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Background Data on the prognostic value of left ventricular (LV) morphological and functional parameters including LV rotation in patients with dilated cardiomyopathy (DCM) using cardiovascular magnetic resonance (CMR) are currently scarce. In this study, we assessed the prognostic value of global longitudinal strain (GLS), global circumferential strain (GCS), global radial strain (GRS) and LV torsion using CMR feature tracking (FT). Methods CMR was performed in 350 DCM patients and 70 healthy subjects across 5 different European CMR Centers. Myocardial strain parameters were retrospectively assessed from conventional balanced steady-state free precession cine images applying FT. A combined primary endpoint (cardiac death, heart transplantation, aborted sudden cardiac death) was defined for the assessment of clinical outcome. Results GLS, GCS, GRS and LV torsion were significantly lower in DCM patients than in healthy subjects (all p Conclusion LV strain assessed with CMR FT has a high prognostic value in patients with DCM, surpassing routine and dedicated functional parameters. Thus, CMR strain imaging may contribute to the improvement of risk stratification in DCM.

Amyloidosis is a rare multiorgan disease defined by a process of irreversible, extracellular accumulation of fibrillar proteins in the tissues, including the heart. Cardiac involvement is seen in most forms of amyloidosis, but it is frequently present and clinically significant in light chain (AL)-amyloidosis as well as transthyretin amyloidosis (ATTR). Cardiac amyloid accumulation leads to a restrictive filling pattern, which must be differentiated from other forms of restrictive and hypertrophic cardiomyopathies due to consequences for the treatment. Evolving knowledge of the disease has led to a definite diagnosis of the cardiac amyloidosis (CA) using non-invasive and low-risk diagnostic features, such as scintigraphy (gamma scan) and cardiovascular magnetic resonance (CMR) imaging using late gadolinium enhancement (LGE) and T1 mapping technics. The availability and diagnostic accuracy of these technics has reduced the need for cardiac biopsy. In the following chapter, we will describe common types of CA, the basic concepts, and updates of non-invasive diagnostic features.

Reduced aerobic capacity and deconditioning contributes to morbidity and mortality in elderly acute heart failure (AHF) patients. Electrical muscle stimulation (EMS) has shown to be a suitable alternative to exercise in AHF. However, feasibility and efficacy are unknown in a real-world setting.This is a prospective, open label blinded, randomized, controlled study, investigating feasibility and efficacy of high-intensity versus low-intensity EMS versus controls in elderly AHF patients. Patients and investigators were blinded to the intervention. EMS was offered to60 years old AHF patients, initiated during hospitalization and continued at home. Outcome measures included changes in 6-min walking test distance (6-MWTD), functional capacity and quality-of-life at 3 and 6 weeks.Among 97 consecutive AHF patients (78.1 ± 9.4 years, 42.3% females), 60 (61.9%) were eligible for EMS. Of these, 27 provided written informed consent and were randomly assigned to high-intensity (n = 10), low-intensity EMS (n = 9) and controls (n = 8). 13/27 completed the intervention. Main reason for dropouts was intolerance of the overall intervention burden. MACE occurred in 5 and were not associated with the study. EMS groups showed significant improvement of 6-MWTD (controls vs low-intensity p = 0.018) and of independence in daily living (for both p 0.05).Changes in 6-MWTD suggest efficacy of EMS. Whereas all tolerated EMS well, the burden of study intervention was too high and resulted in a consent rate of50% and high dropouts, which limit the interpretability of our data. Less demanding EMS protocols are required to evaluate the full potential of EMS in elderly AHF patients.

Background The differentiated assessment of functional parameters besides morphological changes is essential for the evaluation of prognosis in systemic immunoglobulin light chain (AL) amyloidosis. Methods Seventy-four subjects with AL amyloidosis and presence of late gadolinium enhancement (LGE) pattern typical for cardiac amyloidosis were analyzed. Long axis strain (LAS) and myocardial contraction fraction (MCF), as well as morphological and functional markers, were measured. The primary endpoint was death, while death and heart transplantation served as a composite secondary endpoint. Results After a median follow-up of 41 months, 29 out of 74 patients died and 10 received a heart transplant. Left ventricular (LV) functional parameters were reduced in patients, who met the composite endpoint (LV ejection fraction 51% vs. 61%, LAS − 6.9% vs − 10%, GLS − 12% vs − 15% and MCF 42% vs. 69%; p

Chagas heart disease is becoming a worldwide health burden and represents a major cause of cardiovascular death in areas where it is endemic.

Anamnese: Ein 36-jahriger Mann mit PR3-ANCA positive Granulomatosis mit Polyangiitis stellt sich mit Thoraxschmerzen auf der Notfallstation vor. Im Rahmen seiner Grunderkrankung wurde er regelmasig mit Rituximab therapiert. Zuletzt wurde die Rituximab-Infusion am Vortag verabreicht. Untersuchung: Das EKG zeigt ausgepragte ST-Hebungen in V1-V4. Diagnose, Therapie und Verlauf: Es wird ein akuter Vorderwandinfarkt diagnostiziert und der Patient fur eine perkutane transluminale Koronarangioplastie vorbereitet. Wahrend der Patient in das Herzkatheterlabor transportiert wird, kommt es zu einem Kreislaufstillstand bei Kammerflimmern. Nach erfolgreicher elektromechanischer Reanimation kann in der Herzkatheteruntersuchung keine relevante Koronarstenose nachgewiesen werden. Wegen des Verdachts auf einen Koronarspasmus des Ramus interventricularis anterior wird die medikamentose Therapie mit einem Kalziumantagonisten erweitert. In sekundarpraventiver Absicht wird ein Einkammer- Kardioverter-Defibrillator implantiert. Folgerung: Das akute Koronarsyndrom ist eine mogliche Nebenwirkung einer Rituximab-Therapie. Im dargestellten Fall kann ein Zusammenhang zwischen der am Vortag verabreichten Rituximab-Infusion und dem kardialen Ereignis nicht ausgeschlossen werden.

