave inversion).

Results

Of the 871 patients admitted with suspected STEMI, 11% (n = 95) had non-significant CAD. Of these, 67% (n = 64) had elevated cardiac biomarkers or dynamic ECG changes and were accordingly diagnosed with acute cardiac disorders. In the remaining 33% (n = 31) of patients, cardiac biomarkers were normal and ECG changes remained stationary.

Conclusions

Acute cardiac disorders were diagnosed in two thirds of patients with suspected STEMI and non-significant CAD.     

A multi-biomarker risk score improves prediction of long-term mortality in patients with advanced heart failure

Background

Accurate risk prediction is important for an adequate management of heart failure (HF) patients. We assessed the incremental prognostic ability of a multi-biomarker approach in advanced HF.

Methods

In 349 patients with advanced HF (median 75 years, 66% male) we investigated the incremental prognostic value of 12 novel biomarkers involved in different pathophysiological pathways including inflammation, immunological activation, oxidative stress, cell growth, remodeling, angiogenesis and apoptosis.

Results

During a median follow-up of 4.9 years 55.9% of patients died. Using multivariable Cox regression and bootstrap variable-selection age, chronic obstructive pulmonary disease, N-terminal pro-B-type natriuretic peptide (NT-proBNP) and the following 5 novel biomarkers were retained in the best mortality prediction model: the chemokine fractalkine, the angiogenic and mitogenic hepatocyte growth factor (HGF), the growth differentiation factor 15 (GDF-15) influencing cardiac remodeling and apoptosis, and the 2 pro-apoptotic molecules soluble apoptosis-stimulating fragment (sFAS) and soluble tumor necrosis factor-related apoptosis-inducing ligand (sTRAIL). This multi-biomarker score had strong discriminatory power for 5-year mortality (area under the Receiver Operating Characteristic curve [AUC] = 0.81) and improved risk prediction beyond the prognostic power of a comprehensive conventional risk score including known clinical predictors and NT-proBNP (AUC = 0.77). Net reclassification confirmed a significant improvement of individual risk prediction (p = 0.003).

Conclusions

Risk prediction by a multi-biomarker score is superior to a conventional risk score including clinical parameters and NT-proBNP. Additional predictive information from different biological pathways reflects the multisystemic character of HF.     

NT-proB natriuretic peptide,risk factors and asymptomatic left ventricular dysfunction: Results of the SCReening Evaluation of the Evolution of New Heart Failure Study (SCREEN-HF)

Background

We assessed left ventricular dysfunction in a population at high risk for heart failure (HF), and explored associations between ventricular function, HF risk factors and NT-proB natriuretic peptide (NT-proBNP).

Methods and results

3550 subjects at high risk for incident HF (≥ 60 years plus ≥ 1 HF risk factor), but without pre-existing HF or left ventricular dysfunction, were recruited. Anthropomorphic data, medical history and blood for NT-proBNP were collected. Participants at highest risk (n = 664) (NT-proBNP highest quintile; > 30.0 pmol/L) and a sample (n = 51) from the lowest NT-proBNP quintile underwent echocardiography.Participants in the highest NT-proBNP quintile, compared to the lowest, were older (74 years vs. 67 years; p < 0.001) and more likely to have coronary artery disease, stroke or renal impairment. In the top NT-proBNP quintile (n = 664), left ventricular systolic impairment was observed in 6.6% (95% CI: 4 to 8%) of participants and was associated with male gender, coronary artery disease, hypertension and NT-proBNP. At least moderate diastolic dysfunction was observed in 24% (95% CI 20 to 27%) of participants and was associated with diabetes and NT-proBNP. In this high risk population, NT-proBNP was associated with left ventricular systolic impairment (p < 0.001) and moderate to severe diastolic dysfunction (p < 0.001) after adjustment for age, gender, coronary artery disease, diabetes, hypertension and obesity.

Conclusion

A high burden of ventricular dysfunction was observed in this high risk group. Combining NT-proBNP and HF risk factors may identify those with ventricular dysfunction. This would allow resources to be focused on those at greatest risk of progression to overt HF.     

