Dunnigan lipodystrophy syndrome: French National Diagnosis and Care Protocol (PNDS; Protocole National de Diagnostic et de Soins).

Dunnigan syndrome, or Familial Partial Lipodystrophy type 2 (FPLD2; ORPHA 2348), is a rare autosomal dominant disorder due to pathogenic variants of the LMNA gene. The objective of the French National Diagnosis and Care Protocol (PNDS; Protocole National de Diagnostic et de Soins), is to provide health professionals with a guide to optimal management and care of patients with FPLD2, based on a critical literature review and multidisciplinary expert consensus. The PNDS, written by members of the French National Reference Center for Rare Diseases of Insulin Secretion and Insulin Sensitivity (PRISIS), is available on the French Health Authority website (in French). Dunnigan syndrome is characterized by a partial atrophy of the subcutaneous adipose tissue and by an insulin resistance syndrome, associated with a risk of metabolic, cardiovascular and muscular complications. Its prevalence, assessed at 1/100.000 in Europe, is probably considerably underestimated. Thorough clinical examination is key to diagnosis. Biochemical testing frequently shows hyperinsulinemia, abnormal glucose tolerance and hypertriglyceridemia. Elevated hepatic transaminases (hepatic steatosis) and creatine phosphokinase, and hyperandrogenism in women, are common. Molecular analysis of the LMNA gene confirms diagnosis and allows for family investigations. Regular screening and multidisciplinary monitoring of the associated complications are necessary. Diabetes frequently develops from puberty onwards. Hypertriglyceridemia may lead to acute pancreatitis. Early atherosclerosis and cardiomyopathy should be monitored. In women, polycystic ovary syndrome is common. Overall, the management of patients with Dunnigan syndrome requires the collaboration of several health care providers. The attending physician, in conjunction with the national care network, will ensure that the patient receives optimal care through regular follow-up and screening. The various elements of this PNDS are described to provide such a support.

Comparison of HIV-Infected and Noninfected Patients Undergoing Bariatric Surgery: The ObeVIH Study.

OBJECTIVE: The aim of this study was to compare clinical characteristics and adipose/liver tissue histology analysis in HIV-infected and HIV-uninfected subjects undergoing bariatric surgery. DESIGN: This was a cross-sectional study of HIV-infected subjects undergoing single-port sleeve gastrectomy with prospective enrolment and frequency age (±5 years), sex, and body mass index (BMI, ± 5 kg/m2) matched on HIV-uninfected subjects. METHODS: This study was conducted at a single clinical site at Pitié-Salpêtrière hospital-Paris-France comprising 19 HIV-uninfected and 21 HIV-infected subjects with plasma VL < 20 copies/mL, all with a BMI > 40 kg/m2 or >35 kg/m2 with comorbidities. Histology of subcutaneous and visceral abdominal adipose tissue (SCAT/VAT) and liver biopsies was collected during single-port sleeve gastrectomy. Outcomes included anthropometric characteristics, comorbidities, cardiovascular parameters, adipose tissue, and liver histology. RESULTS: The age of HIV-infected participants was (median, interquartile range IQR) 48 y (42-51), with 76.2% females, a BMI of 41.4 kg/m2 (37.3-44.4), an antiretroviral duration of 16 y (8-21), current integrase strand transfer inhibitor (INSTI)-based regimen in 15 participants and non-INSTI regimen in 6 participants, and a CD4 count of 864/mm3 (560-1066). The age of controls was 43 y (37-51), with 78.9% females and a BMI of 39.2 kg/m2 (36.3-42.6). Anthropometric characteristics, comorbidities, and cardiovascular parameters did not differ according to HIV status and INSTI treatment. The number of macrophage crown-like structures in SCAT was lower in INSTI-treated participants than in HIV-uninfected participants (P = 0.02) and non-INSTI-treated HIV-infected subjects (P = 0.07). Hepatic steatosis and liver disease severity global score were lower in INSTI-treated participants than in non-INSTI-treated HIV-infected participants (P = 0.05 and P = 0.04, respectively). CONCLUSIONS: HIV-infected and HIV-uninfected subjects undergoing bariatric surgery presented a similar profile regarding anthropometric measures, cardiovascular parameters, and comorbidities. However, INSTI-treated participants presented milder SCAT and liver alterations than non-INSTI-treated participants.

