Left Atrial Function in Patients with Chronic Chagasic Cardiomyopathy

Background

Chagas disease is a cause of dilated cardiomyopathy, and information about left atrial (LA) function in this disease still lacks.

Objective

To assess the different LA functions (reservoir, conduit and pump functions) and their correlation with the echocardiographic parameters of left ventricular (LV) systolic and diastolic functions.

Methods

10 control subjects (CG), and patients with Chagas disease as follows: 26 with the indeterminate form (GI); 30 with ECG alterations (GII); and 19 with LV dysfunction (GIII). All patients underwent M-mode and two-dimensional echocardiography, pulsed-wave Doppler and tissue Doppler imaging.

Results

Reservoir function (Total Emptying Fraction: TEF): (p <0.0001), lower in GIII as compared to CG (p = 0.003), GI (p <0.001) and GII (p <0.001). Conduit function (Passive Emptying Fraction: PEF): (p = 0.004), lower in GIII (GIII and CG, p = 0.06; GI and GII, p = 0.06; and GII and GIII, p = 0.07). Pump function (Active Emptying Fraction: AEF): (p = 0.0001), lower in GIII as compared to CG (p = 0.05), GI (p<0.0001) and GII (p = 0.002). There was a negative correlation of E/e’_average with the reservoir and pump functions (TEF and AEF), and a positive correlation of e’_average with s’ wave (both septal and lateral walls) and the reservoir, conduit and pump LA functions.

Conclusion

An impairment of LA functions in Chagas cardiomyopathy was observed.     

Right Ventricular Doppler Echocardiographic Study of Indeterminate Form of Chagas Disease

Background

Patients with indeterminate form of Chagas disease/cardiac normality (ICD/CN) exhibited normal electrocardiograms and chest X-rays; however, more sophisticated tests detected some degree of morphological and functional changes in the heart.

Objective

To assess the prevalence of systolic and diastolic dysfunction of the right ventricle (RV) in patients with ICD/CN.

Methods

This was a case–control and prevalence study. Using Doppler two-dimensional echocardiography (2D), 92 patients were assessed and divided into two groups: group I (normal, n = 31) and group II (ICD/CN, n = 61).

Results

The prevalence of RV systolic dysfunction in patients in groups I and II was as follows: fractional area change (0.0% versus 0.6%), mobility of the tricuspid annulus (0.0% versus 0.0%), and S-wave tissue Doppler (6.4% versus 26.0%, p = 0.016). The prevalence of global disorders such as the right myocardial performance index using tissue Doppler (16.1% versus 27.8%, p = 0.099) and pulsed Doppler (61.3% versus 68%, p = 0.141) and diastolic disorders such as abnormal relaxation (0.0% versus 6.0%), pseudonormal pattern (0.0% versus 0.0%), and restrictive pattern (0.0% versus 0.0%) was not statistically different between groups.

Conclusion

The prevalence of RV systolic dysfunction was estimated to be 26% (S wave velocity compared with other variables), suggesting incipient changes in RV systolic function in the ICD/CN group.     

Echocardiographic Parameters and Survival in Chagas Heart Disease with Severe Systolic Dysfunction

Background

Echocardiography provides important information on the cardiac evaluation of patients with heart failure. The identification of echocardiographic parameters in severe Chagas heart disease would help implement treatment and assess prognosis.

Objective

To correlate echocardiographic parameters with the endpoint cardiovascular mortality in patients with ejection fraction < 35%.

Methods

Study with retrospective analysis of pre-specified echocardiographic parameters prospectively collected from 60 patients included in the Multicenter Randomized Trial of Cell Therapy in Patients with Heart Diseases (Estudo Multicêntrico Randomizado de Terapia Celular em Cardiopatias) - Chagas heart disease arm. The following parameters were collected: left ventricular systolic and diastolic diameters and volumes; ejection fraction; left atrial diameter; left atrial volume; indexed left atrial volume; systolic pulmonary artery pressure; integral of the aortic flow velocity; myocardial performance index; rate of increase of left ventricular pressure; isovolumic relaxation time; E, A, Em, Am and Sm wave velocities; E wave deceleration time; E/A and E/Em ratios; and mitral regurgitation.