Validation de la reproductibilité de la mesure de la surface de l’orifice régurgitant par planimétrie dans l’insuffisance aortique : une étude préliminaire d’échocardiographie trans-œsophagienne tridimensionnelle

Background

Aortic regurgitation is mainly evaluated by trans-thoracic echocardiography using multi-parametric qualitative and semi quantitative tools. All those parameters can fail to meet expectations, resulting in an imperfect diagnostic reliability and assessment of aortic regurgitation severity can be challenging.

Objectives

We sought to evaluate feasibility and intra- and inter-observer reproducibility of aortic regurgitant orifice area measured by planimetry with tridimensional trans-esophageal echocardiography on patients with at least grade 2/4 aortic regurgitation.

Patients and methods

Consecutive patients with at least grade 2/4 aortic regurgitation measured by trans-thoracic echocardiography and referred for trans-esophageal echocardiography for any reason were included. Planimetric reconstructions of regurgitant orifice area were studied and reproducibility indexes between senior and junior observers were calculated.

Results

Twenty-three patients were included in this study. Intra- and inter-observer reproducibility were excellent with an ICC of 0.95 [0.88–0.98], P < 0.0001 and 0.91 [0.79–0.96], P < 0.0001, respectively. Mean length of the measurement was 6.6 ± 0.9 min [CI95% 6.23–7.01].

Conclusion

Planimetric measurement of the aortic regurgitant orifice using tridimensional trans-esophageal echocardiography seems to be feasible and has great intra- and inter-observer reproducibility. Reconstruction durations were compatible with a daily use. There is a need now to investigate the reliability of this measurement as compared with the reference technique.     

Synergistic impact of endurance training and intermittent hypobaric hypoxia on cardiac function and mitochondrial energetic and signaling

Background

Intermittent hypobaric-hypoxia (IHH) and endurance-training (ET) are cardioprotective strategies against stress-stimuli. Mitochondrial modulation appears to be an important step of the process. This study aimed to analyze whether a combination of these approaches provides additive or synergistic effects improving heart-mitochondrial and cardiac-function.

Methods

Two-sets of rats were divided into normoxic-sedentary (NS), normoxic-exercised (NE, 1 h/day/5 weeks treadmill-running), hypoxic-sedentary (HS, 6000 m, 5 h/day/5 weeks) and hypoxic-exercised (HE) to study overall cardiac and mitochondrial function. In vitro cardiac mitochondrial oxygen consumption and transmembrane potential were evaluated. OXPHOS subunits and ANT protein content were semi-quantified by Western blotting. HIF-1α, VEGF, VEGF-R1 VEGF-R2, BNP, SERCA2a and PLB expressions were measured by qRT-PCR and cardiac function was characterized by echocardiography and hemodynamic parameters.

Results

Respiratory control ratio (RCR) increased in NE, HS and HE vs. NS. Susceptibility to anoxia/reoxygenation-induced dysfunction decreased in NE, HS and HE vs. NS. HS decreased mitochondrial complex-I and -II subunits; however HE completely reverted the decreased content in complex-II subunits. ANT increased in HE. HE presented normalized ventricular–arterial coupling (Ea) and BNP myocardial levels and significantly improved myocardial performance as evaluated by increased cardiac output and normalization of the Tei index vs. HS.

Conclusion

Data demonstrates that IHH and ET confer cardiac mitochondria with a more resistant phenotype although without visible addictive effects at least under basal conditions. It is suggested that the combination of both strategies, although not additive, results into improved cardiac function.     

Cardiac cachexia is associated with right ventricular failure and liver dysfunction

Background

The mechanisms involved in cardiac cachexia remain poorly understood. We examined the association of right ventricular (RV) and hepatic dysfunction with cardiac cachexia.

Methods

We prospectively enrolled 118 patients with left ventricular ejection fraction (LVEF) ≤ 40%, which were subgrouped as follows: New York Heart Association (NYHA) class II (n = 59), NYHA class III without cachexia (n = 41) and NYHA class III with cachexia (n = 18). All patients underwent blood collection, echocardiography and exercise testing.

