Feasibility and accuracy of linking a heart failure registry to the national claims database using indirect identifiers.

BACKGROUND: Heart failure (HF) registries include rich data on patient inclusion characteristics, but follow-up information is often incomplete. Medicoadministrative databases may provide less clinical information than registries, e.g. on left ventricular ejection fraction (LVEF), but long-term data are exhaustive and reliable. The combination of the two types of database is therefore appealing, but the feasibility and accuracy of such linking are largely unexplored. AIMS: To assess the feasibility and accuracy of linking an HF registry (FRESH; FREnch Survey on Heart Failure) with the French National Healthcare System database (SNDS). METHODS: A probabilistic algorithm was developed to link and match patient data included in the FRESH HF registry with anonymized records from the SNDS, which include: hospitalizations and diagnostic codes; all care-related reimbursements by national health system; and deaths. Consistency was assessed between deaths recorded in the registry and in the SNDS. A comparison between the two databases was carried out on several identifiable clinical characteristics (history of HF hospitalization, diabetes, atrial fibrillation, chronic bronchopneumopathy, severe renal failure and stroke) and on events during 1-year follow-up after inclusion. RESULTS: Of 2719 patients included in the FRESH registry (1049 during decompensation; 1670 during outpatient follow-up), 1885 could be matched with a high accuracy of 94.3% for deaths. Mortality curves were superimposable, including curves according to type of HF and LVEF. The rates of missing data in the FRESH registry were 2.3-8.4% for clinical characteristics and 17.5% for hospitalizations during follow-up. The discrepancy rate for clinical characteristics was 3-13%. Hospitalization rates were significantly higher in the SNDS than in the registry cohort. CONCLUSIONS: The anonymous matching of an HF research cohort with a national health database is feasible, with a significant proportion of patients being accurately matched, and facilitates combination of clinical data and a reduced rate of losses to follow-up.

[Interest of ambulatory management of patients with chronic heart failure by protocolized follow-up and therapeutic education: results of the USICAR experiment]. / Intérêt de la prise en charge ambulatoire des patients insuffisants cardiaques chroniques par suivi protocolisé et éducation thérapeutique : résultats de l'expérimentation USICAR.

OBJECTIVE: The objective of this study is to determine whether the implementation of regular and structured follow-up of patients with chronic heart failure (CHF), combined with therapeutic education, led to better management of these patients. PATIENTS AND METHOD: This was a monocentric, retrospective study on a cohort of patients with a proven CHF, followed in the Mulhouse region (France), between January 2016 and December 2017, by the Unit for Monitoring Heart Failure Patients (USICAR). These patients benefited from a regular protocolized follow-up and a therapeutic education program for a period of 2 years. The main criterion of this study was: the number of days of hospitalization for HF per year and per patient. The secondary endpoints were: the number of days of hospitalization for cardiac causes other than HF and the number of hospital stays for HF per patient. These criteria were collected over the one-year period before inclusion, at one-year-follow-up, and at two-years-follow-up. RESULTS: 159 patients with a mean age of 72.9 years were included in this study. They all had a CHF, mainly stage I-II NYHA (88.7%), of predominantly ischemic origin (50.9%), with altered left ventricular ejection fraction in 69.2% of cases. The primary endpoint averaged 8.33 days (6.84-10.13) in the year prior to inclusion, 2.6 days (1.51-4.47) in the first year of follow-up, and 2.82 days (1.30-6.11) (p <0.01 for both comparisons). The mean number of days of hospitalization for other cardiac causes other than HF to patient numbers was: 1.73 days (1.16-2.6), 1.81 days (1.04-3.16), and 1.32 days (0.57-3.08) (p = ns). The percentage of hospitalization for HF for each patient was: 69.5% (60.2-77.4) before inclusion, 16.2% (10-25.2) during the first year of follow-up and 19.3% (11-31.8) during the second (p < 0.001 for both comparisons). CONCLUSION: This study demonstrates the value of a protocolized follow-up associated with a therapeutic education program to improve the management of ambulatory CHF patients, particularly for moderate CHF.