[Management of the cardiovascular complications of treatment in thoracic oncology]. / Prise en charge des complications cardiovasculaires des traitements en oncologie thoracique.

The management of patients suffering from bronchial and lung tumors depends on conventional chemotherapy and/or targeted molecular therapies. The prescription of these chemotherapies may be accompanied by cardiovascular complications, principally congestive heart failure, arterial hypertension and arterial or venous thrombo-embolism, the frequency of which varies with the molecule administered. The management of these complications is currently poorly standardized and should take account of the patient's oncological prognosis.

Effects of HIV protease inhibitors on cardiac conduction velocity in unselected HIV-infected patients.

We examined the prevalence and the extent of prolongation of the PR and QRS intervals and their relation to anti-HIV treatments and other clinical characteristics in 970 HIV-infected patients, 749 treated with antiretroviral therapy and 221 untreated. Age, body mass index, heart rate, and treatment with ß-blockers and HIV protease inhibitors (PIs) were independent predictors of increase in the duration of the PR interval. Male gender, Caucasian ethnicity, heart rate, duration of antiretroviral therapy, and use of PIs were independent predictors of an increase in the duration of the QRS interval. Users of HIV PIs had an adjusted QRS-interval duration that was 2.6 ms (95% confidence interval (CI) 1.4-3.9) longer than the interval in nonusers (P = 0.0004). The adjusted odds ratios of first-degree atrioventricular block (n = 54) and complete bundle branch block (n = 23) were 1.62 (95% CI 0.90-2.89; P = 0.10) and 2.71 (95% CI 1.10-7.13; P = 0.03), respectively, in patients taking PIs. These findings may have important clinical implications, particularly with respect to QRS prolongation in patients with myocardial ischemia or heart failure.

How to improve the quality of a disease management program for HIV-infected patients using a computerized data system. The Saint-Antoine Orchestra program.

OBJECTIVES: The emergence of non-AIDS-related events in the HIV-infected population experiencing a longer life expectancy implies the implementation of a comprehensive approach of HIV clinical management through better access to care, prevention, and early diagnosis of co-morbidities. METHODS: The Orchestra program is a computer-assisted HIV care and support tool implemented since December 2004 in the outpatient clinic of a University Hospital set in Paris, France. The intervention aims at improving access to HIV information care and support specifically targeted five areas of actions: cardiovascular risk factors; gynecological follow-up; anti-hepatitis B virus (HBV) vaccine coverage; sexuality and prevention of sexually transmitted infections; and compliance to antiretrovirals. The impact of this program was examined prospectively on a "before-after" basis after a two-year implementation. RESULTS: In the two-year period, 1717 patients were regularly followed. The level of the database information significantly increased in time (low density lipoprotein (LDL) cholesterol and glycemia were informed in 74% of patients at inclusion versus 95% at two years, and 83% versus 97%, p < 0.001, respectively). The number of targeted interventions was also higher. For eligible women, papanicolaou smears and mammography were prescribed in 52% of cases after intervention, versus 44% at inclusion, p0.04 and 83% versus 50%, p < 0.001, respectively. Indicators of care eventually improved significantly. Initially 72% non-adherent patients declared to be adherent after the intervention ( p < 0.001) and 67% of patients with initial LDL-hypercholesterolemia normalized their LDL level within two years ( p < 0.001). CONCLUSION: The Orchestra program has provided a unique opportunity to assess and improve prevention and management of co-morbidities in HIV patients.

[Focus on managing AF and preventing stroke]. / Mise au point sur la prise en charge de la FA et prévention des AVC.

Guidelines published from the European Society of Cardiology/American Heart Association, and from the American College of Chest Physicians, clarified the strategy of antithrombotic treatment in AF, which is based on the presence of risk factors for thromboembolism. The European guidelines have been updated in 2010 and differ from the ACCP guidelines. They integrated the CHA(2)DS(2)Vasc score and modified accordingly the previous recommendations based on the CHADS(2)score, which allows physicians to classify patients as at low, moderate or high risk, according to their individual risk characteristics. Recently published registries confirm under-prescription of VKA treatment in the 'real world', even in patients at high thromboembolic risk, and over-prescription for at least one-third of patients at low risk. Therefore reducing the risk of thromboembolism should be the physicians'primary aim, particularly with the advent of alternative treatments and the development of new antithrombotic drugs such as oral thrombin and factor Xa inhibitors, which are currently being evaluated in clinical trials.

