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Objective: Describe the characteristics of patients presenting with TTS during the course of a broad spectrum of systemic diseases, in comparison to classic TTS., Methods: French multicenter retrospective case-control study completed by a literature review., Results: 19 new cases were included in the study. The literature review identified 25 previously published cases. Among the 44 patients, 41 were females, with a median age of 67 years. The main underlying systemic diseases were systemic lupus erythematosus for seven, rheumatoid arthritis for six and primary Sjögren's syndrome for five. A TTS trigger was found in 34 cases, including a systemic disease flare-up in 28. The flare-up was treated in 15 cases, mainly with corticosteroids. One patient died during the episode, unrelated to the TTS. With a median follow-up of 24 months, all patients had recovered a normal LVEF, one had presented a recurrence of TTS, and none had died of a cardiac cause. Finally, the 19 new patients were compared with 19 classic TTS. The disease characteristics were extremely similar, with no significant difference in terms of clinical, electrocardiographic, biological and echocardiographic presentation., Conclusion: A broad spectrum of systemic diseases may rarely be accompanied by TTS, particularly during disease flare-ups. Although uncommon, TTS should be borne in mind in the presence of any cardiac symptomatology during the course of a systemic disease. Compared with classic TTS, their clinical, biological and echographic presentation is unremarkable. The prognosis for TTS appears to be good, with the consistent recovery of LVEF and no cardiac-related deaths., Competing Interests: Declaration of Competing Interest No conflicts of interest needed to be disclosed by any of the authors relative to the submitted work., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Heart failure (HF) has high event rates, mortality, and is challenging to manage in clinical practice. Clinical management is complicated by complex therapeutic strategies in a population with a high prevalence of comorbidity and general frailty. In the last four years, an abundance of research has become available to support multidisciplinary management of heart failure from within the hospital through to discharge and primary care as well as supporting diagnosis and comorbidity management. Within the hospital setting, recent evidence supports sacubitril-valsartan combination in frail, deteriorating or de novo patients with LVEF≤40%. Furthermore, new strategies such as SGLT2 inhibitors and vericiguat provide further benefit for patients with decompensating HF. Studies with tafamidis report major clinical benefits specifically for patients with ATTR cardiac amyloidosis, a remaining underdiagnosed and undertreated disease. New evidence for medical interventions supports his bundle pacing to reduce QRS width and improve haemodynamics as well as ICD defibrillation for non-ischemic cardiomyopathy. The Mitraclip reduces hospitalisations and mortality in patients with symptomatic, secondary mitral regurgitation and ablation reduces mortality and hospitalisations in patients with paroxysmal and persistent atrial fibrillation. In end-stage HF, the 2018 French Heart Allocation policy should improve access to heart transplants for stable, ambulatory patients and, mechanical circulatory support should be considered to avoid deteriorating on the waiting list. In the community, new evidence supports that improving discharge education, treatment and patient support improves outcomes. The authors believe that this review fills the gap between the guidelines and clinical practice and provides practical recommendations to improve HF management., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Objectives: Cardiovascular involvement is a major contributor to mortality in systemic sclerosis (SSc). We examined whether N-terminal pro-brain natriuretic peptide (NT-proBNP) is a reliable predictor of mortality in SSc., Methods and Results: This multicentre prospective cohort study included 523 patients presenting with SSc, whose mean age was 54±13years, mean disease duration 8±9years, and diffuse cutaneous form in 168. Plasma NT-proBNP was measured at baseline and the patients were followed yearly. Overall mortality was measured at 3years. At baseline, cardiovascular involvement was present in 37 