Results

In the mean 24.18-month follow-up, 27 patients died. The mean ejection fraction was 26.6 ± 5.34%. In the multivariate analysis, the parameters ejection fraction (HR = 1.114; p = 0.3704), indexed left atrial volume (HR = 1.033; p < 0.0001) and E/Em ratio (HR = 0.95; p = 0.1261) were excluded. The indexed left atrial volume was an independent predictor in relation to the endpoint, and values > 70.71 mL/m² were associated with a significant increase in mortality (log rank p < 0.0001).

Conclusion

The indexed left atrial volume was the only independent predictor of mortality in this population of Chagasic patients with severe systolic dysfunction.     

Incidence of Ventricular Arrhythmias after Stem Cell Therapy in Patients with Chagas Cardiomyopathy

Background

Treatment with stem cells in several cardiomyopathies may be related to the increase in arrhythmias.

Objectives

To determine whether intracoronary injection of stem cells in patients with Chagas cardiomyopathy is associated with increased incidence of ventricular arrhythmias, compared to the Control Group.

Methods

A retrospective cohort study that evaluated the medical records of 60 patients who participated in a previous cross-sectional study. The following data were collected: age, gender, drugs used and Holter variables that demonstrated the presence of arrhythmias. Holter was performed in four stages: randomization, 2, 6 and 12 months segments. The Control Group received medical treatment and intracoronary injection of placebo and the Study Group had drug treatment and autologous stem cell implant.

Results

There was no difference between Control Group and Study Group when analyzing the arrhythmia criteria. In the intra-group analysis, significant difference was found between the Holter tests of the Study Group for the variable total ventricular premature beats when compared with baseline, with p = 0.014 between Holter at randomization and Holter at 2 months, p = 0.004 between Holter at randomization and Holter at 6 months, and p = 0.014 between Holter at randomization and Holter at 12 months. The variable non-sustained ventricular tachycardia between Holter at randomization and Holter at 6 months showed p = 0.036.

Conclusion

The intracoronary injection of stem cells did not increase the incidence of ventricular arrhythmias in patients with Chagas cardiomyopathy compared to the Control Group.     

The Role of Interleukin-28b Gene Polymorphisms in Chinese Patients With Chronic Hepatitis C Treated With Pegylated Interferon and Ribavirin

Background:

Interleukin-28B (IL28B) single nucleotide polymorphism (SNP) rs8099917 has been described to be associated with response to treatment with pegylated interferon and ribavirin (PEG-IFN/RBV) in patients with chronic hepatitis C from the North America, Europe, Asia countries like Japan and Taiwan. Whether this holds true for Chinese patients remains unknown.

Objectives:

We aimed to study the effects of IL28B rs8099917 on antiviral therapy responses in Chinese patients with hepatitis C.

Patients and Methods:

IL28B rs8099917 was genotyped in 263 patients with hepatitis C virus (HCV) infection and 244 healthy controls in Tianjin, China using TaqMan SNP genotyping method. The roles of rs8099917 and clinical characteristics in antiviral treatment were analyzed by logistic regression.

Results:

Among 263 patients with chronic HCV infection, 223 had a TT genotype (84.8%). Frequencies of TG/GG genotypes in patients with hepatitis C were significantly different from those of healthy controls (15.2% vs. 9.0%; P = 0.033). Patients with HCV infection had a higher G allele frequency than healthy controls (7.8% vs. 4.7%; P = 0.044). Univariate analysis revealed no significant association between rs8099917 and sustained virological response (SVR) (P = 0.612). However, it was found that HCV genotypes 2a/3a, age, prothrombin time (PT), albumin (ALB) and cholesterol (CHO) were associated with SVR. In multivariate analysis, only ALB was significantly an independent predictor of SVR (OR = 1.223; 95%CI: 1.046−1.430; P = 0.011).

Conclusions:

In contrast with T, rs8099917 G is a susceptible allele to HCV in China. ALB can independently predict SVR. Rs8099917 may play a quiet role to predict treatment response of patients with hepatitis C who received PEG−IFN/RBV therapy in China.     

ECG Manifestations of the Biggest Outbreak of Chagas Disease due to Oral Infection in Latin-America

Background

Chagas disease affects more than 15 million people worldwide. Although vector-borne transmission has decreased, oral transmission has become important. Recently, our group published the clinical and epidemiological characteristics of the largest outbreak of orally transmitted Chagas disease reported till date. Objective: To describe electrocardiographic changes occurring in the study population during the outbreak caused by ingestion of contaminated guava juice.

