Christian Eick

Renal sympathetic denervation for treatment of electrical storm: first-in-man experience

IntroductionSympathetic activity plays an important role in the pathogenesis of ventricular tachyarrhythmia. Catheter-based renal sympathetic denervation (RDN) is a novel treatment option for patients with resistant hypertension, proved to reduce local and whole-body sympathetic activity.MethodsTwo patients with chronic heart failure (CHF) (non-obstructive hypertrophic and dilated cardiomyopathy, NYHA III) suffering from therapy resistant electrical storm underwent therapeutic renal denervation. In both patients, RDN was conducted with agreement of the local ethics committee and after obtaining informed consent.ResultsThe patient with hypertrophic cardiomyopathy had recurrent monomorphic ventricular tachycardia despite extensive antiarrhythmic therapy, following repeated endocardial and epicardial electrophysiological ablation attempts to destroy an arrhythmogenic intramural focus in the left ventricle. The second patient, with dilated nonischemic cardiomyopathy, suffered from recurrent episodes of polymorphic ventricular tachycardia and ventricular fibrillation. The patient declined catheter ablation of these tachycardias. In both patients, RDN was performed without procedure-related complications. Following RDN, ventricular tachyarrhythmias were significantly reduced in both patients. Blood pressure and clinical status remained stable during the procedure and follow-up in these patients with CHF.ConclusionOur findings suggest that RDN is feasible even in cardiac unstable patients. Randomized controlled trials are urgently needed to study the effects of RD in patients with electrical storm and CHF.

Impaired cardiac baroreflex sensitivity predicts response to renal sympathetic denervation in patients with resistant hypertension.

OBJECTIVES This study sought to evaluate cardiac baroreflex sensitivity (BRS) as a predictor of response to renal sympathetic denervation (RDN). BACKGROUND Catheter-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. METHODS Fifty 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. RESULTS Six 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. CONCLUSIONS Impaired 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.

Insertable cardiac monitors after cryptogenic stroke – a risk factor based approach to enhance the detection rate for paroxysmal atrial fibrillation

Recently, the CRYSTAL AF trial detected paroxysmal atrial fibrillation (AF) in 12.4% of patients after cryptogenic ischaemic stroke (IS) or cryptogenic transient ischaemic attack (TIA) by an insertable cardiac monitor (ICM) within 1 year of monitoring. Our aim was (i) to assess if an AF risk factor based pre‐selection of ICM candidates would enhance the rate of AF detection and (ii) to determine AF risk factors with significant predictive value for AF detection.

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.

Autologous stem cell transplantation with thiotepa-based conditioning in patients with systemic sclerosis and cardiac manifestations

OBJECTIVE The aim of this study was to find a new and less cardiotoxic conditioning regimen for high-dose chemotherapy and autologous stem cell transplantation (aSCT) in patients with severe SSc and pre-existing cardiac involvement. METHODS Six patients with cardiac involvement were treated for SSc with a conditioning regimen including reduced-dose CYC plus the non-cardiotoxic alkylant thiotepa. All patients received an implantable cardioverter defibrillator (ICD) before aSCT. The response at months 6 and 12 was measured according to reduction of the modified Rodnan skin score (mRSS). CT histography was used to monitor pulmonary manifestations, as were echocardiography, N-terminal pro-brain natriuretic peptide (NT-proBNP) and troponin for the cardiac involvement. Cardiac events were defined as death or hospitalisation due to heart failure or appropriate discharge of the ICD. RESULTS Between December 2008 and May 2012, four male and two female patients with a median age of 41 years received aSCT. The median mRSS significantly decreased from 26.5 to 18 and 17.5 at month 6 and 12, respectively. The total lung volume also significantly improved. Within the median follow-up of 1.6 years (range 1-3.8) two patients experienced a relapse of SSc, which results in a progression-free survival rate of 66.6%. Three patients experienced ICD discharge. CONCLUSION For patients with SSc and cardiac involvement, the use of thiotepa and reduced-dose CYC is feasible and effective. The rate of ICD discharge underlines the need for protection in these endangered patients. This preliminary experience allowed us to use this regimen for our currently recruiting prospective trial (NCT01895244).

