Patients with no histories of heart failure and with left ventricular ejection fractions >50% were classified according to: 1) the 2016 ASE/EACVI scoring system (3); 2) the 2009 ASE/EACVI ...recommendations (considering diastolic function grades 2 and 3); 3) the echocardiographic algorithm of the 2007 consensus statement (2); and 4) the Appleton definition (4) (Figure 1). Similar hard outcomes do exist for DD, including the occurrence of heart failure with preserved ejection fraction (HFpEF), defined as the need for an unplanned hospitalization for heart failure with normal ejection fraction in a population of patients without heart failure at baseline. A big-data approach could be used to develop DD diagnostic software that incorporates clinical decision trees developed by machine learning, which can test multiple diagnostic approaches and select the combination of variables that best predicts clinical events.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Summary Background Vascular Ehlers-Danlos syndrome is a rare severe disease that causes arterial dissections and ruptures that can lead to early death. No preventive treatment has yet been validated. ...Our aim was to assess the ability of celiprolol, a β1 -adrenoceptor antagonist with a β2 -adrenoceptor agonist action, to prevent arterial dissections and ruptures in vascular Ehlers-Danlos syndrome. Methods Our study was a multicentre, randomised, open trial with blinded assessment of clinical events in eight centres in France and one in Belgium. Patients with clinical vascular Ehlers-Danlos syndrome were randomly assigned to 5 years of treatment with celiprolol or to no treatment. Randomisation was done from a centralised, previously established list of sealed envelopes with stratification by patients' age (≤32 years or >32 years). 33 patients were positive for mutation of collagen 3A1 ( COL3A1 ). Celiprolol was administered twice daily and uptitrated every 6 months by steps of 100 mg to a maximum of 400 mg per day. The primary endpoints were arterial events (rupture or dissection, fatal or not). This study is registered with ClinicalTrials.gov , number NCT00190411. Findings 53 patients were randomly assigned to celiprolol (25 patients) or control groups (28). Mean duration of follow-up was 47 (SD 5) months, with the trial stopped early for treatment benefit. The primary endpoints were reached by five (20%) in the celiprolol group and by 14 (50%) controls (hazard ratio HR 0·36; 95% CI 0·15–0·88; p=0·040). Adverse events were severe fatigue in one patient after starting 100 mg celiprolol and mild fatigue in two patients related to dose uptitration. Interpretation We suggest that celiprolol might be the treatment of choice for physicians aiming to prevent major complications in patients with vascular Ehlers-Danlos syndrome. Whether patients with similar clinical presentations and no mutation are also protected remains to be established. Funding French Ministry of Health, Programme Hospitalier de Recherche Clinique 2001.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Aims
Procollagen type I C‐terminal propeptide (PICP) and procollagen type III N‐terminal propeptide (PIIINP) are markers reflecting collagen synthesis in cardiac fibrosis. However, they may be ...influenced by the presence of non‐cardiac comorbidities (e.g. ageing, obesity, renal impairment). Understanding the associations between markers of collagen synthesis and abnormalities of cardiac structure and function is important to screen for myocardial fibrosis and monitor the antifibrotic effect of medications.
Methods and results
The HOMAGE (Heart ‘OMics’ in AGEing) trial showed that spironolactone decreased serum PICP concentrations and improved cardiac remodelling over 9 months in a population at risk of developing heart failure (HF). We evaluated the associations between echocardiographic variables, PICP, PIIINP and galectin‐3 at baseline and during the course of the trial. Among 527 individuals (74 ± 7 years, 26% women), median serum concentrations of PICP, PIIINP and galectin‐3 were 80.6 μg/L (65.1–97.0), 3.9 μg/L (3.1–5.0), and 16.1 μg/L (13.5–19.7), respectively. After adjustment for potential confounders, higher serum PICP was significantly associated with left ventricular hypertrophy, left atrial enlargement, and greater ventricular stiffness (all p < 0.05), whereas serum PIIINP and galectin‐3 were not (all p > 0.05). In patients treated with spironolactone, a reduction in serum PICP during the trial was associated with a decrease in E/e′ (adjusted‐beta = 0.93, 95% confidence interval 0.14–1.73; p = 0.022).
