A prospective study evaluating efficacy of polymer free Pronova XR stent in treatment of denovo coronary artery stenosis

Background

Drug eluting stents have remarkably improved results of percutaneous coronary angioplasty. Most of the currently available drug eluting stents uses a durable polymer as drug carrier which has been implicated in local inflammatory response and continued incidence of late and very late stent thrombosis. The Pronova XR stent is one from those new generation polymer free sirolimus eluting stents in which pharmaceutical excipient is used for the timed release of sirolimus from the XR stent platform instead of a polymeric coating.

Methodology

We consecutively recruited 121 patients undergoing elective or urgent PCI at our center. All the patients were followed up clinically and mandatory follow up angiogram at 6 months was done for one third of the total patients. An independent core lab analyzed paired angiograms.

Results

The primary efficacy endpoint was death, MI, TVR at 6 months which occurred in 6.66% patients. The QCA analysis showed reference vessel diameter of 2.5 + 0.44 mm at baseline and the minimal luminal diameter was 0.88 + 0.43 mm giving baseline diameter stenosis of 65.26 + 15.89%. The immediate post procedure in-segment diameter stenosis assessed was 23.68 + 8.96% which increased to 36.02 + 24.48% at follow up with a late lumen loss of 0.25 + 0.76 mm at mean of 191 days.

Conclusion

Coronary angioplasty with polymer free Pronova XR stents results in acceptable late lumen loss and very low target lesion revascularisation at short and intermediate term in unselected patients.     

One-year clinical outcomes of BioMatrix™-Biolimus A9™ eluting stent: The e-BioMatrix multicenter post marketing surveillance registry in India

Objective

The e-BioMatrix is a post marketing multicenter registry with an objective to evaluate the 2 year clinical safety and efficacy outcomes in patients treated with BioMatrix™ - Biolimus A9™ (BA9™) drug eluting stents (DES).

Background

Drug-eluting stents still have late-stage disadvantages that might be attributable to the permanent polymer. BioMatrix a new generation DES containing anti-proliferative drug Biolimus A9™ incorporating a biodegradable abluminal coating that leaves a polymer-free stent after drug release enhancing strut coverage while preventing neointimal hyperplasia.

Methods

This interim analysis consists of a total of 1189 patients with 1418 lesions treated with BioMatrix stent who entered this multicenter registry in India. We analyzed the incidence of major adverse cardiac events (MACE) and stent thrombosis (ST) at 1, 6, and 12 months with an extended follow-up of 2 years. Recommended antiplatelet regimen included clopidogrel and aspirin for 12 months.

Results

The mean age was 57.6 ± 10.9 years, 81.8% were males, comorbidity index was 1.20 ± 1.33, 68% presented with acute coronary syndrome, 49% had hypertension and 40.8% had diabetes mellitus. One-year clinical follow-up was completed in 987 patients at the time of interim analysis. The incidence of MACE is 0.45 for 1544 person-year follow-up. There were only 03 cases of ST (01 late ST) reported during this time.

Conclusion

This registry demonstrates excellent one-year clinical safety and efficacy of BioMatrix stents. The 1-year result shows that BioMatrix stent may be a suitable alternative as compared to contemporary DESs which are currently available in the market for simple as well complex disease.     

Cardiac I123-MIBG Correlates Better than Ejection Fraction with Symptoms Severity in Systolic Heart Failure

Background

The association of autonomic activation, left ventricular ejection fraction (LVEF) and heart failure functional class is poorly understood.

Objective

Our aim was to correlate symptom severity with cardiac sympathetic activity, through iodine-123-metaiodobenzylguanidine (¹²³I-MIBG) scintigraphy and with LVEF in systolic heart failure (HF) patients without previous beta-blocker treatment.

Methods

Thirty-one patients with systolic HF, class I to IV of the New York Heart Association (NYHA), without previous beta-blocker treatment, were enrolled and submitted to ¹²³I-MIBG scintigraphy and to radionuclide ventriculography for LVEF determination. The early and delayed heart/mediastinum (H/M) ratio and the washout rate (WR) were performed.

