Optimizing resource allocation: Cost-effectiveness of specified D-dimer cut-offs in cancer patients with suspected venous thromboembolism.

An accurate diagnosis of venous thromboembolism (VTE) is crucial, given the potential for high mortality in undetected cases. Strategic D-dimer testing may aid in identifying low-risk patients, preventing overdiagnosis and reducing imaging costs. We conducted a retrospective, comparative analysis to assess the potential cost savings that could be achieved by adopting different approaches to determine the most effective D-dimer cut-off value in cancer patients with suspected VTE, compared to the commonly used rule-out cut-off level of 0.5 mg/L. The study included 526 patients (median age 65, IQR 55-75) with a confirmed cancer diagnosis who underwent D-dimer testing. Among these patients, the VTE prevalence was 29% (n = 152). Each diagnostic strategy's sensitivity, specificity, negative likelihood ratio (NLR), as well as positive likelihood ratio (PLR), and the proportion of patients exhibiting a negative D-dimer test result, were calculated. The diagnostic strategy that demonstrated the best balance between specificity, sensitivity, NLR, and PLR, utilized an inverse age-specific cut-off level for D-dimer [0.5 + (66-age) × 0.01 mg/L]. This method yielded a PLR of 2.9 at a very low NLR for the exclusion of VTE. We observed a significant cost reduction of 4.6% and 1.0% for PE and DVT, respectively. The utilization of an age-adjusted cut-off [patient's age × 0.01 mg/L] resulted in the highest cost savings, reaching 8.1% for PE and 3.4% for DVT. Using specified D-dimer cut-offs in the diagnosis of VTE could improve economics, considering the limited occurrence of confirmed cases among patients with suspected VTE.

microRNA neural networks improve diagnosis of acute coronary syndrome (ACS).

BACKGROUND: Cardiac troponins are the preferred biomarkers of acute myocardial infarction. Despite superior sensitivity, serial testing of Troponins to identify patients suffering acute coronary syndromes is still required in many cases to overcome limited specificity. Moreover, unstable angina pectoris relies on reported symptoms in the troponin-negative group. In this study, we investigated genome-wide miRNA levels in a prospective cohort of patients with clinically suspected ACS and determined their diagnostic value by applying an in silico neural network. METHODS: PAXgene blood and serum samples were drawn and hsTnT was measured in patients at initial presentation to our Chest-Pain Unit. After clinical and diagnostic workup, patients were adjudicated by senior cardiologists in duty to their final diagnosis: STEMI, NSTEMI, unstable angina pectoris and non-ACS patients. ACS patients and a cohort of healthy controls underwent deep transcriptome sequencing. Machine learning was implemented to construct diagnostic miRNA classifiers. RESULTS: We developed a neural network model which incorporates 34 validated ACS miRNAs, showing excellent classification results. By further developing additional machine learning models and selecting the best miRNAs, we achieved an accuracy of 0.96 (95% CI 0.96-0.97), sensitivity of 0.95, specificity of 0.96 and AUC of 0.99. The one-point hsTnT value reached an accuracy of 0.89, sensitivity of 0.82, specificity of 0.96, and AUC of 0.96. CONCLUSIONS: Here we show the concept of neural network based biomarkers for ACS. This approach also opens the possibility to include multi-modal data points to further increase precision and perform classification of other ACS differential diagnoses.

Presence of contractile impairment appears crucial for structural remodeling in idiopathic left bundle-branch block.

