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Background: The results of telemedicine intervention studies in patients with heart failure (HF) to reduce rehospitalization rate and mortality by early detection of HF decompensation are encouraging. However, the benefits are lower than expected. A possible reason for this could be the fact that vital signs, including blood pressure, heart rate, heart rhythm, and weight changes, may not be ideal indicators of the early stages of HF decompensation but are more sensitive for acute events triggered by ischemic episodes or rhythm disturbances. Preliminary results indicate a potential role of ambient sensor-derived digital biomarkers in this setting., Objective: The aim of this study is to identify changes in ambient sensor system-derived digital biomarkers with a high potential for early detection of HF decompensation., Methods: This is a prospective interventional cohort study. A total of 24 consecutive patients with HF aged 70 years and older, living alone, and hospitalized for HF decompensation will be included. Physical activity in the apartment and toilet visits are quantified using a commercially available, passive, infrared motion sensing system (DomoHealth SA). Heart rate, respiration rate, and toss-and-turns in bed are recorded by using a commercially available Emfit QS device (Emfit Ltd), which is a contact-free piezoelectric sensor placed under the participant's mattress. Sensor data are visualized on a dedicated dashboard for easy monitoring by health professionals. Digital biomarkers are evaluated for predefined signs of HF decompensation, including particularly decreased physical activity; time spent in bed; increasing numbers of toilet visits at night; and increasing heart rate, respiration rate, and motion in bed at night. When predefined changes in digital biomarkers occur, patients will be called in for clinical evaluation, and N-terminal pro b-type natriuretic peptide measurement (an increase of >30% considered as significant) will be performed. The sensitivity and specificity of the different biomarkers and their combinations for the detection of HF decompensation will be calculated., Results: The study is in the data collection phase. Study recruitment started in February 2024. Data analysis is scheduled to start after all data are collected. As of manuscript submission, 5 patients have been recruited. Results are expected to be published by the end of 2025., Conclusions: The results of this study will add to the current knowledge about opportunities for telemedicine to monitor older patients with HF living at home alone by evaluating the potential of ambient sensor systems for this purpose. Timely recognition of HF decompensation could enable proactive management, potentially reducing health care costs associated with preventable emergency presentations or hospitalizations., Trial Registration: ClinicalTrials.gov NCT06126848; https://clinicaltrials.gov/study/NCT06126848., International Registered Report Identifier (irrid): PRR1-10.2196/55953., (©Benjamin Vögeli, Nisha Arenja, Narayan Schütz, Tobias Nef, Philipp Buluschek, Hugo Saner. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 31.05.2024.)

Purpose : Acute heart failure (AHF) is associated with high morbidity and mortality, and the prognosis is particularly poor in older patients. Although the application of guideline-directed medical therapy (GDMT) has shown a positive impact on prognosis, the effects are less clear in older age groups. The aim of this study was to analyze real-world data regarding GDMT and outcomes in older HF patients. Methods : This is a prospective cohort study from a secondary care hospital in central Switzerland. A total of 97 consecutive patients aged ≥60 years were enrolled between January 2019 and 2022. The main outcome parameters were prescribed GDMT at discharge, and in case of rehospitalization, GDMT at readmission, and survival in terms of all-cause mortality and HF-related hospitalizations during a 3-year follow-up period. Results : Follow-up data were available for 93/97 patients. The mean age was 77.8 ± 9.8 years, 46% being female. The mean left ventricular ejection fraction (LVEF) was 35.3 ± 13.9%, with a mean BNP level of 2204.3 ± 239 ng/L. Upon discharge, 86% received beta-blockers and 76.3% received renin-angiotensin system (RAS) inhibitors. At rehospitalization for AHF, beta-blockers use was significantly lower and decreased to 52.8% ( p = 0.003), whereas RAS inhibitor use increased slightly to 88.9% ( p = 0.07), and SGLT-2 inhibitors showed a significant increase from 5.4% vs. 47.2% ( p = 0.04). GDMT prescription was not dependent on LVEF. Overall, 73.1% of patients received two-stage or three-stage GDMT at discharge, whereas this percentage decreased to 61% at rehospitalization ( p = 0.01). Kaplan-Meier analysis for the combined outcome rehospitalization and death stratified by LV function showed significant differences between LVEF groups (aHR: 0.6 [95% CI: 0.44 to 0.8]; p = 0.0023). Conclusions : Our results indicate that first, the majority of older AHF patients from a secondary care hospital in Switzerland were not on optimal GDMT at discharge and even fewer at readmission, and second, that prognosis of the population is still poor, with almost half of the patients having been rehospitalized or died during a 3-year follow-up period under real-world conditions, without significant difference between women and men. Our findings underline the need for further improvements in the medical treatment of AHF, in particular in older patients, to improve prognosis and to reduce the burden of disease.