Results

According with symptom severity, patients were divided into group A, 13 patients in NYHA class I/II, and group B, 18 patients in NYHA class III/IV. Compared with group B patients, group A had a significantly higher LVEF (25% ± 12% in group B vs. 32% ± 7% in group A, p = 0.04). Group B early and delayed H/M ratios were lower than group A ratios (early H/M 1.49 ± 0.15 vs. 1.64 ± 0.14, p = 0.02; delayed H/M 1.39 ± 0.13 vs. 1.58 ± 0.16, p = 0.001, respectively). WR was significantly higher in group B (36% ± 17% vs. 30% ± 12%, p= 0.04). The variable that showed the best correlation with NYHA class was the delayed H/M ratio (r= -0.585; p=0.001), adjusted for age and sex.

Conclusion

This study showed that cardiac ¹²³I-MIBG correlates better than ejection fraction with symptom severity in systolic heart failure patients without previous beta-blocker treatment.     

Cardiac Sympathetic Hyperactivity after Chemotherapy: Early Sign of Cardiotoxicity?

Background

Chemotherapy with anthracyclines and trastuzumab can cause cardiotoxicity. Alteration of cardiac adrenergic function assessed by metaiodobenzylguanidine labeled with iodine-123 (¹²³I-mIBG) seems to precede the drop in left ventricular ejection fraction.

Objective

To evaluate and to compare the presence of cardiovascular abnormalities among patients with breast cancer undergoing chemotherapy with anthracyclines and trastuzumab, and only with anthracycline.

Methods

Patients with breast cancer were analyzed clinical, laboratory, electrocardiographic and echocardiographic and cardiac sympathetic activity. In scintigraphic images, the ratio of ¹²³I-mIBG uptake between the heart and mediastinum, and the washout rate were calculated. The variables were compared between patients who received anthracyclines and trastuzumab (Group 1) and only anthracyclines (Group 2).

Results

Twenty patients, with mean age 57 ± 14 years, were studied. The mean left ventricular ejection fraction by echocardiography was 67.8 ± 4.0%. Mean washout rate was 28.39 ± 9.23% and the ratio of ¹²³I-mIBG uptake between the heart and mediastinum was 2.07 ± 0.28. Of the patients, 82% showed an increased in washout rate, and the ratio of ¹²³I-mIBG uptake between the heart and mediastinum decreased in 25%. Concerning the groups, the mean washout rate of Group 1 was 32.68 ± 9.30% and of Group 2 was 24.56 ± 7.72% (p = 0,06). The ratio of ¹²³I-mIBG uptake between the heart and mediastinum was normal in all patients in Group 2, however, the Group 1, showed 50% the ratio of ¹²³I-mIBG uptake between the heart and mediastinum ≤ 1.8 (p = 0.02).

Conclusion

In women with breast cancer undergoing chemotherapy, assessment of cardiac sympathetic activity with ¹²³I-mIBG appears to be an early marker of cardiotoxicity. The combination of chemotherapy showed higher risk of cardiac adrenergic hyperactivity.     

Real world experience with an indigenously manufactured stent Cobal C – A retrospective study

Background

Second generation bare metal stents made of cobalt chromium alloy are superior to first generation stain less steel stents. The thin struts are shown to reduce clinical and angiographic adverse outcomes.

Objective

To study the long term clinical and angiographic outcomes in patients who underwent coronary angioplasty with an indigenously made cobalt chromium bare metal stents with thin strut Cobal+C™ (Relisys).

Methods

A total of 268 consecutive patients who underwent coronary angioplasty with Cobal+C stents were studied retrospectively. Clinical follow up was done after a minimum period of nine months through telephonic interview and angiographic follow up was done in 80 patients chosen randomly. The end points analyzed included major adverse cardiac events (MACE) at nine months and the rate of binary restenosis at follow up angiogram done between 9 and 15 months post angioplasty.

Results

Thirty four percent were diabetic and 33% had acute myocardial infarction. Females constituted 17%. Mean stent diameter was 2.88 ± 0.28 and mean stent length 18.8 ± 4.2. MACE at nine months was 4.5% with TLR 0.3%. The rate of binary restenosis was 21%. Patients with longer stent lengths and non-compliance with medications had significantly higher rates of binary restenosis.