Methods

We evaluated 103 positive cases, of which 76 (74%) were aged ≤ 18 years (average age: 9.1 ± 3.1 years) and 27 (26%) were aged > 18 years (average age: 46 ± 11.8 years). All patients underwent clinical evaluations and ECG. If the patients had palpitations or evident alterations of rhythm at baseline, ambulatory ECG monitoring was performed.

Results

A total of 68 cases (66%; 53 children and 15 adults) had ECG abnormalities. Further, 69.7% (53/76) of those aged ≤ 18 years and 56% (15/27) of those aged >18 years showed some ECG alteration (p = ns). ST-T abnormalities were observed in 37.86% cases (39/103) and arrhythmias were evident in 28.16% cases (29/103). ST alterations occurred in 72% of those aged ≤18 years compared with 19% of th ose aged >18 years (p < 0.0001).

Conclusion

This study reports the largest number of cases in the same outbreak of acute Chagas disease caused by oral contamination, with recorded ECGs. ECG changes suggestive of acute myocarditis and arrhythmias were the most frequent abnormalities found.     

Baroreflex Sensitivity and its Association with Arrhythmic Events in Chagas Disease

Background

Sudden death is the leading cause of death in Chagas disease (CD), even in patients with preserved ejection fraction (EF), suggesting that destabilizing factors of the arrhythmogenic substrate (autonomic modulation) contribute to its occurrence.

Objective

To determine baroreflex sensitivity (BRS) in patients with undetermined CD (GI), arrhythmogenic CD with nonsustained ventricular tachycardia (NSVT) (GII) and CD with spontaneous sustained ventricular tachycardia (STV) (GIII), to evaluate its association with the occurrence and complexity of arrhythmias.

Method

Forty-two patients with CD underwent ECG and continuous and noninvasive BP monitoring (TASK force monitor). The following were determined: BRS (phenylephrine method); heart rate variability (HRV) on 24-h Holter; and EF (echocardiogram).

Results

GIII had lower BRS (6.09 ms/mm Hg) as compared to GII (11.84) and GI (15.23). The difference was significant between GI and GIII (p = 0.01). Correlating BRS with the density of ventricular extrasystoles (VE), low VE density (<10/h) was associated with preserved BRS. Only 59% of the patients with high VE density (> 10/h) had preserved BRS (p = 0.003). Patients with depressed BRS had higher VE density (p = 0.01), regardless of the EF. The BRS was the only variable related to the occurrence of SVT (p = 0.028).

Conclusion

The BRS is preserved in undetermined CD. The BRS impairment increases as disease progresses, being more severe in patients with more complex ventricular arrhythmias. The degree of autonomic dysfunction did not correlate with EF, but with the density and complexity of ventricular arrhythmias.     

Etanercept Induces Low QRS Voltage and Autonomic Dysfunction in Mice with Experimental Chagas Disease

Background

Chagas disease is a tropical parasitic disease caused by the flagellate protozoan Trypanosoma cruzi. Chagasic cardiomyopathy is characterized by disorders of autonomic regulation and action potential conduction in the acute and chronic phases of infection. Although tumor necrosis factor alpha (TNF-α) has been linked to cardiomyopathy in experimental models and in patients with Chagas disease, other reports suggest that TNF-α may exert anti-parasitic actions during the acute phase of infection.

Objectives

This study aimed to determine the effects of a soluble TNF-α blocker, etanercept, on electrocardiographic parameters in the acute phase of experimental infection with Trypanosoma cruzi.

Methods

Electrocardiograms were obtained from untreated infected mice and infected mice who were treated with etanercept 7 days after infection. ECG wave and heart rate variability parameters were determined using Chart for Windows.

Results

Etanercept treatment resulted in a low QRS voltage and decreased heart rate variability compared with no treatment. However, the treated mice exhibited a delay in the fall of the survival curve during the acute phase.

Conclusion

The results of this study suggest that although etanercept treatment promotes survival in mice infected with a virulent T. cruzi strain, TNF-α blockade generates a low voltage complex and autonomic dysfunction during the acute phase of infection. These findings indicate that mortality during the acute phase can be attributed to a systemic inflammatory response rather than cardiac dysfunction.     