Benefit of Ambulatory Management of Patients with Chronic Heart Failure by Protocolized Follow-Up Therapeutic Education and Remote Monitoring Solution: An Original Study in 159 Patients.

This study sought to determine whether the implementation of regular and structured follow-up of patients with chronic heart failure (CHF), combined with therapeutic education and remote monitoring solution, leads to better management. This was a single-center retrospective study conducted in a cohort of patients with proven CHF who were followed up in the Mulhouse region (France) between January 2016 and December 2017 by the Unité de Suivi des Patients Insuffisants Cardiaques (USICAR) unit. These patients received regular protocolized follow-up, a therapeutic education program, and several used a telemedicine platform for a two-year period. The primary endpoint was the number of days hospitalized for heart failure (HF) per patient per year. The main secondary endpoints included the number of days hospitalized for a heart condition other than HF and the number of hospital stays for HF per patient. These endpoints were collected during the year preceding enrollment, at one year of follow-up, and at two years of follow-up. The remote monitoring solution was evaluated on the same criterion. Overall, 159 patients with a mean age of 72.9 years were included in this study. They all had CHF, mainly NYHA Class I-II (88.7%), predominantly of ischemic origin (50.9%), and with altered left ventricular ejection fraction in 69.2% of cases. The mean number of days hospitalized for HF per patient per year was 8.33 (6.84-10.13) in the year preceding enrollment, 2.6 (1.51-4.47) at one year of follow-up, and 2.82 at two years of follow-up (1.30-6.11) (p < 0.01 for both comparisons). The mean number of days hospitalized for a heart condition other than HF was 1.73 (1.16-2.6), 1.81 (1.04-3.16), and 1.32 (0.57-3.08), respectively (p = ns). The percentage of hospitalization for HF for each patient was 69.5% (60.2-77.4), 16.2% (10-25.2), and 19.3% (11-31.8), respectively (p < 0.001 for both comparisons). In the group telemedicine, the mean number of days hospitalized for HF per patient per year was 8.33 during the year preceding enrollment, 2.3 during the first year of follow-up, and 1.7 during the second. This difference was significant (p < 0.001). The "number of days hospitalized for a heart condition other than HF" was significantly reduced in the group of patient's beneficiating from the remote monitoring solution. This study demonstrates the value of a protocolized follow-up associated with a therapeutic optimization, therapeutic education program, and the use of a remote monitoring solution to improve the management of ambulatory patients with CHF, particularly of moderate severity.

Evaluation of the French National Program on Home Return of Patients with Chronic Heart Failure (PRADO-IC): Pilot Study of 91 Patients During Its Deployment in the Bas Rhin Area.

OBJECTIVE: The main objective of this study was to evaluate the impact of the French national program on home return of chronic heart failure patients (PRADO-IC) in terms of re-hospitalizations for heart failure (HF) during its deployment in the Bas-Rhin (France). PATIENTS AND METHODS: This was a pilot, descriptive, quantitative, retrospective, and bi-centric study (University Hospitals of Strasbourg and Haguenau Hospital Center, France). It included all patients included in the PRADO-IC program from these centers between January 1, 2015 and December 31, 2015. The primary endpoint of our study was the evaluation of the number of 1-year, 6-month, and 30-day re-admissions to the hospital in relation to an acute HF episode, before and after the inclusion of patients in the PRADO-IC program. The secondary endpoints were the number of overall re-hospitalizations (all-cause); the number of days of hospitalization for HF; the time to first re-hospitalization and the average length of hospital stay, before and after inclusion in PRADO-IC; and the overall and cardiovascular mortality rates. RESULTS: 91 patients out of 271 (33,6%) with a mean age of 79.2 years (67-94) were included. They all had chronic HF, essentially class II-III NYHA (90.1%), mostly of ischemic origin (41.9%), with altered left ventricular ejection fraction in 71.4% of cases. A reduction in the mean number of hospitalizations for HF per patient at 30 days, 6 months and 1 year was observed, respectively, from 0.18 ± 0.42 per patient before inclusion to 0.15 ± 0.36 after inclusion (p = 0.56); 0.98 ± 1.04 hospitalizations to 0.53 ± 0.81 at 6 months (p < 0.01); and 1.64 ± 1.14 hospitalizations 1.04 ± 1.05 at 1 year (p < 0.001). Patients were hospitalized less overall after inclusion in the PRADO-IC program. The number of days of hospitalization for HF was reduced after inclusion of patients from 18.02 ± 7.78 days before inclusion to 14.28 ± 11.57 days for the 6 month follow-up (p = 0.006), and from 22.07 ± 10.33 days before inclusion to 16.39 ± 15.94 days for the 1 year follow-up (p < 0.001). In contrast, inclusion in PRADO-IC statistically increased the mean time to first re-hospitalization for HF from mean 99.36 ± 72.39 days before inclusion to 148.11 ± 112.77 days after inclusion (p < 0.001). CONCLUSION: This study seems to demonstrate that the PRADO-IC program could improve the management of chronic HF patients in ambulatory care, particularly regarding HF re-hospitalization. However, due to the limitations of the methodology used and the small number of patients, it is advisable to consolidate its initial results with a randomized controlled study on a larger number of patients. In our opinion, its results need to be communicated because, to our knowledge, no equivalent study exists.