Conclusions

The use of Relisys Cobal+C stents was associated with good long term clinical and angiographic outcomes as evidenced by low incidence of MACE and binary restenosis rates for a bare metal stent.     

Cardiovascular Autonomic Dysfunction in Patients with Morbid Obesity

Background

Morbid obesity is directly related to deterioration in cardiorespiratory capacity, including changes in cardiovascular autonomic modulation.

Objective

This study aimed to assess the cardiovascular autonomic function in morbidly obese individuals.

Methods

Cross-sectional study, including two groups of participants: Group I, composed by 50 morbidly obese subjects, and Group II, composed by 30 nonobese subjects. The autonomic function was assessed by heart rate variability in the time domain (standard deviation of all normal RR intervals [SDNN]; standard deviation of the normal R-R intervals [SDNN]; square root of the mean squared differences of successive R-R intervals [RMSSD]; and the percentage of interval differences of successive R-R intervals greater than 50 milliseconds [pNN50] than the adjacent interval), and in the frequency domain (high frequency [HF]; low frequency [LF]: integration of power spectral density function in high frequency and low frequency ranges respectively). Between-group comparisons were performed by the Student’s t-test, with a level of significance of 5%.

Results

Obese subjects had lower values of SDNN (40.0 ± 18.0 ms vs. 70.0 ± 27.8 ms; p = 0.0004), RMSSD (23.7 ± 13.0 ms vs. 40.3 ± 22.4 ms; p = 0.0030), pNN50 (14.8 ± 10.4 % vs. 25.9 ± 7.2%; p = 0.0061) and HF (30.0 ± 17.5 Hz vs. 51.7 ± 25.5 Hz; p = 0.0023) than controls. Mean LF/HF ratio was higher in Group I (5.0 ± 2.8 vs. 1.0 ± 0.9; p = 0.0189), indicating changes in the sympathovagal balance. No statistical difference in LF was observed between Group I and Group II (50.1 ± 30.2 Hz vs. 40.9 ± 23.9 Hz; p = 0.9013).

Conclusion

morbidly obese individuals have increased sympathetic activity and reduced parasympathetic activity, featuring cardiovascular autonomic dysfunction.     

Increased QT dispersion and P wave dispersion in major depressive disorder

BACKGROUND:

QT and P wave dispersion parameters can indicate abnormalities in autonomic nervous system and cardiac functioning.

OBJECTIVES:

To determine QT and P wave dispersion in patients with major depressive disorder compared with healthy volunteers.

METHODS:

Fifty newly diagnosed patients with major depressive disorder and 50 age- and sex-matched healthy volunteers underwent 12-lead electrocardiography. QT interval, QT dispersion, heart rate-corrected QT dispersion and P wave dispersions were calculated manually by a blinded specialist.

RESULTS:

Groups were comparable in terms of age, sex, body mass index, smoking status, metabolic diseases and left ventricular ejection fraction. The major depressive disorder group had significantly higher QT dispersion (58.5±9.9 versus 41.7±3.8; P<0.001), heart rate-corrected QT dispersion (62.5±10.0 versus 45.2±4.3; P<0.001) and P wave dispersion (46.9±4.8 versus 41.5±5.1; P<0.001).

CONCLUSION:

Increased QT dispersion, heart-rate corrected QT dispersion and P wave dispersion in major depressive disorder patients may be indicative of autonomic imbalance and increased risk of cardiac morbidity and mortality.     

A prospective,multi-centric,observational registry to evaluate performance of Excel™ DES in ‘Real World,All Comers’ patient population

Objectives

This study aims to assess the safety and efficacy of a biodegradable polymer-coated Rapamycin-Eluting Stent (Excel) used in conjunction with six-month dual antiplatelet therapy in daily practice.

Background

The polymeric material of cardiac stents has been reported to adversely affect the safety profile of the drug-eluting stents and is also suspected to cause serious long-term complications. It has been proposed that the biodegradable polymer coatings may reduce such late-stage adverse effects.

Methods

This is a prospective, multi-center registry of 654 patients from across 9 cardiology centers in India, who were enrolled and exclusively treated with Excel stents between February 2008 and May 2010. The recommended antiplatelet regimen included clopidogrel and aspirin for 6 months period, followed by lifelong aspirin therapy.