BACKGROUND Patients with atrial fibrillation (AF) have an increased risk of cognitive decline, potentially resulting from clinically unrecognized vascular brain lesions. OBJECTIVES This study sought to assess the relationships between cognitive function and vascular brain lesions in patients with AF. METHODS Patients with known AF were enrolled in a multicenter study in Switzerland. Brain magnetic resonance imaging (MRI) and cognitive testing using the Montreal Cognitive Assessment (MoCA) were performed in all participants. Large noncortical or cortical infarcts (LNCCIs), small noncortical infarcts (SNCIs), microbleeds, and white matter lesions were quantified by a central core laboratory. Clinically silent infarcts were defined as infarcts on brain MRI in patients without a clinical history of stroke or transient ischemic attack. RESULTS The study included 1,737 patients with a mean age of 73 ± 8 years (28% women, 90% taking oral anticoagulant agents). On MRI, LNCCIs were found in 387 patients (22%), SNCIs in 368 (21%), microbleeds in 372 (22%), and white matter lesions in 1715 (99%). Clinically silent infarcts among the 1,390 patients without a history of stroke or transient ischemic attack were found in 201 patients with LNCCIs (15%) and 245 patients with SNCIs (18%). The MoCA score was 24.7 ± 3.3 in patients with and 25.8 ± 2.9 in those without LNCCIs on brain MRI (p < 0.001). The difference in MoCA score remained similar when only clinically silent LNCCIs were considered (24.9 ± 3.1 vs. 25.8 ± 2.9; p < 0.001). In a multivariable regression model including all vascular brain lesion parameters, LNCCI volume was the strongest predictor of a reduced MoCA (β = -0.26; 95% confidence interval: -0.40 to -0.13; p < 0.001). CONCLUSIONS Patients with AF have a high burden of LNCCIs and other brain lesions on systematic brain MRI screening, and most of these lesions are clinically silent. LNCCIs were associated with worse cognitive function, even among patients with clinically silent infarcts. Our findings raise the question of MRI screening in patients with AF.

Importance Short-term infusions of single vasodilators, usually given in a fixed dose, have not improved outcomes in patients with acute heart failure (AHF). Objective To evaluate the effect of a strategy that emphasized early intensive and sustained vasodilation using individualized up-titrated doses of established vasodilators in patients with AHF. Design, Setting, and Participants Randomized, open-label blinded-end-point trial enrolling 788 patients hospitalized for AHF with dyspnea, increased plasma concentrations of natriuretic peptides, systolic blood pressure of at least 100 mm Hg, and plan for treatment in a general ward in 10 tertiary and secondary hospitals in Switzerland, Bulgaria, Germany, Brazil, and Spain. Enrollment began in December 2007 and follow-up was completed in February 2019. Interventions Patients were randomized 1:1 to a strategy of early intensive and sustained vasodilation throughout the hospitalization (n = 386) or usual care (n = 402). Early intensive and sustained vasodilation was a comprehensive pragmatic approach of maximal and sustained vasodilation combining individualized doses of sublingual and transdermal nitrates, low-dose oral hydralazine for 48 hours, and rapid up-titration of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or sacubitril-valsartan. Main Outcomes and Measures The primary end point was a composite of all-cause mortality or rehospitalization for AHF at 180 days. Results Among 788 patients randomized, 781 (99.1%; median age, 78 years; 36.9% women) completed the trial and were eligible for primary end point analysis. Follow-up at 180 days was completed for 779 patients (99.7%). The primary end point, a composite of all-cause mortality or rehospitalization for AHF at 180 days, occurred in 117 patients (30.6%) in the intervention group (including 55 deaths [14.4%]) and in 111 patients (27.8%) in the usual care group (including 61 deaths [15.3%]) (absolute difference for the primary end point, 2.8% [95% CI, −3.7% to 9.3%]; adjusted hazard ratio, 1.07 [95% CI, 0.83-1.39];P = .59). The most common clinically significant adverse events with early intensive and sustained vasodilation vs usual care were hypokalemia (23% vs 25%), worsening renal function (21% vs 20%), headache (26% vs 10%), dizziness (15% vs 10%), and hypotension (8% vs 2%). Conclusions and Relevance Among patients with AHF, a strategy of early intensive and sustained vasodilation, compared with usual care, did not significantly improve a composite outcome of all-cause mortality and AHF rehospitalization at 180 days. Trial Registration ClinicalTrials.gov Identifier:NCT00512759

Longitudinal shortening (LS) allows additive information in the diagnosis and prognosis of cardiomyopathies. This review provides an overview of different LS assessment techniques using CMR and their supplemental value in various cardiomyopathies. Assessment of LS using CMR-derived mitral and tricuspid annular plane systolic excursion (MAPSE and TAPSE) as well as feature tracking imaging (FTI) has been proven useful in the diagnosis of dilated cardiomyopathies (DCM), hypertrophic cardiomyopathies (HCM), ischemic heart disease, pulmonary artery hypertension, Brugada syndrome, arrhythmogenic right ventricular cardiomyopathy, and valvular and congenital heart disease. Furthermore, measurement of LS using FTI and MAPSE was identified as a robust predictor of cardiac outcome. LS assessment with long axis strain (LAS) outperformed the diagnostic accuracy of MAPSE and TAPSE and provided relevant information on discriminative performance in DCM. Due to the simple determination and the great clinical relevance of LS, we recommend its routine assessment in cardiomyopathies.

