Ala12Ala genotype of the peroxisome proliferator-activated receptor gamma2 protects against atherosclerosis

A mutation in the peroxisome proliferator-activated receptor gamma2 (PPARgamma2) gene with a cytosine to guanine substitution results in an exchange of proline (Pro) with alanine (Ala) in exon B (codon 12) of this gene. This polymorphism has been associated with high insulin sensitivity and low body weight, but no data have been published to date about its effect on early atherosclerosis. We investigated the relationship of the Pro(12)Ala polymorphism to early atherosclerosis, measured by the intima-media thickness (IMT). A total of 622 subjects were included, aged 40-70 yr, who were participants of the RIAD (Risk factors in Impaired glucose tolerance for Atherosclerosis and Diabetes) study and were at risk of developing type 2 diabetes. Altogether, 449 of the subjects had the common genotype (Pro(12)Pro), 162 had the Pro(12)Ala genotype, and 11 the Ala(12)Ala genotype. IMT was significantly decreased in subjects with the Ala(12)Ala genotype compared with subjects with the other two genotypes. Body mass index, free fatty acid levels, and leukocyte count were lower in subjects with the Ala(12)Ala genotype compared with subjects with the Pro(12)Pro or Pro(12)Ala genotypes. In multivariate analysis, the Ala(12)Ala genotype was a significant independent determinant of IMT. Furthermore, we demonstrated specific expression of the PPARgamma2 gene in human atherosclerotic lesions as well as in cultured primary macrophages and foam cells. In conclusion, our data suggest that the Ala(12)Ala genotype of the PPARgamma2 gene may protect from early atherosclerosis in subjects at risk for diabetes.     

Oxygen uptake efficiency slope, a new submaximal parameter in evaluating exercise capacity in chronic heart failure patients

Background

The oxygen uptake efficiency slope (OUES) is a new submaximal parameter which objectively predicts the maximal exercise capacity in children and healthy subjects. However, the usefulness of OUES in adult patients with and without advanced heart failure remains undetermined. The present study investigates the stability and the usefulness of OUES in adult cardiac patients with and without heart failure.

Methods

Forty-five patients with advanced heart failure (group A) and 35 patients with ischemic heart disease but normal left ventricular ejection fraction (group B) performed a maximal exercise test. PeakVO₂ and percentage of predicted peakVO₂ were markers of maximal exercise capacity, whereas OUES, ventilatory anaerobic threshold (VAT), and slope VE/VCO₂ were calculated as parameters of submaximal exercise.

Results

Group A patients had lower peakVO₂ (P < .001), lower percentage of predicted peakVO₂ (P = .001), lower VAT (P < .05), steeper slope VE/VCO₂ (P < .001), and lower OUES (P < .02). Within group A, significant differences were found for VAT, slope VE/VCO₂, and OUES (all P < .01) between patients with peakVO₂ above and below 14 mL O₂/kg/min. Of all the submaximal parameters, VAT correlated best with peakVO₂ (r =.814, P < .01) followed by OUES/kg (r = .781, P < .01), and slope VE/VCO₂ (r = −.492, P < .001). However, VAT could not be determined in 18 (23%) patients.

Conclusions

OUES remains stable over the entire exercise duration and is significantly correlated with peakVO₂ in adult cardiac patients with and without impaired LVEF. Therefore, OUES could be helpful to assess exercise performance in advanced heart failure patients unable to perform a maximal exercise test. Further studies are needed to confirm our hypothesis.     