Increased expression of blood muscarinic receptors in patients with reflex syncope.

AIMS: Pathophysiology of reflex syncope is not fully understood but a vagal overactivity might be involved in this syncope. Previously, overexpression of muscarinic M2 receptors and acetylcholinesterase was found in particular in the heart and in lymphocytes of rabbits with vagal overactivity as well as in hearts of Sudden Infant Death Syndromes. The aim of this present study was to look at M2 receptor expression in blood of patients with reflex syncope. The second objective was to measure acetylcholinesterase expression in these patients. METHODS AND RESULTS: 136 subjects were enrolled. This monocenter study pooled 45 adults exhibiting recurrent reflex syncope compared with 32 healthy adult volunteers (18-50 years) and 38 children exhibiting reflex syncope requiring hospitalization compared with 21 controls (1-17 years). One blood sample was taken from each subject and blood mRNA expression of M2 receptors was assessed by qRT-PCR. Taking into account the non-symmetric distributions of values in both groups, statistical interferences were assessed using bayesian techniques. A M2 receptor overexpression was observed in adult and pediatric patients compared to controls. The medians [q1;q3] were 0.9 [0.3;1.9] in patients versus 0.2 [0.1;1.0] in controls; the probability that M2 receptor expression was higher in patients than in controls (Pr[patients>controls]) was estimated at 0.99. Acetylcholinesterase expression was also increased 0.7 [0.4;1.6] in patients versus 0.4 [0.2;1.1] in controls; the probability that acetylcholinesterase expression was higher in patients than in controls (Pr[patients>controls]) was estimated at 0.97. Both in adults and children, the expression ratio of M2 receptors over acetylcholinesterase was greater in the patient group compared with the control group. CONCLUSION: M2 receptor overexpression has been detected in the blood of both, adults and children, exhibiting reflex syncope. As in our experimental model, i.e. rabbits with vagal overactivity, acetylcholinesterase overexpression was associated with M2 receptor overexpression. For the first time, biological abnormalities are identified in vagal syncope in which only clinical signs are, so far, taken into account for differential diagnosis and therapeutic management. Further work will be needed to validate potential biomarkers of risk or severity associated with the cholinergic system.

Pulmonary hypertension in chronic heart failure: definitions, advances, and unanswered issues.

Pulmonary hypertension (PH) is a common and severe complication of heart failure (HF). Consequently, HF is the leading cause of PH. For many years, specialists have attempted to better understand the pathophysiology of PH in HF, to define its prevalence and its impact on prognosis in order to improve the therapeutic management of these patients. Nowadays, despite the recent guidelines published on the subject, several points remain unclear or debated, and until now, no study has demonstrated the efficacy of any treatment. The aim of this review is to report the evolution of the concepts on post-capillary PH (diagnosis, prevalence, prognosis, and therapeutics). The main issues are raised, focusing especially on the link between structural alterations and haemodynamic abnormalities, to discuss the possible reasons for treatment failures and future potential targets.

Practical management of concomitant acute heart failure and worsening renal function in the emergency department.