patients, including 17 with pulmonary artery hypertension (PAH) and 20 with a left ventricular ejection fraction (LVEF) <55%. At 3years, 32 (7%) patients had died. The median [25th-75th percentile] NT-proBNP concentration was 203ng/l [129-514] in patients who died within 3years, versus 88ng/l [47-167] in survivors (P<0.001). NT-proBNP was an independent predictor of 3-years mortality in multivariate analysis (P=0.046). The optimal cut-off derived from the ROC curve was 129ng/l; sensitivity and specificity to predict 3y mortality were 78.1 and 66.7%. Using the previously recommended 125-ng/l concentration as threshold value, NT-proBNP reliably and independently predicted 3year mortality, with a sensitivity of 78.1 and a negative predictive value of 97.6%, respectively (P=0.006). The consideration of SSc patients without PAH or LVEF<55% at baseline yielded similar results., Conclusion: NT-proBNP appears as a reliable and independent predictor of mortality in patients with SSc., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: The introduction of high-sensitivity cardiac troponin (hs-cTn) assays allows the assessment of clinical decision values below the 99th percentile., Methods: Final diagnosis and one-year mortality were adjudicated in a multicenter, prospective cohort of 1181 patients presenting with acute chest pain to the emergency department. Hs-cTnT (Roche) and cTnI-ultra (Siemens) were measured in a blinded fashion., Results: At presentation hs-cTnT and cTnI-ultra were below the limit of blank (LOB) in 201 (17%) and 549 (47%) patients, below the 75th percentile in 379 (32%) and 623 (53%) patients, below the 95th percentile in 603 (51%) and 808 (68%), and below the 99th percentile in 748 (63%) and 913 (77%), respectively. Sensitivities for the diagnosis of AMI were 100.0% and 96.8% respectively for hs-cTnT and cTnI-ultra (LOB as cut-off value), 99.5% and 96.2% (75th percentile), 96.8% and 93.0% (95th percentile), and 94.1% and 88.1% (99th percentile). The proportion of patients correctly classified as having or not AMI increased from 32.9% (LOB as cut-off value) to 47.8% (75th percentile), 65.9% (95th percentile) and 77.3% (99th percentile) for hs-cTnT and from 61.2% to 67.3%, 81.9% and 89.3% respectively for cTnI-ultra. At 1 year, all-cause mortality was very low and similar for patients below all of these cut-off levels (between 0.7% and 1.5%, p=0.748 for all-groups comparison)., Conclusion: cTn should be considered as a continuous variable. Decision values below the 99th percentile (e.g. the 75th percentile) are associated with a very high NPV for the diagnosis of AMI, but have a lower accuracy than the 99th percentile., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Background: The purpose of this study was to investigate the utility of mid-regional pro-adrenomedullin (MR-proADM) in the early diagnosis and risk stratification of patients with acute chest pain in comparison with established and novel biomarkers and risk scores., Methods: In this prospective, observational, international, multi-center trial (APACE), MR-proADM was determined in 1179 unselected patients with acute chest pain. Patients were followed for 24 months., Results: MR-proADM concentrations at presentation were higher in patients with AMI (median: 0.78 nmol/l, IQR 0.60-1.13) than in patients with other diagnoses (0.64 nmol/l, IQR 0.49-0.86 nmol/l; p<0.001). The diagnostic accuracy of MR-proADM for AMI as quantified by the area under the receiver operating characteristic curve (AUC) was 0.66. Adding MR-proADM to hs-cTnT could not improve its diagnostic accuracy for AMI (p=0.431). Seventy-six percent of all deaths occurred in the fourth quartile of MR-proADM (>0.90 nmol/l). Adding MR-proADM to the TIMI-score (AUC 0.87) predicted 1-year mortality more accurately than the TIMI-score alone (AUC 0.82; p<0.001). Net reclassification improvement (TIMI vs. additionally MR-proADM) amounted to 0.137 (p=0.012). MR-proADM had higher prognostic accuracy as compared to hs-cTnT in patients with AMI (p=0.015) and in those without AMI (p=0.003). MR-proADM at presentation was tantamount to GRACE score and BNP as to its prognostic accuracy for mortality. The AUC for the prediction of cardiovascular events amounted to 0.63., Conclusions: While MR-proADM does not have clinical utility in the early diagnosis of AMI or predicting cardiovascular events in patients with acute chest pain, it may provide prognostic value