Results

Reduced systolic RV function (tricuspid annular plane systolic excursion [TAPSE] ≤ 15 mm), was present in 80% of cachectic patients. When comparing NYHA class II patients vs. non-cachectic and cachectic NYHA class III patients we found a stepwise decrease in systolic RV function (TAPSE 19 [16–23] vs. 16 [13–19] vs. 14 [9–15] mm, respectively; p < 0.001) and an increase in right atrial pressure (RAP; > 10 mm Hg: 6.8 vs. 27.5 vs. 75.0%, respectively; p < 0.001), indicating a higher degree of congestive right HF in cardiac cachexia. Systolic and diastolic function of the left ventricle did not differ between non-cachectic and cachectic patients in NYHA class III. Serum alkaline phosphatase and direct bilirubin correlated with TAPSE and RAP, and were highest in cachectic patients (all p ≤ 0.002), suggesting cholestatic dysfunction due to liver congestion. In multivariable regression analysis, RV dysfunction, cholestatic liver parameters and albumin were independently associated with the presence of cardiac cachexia.

Conclusion

Patients with cardiac cachexia display a more pronounced degree of right HF, cholestatic liver dysfunction and hypoalbuminemia compared to non-cachectic patients of similar LVEF and NYHA class.     

IRON-HF study: A randomized trial to assess the effects of iron in heart failure patients with anemia

Background

Anemia in heart failure patients and has been associated with increased morbi–mortality. Previous studies have treated anemia in heart failure patients with either erythropoietin alone or combination of erythropoietin and intravenous (IV) iron. However, the effect of IV or oral (PO) iron supplementation alone in heart failure patients with anemia was virtually unknown.

Aim

To compare, in a double-blind design, the effects of IV iron versus PO iron in anemic heart failure patients.

Methods

IRON-HF study was a multicenter, investigator initiated, randomized, double-blind, placebo controlled trial that enrolled anemic heart failure patients with preserved renal function, low transferrin saturation (TSat) and low-to-moderately elevated ferritin levels. Interventions were Iron Sucrose IV 200 mg, once a week, for 5 weeks, ferrous sulfate 200 mg PO TID, for 8 weeks, or placebo. Primary endpoint was variation of peak oxygen consumption (peak VO₂) assessed by ergospirometry over 3 month follow-up.

Results

Eighteen patients had full follow-up data. There was an increment of 3.5 ml/kg/min in peak VO₂ in the IV iron group. There was no increment in peak VO₂ in the PO iron group. Patients' ferritin and TSat increased significantly in both treated groups. Hemoglobin increased similarly in all groups.

Conclusion

IV iron seems to be superior in improving functional capacity of heart failure patients. However, correction of anemia seems to be at least similar between PO iron and IV iron supplementation.     

The efficacy of transdermal fentanyl for pain relief after endoscopic submucosal dissection: A prospective,randomised controlled trial

Objective

Epigastric pain management following endoscopic submucosal dissection is an important consideration. This study aimed to investigate the utility and safety of fentanyl patches for pain relief after the procedure.

Methods

Patients who were scheduled to undergo endoscopic submucosal dissection were prospectively randomised to either a transdermal fentanyl patch group or a placebo control group. An additional pethidine was intravenously administered when pain developed and a numerical rating scale was used to evaluate both pre- and post-procedural pain.

Results

One hundred and ten patients were randomly assigned to receive either a 12 mcg/h fentanyl patch or a control patch on the night before the procedure. The fentanyl patch group had significantly lower pain scores immediately following the procedure (mean, 5.17 vs. 4.26, p = 0.030). Maximal pain scores during the first 24 h (5.43 vs. 4.46, p = 0.038) and pain scores on the day after the procedure (2.98 vs. 1.20, p < 0.001) were also lower in the fentanyl patch group. In addition, the fentanyl patch group required a significantly lower dose of pethidine for pain management (24.54 vs. 11.25, p = 0.004).

Conclusions

The application of a transdermal fentanyl patch is an effective, convenient, and safe method to control epigastric pain after endoscopic submucosal dissection.     

Dilated cardiomyopathy in patients with mutations in anoctamin 5

Background

Homozygous mutations in ANO5, a gene encoding anoctamin 5, a putative calcium-activated chloride channel, have recently been reported in patients with adult-onset myopathies or isolated high-CK levels. Cardiomyopathy has not previously been reported in these populations despite a proven expression of anoctamin 5 in the cardiac muscle.

Methods

Patients presenting for the management of high-CK levels or overt myopathy with proven ANO5 mutations were prospectively investigated between June 2010 and March 2012 in Pitié Salpêtrière Hospital, according to a standardised protocol. Neurological and cardiological clinical examinations, CK assessment, electrocardiogram (ECG), and echocardiography were performed, as well as cardiac MRI and coronary CT angiography in patients with left ventricular (LV) dysfunction.