Results

The study population included 46.94% diabetics, 24.31% smokers, 48.93% hypertensives and 14.98% hyperlipidemics. The cumulative rates of major adverse cardiac events were 0.153% at discharge and 1.38% at 12 months. The mean percentage of stenosis was 88.24 ± 9.17% No events occurred between 6 and 12 months.

Conclusions

This multi-center registry study on “real world, all comers” has, thus, showed that EXCEL™ stent which is PLA-coated biodegradable Rapamycin-Eluting Stent exhibited high efficacy and safety profile in treatment of patients undergoing PCI as evidenced by significantly lower rates of MACE and no case of stent thrombosis. There was no event even after DAPT was discontinued after 6 months.     

Post-transplant lymphoproliferative disorder in liver transplant recipients: Characteristics,management and outcome from a single-centre experience with >1000 liver transplantations

BACKGROUND:

The literature regarding post-transplant lymphoproliferative disorder (PTLD) in liver transplant recipients (LTRs) is limited.

OBJECTIVES:

To study the incidence, predictors and outcomes of PTLD after liver transplantation in a single, large-volume centre.

METHODS:

The charts of all LTRs (n=1372) in the authors’ centre between January 2000 and June 2012 were retrospectively reviewed and those who developed PTLD were identified. Demographic, clinical and treatment data were prospectively collected. Responses to treatment, including complete response, no response, relapse and survival, were recorded.

RESULTS:

The incidence of PTLD in LTRs was 32 in 1372 (2.3%). Overall, median survival was 37 months (range 0.5 to 195 months), with one-, three- and five-year survival rates of 81%, 74% and 60%, respectively. Epstein-Barr virus (EBV)-negative patients had a better mean (± SD) survival (95±79 months) than EBV-positive patients (41±42 months) (P=0.02). For stage I/II PTLD, one-, three- and five-year actuarial survival was 87%, 87% and 75%, compared with 50%, 30% and 0% for stage III/IV PTLD, respectively (P=0.001). In patients with complete response, median survival was 58 months (range 10 to 195 months); and one-, three- and five-year actuarial survival was 100%, 94% and 76%, respectively, after diagnosis of PTLD. Changing immunosuppression (IS) from calcineurin inhibitor to sirolimus at the time of diagnosis may have improved survival (seven of seven survivors) compared with only decreasing or stopping IS (14 of 25 survivors) (P=0.07).

CONCLUSIONS:

This series from a single large-volume centre showed excellent short and long-term survival after PTLD in adult LTRs who were EBV negative, had early disease and showed complete response. Consistent with the known in vitro antiproliferative effect of sirolimus, switching IS from calcineurin inhibitor to sirolimus may improve survival.     

Prevention of Pazopanib-Induced Prolonged Cardiac Repolarization and Proarrhythmic Effects

Background

Pazopanib (PZP) may induce prolonged cardiac repolarization and proarrhythmic effects, similarly to other tyrosine kinase inhibitors.

Objectives

To demonstrate PZP-induced prolonged cardiac repolarization and proarrhythmic electrophysiological effects and to investigate possible preventive effects of metoprolol and diltiazem on ECG changes (prolonged QT) in an experimental rat model.

Methods

Twenty-four Sprague-Dawley adult male rats were randomly assigned to 4 groups (n = 6). The first group (normal group) received 4 mL of tap water and the other groups received 100 mg/kg of PZP (Votrient^® tablet) perorally, via orogastric tubes. After 3 hours, the following solutions were intraperitoneally administered to the animals: physiological saline solution (SP), to the normal group and to the second group (control-PZP+SP group); 1 mg/kg metoprolol (Beloc, Ampule, AstraZeneca), to the third group (PZP+metoprolol group); and 1mg/kg diltiazem (Diltiazem, Mustafa Nevzat), to the fourth group (PZP+diltiazem group). One hour after, and under anesthesia, QTc was calculated by recording ECG on lead I.

Results

The mean QTc interval values were as follows: normal group, 99.93 ± 3.62 ms; control-PZP+SP group, 131.23 ± 12.21 ms; PZP+metoprolol group, 89.36 ± 3.61 ms; and PZP+diltiazem group, 88.86 ± 4.04 ms. Both PZP+metoprolol and PZP+diltiazem groups had significantly shorter QTc intervals compared to the control-PZP+SP group (p < 0.001).

