National institutions should improve the information made available to patients about cervical smears.

OBJECTIVE: To assess the quality of the content of leaflets tools and websites of national institutions in United Kingdom and France informing patients about cervical smears. METHODS: We collected and analyzed the data and information on these two websites and leaflets made for patients. We screened those tools with the UP TO DATE SCIENTIFIC EVIDENCE IPDAS grid. RESULTS: None of the tools specify the level of evidence of the studies on which cervix cancer screening is based. The risk of complication due to cancer is poor. The effectiveness of screening in absolute value is not available. The risks and side-effects due to cervical smears are specified without the frequency. CONCLUSION: Information is truncated and pushes readers towards taking part in screening. This is not in accordance with the quality criteria of shared decision making. PRACTICE IMPLICATIONS: Patients should take part in the creation of decision making tools, so that the information is the most suited to their representations and understanding. This is why the documents made available by institutions should be based on recognized scientific sources. Responsible of health programs should be independent and separated from those responsible of information tool creation.

Contractibility sensor signal evolution predicts cardiovascular events in patients with cardiac resynchronization therapy.

BACKGROUND: While a multicentre trial has demonstrated that the SonR™ contractibility sensor is as effective as echocardiography-guided optimization at improving response to cardiac resynchronization therapy, an association between SonR™ values and clinical endpoints has not been established. AIMS: The primary objective was to assess the predictive value of SonR™ signal evolution regarding cardiovascular events in patients implanted with a cardiac resynchronization therapy device. The secondary objective was to evaluate whether SonR™ signal evolution was associated with cardiovascular death. METHODS: All patients with a SonR™ system implanted between 2012 and 2016 were included in this retrospective study. SonR™ signal evolution was calculated over the first 6 months after implantation: ([month 6 value-month 1 value]/month 1 value)*100. The primary endpoint (cardiovascular events) was a composite of cardiovascular death, hospitalization for acute heart failure or ventricular arrhythmia. RESULTS: Seventy-four patients (median age 67 years; 81% men) were followed up over a median 20 (13; 29) months. Cumulative incidence function showed that SonR™ signal evolution was predictive of cardiovascular events (threshold<10.70%; P=0.023) and predictive of cardiovascular death (P=0.0018). After multivariable analysis, SonR™ signal evolution was independently associated with the onset of cardiovascular events (hazard ratio: 4.03, 95% confidence interval: 1.31-12.43; P=0.015), even after adjustment for left bundle branch block and chronic kidney disease. CONCLUSIONS: In this first study publishing data on SonR™ signals in a real-life setting, SonR™ signal evolution over the first 6 months after cardiac resynchronization implantation was an independent predictor of cardiovascular events at follow-up. This variable could be useful to identify patients at higher risk of further adverse events after cardiac resynchronization implantation.

Prognostic value of plasma MR-proADM vs NT-proBNP for heart failure in people with type 2 diabetes: the SURDIAGENE prospective study.

AIMS/HYPOTHESIS: N-terminal pro-B-type natriuretic peptide (NT-proBNP) is the gold standard prognostic biomarker for diagnosis and occurrence of heart failure. Here, we compared its prognostic value for the occurrence of congestive heart failure with that of plasma mid-region pro-adrenomedullin (MR-proADM), a surrogate for adrenomedullin, a vasoactive peptide with vasodilator and natriuretic properties, in people with type 2 diabetes. METHODS: Plasma MR-proADM concentration was measured in baseline samples of a hospital-based cohort of consecutively recruited participants with type 2 diabetes. Our primary endpoint was heart failure requiring hospitalisation. RESULTS: We included 1438 participants (age 65 ± 11 years; 604 women and 834 men). Hospitalisation for heart failure occurred during follow-up (median 64 months) in 206 participants; the incidence rate of heart failure was 2.5 (95% CI 2.2, 2.9) per 100 person-years. Plasma concentrations of MR-proADM and NT-proBNP were significantly associated with heart failure in a Cox multivariable analysis model when adjusted for age, diabetes duration, history of coronary heart disease, proteinuria and baseline eGFR (adjHR [95%CI] 1.83 [1.51, 2.21] and 2.20 [1.86, 2.61], respectively, per 1 SD log10 increment, both p < 0.001). MR-proADM contributed significant supplementary information to the prognosis of heart failure when we considered the clinical risk factors (integrated discrimination improvement [IDI, mean ± SEM] 0.021 ± 0.007, p = 0.001) (Table 3). Inclusion of NT-proBNP in the multivariable model including MR-proADM contributed significant complementary information on prediction of heart failure (IDI [mean ± SEM] 0.028 ± 0.008, p < 0.001). By contrast, MR-proADM did not contribute supplementary information on prediction of heart failure in a model including NT-proBNP (IDI [mean ± SEM] 0.003 ± 0.003, p = 0.27), with similar results for heart failure with reduced ejection fraction and preserved ejection fraction. CONCLUSIONS/INTERPRETATION: MR-proADM is a prognostic biomarker for heart failure in people with type 2 diabetes but gives no significant complementary information on prediction of heart failure compared with NT-proBNP.