Background: The characterization of the different pathophysiological mechanisms involved in normotensive versus hypertensive acute heart failure (AHF) might help to develop individualized treatments., Methods: The extent of hemodynamic cardiac stress and cardiomyocyte injury was quantified by measuring the B-type natriuretic peptide (BNP), N-terminal proBNP (NT-proBNP), and high-sensitivity cardiac troponin T (hs-cTnT) concentrations in 1152 patients presenting with centrally adjudicated AHF to the emergency department (ED) (derivation cohort). AHF was classified as normotensive with a systolic blood pressure (SBP) of 90-140 mmHg and hypertensive with SBP > 140 mmHg at presentation to the ED. Findings were externally validated in an independent AHF cohort (n = 324)., Results: In the derivation cohort, with a median age of 79 years, 43% being women, 667 (58%) patients had normotensive and 485 (42%) patients hypertensive AHF. Hemodynamic cardiac stress, as quantified by the BNP and NT-proBNP, was significantly higher in normotensive as compared to hypertensive AHF [1105 (611-1956) versus 827 (448-1419) pg/mL, and 5890 (2959-12,162) versus 4068 (1986-8118) pg/mL, both p < 0.001, respectively]. Similarly, the extent of cardiomyocyte injury, as quantified by hs-cTnT, was significantly higher in normotensive AHF as compared to hypertensive AHF [41 (24-71) versus 33 (19-59) ng/L, p < 0.001]. A total of 313 (28%) patients died during 360 days of follow-up. All-cause mortality was higher in patients with normotensive AHF vs. patients with hypertensive AHF (hazard ratio 1.66, 95%CI 1.31-2.10; p < 0.001). Normotensive patients with a high BNP, NT-proBNP, or hs-cTnT had the highest mortality. The findings were confirmed in the validation cohort., Conclusion: Biomarker profiling revealed a higher extent of hemodynamic stress and cardiomyocyte injury in patients with normotensive versus hypertensive AHF.

Aims: Sex-specific differences in acute heart failure (AHF) are both relevant and underappreciated. Therefore, it is crucial to evaluate the risk/benefit ratio and the implementation of novel AHF therapies in women and men separately., Methods and Results: We performed a pre-defined sex-specific analysis in AHF patients randomized to a strategy of early intensive and sustained vasodilatation versus usual care in an international, multicentre, open-label, blinded endpoint trial. Inclusion criteria were AHF with increased plasma concentrations of natriuretic peptides, systolic blood pressure ≥100 mmHg, and plan for treatment in a general ward. Among 781 eligible patients, 288 (37%) were women. Women were older (median 83 vs. 76 years), had a lower body weight (median 64.5 vs. 77.6 kg) and lower estimated glomerular filtration rate (median 48 vs. 54 ml/min/1.73 m 2 ). The primary endpoint, a composite of all-cause mortality or rehospitalization for AHF at 180 days, showed a significant interaction of treatment strategy and sex (p for interaction = 0.03; hazard ratio adjusted for female sex 1.62, 95% confidence interval 1.05-2.50; p = 0.03). The combined endpoint occurred in 53 women (38%) in the intervention group and in 35 (24%) in the usual care group. The implementation of rapid up-titration of renin-angiotensin-aldosterone system (RAAS) inhibitors was less successful in women versus men in the overall cohort and in patients with heart failure with reduced ejection fraction (median discharge % target dose in patients randomized to intervention: 50% in women vs. 75% in men)., Conclusion: Rapid up-titration of RAAS inhibitors was less successfully implemented in women possibly explaining their higher rate of all-cause mortality and rehospitalization for AHF., Clinical Trial Registration: ClinicalTrials.gov, unique identifier NCT00512759., (© 2023 European Society of Cardiology.)