BACKGROUND: To differentiate effects of ventricular asynchrony from an underlying hypocontractile cardiomyopathy this study aimed to enhance the understanding of functional impairment and structural remodeling in idiopathic left bundle-branch block (LBBB). We hypothesize, that functional asynchrony with septal flash volume effects alone might not entirely explain the degree of functional impairment. Hence, we suggest the presence of a superimposed contractile cardiomyopathy. METHODS: In this retrospective study, 53 patients with idiopathic LBBB were identified and matched to controls with and without cardiovascular risk factors. Cardiovascular magnetic resonance (CMR) was used to evaluate cardiac function, volumes and myocardial fibrosis using native T1 mapping and late gadolinium enhancement (LGE). Septal flash volume was assessed by CMR volumetric measurements and allowed to stratify patients with systolic dysfunction solely due to isolated ventricular asynchrony or superimposed contractile impairment. RESULTS: Reduced systolic LV-function, increased LV-volumes and septal myocardial fibrosis were found in patients with idiopathic LBBB compared to healthy controls. LV-volumes increased and systolic LV-function declined with prolonged QRS duration. Fibrosis was typically located at the right ventricular insertion points. Subgroups with superimposed contractile impairment appeared with pronounced LV dilation and increased fibrotic remodeling compared to individuals with isolated ventricular asynchrony. CONCLUSIONS: The presence of superimposed contractile impairment in idiopathic LBBB is crucial to identify patients with enhanced structural remodeling. This finding suggests an underlying cardiomyopathy. Future studies are needed to assess a possible prognostic impact of this entity and the development of heart failure. TRIAL REGISTRATION: This study was retrospectively registered.

The impact of Wilson disease on myocardial tissue and function: a cardiovascular magnetic resonance study.

BACKGROUND: Systemic effects of altered serum copper processing in Wilson Disease (WD) might induce myocardial copper deposition and consequently myocardial dysfunction and structural remodeling. This study sought to investigate the prevalence, manifestation and predictors of myocardial tissue abnormalities in WD patients. METHODS: We prospectively enrolled WD patients and an age-matched group of healthy individuals. We applied cardiovascular magnetic resonance (CMR) to analyze myocardial function, strain, and tissue characteristics. A subgroup analysis of WD patients with predominant neurological (WD-neuro+) or hepatic manifestation only (WD-neuro-) was performed. RESULTS: Seventy-six patients (37 years (27-49), 47% women) with known WD and 76 age-matched healthy control subjects were studied. The prevalence of atrial fibrillation in WD patients was 5% and the prevalence of symptomatic heart failure was 2.6%. Compared to healthy controls, patients with WD had a reduced left ventricular global circumferential strain (LV-GCS), and also showed abnormalities consistent with global and regional myocardial fibrosis. WD-neuro+ patients presented with more severe structural remodeling and functional impairment when compared to WD-neuro- patients. CONCLUSIONS: In a large cohort, WD was not linked to a distinct cardiac phenotype except CMR indexes of myocardial fibrosis. More research is warranted to assess the prognostic implications of these findings. TRIAL REGISTRATION: This trial is registered at the local institutional ethics committee (S-188/2018).

Comparison of the analytical performance of the PATHFAST high sensitivity cardiac troponin I using fresh whole blood vs. fresh plasma samples.

OBJECTIVES: The PATHFAST hs-cTnI (high-sensitivity cardiac troponin) assay is the first point-of-care assay with a high-sensitivity designation that received FDA approval for diagnosis of myocardial infarction (MI). Testing from whole blood does not need centrifugation and therefore is faster and more convenient in the emergency room instead of plasma. However, there is sparse evidence whether point-of-care testing of Tn from whole blood is as reliable as from plasma samples. METHODS: We investigated the agreement between plasma and whole blood hs-cTnI by using the PATHFAST hs-cTnI assay. Hs-cTnT measured on Cobas 602 in the central laboratory and compared to a final diagnosis of NSTEMI using serial hs-cTnT served as reference. We assessed biases, limits of agreement (±1.96 SD) and coefficients of correlation, and tested the discriminatory ability of the baseline sample of plasma and whole blood hs-cTnI and plasma hs-cTnT to discriminate non-ST-segment elevation myocardial infarction (NSTEMI). RESULTS: A total of 224 paired fresh samples were collected simultaneously from 191 patients presenting with suspected acute coronary syndrome. There was an excellent correlation between plasma and whole blood hs-cTnI (r=0.99), and a very good inter-rater agreement (k=0.93) between elevated and normal plasma and whole blood results. Precision evaluation according to CLSI ep 15 revealed comparable coefficients of variation (CV) in whole blood and plasma. The discriminatory ability of baseline hs-cTnT, plasma and whole blood hs-cTnI was excellent (AUC 0.967, AUC 0.954 and AUC 0.953) without significant difference. CONCLUSIONS: Whole blood can be used interchangeably with plasma for more convenient and less time and labor-consuming testing of hs-cTnI on the PATHFAST instrument.