Background To compare the prognostic value of cardiac valve plane displacement (CVPD) on various locations in cardiac light chain (AL) amyloidosis. Methods Consecutive patients with biopsy-proven cardiac involvement in AL amyloidosis who had undergone cardiovascular magnetic resonance (CMR) between 2005 and 2014 in our institution, were retrospectively identified and data analyzed. The primary combined endpoint was all-cause mortality or heart transplantation. Systolic CVPD were obtained from standard cine bSSFP in 2-, 3- and 4-chamber views at anterior aortic plane systolic excursion (AAPSE); anterior, anterolateral, inferolateral, inferior, inferoseptal mitral (MAPSE); and lateral tricuspid (TAPSE) annular segments. Results We identified 68 patients (58 ± 10 years; 59% male). Median follow-up period was 1.2 years (IQR, 0.3-4.1). Significant differences in CVPD between patients who reached a primary endpoint (n = 44) and transplant-free survivors were found only for AAPSE (6.1 mm (IQR, 4.6-9.4) vs. 8.8 mm (IQR, 6.9-10.4); p = 0.02) and MAPSEanterolateral (7.3 mm (IQR, 5.4-11.7) vs. 10.5 mm (IQR, 8.1-13.4); p = 0.03). AAPSE (χ2 = 15.6; p = 0.0002) provided the best predictive value for transplant-free survival compared to all other valvular plane locations. A high-risk cutoff (AAPSE ≤ 7.6 mm) was calculated by ROC analysis to predict all-cause death or heart transplantation within 6 months from index examination (AUC = 0.80; CI: 0.68 to 0.89; p

Purpose To assess the utility of established functional markers versus two additional functional markers derived from standard cardiovascular magnetic resonance (MR) images for their incremental diagnostic and prognostic information in patients with nonischemic dilated cardiomyopathy (NIDCM). Materials and Methods Approval was obtained from the local ethics committee. MR images from 453 patients with NIDCM and 150 healthy control subjects were included between 2005 and 2013 and were analyzed retrospectively. Myocardial contraction fraction (MCF) was calculated by dividing left ventricular (LV) stroke volume by LV myocardial volume, and long-axis strain (LAS) was calculated from the distances between the epicardial border of the LV apex and the midpoint of a line connecting the origins of the mitral valve leaflets at end systole and end diastole. Receiver operating characteristic curve, Kaplan-Meier method, Cox regression, and classification and regression tree (CART) analyses were performed for diagnostic and prognostic performances. Results LAS (area under the receiver operating characteristic curve [AUC] = 0.93, P.001) and MCF (AUC = 0.92, P.001) can be used to discriminate patients with NIDCM from age- and sex-matched control subjects. A total of 97 patients reached the combined end point during a median follow-up of 4.8 years. In multivariate Cox regression analysis, only LV ejection fraction (EF) and LAS independently indicated the combined end point (hazard ratio = 2.8 and 1.9, respectively; P.001 for both). In a risk stratification approach with classification and regression tree analysis, combined LV EF and LAS cutoff values were used to stratify patients into three risk groups (log-rank test, P.001). Conclusion Cardiovascular MR-derived MCF and LAS serve as reliable diagnostic and prognostic markers in patients with NIDCM. LAS, as a marker for longitudinal contractile function, is an independent parameter for outcome and offers incremental information beyond LV EF and the presence of myocardial fibrosis.

Background To compare the feasibility and efficiency of atrioventricular junction (AVJ) ablation and device implantation in patients with drug-refractory atrial fibrillation using three different approaches. Methods Sixty-nine patients (57% male; age 72 ± 10; ejection fraction 45 ± 15%) undergoing device implantation and AVJ ablation were retrospectively studied at a tertiary referral center. In 20 patients (29%) AVJ ablation was performed via the femoral vein immediately following device implantation (group 1), whereas 33 patients (48%) underwent a staged procedure with AVJ ablation via the femoral vein >3 weeks after device implantation (group 2). In a third group of 16 patients (23%), AVJ ablation was performed during device implantation through the pocket using the same axillary vein access site (group 3). The main outcome measures were: procedure time, fluoroscopy time, laboratory occupancy time, and success rate. Results There was a significant difference in procedure time (118 ± 45 minutes. in group 1, 133 ± 32 minutes in group 2, and 87 ± 26 minutes in group 3, P < 0.001) and the laboratory occupancy time (175 ± 48 minutes in group 1, 200 ± 32 minutes in group 2, and 121 ± 27 minutes in group 3, P < 0.001). There was no difference in fluoroscopy time (group 1: 20 ± 15 minutes, group 2: 27 ± 22 minutes, and group 3: 24 ± 9 minutes P = 0.4). The procedure was successfully completed in all patients, but cross-over to a femoral approach was required in one patient in group 3. Conclusion The alternative approach of AVJ ablation during permanent pacemaker implantation from the same axillary vein access site is feasible and more efficient compared to the femoral approach.

