Slice positioning in phase-contrast MRI impacts aortic stenosis assessment.

AIMS: To determine the phase-contrast cardiovascular magnetic resonance imaging (PC-CMR) slice-position above aortic leaflet-attachment-plane (LAP) that provides flow-velocity, -volume and aortic valve area (AVA) measurements with best agreement to invasive and echocardiographic measurements in aortic stenosis (AS). METHODS AND RESULTS: Fifty-five patients with moderate/severe AS underwent cardiac catheterization, transthoracic echocardiography (TTE) and CMR. Overall, 171 image-planes parallel to LAP were measured via PC-CMR between 22 mm below and 24 mm above LAP. AVA via PC-CMR was calculated as flow-volume divided by peak-velocity during systole. Stroke volume (SV) and AVA were compared to volumetric SV and invasive AVA via the Gorlin-formula, respectively. Above LAP, SV by PC-CMR showed no significant dependence on image-plane-position and correlated strongly with volumetry (rho: 0.633, p < 0.001, marginal-mean-difference (MMD): 1 ml, 95 % confidence-interval (CI): -4 to 6). AVA assessed in image-planes 0-10 mm above LAP differed significantly from invasive measurement (MMD: -0.14 cm2, 95 %CI: 0.08-0.21). In contrast, AVA-values by PC-CMR measured 10-20 mm above LAP showed good agreement with invasive determination without significant MMD (0.003 cm2, 95 %CI: -0.09 to 0.09). Within these measurements, a plane 15 mm above LAP resulted in the lowest bias (MMD: 0.02 cm2, 95 %CI:-0.29 to 0.33). SV and AVA via TTE correlated moderately with volumetry (rho: 0.461, p < 0.001; bias: 15 ml, p < 0.001) and cardiac catheterization (rho: 0.486, p < 0.001, bias: -0.13 cm2, p < 0.001), respectively. CONCLUSION: PC-CMR measurements at 0-10 mm above LAP should be avoided due to significant AVA-overestimation compared to invasive determination. AVA-assessment by PC-CMR between 10 and 20 mm above LAP did not differ from invasive measurements, with the lowest intermethodical bias measured 15 mm above LAP.

Telemedical cardiac risk assessment by implantable cardiac monitors in patients after myocardial infarction with autonomic dysfunction (SMART-MI-DZHK9): a prospective investigator-initiated, randomised, multicentre, open-label, diagnostic trial.

BACKGROUND: Cardiac autonomic dysfunction after myocardial infarction identifies patients at high risk despite only moderately reduced left ventricular ejection fraction. We aimed to show that telemedical monitoring with implantable cardiac monitors in these patients can improve early detection of subclinical but prognostically relevant arrhythmic events. METHODS: We did a prospective investigator-initiated, randomised, multicentre, open-label, diagnostic trial at 33 centres in Germany and Austria. Survivors of acute myocardial infarction with left ventricular ejection fraction of 36-50% had biosignal analysis for assessment of cardiac autonomic function. Patients with abnormal periodic repolarisation dynamics (≥5·75 deg2) or abnormal deceleration capacity (≤2·5 ms) were randomly assigned (1:1) to telemedical monitoring with implantable cardiac monitors or conventional follow-up. Primary endpoint was time to detection of serious arrhythmic events defined by atrial fibrillation 6 min or longer, atrioventricular block class IIb or higher and fast non-sustained (>187 beats per min; ≥40 beats) or sustained ventricular tachycardia or fibrillation. This study is registered with ClinicalTrials.gov, NCT02594488. FINDINGS: Between May 12, 2016, and July 20, 2020, 1305 individuals were screened and 400 patients at high risk were randomly assigned (median age 64 years [IQR 57-73]); left ventricular ejection fraction 45% [40-48]) to telemedical monitoring with implantable cardiac monitors (implantable cardiac monitor group; n=201) or conventional follow-up (control group; n=199). During median follow-up of 21 months, serious arrhythmic events were detected in 60 (30%) patients of the implantable cardiac monitor group and 12 (6%) patients of the control group (hazard ratio 6·33 [IQR 3·40-11·78]; p<0·001). An improved detection rate by implantable cardiac monitors was observed for all types of serious arrhythmic events: atrial fibrillation 6 min or longer (47 [23%] patients vs 11 [6%] patients; p<0·001), atrioventricular block class IIb or higher (14 [7%] vs 0; p<0·001) and ventricular tachycardia or ventricular fibrillation (nine [4%] patients vs two [1%] patients; p=0·054). INTERPRETATION: In patients at high risk after myocardial infarction and cardiac autonomic dysfunction but only moderately reduced left ventricular ejection fraction, telemedical monitoring with implantable cardiac monitors was highly effective in early detection of subclinical, prognostically relevant serious arrhythmic events. FUNDING: German Centre for Cardiovascular Research (DZHK) and Medtronic Bakken Research Center.