for all-cause mortality., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Background: Patients with acute chest pain having serial undetectable cardiac troponin (cTn) levels, as measured with conventional assays, are considered at very low risk. The aim of this multicenter study was to determine the accuracy of multiple biomarkers in these patients., Methods: We enrolled 1247 consecutive patients with suspected AMI. Of these, 325 had undetectable levels of cTnT (Roche, 4th generation assay) at presentation and at 6h. Fourteen novel markers quantifying cardiomyocyte damage, inflammation and/or plaque rupture, and neurohormonal activation were measured at presentation. The occurrence of death or acute myocardial infarction (AMI) (primary end point) and unplanned coronary revascularization (secondary endpoint) were recorded during long-term follow-up., Results: During a mean follow-up of 668 ± 241 days, death/AMI occurred in 23 patients (7%), unplanned revascularization in 46 (14%). Among all biomarkers, high-sensitive cTnT (hs-cTnT), Midregional pro-adrenomedullin (MR-proADM) and growth differentiation factor-15 (GDF-15) were independently associated with future death/AMI; hs-cTnT was 0.013 (0.008-0.017) μg/l versus 0.006 (0.003-0.010) μg/l, MR-proADM was 0.78 (0.66-1.09) nmol/l versus 0.60 (0.18-0.80) nmol/l and GDF-15 was 1800 (1600-2200) ng/l versus 1100 (800-1700) ng/l in patients with versus without death/AMI during follow-up (p<0.001 each). The area under the receiver-operating characteristics curve to predict death/AMI was 0.73 (95%CI 0.63-0.83) for hs-cTnT, 0.71 (95% CI 0.62-0.81) for MR-proADM and 0.78 (95%CI 0.71-0.86) for GDF-15., Conclusion: Patients with serial undetectable levels of cTnT using the contemporary 4th generation assay are at low but not negligible risk of future cardiac events. Hs-cTnT, MR-proADM and/or GDF-15 might help to further improve risk-stratification in this group., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Background: Community-acquired pneumonia (CAP) is common and associated with a considerable risk of acute kidney injury (AKI)., Methods: We prospectively enrolled 341 patients presenting to the emergency department with CAP (mean age 72, male 61%). Blinded measurements of three natriuretic peptides (NT-proBNP, MR-proANP and BNP) were performed upon presentation. The primary endpoint was the accuracy of the natriuretic peptides to predict AKI within 48h., Results: AKI occurred in 24 patients (7.6%) within the first 48h. NPs and creatinine were significantly higher in AKI compared with patients without AKI (NT-proBNP 9517 [2042-26,792] vs 1177 [280-4167]pg/ml; MR-proANP 641 [196-1075] vs 182 [99-352]pmol/l; BNP 592 [230-1630] vs 160 [64-463]pg/ml; creatinine 166 [131-289] versus 100 [78-134] μmol/l, P<0.001 for each). Predictive accuracy as quantified by the area under the receiver operating characteristics curve was moderate to high: NT-proBNP 0.79 (95%CI 0.70-0.88), MR-proANP 0.78 (95%CI 0.67-0.88), BNP 0.74 (95%CI 0.63-0.85), creatinine 0.77 (95%CI 0.66-0.88). In multivariate logistic regression analysis, NPs remained the only independent AKI predictors: NT-proBNP (increase of 200 pg/ml) OR=1.01, 95%CI 1.00-1.01, P=0.009; MR-proANP (increase of 100 pg/ml) OR=1.23, 95%CI 1.09-1.39, P=0.001; BNP (increase of 100 pg/ml) OR=1.08, 95%CI 1.03-1.14, P=0.002., Conclusions: NP levels are significantly elevated in CAP-patients experiencing early AKI. Their potential to predict early AKI is comparable to serum creatinine and might be useful in cases of diagnostic uncertainty., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Background: Early and accurate risk stratification for patients with community-acquired pneumonia (CAP) is an unmet clinical need., Methods: We enrolled 341 unselected patients presenting to the ED with CAP in whom blinded measurements of N-terminal pro-B-type natriuretic peptide (NT-proBNP), midregional pro-atrial natriuretic peptide (MR-proANP), and B-type natriuretic peptide (BNP) were performed. The potential of these natriuretic peptides to predict short- (30-day) and long-term mortality was compared with the pneumonia severity index (PSI) and CURB-65 (confusion, urea plasma level, respiratory rate, BP, age over 65 years). The median follow-up was 942 days., Results: NT-proBNP, MR-proANP, and BNP levels at presentation were higher in short-term (median 4,882 pg/mL vs 1,133 pg/mL; 426 pmol/L vs 178 pmol/L; 