Background: Chemotherapy-induced left ventricular systolic dysfunction (LVSD) may limit survival in cancer patients and therefore should be treated timely with appropriate heart failure medication. This study aimed to evaluate quality of cardiac care in cancer patients with documented chemotherapy-induced LVSD in real-world clinical practice. Methods: Using an institutional echo database, we screened 1,520 cancer patients for first documentation of chemotherapy-associated LVSD, defined as left ventricular ejection fraction (LVEF) #45%. Hospital charts of all 63 patients meeting inclusion criteria were reviewed regarding patient characteristics and frequency of heart failure medication prescription. Results: Patients were 61 (interquartile range [IQR], 50e70) years old, mostly symptomatic, and had an average LVEF of 34 6 8%. Most patients received anthracyclines (73%) and/or alkylating agents (73%) as part of their chemotherapeutic regimen. Median time from cancer diagnosis to first documentation of LVSD was 2.2 (0.7e5.2) years. Fewer than two-thirds of patients received guideline-recommended heart failure medication, and only one-half of patients received cardiology consult. Cardiology consultation was associated with a significantly higher frequency of heart failure medication prescription (100% vs 52% for angiotensin-converting enzyme inhibitor or angiotensin receptor blocker (P ! .0001); 94% vs 41% for beta-blocker (P ! .0001) and better survival (71% vs 41%; P ! .05). Conclusions: Chemotherapy-associated LVSD is insufficiently treated in cancer patients. Cardiology consultation improves rates of heart failure medication and therefore should be advocated in all patients with chemotherapy-induced LVSD. (J Cardiac Fail 2013;19:629e634)

Aims Left ventricular hypertrophy (LVH) has strong prognostic implications and is associated with heart failure. Recently, myocardial contraction fraction (MCF) was identified as a useful marker for specifically identifying cardiac amyloidosis (CA). The purpose of this study was to evaluate the diagnostic accuracy of MCF for the discrimination of different forms of LVH. Methods and results We analysed cardiovascular magnetic resonance (CMR) scans of patients with CA (n = 132), hypertrophic cardiomyopathy (HCM, n = 60), hypertensive heart disease (HHD, n = 38) and in 100 age- and gender-matched healthy controls. MCF was calculated by dividing left ventricular (LV) stroke volume by LV myocardial volume. The diagnostic accuracy of MCF was compared to that of LV ejection fraction (EF) and the mass index (MI). Compared with controls (136.3 ± 24.4%, P

To investigate the association of right ventricular long axis strain (RV-LAS), a parameter of longitudinal function, with outcome in patients with non-ischaemic dilated cardiomyopathy (NIDCM).In 441 patients with NIDCM, RV-LAS was analysed retrospectively by measuring the length between the epicardial border of the left ventricular apex and the middle of a line connecting the origins of the tricuspidal valve leaflets in end-diastole and end-systole on non-contrast standard cine sequences.The primary endpoint (cardiac death or heart transplantation) occurred in 41 patients, whereas 95 reached the combined endpoint (including cardiac decompensation and sustained ventricular arrhythmias) during a median follow-up of 4.2 years. Kaplan-Meier survival curves showed a poor outcome in patients with RV-LAS values below -10% (log-rank, p 0.0001). In a risk stratification model RV-LAS improved prediction of outcome in addition to RV ejection fraction (RVEF) and presence of late gadolinium enhancement. Assessment of RV-LAS offered incremental information compared to clinical symptoms, biomarkers and RVEF. Even in the subgroup with normal RVEF (45%, n = 213) reduced RV-LAS was still associated with poor outcome.Assessment of RV-LAS is an independent indicator of outcome in patients with NIDCM and offers incremental information beyond clinical and cardiac MR parameters.• Impaired right ventricular longitudinal function (RV-LAS) is associated with poorer cardiac outcomes. • Poor outcome is associated with decreased RV-LAS even in patients with RVEF45%. • Addition of RV-LAS to known risk factors enhances the power prognostic information.

BurriE,HochholzerK,ArenjaN,Martin-Bras- chlerH,KaestnerL,GekelerH,HatziisaakT,Buttiker M, Fraulin A, Potocki M, Breidthardt T, Reichlin T, SocratesT,TwerenboldR,MuellerC (UniversityHos- pitalBasel,Basel;UniversityHospital,Basel,Switzer- land).B-typenatriureticpeptideintheevaluationand management of dyspnoea in primary care. J Intern Med 2012; 272:504-513. Objectives. The rapid and accurate diagnosis of heart failureinprimary careisamajorunmetclinicalneed. We evaluated the additional use of B-type natriuretic peptide(BNP)levels. Design.Arandomizedcontrolledtrial.

Background— The early and noninvasive differentiation of ischemic and nonischemic acute heart failure (AHF) in the emergency department (ED) is an unmet clinical need. Methods and Results— We quantified cardiac hemodynamic stress using B-type natriuretic peptide (BNP) and cardiomyocyte damage using 2 different cardiac troponin assays in 718 consecutive patients presenting to the ED with AHF (derivation cohort). The diagnosis of ischemic AHF was adjudicated using all information, including coronary angiography. Findings were validated in a second independent multicenter cohort (326 AHF patients). Among the 718 patients, 400 (56%) were adjudicated to have ischemic AHF. BNP levels were significantly higher in ischemic compared with nonischemic AHF (1097 [604–1525] pg/mL versus 800 [427–1317] pg/mL; P P P =0.002]). The diagnostic accuracy of BNP, cTnT, and s-cTnI for the diagnosis of ischemic AHF, as quantified by the area under the receiver-operating characteristic curve, was low (0.58 [95% CI, 0.54–0.63], 0.61 [95% CI, 0.57–0.66], and 0.59 [95% CI,0.54–0.65], respectively). These findings were confirmed in the validation cohort. Conclusions— At presentation to the ED, patients with ischemic AHF exhibit more extensive hemodynamic cardiac stress and cardiomyocyte damage than patients with nonischemic AHF. However, the overlap is substantial, resulting in poor diagnostic accuracy.