Prognostic relevance of global work index and global constructive work in patients with non-ischemic dilated cardiomyopathy.

Myocardial work (MW) derived from pressure-strain loops is a novel non-invasive tool to assess left ventricular (LV) function, incorporating global longitudinal strain (GLS) by speckle tracking echocardiography and non-invasively assessed blood pressure. Studies on the role of MW in dilated cardiomyopathy (DCM) are still limited. Therefore, the aim of this study was to evaluate the potential value of MW for predicting adverse outcomes in patients with DCM. 116 consecutive patients with DCM who underwent heart catheterization were retrospectively recruited from June 2009 to July 2014. 34 patients (30%) met the composite endpoints for major adverse cardiac events (MACE) of cardiac transplantation, need for implantable cardioverter-defibrillator (ICD) therapy, heart failure hospitalization and all-cause mortality. Patients with DCM were followed up for a mean of 5.1 years (IQR: 2.2-9.1 years). Global work index (GWI) and global constructive work (GCW) were not only independent predictors but also provided incremental predictive values (Integrated discrimination improvement [IDI] > 0) of MACE in multivariate Cox models. Furthermore, Patients with GWI < 788 mm Hg% (HR 5.46, 95%CI 1.66-17.92, p = 0.005) and GCW < 1,238 mm Hg% (HR 4.46, 95%CI 1.53-12.98, p = 0.006) had higher risks of MACE. GWI and GCW assessed by strain imaging echocardiography may have an additional value beyond LV-EF and GLS for predicting adverse outcomes in DCM.

Design, Rationale and Initial Findings From HERA-FIB on 10 222 Patients With Atrial Fibrillation Presenting to an Emergency Department Over An 11-Year Period.

BACKGROUND: For the majority of patients with atrial fibrillation (AF), disease management has improved in recent years. However, there are still populations underrepresented or excluded in current registries and randomized controlled trials. HERA-FIB (Heidelberg Registry of Atrial Fibrillation) was planned to assess real-world evidence for the prevalence, demographic characteristics and management of patients with the diagnosis of AF presenting consecutively to a chest pain unit. METHODS AND RESULTS: HERA-FIB is a retrospective, observational, single-center study on patients with a diagnosis of AF presenting to a chest pain unit from June 2009 until March 2020. This article describes the structure, governance, outcome assessment, quality and data collection processes of the registry. Additionally, characteristics of populations of special interest are described. The study consecutively enrolled 10 222 patients presenting with AF to the chest pain unit of the University Hospital of Heidelberg. Clinical parameters and patient characteristics were assessed retrospectively. Outcome parameters included rates for all-cause death, stroke, myocardial infarction and major bleedings. We were able to investigate patient cohorts of special interest such as advanced chronic kidney disease, octogenarians, and those with acute coronary syndrome who are often underrepresented in current studies and randomized controlled trials. CONCLUSIONS: HERA-FIB is one of the largest real-world single-center retrospective registries on patients with AF, which captures the era of transition from vitamin K antagonists to non-vitamin K oral anticoagulation regimens in clinical practice and offers the possibility to investigate patient populations usually underrepresented or excluded in current available randomized controlled trials and registries. REGISTRATION: URL: https://www.clinicaltrials.gov; unique identifier: NCT05995561.

Role of Copeptin and hs-cTnT to Discriminate AHF from Uncomplicated NSTE-ACS with Baseline Elevated hs-cTnT-A Derivation and External Validation Study.