Conclusion

Both metoprolol and diltiazem prevented PZP-induced QT interval prolongation. These drugs may provide a promising prophylactic strategy for the prolonged QTc interval associated with tyrosine kinase inhibitor use.     

Effect of Beta-Carotene on Oxidative Stress and Expression of Cardiac Connexin 43

Background

Intervention studies have shown an increased mortality in patients who received beta-carotene. However, the mechanisms involved in this phenomenon are still unknown.

Objective

Evaluate the influence of beta-carotene on oxidative stress and the expression of connexin 43 in rat hearts.

Methods

Wistar rats, weighing approximately 100 g, were allocated in two groups: Control Group (n = 30), that received the diet routinely used in our laboratory, and Beta-Carotene Group (n = 28), which received beta-carotene (in crystal form, added and mixed to the diet) at a dose of 500 mg of beta carotene/kg of diet. The animals received the treatment until they reached 200-250g, when they were sacrificed. Samples of blood, liver and heart were collected to perform Western blotting and immunohistochemistry for connexin 43; morphometric studies, dosages of beta carotene by high performance liquid chromatography as well as reduced glutathione, oxidized glutathione and lipids hydroperoxides were performed by biochemical analysis.

Results

Beta-carotene was detected only in the liver of Beta-Carotene Group animals (288 ± 94.7 μg/kg). Levels of reduced/ oxidized glutathione were higher in the liver and heart of Beta-Carotene Group animals (liver - Control Group: 42.60 ± 1.62; liver - Beta-Carotene Group: 57.40 ± 5.90; p = 0.04; heart: - Control Group: 117.40 ± 1.01; heart - Beta-Carotene Group: 121.81 ± 1.32 nmol/mg protein; p = 0.03). The content of total connexin 43 was larger in Beta-Carotene Group.

Conclusion

Beta-carotene demonstrated a positive effect, characterized by the increase of intercellular communication and improvement of anti-oxidizing defense system. In this model, mechanism does not explain the increased mortality rate observed with the beta-carotene supplementation in clinical studies.     

Evaluation of a novel method of teaching endobronchial ultrasound: Physician- versus respiratory therapist-proctored simulation training

BACKGROUND:

Computer endobronchial ultrasound (EBUS) simulators have been demonstrated to improve trainee procedural skills before attempting to perform EBUS procedures on patients.

OBJECTIVE:

To compare EBUS performance following training with computer simulation proctored by EBUS-trained respiratory therapists versus the same simulation training proctored by an interventional respirologist.

METHODS:

The present analysis was a prospective study of respiratory medicine trainees learning EBUS. Two cohorts of trainees were evaluated using a previously validated method using simulated cases with performance metrics measured by the simulator. Group 1 underwent EBUS training by performing 15 procedures on an EBUS simulator (n=4) proctored by an interventional respirologist. Group 2 received identical training proctored by a respiratory therapist with special training in EBUS (n=10).

RESULTS:

No significant differences between group 1 and group 2 were apparent for the primary outcome measures of total procedure time (15.15±1.34 min versus 14.78±2.88 min; P=0.816), the percentage of lymph nodes successfully identified (88.8±5.4 versus 80.91±8.9; P=0.092) or the percentage of successful biopsies (100.0±0.0 versus 98.75±3.95; P=0.549). The learning curves were similar between groups, and did not show an obvious plateau after 19 simulated procedures in either group.

DISCUSSION:

Acquisition of basic EBUS technical skills can be achieved using computer EBUS simulation proctored by specially trained respiratory therapists or by an interventional respirologist. There appeared to be no significant advantage to having an interventional respirologist proctor the computer EBUS simulation.     

Plasma Osteopontin Level in Chronic Liver Disease and Hepatocellular Carcinoma

Background

Osteopontin (OPN) is a secreted glycoprotein and is frequently associated with various tumors.

Objectives

We sought to investigate the clinical usefulness of the level of plasma OPN, compared to α-fetoprotein (AFP), as a biomarker for hepatocellular carcinoma (HCC) and to evaluate its diagnostic value in nonalcoholic fatty liver disease (NAFLD) and its relationship with clinical and laboratory features of HCC and NAFLD.