Coronary artery bypass graft in HIV-infected patients: a multicenter case control study.

Coronary artery disease (CAD) is an emerging complication in HIV-infected patients treated with highly active antiretroviral therapy. Immediate results and long-term outcome after coronary artery bypass graft (CABG) have not been yet evaluated in this population. Between January 1997 and December 2005, we compared baseline characteristics, immediate results and clinical outcome [Major Adverse Cardiac Events (MACE): death for cardiac cause, myocardial infarction (MI), coronary revascularization] at 41 months in 27 consecutive HIV-infected (HIV+) patients and 54 HIV-uninfected (HIV-) controls matched for age and gender (mean age of the cohort, 49+/-8 years; 96% male) who underwent CABG. Cardiovascular risk factors were well-balanced and nearly identical in both groups. In HIV+ group, mean preoperative CD4 was 502+/-192/mm(3) compared with 426.2+/-152.6/mm(3) postoperatively (p=0.004) without clinical manifestations at follow-up. At 30-day, the rate of post-operative death, MI, stroke, mediastinitis, re-intervention was identical in both groups. At follow-up [median: 41-months (range: 34-60)], rate of occurrence of 1(st) MACE was higher in HIV+ group compared with HIV- group (11, 42% versus 13, 25%, p=0.03), mostly due to the need of repeated revascularization using percutaneous coronary intervention of the native coronary arteries but not of the grafts in the HIV+ group [9 (35%) versus 6 (11%), p=0.02]. CABG is a feasible and safe revascularization procedure in HIV+ patients with multivessel CAD. Immediate postoperative outcome was similar compared to controls. However, long-term follow-up was significantly different, due to an increased rate of repeated revascularization procedure in the native coronary arteries of HIV+ patients.

[Early diagnosis and prevention of comorbidities among HIV-infected patients: the Orchestra Saint-Antoine Program]. / Dépistage et prévention des comorbidités chez les patients infectés par le VIH: le programme Orchestra Saint-Antoine.

OBJECTIVES: The Saint-Antoine Orchestra Program aims at improving the clinical management of HIV-infected patients through access to care, prevention and early diagnosis of comorbidities. METHODS: The program was initiated in December 2004 on the whole database. The following topics were concerned: cardiovascular risk factors, gynecological follow-up, anti-HBV vaccinal coverage, sexuality and prevention of STIs, therapeutic adherence and counsels to travelers. The program included several actions: diffusion of information to patients, development of a computerized chart (alert pop-ups), individualized prescription advice and recommendations for specialist referral. RESULTS: The program was applied to 1959 patients whose initial characteristics were: mean age: 43+/-10 years; ratio M/W: 1466/493; European origin: 69%; sub-Saharan: 19%; mean duration of HIV infection: 9.3+/-6 years; naïve of antiretrovirals: 14%; mean CD4+count: 494+/-277/mm(3); HIV viral load inferior to 50 cp/ml: 62%. Among 1347 patients for whom cardiovascular risk factors were completely informed, 42% had two or more factors. In particular, 31% of them were smokers, 7% had an arterial pressure superior to 140/90 mmHg and 11% had LDL-cholesterolemia superior to 4.1 mmol/l. Among 1448 untreated patients, 70% were initially considered as adherent. Half of the concerned women had neither cervical smear nor mammography up to date. Among 67% patients with an informed complete HBV serology, 27% were seronegative among which 310 (86%) were eligible for the vaccine. Problems of sexual difficulties or prevention were initially discussed for 11% of patients. Among them, 14% had a problem of prevention and 148 (66%) recognized sexual difficulties. CONCLUSION: The initiation of the Saint-Antoine Orchestra program has provided a unique opportunity to assess and improve the prevention and management of comorbidities in HIV patients. Also, this program aimed to improve professional practices.

Role of drug eluting stents in diabetic patients.