Does resting heart rate measured by the physician reflect the patient's true resting heart rate? White-coat heart rate.

OBJECTIVES: In cardiology, resting heart rate (HR) and blood pressure (BP) are key elements and are used to adapt treatment. However HR measured in consultation may not reflect true resting HR. We hypothesize that there may be a "white-coat" effect like with BP and that there may be an association between HR variations and BP variations. METHODS: This prospective, monocentric, observational, pilot study (January-April 2016) included 57 consecutive ambulatory patients at Poitiers University Hospital, France (58% male, mean age 64 years). Patients' resting HR and BP were recorded with the same automated blood pressure sphygmomanometer in consultation by the physician then with self-measurement at home. RESULTS: In the overall cohort, we found that HR was significantly higher in consultation (70.5bpm±12.6 vs. 68.1bpm±10.1, p=0.034). HR also correlated with diastolic BP (r=0.45, p=0.001). Patients were divided into three groups to look for associations with BP: masked HR, (higher HR at home, 38.6%), white-coat HR, (lower HR at home 52.6%) and iso HR, (no change between HR at home and consultation, 8.8%). Although there was no difference between groups in diastolic BP measured in consultation, home diastolic BP was lower in the white-coat HR group (74.3mmHg±9.8 vs. 77.9mmHg±7.5, p=0.016). CONCLUSIONS: Our study brings to light an exciting idea that could have a major therapeutic and maybe prognostic impact in cardiology: resting HR measured by the physician in consultation does not reflect true resting HR. This must be taken into account to adapt treatment.

Circulating Concentrations of Redox Biomarkers Do Not Improve the Prediction of Adverse Cardiovascular Events in Patients With Type 2 Diabetes Mellitus.

BACKGROUND: Despite pathophysiological relevance and promising experimental data, the usefulness of biomarkers of oxidative stress for cardiac risk prediction is unclear. The aim of our study was to investigate the prognostic value of 6 biomarkers exploring different pathways of oxidative stress for predicting adverse cardiovascular outcomes in patients with type 2 diabetes mellitus beyond established risk factors. METHODS AND RESULTS: The SURDIAGENE (Survie, Diabete de type 2 et Genetique) prospective cohort study consecutively recruited 1468 patients with type 2 diabetes mellitus. Assays were performed at baseline, and incident cases of major adverse cardiovascular events (MACE)-first occurrence of cardiovascular death, nonfatal myocardial infarction, or stroke-were recorded during a median of 64 months. Advanced oxidation protein products, oxidative hemolysis inhibition assay, ischemia-modified albumin, and total reductive capacity of plasma were not associated with the risk of MACE in univariate analyses. Fluorescent advanced glycation end products and carbonyls were associated with MACE (hazard ratio=1.38 per SD, 95% confidence interval 1.24-1.54, P<0.001 and hazard ratio=1.15 per SD, 95% confidence interval 1.04-1.27, P=0.006, respectively) in univariate analysis, but when added to a multivariate predictive model including traditional risk factors for MACE, these markers did not significantly improve c-statistics or integrated discrimination index of the model. CONCLUSIONS: These plasma concentrations of 6 markers, which cover a broad spectrum of oxidative processes, were not significantly associated with MACE occurrence and were not able to improve MACE risk discrimination and classification beyond classical risk factors in type 2 diabetes mellitus patients.