436 pg/mL vs 155 pg/mL, all P < .001) and long-term nonsurvivors (3,515 pg/mL vs 548 pg/mL; 283 pmol/L vs 136 pmol/L; 318 pg/mL vs 103 pg/mL, all P < .001) as compared with survivors. Receiver operating characteristics analysis to quantify the prognostic accuracy showed comparable areas under the curve for the three natriuretic peptides to PSI for short-term (PSI 0.76, 95% CI, 0.71-0.81; NT-proBNP 0.73, 95% CI, 0.67-0.77; MR-proANP 0.72, 95% CI, 0.67-0.77; BNP 0.68, 95% CI, 0.63-0.73) and long-term (PSI 0.72, 95% CI, 0.66-0.77; NT-proBNP 0.75, 95% CI, 0.70-0.80; MR-proANP 0.73, 95% CI, 0.67-0.77, BNP 0.70, 95% CI, 0.65-0.75) mortality. In multivariable Cox-regression analysis, NT-proBNP remained an independent mortality predictor (hazard ratio 1.004, 95% CI, 1.00-1.01, P = .02 for short-term; hazard ratio 1.004, 95% CI, 1.00-1.01, P = .001 for long-term, increase of 300 pg/mL). A categorical approach combining PSI point values and NT-pro-BNP levels adequately identified patients at low, medium, and high short- and long-term mortality risk., Conclusions: Natriuretic peptides are simple and powerful predictors of short- and long-term mortality for patients with CAP. Their prognostic accuracy is comparable to PSI.

Background: Recently, concerns have been raised about a possible lack of sensitivity of biomarkers to detect left ventricular (LV) dysfunction in patients with myopathies. We examined the ability of the N-terminal brain natriuretic peptide (NT-proBNP) to detect LV or right ventricular (RV) dysfunction in patients with lamin A/C (LMNA) gene mutations., Methods: We prospectively measured plasma NT-proBNP in consecutive patients with documented LMNA mutations and age-sex matched controls. All patients underwent standard echocardiography implemented by pulsed tissue-Doppler echocardiography (TDE)., Results: Twenty-three patients were included (10 males, mean age 39.2 ± 18.9 years);10 had previous atrial arrhythmias, 8 had been implanted with cardioverter defibrillator for primary prevention of sudden death, 5 patients were of NYHA class II and 18 of NHYA class I. Sinus rhythm was recorded in all. NT-proBNP was increased in LMNA patients versus controls (123 ± 229 versus 26 ± 78 pg/ml, p=0.0004); 7 patients had depressed LV and/or RV contractility. Patients with reduced LV or RV contractility had increased mean NT-proBNP (341 ± 1032 pg/ml versus 80 ± 79 pg/ml in patients with normal myocardial contractility, p=0.004). Receiver-operating-characteristics analysis shows that NT-proBNP reliably detected depressed contractility (area under the curve 0.889 [0.697-1.000]). Sensitivity and specificity were 88% and 83% respectively, applying manufacturer's recommended cut-off concentration of 125 pg/ml., Conclusion: NT-proBNP reliably detected the presence of reduced LV/RV contractility in LMNA patients., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Oxidative stress contributes to the pathogenesis of Duchenne muscular dystrophy (DMD). Although they have been a model for DMD, mdx mice exhibit slowly developing cardiomyopathy. We hypothesized that disease process was delayed owing to the development of an adaptive mechanism against oxidative stress, involving glutathione synthesis. At 15 to 20 weeks of age, mdx mice displayed a 33% increase in blood glutathione levels compared with age-matched C57BL/6 mice. In contrast, cardiac glutathione content was similar in mdx and C57BL/6 mice as a result of the balanced increased expression of glutamate cysteine ligase catalytic and regulatory subunits ensuring glutathione synthesis in the mdx mouse heart, as well as increased glutathione peroxidase-1 using glutathione. Oral administration from 10 weeks of age of the glutamate cysteine ligase inhibitor, l-buthionine(S,R)-sulfoximine (BSO, 5 mmol/L), led to a 33% and 50% drop in blood and cardiac glutathione, respectively, in 15- to 20-week-old mdx mice. Moreover, 20-week-old BSO-treated mdx mice displayed left ventricular hypertrophy associated with diastolic dysfunction, discontinuities in beta-dystroglycan expression, micronecrosis and microangiopathic injuries. Examination of the glutathione status in four DMD patients showed that three displayed systemic glutathione deficiency as well. In conclusion, low glutathione resource hastens the onset of cardiomyopathy linked to a defect in dystrophin in mdx mice. This is relevant to the glutathione deficiency that DMD patients may suffer.

