Wolfgang Hamm

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.

Prediction of sudden and non-sudden cardiac death in post-infarction patients with reduced left ventricular ejection fraction by periodic repolarization dynamics: MADIT-II substudy

Abstract Aims To test the value of Periodic Repolarization Dynamics (PRD), a recently validated electrocardiographic marker of sympathetic activity, as a novel approach to predict sudden cardiac death (SCD) and non-sudden cardiac death (N-SCD) and to improve identification of patients that profit from ICD-implantation. Methods and results We included 856 post-infarction patients with left-ventricular ejection fraction (LVEF) ≤30% of the MADIT-II trial in sinus rhythm. Of these, 507 and 348 patients were randomized to ICD or conventional treatment. PRD was assessed from multipolar 10-min baseline ECGs. Primary and secondary endpoints were total mortality, SCD and N-SCD. Multivariable analyses included treatment group, QRS-duration, New York Heart Association classification, blood-urea nitrogen, diabetes mellitus, beta-blocker therapy and LVEF. During follow-up of 20.4 months, 119 patients died (53 SCD and 36 N-SCD). On multivariable analyses, increased PRD was a significant predictor of mortality (standardized coefficient 1.37[1.19–1.59]; P < 0.001) and SCD (1.40 [1.13–1.75]; P = 0.003) but also predicted N-SCD (1.41[1.10–1.81]; P = 0.006). While increased PRD predicted SCD in conventionally treated patients (1.61[1.23–2.11]; P < 0.001), it was predictive of N-SCD (1.63[1.28–2.09]; P < 0.001) and adequate ICD-therapies (1.20[1.03–1.39]; P = 0.017) in ICD-treated patients. ICD-treatment substantially reduced mortality in the lowest three PRD-quartiles by 53% (P = 0.001). However, there was no effect in the highest PRD-quartile (mortality increase by 29%; P = 0.412; P < 0.001 for difference) as the reduction of SCD was compensated by an increase of N-SCD. Conclusion In post-infarction patients with impaired LVEF, PRD is a significant predictor of SCD and N-SCD. Assessment of PRD is a promising tool to identify post-MI patients with reduced LVEF who might benefit from intensified treatment.

Bedside autonomic risk stratification after myocardial infarction by means of short-term deceleration capacity of heart rate

Aims Twenty-four-hour deceleration capacity (DC24h) of heart rate is a strong predictor of mortality after myocardial infarction (MI). Assessment of DC from short-term recordings (DCst) would be of practical use in everyday clinical practice but its predictive value is unknown. Here, we test the usefulness of DCst for autonomic bedside risk stratification after MI. Methods and results We included 908 patients after acute MI enrolled in Munich and 478 patients with acute (n = 232) and chronic MI (n = 246) enrolled in Tuebingen, both in Germany. We assessed DCst from high-resolution resting electrocardiogram (ECG) recordings (<30 min) performed under standardized conditions in supine position. In the Munich cohort, we also assessed DC24h from 24-h Holter recordings. Deceleration capacity was dichotomized at the established cut-off value of ≤ 2.5 ms. Primary endpoint was 3-year mortality. Secondary endpoint was 3-year cardiovascular mortality. In addition to DC, multivariable analyses included the Global Registry of Acute Coronary Events score >140 and left ventricular ejection fraction ≤ 35%. During follow-up, 48 (5.3%) and 48 (10.0%) patients died in the Munich and Tuebingen cohorts, respectively. On multivariable analyses, DCst ≤ 2.5 ms was the strongest predictor of mortality, yielding hazard ratios of 5.04 (2.68-9.49; P < 0.001) and 3.19 (1.70-6.02; P < 0.001) in the Munich and Tuebingen cohorts, respectively. Deceleration capacity assessed from short-term recordings ≤ 2.5 ms was also an independent predictor of cardiovascular mortality in both cohorts. Implementation of DCst ≤ 2.5 ms into the multivariable models led to a significant increase of C-statistics and integrated discrimination improvement score. Conclusion Deceleration capacity assessed from short-term recordings is a strong and independent predictor of mortality and cardiovascular mortality after MI, which is complementary to existing risk stratification strategies.