Patients and Methods

The study was performed on 120 subjects classified into 5 groups: Group I included 25 chronic non-cirrhotic hepatitis C virus (HCV)-infected patients; Group II encompassed 25 patients with chronic HCV infection with liver cirrhosis; Group III comprised 25 patients with chronic HCV with liver cirrhosis and HCC; Group IV was comprised of 25 patients with NAFLD; and Group V consisted of 20 healthy age- and sex-matched controls. All the participants were subjected to history taking and clinical and abdominal ultrasonographic examinations as well as the following laboratory investigations: liver function tests, complete blood count, blood sugar, hepatitis B surface antigen, hepatitis C virus antibodies, HCV-RNA by qualitative polymerase chain reaction (for Groups I, II, and III) and serum AFP and plasma OPN levels.

Results

There were statistically significant differences in plasma OPN levels between the HCC group (401 ± 72 ng/mL) and the other groups, between the cirrhotic group (258.3 ± 35 ng/mL) and the non-cirrhotic group (HCV group, 168.7 ± 41 ng/mL; fatty liver group, 106.7 ± 35 ng/mL), and between the chronic non-cirrhotic HCV group and the fatty liver group (I and IV) and the controls (35.1 ± 6 ng/mL). In the HCC group, the diagnostic value of OPN was comparable to that of AFP at a cutoff value of 280 ng/mL, achieving sensitivity, specificity, and overall accuracy of 100%, 98%, and 96%, respectively. Regarding the validity of plasma OPN as a predictor of fatty change, our results revealed a diagnostic accuracy of 50% with 70% sensitivity, 45% specificity, 50% positive predictive value, and 75% negative predictive value at a cutoff value of 134 ng/mL.

Conclusions

Plasma OPN is comparable to AFP as a diagnostic marker and is related to the severity of liver involvement in HCC patients. Plasma OPN is of diagnostic potential value in NAFLD.     

Co-administration of Apelin and T4 Protects Inotropic and Chronotropic Changes Occurring in Hypothyroid Rats

Background

One of the most important thyroid hormone targets is the cardiovascular system. Hemodynamic changes, such as decreased resting heart rate (HR), myocardial contractility, and cardiac output, and increased diastolic pressure and systemic vascular resistance, have been observed in hypothyroid patients. Moreover, in these patients, ECG changes include sinus bradycardia and low voltage complexes (P waves or QRS complexes).

Objective

This study aimed at evaluating the prophylactic effect of apelin on HR changes and QRS voltage that occur in propylthiouracil (PTU)-induced hypothyroid rats.

Method

In this study, 48 adult male Wistar rats weighing 170-235g were randomly divided into 6 groups: Control group (normal saline ip injection + tap water gavage); P group (PTU 0.05%, in drinking water); A group (apelin 200 µg.kg^-1.day^-1, ip); PA group [co-administration of PTU and apelin]; PT group [co-administration of PTU + T4 (0.2 mg/g per day, gavage)]; and PAT group (co-administration of PTU, apelin and T4). All experiments were performed for 28 consecutive days, and then the animals were anesthetized with an ip injection of ketamine (80 mg/kg) and xylazine (12 mg/kg). Lead II electrocardiogram was recorded to calculate HR and QRS voltage.

Results

Heart rate and QRS voltage increased more significantly in the hypothyroid group that consumed both apelin and T4 (201 ± 4 beat/min, 0.71 ± 0.02 mv vs. hypothyroid 145 ± 9 beat/min, 0.563 ± 0.015 mv; respectively).

Conclusion

The co-administration of apelin and T4 showed a protective effect on QRS voltage and HR in PTU‑induced hypothyroid rats.     

Sex-Specific Equations to Estimate Maximum Oxygen Uptake in Cycle Ergometry

Background

Aerobic fitness, assessed by measuring VO₂max in maximum cardiopulmonary exercise testing (CPX) or by estimating VO₂max through the use of equations in exercise testing, is a predictor of mortality. However, the error resulting from this estimate in a given individual can be high, affecting clinical decisions.

Objective

To determine the error of estimate of VO₂max in cycle ergometry in a population attending clinical exercise testing laboratories, and to propose sex-specific equations to minimize that error.