Carvedilol Enhances the Antioxidant Effect of Vitamins E and C in Chronic Chagas Heart Disease

Background

Chagas disease is still an important endemic disease in Brazil, and the cardiac involvement is its more severe manifestation.

Objective

To verify whether the concomitant use of carvedilol will enhance the antioxidant effect of vitamins E and C in reducing the systemic oxidative stress in chronic Chagas heart disease.

Methods

A total of 42 patients with Chagas heart disease were studied. They were divided into four groups according to the modified Los Andes classification: 10 patients in group IA (normal electrocardiogram and echocardiogram; no cardiac involvement); 20 patients in group IB (normal electrocardiogram and abnormal echocardiogram; mild cardiac involvement); eight patients in group II (abnormal electrocardiogram and echocardiogram; no heart failure; moderate cardiac involvement); and four patients in group III (abnormal electrocardiogram and echocardiogram with heart failure; severe cardiac involvement). Blood levels of markers of oxidative stress were determined before and after a six-month period of treatment with carvedilol, and six months after combined therapy of carvedilol with vitamins E and C. The markers analyzed were as follows: activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione S-transferase and reductase, myeloperoxidade and adenosine deaminase; and the levels of reduced glutathione, thiobarbituric-acid reactive substances, protein carbonyls, vitamin E, and nitric oxide.

Results

After treatment with carvedilol, all groups showed significant decrease in protein carbonyls and reduced glutathione levels, whereas nitric oxide levels and adenosine activity increased significantly only in the less severely affected group (IA). In addition, the activity of most of the antioxidant enzymes was decreased in the less severely affected groups (IA and IB). By combining the vitamins with carvedilol, a reduction in protein damage, in glutathione levels, and in the activity of most of the antioxidant enzymes were observed.

Conclusions

The decrease in oxidative stress levels observed by means of the markers tested was more significant when carvedilol was used in combination with the antioxidant vitamins. The findings suggest that both carvedilol alone and in combination with the vitamins were effective in attenuating the systemic oxidative stress in patients with Chagas heart disease, especially those less severely affected, thus suggesting the possibility of synergism between these compounds.     

Assessment of Autonomic Function by Phase Rectification of RRInterval Histogram Analysis in Chagas Disease

Background

In chronic Chagas disease (ChD), impairment of cardiac autonomic function bears prognostic implications. Phase‑rectification of RR-interval series isolates the sympathetic, acceleration phase (AC) and parasympathetic, deceleration phase (DC) influences on cardiac autonomic modulation.

Objective

This study investigated heart rate variability (HRV) as a function of RR-interval to assess autonomic function in healthy and ChD subjects.

Methods

Control (n = 20) and ChD (n = 20) groups were studied. All underwent 60-min head-up tilt table test under ECG recording. Histogram of RR-interval series was calculated, with 100 ms class, ranging from 600–1100 ms. In each class, mean RR-intervals (MNN) and root-mean-squared difference (RMSNN) of consecutive normal RR-intervals that suited a particular class were calculated. Average of all RMSNN values in each class was analyzed as function of MNN, in the whole series (RMSNN_T), and in AC (RMSNN_AC) and DC (RMSNN_DC) phases. Slopes of linear regression lines were compared between groups using Student t-test. Correlation coefficients were tested before comparisons. RMSNN was log-transformed. (α < 0.05).

Results

Correlation coefficient was significant in all regressions (p < 0.05). In the control group, RMSNN_T, RMSNN_AC, and RMSNN_DC significantly increased linearly with MNN (p < 0.05). In ChD, only RMSNN_AC showed significant increase as a function of MNN, whereas RMSNN_T and RMSNN_DC did not.

Conclusion

HRV increases in proportion with the RR-interval in healthy subjects. This behavior is lost in ChD, particularly in the DC phase, indicating cardiac vagal incompetence.     

Galectin-3: A Link between Myocardial and Arterial Stiffening in Patients with Acute Decompensated Heart Failure?

Background

Heart failure is accompanied by abnormalities in ventricular-vascular interaction due to increased myocardial and arterial stiffness. Galectin-3 is a recently discovered biomarker that plays an important role in myocardial and vascular fibrosis and heart failure progression.

Objectives

The aim of this study was to determine whether galectin-3 is correlated with arterial stiffening markers and impaired ventricular-arterial coupling in decompensated heart failure patients.