Background: Peri-operative complications are common and associated with high morbidity and mortality. Optimising the use of statins might be of important benefit in peri-operative care and reduce morbidity and mortality., Objective: To evaluate adherence to current guideline recommendations regarding statin therapy and its association with peri-operative and long-term cardiac complications., Design: Prospective cohort study., Setting: Multicentre study with enrolment from October 2014 to February 2018., Patients: Eight thousand one hundred and sixteen high-risk inpatients undergoing major noncardiac surgery who were eligible for the institutional peri-operative myocardial injury/infarction (PMI) active surveillance and response program., Main Outcome Measures: Class I indications for statin therapy were derived from the current ESC Clinical Practice Guidelines during the time of enrolment. PMI was prospectively defined as an absolute increase in cTn concentration of the 99th percentile in healthy individuals above the preoperative concentration within the first three postoperative days. Long-term cardiac complications included cardiovascular death and spontaneous myocardial infarction (MI) within 120 days., Results: The mean age was 73.7 years; 45.2% were women. Four thousand two hundred and twenty-seven of 8116 patients (52.1%) had a class I indication for statin therapy. Of these, 2440 of 4227 patients (57.7%) were on statins preoperatively. Adherence to statins was lower in women than in men (46.9 versus 63.9%, P  < 0.001). PMI due to type 1 myocardial infarction/injury (T1MI; n  = 42), or likely type 2 MI (lT2MI; n  = 466) occurred in 508 of 4170 (12.2%) patients. The weighted odds ratio in patients on statin therapy was 1.15 [95% confidence interval (CI) 1.01 to 1.31, P  = 0.036]. During the 120-day follow-up, 192 patients (4.6%) suffered cardiovascular death and spontaneous MI. After multivariable adjustment, preoperative use of statins was associated with reduced risk; weighted hazard ratio 0.59 (95% CI 0.41 to 0.86, P  = 0.006)., Conclusion: Adherence to guideline-recommended statin therapy was suboptimal, particularly in women. Statin use was associated with an increased risk of PMI due to T1MI and lT2MI but reduced risk of cardiovascular death and spontaneous MI within 120 days., Trial Registration: Clinicaltrials.gov identifier NCT02573532., (Copyright © 2023 European Society of Anaesthesiology and Intensive Care. Unauthorized reproduction of this article is prohibited.)

Background: Pulmonary hypertension (PH) is defined as a progressive disease that leads to right heart failure and death if untreated. This case report presents a young woman with reversible precapillary PH in the setting of a gastric cancer., Case Summary: A 37-year-old woman presented with exertional dyspnoea and syncope. The transthoracic echocardiographic findings were consistent with a cor pulmonale. Right heart catheterization (RHC) proved a precapillary PH. Specific PH therapy with macitentan and tadalafil was initiated. Shortly thereafter, a gastric carcinoma was diagnosed, and oncologic treatment with neoadjuvant chemotherapy and subsequent gastrectomy was promptly initiated. Retrospectively, we considered a pulmonary tumour thrombotic microangiopathy the most probable cause of PH. Follow-up after successful oncologic treatment and cumulative 10 months of specific PH medication showed an excellent clinical response with complete remission of PH confirmed by RHC at rest., Discussion: Tumour-related PH is very rare and might be largely underdiagnosed as the clinical course often results in a rapid deterioration and fatal outcome before diagnostics are completed. Post mortem studies have documented tumoural emboli in pulmonary microcirculation in ∼26% of patients with a solid tumour, markedly associated with adenocarcinoma. Prompt initiation of cancer treatment on tumoural PH is essential. To our knowledge, this report documents the first full recovery of tumoural PH at rest after successful cancer treatment and temporary specific PH medication. We therefore conclude that a multidisciplinary approach with an initially combined oncologic and PH therapy may be most beneficial with the potential of complete remission of PH., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Coronary artery spasm (CAS) is a pathological condition resulting from transient functional narrowing of the coronary arteries leading to myocardial ischaemia and in some rare cases even to sudden cardiac arrest (SCA). The most important preventable risk factor is use of tobacco, whereas possible precipitating factors include some medications and psychological stress., Case Summary: A 32-year-old woman was hospitalized with burning chest pain. The immediate investigations revealed the diagnosis of non-ST-segment elevation myocardial infarction, because of ST elevations in one single lead and increased high-sensitivity troponin. Due to ongoing chest pain and a severe impaired left ventricular ejection fraction (LVEF) of 30% with apical akinesia, a prompt coronary angiography (CAG) was scheduled. After aspirin administration, she developed anaphylaxis with pulseless electrical activity (PEA). She could be resuscitated successfully. CAG revealed multi-vessel CAS for which she received calcium channel blockers. Five days after, she suffered from a second SCA due to ventricular fibrillation and was resuscitated again. Repeated CAG showed no critical coronary artery occlusion. LVEF improved progressively during hospitalization. Drug therapy was increased, and a subcutaneous implantable cardioverter defibrillator (ICD) was implanted for secondary prevention., Discussion: CAS may in some instances lead to SCA, especially in case of multi-vessel involvement. Allergic and anaphylactic events can trigger CAS, which are frequently underestimated. Regardless of the cause, cornerstone of CAS prophylaxes remains optimal medical therapy as in the avoidance of predisposing risk factors. In case of life-threatening arrhythmia, the implantation of an ICD should be considered., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