BACKGROUND: In light of overlapping symptoms, discrimination between non-ST-elevation (NSTE) acute coronary syndrome (ACS) and acute heart failure (HF) is challenging, particularly in patients with equivocal clinical presentation for suspected ACS. We sought to evaluate the diagnostic and prognostic properties of copeptin in this scenario. METHODS: Data from 1088 patients from a single-center observational registry were used to test the ability of serial high sensitivity cardiac troponin T (hs-cTnT)-compared to copeptin, or a combination of copeptin with hs-cTnT-to discriminate acute HF from uncomplicated non-ST-elevation myocardial infarction (NSTEMI) and to evaluate all-cause mortality after 365 days. Patients with STEMI, those with unstable angina and either normal or undetectable hs-cTnT concentrations were excluded. The findings were validated in an independent external NSTE-ACS cohort. RESULTS: A total of 219 patients were included in the analysis. The final diagnosis was acute HF in 56 and NSTE-ACS in 163, with NSTEMI in 78 and unstable angina having stable elevation of hs-cTnT >ULN in 85. The rate of all-cause death at 1 year was 9.6% and occurred significantly more often in acute HF than in NSTE-ACS (15 vs. 6%, p < 0.001). In the test cohort, the area under the receiver operator curve (AUC) for the discrimination of acute HF vs. NSTE-ACS without HF was 0.725 (95% confidence interval [CI] 0.625-0.798) for copeptin and significantly higher than for hs-cTnT at 0 h (AUC = 0.460, 0.370-0.550) or at 3 h (AUC = 0.441, 0.343-0.538). Copeptin and hs-cTnT used either as continuous values or at cutoffs optimized to yield 90% specificity for acute HF were associated with significantly higher age- and sex-adjusted risk for all-cause mortality at 365 days. The findings from the test cohort were consistently replicated in the independent external NSTE-ACS validation cohort. CONCLUSIONS: High concentrations of copeptin in patients with suspected NSTE-ACS and equivocal clinical presentation suggest the presence of acute HF compared to uncomplicated NSTE-ACS and are associated with higher rates of all-cause death at 365 days.

Dynamic Handgrip Exercise: Feasibility and Physiologic Stress Response of a Potential Needle-Free Cardiac Magnetic Resonance Stress Test.

Background: Cardiac magnetic resonance (CMR) pharmacological stress-testing is a well-established technique for detecting myocardial ischemia. Although stressors and contrast agents seem relatively safe, contraindications and side effects must be considered. Substantial costs are further limiting its applicability. Dynamic handgrip exercise (DHE) may have the potential to address these shortcomings as a physiological stressor. We therefore evaluated the feasibility and physiologic stress response of DHE in relation to pharmacological dobutamine-stimulation within the context of CMR examinations. Methods: Two groups were prospectively enrolled: (I) volunteers without relevant disease and (II) patients with known CAD referred for stress-testing. A both-handed, metronome-guided DHE was performed over 2 min continuously with 80 contractions/minute by all participants, whereas dobutamine stress-testing was only performed in group (II). Short axis strain by fast-Strain-ENCoded imaging was acquired at rest, immediately after DHE and during dobutamine infusion. Results: Eighty middle-aged individuals (age 56 ± 17 years, 48 men) were enrolled. DHE triggered significant positive chronotropic (HRrest: 68 ± 10 bpm, HRDHE: 91 ± 13 bpm, p < 0.001) and inotropic stress response (GLSrest: -19.4 ± 1.9%, GLSDHE: -20.6 ± 2.1%, p < 0.001). Exercise-induced increase of longitudinal strain was present in healthy volunteers and patients with CAD to the same extent, but in general more pronounced in the midventricular and apical layers (p < 0.01). DHE was aborted by a minor portion (7%) due to peripheral fatigue. The inotropic effect of DHE appears to be non-inferior to intermediate dobutamine-stimulation (GLSDHE= -19.5 ± 2.3%, GLSDob= -19.1 ± 3.1%, p = n.s.), whereas its chronotropic effect was superior (HRDHE= 89 ± 14 bpm, HRDob= 78 ± 15 bpm, p < 0.001). Conclusions: DHE causes positive ino- and chronotropic effects superior to intermediate dobutamine-stimulation, suggesting a relevant increase of myocardial oxygen demand. DHE appears to be safe and timesaving with broad applicability. The data encourages further studies to determine its potential to detect obstructive CAD.