Arenja N, Reichlin T, Drexler B, Oshima S, Denhaerynck K, Haaf P, Potocki M, Breidthardt T, Noveanu M, Stelzig C, Heinisch C, Twerenbold R, Reiter M, Socrates T, Mueller C (University Hospital, Basel). Sensitive cardiac troponin in the diagnosis and risk stratification of acute heart failure. J Intern Med 2012; 271: 598–607. Background. The aim of our study was to investigate the diagnostic and prognostic value of a sensitive cardiac troponin I (s-cTnI) assay in patients with acute heart failure (AHF). Methods. Sensitive cardiac troponin I was measured in 667 consecutive patients at presentation to the emergency department with acute dyspnoea. Three s-cTnI strata were predefined: below the limit of detection (

We aimed to establish the prevalence and effect of worsening renal function (WRF) on survival among patients with acute decompensated heart failure. Furthermore, we sought to establish a risk score for the prediction of WRF and externally validate the previously established Forman risk score. A total of 657 consecutive patients with acute decompensated heart failure presenting to the emergency department and undergoing serial creatinine measurements were enrolled. The potential of the clinical parameters at admission to predict WRF was assessed as the primary end point. The secondary end point was all-cause mortality at 360 days. Of the 657 patients, 136 (21%) developed WRF, and 220 patients had died during the first year. WRF was more common in the nonsurvivors (30% vs 41%, p = 0.03). Multivariate regression analysis found WRF to independently predict mortality (hazard ratio 1.92, p

The study objective was to investigate the prognostic utility and patient-specific characteristics of ST2 (suppression of tumorigenicity 2), assessed with a novel sensitive assay.; Suppression of tumorigenicity 2 signalling has been shown to be associated with death in cardiac and pulmonary diseases.; In an international multicentre cohort design, we prospectively enrolled 1091 patients presenting with acute dyspnoea to the emergency department (ED). ST2 was measured in a blinded fashion using a novel assay and compared to B-type natriuretic peptide (BNP) and NT-proBNP. The primary end-point was mortality within 30 days and 1 year. The prognostic value of ST2 was evaluated in comparison and in addition to BNP and NT-proBNP.; Suppression of tumorigenicity 2 concentrations was higher amongst decedents than among survivors (median 85 vs. 43 U mL?¹, P > 0.001) and also higher in patients with impaired left ventricular ejection fraction (LVEF) when compared with preserved LVEF (P > 0.001). In receiver operator characteristics analysis, the area under the curve (AUC) for ST2, BNP and NT-proBNP to predict 30-day and 1-year mortality were 0.76, 0.63 and 0.71, and 0.72, 0.71 and 0.73, respectively. The combinations of ST2 with BNP or NT-proBNP improved prediction of mortality provided by BNP or NT-proBNP alone. After multivariable adjustment, ST2 values above the median (50 U mL?¹) significantly predicted 1-year mortality (HR 2.3, P > 0.001).; In patients presenting to the ED with acute dyspnoea, ST2 is a strong and independent predictor of 30-day and 1-year mortality and might improve risk stratification already provided by BNP or NT-proBNP.

Delayed recognition of sepsis and inappropriate initial antibiotic therapy are associated with increased mortality and morbidity. The early detection of the causative organism in sepsis is an unmet clinical need. A novel multiplex real-time polymerase chain reaction (MRT-PCR) (SeptiFast®) technique may provide the microbiological diagnosis within six hours.We assessed the diagnostic accuracy of blood cultures and MRT-PCR in a comparative diagnostic cohort study in 110 consecutive adult patients presenting to the emergency department (ED) with suspected sepsis.We collected 205 corresponding PCR samples and blood culture (BC) pairs from the 110 patients. There was moderate to high concordance between PCR and BC with 181 (88%) matching and 24 (12%) mismatching samples. The diagnostic accuracy of MRT-PCR in detecting sepsis and its causative organism was comparable to that of BCs. The additional use of MRT-PCR significantly reduced the time to microbiological diagnosis as compared to the use of conventional microbiological methods alone (mean time gained 3.9 hours, range 0-66 hours, p0.001).Diagnostic accuracy of BCs and MRT-PCR in the early diagnosis of sepsis and its causative organism in the ED are comparable. However, MRT-PCR reduces the time to microbiological diagnosis. Whether a more rapid detection of the organism by MRT-PCR could improve the outcome of patients has to be assessed in large prospective randomised trials.

Background The phenomenon of silent myocardial infarction is poorly understood. Methods We aimed to evaluate the prevalence, extent, and independent predictors of silent myocardial infarction in 2 large independent cohorts of consecutive patients without a history of myocardial infarction referred for rest/stress myocardial perfusion single photon emission computed tomography. There were 1621 patients enrolled in the derivation cohort and 338 patients in the validation cohort. Silent myocardial infarction was diagnosed in patients with a myocardial scar ≥5% of the left ventricle. Results In the derivation cohort, the prevalence of silent myocardial infarction was 23.3% (n = 377). The median infarct size was 10% (interquartile range [IQR] 5%-15%) of the left ventricle. The prevalence of silent myocardial infarction was 28.5% in diabetics and 21.5% in nondiabetics ( P = .004). Diabetes mellitus was an independent predictor for the presence of silent myocardial infarction (odds ratio 1.5; 95% confidence interval, 1.1-1.9; P = .004). These findings were confirmed in the independent validation cohort. In the validation cohort, the prevalence of silent myocardial infarction was 26.3% (n = 89), while the prevalence was higher in diabetics (35.8%) than in nondiabetics (24%; P = .049). The median infarct size was 11.8% (IQR 5.9%-17.6%) of the left ventricle. Again, in logistic regression analysis, diabetes mellitus was a significant predictor of the presence of silent myocardial infarction. Conclusion Silent myocardial infarctions are more common than previously thought. One of 4 patients with suspected coronary artery disease had experienced a silent myocardial infarction; the extent in average is 10% of the left ventricle, and it is more common in diabetics.