Gastrointestinal tuberculosis: 17 cases collected in 4 hospitals in the northeastern suburb of Paris

Gastrointestinal tuberculosis is a rare form of extrapulmonary tuberculosis and its diagnosis can be difficult. AIMS: To analyze the diagnostic and therapeutic characteristics of gastrointestinal tuberculosis. METHODS: Retrospective study from 17 cases collected in 4 hospitals in Seine Saint-Denis between 1987 and 2002. RESULTS: Seventeen cases and 19 localizations were collected: small intestine (N = 7), ileocecum (N = 6), colon (N = 4) and gastroduodenum (N = 2). Two patients had two localizations. Mean age was 43.9 years. Subjects from immigrant populations (76.5%) were preferentially affected. Twenty-three percent of patients (13 tested) were infected by human immunodeficiency virus. Weight-loss and general weakness (88%), abdominal pain (88%), fever (59%), nausea/vomiting (53%) were the predominant symptoms. The delay in diagnosis was 82 days (range: 7-180) and time before specific treatment 31.6 days (range: 7-90). Histological evidence of caseating granuloma was found in six patients. Mycobacterium tuberculosis was detected in six. Digestive imaging was abnormal in 15 patients. Mesenteric lymph nodes were the most common associated site of tuberculosis (N = 8, 47%). Mean duration of treatment was 8.2 months (range: 6-12). Thirteen patients were cured, three died and one was lost to follow up. CONCLUSION: Gastrointestinal tuberculosis is not an uncommon diagnosis in the north-eastern Parisian area, especially among immigrant populations and immunodeficient patients. The most frequent localizations are the small intestine and ileocecum. Diagnosis can be made by pathology and/or bacteriology on endoscopic and/or surgical biopsy samples.     

Myocardial contractility is early affected in systemic sclerosis: a tissue Doppler echocardiography study.

AIMS: Systemic sclerosis (SSc) is a connective tissue disorder characterized by frequent myocardial involvement. Alteration in left ventricular (LV) function is reported to be rare; however, it may be underestimated by conventional measurements. Our aim was to prospectively investigate LV function in SSc patients, using Tissue Doppler echocardiography (TDE), a modern and accurate method of assessing myocardial function. METHODS AND RESULTS: Seventeen consecutive SSc patients with normal cardiac examination, pulmonary artery pressure (PAP) and radionuclide LV ejection fraction (EF) were prospectively investigated. Myocardial perfusion was investigated using single-photon-emission computerized tomography (SPECT). Echocardiography (ECHO), systolic and diastolic strain-rate (SR) measured in the posterior wall by TDE were used to investigate myocardial function, and compared with results of 15 matched controls. All patients (53+/-8 years; 14 women; systolic PAP 33+/-6 mmHg; LVEF 67+/-8%) had myocardial SPECT perfusion abnormalities. Despite normal ECHO, they had lower systolic SR than controls (1.7+/-0.5 versus 3.8+/-1.7 cm-1, p<0.0001), and lower diastolic SR (3.7+/-1.5 versus 5.6+/-1.2 cm-1, p=0.0004). Ten SSc patients had reduced systolic SR<1.7 cm-1 and 11 reduced diastolic SR<3.5 cm-1. CONCLUSION: Frequent abnormal myocardial perfusion is confirmed in SSc patients. Reduced contractility is also frequent as detected by TDE, despite normal radionuclide LVEF.     

Sexually transmitted acute infection with a clustered genotype 4 hepatitis C virus in HIV-1-infected men and inefficacy of early antiviral therapy

BACKGROUND: Recent studies have suggested an increased risk of acute hepatitis C (HCV) infection in homosexual HIV-infected men and that early treatment with standard or pegylated interferon-alfa, alone or associated with ribavirin, significantly reduces the risk of chronic evolution in HIV-infected patients. METHODS: A retrospective analysis of 12 HIV-infected patients who were consecutively diagnosed as developing acute HCV infection, defined by both seroconversion of anti-HCV antibodies and detection of serum HCV RNA in those with previous negative results. Ten of these patients received early antiviral treatment with standard or pegylated interferon-alfa, alone or associated with ribavirin. RESULTS: The only risk factor in these patients was unprotected sexual intercourse with men. Acute HCV infection was asymptomatic in 10 patients, and the HCV genotype was 4d in 10 patients. The 10 genotype 4d viruses formed a monophylogenetic group and clustered separately from other local sequences of HCV genotype 4d, suggesting a common source of infection. None of the 10 patients who were treated early with antiviral therapy had a sustained virological response, as defined by undetectable HCV RNA 6 months after therapy. CONCLUSIONS: There is a risk of sexual transmission of HCV in HIV-infected men who have sex with men; the cluster of HCV genotype 4d suggested a common source of infection and a failure in prevention counselling. Early treatment with standard interferon-alfa failed to prevent chronic evolution of HCV infection in this particular group of HIV-infected patients who had acquired this peculiar cluster of genotype 4 strains.     

