Effect of Hyperventilation on Periodic Repolarization Dynamics

Heart and lung functions are closely connected, and the interaction is mediated by the autonomic nervous system. Hyperventilation has been demonstrated to especially activate its sympathetic branch. However, there is still a lack of methods to assess autonomic activity within this cardiorespiratory coupling. Periodic repolarization dynamics (PRD) is an ECG-based biomarker mirroring the effect of efferent cardiac sympathetic activity on the ventricular myocardium. Its calculation is based on beat-to-beat variations of the T wave vector (dT degrees). In the present study, we investigated the effects of a standardized hyperventilation maneuver on changes of PRD and its underlyingdT degrees signal in 11 healthy subjects. In response to hyperventilation,dT degrees revealed a characteristic pattern and normalizeddT degrees values increased significantly compared to baseline [0.063 (IQR 0.032) vs. 0.376 (IQR 0.093),p< 0.001] and recovery [0.082 (IQR 0.029) vs. 0.376 (IQR 0.093),p< 0.001]. During recovery,dT degrees remained on a higher level compared to baseline (p= 0.019). When calculating PRD, we found significantly increased PRD values after hyperventilation compared to baseline [3.30 (IQR 2.29) deg(2)vs. 2.76 (IQR 1.43) deg(2),p= 0.018]. Linear regression analysis revealed that the increase in PRD level was independent of heart rate (p= 0.63). Our pilot data provide further insights in the effect of hyperventilation on sympathetic activity associated repolarization instability

Association of prehospital acetylsalicylic acid and heparin administration with favorable neurological outcome after out-of-hospital cardiac arrest: a matched cohort analysis of the German Resuscitation Registry

Purpose!#!To investigate the global burden of sepsis in hospitalized adults by updating and expanding a systematic review and meta-analysis and to compare findings with recent Institute for Health Metrics and Evaluation (IHME) sepsis estimates.!##!Methods!#!Thirteen electronic databases were searched for studies on population-level sepsis incidence defined according to clinical criteria (Sepsis-1, -2: severe sepsis criteria, or sepsis-3: sepsis criteria) or relevant ICD-codes. The search of the original systematic review was updated for studies published 05/2015-02/2019 and complemented by a search targeting low- or middle-income-country (LMIC) studies published 01/1979-02/2019. We performed a random-effects meta-analysis with incidence of hospital- and ICU-treated sepsis and proportion of deaths among these sepsis cases as outcomes.!##!Results!#!Of 4746 results, 28 met the inclusion criteria. 21 studies contributed data for the meta-analysis and were pooled with 30 studies from the original meta-analysis. Pooled incidence was 189 [95% CI 133, 267] hospital-treated sepsis cases per 100,000 person-years. An estimated 26.7% [22.9, 30.7] of sepsis patients died. Estimated incidence of ICU-treated sepsis was 58 [42, 81] per 100,000 person-years, of which 41.9% [95% CI 36.2, 47.7] died prior to hospital discharge. There was a considerably higher incidence of hospital-treated sepsis observed after 2008 (+ 46% compared to the overall time frame).!##!Conclusions!#!Compared to results from the IHME study, we found an approximately 50% lower incidence of hospital-treated sepsis. The majority of studies included were based on administrative data, thus limiting our ability to assess temporal trends and regional differences. The incidence of sepsis remains unknown for the vast majority of LMICs, highlighting the urgent need for improved epidemiological sepsis surveillance

Impaired Cardiac Baroreflex Sensitivity Predicts Response to Renal Sympathetic Denervation in Patients With Resistant Hypertension

ObjectivesThis study sought to evaluate cardiac baroreflex sensitivity (BRS) as a predictor of response to renal sympathetic denervation (RDN).BackgroundCatheter-based RDN is a novel treatment option for patients with resistant arterial hypertension. It is assumed that RDN reduces efferent renal and central sympathetic activity.MethodsFifty patients (age 60.3 ± 13.8 years [mean ± SD mean systolic blood pressure (BP) on ambulatory blood pressure monitoring (ABPM) 157 ± 22 mm Hg, despite medication with 5.4 ± 1.4 antihypertensive drugs) underwent RDN. Prior to RDN, a 30-min recording of continuous arterial BP (Finapres; TNO-TPD Biomedical Instrumentation, Amsterdam, the Netherlands) and high-resolution electrocardiography (1.6 kHz in orthogonal XYZ leads) was performed in all patients under standardized conditions. Cardiac BRS was assessed by phase-rectified signal averaging (BRSPRSA) according to previously published technologies. Response to RDN was defined as a reduction of mean systolic BP on ABPM by 10 mm Hg or more at 6 months after RDN.ResultsSix months after RDN, mean systolic BP on ABPM was significantly reduced from 157 ± 22 mm Hg to 149 ± 20 mm Hg (p = 0.003). Twenty-six of the 50 patients (52%) were classified as responders. BRSPRSA was significantly lower in responders than nonresponders (0.16 ± 0.75 ms/mm Hg vs. 1.54 ± 1.73 ms/mm Hg; p < 0.001). Receiver-operator characteristics analysis revealed an area under the curve for prediction of response to RDN by BRSPRSA of 81.2% (95% confidence interval: 70.0% to 90.1%; p < 0.001). On multivariable logistic regression analysis, reduced BRSPRSA was the strongest predictor of response to RDN, which was independent of all other variables tested.ConclusionsImpaired cardiac BRS identifies patients with resistant hypertension who respond to RDN