Worsening renal function (i.e. any increase in creatinine or decrease in the estimated glomerular filtration rate) is common in patients admitted for acute heart failure in the emergency department. Although worsening renal function (WRF) has been associated with the occurrence of dismal outcomes, this only appears to be the case when associated with clinical deterioration. However, if the clinical status of the patient is improving, a certain increase in serum creatinine may be acceptable. This WRF, which is not associated with clinical deterioration or adverse outcomes (e.g. during treatment up-titration), has been referred to as 'pseudo-WRF' and should not detract clinicians from targeting 'guideline-recommended' therapies. This is an important message for emergency physicians to pursue diuretics as long as signs of pulmonary congestion persist to improve the clinical status of the patient. In the present review, we aim to provide clinicians in acute settings with an integrative and comprehensive approach to cardiorenal interactions in acute heart failure.

Comparison of the long-term reproducibility of the walk test and of exercise peak oxygen consumption in patients with preserved exercise capacity.

Short-term and long-term reproducibility of the cardiopulmonary (CPX) exercise test have been established. Though short and mid-term reproducibility of the walk test has been ascertained, this was not extensively done for the long-term reproducibility. The aim of the study was to examine the long-term reproducibility of distance walked in an allotted time and to check the stability of the relationship between walked distance and exercise peak VO2 (pVO2). METHODS: Forty six subjects (33 men; 57 ± 14 years), referred for functional capacity assessment, were studied twice by CPX and walking test. On the same day, CPX was performed on a bicycle or a treadmill and walk test in a corridor as required by specific guidelines. We performed a 12-minute walk test and the distance covered in six minutes was systematically taken down. A free time interval of 1.5 hours was observed between the exercise tests. Distance walked in the allotted time and pVO2 were analysed. Reproducibility was assessed according to Bland and Altman plots and intra-class coefficient correlation (ICC). The relationship between distance ambulated and pVO2 was analysed by the Spearman coefficient correlation. RESULTS: The time interval between the two evaluations was 290 ± 10 days. During this meantime, for those subjects having drug treatment, no change was recorded in their regimen. BMI remained stable for the entire studied population (28 ± 5 kg/m2). Minute walked distance was respectively 522 ± 83 and 527 ± 76 m in six minutes, 1033 ± 182 and 1041 ± 153 m in 12 minutes. pVO2 was 21 ± 7 and 22 ± 7 ml/kg/min (all p = NS). The walk test was reproducible in the long-term, regardless of the modality (6 or 12-minute walk) as shown by the Bland-Altman plots and the high ICC of .89. Spearman's rho coefficient between distance ambulated and pVO2 was modest and remained stable over time whatever the allotted time: Spearman's r = .54; p = .0011 (1st evaluation) and Spearman's r = .51; p = .0019 (2nd evaluation) between 6-minute distance walked and pVO2. CONCLUSIONS: The walking distance in an allotted time seems highly reproducible in the long-term. Its relationship with pVO2 remains stable over time. It could be of value for repeated assessment of patients' exercise capacity in a first step. Further evaluation in a larger population is needed to confirm our result and its usefulness in clinical practice.

Impact of fondaparinux versus enoxaparin on in-hospital bleeding and 1-year death in non-ST-segment elevation myocardial infarction. FAST-MI (French Registry of Acute ST-elevation and non-ST-elevation Myocardial Infarction) 2010.