Low-Level Elevations of Procalcitonin Are Associated with Increased Mortality in Acute Heart Failure Patients, Independent of Concomitant Infection.

We aimed to evaluate the prognostic value of procalcitonin (PCT) in acute heart failure (AHF) patients, especially in those without underlying infection. We enrolled patients presenting with acute dyspnea to the emergency department (ED) of Heidelberg University Hospital and studied the prognostic role of PCT on all-cause death. Of 312 patients, AHF was diagnosed in 139 patients. Of these, 125 patients had AHF without signs of infection, and 14 had AHF complicated by respiratory or other infection. The optimal prognostic PCT cutoff value for mortality prediction was calculated by a receiver operating characteristics curve. In patients with AHF, the prognostic PCT cutoff value was 0.08 ng/mL. The Kaplan-Meier survival analysis showed that AHF patients with PCT values > 0.08 ng/mL had a higher all-cause mortality at 120 days than those with PCT values ≤ 0.08 ng/mL (log-rank p = 0.0123). Similar results could be obtained after subdivision into AHF patients with and without signs of overt infection. In both cases, mortality was higher in patients with PCT levels above the prognostic PCT cutoff than in those with values ranging below this threshold. Moreover, we show that the prognostic PCT cutoff values for mortality prediction ranged below the established PCT cutoff for the guidance of antibiotic therapy. In conclusion, the data of our study revealed that low-level elevations of PCT were associated with an increased mortality in patients with AHF, irrespective of concomitant respiratory or other infection. PCT should thus be further used as a marker in the risk stratification of AHF.

Diagnostic performance of D-dimer in predicting venous thromboembolism and acute aortic dissection.

BACKGROUND: D-dimer is elevated in a variety of conditions. The purpose of this study was to assess the positive predictive value of D-dimer to rule in patients with confirmed pulmonary embolism, deep vein thrombosis, acute aortic dissection or thrombosis of the upper extremity in comparison to patients with elevated D-dimer for other reasons. METHODS AND RESULTS: We studied 1334 patients presenting to the emergency department with pulmonary embolism (n=193), deep vein thrombosis (n=73), acute aortic dissection (n=22), thrombosis of the upper extremity (n=8) and 1038 controls. The positive predictive value was increased with higher D-dimer concentrations improving the ability to identify diseases with high thrombus burden. Patients with venous thromboembolism, acute aortic dissection and thrombosis of the upper extremity showed a maximum positive predictive value of 85.2% at a D-dimer level of 7.8 mg/L (95% confidence interval (CI) 78.1 to 90.4). The maximum positive predictive value was lower in cancer patients with venous thromboembolism, acute aortic dissection and thrombosis of the upper extremity, reaching 68.9% at a D-dimer level of 7.5 mg/L (95% CI 57.4 to 78.4). The positive likelihood ratio was very consistent with the positive predictive value. Using a cut-off level of 0.5 mg/L, D-dimer showed a high sensitivity of at least 93%, but a very low specificity of nearly 0%. Conversely, an optimised cut-off value of 4.6 mg/L increased specificity to 95% for the detection of life-threatening venous thromboembolism, acute aortic dissection or thrombosis of the upper extremity at the costs of moderate sensitivities (58% for pulmonary embolism, 41% for deep vein thrombosis, 65% for pulmonary embolism with co-existent deep vein thrombosis, 50% for acute aortic dissection and 13% for thrombosis of the upper extremity). Using the same cut-off in cancer patients, higher values were observed for sensitivity at a specificity level of more than 95%. The area under the curve for the discrimination of venous thromboembolism/acute aortic dissection/thrombosis of the upper extremity from controls was significantly higher in cancer versus non-cancer patients (area under the curve 0.905 in cancer patients, 95% CI 0.89 to 0.92, vs. area under the curve 0.857 in non-cancer patients, 95% CI 0.84 to 0.88; P=0.0349). CONCLUSION: D-dimers are useful not only to rule out but also to rule in venous thromboembolism and acute aortic dissection with an at least moderate discriminatory ability, both in patients with and without cancer.