Methods

A total of 79 inpatients with acute decompensated heart failure were evaluated. Serum galectin-3 was determined at baseline, and during admission, transthoracic echocardiography and measurements of vascular indices by Doppler ultrasonography were performed.

Results

Elevated pulse wave velocity and low arterial carotid distensibility are associated with heart failure in patients with preserved ejection fraction (p = 0.04, p = 0.009). Pulse wave velocity, carotid distensibility and Young’s modulus did not correlate with serum galectin-3 levels. Conversely, raised galectin-3 levels correlated with an increased ventricular-arterial coupling ratio (Ea/Elv) p = 0.047, OR = 1.9, 95% CI (1.0‑3.6). Increased galectin-3 levels were associated with lower rates of left ventricular pressure rise in early systole (dp/dt) (p=0.018) and raised pulmonary artery pressure (p = 0.046). High galectin-3 levels (p = 0.038, HR = 3.07) and arterial pulmonary pressure (p = 0.007, HR = 1.06) were found to be independent risk factors for all-cause mortality and readmissions.

Conclusions

This study showed no significant correlation between serum galectin-3 levels and arterial stiffening markers. Instead, high galectin-3 levels predicted impaired ventricular-arterial coupling. Galectin-3 may be predictive of raised pulmonary artery pressures. Elevated galectin-3 levels correlate with severe systolic dysfunction and together with pulmonary hypertension are independent markers of outcome.     

Association of IL28B Polymorphisms With the Response to Peginterferon Plus Ribavirin Combined Therapy in Polish Patients Infected With HCV Genotype 1 and 4

Background

Three single nucleotide polymorphisms (SNPs) near interleukin-28B (IL-28B) gene were shown to be highly associated with treatment response (SVR) in patients with chronic hepatitis C virus (HCV) infection. There is limited data about the role of single and combined IL-28B polymorphisms in HCV-infected Polish population.

Objectives

This study''s aim was to determine predictability of three IL-28B gene polymorphisms and other known prognostic factors on the treatment response in HCV genotype 1 and 4 infected Polish patients. The effect of IL-28B polymorphisms on therapy was also compared with other known prognostic factors.

Patients and Methods

We genotyped IL-28B polymorphisms (rs12979860, rs12980275 and rs8099917) by polymerase chain reaction-based restriction fragment length polymorphism assay in a group of 293 patients from which a selected cohort of 174 treatment-naiev patients underwent treatment.

Results

We showed that rs12979860 CC [odds ratio (OR) = 4.6, P < 0.001], rs12980275 AA (OR = 2.9, P = 0.002) and rs8099917 TT (OR = 2.2, P = 0.016) genotypes were associated with successful treatment compared to the rs12979860 CT-TT, rs12980275 AG-GG and rs8099917 TG-GG, respectively. Patients bearing of IL-28B profile including the three favourable genotypes do not have much chance of a recovery (OR = 3.4, P = 0.002). Except for IL-28B polymorphisms, there was no association of SVR with any other pretreatment clinical data in analyzed group. The correlation of SNPs with other host and viral factors revealed association of favorable genotypes of IL-28B markers with high levels of alanine aminotransferase and baseline HCV viral load.

Conclusions

IL-28B polymorphisms were the strongest pretreatment predictors of response to pegylated interferon and ribavirin in Polish patients chronically infected with HCV genotype 1 and 4. This study confirm the strongest impact of IL-28B rs12979860 on SVR, nevertheless rs12980275 AA seems to be more important than rs8099917 TT in predicting positive treatment response.     

HLA-DPB1 Variant Effect on Hepatitis B Virus Clearance and Liver Cirrhosis Development Among Southwest Chinese Population

Background:

Previous studies have shown that genetic variants in HLA-DP genes affect disease progression in hepatitis B virus (HBV) infection.

Objectives:

We aimed to evaluate possible association between HLA-DPB1 rs9277534 polymorphism and different clinical complications of hepatitis B virus (HBV) infection.

Materials and Methods:

Snapshot assay was used to investigate the association of rs9277534 polymorphism in 342 patients with persistent HBV infection and 342 age and gender-matched HBV spontaneous clearance controls. Patients were categorized into asymptomatic HBV carriers (AsC, n = 104), chronic hepatitis B (CHB, n = 116), and liver cirrhosis (LC, n = 122) subgroups.