There is a clear need for a large multicentre trial comparing the efficacy of the two available drug eluting stents, sirolimus and paclitaxel, in diabetic patients with multivessel disease.

[Low molecular weight heparin and non valvular atrial fibrillation]. / Héparines de bas poids moléculaire et fibrillation auriculaire non valvulaire.

Low molecular weight heparin (LMWH) are obtained through chemical or enzyme depolymerisation of unfractioned heparins (UFH). LMWHs present several advantages over UFH: they exhibit a smaller interindividual variability of the anticoagulant effect, they have a greater bioavailability, a longer plasma half-life and do not require monitoring of the anticoagulant effect. LMWH have restrictive indications in AF patients, cardioversion (II level C and TEE for ACC/AHA/ESC and 2C for ACCP guidelines) or use as a bridge therapy (IIB, level C for ACC/AHA/ESC). The ACE study (Anticoagulation for cardioversion using enoxaparin), showed a reduction, though not statistically significant, of 42% of the composite end point (embolic event, major bleeding and death) 2.8% under enoxaparin vs. 4.8 % under conventional treatment, relative risk 0.58, CI 95% 0.23-1.46). Other studies, using dalteparin, confirmed that an anticoagulant treatment using LMWH followed by warfarin was at least as good as conventional management. ACUTE II (Assessment of cardioversion using transesophageal echochardiography), a randomized multicenter trial, compared the efficacy and tolerance of enoxaparin (1 mg/kg every 12 hours) and UFH in 155 patients eligible for a TEE-guided cardioversion. These patients were administered LMWH or UFH for 24 hours before TEE or cardioversion. There were no significative differences regarding the incidence of the study end points, in particular stroke and bleeding, and no death occurred. HAEST (Heparin in acute embolic stroke trial), a randomized, placebo-controlled, double blind trial failed to show the LMWH superiority over aspirin in patients with acute ischemic stroke and atrial fibrillation. Finally, LMWH have been proposed as a bridge therapy in patients under chronic VKA prior to surgery or invasive procedures. This strategy resulted in a low rate of thromboembolic events and major bleedings.

[Acute pulmonary edema during preterm labor: role of nicardipine tocolysis (three cases)]. / OEdème pulmonaire aigu lors d'une menace d'accouchement prématuré: rôle de la tocolyse par la nicardipine: à propos de 3 observations.

Beta adrenergic agonists are still used as first line treatment for preterm labor in many institutions, but their side effects lead to use alternative tocolytic drugs such as calcium channel blockers. We report three cases of pulmonary edema during preterm labor associated with the use of calcium channel blocker, intravenous nicardipine, widely used for tocolysis in France. In this article, potential mechanisms of this severe complication are briefly discussed: pregnancy-induced overload, deleterious hemodynamic effects of calcium channel blockers, concomitant administration of calcium channel blockers and/or beta-agonists and finally concomitant administration of physiological saline and/or glucocorticoids. Based on our experience, we recommend avoiding the association of calcium channel blockers and beta-agonists for preterm labor. Nicardipine, if used, should be administered at an adjusted dose with electric syringe to reduce volume infusion.

[Preventing cerebrovascular accidents during atrial fibrillation]. / Prévention des accidents vasculaires cérébraux dans la fibrillation auriculaire.