Rationale and design of a digital trial using smartphones to detect subclinical atrial fibrillation in a population at risk: The eHealth-based bavarian alternative detection of Atrial Fibrillation (eBRAVE-AF) trial.

Current guidelines recommend opportunistic screening for subclinical atrial fibrillation (AF) taking advantage of e-health-based technologies. However, the efficacy of a fully scalable e-health-based strategy for AF detection in a head-to-head comparison with routine symptom-based screening is unknown. eBRAVE-AF is an investigator-initiated, digital, prospective, randomized, siteless, open-label, cross-over study to evaluate an e-health-based strategy for detection of AF in a real-world setting. 67,488 policyholders of a large German health insurance company (Versicherungskammer Bayern, Germany) selected by age ≥ 50 years and a CHA2DS2-VASc score ≥ 1 (females ≥2) are invited to participate. Subjects with known AF or on treatment with oral anticoagulation are excluded. After obtaining electronic informed consent, at least 4,400 participants will be randomly assigned to an e-health-based screening strategy or routine symptom-based screening. The e-health-based strategy consists of repetitive one-minute photoplethysmographic (PPG) pulse wave assessments using a certified smartphone app (Preventicus Heartbeats, Preventicus, Jena, Germany), followed by a confirmatory 14-day ECG patch (CardioMem CM 100 XT, Getemed, Teltow, Germany) in case of abnormal findings. After 6 months, participants are crossed over to the other study arm. Primary endpoint is the incidence of newly diagnosed AF leading to oral anticoagulation indicated by an independent physician. Clinical follow-up will be at least 12 months. In both groups, follow-up is performed by 4-week app-based questionnaires, personal contact in case of abnormal findings, and matching with claim-based insurance data and medical reports. At time of writing enrollment is completed. First results are expected to be available in mid-2021.

Global longitudinal strain improves risk assessment after ST-segment elevation myocardial infarction: a comparative prognostic evaluation of left ventricular functional parameters.

AIM: We aimed to investigate the comparative prognostic value of left ventricular ejection fraction (LVEF), mitral annular plane systolic excursion (MAPSE), fast manual long-axis strain (LAS) and global longitudinal strain (GLS) determined by cardiac magnetic resonance (CMR) in patients after ST-segment elevation myocardial infarction (STEMI). METHODS AND RESULTS: This observational cohort study included 445 acute STEMI patients treated with primary percutaneous coronary intervention (pPCI). Comprehensive CMR examinations were performed 3 [interquartile range (IQR): 2-4] days after pPCI for the determination of left ventricular (LV) functional parameters and infarct characteristics. Primary endpoint was the occurrence of major adverse cardiac events (MACE) defined as composite of death, re-infarction and congestive heart failure. During a follow-up of 16 [IQR: 12-49] months, 48 (11%) patients experienced a MACE. LVEF (p = 0.023), MAPSE (p < 0.001), LAS (p < 0.001) and GLS (p < 0.001) were significantly related to MACE. According to receiver operating characteristic analyses, only the area under the curve (AUC) of GLS was significantly higher compared to LVEF (0.69, 95% confidence interval (CI) 0.64-0.73; p < 0.001 vs. 0.60, 95% CI 0.55-0.65; p = 0.031. AUC difference: 0.09, p = 0.020). After multivariable analysis, GLS emerged as independent predictor of MACE even after adjustment for LV function, infarct size and microvascular obstruction (hazard ratio (HR): 1.13, 95% CI 1.01-1.27; p = 0.030), as well as angiographical (HR: 1.13, 95% CI 1.01-1.28; p = 0.037) and clinical parameters (HR: 1.16, 95% CI 1.05-1.29; p = 0.003). CONCLUSION: GLS emerged as independent predictor of MACE after adjustment for parameters of LV function and myocardial damage as well as angiographical and clinical characteristics with superior prognostic validity compared to LVEF.