Automated Assessment of Cardiac Autonomic Function by Means of Deceleration Capacity from Noisy, Nonstationary ECG Signals: Validation Study

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.

Severe autonomic failure as a predictor of mortality in aortic valve stenosis

BACKGROUND Identification of new risk markers in aortic valve stenosis (AS) is of great interest. Here, we hypothesized that the presence of severe autonomic failure (SAF) is an important prognostic marker in both, symptomatic patients undergoing invasive treatment for severe AS, and in asymptomatic patients with severe AS who were primarily treated conservatively. METHODS We prospectively enrolled 300 patients with severe AS (aortic valve area<1.0 cm2 or mean aortic gradient>40 mmHg) in sinus rhythm. All patients underwent a 24-h Holter recording for assessment of heart rate turbulence (HRT) and deceleration capacity (DC). Patients with both, abnormal DC and HRT were considered to suffer from SAF. RESULTS The first hypothesis was tested in 216 symptomatic patients who underwent successful aortic valve replacement (AVR) or transcatheter aortic valve implantation (TAVI). During follow-up of 2 years, 29 of these patients died. SAF was the strongest independent predictor of mortality (hazard ratio 5.6, 95% confidence interval 2.6-12.0; p<0.001) with 2-year mortality rates of 50.0% and 10.7% in SAF-positive and SAF-negative patients, respectively (p<0.001). The second hypothesis was tested in 71 patients, who were asymptomatic at study entry and for whom a primarily conservative treatment strategy was proposed. During follow-up, 10 of these patients died. SAF also predicted death in asymptomatic patients with 2-year mortality rates of 52.4% and 8.7% in SAF-positive and SAF-negative patients, respectively (p=0.010). CONCLUSIONS SAF is a strong and independent predictor of mortality in symptomatic and asymptomatic patients with severe AS.

Inhibition of the renin-angiotensin system: effects on tachycardia-induced early electrical remodelling in rabbit atrium

Introduction. Tachycardia-induced atrial remodelling (as an equivalent to atrial fibrillation) can be influenced by the renin-angiotensin system. Effects of a seven-day enalapril pre-treatment (EPT, 0.16 mg/kg body weight subcutaneously every 24 h) on ionic currents underlying tachycardia-induced early electrical remodelling after 24 h rapid atrial pacing (RAP, 600 beats/min) in rabbit atrium were studied. Materials and methods. Animals were divided into four groups (n=4 each): control; paced only; enalapril only; and enalapril and paced, respectively. Using patch-clamp technique in whole-cell mode, current densities were measured in isolated atrial myocytes. Results. EPT nearly doubled L-type calcium current (ICa,L, −7.7±0.6 pA/pF [control] vs. f −12.3±1.2 pA/pF [enalapril only]). RAP reduced ICa,L to −3.6±0.7 pA/pF (paced only). Also after EPT, RAP led to a significant downregulation of ICa,L by 39% (−7.5±1.3 pA/pF [paced and enalapril]). RAP decreased transient outward potassium current (Ito, −45%, 51.5±3.9 pA/pF [control] vs. 28.5±4.5 pA/pF [paced only]). EPT did not alter Ito (44.2±8.1 pA/pF [enalapril only]). However, RAP did not affect Ito in enalapril-treated animals and averaged 50.4±9.8 pA/pF (paced and enalapril). Conclusions. In summary, EPT has several effects on ion channels in rabbit atrium: 1) EPT increases ICa,L current density, but cannot prevent its downregulation due to RAP; 2) EPT has no influence on Ito current density, but can prevent its downregulation due to RAP. Although changes of single ion channels must be interpreted in context of the complex atrial electrophysiology as a whole, our results provide a possible explanation of the in vivo observation that angiotensin-converting enzyme inhibition is mainly beneficial on the early electrical remodelling due to the atrial fibrillation-equivalent RAP.

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.