This review serves as a synopsis of multimodality imaging in cardiac amyloidosis (CA), which is a disease characterized by deposition of misfolded protein fragments in the heart. It emphasizes and summarizes the diagnostic possibilities and their prognostic values. In general, echocardiography is the first diagnostic tool in patients with an identified systemic disease or unclear left ventricular hypertrophy. Several echocardiographic parameters will raise suspicion and lead to further testing. Cardiac magnetic resonance and scintigraphy with bone avid radiotracers are crucial for diagnosis of CA and even enable a distinction between different subtypes. The subject is illuminated with established guidelines and innovative recent publications to further improve early diagnosis of cardiac amyloidosis in light of current treatment options.

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 < 0.001). The primary endpoint occurred in 59 (18.7%) patients [median follow-up 4.2 (2.0-5.6) years]. In the univariate analyses all strain parameters showed a significant prognostic value (p < 0.05). In the multivariate model, LV strain parameters, particularly GLS provided an incremental prognostic value compared to established CMR parameters like LV ejection fraction and late gadolinium enhancement. A scoring model including six categorical variables of standard CMR and strain parameters differentiated further risk subgroups., 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., (© 2021. The Author(s).)

Background: 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., Methods: 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 to > 60 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., Results: 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)., Conclusions: 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 of <50% 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., (Copyright © 2021 Elsevier B.V. All rights reserved.)

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.

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 <  0.001 for all). In unadjusted univariate analysis, LAS (HR = 1.05, p <  0.001) and MCF (HR = 0.96, p <  0.001) were associated with reduced transplant-free survival. Kaplan-Meier analyses showed a significantly lower event-free survival in patients with reduced MCF. MCF and LAS performed best to identify high risk patients for secondary endpoint (Log-rank test p <  0.001) in a combined model. Using sequential Cox regression analysis, the addition of LAS and MCF to LV ejection fraction led to a significant increase in the predictive power of the model (χ 2 (df = 1) = 28.2, p <  0.001)., Conclusions: LAS and MCF as routinely available and robust CMR-derived parameters predict outcome in LGE positive AL amyloidosis. Patients with impaired LV function in combination with reduced LAS and MCF are at the highest risk for death and heart transplantation.

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 < 0.05), mean values for MCF were significantly reduced in LVH (HHD:92.6 ± 20%, HCM:80 ± 20.3%, transthyretin CA:74.9 ± 32.2% and light-chain (AL) CA:50.5 ± 21.4%). MCF performed better than LVEF (AUC = 0.96 vs. AUC = 0.6, P < 0.001) and was comparable to LVMI (AUC = 0.95, P = 0.4) in discriminating LVH from controls. There was a significant yet weak correlation between MCF and LVEF (r = 0.43, P < 0.0001). MCF outperformed LVEF and LVMI in discriminating between different etiologies of LVH and between AL and other forms of LVH (AUC = 0.84, P < 0.0001). Moreover, cut-off values for MCF <50% and LVEF <60% allowed to identify patients with high probability for CA., Conclusion: In patients with heart failure MCF discriminates CA from other forms of LVH. As it can easily be derived from standard, non-contrast cine images, it may be a very useful marker in the diagnostic workup of patients with LVH., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.)

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 MAPSE anterolateral (7.3 mm (IQR, 5.4-11.7) vs. 10.5 mm (IQR, 8.1-13.4); p = 0.03). AAPSE (χ 2  = 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 < 0.0001). AAPSE added incremental prognostic power to an imaging prediction model of late gadolinium enhancement and global longitudinal strain (GLS) (∆χ 2  = 5.8, p = 0.02) as well as to a clinical model including Karnofsky index and NT-proBNP (∆χ 2  = 6.2, p = 0.01)., Conclusion: In patients with cardiac involvement in AL amyloidosis, systolic CVPD obtained from standard long axis cine views appear to indicate outcome better, when obtained in the anterior aortic plane (AAPSE) and provide incremental prognostic value to LGE and strain measurements.