Conclusions
In individuals at high risk of developing HF, serum PICP was associated with cardiac structural and functional abnormalities, and a decrease in PICP with spironolactone was correlated with improved diastolic dysfunction as assessed by E/e′. In contrast, no such associations were present for serum PIIINP and galectin‐3.
In a population at risk of HF, independent of clinical confounders, higher serum concentration of procollagen type I C‐terminal propeptide (PICP) was associated with the presence of left ventricular (LV) hypertrophy and diastolic functional abnormalities (specifically, with greater left atrial LA volume indexed for body surface area and lower e′). In contrast, serum concentrations of procollagen type III N‐terminal propeptide (PIIINP) and galectin‐3 were not associated with abnormalities in any of the measures of cardiac structure or function. Additionally, in individuals treated with spironolactone, a decrease in serum PICP during a 9‐month period paralleled a decrease in E/e′.
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BFBNIB, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
The attenuation of physiological nocturnal decline of blood pressure (BP)-called nondipper pattern-has previously been reported to be associated with target organ damage in hypertensive subjects. ...However, this association remains debated and poorly studied in normotensive patients. This study aimed to investigate the association between nondipper pattern and subclinical cardiovascular and renal damage in an initially healthy population-based cohort study.
The STANISLAS Cohort is a single-center, familial longitudinal cohort composed of 1,006 families (4,295 subjects) recruited in 1993-1995 for a 5-year periodic health examination. A total of 1,334 subjects from the 4th visit (2011-2016) of the STANISLAS cohort were included. This 4th examination included estimated glomerular filtration rate, albumin/creatinine ratio, pulse wave velocity, central systolic BP, carotid intima-media thickness and distensibility, left ventricular mass index, left ventricular hypertrophy, diastolic dysfunction, and ambulatory blood pressure monitoring (ABPM). Nondipping status was defined as a mean reduction in systolic BP (SBP) or diastolic BP (DBP) lower than 10% during nighttime.
Data were obtained from 798 normotensive subjects (45 ± 14 years, 395 49% nondippers, SBP/DBP mmHg 24 hours: 116/71 ± 7/5) and 536 hypertensive patients (56 ± 11 years, 257 48% nondippers, SBP/DBP mmHg 24 hours: 127/78 ± 10/7). Mean 24-hour and daytime ABPM measurements were within the normal range, even in hypertensive participants (19% treated). The nondipping pattern was not associated with cardiovascular or renal alterations in this population.
In this middle-aged population with an overall 24-hour optimal BP control, the nondipper pattern was not associated with increased cardiovascular or renal damage.
Chest X-ray (CXR) widely used, but the prognostic value of congestion quantification using CXR remains uncertain. The main objective of the present study was to assess whether initial quantification ...of lung congestion evaluated by CXR and its interplay with estimated plasma volume status (ePVS) in patients with worsening heart failure (WHF) is associated with in-hospital and short-term clinical outcome.
We studied 117 patients hospitalized for WHF in the ICALOR HF disease management program. Pulmonary congestion was estimated using congestion score index (CSI, range 0 to 3) evaluated from 6 lung areas on CXR. Systemic congestion was assessed by ePVS. Logistic regression analysis was used to assess length of stay and the composite of all-cause death or HF re-hospitalization at 90 days.
Patients were divided according to the median of admission CSI (median = 2.20) and ePVS (median = 5.38). Higher CSI was significantly associated with higher pulmonary arterial systolic pressure in multivariable models. Multivariable models showed patients with high CSI/high ePVS had a 6-day longer length of stay OR (95% CI) = 6.78 (1.82–29.79), p < 0.01 and 5-fold higher risk of 90-day composite outcome OR (95% CI) = 5.13 (1.26–25.11) p = 0.03 compared to patients with low CSI/low ePVS, while other configurations (either isolated high CSI or high ePVS) yielded neutral associations. Furthermore, CSI and ePVS significantly improved reclassification on top of clinical covariates for the composite outcome Net reclassification index = 37.3% (0.52–87.0), p = 0.046.