Implantable cardiac monitors in high-risk post-infarction patients with cardiac autonomic dysfunction and moderately reduced left ventricular ejection fraction: Design and rationale of the SMART-MI trial

BACKGROUND Most deaths after myocardial infarction (MI) occur in patients with left ventricular ejection fraction (LVEF) >35%, for whom no specific prophylactic strategies exist. Deceleration capacity (DC) of heart rate and periodic repolarization dynamics (PRD) are noninvasive electrophysiological markers depending on the vagal and sympathetic tone. The combination of abnormal DC and/or PRD identifies a new high-risk group among postinfarction patients with LVEF 36%-50%. This new high-risk group has similar characteristics with respect to prognosis and patient numbers to those of the established high-risk group identified by LVEF ≤ 35%. STUDY DESIGN The SMART-MI trial is an investigator-initiated randomized prospective multicenter trial that tests the efficacy of implantable cardiac monitors (ICM) in this new high-risk group. The study will enroll approximately 1,600 survivors of acute MI with sinus rhythm and an LVEF of 35%-50% in 17 centers in Germany who will be tested for presence of cardiac autonomic dysfunction. Four hundred patients with either abnormal DC (≤2.5 ms) and/or PRD (≥5.75deg2) will be randomized in a 1:1 fashion to intensive follow-up via telemonitoring using an ICM device (experimental arm) or conventional follow-up (control arm). For the ICM arm, specific treatment paths have been developed according to current guidelines. OUTCOMES The primary end point is time to detection of predefined serious arrhythmic events during follow-up, including atrial fibrillation ≥6minutes, nonsustained ventricular tachycardia (cycle length≤320 ms; ≥40 beats), atrioventricular block ≥IIb, and sustained ventricular tachycardia/ventricular fibrillation. The median follow-up period is 18months with a minimum follow-up of 6months. The effect of remote monitoring on clinical outcomes will be tested as secondary outcome measure (ClinicalTrials.gov NCT02594488).

Periodic Repolarisation Dynamics: A Natural Probe of the Ventricular Response to Sympathetic Activation.

Periodic repolarisation dynamics (PRD) refers to low-frequency (≤0.1Hz) modulations of cardiac repolarisation instability. Spontaneous PRD can be assessed non-invasively from 3D high-resolution resting ECGs. Physiological and experimental studies have indicated that PRD correlates with efferent sympathetic nerve activity, which clusters in low-frequency bursts. PRD is increased by physiological provocations that lead to an enhancement of sympathetic activity, whereas it is suppressed by pharmacological β-blockade. Electrophysiological studies revealed that PRD occurs independently from heart rate variability. Increased PRD under resting conditions is a strong predictor of mortality in post-myocardial infarction (post-MI) patients, yielding independent prognostic value from left-ventricular ejection fraction (LVEF), heart rate variability, the Global Registry of Acute Coronary Events score and other established risk markers. The predictive value of PRD is particularly strong in post-MI patients with preserved LVEF (>35 %) in whom it identifies a new high-risk group of patients. The upcoming Implantable Cardiac Monitors in High-Risk Post-Infarction Patients with Cardiac Autonomic Dysfunction and Moderately Reduced Left Ventricular Ejection Fraction (SMART-MI) trial will test prophylactic strategies in high-risk post-MI patients with LVEF 36-50 % identified by PRD and deceleration capacity of heart rate (NCT02594488).