Results:

There was a significantly higher proportion of the rs9277534 minor allele A in HBV spontaneous clearance control than that in HBV persistent infection group (OR = 0.58, 95%CI = 0.46-0.73, P < 0.0001). Genotypic analysis showed that GA and AA genotypes were associated with HBV spontaneous clearance (GA: OR = 0.56, 95%CI = 0.40-0.79, P = 0.019; AA: OR = 0.24, 95%CI = 0.14-0.44, P < 0.0001). A significant difference was found between AsC and LC groups in the distribution of AA genotype (OR = 9.32, 95%CI = 1.293-67.14, P = 0.027).

Conclusions:

Variant at rs9277534 could affect both the spontaneous clearance of HBV infection and progression from asymptomatic HBV carriers to HBV-related liver cirrhosis in Southwest Han Chinese population.     

The Impact of IFNL4 rs12979860 Polymorphism on Spontaneous Clearance of Hepatitis C; A Case-Control Study

Background:

About 30% of individuals with hepatitis C virus (HCV) infection are able to clear HCV spontaneously. Differences in host genetics affect the outcome of HCV infection. Single nucleotide polymorphisms (SNPs) of the Interferon lambda (IFNL) genes were associated with spontaneous and treatment-induced clearance of HCV infection.

Objectives:

The aim of this study was to evaluate the association between the IFNL4 rs12979860 SNP and spontaneous clearance of HCV infection in Iranian population.

Materials and Methods:

A case-control study was designed on 91 cases with spontaneous HCV infection clearance and 259 patients with persistent HCV infection as the control group. The rs12979860 SNP was assessed as the most common IFNL polymorphism by PCR-RFLP method.

Results:

Distribution of rs12979860 CC genotype in the spontaneous clearance group was around two folds of its distribution in chronic hepatitis C group (P < 0.001, OR = 4.09, 95% CI = 2.44-6.86).

Conclusions:

The rs12979860 SNP was observed as a strong host genetic factor associated with spontaneous clearance of hepatitis C infection.     

Aortic Counterpulsation Therapy in Patients with Advanced Heart Failure: Analysis of the TBRIDGE Registry

Background

The use of aortic counterpulsation therapy in advanced heart failure is controversial.

Objectives

To evaluate the hemodynamic and metabolic effects of intra-aortic balloon pump (IABP) and its impact on 30-day mortality in patients with heart failure.

Methods

Historical prospective, unicentric study to evaluate all patients treated with IABP betwen August/2008 and July/2013, included in an institutional registry named TBRIDGE (The Brazilian Registry of Intra-aortic balloon pump in Decompensated heart failure - Global Evaluation). We analyzed changes in oxygen central venous saturation (ScvO₂), arterial lactate, and use of vasoactive drugs at 48 hours after IABP insertion. The 30-day mortality was estimated by the Kaplan-Meier method and diferences in subgroups were evaluated by the Log-rank test.

Results

A total of 223 patients (mean age 49 ± 14 years) were included. Mean left ventricle ejection fraction was 24 ± 10%, and 30% of patients had Chagas disease. Compared with pre-IABP insertion, we observed an increase in ScvO₂ (50.5% vs. 65.5%, p < 0.001) and use of nitroprusside (33.6% vs. 47.5%, p < 0.001), and a decrease in lactate levels (31.4 vs. 16.7 mg/dL, p < 0.001) and use of vasopressors (36.3% vs. 25.6%, p = 0.003) after IABP insertion. Thirty-day survival was 69%, with lower mortality in Chagas disease patients compared without the disease (p = 0.008).

Conclusion

After 48 hours of use, IABP promoted changes in the use of vasoactive drugs, improved tissue perfusion. Chagas etiology was associated with lower 30-day mortality. Aortic counterpulsation therapy is an effective method of circulatory support for patients waiting for heart transplantation.     

Correlation Between Patatin-Like Phospholipase Domain-Containing Protein 3 Gene Polymorphisms and Liver Cirrhosis in a Chinese Han Population With Chronic Hepatitis B

Background:

A single nucleotide polymorphism (SNP) of patatin-like phospholipase domain-containing 3 (PNPLA3) genes (rs738409) is associated with the severity of fibrosis and cirrhosis in patients with fatty liver disease. However, in a small group of Italian patients, there was no significant correlation between the rs738409 SNP and hepatitis B virus (HBV) infection-associated liver cirrhosis.