Background: Bed rest is often recommended as part of the management of deep vein thrombosis (DVT) and pulmonary embolism (PE), though this recommendation is not clearly evidence-based., Methods: Using the Cochrane Central Register of Controlled Trials, Medline, and Embase, this meta-analysis considered all randomized studies and prospective registries that compared the outcomes of patients with DVT, PE, or both, managed with bed rest versus early ambulation, in addition to anticoagulation. For each study, data regarding the incidence of new PE, new or progression of DVT, and death from all causes, were used to calculate relative risks (RR) and 95% confidence intervals (CI)., Results: The 5 studies retained in this analysis included a total of 3048 patients. When compared to bed rest, early ambulation was not associated with a higher incidence of a new PE (RR 1.03; 95% CI 0.65-1.63; p=0.90). Furthermore, early ambulation was associated with a trend toward a lower incidence of new PE and new or progression of DVT than bed rest (RR 0.79; 95% CI 0.55-1.14; p=0.21) and lower incidence of new PE and overall mortality (RR 0.79; 95% CI 0.402-1.56; p=0.50)., Conclusions: Compared with bed rest, early ambulation of patients with DVT, PE or both, was not associated with a higher risk of progression of DVT, new PE or death. This meta-analysis does not support the systematic recommendation of bed rest as part of the early management of patients presenting with DVT, PE of both.

Since the introduction of routine assay for natriuretic peptides, there are a growing number of clinical applications for those new tests. Numerous studies have defined analytical characteristics and clinical interest of NT-proBNP assay. Originally limited to acute heart failure diagnosis in the emergency room, NT-proBNP assay has now a wide number of applications. This literature review presents the "state of art" of this marker, detailing NT-proBNP physiological recent knowledge and its recognized or investigated clinical applications.

Background: By inhibiting prostaglandins, aspirin may be deleterious in congestive heart failure (CHF) and/or partially counteract the efficacy of angiotensin-converting enzyme inhibitors (ACEI). Conversely, clopidogrel has no effect on prostaglandin metabolism. The aim of this study was to prospectively investigate the effect of aspirin and clopidogrel on arterial functional properties in CHF patients treated with ACEI., Methods: Forty-five patients with stable NYHA class II-IV CHF (64.0+/-15.5 years), ejection fraction <40%, were included in this prospective double-blind study and randomized to receive aspirin 325 mg/day or clopidogrel 75 mg/day for 14 days. Reflected wave assessed by radial applanation tonometry and pulse wave velocity (PWV) were measured at day 0 and day 14., Results: Aspirin resulted in an increase in the augmentation index of the reflected wave (Delta=+3.5+/-5.2%, p=0.005) and the height above the shoulder of the reflected wave (Delta=+1.7+/-3.1 mm Hg, p=0.023), without statistically variation in PWV. Conversely, clopidogrel had no effect on the same parameters (p=0.512, p=0.677 and 0.801, respectively). Overall, variations in the augmentation index of reflected wave significantly differed when compared aspirin with clopidogrel (p=0.0261)., Conclusion: This study demonstrates the existence of a negative effect of aspirin 325 mg/day when compared to clopidogrel 75 mg/day on arterial functional properties in CHF patients treated with ACEI.

A 24-year-old woman, with known antiphospholid antibodies (APS), presented with an acute myocardial infarction (AMI) that occurred three months after delivery. No risk factors for arteriosclerosis and no past history of arterial/venous thrombosis were noted. During pregnancy, aspirin prophylaxis was prescribed and followed by steroids after caesarian section. Steroids withdrawal was followed by AMI. Immediate coronary angiography revealed thrombotic occlusion of the left descending coronary artery; PTCA was successfully performed. She was discharged with an antiplatelet and anticoagulant regimen. No recurrent coronary event occurred during follow-up.