Power of resting echocardiographic measurements to classify pulmonary hypertension patients according to European society of cardiology exercise testing risk stratification cut-offs.

BACKGROUND: Right ventricular function is the major determinant of morbidity and mortality in pulmonary arterial hypertension (PAH). The ESC risk assessment strategy for PAH is based on clinical status, exercise testing, NTproBNP, imaging and haemodynamics but does not include right ventricular function. Our aims were to test the power of resting echocardiographic measurements to classify PAH patients according to ESC exercise testing risk stratification cut-offs and to determine if the classification power of echocardiographic parameters varied in chronic thrombo-embolic pulmonary hypertension (CTEPH). METHODS: We prospectively and consecutively recruited 46 PAH patients and 42 CTEPH patients referred for cardio-pulmonary exercise testing and comprehensive transthoracic echocardiography. Exercise testing parameters analyzed were peak oxygen consumption, percentage of predicted maximal oxygen consumption and the slope of ventilation against carbon dioxide production. Receiver operator characteristic curves were used to determine the optimal diagnostic cut-off values of echocardiographic parameters for classifying the patients in intermediate or high risk category according to exercise testing. RESULTS: Measurements of right ventricular systolic function were the best for classifying in PAH (area under the curve 0.815 to 0.935). Measurements of right ventricular pressure overload (0.810 to 0.909) were optimal for classifying according to exercise testing in CTEPH. Measurements of left ventricular function were of no use in either group. CONCLUSIONS: Measurements of right ventricular systolic function can classify according to exercise testing risk stratification cut-offs in PAH. However, this is not the case in CTEPH where pressure overload, rather than right ventricular function seems to be linked to exercise performance.

Resting right ventricular function is associated with exercise performance in PAH, but not in CTEPH.

Aims: To assess whether resting right ventricular (RV) function assessed by Global RV longitudinal strain (RVLS) and RV fractional area change (FAC) is associated with exercise performance in pulmonary arterial hypertension (PAH) and in chronic thromboembolic pulmonary hypertension (CTEPH). Methods and results: We prospectively recruited 46 consecutive patients with PAH and 42 patients with CTEPH who were referred for cardio-pulmonary exercise testing (CPET) and transthoracic echocardiography. Resting RV systolic function was assessed with RVLS and FAC. CPET parameters analyzed were percentage of predicted maximal oxygen consumption (VO2max) and the slope of ventilation against carbon dioxide production (VE/VCO2). Spearman correlation was performed between echocardiographic measurements and CPET measurements. In PAH, spearman correlation found an association between RVLS and VE/VCO2 (coefficient = 0.556, P < 0.001) and percentage predicted VO2max (coefficient = -0.393, P = 0.007), while FAC was associated with VE/VCO2 (coefficient = -0.481, P = 0.001) and percentage of predicted VO2max (coefficient = 0.356, P = 0.015). Conversely, in CTEPH, resting RV function was neither associated with percentage of predicted VO2max nor with VE/VCO2, whether assessed by RVLS or FAC. Conclusion: In PAH, resting RV function as assessed by FAC or RVLS is associated with exercise performance and could therefore make a significant contribution to non-invasive assessment in PAH patients. This association is not found in CTEPH, suggesting a disconnection between resting RV function and exercise performance, with implications for the use of exercise measurements as a prognostic marker and clinical/research endpoint in CTEPH.

Pancarditis: an unusual complication of a group B streptococcal infection.