Point-of-care testing of cardiac autonomic function for risk assessment in patients with suspected acute coronary syndromes.

BACKGROUND: Impaired cardiac autonomic function has been linked to adverse outcomes in patients with acute coronary syndromes (ACS) but is not included in clinical risk models. This is the first study to investigate whether point-of-care testing of cardiac autonomic function by means of short-term deceleration capacity (DC) of heart rate improves risk assessment in patients with suspected ACS. METHODS: 1821 patients with suspected ACS were prospectively enrolled if they were older than 17 years and in sinus rhythm. Short-term DC was automatically assessed from monitor recordings at hospital admission. The Global Registry of Acute Coronary Events (GRACE) score was used as gold standard risk predictor. Primary endpoint was the composite of intrahospital and 30-day mortality. Secondary endpoint was 180-day mortality. RESULTS: Of the 1,821 patients with suspected ACS, 28 (1.5%) and 60 (3.3%) reached the primary and secondary endpoints, respectively. DC was a highly significant predictor of both endpoints, yielding areas under the curve (AUC) of 0.784 (95% CI 0.714-0.854) and 0.781 (0.727-0.832) (p < 0.001 for both), respectively. Implementing DC into the GRACE-risk model leads to a significant increase of the C-statistics from 0.788 (0.703-0.874) to 0.825 (0.750-0.900; p < 0.01 for difference) and from 0.814 (0.759-0.864) to 0.851 (0.808-0.889; p < 0.01 for difference) for the primary and secondary endpoints, respectively. Stratification by dichotomized DC was especially powerful in patients with GRACE score <140. CONCLUSIONS: In patients with suspected ACS, point-of-care testing of cardiac autonomic function by means of DC is feasible and improves risk assessment by the GRACE score. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov NCT01486589.

Autonomic nervous system activity as risk predictor in the medical emergency department: a prospective cohort study.

OBJECTIVES: To evaluate heart rate deceleration capacity, an electrocardiogram-based marker of autonomic nervous system activity, as risk predictor in a medical emergency department and to test its incremental predictive value to the modified early warning score. DESIGN: Prospective cohort study. SETTING: Medical emergency department of a large university hospital. PATIENTS: Five thousand seven hundred thirty consecutive patients of either sex in sinus rhythm, who were admitted to the medical emergency department of the University of Tübingen, Germany, between November 2010 and March 2012. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Deceleration capacity of heart rate was calculated within the first minutes after emergency department admission. The modified early warning score was assessed from respiratory rate, heart rate, systolic blood pressure, body temperature, and level of consciousness as previously described. Primary endpoint was intrahospital mortality; secondary endpoints included transfer to the ICU as well as 30-day and 180-day mortality. One hundred forty-two patients (2.5%) reached the primary endpoint. Deceleration capacity was highly significantly lower in nonsurvivors than survivors (2.9 ± 2.1 ms vs 5.6 ± 2.9 ms; p < 0.001) and yielded an area under the receiver-operator characteristic curve of 0.780 (95% CI, 0.745-0.813). The modified early warning score model yielded an area under the receiver-operator characteristic curve of 0.706 (0.667-0.750). Implementing deceleration capacity into the modified early warning score model led to a highly significant increase of the area under the receiver-operator characteristic curve to 0.804 (0.770-0.835; p < 0.001 for difference). Deceleration capacity was also a highly significant predictor of 30-day and 180-day mortality as well as transfer to the ICU. CONCLUSIONS: Deceleration capacity is a strong and independent predictor of short-term mortality among patients admitted to a medical emergency department.