Results

Our study included 19 consecutive patients (male = 15, age = 46.2 ± 12.7 years) from 16 families. Five had asymptomatic high-CK levels and 14 had overt myopathy. One patient had a personal history of stable coronary artery disease with normal ventricular function. ECG showed ventricular premature beats in one patient. Echocardiography displayed LV dilatation in two patients, LV dysfunction in one, and both abnormalities in two who fulfilled criteria for dilated cardiomyopathy which was confirmed by cardiac MRI and normal CT angiography.

Conclusions

Dilated cardiomyopathy is a potential complication in patients with myopathies due to mutations in the ANO5 gene whose screening requires specific procedures.     

N-terminal Pro brain natriuretic peptide is a reliable biomarker of reduced myocardial contractility in patients with lamin A/C gene mutations

Background

Recently, concerns have been raised about a possible lack of sensitivity of biomarkers to detect left ventricular (LV) dysfunction in patients with myopathies. We examined the ability of the N-terminal brain natriuretic peptide (NT-proBNP) to detect LV or right ventricular (RV) dysfunction in patients with lamin A/C (LMNA) gene mutations.

Methods

We prospectively measured plasma NT-proBNP in consecutive patients with documented LMNA mutations and age-sex matched controls. All patients underwent standard echocardiography implemented by pulsed tissue-Doppler echocardiography (TDE).

Results

Twenty-three patients were included (10 males, mean age 39.2 ± 18.9 years);10 had previous atrial arrhythmias, 8 had been implanted with cardioverter defibrillator for primary prevention of sudden death, 5 patients were of NYHA class II and 18 of NHYA class I. Sinus rhythm was recorded in all. NT-proBNP was increased in LMNA patients versus controls (123 ± 229 versus 26 ± 78 pg/ml, p = 0.0004); 7 patients had depressed LV and/or RV contractility. Patients with reduced LV or RV contractility had increased mean NT-proBNP (341 ± 1032 pg/ml versus 80 ± 79 pg/ml in patients with normal myocardial contractility, p = 0.004). Receiver-operating-characteristics analysis shows that NT-proBNP reliably detected depressed contractility (area under the curve 0.889 [0.697-1.000]). Sensitivity and specificity were 88% and 83% respectively, applying manufacturer's recommended cut-off concentration of 125 pg/ml.

Conclusion

NT-proBNP reliably detected the presence of reduced LV/RV contractility in LMNA patients.     

The xanthine oxidase inhibitor oxypurinol reduces cancer cachexia-induced cardiomyopathy

Background

Cachexia is a common complication of cancer and may be responsible for 22% of all cancer-related deaths. The exact cause of death in cancer cachexia patients is unknown. Recently, atrophy of the heart has been described in cancer cachexia animal models, which resulted in impaired cardiac function and is likely to contribute to mortality. In cancer patients hyperuricaemia independent of tumour lysis syndrome is often associated with a worse prognosis. Xanthine oxidase (XO) metabolizes purines to uric acid and its inhibition has been shown to improve clinical outcome in patients with chronic heart failure.

Methods

The rat Yoshida AH-130 hepatoma cancer cachexia model was used in this study. Rats were treated with 4 or 40 mg/kg/d oxypurinol or placebo starting one day after tumour-inoculation for maximal 15 days. Cardiac function was analyzed by echocardiography on day 11.

Results

Here we show that inhibition of XO by oxypurinol significantly reduces wasting of the heart and preserves cardiac function. LVEF was higher in tumour-bearing rats treated with 4 mg/kg/d (61 ± 4%) or 40 mg/kg/d (64 ± 5%) oxypurinol vs placebo (51 ± 3%, both p < 0.05). Fractional shortening was improved by 4 mg/kg/d (43 ± 3%) oxypurinol vs placebo (30 ± 2, p < 0.05), while 40 mg/kg/d oxypurinol (41 ± 5%) did not reach statistical significance. Cardiac output was increased in the 4 mg/kg/d dose only (71 ± 11 mL/min vs placebo 38 ± 4 mL/min, p < 0.01).

Conclusion

Inhibition of XO with oxypurinol has beneficial effects on cardiac mass and function in a rat model of severe cancer cachexia, suggesting that XO might be a viable drug target in cancer cachexia.