Pancarditis is a rare condition with a poor prognosis combining endocarditis, myocarditis with abscess formation, and purulent pericarditis. Diagnosis is often delayed and the clinical signs are predominantly those of the embolic complications. Literature is scarce. We present a unique and rare case of pancarditis, complicating a Streptococcal B infection in an immunocompetent, healthy, 54 year-old woman. The evolution was favourable under medical therapy alone and thanks to multimodality cardiac imaging diagnosis and follow-up.

Right ventricular longitudinal strain: a tool for diagnosis and prognosis in light-chain amyloidosis.

OBJECTIVES: Light-chain (AL) amyloidosis can lead to an infiltrative cardiomyopathy with increased wall thickness (IWT) of very poor prognosis. Our primary aim was to analyse the right ventricle (RV) in patients with IWT to discriminate AL amyloidosis from IWT due to hypertrophic cardiomyopathy (HCM) or to arterial hypertension (HTN). Our secondary aim was to assess if RV dysfunction predicts overall mortality in cardiac AL amyloidosis. METHODS: We retrospectively and consecutively compared clinical, biological and echocardiographic data of 315 patients with IWT: 105 biopsy-proven AL amyloidosis patients, 105 patients with HCM and 105 patients with HTN. The prognostic value of these parameters was analysed in the AL amyloidosis group. RESULTS: Free-wall right ventricular longitudinal strain (FWRVLS) worse than -21.2% discriminates AL amyloidosis [area under the curve (AUC) = 0.744)] from patients with IWT due to other aetiologies. In AL amyloidosis, FWRVLS is the strongest echocardiographic prognostic marker with AUC =0.722 and -16.5% as the optimal cut-off value, beyond which overall mortality increases significantly. It is also the only independent echocardiographic predictor of overall mortality (HR =1.113; 95%CI 1.029-1.204; p = .007), even when adjusted to the Mayo stage and global left ventricular longitudinal strain. CONCLUSIONS: FWRVLS should be considered in the diagnostic and prognostic workup in light-chain amyloidosis.

Evolution of subclinical myocardial dysfunction detected by two-dimensional and three-dimensional speckle tracking in asymptomatic type 1 diabetic patients: a long­term follow-up study.

BACKGROUND: We sought to assess the long-term evolution of left ventricular (LV) function using two-dimensional (2D) and three-dimensional (3D) speckle tracking echocardiography (STE) for the detection of preclinical diabetic cardiomyopathy, in asymptomatic type 1 diabetic patients, over a 6-year follow-up. DESIGN AND METHODS: Sixty-six asymptomatic type 1 diabetic patients with no cardiovascular risk factors were compared to 26 matched healthy controls. Conventional, 2D and 3D-STE were performed at baseline. A subgroup of 14 patients underwent a 6-year follow-up evaluation. RESULTS: At baseline, diabetic patients had similar LV ejection fraction (60 vs 61%; P = NS), but impaired longitudinal function, as assessed by 2D-global longitudinal strain (GLS) (-18.9 ± 2 vs -20.5 ± 2; P = 0.0002) and 3D-GLS (-17.5 ± 2 vs -19 ± 2; P = 0.003). At follow-up, diabetic patients had worsened longitudinal function compared to baseline (2D-GLS: -18.4 ± 1 vs -19.2 ± 1; P = 0.03). Global circumferential (GCS) and radial (GRS) strains were unchanged at baseline and during follow-up. Metabolic status did not correlate with GLS, whereas GCS and GRS showed a good correlation, suggestive of a compensatory increase of circumferential and radial functions in advanced stages of the disease - long-term diabetes (GCS: -26 ± 3 vs -23.3 ± 3; P = 0.008) and in the presence of microvascular complications (GRS: 38.8 ± 9 vs 34.3 ± 8; P = 0.04). CONCLUSIONS: Subclinical myocardial dysfunction can be detected by 2D and 3D-STE in type 1 diabetic patients, independently of any other cardiovascular risk factors. Diabetic cardiomyopathy progression was suggested by a mild decrease in longitudinal function at the follow-up, but did not extend to a clinical expression of the disease, as no death or over heart failure was reported.

Even if they are not aware of it, general practitioners improve well-being in their adolescent patients.