Objectives:

This study aimed to investigate whether PNPLA3 polymorphisms are a risk factor for liver cirrhosis in a Chinese Han population with chronic hepatitis B (CHB).

Patients and Methods:

The study population consisted of 344 Chinese Han patients with CHB, among which 203 presented with liver cirrhosis (LC group) and 141 had no sign of liver cirrhosis (CHB group). TaqMan genotyping assay was used to investigate the association of two PNPLA3 SNPs (rs738409 and rs2281135) with the risk of liver cirrhosis.

Results:

The allele and genotype distributions of PNPLA3 rs738409 and rs2281135 were not significantly different between the CHB and LC groups. After segregation on the basis of sex, no significant correlation between PNPLA3 (rs738409 and rs2281135) genotypes/alleles and liver cirrhosis was detected. Moreover, none of the haplotypes in PNPLA3 (rs738409 and rs2281135) was found to be statistically different between the two groups.

Conclusions:

Our results showed no association between PNPLA3 polymorphisms (rs738409 and rs2281135) and the susceptibility to HBV-related liver cirrhosis in a Chinese Han population.     

Effects of Exercise Training on Heart Rate Variability in Chagas Heart Disease

Background:

Heart rate variability (HRV) is a marker of autonomic dysfunction severity. The effects of physical training on HRV indexes in Chagas heart disease (CHD) are not well established.

Objective:

To evaluate the changes in HRV indexes in response to physical training in CHD.

Methods:

Patients with CHD and left ventricular (LV) dysfunction, physically inactive, were randomized either to the intervention (IG, N = 18) or control group (CG, N = 19). The IG participated in a 12-week exercise program consisting of 3 sessions/week.

Results:

Mean age was 49.5 ± 8 years, 59% males, mean LVEF was 36.3 ± 7.8%. Baseline HRV indexes were similar between groups. From baseline to follow-up, total power (TP): 1653 (IQ 625 - 3418) to 2794 (1617 - 4452) ms, p = 0.02) and very low frequency power: 586 (290 - 1565) to 815 (610 - 1425) ms, p = 0.047) increased in the IG, but not in the CG. The delta (post - pre) HRV indexes were similar: SDNN 11.5 ± 30.0 vs. 3.7 ± 25.1 ms. p = 0.10; rMSSD 2 (6 - 17) vs. 1 (21 - 9) ms. p = 0.43; TP 943 (731 - 3130) vs. 1780 (921 - 2743) Hz. p = 0.46; low frequency power (LFP) 1.0 (150 - 197) vs. 60 (111 - 146) Hz. p = 0.85; except for high frequency power, which tended to increase in the IG: 42 (133 - 92) vs. 79 (61 - 328) Hz. p = 0.08).

Conclusion:

In the studied population, the variation of HRV indexes was similar between the active and inactive groups. Clinical improvement with physical activity seems to be independent from autonomic dysfunction markers in CHD.     

Single nucleotide polymorphisms of the IL28B and sustained virologic response of patients with chronic hepatitis C to PEG-interferon/ribavirin therapy: A meta-analysis: Meta-analysis of IL28B

Background

Hepatitis C is a global health problem and represents a major cause of liver disease and socioeconomic burden. Effective antiviral therapy may prevent these complications, but the current treatment for patients with chronic hepatitis C virus (HCV) infection does not produce sustained virologic response. Therefore, identification of the determinants of response to treatment is a high priority. A number of host and viral factors have been associated with treatment outcomes.

Objectives

To assess the associations of single nucleotide polymorphisms (SNP) of the IL28B and sustained virologic response (SVR) of patients with chronic hepatitis C to PEG-interferon/ribavirin therapy.

Materials and Methods

We searched PubMed, Medline and Cochrane Library, and found 7 eligible papers involved in this study. Then we performed a meta-analysis comparing the SVR rate at SNP of the IL28B in individuals with PEG-interferon/ribavirin therapy. Meanwhile, the SVR rate between different races and HCV genotypes was studied.