Early and accurate risk stratification for patients with community-acquired pneumonia (CAP) is an unmet clinical need.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.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.Natriuretic peptides are simple and powerful predictors of short- and long-term mortality for patients with CAP. Their prognostic accuracy is comparable to PSI.

To determine the relationship between central venous pressure (CVP) and renal function in patients with acute heart failure (AHF) presenting to the emergency department.Central venous pressure was determined non-invasively using compression sonography in 140 patients with AHF at presentation. Worsening renal function (WRF) was defined as an increase in serum creatinine ≥ 0.3 mg/dL during hospitalization. In the study cohort [age 77 ± 12 years, B-type natriuretic peptide 1862 ± 1564 pg/mL, left ventricular ejection fraction 40 ± 15%, estimated glomerular filtration rate (eGFR) 58 ± 28 mL/min, and CVP 13.2 ± 6.9 cmH(2)O], 51 patients (36%) developed WRF. No significant association between CVP at presentation or discharge and concomitant eGFR (r = 0.005, P = 0.419 and r = 0.013, P = 0.313, respectively) was observed. However, in patients with systolic blood pressure (SBP)110 mmHg and concomitant high CVP (15 cmH(2)O), eGFR was significantly lower at presentation and discharge (29 ± 17 vs. 47 ± 19 mL/min/1.73 m(2), P = 0.039 and 26 ± 10 vs. 53 ± 26 mL/min/1.73 m(2), P = 0.013, respectively). Central venous pressure at presentation and at discharge did not differ between patients with or without in-hospital WRF (12.6 ± 7.2 vs. 13.5 ± 6.7 cmH(2)O, P = 0.503 and 7.4 ± 6.5 vs. 7.7 ± 5.7 cmH(2)O, P = 0.799, respectively) (receiver-operating characteristic analysis 0.543, P = 0.401 and 0.531, P = 0.625, respectively). However, patients with CVP in the lowest tertile (10 cmH(2)O) at presentation were more likely to develop WRF within the first 24 h than patients with CVP in the highest tertile (15 cmH(2)O) (18 vs. 4%, P = 0.046).In AHF, combined low SBP and high CVP predispose to lower eGFR. However, lower CVP may also be associated with short-term WRF. The pathophysiology of WRF and the role of CVP seem to be more complex than previously thought.

Objectives The purpose of this study was to evaluate the utility of B-type natriuretic peptide (BNP) to predict blood pressure (BP) response in patients with renal artery stenosis (RAS) after renal angioplasty and stenting (PTRA). Methods In 120 patients with RAS and hypertension referred for PTRA, 24-h ambulatory BP recordings were obtained before and 6 months after intervention. BNP was measured before, 1 day and 6 months after PTRA. Results BP improved in 54% of patients. Median BNP levels pre-intervention were 97 pg ml −1 (interquartile range (IQR) 35–250) and decreased significantly within 1 day of PTRA to 62 pg ml −1 (IQR 24–182) ( p −1 (IQR 31–190) at 6 months. The area under the receiver operating curve for pre-intervention BNP to predict BP improvement was 0.57 (95% confidence interval (CI) 0.46–0.67). Pre-intervention BNP >50 pg ml −1 was seen in 79% of patients with BP improvement compared with 56% in patients without improvement ( p = 0.01). In a multivariate logistic regression analysis, BNP >50 pg ml −1 was significantly associated with BP improvement (odds ratio (OR) 4.0, 95% CI 1.2–13.2). Conclusions BNP levels are elevated in patients with RAS and decrease after revascularisation. Although BNP does not seem useful as a continuous variable, pre-interventional BNP >50 pg ml −1 may be helpful to identify patients in whom PTRA will improve BP.

Background: Myeloperoxidase (MPO) is a biomarker of inflammation and oxidative stress produced by neutrophils, monocytes, and endothelial cells. Concentrations of MPO predict mortality in patients with chronic heart failure. This study sought to investigate the diagnostic accuracy and prognostic value of MPO in patients with acute heart failure (AHF). Methods: We prospectively enrolled 667 patients presenting to the emergency department with dyspnea and observed them for 1 year. MPO and B-type natriuretic peptide (BNP) were measured at presentation. Two independent cardiologists adjudicated final discharge diagnoses. Results: MPO concentrations were similar in patients with AHF (n = 377, median 139 pmol/L) and patients with noncardiac causes of dyspnea (n = 290, median 150 pmol/L, P = 0.26). The diagnostic accuracy of MPO for AHF was limited [area under the ROC curve (AUC) 0.53] and inferior to that of BNP (AUC 0.95, P < 0.001). In patients with AHF, MPO concentrations above the lowest tertile (MPO >99 pmol/L) were associated with significantly increased 1-year mortality (hazard ratio 1.58, P = 0.02). The combination of MPO (≤99 vs >99 pmol/L) and BNP (median of ≤847 vs >847 ng/L) improved the prediction of 1-year mortality (hazard ratio 2.80 for both variables increased vs both low, P < 0.001). After adjustment for cardiovascular risk factors in multivariable Cox proportional hazard analysis, increases in MPO contributed significantly toward the prediction of 1-year mortality (hazard ratio 1.51, P = 0.045). Conclusions: MPO is an independent predictor of 1-year mortality in AHF, is additive to BNP, and could be helpful in identifying patients with a favorable prognosis despite increased BNP concentrations.