Diagnostic performance of D-dimer in predicting venous thromboembolism and acute aortic dissection.

BACKGROUND: D-dimer is elevated in a variety of conditions. The purpose of this study was to assess the positive predictive value of D-dimer to rule in patients with confirmed pulmonary embolism, deep vein thrombosis, acute aortic dissection or thrombosis of the upper extremity in comparison to patients with elevated D-dimer for other reasons. METHODS AND RESULTS: We studied 1334 patients presenting to the emergency department with pulmonary embolism (n=193), deep vein thrombosis (n=73), acute aortic dissection (n=22), thrombosis of the upper extremity (n=8) and 1038 controls. The positive predictive value was increased with higher D-dimer concentrations improving the ability to identify diseases with high thrombus burden. Patients with venous thromboembolism, acute aortic dissection and thrombosis of the upper extremity showed a maximum positive predictive value of 85.2% at a D-dimer level of 7.8 mg/L (95% confidence interval (CI) 78.1 to 90.4). The maximum positive predictive value was lower in cancer patients with venous thromboembolism, acute aortic dissection and thrombosis of the upper extremity, reaching 68.9% at a D-dimer level of 7.5 mg/L (95% CI 57.4 to 78.4). The positive likelihood ratio was very consistent with the positive predictive value. Using a cut-off level of 0.5 mg/L, D-dimer showed a high sensitivity of at least 93%, but a very low specificity of nearly 0%. Conversely, an optimised cut-off value of 4.6 mg/L increased specificity to 95% for the detection of life-threatening venous thromboembolism, acute aortic dissection or thrombosis of the upper extremity at the costs of moderate sensitivities (58% for pulmonary embolism, 41% for deep vein thrombosis, 65% for pulmonary embolism with co-existent deep vein thrombosis, 50% for acute aortic dissection and 13% for thrombosis of the upper extremity). Using the same cut-off in cancer patients, higher values were observed for sensitivity at a specificity level of more than 95%. The area under the curve for the discrimination of venous thromboembolism/acute aortic dissection/thrombosis of the upper extremity from controls was significantly higher in cancer versus non-cancer patients (area under the curve 0.905 in cancer patients, 95% CI 0.89 to 0.92, vs. area under the curve 0.857 in non-cancer patients, 95% CI 0.84 to 0.88; P=0.0349). CONCLUSION: D-dimers are useful not only to rule out but also to rule in venous thromboembolism and acute aortic dissection with an at least moderate discriminatory ability, both in patients with and without cancer.

Long-term biological variation of high-sensitivity cardiac troponin T using minimal important differences and reference change values in stable outpatients with cardiovascular disease.

OBJECTIVE: To evaluate the long term biological variation of high-sensitivity cardiac troponin T (hs-cTnT) in stable outpatients with cardiovascular disease (CVD). METHODS: After applying 8 exclusion criteria to 965 patients, hs-cTnT was measured at index visit and at a 12-month interval in 169 stable outpatients presenting for routine follow-up visits for any CVD. Stability was defined as absence of any endpoint within the follow-up period. Reference change values (RCVs) and minimal important differences (MIDs) were determined to assess biological variation of hs-cTnT. RESULTS: MID and RCV for the 12 months interval in patients were 3.8 ng/L or 44.2%, respectively. MID and transformed MID values were lower than the corresponding RCV with a value of 5.1 ng/L for the transformed RCV and 28.1% for the transformed MID. Similar patterns were shown in different subgroups as sex, age, and renal function. We observed a baseline hs-cTnT value dependent change of MID and RCV with increasing values for MID and decreasing values for RCV which converge to stable values between a baseline hs-cTNT value of 11 to 25 ng/L. CONCLUSIONS: Biological variation of hs-cTnT over 12 months in stable outpatients depends on the concentration at index visit, and is consistent among important prespecified subgroups. MID shows a low biovariability over 12 months. Clinical Trials Identifier:NCT01954303.