Results

The sustained virologic response rate was higher in patients with the rs12979860 CC and rs8099917 TT alleles in the IL28B SNP, comparing with the rs12979860 CT, or TT and rs8099917 TG or GG. Furthermore, a higher SVR was observed in the Caucasians than in Afro-Americans (OR = 3.85, 95% CI: 3.06-4.83); the percentage of rs12979860 TT genotype was lower in Caucasians (OR = 0.25, 95% CI: 0.20-0.31) and the percentage of rs12979860 CC genotype was higher in Caucasians than that of Afro-Americans (OR = 3.45, 95% CI = 2.68-4.44). Between different HCV genotypes, the SVR was much lower in those with HCV genotype 1 than those with genotype 2/3 (OR = 0.16, 95% CI: 0.11-0.24).

Conclusions

IL28B is significantly associated with response to PEG-interferon/ribavirin therapy of patients with chronic HCV infection. Both the rs12979860 and rs8099917 alleles could be used as independent predictors of the treatment response. The rs12979860 allele in particular, is more important from our study. The polymorphism even explains part the difference in response rate between different ethnic groups and HCV genotypes.     

Relationship between Fibrosis and Ventricular Arrhythmias in Chagas Heart Disease Without Ventricular Dysfunction

Background

Patients with Chagas disease and segmental wall motion abnormality (SWMA) have worse prognosis independent of left ventricular ejection fraction (LVEF). Cardiac magnetic resonance (CMR) is currently the best method to detect SWMA and to assess fibrosis.

Objective

To quantify fibrosis by using late gadolinium enhancement CMR in patients with Chagas disease and preserved or minimally impaired ventricular function (> 45%), and to detect patterns of dependence between fibrosis, SWMA and LVEF in the presence of ventricular arrhythmia.

Methods

Electrocardiogram, treadmill exercise test, Holter and CMR were carried out in 61 patients, who were divided into three groups as follows: (1) normal electrocardiogram and CMR without SWMA; (2) abnormal electrocardiogram and CMR without SWMA; (3) CMR with SWMA independently of electrocardiogram.

Results

The number of patients with ventricular arrhythmia in relation to the total of patients, the percentage of fibrosis, and the LVEF were, respectively: Group 1, 4/26, 0.74% and 74.34%; Group 2, 4/16, 3.96% and 68.5%; and Group 3, 11/19, 14.07% and 55.59%. Ventricular arrhythmia was found in 31.1% of the patients. Those with and without ventricular arrhythmia had mean LVEF of 59.87% and 70.18%, respectively, and fibrosis percentage of 11.03% and 3.01%, respectively. Of the variables SWMA, groups, age, LVEF and fibrosis, only the latter was significant for the presence of ventricular arrhythmia, with a cutoff point of 11.78% for fibrosis mass (p < 0.001).

Conclusion

Even in patients with Chagas disease and preserved or minimally impaired ventricular function, electrical instability can be present. Regarding the presence of ventricular arrhythmia, fibrosis is the most important variable, its amount being proportional to the complexity of the groups.     

Predictors of Conversion from Radial Into Femoral Access in Cardiac Catheterization

Background

Fewer bleeding complications and early ambulation make radial access a privileged route for cardiac catheterization. However, transradial (TR) approach is not always successful, requiring its conversion into femoral access.

Objectives

To evaluate the rate of conversion from radial into femoral access in cardiac catheterization and to identify its predictors.

Methods

Prospective dual-center registry, including 7632 consecutive patients undergoing catheterization via the radial access between Jan/2009 and Oct/2012. We evaluated the incidence of conversion into femoral access and its predictors by logistic regression analysis.

Results

The patients’ mean age was 66 ± 11 years, and 32% were women. A total of 2969 procedures (38.4%) were percutaneous coronary interventions (PCI), and the most used first intention arterial access was the right radial artery (97.6%). Radial access failure rate was 5.8%. Independent predictors of conversion from radial into femoral access were the use of short introducer sheaths (OR 3.047, CI: 2.380-3.902; p < 0.001), PCI (OR 1.729, CI: 1.375-2.173; p < 0.001), female sex (OR 1.569, CI: 1.234-1.996; p < 0.001), multivessel disease (OR 1.457, CI: 1.167-1.819; p = 0.001), body surface area (BSA) ≤ 1.938 (OR 1.448, CI: 1.120-1.871; p = 0.005) and age > 66 years (OR 1.354, CI: 1.088-1.684; p = 0.007).

Conclusion

Transradial approach for cardiac catheterization has a high success rate and the need for its conversion into femoral access in this cohort was low. Female sex, older age, smaller BSA, the use of short introducer sheaths, multivessel disease and PCI were independent predictors of conversion into femoral access.