Atrial fibrillation, the most commonly encountered arrhythmia in clinical practice, is associated with substantial morbidity and mortality. Its incidence and prevalence are increasing, and it represents a growing clinical and economic burden. Recent research has highlighted new approaches to both pharmacological and non-pharmacological management. Pooled data from trials comparing antithrombotic treatment with placebo show that warfarin reduces the risk of stroke by 62% and that aspirin alone reduces the risk by 22%. Overall, in high-risk patients, warfarin was better than aspirin in preventing strokes, with a relative risk reduction of 36%, but the risk of major hemorrhage with warfarin was twice that with aspirin. Anticoagulation treatment needs to be tailored individually for patients on the basis of age, comorbidities, and contraindications. However, warfarin remains under-prescribed in clinical practice, for reasons related to patients (comorbidities) and physicians. The limitations of warfarin treatment have prompted the development of new anticoagulants with predictable pharmacokinetics that do not require as frequent monitoring. Ximelagatran, an oral direct thrombin inhibitor, was compared with warfarin in the SPORTIF program, which found both agents to be broadly effective in the prevention of embolic events, but observed abnormal liver function tests in 6% of patients on ximelagatran. Liver function monitoring during treatment is thus needed. Idraparinux, a factor Xa inhibitor administered by once weekly subcutaneous injections, is being evaluated in patients with atrial fibrillation. The ACTIVE trial is currently assessing the role of aspirin plus clopidogrel, compared with adjusted dose warfarin, in the prevention of vascular events in high-risk patients with atrial fibrillation. Angiotensin-converting enzyme inhibitors and angiotensin II receptor-blocking drugs interfere with atrial remodeling and show promise in atrial fibrillation, as suggested in the LIFE trial. Preliminary studies suggest that statins may reduce the risk of recurrence after electrical cardioversion. Finally, percutaneous methods for occlusion of the left atrial appendage are currently under investigation in patients at high risk of thromboembolism but with contraindications for chronic warfarin.

Clinical characteristics and mid-term prognosis of acute coronary syndrome in HIV-infected patients on antiretroviral therapy.

OBJECTIVES: Acute coronary syndromes (ACSs) and coronary artery disease are emerging complications in HIV-infected patients on highly active antiretroviral treatment. The aim of this study was to determine the mid-term prognosis of ACS in HIV-infected patients. METHODS: We evaluated the clinical characteristics and follow-up profile [38+/-15 months; mean+/-standard deviation (SD)] of ACS in 20 HIV-infected patients (mean +/-SD: age 44+/-8 years; range 35-65 years). All had coronary angiograms performed mean time 3+/-48 h after the onset of symptoms. RESULTS: Eighteen patients were on antiretroviral therapy, of whom 13 patients were on regimens including protease inhibitors (mean duration+/-SD: 19+/-13 months). Fifteen patients had a first episode of ST segment elevation ACS and five had non-ST segment elevation ACS. Tobacco consumption (80%) and hypercholesterolaemia (50%) were the most frequent cardiovascular risk factors. During initial hospitalization, four patients were treated with thrombolysis, two had primary coronary angioplasty and seven had secondary coronary angioplasty. At follow up, 10 patients (50%) had had 18 cardiovascular events: one cardiovascular death, seven episodes of recurrent myocardial ischaemia in four patients, three pulmonary oedemas in two patients, and seven revascularization procedures in five patients. CONCLUSIONS: This preliminary report highlights the risk of ACS and related complications in HIV-infected patients and raises questions regarding the implications of antiretroviral treatment.

Interplay of diabetes and coronary heart disease on cardiovascular mortality.

Patients with both diabetes mellitus and prior myocardial infarction are at particularly high risk for cardiovascular mortality.

[A new cause of increased troponin levels: junctional tachycardia]. / Une nouvelle cause d'élévation de la troponine: la tachycardie jonctionnelle.

The authors report 4 cases of acute coronary syndromes with increased troponine levels during junctional tachycardia in patients with angiographically normal coronary arteries. ST segment changes during junctional tachycardia have no predictive value for the detection of coronary artery disease. Increased troponine, a marker of myocardial cellular necrosis, is not a sign of coronary lesions. A disequilibrium between the increased metabolic and energetic requirements of the myocardium and decreased perfusion due to the tachycardia could explain this observation. The recommended management of these patients is not to perform coronary angiography initially in the absence of cerebrovascular risk factors, but rather to document myocardial ischaemia by a non-invasive method such as echocardiography or scintigraphy.

[Symptomatic left ventricular dysfunction and Behçet disease. Report of 2 cases]. / Dysfonction ventriculaire gauche symptomatique et maladie de Behçet. A propos de 2 cas.

Behçet's disease is associated with cardiac complications which may affect all three cardiac layers in 1 to 6% of cases. Although pericardial and coronary disease are the most common, the myocardium may also be affected. The clinical presentation may be left ventricular dysfunction with signs of dilated cardiomyopathy. The cause of the left ventricular dysfunction is usually coronary artery disease but it can also be inflammatory, resulting in a myocarditis with normal coronary arteries. The authors report two cases of Behçet's disease with symptomatic left ventricular dysfunction presenting as dilated cardiomyopathy with normal coronary arteries in one of the cases. Recent echocardiographic studies suggest that the incidence of myocardial disease is underestimated in this pathology: 20 to 35% of patients with Behçet's disease but no cardiac symptoms had left ventricular diastolic dysfunction. A more attentive investigation of left ventricular diastolic function in these patients should enable earlier diagnosis of this complication.