Pathophysiological background and prognostic implication of systolic aortic root motion in non-ischemic dilated cardiomyopathy.

Recordings of aortic root movement represent one of the first accomplishments of ultrasound in medicine and mark the beginning of functional cardiac imaging. However, the underlying mechanism is not completely understood. Since the aortic root is directly connected to the cardiac skeleton we hypothesize, that the amplitude of systolic aortic root motion (SARM) may be mainly caused by displacement of the cardiac base towards the apex and might therefore be used as measure of left ventricular longitudinal function (LV-LF). One hundred and eighty patients with dilated cardiomyopathy and 180 healthy controls were prospectively included into this study. SARM was lower in patients compared to controls (9 ± 3 mm vs. 12 ± 2 mm, p < 0.001) and lowest in patients with cardiovascular events (9 ± 3 mm vs. 7 ± 3 mm, p < 0.001). During a median follow-up time of 38 months, the combined end-point of cardiovascular death or hospitalization for heart failure was reached by 25 patients (13.9%). Reduced SARM had significant prognostic impact on outcome (hazard ratio 0.74, 95% confidence interval 0.63-0.88, p < 0.001) and remained an independent predictor in the multivariate analysis. Compared to parameters with potential influence on its mechanism, SARM correlated best (r = 0.75, p < 0.001) with global longitudinal strain (GLS). SARM may therefore represent an alternative echocardiographic parameter for the assessment of LV-LF, particularly when GLS is not feasible or apical views are not available.

Unidimensional Longitudinal Strain: A Simple Approach for the Assessment of Longitudinal Myocardial Deformation by Echocardiography.

BACKGROUND: Impaired left ventricular (LV) longitudinal function (LF) is a known predictor of cardiac events in patients with heart failure, but two-dimensional strain imaging, the reference method to measure myocardial deformation, is not always feasible or available. Therefore, reliable and reproducible alternatives are needed. The aim of the present study was to evaluate unidimensional longitudinal strain (ULS) as a simple echocardiographic parameter for the assessment of LV LF. METHODS: Two hundred two patients with dilated cardiomyopathy who had their first presentation in the authors' cardiology department, as well as the same number of age- and gender-matched control subjects, were prospectively included in this study. ULS was compared with global longitudinal strain (GLS), the current gold standard for LV LF assessment by echocardiography. Uni- and multivariate Cox regression analyses were conducted to evaluate the prognostic value of ULS. RESULTS: LV LF was higher in the control group compared with patients: GLS -19.5 ± 1.7% versus -12.6 ± 4.8% and ULS -16.3 ± 1.5% versus -10.2 ± 3.9% (P < .001 for each). Correlation between ULS and GLS was excellent (r = 0.94), while Bland-Altman plots revealed lower values for ULS (bias -2.76%, limits of agreement ±3.31%). During a mean follow-up time of 39 months, the combined end point of cardiovascular death or hospitalization for acute cardiac decompensation was reached by 28 patients (13.9%). GLS (hazard ratio, 1.21; 95% CI, 1.10-1.34; P < .001) and ULS (hazard ratio, 1.24; 95% CI, 1.12-1.39; P < .001) had comparable prognostic impact on patient outcomes. CONCLUSIONS: ULS might be an alternative echocardiographic method for the assessment of LV LF, with similar diagnostic and prognostic value compared with GLS.