BACKGROUND: Most adolescents consult their general practitioner (GP) for common reasons, somatic or administrative but many of them have hidden feelings of distress. OBJECTIVES: To assess the immediate impact of 'ordinary' consultations on feelings of distress among adolescents and to compare adolescents experiencing difficulties (D) to those with no difficulties (N). To analyse how accurately GPs assess the impact of their consultation on adolescents' feelings. METHODS: GPs were randomly selected from two non-contiguous French administrative areas between April and June 2006. Fifty-three GPs gave two questionnaires to the first 10 to 15 adolescents aged 12 to 20 seen in consultation. One questionnaire was issued before the consultation and the other one afterwards. Adolescents had to position themselves about different aspects of well-being and say where they would seek help if they had problems. A GP questionnaire assessed how well they estimated their impact on the adolescent's feeling of well-being. RESULTS: Six hundred and sixty-five adolescents were assessed. They reported feeling better about their health, being able to talk, having someone to talk to or to confide in and on feeling understood. The D group (n = 147) felt significantly better compared to the N group (n = 518). GPs tended to underestimate this improvement, especially regarding adolescents in the D group feeling better about their health. CONCLUSIONS: Consulting a GP generates increased well-being among adolescents, especially for those experiencing difficulties. GPs tend to underestimate the positive impact they may have. Further studies are needed to explore if this benefit is permanent over time.

Left ventricular longitudinal strain impairment predicts cardiovascular events in asymptomatic type 1 myotonic dystrophy.

BACKGROUND: Type 1 myotonic dystrophy (DM1) patients' prognosis is very poor. Up until now, only a few prognostic factors for cardiovascular events have been identified, and they are predictive of end-stage disease. The aim was to assess the prognostic value of global longitudinal strain (GLS) for cardiovascular events in asymptomatic DM1 patients. METHODS: DM1 patients were included between 2011 and 2015 and followed up until January 2016. Patients underwent a transthoracic echocardiography at inclusion. The primary endpoint was a composite of all-cause mortality, type 2 Mobitz 2 and type 3 atrioventricular block, symptomatic sino-atrial block, HV interval≥70ms at invasive electrophysiology exploration, left ventricular ejection fraction (LVEF) ≤45% and newly developed atrial fibrillation. RESULTS: Forty-six patients (25 males, mean age 40years old) were included. The primary outcome was reached in 14 patients with a mean follow-up of 38months. GLS of patients who reached the primary endpoint was significantly impaired as compared to those who did not (-15.1 [-16.7; -12.7] vs. -18.2 [-19.2; -16.7] respectively; P=0.001). According to ROC curve analysis, probability of primary outcome occurrence was significantly greater in patients with GLS values≥-17.2% (P=0.001). On multivariate analysis, PR electrocardiogram interval and GLS remained significantly and independently associated with the primary endpoint [hazard ratio (HR) 1.03, 95% confidence interval (CI) 1.01-1.04, P=0.006 for PR interval; HR 1.4, 95% CI 1.1-1.7, P=0.002 for GLS] while LVEF alone was not. CONCLUSION: Left ventricular GLS is a powerful marker to predict cardiovascular events in asymptomatic DM1 patients, independently of LVEF.

Efficacy and safety of insulin in type 2 diabetes: meta-analysis of randomised controlled trials.