Myocarditis in patients with clinical presentation of myocardial infarction and normal coronary angiograms.

OBJECTIVES: The aim of this study was to assess the diagnosis of myocarditis in patients presenting with acute myocardial infarction (MI) and normal coronary angiograms. BACKGROUND: Most often in these patients, the etiologic diagnosis remains unclear once they are found to have normal coronary arteries. The diagnosis of myocarditis mimicking MI is clinically relevant, because numerous arguments suggest a relation between myocarditis and dilated cardiomyopathy. Myocardial indium-111 (111In)-antimyosin antibody (AMA)/rest thallium-201 (201Tl) imaging allows noninvasive detection of myocarditis. METHODS: Forty-five patients admitted to three intensive care units for suspicion of acute MI, with normal coronary angiograms, were investigated. Indium-111-AMA planar images and then a dual-isotope rest AMA/201Tl tomographic study were performed. Six-month echocardiographic follow-up was obtained in 80% of the patients with initial left ventricular (LV) wall motion abnormalities. RESULTS: In eight patients, AMA and 201Tl scintigraphy were negative. In two patients, a matched 201Tl defect and focal AMA uptake suggested acute MI (due to prolonged vasospasm or spontaneously reperfused coronary occlusion). In 17 patients, diffuse AMA uptake over the whole LV suggested diffuse myocarditis. In 18 patients, focal AMA uptake with a normal 201Tl scan suggested diffuse but heterogeneous, or focal myocarditis. Complete functional recovery was observed in 81% of the patients with a pattern of myocarditis. CONCLUSIONS: Among 45 patients presenting with acute MI and normal coronary angiograms, 38% had diffuse myocarditis and 40% had a scintigraphic pattern of heterogeneous or focal myocarditis. Short-term follow-up showed complete LV functional recovery in 81% of these patients.

[Does Doppler analysis of hepatic venous flow predict increased right atrial pressure and right ventricular dysfunction?]. / L'analyse doppler du flux des veines sus-hépatiques permet-elle de prédire le niveau de pression auriculaire droite au cours de l'infarctus du ventricule droit?

The aim of this study was to test the hypothesis that Doppler study of hepatic venous flow, reflecting right atrial pressures and right ventricular dysfunction, allows prediction of increased right atrial pressure and right ventricular dysfunction in patients with right ventricular infarction. The authors studied 30 patients (27 men, mean age 54 +/- 12 years) in sinus rhythm with acute inferior myocardial infarction who underwent right heart catheterisation and Doppler echocardiography including recording of regurgitant and hepatic vein flow within 48 hours of hospital admission. Hepatic venous flow was used to measure peak velocity and velocity time integrals (VTI) of the systolic (S), diastolic (D) and atrial (a) contraction waves. The fraction of systolic filling was calculated: VTI S/VTI S + VTI D. The pressure half-time of pulmonary regurgitant flow (PHT IP) was also measured. Using haemodynamic criteria (non-compliant right atrial pressure wave form or right ventricular end diastolic pressure/pulmonary capillary pressure > or = 0.8), patients were divided into two groups: Group 1: right ventricular infarction (VD+, N = 22). Group 2: no right ventricular infarction (VD-, N = 8). No correlation was observed between Doppler parameters of hepatic venous flow and haemodynamic data, in particular right atrial pressure and pressure wave form. Moreover, no statistically significant difference was observed between the two groups with respect to the Doppler parameters derived from hepatic venous flow. On the other hand, the results confirmed good diagnostic performance of Doppler analysis of pulmonary regurgitant flow: sensitivity 80%, specificity 83%, positive predictive value 94%, negative predictive value 55%. The authors conclude that, in patients with acute inferior wall infarction, Doppler analysis of hepatic venous flow does not allow assessment of right atrial pressure or of ischaemic right ventricular dysfunction.