Comparative accuracy of NT-proBNP and MR-proANP for the diagnosis of acute heart failure in dyspnoeic patients.

AIMS: To compare the performance of the natriuretic peptides (NPs) NT-proBNP and MR-proANP for the diagnosis of acute heart failure (AHF) in subsets of conditions potentially confounding the interpretation of NPs. METHODS AND RESULTS: We studied 312 patients, presenting to the emergency department with new onset of dyspnoea or worsening of chronic dyspnoea within the last 2 weeks. Performance of NPs for the diagnosis of AHF was tested and compared using C-statistics in the entire cohort and in conditions previously described to confound interpretation of NPs such as older age, renal failure, obesity, atrial fibrillation or paced rhythm, and in the NT-proBNP grey zone. AHF was diagnosed in 139 patients. In the entire cohort, the diagnostic performance of NT-proBNP was comparable with that of MR-proANP. Receiver operating characteristic analysis demonstrated that optimal diagnostic cut-offs were higher in the presence of older age, kidney failure or rhythm disorder. However, there were no statistically relevant differences between the receiver operating characteristic curves analysed in the total population and those studied in the pre-specified subsets severe kidney failure, advanced age, obesity, atrial fibrillation and paced rhythm, and grey zone NT-proBNP values. Moreover, the diagnostic performance of NT-proBNP was comparable with that of MR-proANP in the subsets. CONCLUSIONS: The performance of NT-proBNP and MR-proANP for AHF is comparable in the total population as well as in the subsets with potentially confounding characteristics such as older age, renal dysfunction, obesity, atrial fibrillation and paced rhythm, or those with NT-proBNP values in the grey zone.

A comprehensive analysis of cardiac valve plane displacement in healthy adults: age-stratified normal values by cardiac magnetic resonance.

Cardiac valve plane displacement (CVPD) reflects longitudinal LV function. The purpose of the present study was to determine regional heterogeneity of CVPD in healthy adults to provide normal values by cardiac magnetic resonance (CMR). We measured the anterior aortic plane systolic excursion (AAPSE); the anterior, anterolateral, inferolateral, inferior, and inferoseptal mitral annular plane systolic excursion (MAPSE); and the lateral tricuspid annulus plane systolic excursion (TAPSE). Systolic excursion was measured as the distance from peak end-diastolic to peak end-sysstolic annular position (peak-to-peak) in cine images acquired in 2-, 3- and 4-chamber views. Echocardiographic measurements of CVPD were performed in M-Mode as previously described. We retrospectively analyzed 209 healthy Caucasians (57% men), who participated in the Heidelberg normal cohort between March 2009 and September 2014. The analysis was possible in all participants. Mean values were: AAPSE = 14 ± 3 mm (8-20); MAPSEanterior = 14 ± 3 mm (8-20); MAPSEanterolateral = 16 ± 3 mm (10-22); MAPSEinferolateral = 16 ± 3 mm (10-22); MAPSEinferior = 17 ± 3 mm (11-23); MAPSEinferoseptal = 13 ± 3 mm (7-19) and TAPSE = 26 ± 4 mm (18-34) respectively. MAPSE was significantly elevated in lateral compared to septal regions (p = 0.0001). Sex-differences for CVPD were not found. Age-dependency of CVPD revealed distinct regional differences. AAPSE decreased the most with age (B=-0.48; p = 0.0001), whereas MAPSEinferior was the least age-dependent site (B=-0.17; p = 0.01). AAPSE revealed favorable intra-/interobserver reproducibility and interstudy agreement. Intermethod-comparison of CMR and M-Mode echocardiography showed good agreement between both measurements of CVPD. Age-stratified normal values of regional CVPD are provided. AAPSE revealed the most pronounced age-related decrease and provided favorable reproducibility compared to other regions of cardiac valve plane.

Myocardial contraction fraction derived from cardiovascular magnetic resonance cine images-reference values and performance in patients with heart failure and left ventricular hypertrophy.

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.