Objective: 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)., Methods: 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., Results: 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., Conclusion: Assessment of RV-LAS is an independent indicator of outcome in patients with NIDCM and offers incremental information beyond clinical and cardiac MR parameters., Key Points: • 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 RVEF >45%. • Addition of RV-LAS to known risk factors enhances the power prognostic information.

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. © RSNA, 2017 Online supplemental material is available for this article.

Purpose: Right ventricular longitudinal axis strain (RV-LAS) is a simple measure of RV longitudinal function. The purpose of this study was the evaluation of its diagnostic performance in non-ischemic dilated cardiomyopathy (NIDCM) and the determination of reference values in controls., Methods: 217 NIDCM patients and 200 healthy controls were analysed retrospectively regarding the diagnostic performance of RV-LAS using receiver operating characteristic curves in comparison with RV ejection fraction (RVEF), tricuspid annular plane systolic excursion (TAPSE) and global longitudinal strain (RV-GLS). Hereby, four different approaches were evaluated to assess RV-LAS based on different reference points. RV-LAS LVapex/mid was defined as the change in distance between the LV apex and the middle of a line connecting the origins of the tricuspidal valve leaflets in systole and diastole. The ethical approval was obtained in all participants., Results: NIDCM and controls were 48 years in mean. Controls were equally gender distributed, while the proportion of men with NIDCM was higher with 77%. Among the four approaches RV-LAS LVapex/mid provided the highest diagnostic performance for discrimination between NIDCM and controls (AUC=0.94). Of all RV functional parameters RV-LAS LVapex/mid preformed significantly better than RVEF (delta AUC=0.05; p=0.003), TAPSE (delta AUC=0.23; p<0.0001) and RV-GLS (delta AUC=0.31; p<0.0001). A significant correlation was found between RV-LAS LVapex/mid and RVEF (r=-0.65; p<0.0001). The reference mean values for RV-LAS LVapex/mid were -17.4±3.5 for men and -18.5±3.7 for women., Conclusion: RV-LAS showed better diagnostic accuracy for RV dysfunction than RVEF, TAPSE and RV-GLS. Furthermore, it has a rapid accessibility and low intra- and interobserver variability., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

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 < 0.05), presence of LGE (HR: 2.51, p < 0.05) and LAS (HR: 1.28, p < 0.05) were independent predictors for cardiac events. In a sequential cox regression analysis LAS offered significant incremental information (p < 0.05) for the prediction of outcome in addition to LGE and LVEDV/BSA. Using a dichotomous three point scoring model for risk stratification, including LVEF <35 %, LAS > -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.

History: A 36-year-old man with a history of PR3-ANCA positive granulomatosis with polyangiitis presented with chest pain at the emergency department. Due to his underlying disease, he was treated with Rituximab in regular intervals. The last Rituximab infusion was admitted one day before presentation., Investigation: The ECG showed marked ST elevation in V1-V4., Diagnosis, Treatment and Course: After the diagnosis of an acute anterior myocardial infarction, the patient was prepared for acute percutaneous coronary intervention. During transport to the cardiac catheterization laboratory, he suffered a cardiac arrest due to ventricular fibrillation. After successful resuscitation, the cardiac catheterization showed no evidence of relevant coronary stenosis. Because of suspected coronary spasm of left anterior descending artery the therapy was extended with a calcium channel blocker. A single chamber cardiac defibrillator was implanted for secondary prevention., Conclusion: Acute coronary syndrome is a possible side effect of rituximab therapy. The reported case emphasizes a correlation between Rituximab therapy and cardiac event., (© Georg Thieme Verlag KG Stuttgart · New York.)

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., (©2014 Wiley Periodicals, Inc.)

Sudden cardiac death is one of the leading causes of death in industrialized countries. The implantable cardioverter/defibrillator (ICD) is the most effective treatment for malignant ventricular tachyarrhythmias. Current guidelines recommend the implantation of a defibrillator in patients who experienced ventricular tachycardia or fibrillation (secondary prevention of sudden cardiac death), as well as in high risk patients for primary prevention. The latter are patients with impaired left ventricular function ≤ 35 %. With the exception of secondary prevention indications (ie. after a "survived sudden cardiac death") indications for ICD implantation in the context of other cardiomyopathies, such as hypertrophic (obstructive) cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy (ARVC), and of channelopathies, such as Brugada syndrome and long QT syndrome are complex. Before deciding to implant an ICD, the indication as well as the potential complications (inappropriate shocks, risk of infection, device or lead replacement, costs, etc.) have to be considered and discussed in detail with the patients and their relatives. There are very few specific hazards or significant limitations in daily life for the patient and his environment caused by the ICD. An ICD can be transiently deactivated if necessary by using a magnet (eg. during surgery) or permanently deactivated by re-programming the device (eg. palliative care).