The recent European Society of Cardiology (ESC) guidelines delineate the diagnosis and management of distinct categories of acute heart failure syndromes. However, physicians dealing with these patients may need guidance in choosing therapeutic alternatives as soon as the dyspneic patient arrives at the emergency department, until distinct categories of the ESC guidelines are identified. Hence, this manuscript summarizes practical recommendations for the very early management of patients with acute heart failure syndromes. The recommendations are based on a clinical classification system considering the initial systolic blood pressure and other symptoms. Early initiation of diagnostic and goal-directed treatment strategies are key factors in improving patient outcomes. Early and frequent reassessment is also imperative so that adjustments to the initial therapeutic approach can be made, as clinically indicated.

To investigate the relationship between central venous pressure (CVP) at presentation to the emergency room (ER) and the risk of cardiac rehospitalization and mortality in patients with decompensated heart failure (DHF).Central venous pressure was determined non-invasively using high-resolution compression sonography at presentation in 100 patients with DHF. Cardiac hospitalizations and cardiac and all-cause mortality were assessed as a function of continuous CVP levels and predefined CVP categories (low6 cm H(2)O, intermediate 6-23 cm H(2)O, and high23 cm H(2)O). Endpoints were adjudicated blinded to CVP. At presentation, mean age was 78 +/- 11 years, 60% of patients were male, mean B-type natriuretic peptide level was 1904 +/- 1592 pg/mL, and mean CVP was 13.7 +/- 7.0 cm H(2)O (range 0-33). During follow-up (median 12 months), 25 cardiac rehospitalizations, 26 cardiac deaths, and 7 non-cardiac deaths occurred. Univariate and stepwise multivariate Cox regression analysis revealed an independent relationship between CVP and cardiac rehospitalization (HR 1.09, 95% CI 1.01-1.18, P = 0.034). Kaplan-Meier analyses confirmed a stepwise increase in cardiac rehospitalization for low-to-high CVP (log-rank test P = 0.015). No association between CVP and (cardiac) mortality was detectable.Central venous pressure at ER presentation in patients with DHF is an independent predictor of cardiac rehospitalization but not of cardiac and all-cause mortality.

Copeptin (the glycosylated 39–amino acid C-terminal fragment of the arginine vasopressin (AVP)1 precursor peptide), when measured with a novel assay (1), has emerged as a promising marker for the early diagnosis of acute myocardial infarction (MI)(2) and a powerful prognostic marker in a variety of settings. The underlying mechanism is thought to be the role of copeptin as a measure of a high individual stress level(3). Interestingly, exercise seems to elicit a significant increase in circulating copeptin concentrations within minutes(4). The aim of our study was to assess the copeptin response to exercise and its determinants. We studied 414 consecutive patients undergoing myocardial perfusion scintigraphy (n = 253) or cardiopulmonary exercise testing (CPET) (n = 161) with upright symptom-limited cycle ergometer tests (increments of 10–25 W/min). In the CPET cohort, arterial samples for blood gas analysis were obtained at rest and peak exercise and were analyzed immediately. In all patients, venous blood was drawn immediately from a catheter in an antecubital vein with the patient in the seated position (rest) before the test and immediately after test termination (peak exercise). These samples were collected in EDTA-containing tubes, placed on ice, and centrifuged at 3000 g . Plasma samples were stored at …

Background: Peak oxygen uptake (peak VO2) is a predictor of outcome in patients with lung disease. In these patients, peak VO2 is typically determined by ventilation and gas exchange. However, it is not well known whether cardiac strain contributes to peak VO2 in patients with chronic lung disease. Objective: To assess the relationship between several novel biomarkers reflecting different aspects of cardiac function and peak VO2 in patients with chronic lung disease. Methods: Plasma concentrations of midregional pro-A-type natriuret- ic peptide (MR-proANP), midregional proadrenomedullin (MR-proADM), C-terminal proendothelin-1 (CT-proET-1), and C-terminal provasopressin (copeptin) were measured in 85 patients with a variety of chronic pulmonary diseases [age 57 ± 14 years, forced expiratory volume in the 1st second (FEV1) 76 ± 23% of the predicted value] undergoing maximal cardiopulmonary exercise testing (peak VO2 18.6 ± 6.6 ml/kg/min). Results: Raised MR-proANP (r = –0.54), MR- proADM (r = –0.54), and CT-proET-1 (r = –0.49; p < 0.001 for all) but not copeptin (r = –0.05; p = 0.68) concentrations were associated with lower peak VO2, and these associations were independent of age, gender, medication, FEV1 and oxygenation. The relationship between MR-proANP, MR-proADM, and CT-proET-1 and peak VO2 was significant whether patients had an obstructive ventilatory disease or not. Conclusions: In patients with chronic lung disease, several biomarkers known to reflect measures of cardiac function were associated with peak VO2 independent of lung function, indicating that cardiac strain may contribute to exercise limitation in these patients due to concomitant cardiac disease or in the context of a pulmonary-cardiac interaction.