BACKGROUND: It is essential to anticipate and limit the social, economic and sanitary cost of type 2 diabetes (T2D), which is in constant progression worldwide. When blood glucose targets are not achieved with diet and lifestyle intervention, insulin is recommended whether or not the patient is already taking hypoglycaemic drugs. However, the benefit/risk balance of insulin remains controversial. Our aim was to determine the efficacy and safety of insulin vs. hypoglycaemic drugs or diet/placebo on clinically relevant endpoints. METHODS: A systematic literature review (Pubmed, Embase, Cochrane Library) including all randomised clinical trials (RCT) analysing insulin vs. hypoglycaemic drugs or diet/placebo, published between 1950 and 2013, was performed. We included all RCTs reporting effects on all-cause mortality, cardiovascular mortality, death by cancer, cardiovascular morbidity, microvascular complications and hypoglycaemia in adults ≥ 18 years with T2D. Two authors independently assessed trial eligibility and extracted the data. Internal validity of studies was analyzed according to the Cochrane Risk of Bias tool. Risk ratios (RR) with 95 % confidence intervals (95 % CI) were calculated, using the fixed effect model in first approach. The I(2) statistic assessed heterogeneity. In case of statistical heterogeneity, subgroup and sensitivity analyses then a random effect model were performed. The alpha threshold was 0.05. Primary outcomes were all-cause mortality and cardiovascular mortality. Secondary outcomes were non-fatal cardiovascular events, hypoglycaemic events, death from cancer, and macro- or microvascular complications. RESULTS: Twenty RCTs were included out of the 1632 initially identified studies. 18 599 patients were analysed: Insulin had no effect vs. hypoglycaemic drugs on all-cause mortality RR = 0.99 (95 % CI =0.92-1.06) and cardiovascular mortality RR = 0.99 (95 % CI =0.90-1.09), nor vs. diet/placebo RR = 0.92 (95 % CI = 0.80-1.07) and RR = 0.95 (95 % CI 0.77-1.18) respectively. No effect was found on secondary outcomes either. However, severe hypoglycaemia was more frequent with insulin compared to hypoglycaemic drugs RR = 1.70 (95 % CI = 1.51-1.91). CONCLUSIONS: There is no significant evidence of long term efficacy of insulin on any clinical outcome in T2D. However, there is a trend to clinically harmful adverse effects such as hypoglycaemia and weight gain. The only benefit could be limited to reducing short term hyperglycemia. This needs to be confirmed with further studies.

Do optimal prognostic thresholds in continuous physiological variables really exist? Analysis of origin of apparent thresholds, with systematic review for peak oxygen consumption, ejection fraction and BNP.

BACKGROUND: Clinicians are sometimes advised to make decisions using thresholds in measured variables, derived from prognostic studies. OBJECTIVES: We studied why there are conflicting apparently-optimal prognostic thresholds, for example in exercise peak oxygen uptake (pVO2), ejection fraction (EF), and Brain Natriuretic Peptide (BNP) in heart failure (HF). DATA SOURCES AND ELIGIBILITY CRITERIA: Studies testing pVO2, EF or BNP prognostic thresholds in heart failure, published between 1990 and 2010, listed on Pubmed. METHODS: First, we examined studies testing pVO2, EF or BNP prognostic thresholds. Second, we created repeated simulations of 1500 patients to identify whether an apparently-optimal prognostic threshold indicates step change in risk. RESULTS: 33 studies (8946 patients) tested a pVO2 threshold. 18 found it prognostically significant: the actual reported threshold ranged widely (10-18 ml/kg/min) but was overwhelmingly controlled by the individual study population's mean pVO2 (r = 0.86, p<0.00001). In contrast, the 15 negative publications were testing thresholds 199% further from their means (p = 0.0001). Likewise, of 35 EF studies (10220 patients), the thresholds in the 22 positive reports were strongly determined by study means (r = 0.90, p<0.0001). Similarly, in the 19 positives of 20 BNP studies (9725 patients): r = 0.86 (p<0.0001). Second, survival simulations always discovered a "most significant" threshold, even when there was definitely no step change in mortality. With linear increase in risk, the apparently-optimal threshold was always near the sample mean (r = 0.99, p<0.001). LIMITATIONS: This study cannot report the best threshold for any of these variables; instead it explains how common clinical research procedures routinely produce false thresholds. KEY FINDINGS: First, shifting (and/or disappearance) of an apparently-optimal prognostic threshold is strongly determined by studies' average pVO2, EF or BNP. Second, apparently-optimal thresholds always appear, even with no step in prognosis. CONCLUSIONS: Emphatic therapeutic guidance based on thresholds from observational studies may be ill-founded. We should not assume that optimal thresholds, or any thresholds, exist.