Risk prediction in post-infarction patients with moderately reduced left ventricular ejection fraction by combined assessment of the sympathetic and vagal cardiac autonomic nervous system

AIM Most deaths after myocardial infarction (MI) occur in patients with normal or moderately reduced left ventricular ejection fraction (LVEF >35%). Periodic repolarization dynamics (PRD) and deceleration capacity (DC) are novel ECG-based markers related to sympathetic and vagal cardiac autonomic nervous system activity. Here, we test the combination of PRD and DC to predict risk in post-infarction patients with LVEF >35%. METHODS AND RESULTS We included 823 survivors of acute MI with LVEF >35%, aged ≤80years and in sinus rhythm. PRD and DC were obtained from 30-min ECG-recordings within the second week after index infarction and dichotomized at established cut-off values of ≥5.75deg2 and ≤2.5ms, respectively. Patients were classified as having normal (CAF 0), partly abnormal (DC or PRD abnormal; CAF 1) or abnormal cardiac autonomic function (DC and PRD abnormal; CAF 2). Primary endpoint was 5-year all-cause mortality. Within the first 5years of follow-up, 51 patients died (6.2%). PRD and DC effectively stratified patients into low-risk (CAF 0; n=562), intermediate-risk (CAF 1; n=193) and high-risk patients (CAF 2; n=68) with cumulative 5-year mortality rates of 2.9%, 9.4% and 25.2%, respectively (p<0.001). On multivariable analyses, CAF was independent from established risk factors (GRACE-score, diabetes mellitus, mean heart rate, heart rate variability). Addition of CAF significantly improved the model (increase of C-statistics from 0.732 (0.651-0.812) to 0.777 (0.703-0.850), p=0.047; continuous NRI (0.400, 95% CI 0.230-0.560, p<0.001); IDI (0.056, 95% CI 0.022-0.122, p<0.001)). CONCLUSION CAF identifies new high-risk post-MI patients with LVEF >35% which might benefit from prophylactic strategies.

Effect of Physical Exercise on Platelet Reactivity in Patients with Dual Antiplatelet Therapy

It is known that physical exercise may increase platelet activity. However, the effect of exercise on platelet reactivity in patients on dual antiplatelet therapy has not been investigated yet. In our study, 21 patients with coronary artery disease on dual antiplatelet therapy and 10 controls were enrolled. We performed an exercise test using a cycle ergometer and determined the adenosine diphosphate-induced platelet reactivity before and immediately after exercise testing. Additionally, we analysed maximal exercise capacity and an electrocardiogram. Further, we assessed chromogranin A and P-selectin levels and platelet counts.

Deceleration Capacity of Heart Rate After Acute Altitude Exposure

Hamm, Wolfgang, Lukas von Stülpnagel, Mathias Klemm, Monika Baylacher, Konstantinos D. Rizas, Axel Bauer, and Stefan Brunner. Deceleration capacity of heart rate after acute altitude exposure. High Alt Med Biol 19:299-302, 2018. BACKGROUND The autonomic nervous system plays a crucial role in adaptive changes after high-altitude exposure. Deceleration capacity (DC) of heart rate is an advanced marker of heart rate variability (HRV) that predominantly reflects the vagal activity of the cardiac autonomic nervous system. The impact of high-altitude exposure on DC has not been investigated yet. METHODS In eight healthy individuals we performed a high-resolution digital 30-min electrocardiography in Frank leads configuration at baseline (521 m altitude), immediately after ascent to the Environmental Research Station Schneefernerhaus (UFS) at Zugspitze (2650 m altitude) and after a sojourn of 24 hours at this altitude. DC of heart rate was assessed using customized software. In addition, standard parameters of HRV were assessed. RESULTS DC decreased significantly from 10.2 ± 0.8 ms to 8.9 ± 1.0 ms (p < 0.05) after acute altitude exposure. After a sojourn of 24 hours at high altitude, DC remained low at 8.6 ± 1.2 ms. There were no significant changes in standard parameters of HRV. CONCLUSION Our findings show for the first time a decrease of DC of heart rate providing a novel insight into the dysbalance of autonomic nervous system at high altitude.

Periodic repolarization dynamics quantified by phase-rectified-signal-averaging is a strong and robust predictor of mortality after myocardial infarction

Published on behalf of the European Society of Cardiology. All rights reserved.

Impact of gender on risk predictive power of periodic repolarization dynamics

Published on behalf of the European Society of Cardiology. All rights reserved.