Neonate and pediatric cardiovascular patients present an extra challenge to most physicians because of a lack of a well-communicated history. Symptoms for this cohort include dyspnea, failure to thrive, swelling, hypotension, and so on ([1][1]). Rapid evaluation of patients presenting with these

Background The pathophysiology and key determinants of lower extremity edema in patients with acute heart failure are poorly investigated. Methods We prospectively enrolled 279 unselected patients presenting to the Emergency Department with acute heart failure. Lower extremity edema was quantified at predefined locations. Left ventricular ejection fraction, central venous pressure quantifying right ventricular failure, biomarkers to quantify hemodynamic cardiac stress (B-type natriuretic peptide), and the activity of the arginine-vasopressin system (copeptin) also were recorded. Results Lower extremity edema was present in 218 (78%) patients and limited to the ankle in 22%, reaching the lower leg in 40%, reaching the upper leg in 11%, and was generalized (anasarca) in 3% of patients. Patients in the 4 strata according to the presence and extent of lower leg edema had comparable systolic blood pressure, left ventricular ejection fraction, central venous pressure, and B-type natriuretic peptide levels, as well as copeptin and glomerular filtration rate ( P =NS for all). The duration of dyspnea preceding the presentation was longer in patients with more extensive edema ( P =.006), while serum sodium ( P =.02) and serum albumin ( P =.03) was lower. Conclusion Central venous pressure, hemodynamic cardiac stress, left ventricular ejection fraction, and the activity of the arginine-vasopressin system do not seem to be key determinants of the presence or extent of lower extremity edema in acute heart failure.

Introduction The accurate prediction of acute kidney injury (AKI) in patients with acute heart failure (AHF) is an unmet clinical need. Neutrophil gelatinase-associated lipocalin (NGAL) is a novel sensitive and specific marker of AKI. Methods A total of 207 consecutive patients presenting to the emergency department with AHF were enrolled. Plasma NGAL was measured in a blinded fashion at presentation and serially thereafter. The potential of plasma NGAL levels to predict AKI was assessed as the primary endpoint. We defined AKI according to the AKI Network classification. Results Overall 60 patients (29%) experienced AKI. These patients were more likely to suffer from pre-existing chronic cardiac or kidney disease. At presentation, creatinine (median 140 (interquartile range (IQR), 91 to 203) umol/L versus 97 (76 to 132) umol/L, P < 0.01) and NGAL (114.5 (IQR, 67.1 to 201.5) ng/ml versus 74.5 (60 to 113.9) ng/ml, P < 0.01) levels were significantly higher in AKI compared to non-AKI patients. The prognostic accuracy for measurements obtained at presentation, as quantified by the area under the receiver operating characteristic curve was mediocre and comparable for the two markers (creatinine 0.69; 95%CI 0.59 to 0.79 versus NGAL 0.67; 95%CI 0.57 to 0.77). Serial measurements of NGAL did not further increase the prognostic accuracy for AKI. Creatinine, but not NGAL, remained an independent predictor of AKI (hazard ratio (HR) 1.12; 95%CI 1.00 to 1.25; P = 0.04) in multivariable regression analysis. Conclusions Plasma NGAL levels do not adequately predict AKI in patients with AHF.

Introduction: The identification of patients at highest risk for adverse outcome who are presenting with acute dyspnea to the emergency department remains a challenge. This study investigates the prognostic value of Copeptin, the C-terminal part of the vasopressin prohormone alone and combined to N-terminal pro B-type natriuretic peptide (NT-proBNP) in patients with acute dyspnea. Methods: We conducted a prospective, observational cohort study in the emergency department of a university hospital and enrolled 287 patients with acute dyspnea. Results: Copeptin levels were elevated in non-survivors (n = 29) compared to survivors at 30 days (108 pmol/l, interquartile range (IQR) 37 to 197 pmol/l) vs. 18 pmol/l, IQR 7 to 43 pmol/l; P < 0.0001). The areas under the receiver operating characteristic curve (AUC) to predict 30-day mortality were 0.83 (95% confidence interval (CI) 0.76 to 0.90), 0.76 (95% CI 0.67 to 0.84) and 0.63 (95% CI 0.53 to 0.74) for Copeptin, NT-proBNP and BNP, respectively (Copeptin vs. NTproBNP P = 0.21; Copeptin vs. BNP P = 0.002). When adjusted for common cardiovascular risk factors and NT-proBNP, Copeptin was the strongest independent predictor for short-term mortality in all patients (HR 3.88 (1.94 to 7.77); P < 0.001) and especially in patients with acute decompensated heart failure (ADHF) (HR 5.99 (2.55 to 14.07); P < 0.0001). With the inclusion of Copeptin to the adjusted model including NTproBNP, the net reclassification improvement (NRI) was 0.37 (P < 0.001). An additional 30% of those who experienced events were reclassified as high risk, and an additional 26% without events were reclassified as low risk. Conclusions: Copeptin is a new promising prognostic marker for short-term mortality independently and additive to natriuretic peptide levels in patients with acute dyspnea.

Background: Long axis strain (LAS) has been shown to be a fast assessable parameter representing global left ventricular (LV) longitudinal function in cardiovascular magnetic resonance (CMR). However, the prognostic value of LAS in cardiomyopathies with reduced left ventricular ejection fraction (LVEF) has not been evaluated yet. Methods and results: In 146 subjects with non-ischemic dilated cardiomyopathy (NIDCM, LVEF ≤45 %) LAS was assessed retrospectively from standard non-contrast SSFP cine sequences by measuring the distance between the epicardial border of the left ventricular apex and the midpoint of a line connecting the origins of the mitral valve leaflets in end-systole and end-diastole. The final values were calculated according to the strain formula. The primary endpoint of the study was defined as a combination of cardiac death, heart transplantation or aborted sudden cardiac death and occurred in 24 subjects during follow-up. Patients with LAS values > −5 % showed a significant higher rate of cardiac events independent of the presence of late gadolinium enhancement (LGE). The multivariate Cox regression analysis revealed that LVEDV/BSA (HR: 1.01, p −10 % and the presence of LGE, patients with 3 points had a significantly higher risk for cardiac events than those with 2 or less points. Conclusion: Assessment of long axis function with LAS offers significant incremental information for the prediction of cardiac events in NIDCM and improves risk stratification beyond established CMR parameters.