An admission assessment of pulmonary and systemic congestion in WHF patients using CSI and ePVS can identify a cluster of high-risk patients at short-term outcomes.
•Higher admission chest X-rays pulmonary congestion was associated with higher pulmonary arterial systolic pressure.•Concomitant increased pulmonary congestion and plasma volume at admission were associated with a higher risk of events.•Combined assessment of chest X-ray and hemoglobin/hematocrit could help risk-stratification in patients with worsening HF
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background
Carotid intima–media thickness (cIMT) is a noninvasive marker of cardiovascular risk. The cIMT may be increased in patients with harmonisation, but little is known regarding the functional ...form of the association between blood pressure (BP) and cIMT in hypertensive and nonhypertensive persons. We aimed to define the shape of the association between BP and cIMT.
Methods and Results
We studied cIMT and ambulatory BP monitoring data from a single‐center, cross‐sectional, population‐based study involving 696 adult participants from the STANISLAS cohort, a familial longitudinal cohort from the Nancy region of France. Participants with a history of hypertension were more likely to have a cIMT >900 μm and had higher mean cIMT (both P<0.001). The risk of cIMT >900 μm increased linearly with higher 24‐hour and daytime systolic BP in participants both with and without history of hypertension. The relationship between systolic BP and the risk of cIMT >900 μm was not dependent on hypertension status (all P for interaction >0.10). In multivariable analysis adjusted on cardiovascular risk factors, each 5‐mm Hg increase in systolic BP was associated with an 8‐μm increase in cIMT (β=8.249 95% CI 2.490–14.008, P=0.005). In contrast, the association between diastolic BP and cIMT was weaker and not significant.
Conclusions
Systolic BP is linearly and continuously associated with higher cIMT in both hypertensive and nonhypertensive persons, suggesting a detrimental effect of BP on the vascular tree prior to overt hypertension. Similarly, it suggests a detrimental effect of BP at the higher end of the normal range in treated hypertensive patients.
Clinical Trial Registration
URL: https://www.clinicaltrials.gov/. Unique identifier: NCT01391442.
There is limited evidence regarding intra-observer and inter-observer variations in echocardiographic measurements of diastolic function. This study aimed to assess this reproducibly within a ...population-based cohort study.
Sixty subjects in sinus rhythm were randomly selected among 4th visit participants of the STANISLAS Cohort (Lorraine region, France). This 4th examination systematically included M-mode, 2-dimensional, DTI and pulsed-wave Doppler echocardiograms. Reproducibility of variables was studied by intra-class correlation coefficients (ICC) and Bland Altman plots.
Our population was on average middle-aged (50 ± 14 y), overweight (BMI = 26 ± 6 kg/m2) and non-smoking (87%) with a quarter of the participants having self-declared hypertension or treated with anti-hypertensive medication(s). Intra-observer ICC were > 0.90 for all analyzed parameters except for left ventricular ejection fraction (LVEF) which was 0.89 (0.81-0.93). The mean relative intra-observer differences were small and limits of agreement of relative differences were narrow for all considered parameters (<5% and <15% respectively). Inter-observer ICC were > 0.90 for all analyzed parameters except for LVEF (ICC = 0.87) and both mitral and pulmonary A wave duration (0.83 and 0.73 respectively). The mean relative inter-observer differences were <5% for all parameters except for pulmonary A wave duration (mean difference = 6.5%). Limits of agreement of relative differences were narrow (<15%), except for mitral A wave duration and velocity (both <20%) as well as left ventricular mass and pulmonary A wave duration (both <30%). Intra-observer agreements with regard to the presence and severity of diastolic dysfunction were excellent (Kappa = 0.93 (0.83-1.00) and 0.88 (0.75-0.99), respectively).