Biventricular stimulation to prevent cardiac desynchronization: rationale, design, and endpoints of the 'Biventricular Pacing for Atrioventricular Block to Prevent Cardiac Desynchronization (BioPace)' study.

Despite the deleterious effects of cardiac dyssynchrony and the positive effects of cardiac resynchronization therapy, patients with high-degree atrioventricular block continue to receive desynchronizing right ventricular (RV) pacing systems. Although it is unclear whether the negative effects of RV pacing and left bundle branch block (LBBB) are comparable, and whether they depend on the presence and the degree of structural heart disease, one may hypothesize that RV pacing may have similar effects to LBBB. In the BioPace trial, the long-term effects of RV pacing vs. biventricular pacing will be prospectively compared in 1200 pacemaker patients with high likelihood of mostly paced ventricular events, regardless of whether in sinus rhythm or in atrial fibrillation (AF). After echocardiographic examination of left ventricular (LV) function, patients will be randomly assigned to the implantation of an RV vs. a biventricular pacing system and followed for up to 5 years. Primary study endpoints are survival, quality of life (QoL), and the distance covered in a 6-min hall walk (6-MHW) at 24 months after implantation. Secondary endpoints are QoL and the 6-MHW result at 12 months after implantation, hospitalization rate, LV dimensions, LV ejection fraction, and the development of chronic AF and other adverse events.     

Left Ventricular Rapid Pacing Via the Valve Delivery Guidewire in Transcatheter Aortic Valve Replacement

ObjectivesThis study investigated whether left ventricular (LV) stimulation via a guidewire-reduced procedure duration while maintaining efficacy and safety compared with standard right ventricular (RV) stimulation.BackgroundRapid ventricular pacing is necessary to ensure cardiac standstill during transcatheter aortic valve replacement (TAVR).MethodsThis is a prospective, multicenter, single-blinded, superiority, randomized controlled trial. Patients undergoing transfemoral TAVR with a SAPIEN valve (Edwards Lifesciences, Irvine, California) were allocated to LV or RV stimulation. The primary endpoint was procedure duration. Secondary endpoints included efficacy, safety, and cost at 30 days.ResultsBetween May 2017 and May 2018, 307 patients were randomized, but 4 were excluded because they did not receive the intended treatment: 303 patients were analyzed in the LV (n = 151) or RV (n = 152) stimulation groups. Mean procedure duration was significantly shorter in the LV stimulation group (48.4 ± 16.9 min vs. 55.6 ± 26.9 min; p = 0.0013), with a difference of –0.12 (95% confidence interval: –0.20 to –0.05) in the log-transformed procedure duration (p = 0.0012). Effective stimulation was similar in the LV and RV stimulation groups: 124 (84.9%) versus 128 (87.1%) (p = 0.60). Safety of stimulation was also similar in the LV and RV stimulation groups: procedural success occurred in 151 (100%) versus 151 (99.3%) patients (p = 0.99); 30-day MACE-TAVR (major adverse cardiovascular event-transcatheter aortic valve replacement) occurred in 21 (13.9%) versus 26 (17.1%) patients (p = 0.44); fluoroscopy time (min) was lower in the LV stimulation group (13.48 ± 5.98 vs. 14.60 ± 5.59; p = 0.02), as was cost (€18,807 ± 1,318 vs. €19,437 ± 2,318; p = 0.001).ConclusionsCompared with RV stimulation, LV stimulation during TAVR was associated with significantly reduced procedure duration, fluoroscopy time, and cost, with similar efficacy and safety. (Direct Left Ventricular Rapid Pacing Via the Valve Delivery Guide-wire in TAVR [EASY TAVI]; NCT02781896)