Assessment of coupling between trans-abdominally acquired fetal ECG and uterine activity by bivariate phase-rectified signal averaging analysis.

UNLABELLED: Couplings between uterine contractions (UC) and fetal heart rate (fHR) provide important information on fetal condition during labor. At present, couplings between UC and fHR are assessed by visual analysis and interpretation of cardiotocography. The application of computerized approaches is restricted due to the non-stationarity of the signal, missing data and noise, typical for fHR. Herein, we propose a novel approach to assess couplings between UC and fHR, based on a signal-processing algorithm termed bivariate phase-rectified signal averaging (BPRSA). METHODS: Electrohysterogram (EHG) and fetal electrocardiogram (fECG) were recorded non-invasively by a trans-abdominal device in 73 women at term with uneventful singleton pregnancy during the first stage of labor. Coupling between UC and fHR was analyzed by BPRSA and by conventional cross power spectral density analysis (CPSD). For both methods, degree of coupling was assessed by the maximum coefficient of coherence (CPRSA and CRAW, respectively) in the UC frequency domain. Coherence values greater than 0.50 were consider significant. CPRSA and CRAW were compared by Wilcoxon test. RESULTS: At visual inspection BPRSA analysis identified coupled periodicities in 86.3% (63/73) of the cases. 11/73 (15%) cases were excluded from further analysis because no 30 minutes of fECG recording without signal loss was available for spectral analysis. Significant coupling was found in 90.3% (56/62) of the cases analyzed by BPRSA, and in 24.2% (15/62) of the cases analyzed by CPSD, respectively. The difference between median value of CPRSA and CRAW was highly significant (0.79 [IQR 0.69-0.90] and 0.29 [IQR 0.17-0.47], respectively; p<0.0001). CONCLUSION: BPRSA is a novel computer-based approach that can be reliably applied to trans-abdominally acquired EHG-fECG. It allows the assessment of correlations between UC and fHR patterns in the majority of labors, overcoming the limitations of non-stationarity and artifacts. Compared to standard techniques of cross-correlations, such as CPSD, BPRSA is significantly superior.

Automated assessment of cardiac autonomic function by means of deceleration capacity from noisy, nonstationary ECG signals: validation study.

BACKGROUND: Assessment of heart rate variability by means of deceleration capacity (DC) provides a noninvasive probe of cardiac autonomic activity. However, clinical use of DC is limited by the need of manual review of the ECG signals to eliminate artifacts, noise, and nonstationarities. OBJECTIVE: To validate a novel approach to fully automatically assess DC from noisy, nonstationary signals METHODS: We analyzed 100 randomly selected ECG tracings recorded for 10 minutes by routine monitor devices (GE DASH 4000, sample size 100 Hz) in a medical emergency department. We used a novel automated R-peak detection algorithm, which is mainly based on a Shannon energy envelope estimator and a Hilbert transformation. We transformed the automatically generated RR interval time series by phase-rectified signal averaging (PRSA) to assess DC of heart rate (DCauto ). DCauto was compared to DCmanual , which was obtained from the same manually preprocessed ECG signals. RESULTS: DCauto and DCmanual showed good correlation and agreement, particularly if a low-pass filter was implemented into the PRSA algorithm. Correlation coefficient between DCauto and DCmanual was 0.983 (P < 0.0001). Average difference between DCauto and DCmanual was -0.23±0.49 ms with limits of agreement ranging from -1.19 to 0.73 ms. Significantly lower correlations were observed when a different R-peak detection algorithm or conventional heart rate variability (HRV) measures were tested. CONCLUSIONS: DC can be fully automatically assessed from noisy, nonstationary ECG signals.