Methods

This study assessed 1715 adults (18 to 91 years, 68% men) undertaking maximum CPX in a lower limbs cycle ergometer (LLCE) with ramp protocol. The percentage error (E%) between measured VO₂max and that estimated from the modified ACSM equation (Lang et al. MSSE, 1992) was calculated. Then, estimation equations were developed: 1) for all the population tested (C-GENERAL); and 2) separately by sex (C-MEN and C-WOMEN).

Results

Measured VO₂max was higher in men than in WOMEN: -29.4 ± 10.5 and 24.2 ± 9.2 mL.(kg.min)^-1 (p < 0.01). The equations for estimating VO₂max [in mL.(kg.min)^-1] were: C-GENERAL = [final workload (W)/body weight (kg)] x 10.483 + 7; C-MEN = [final workload (W)/body weight (kg)] x 10.791 + 7; and C-WOMEN = [final workload (W)/body weight (kg)] x 9.820 + 7. The E% for MEN was: -3.4 ± 13.4% (modified ACSM); 1.2 ± 13.2% (C-GENERAL); and -0.9 ± 13.4% (C-MEN) (p < 0.01). For WOMEN: -14.7 ± 17.4% (modified ACSM); -6.3 ± 16.5% (C-GENERAL); and -1.7 ± 16.2% (C-WOMEN) (p < 0.01).

Conclusion

The error of estimate of VO₂max by use of sex-specific equations was reduced, but not eliminated, in exercise tests on LLCE.     

Left Ventricular Synchrony and Function in Pediatric Patients with Definitive Pacemakers

Background

Chronic right ventricular pacing (RVP) induces a dyssynchronous contraction pattern, producing interventricular and intraventricular asynchrony. Many studies have shown the relationship of RVP with impaired left ventricular (LV) form and function.

Objective

The aim of this study was to evaluate LV synchrony and function in pediatric patients receiving RVP in comparison with those receiving LV pacing (LVP).

Methods

LV systolic and diastolic function and synchrony were evaluated in 80 pediatric patients with either nonsurgical or postsurgical complete atrioventricular block, with pacing from either the RV endocardium (n = 40) or the LV epicardium (n = 40). Echocardiographic data obtained before pacemaker implantation, immediately after it, and at the end of a mean follow-up of 6.8 years were analyzed.

Results

LV diastolic function did not change in any patient during follow-up. LV systolic function was preserved in patients with LVP. However, in children with RVP the shortening fraction and ejection fraction decreased from medians of 41% ± 2.6% and 70% ± 6.9% before implantation to 32% ± 4.2% and 64% ± 2.5% (p < 0.0001 and p < 0.0001), respectively, at final follow-up. Interventricular mechanical delay was significantly larger with RVP (66 ± 13 ms) than with LVP (20 ± 8 ms). Similarly, the following parameters were significantly different in the two groups: LV mechanical delay (RVP: 69 ± 6 ms, LVP: 30 ± 11 ms, p < 0.0001); septal to lateral wall motion delay (RVP: 75 ± 19 ms, LVP: 42 ± 10 ms, p < 0.0001); and, septal to posterior wall motion delay (RVP: 127 ± 33 ms, LVP: 58 ± 17 ms, p < 0.0001).

Conclusion

Compared with RV endocardium, LV epicardium is an optimal site for pacing to preserve cardiac synchrony and function.     

Evaluation of von Willebrand factor in COPD patients

OBJECTIVE:

To compare the absolute serum von Willebrand factor (vWF) levels and relative serum vWF activity in patients with clinically stable COPD, smokers without airway obstruction, and healthy never-smokers.

METHODS:

The study included 57 subjects, in three groups: COPD (n = 36); smoker (n = 12); and control (n = 9). During the selection phase, all participants underwent chest X-rays, spirometry, and blood testing. Absolute serum vWF levels and relative serum vWF activity were obtained by turbidimetry and ELISA, respectively. The modified Medical Research Council scale (cut-off score = 2) was used in order to classify COPD patients as symptomatic or mildly symptomatic/asymptomatic.