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], 50-70) years old, mostly symptomatic, and had an average LVEF of 34 ± 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 (0.7-5.2) 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., (Copyright © 2013 Elsevier Inc. All rights reserved.)

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., (Copyright © 2013 Elsevier Inc. All rights reserved.)

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., (Copyright © 2012 Elsevier Inc. 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.

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.

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<0.001). Cardiac troponin T (cTnT) and sensitive cardiac troponin I (s-cTnI) were also significantly higher in ischemic compared with nonischemic AHF patients (0.040 [0.010-0.306] μg/L versus 0.018 [0.010-0.060] μg/L [P<0.001]; 0.024 [0.008-0.106] μg/L versus 0.016 [0.004-0.044 ] μg/L [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.

Aims: To determine the relationship between central venous pressure (CVP) and renal function in patients with acute heart failure (AHF) presenting to the emergency department., Methods and Results: 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)., Conclusion: 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.

Introduction: Monitoring treatment efficacy and assessing outcome by serial measurements of natriuretic peptides in acute decompensated heart failure (ADHF) patients may help to improve outcome., Methods: This was a prospective multi-center study of 171 consecutive patients (mean age 80 73-85 years) presenting to the emergency department with ADHF. Measurement of BNP and NT-proBNP was performed at presentation, 24 hours, 48 hours and at discharge. The primary endpoint was one-year all-cause mortality; secondary endpoints were 30-days all-cause mortality and one-year heart failure (HF) readmission., Results: During one-year follow-up, a total of 60 (35%) patients died. BNP and NT-proBNP levels were higher in non-survivors at all time points (all P < 0.001). In survivors, treatment reduced BNP and NT-proBNP levels by more than 50% (P < 0.001), while in non-survivors treatment did not lower BNP and NT-proBNP levels. The area under the ROC curve (AUC) for the prediction of one-year mortality increased during the course of hospitalization for BNP (AUC presentation: 0.67; AUC 24 h: 0.77; AUC 48 h: 0.78; AUC discharge: 0.78) and NT-proBNP (AUC presentation: 0.67; AUC 24 h: 0.73; AUC 48 h: 0.75; AUC discharge: 0.77). In multivariate analysis, BNP at 24 h (1.02 [1.01-1.04], P = 0.003), 48 h (1.04 [1.02-1.06], P < 0.001) and discharge (1.02 [1.01-1.03], P < 0.001) independently predicted one-year mortality, while only pre-discharge NT-proBNP was predictive (1.07 [1.01-1.13], P = 0.016). Comparable results could be obtained for the secondary endpoint 30-days mortality but not for one-year HF readmissions., Conclusions: BNP and NT-proBNP reliably predict one-year mortality in patients with ADHF. Prognostic accuracy of both biomarker increases during the course of hospitalization. In survivors BNP levels decline more rapidly than NT-proBNP levels and thus seem to allow earlier assessment of treatment efficacy. Ability to predict one-year HF readmission was poor for BNP and NT-proBNP., Trial Registration: ClinicalTrials.gov identifier: NCT00514384.

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 (< or = 99 vs >99 pmol/L) and BNP (median of < or = 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.

Aims: 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)., Methods and Results: 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 (low <6 cm H(2)O, intermediate 6-23 cm H(2)O, and high >23 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., Conclusion: 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.

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: Peak oxygen uptake (peak VO(2)) is a predictor of outcome in patients with lung disease. In these patients, peak VO(2) is typically determined by ventilation and gas exchange. However, it is not well known whether cardiac strain contributes to peak VO(2) in patients with chronic lung disease., Objective: To assess the relationship between several novel biomarkers reflecting different aspects of cardiac function and peak VO(2) 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 (FEV(1)) 76 ± 23% of the predicted value] undergoing maximal cardiopulmonary exercise testing (peak VO(2) 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 VO(2), and these associations were independent of age, gender, medication, FEV(1) and oxygenation. The relationship between MR-proANP, MR-proADM, and CT-proET-1 and peak VO(2) 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 VO(2) 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., (Copyright © 2010 S. Karger AG, Basel.)