Bivariate phase-rectified signal averaging for assessment of spontaneous baroreflex sensitivity: normalization of the results.

BACKGROUND: Previously proposed technique for assessment of spontaneous baroreflex sensitivity (BRS) based on bivariate phase-rectified signal averaging measures averaged R-R interval (RRI) changes triggered by beat-to-beat increases in systolic blood pressure (SBP). In this study, we investigate a normalized version of the method that relates the averaged RRI changes to the triggering blood pressure changes, thus providing the results in measurement units comparable with existing literature. METHODS: Data of previously reported prospective observational study were used. In each of 146 heart failure patients presenting with sinus rhythm, 10-minute recordings of electrocardiogram and arterial and blood pressures were obtained in the supine resting position. The averaged RRI increases initiated by beat-to-beat SBP increases were measured (original BRS result in milliseconds) and normalized for the averaged beat-to-beat SBP increases (normalized BRS result in milliseconds per millimeters of mercury). Both results were compared in terms of predicting all-cause mortality during a mean follow-up of 2.7 ± 1.1 years when 42 patients (28.8%) died. RESULTS: Both types of results were highly correlated (r = 0.938, P < .001) and led to similarly strong separation of high- and low-risk groups. The receiver operator characteristics of both indices were well within the 95% confidence intervals of each other, and the areas under the characteristics were practically identical: 71.1% (95% confidence interval, 60.7%-80.9%) for original BRS and 69.7% (58.9%-79.2%) for normalized BRS. CONCLUSION: The results might question the concept of a linear relationship between the SBP changes and RRI changes. The phase-rectified signal averaging-based assessment of BRS may be used with equal legitimacy in the nonnormalized and normalized forms; the normalized form provides results in conventional measurement units.

Bivariate phase-rectified signal averaging for assessment of spontaneous baroreflex sensitivity: pilot study of the technology.

BACKGROUND: Assessment of spontaneous baroreflex sensitivity (BRS), an index of autonomic function, poses practical challenges. In this pilot study, we propose a novel technique for assessment of spontaneous BRS based on bivariate phase-rectified signal averaging (PRSA). This is an extension of the monovariate PRSA technology used for calculation of deceleration capacity. METHODS: A prospective, observational study was conducted in a training cohort of 146 patients with heart failure (New York Heart Association class 2.7 ± 0.8, left ventricular ejection fraction 23.6% ± 9.0%) presenting with sinus rhythm. In all patients, 10-minute recordings of ECG and arterial and blood pressure were obtained in the supine resting position. The algorithm for BRS assessment based on bivariate PRSA (BRS(PRSA)) included (1) identification of heartbeat intervals occurring at the time of systolic pressure increases, (2) selection of heartbeat adjacent interval sections, (3) alignment and (4) averaging of these segments, and (5) quantification of the average heart beat interval change by Haar wavelet analysis. Primary end point was death of any cause. During mean follow-up of 2.7 ± 1.1 years, 42 patients (28.8%) died. RESULTS: BRS(PRSA) was significantly associated with the primary end point (3.7 ± 5.3 ms vs -0.33 ± 6.6 ms in survivors and nonsurvivors, respectively). BRS(PRSA) yielded an area under the receiver operating characteristics curve of 69.8% (95% confidence interval, 59.9-79.7), which was comparable to the area under the curve of left ventricular ejection fraction (70.4%; 95% confidence interval, 61.3-79.5). Using the optimum dichotomy for BRS(PRSA) of 1.14 milliseconds, 52 (36%) patients had an abnormal BRS(PRSA). The 3-year mortality risk of these patients was 45.3% compared to 19.0% in patients with normal BRS(PRSA). On multivariate analysis, abnormal BRS(PRSA) was an independent risk factor from left ventricular ejection fraction ≤ 30% and New York Heart Association class > II. CONCLUSION: BRS(PRSA) is an independent and strong predictor of mortality in patients with heart failure. Prospective validation and comparisons with standard measures of BRS are needed.