RESULTS:

Absolute vWF levels were significantly lower in the control group than in the smoker and COPD groups: 989 ± 436 pg/mL vs. 2,220 ± 746 pg/mL (p < 0.001) and 1,865 ± 592 pg/mL (p < 0.01). Relative serum vWF activity was significantly higher in the COPD group than in the smoker group (136.7 ± 46.0% vs. 92.8 ± 34.0%; p < 0.05), as well as being significantly higher in the symptomatic COPD subgroup than in the mildly symptomatic/asymptomatic COPD subgroup (154 ± 48% vs. 119 ± 8%; p < 0.05). In all three groups, there was a negative correlation between FEV₁ (% of predicted) and relative serum vWF activity (r² = −0.13; p = 0.009).

CONCLUSIONS:

Our results suggest that increases in vWF levels and activity contribute to the persistence of systemic inflammation, as well as increasing cardiovascular risk, in COPD patients.     

Lycopene supplementation reduces TNF-α via RAGE in the kidney of obese rats

Background:

The kidney is a target organ for injuries caused by advanced glycation end products (AGEs) in obesity. The receptor of AGEs (RAGE) is proinflammatory and appears to have a role in the pathogenesis of renal disease due to obesity.

Objective:

The aim was to verify the effect of obesity on renal damage and the effect of lycopene on these complications

Design and Methods:

Male Wistar rats were randomly assigned to receive a control diet (C, n=7) or a high-fat diet plus sucrose (HD+S, n=14) for 6 weeks. After this period, the HD+S animals were randomized into two groups: HD+S (n=7) and HD+S supplemented with lycopene (HD+S+L, n=7). The animals received maize oil (C and HD+S) or lycopene (HD+S+L) for a 6-week period.

Results:

The HD+S and HD+S+L animals demonstrated insulin resistance (OGTT glucose after 150 min; C: 117.6±3.9<HD+S: 138.1±5.1=HD+S+L: 137.8±5.2 mg dl⁻¹; P=0.01); however, no changes were seen in fasting glucose, plasma lipids, blood pressure or renal function. Renal concentrations of RAGE and TNF-α increased in the HD+S group and lycopene supplementation restored these to control group values (RAGE: C: 3.1±0.3=DH+S+L: 3.1±0.3<DH+S: 3.6±0.4 μg g⁻¹; P=0.014; TNF-α: C: 227.8±2.7=DH+S+L: 227.4±2.2<DH+S: 238.7±3.0 pg/ml; P=0.014).

Conclusions:

Lycopene may be beneficial in the prevention and treatment of oxidative stress and inflammation in the kidney due to obesity.     

Three Decades of Progress in Treating Childhood-Onset Lupus Nephritis

Summary

Background and objectives

Childhood-onset lupus nephritis (LN) carries a worse renal prognosis compared with adults. Controlled treatment trials in children are lacking. We compared renal and patient survival in a cohort of pediatric patients followed over 3 decades.

Design, settings, participants, & measurements

A retrospective analysis was conducted on 138 patients with childhood-onset systemic lupus erythematosus from 1980 to 2010. The core cohort included 95 with severe LN: 28 progressed to end-stage renal disease (ESRD group) whereas 67 did not (no-ESRD group). Patients were stratified into four “eras” according to the introduction of the primary immuno-suppressive drug: era 1: triple oral therapy with corticosteroids (CS), cyclophosphamide (CYC), and azathioprine (AZA); era 2: intravenous CYC; era 3: mycophenolate mofetil (MMF) ± CYC; era 4: rituximab (RTX) ± CYC ± MMF.

Results

Mean age at diagnosis was 12.3 ± 2.9 years with median follow-up of 5 years. Poor renal function (estimated GFR < 60 ml/min per 1.73 m²) and nephrotic proteinuria at diagnosis imparted a poor prognosis. Increasing proteinuria correlated with progression of kidney disease. The addition of MMF in era 3 improved 5-year renal survival from 52% to 91% and overall patient survival from 83% to 97%. African-American ethnicity was associated with significant risk for progression to ESRD whereas Hispanic ethnicity conferred an advantage. Infection and cardiovascular disease were the primary causes of patient demise.

Conclusions

Renal and patient survival in childhood-onset LN has improved during the past 3 decades with progressive treatment regimens. Future trials in children are very much warranted.