AIMS: Fondaparinux is an alternative to low molecular weight heparin (LMWH) for non-ST-elevation myocardial infarction (NSTEMI) with levels of recommendation that differ according to guidelines. The aim of this study was to assess outcomes in real world practice in NSTEMI patients participating in the French Registry of ST-elevation and non-ST-elevation Myocardial Infarction (FAST-MI) 2010 according to the use of fondaparinux, in comparison with patients receiving enoxaparin. METHODS AND RESULTS: FAST-MI 2010 is a nationwide French registry that included 4,169 patients with acute myocardial infarction at the end of 2010 in 213 centres (76% of active centres in France); 1,734 had NSTEMI, with 240 receiving fondaparinux and 1,027 enoxaparin. Patients receiving enoxaparin vs. fondaparinux had essentially characteristics with a similar GRACE (Global Registry of Acute Coronary Events) score. Invasive strategy was used in 69% in both groups. In-hospital bleeding was similar with both anticoagulant strategies and 1-year survival was 94.6% and 91.7%, respectively. Using fully adjusted Cox multivariate analysis, the use of fondaparinux was not associated with a reduced risk of death (hazard ratio: 1.35; 95% confidence interval: 0.70-2.51). After propensity score matching (207 patients per group), 1-year survival was similar with both strategies. There was, however, an interaction between fondaparinux and unfractionated heparin, with higher survival in fondaparinux-treated patients who received UFH, compared with those who did not. CONCLUSIONS: In this French cohort of NSTEMI patients, predominantly managed invasively, there was no evidence that fondaparinux was superior to enoxaparin as regards bleeding events or 1-year mortality (FAST-MI 2010; NCT01237418).

Can we obtain a noninvasive and continuous estimation of cardiac output? Comparison between three noninvasive methods.

Cardiac output (CO) is often desirable for assessing the hemodynamic condition of a patient, especially in critically ill cardiac patients. Various noninvasive methods are available for this purpose. Inert gas rebreathing (IGR) and 2D-Doppler echocardiography methods have been validated. Based on the relationship between pulse wave transit time and stroke volume, the VISMO® provides an estimated continuous cardiac output (esCCO) measurement using only an electrocardiogram, pulse oximeter wave, and cuff arterial blood pressure. Doppler echocardiography is being currently used in every day practice in this setting and IGR is a validated method, thus we wanted to assess the agreement between these 3 methods for noninvasive CO calculation and reproducibility of esCCO. Patients followed in our cardiology department received on the same day a CO analysis by esCCO, Doppler echocardiography and IGR. Thirty-four patients were included (16 women, mean age 65 ± 15 years). Bland and Altman plots showed a good agreement between IGR and 2D-Doppler echocardiography (bias = 0.31 L/minute). Though there was also an agreement between esCCO and the other 2, the bias was rather large: 1.18 L/minute with IGR and 1.51 L/min with 2D-Doppler echo. The intraclass correlation coefficient was poor whatever the methods. However, esCCO had a satisfactory reproducibility and accuracy compared rather well with the other 2. This method could be suitable for patient screening and monitoring.

In-hospital complications after invasive strategy for the management of Non STEMI: women fare as well as men.

BACKGROUND: To analyze the in-hospital complication rate in women suffering from non-ST elevation myocardial infarction treated with percutaneous coronary intervention (PCI) compared to men. METHODS: The files of 479 consecutive patients (133 women and 346 men) suffering from a Non STEMI (Non ST-segment elevation myocardial infarction) between the January 1st 2006 and March 21st 2009 were retrospectively analyzed with special attention to every single complication occurring during hospital stay. Data were analyzed using nonparametric tests and are reported as median unless otherwise specified. A p value < .05 was considered significant. RESULTS: As compared to men, women were significantly older (75.8 vs. 65.2 years; p < .005). All cardiovascular risk factors but tobacco and hypertension were similar between the groups: men were noticeably more often smoker (p < .0001) and women more hypertensive (p < .005). No difference was noticed for pre-hospital cardiovascular drug treatment. However women were slightly more severe at entry (more Killip class IV; p = .0023; higher GRACE score for in-hospital death - p = .008 and CRUSADE score for bleeding - p < .0001). All the patients underwent PCI of the infarct-related artery after 24 or 48 hrs post admission without sex-related difference either for timing of PCI or primary success rate. During hospitalization, 130 complications were recorded. Though the event rate was slightly higher in women (30% vs. 26% - p = NS), no single event was significantly gender related. The logistic regression identified age and CRP concentration as the only predictive variables in the whole group. After splitting for genders, these parameters were still predictive of events in men. In women however, CRP was the only one with a borderline p value. CONCLUSIONS: Our study does not support any gender difference for in-hospital adverse events in patients treated invasively for an acute coronary syndrome without ST-segment elevation and elevated troponin.