Effects of Renal Sympathetic Denervation on 24-hour Blood Pressure Variability

Background: In patients with arterial hypertension, increased blood pressure (BP) variability contributes to end organ damage independently from mean levels of arterial BP. Increased BP variability has been linked to alterations in autonomic function including sympathetic overdrive. We hypothesized that catheter-based renal sympathetic denervation (RDN) confers beneficial effects on BP variability. Methods and Results: Eleven consecutive patients with therapy-refractory arterial hypertension (age 68.9 ± 7.0 years; baseline systolic BP 189 ± 23 mmHg despite medication with 5.6 ± 2.1 antihypertensive drugs) underwent bilateral RDN. Twenty-four hour ambulatory BP monitoring (ABPM) was performed before RDN and 6 months thereafter. BP variability was primarily assessed by means of standard deviation of 24-h systolic arterial BP (SDsys). Secondary measures of BP variability were maximum systolic BP (MAXsys) and maximum difference between two consecutive readings of systolic BP (Δmaxsys) over 24 h. Six months after RDN, SDsys, MAXsys, and Δmaxsys were significantly reduced from 16.9 ± 4.6 to 13.5 ± 2.5 mmHg (p = 0.003), from 190 ± 22 to 172 ± 20 mmHg (p < 0.001), and from 40 ± 15 to 28 ± 7 mmHg (p = 0.006), respectively, without changes in concomitant antihypertensive therapy. Reductions of SDsys, MAXsys, and Δmaxsys were observed in 10/11 (90.9%), 11/11 (100%), and 9/11 (81.8%) patients, respectively. Although we noted a significant reduction of systolic office BP by 30.4 ± 27.7 mmHg (p = 0.007), there was only a trend in reduction of average systolic BP assessed from ABPM (149 ± 19 to 142 ± 18 mmHg; p = 0.086). Conclusion: In patients with therapy-refractory arterial hypertension, RDN leads to significant reductions of BP variability. Effects of RDN on BP variability over 24 h were more pronounced than on average levels of BP

Association of Heart Rate Variability With Silent Brain Infarcts in Patients With Atrial Fibrillation

Purpose: Silent brain infarcts (SBI) are frequently detected in patients with atrial fibrillation (AF), but it is unknown whether SBI are linked to autonomic dysfunction. We aimed to explore the association of autonomic dysfunction with SBI in AF patients. Methods: 1,358 AF patients without prior stroke or TIA underwent brain MRI and 5-min resting ECG. We divided our cohort into AF patients who presented in sinus rhythm (SR-group, n = 816) or AF (AF-group, n = 542). HRV triangular index (HRVI), standard deviation of normal-to-normal intervals, mean heart rate, root mean square root of successive differences of normal-to-normal intervals, 5-min total power and power in the low frequency, high frequency and very low frequency range were calculated. Primary outcome was presence of SBI in the SR group, defined as large non-cortical or cortical infarcts. Secondary outcomes were SBI volumes and topography. Results: Mean age was 72 ± 9 years, 27% were female. SBI were detected in 10.5% of the SR group and in 19.9% of the AF group (p < 0.001). HRVI <15 was the only HRV parameter associated with the presence of SBI after adjustment for clinical covariates in the SR group [odds ratio (OR) 1.67; 95% confidence interval (CI): 1.03–2.70; p = 0.037]. HRVI <15 was associated with larger brain infarct volumes [β (95% CI) −0.47 (−0.84; −0.09), p = 0.016] in the SR group and was more frequently observed in patients with right- than left-hemispheric SBI (p = 0.017). Conclusion: Impaired HRVI is associated with SBI in AF patients. AF patients with autonomic dysfunction might undergo systematic brain MRI screening to initiate intensified medical treatment

Cardiovascular Mortality Can Be Predicted by Heart Rate Turbulence in Hemodialysis Patients

Background: Excess mortality in hemodialysis patients is mostly of cardiovascular origin. We examined the association of heart rate turbulence (HRT), a marker of baroreflex sensitivity, with cardiovascular mortality in hemodialysis patients. Methods: A population of 290 prevalent hemodialysis patients was followed up for a median of 3 years. HRT categories 0 (both turbulence onset [TO] and slope [TS] normal), 1 (TO or TS abnormal), and 2 (both TO and TS abnormal) were obtained from 24 h Holter recordings. The primary end-point was cardiovascular mortality. Associations of HRT categories with the endpoints were analyzed by multivariable Cox regression models including HRT, age, albumin, and the improved Charlson Comorbidity Index for hemodialysis patients. Multivariable linear regression analysis identified factors associated with TO and TS. Results: During the follow-up period, 20 patients died from cardiovascular causes. In patients with HRT categories 0, 1 and 2, cardiovascular mortality was 1, 10, and 22%, respectively. HRT category 2 showed the strongest independent association with cardiovascular mortality with a hazard ratio of 19.3 (95% confidence interval: 3.69-92.03;P < 0.001). Age, calcium phosphate product, and smoking status were associated with TO and TS. Diabetes mellitus and diastolic blood pressure were only associated with TS. Conclusion: Independent of known risk factors, HRT assessment allows identification of hemodialysis patients with low, intermediate, and high risk of cardiovascular mortality. Future prospective studies are needed to translate risk prediction into risk reduction in hemodialysis patients