In this validation study within the STANISLAS cohort, diastolic function echocardiographic parameters were found to be highly reproducible. Diastolic dysfunction consequently appears as a highly effective clinical and research tool.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Higher serum bilirubin has been associated with poorer prognosis in patients with heart failure (HF). We examined the association between serum bilirubin and clinical outcomes in patients with ...clinical signs of HF and/or left ventricular systolic dysfunction after acute myocardial infarction (MI). A total of 7,467 patients from the High-Risk Myocardial Infarction Database Initiative with an available baseline total bilirubin concentration were studied. The association between baseline bilirubin concentrations and the composite outcome of cardiovascular mortality (CVM), nonfatal stroke, nonfatal MI or hospitalization for HF, CVM, and all-cause mortality were assessed using Cox proportional hazards models. An interaction with time was observed with associations present only in the first 90 days after randomization. The median (percentile25-75) baseline total bilirubin concentration was 11 (8 to 14) µmol/L and was above the “normal” range (>17.1 µmol/L) in 1,053 (14.1%) patients. In multivariable analysis, with adjustment for baseline characteristics (demographic, co-morbidities, Killip score, left ventricular ejection fraction, and laboratory variables), patients with a bilirubin concentration of >17.1 µmol/L had a significantly higher risk of all the studied outcomes at 90 days (e.g., CVM: adjusted hazard ratio 1.45, 95% confidence interval 1.14 to 1.86, p = 0.003). The addition of bilirubin to a validated survival model modestly improved the risk reclassification to predict 90-day events (continuous net reclassification improvement for CVM 6.4%, 95% confidence interval 0.7% to 9.6%, p = 0.04). In patients with MI complicated with HF and/or systolic dysfunction, bilirubin concentration is an independent predictor of mortality and may improve risk stratification.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
To investigate the influence of increasing age on clinical presentation, treatment and long-term outcome in patients with inducible paroxysmal supraventricular tachycardia (SVT) without ...pre-excitation syndromes.
Clinical and electrophysiological study (EPS) data, as well as long-term clinical outcome (mean follow-up 2.4±4.0 years) were collected in patients referred for regular tachycardia with inducible SVT during EPS without pre-excitation.
Among 1960 referred patients, 301 patients (15.4%) were aged ≥70 (70-97). In this subset, anticoagulants were prescribed in 49 patients following an erroneous diagnosis of atrial tachycardia and 14 were previously erroneously diagnosed with ventricular tachycardia because of wide QRS. Ablation was performed more frequently in patients ≥70 despite more frequent failure and complications. During follow-up, higher risks of AF, stroke, pacemaker implantation and death were observed in patients ≥70 whereas SVT recurrences were similar in both age groups. In multivariable analysis, age ≥70 was independently associated with higher risks of SVT-related adverse events prior to ablation (OR = 1.93, 1.41-2.62, p<0.001), conduction disturbances (OR = 11.27, 5.89-21.50, p<0.001), history of AF (OR = 2.18, 1.22-3.90, p = 0.009) and erroneous diagnosis at baseline (OR = 9.14, 5.93-14.09, p<0.001) as well as high rates of procedural complications (OR = 2.13, 1.19-3.81, p = 0.01) and ablation failure (OR = 1.68, 1.08-2.62, p = 0.02). In contrast, age ≥70 was not significantly associated with a higher risk of AF in multivariable analysis.
A sizeable proportion of patients with inducible SVT without pre-excitation syndromes are elderly. These patients exhibit higher risks of erroneous tachycardia diagnosis prior to EPS as well as failure and/or complication of ablation, but similar risk of SVT recurrence. These results support performing transesophageal EPS in most patients and intracardiac EPS in selected patients. EPS may furthermore prove useful in elderly patients with regular tachycardia, mainly by avoiding treatment based on an erroneous diagnosis.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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