[Anthracycline-induced cardiomyopathy]. / Cardiopathie aux anthracyclines.

Anthracycline-based antineoplastic therapy is the standard of care for various cancers today and represents a breakthrough in this area. The cardiac toxicity of anthracyclines is well established. The acute form is often reversible and has no predictive value for the future. This early form does not prevent continuation of chemotherapy. Late cardiac toxicity due to anthracycline is the leading limiting factor in its use. In adults, this resembles dilated cardiomyopathy, while in children it may be expressed as restrictive cardiomyopathy. The discovery of modifiable risk factors has made it possible to identify patients at high risk of developing late cardiac toxicity and heart failure. Because left ventricular dysfunction and heart failure may develop long after anthracycline treatment ends, prolonged close follow-up is mandatory in asymptomatic subjects. Follow-up of asymptomatic patients requires serial echocardiography (M-mode, 2D echo, Doppler, tissue Doppler, speckle tracking, etc.). Anthracycline-induced cardiomyopathy must be treated according to the standard guidelines for chronic heart failure with left ventricular dysfunction, by angiotensin-converting enzyme (ACE) inhibitors and beta-blockers. Lifestyle changes may reduce the long-term risk. Close collaboration between cardiologists and oncologists is highly desirable for optimizing management of these patients.

Lower circulating Sta-Liatest D-Di levels in patients with aortic intramural hematoma compared with classical aortic dissection.

OBJECTIVE: To compare the diagnostic value of circulating Sta-Liatest D-Di levels in classic acute aortic dissection (AAD) and in aortic intramural hematoma (AIH), a variant of AAD without a patent false lumen. DESIGN: Single-center retrospective case-control study. SETTING: University Hospital of Strasbourg, France. PATIENTS: Ninety-four consecutive patients with both confirmed AAD and d-dimer measurements at entry were included. d-dimer levels were assayed by the immunoturbidimetric method Sta-Liatest D-Di (Diagnostica Stago, Asnieres sur Seine, France). INTERVENTION: Patient characteristics and clinical evolution were analyzed. MEASUREMENTS AND MAIN RESULTS: Eighty-four patients (89%) presented a classic AAD with patent false lumen and ten (11%) presented an AIH. Clinical presentation did not differ between the two groups. The mortality rate was 0% in AIH and 26% in classic AAD. d-dimer levels were significantly lower in patients with AIH (median, 1230 ng/mL; interquartile range, 685-2645 ng/mL) than in patients with AAD with patent false lumen (median value, 9290 ng/mL; interquartile range, 3890-20,000 ng/mL; p = 0.008). All patients with AAD and patent false lumen had d-dimer levels above the threshold of 400 ng/mL (sensitivity 100%). However, one patient with AIH presented d-dimer levels below the threshold. Therefore, the sensitivity of the d-dimer test in detecting AIH was 90%. CONCLUSIONS: Sta-Liatest D-Di levels are lower in AIH than in AAD with patent false lumen. This test can quite possibly be negative in the case of intramural hematoma. This feature must be considered when interpreting d-dimer levels in patients with acute aortic syndrome.

Prognostic value of C-reactive protein and cardiac troponin I in primary percutaneous interventions for ST-elevation myocardial infarction.

BACKGROUND: The rise in cardiac troponin I after ST-elevation myocardial infarction treated by primary percutaneous coronary interventions (PCIs) is predictive of infarct size and left ventricular ejection fraction (LVEF). However, the comparative value of C-reactive protein (CRP) and troponin I for infarct size evaluation and the respective relationships between these biomarkers and mortality have not been investigated. METHODS: We studied 87 patients who underwent primary PCI for ST-elevation myocardial infarction. Concentrations of troponin I and CRP were measured before and for 72 hours after PCI. Infarct size was measured by the cumulative release of alpha-hydroxybutyrate deshydrogenase during the 72 hours after PCI (QHBDH72) and by delayed radionuclide LVEF (at 4.6 +/- 1.7 weeks). RESULTS: Concentrations of CRP at peak and at 24, 48 and 72 hours, and of troponin I at 6 and 72 hours, correlated with QHBDH72 and LVEF. In single variable analysis, at a mean follow-up of 42 +/- 8 months, Killip score of 3 to 4, CRP at baseline and at 48 hours, and troponin I at 6 and 72 hours were related to mortality. By multiple variable analysis, Killip score (OR 9.9, CI 1.6-58.8) and troponin I at 72 hours (OR 9.43, CI 2.1-43.5) were the only independent predictors of mortality. CONCLUSIONS: Plasma concentrations of CRP and troponin I after PCI were related to infarct size and mortality. However, Killip class and troponin I at 72 hours were the only independent predictors of mortality at long-term follow-up.

Diagnostic and prognostic value of circulating D-Dimers in patients with acute aortic dissection.

OBJECTIVE: We sought to determine whether assessing D-Dimer might be helpful for the management of acute aortic dissection (AAD). DESIGN: Single-center retrospective case-control study. SETTING: University Hospital of Strasbourg France. PATIENTS: Patients were 94 consecutive patients admitted to our institution with confirmed AAD and in whom D-Dimer test had been performed at presentation. These patients were matched with 94 controls presenting with clinical suspicion of dissection, which was later ruled out. INTERVENTIONS: Patient characteristics and clinical course were analyzed. MEASUREMENTS AND MAIN RESULTS: Ninety-three (99%) patients with AAD had elevated D-Dimer (>400 ng/mL) with a median D-Dimer value of 8610 ng/mL (interquartile range, 2982-20,000 ng/mL). Receiver operating characteristic curves analysis showed that D-Dimer, but not C-reactive protein, troponin, lactate dehydrogenase, or leukocyte count, was predictive of a diagnosis of AAD, with a sensitivity and specificity of 99% and 34%, respectively. D-Dimer concentration positively correlated with the anatomical extension of the dissection to the different segments of the aorta (R = .47, p < .0001). A positive relationship was observed between D-Dimer and in-hospital mortality rate among patients with AAD (p = .037). On multivariate analysis, the independent predictors of in-hospital mortality were the presence of pericardial effusion (odds ratio, 6.80; confidence interval, 1.87-27.60), D-Dimer >5200 ng/mL (odds ratio, 5.38; confidence interval, 1.27-30.87), and female gender (odds ratio, 4.96; confidence interval, 1.39-19.95). CONCLUSIONS: D-Dimers are elevated in patients with AAD and provide valuable diagnostic and prognostic information. In patients with acute chest pain and elevated D-Dimer, a diagnosis of AAD should also be considered. D-Dimer might be a useful complementary tool to the current diagnostic work-up of patients with suspected AAD.

Deletion of MLCK210 induces subtle changes in vascular reactivity but does not affect cardiac function.

Myosin light chain kinase (MLCK) plays a key role in the regulation of actomyosin contraction in a large variety of cells. Two isoforms have been described: a short isoform, widely expressed in smooth muscle cells; and a long isoform (MLCK210), mainly localized in the endothelium. This study investigated the consequences on different cardiovascular parameters of MLCK210 gene deletion using MLCK210 knockout mice and of pharmacological inhibition of the kinase using a specific MLCK inhibitor. Deletion of MLCK210 did not affect systolic blood pressure and heart rate or echocardiographic measurements. Electrocardiographic analysis showed neither atrio- nor intraventricular conduction or repolarization defects. Ex vivo responses of aortic rings to vasoconstrictor and vasodilator agonists were not modified in MLCK210 null mice. However, deletion of MLCK210 attenuated shear stress-induced dilation and produced changes in the balance of endothelial-relaxing factors of small mesenteric arteries (SMA). In particular, a reduced flow-mediated NO-dependent dilation was observed. However, it was partially compensated by enhanced indomethacin-sensitive dilation. No significant changes were detected in the endothelium-derived hyperpolarizing component of the vasodilator response. The above effects of MLCK210 gene deletion were confirmed in SMA from wild-type mice by the use of the MLCK enzymatic inhibitor MMZ-10-057. In summary, deletion of MLCK210 was not associated with abnormalities of main in vivo cardiovascular parameters in mice. This study demonstrates a role for MLCK210 in the regulation of flow-dependent dilation in SMA.