Ralf Surber

Angiographic Assessment of Collateral Connections in Comparison With Invasively Determined Collateral Function in Chronic Coronary Occlusions

Background—The evaluation of new therapeutic modalities to induce collateral growth in coronary artery disease require improved methods of angiographic characterization of collaterals, which should be validated by quantitative assessment of collateral function. Methods and Results—In 100 patients with total chronic occlusion of a major coronary artery (duration >2 weeks) collaterals were assessed angiographically by the Rentrop grading, by their anatomic location, and by a new grading of collateral connections (CC grade 0: no continuous connection, CC1: threadlike continuous connection, CC2: side branch–like connection). The interobserver variability was 10%. Collateral function was assessed by Doppler flow (average peak velocity) and pressure recordings distal to the occlusion before recanalization. A collateral resistance index (RColl) was calculated. Recruitable collateral flow was measured during a final balloon inflation >30 minutes after the baseline measurement. The comparison of the anatomic location, the Rentrop, and the collateral connection grade showed only for the latter an independent and significant relation with RColl. CC2 collaterals preserved regional left ventricular function better than did CC1 collaterals and provided a higher collateral flow reserve during adenosine infusion. CC0 collaterals were predominantly observed in recent occlusions of 2 to 4 weeks’ duration, with the highest RColl. During balloon reocclusion, recruitable collateral function was best preserved with CC2 and least with CC0. Conclusions—The angiographic grading of collateral connections in total chronic occlusions could differentiate collaterals according to their functional capacity to preserve regional left ventricular function and was closely associated with invasively determined parameters of collateral hemodynamics.

SCN5A channelopathies--an update on mutations and mechanisms.

Voltage-gated Na+ channels mediate the rapid upstroke of the action potential in excitable tissues. Na(v)1.5, encoded by the SCN5A gene, is the predominant isoform in the heart. Mutations in SCN5A are associated with distinct cardiac excitation disorders often resulting in life-threatening arrhythmias. This review outlines the currently known SCN5A mutations linked to three distinct cardiac rhythm disorders: long QT syndrome subtype 3 (LQT3), Brugada syndrome (BS), and cardiac conduction disease (CCD). Electrophysiological properties of the mutant channels are summarized and discussed in terms of Na+ channel structure-function relationships and regarding molecular mechanisms underlying the respective cardiac dysfunction. Possible reasons for less convincing genotype-phenotype correlations are suggested.

Catheter-based renal denervation for drug-resistant hypertension by using a standard electrophysiology catheter.

AIMS The endovascular application of low-dose radiofrequency (RF) energy to the renal arteries results in effective ablation of sympathetic nerve fibres leading to a significant lowering of blood pressure (BP). This study aims to examine the feasibility and safety of renal denervation by the use of a standard electrophysiology (EP) catheter. METHODS AND RESULTS Twelve patients (mean age 62±14 years, nine male) with drug resistant hypertension despite medical treatment with at least four antihypertensive drugs underwent renal denervation by using a standard steerable RF ablation catheter with a 7 Fr diameter (Marinr®; Medtronic Inc., Minneapolis, MN, USA). Low-power RF applications have been applied along the length of both renal arteries, consecutively. Assessment of 24 hour ambulatory BP was done at baseline, at one, and at three months following RF ablation. The mean reduction of 24 hour ambulatory BP was -11/-7 mmHg at one month and -24/-14 mmHg at three months (p<0.01 for systolic and p<0.03 for diastolic blood pressure) with unchanged medication. No vascular complications have been observed in the short-term follow-up. The renal function as assessed by serum creatinine and proteinuria remained unchanged from baseline. CONCLUSIONS Our preliminary results indicate that the use of a standard RF ablation catheter is feasible and safe for sympathetic renal denervation as shown by a significant lowering of mean 24 hour ambulatory BP in comparison to baseline during short-term follow-up. Whether the use of a standard EP catheter for sympathetic renal denervation indeed improves the long-term outcome in resistant hypertension, however, remains to be investigated.

Efficacy of renal denervation with a standard EP catheter in the 24-h ambulatory blood pressure monitoring—long-term follow-up

Resistant hypertension (HTN), defined as ambulatory blood pressure (BP) above 140/90 mmHg in spite of the concurrent use of three or more antihypertensive drugs, is a serious global health issue. It has been estimated that it may affect 20% to 30% of the HTN population [1]. Only about 30% of these patients are actually adequately controlled according to the target BP. A critical factor in resistant HTN is the hyperactivity of the sympathetic nervous system, which increases progressively and in parallel with HTN stages, indicating that more advanced stages of HTN have a greater adrenergic activity [2]. Recent research could show that catheter-based renal sympathetic denervation is effective in BP lowering in patients with resistant hypertension [3–7]. Usually, a special ablation catheter (Symplicity®, Flex-Catheter, Medtronic/Ardian Inc. USA) is used for this purpose. We could recently show that sympathetic denervation with a standard electrophysiology (EP) catheter is also effective in reduction of blood pressure during 3month follow-up (FU) [7]. The aim of this study was to evaluate the efficacy (measured in the 24-h ambulatory BPmonitoring) and safety of renal sympathetic denervation by using a standard EP catheter during long-term FU (12 months) with a larger group of patients. Therefore, 30 patients with drug-resistant hypertension despite treatment with at least four antihypertensive drugs (mean 6) were treated with RF ablation of the renal artery for sympathetic denervation. Baseline evaluation of patients included physical examination, review of medications, basic blood chemistries (including serum creatinine and proteinuria), and 24-h ambulatory BP measurement. All patients have had secondary forms of hypertension excluded. Baseline parameters and comorbidity of patients are shown in Table 1. The method of the ablation procedure with a standard EP catheter has been previously described indetail [7]. In brief, renal artery stenosiswas excludedby renal angiogram via femoral access. After this, a standard steerable radiofrequency (RF) ablation catheter with a 7-French diameter (Marinr®; Medtronic Inc., Minneapolis, MN, USA) was introduced into both renal arteries, consecutively. We applied six low-power RF applications along the length of each renal artery to create lesions (up to 1 min each). Energy delivery was titrated up to a maximum of 8–13 watts under continuously monitoring of impedance and temperature. During RF ablation, we administered intravenous unfractionated heparin with an activated clotting time target range between 250 and 300 s. Aspirin (100 mg per day) was given at least for 3 months following the procedure. Since RF ablation was accompanied by diffuse visceral abdominal pain, patients received intravenous analgesia (fentanyl at doses up to 0.15 mg and midazolam at doses up to 4 mg). The final renal angiogram at procedure termination showed only renal artery irregularities which were not flow limiting. The median fluoroscopy time in our study was 7.5±3.4 min. We did not observe any complications or side effects during FU. The mean reduction of 24-h ambulatory BP was −15.5 mmHg in systolic BP (p=0.01) and −3.4 mmHg in diastolic BP (p=0.03) at 1 month (n=30), −25.5 mmHg in systolic BP (p=0.0001) and −10.9 mmHg in diastolic BP (p=0.01) at 3 months (n=30), −24.1 mmHg in systolic BP (p=0.0003) and −10.6 mmHg in diastolic BP (p=0.002) at 6 months (n=20), and −15 mmHg in systolic BP (p=0.04) and −4.3 mmHg in diastolic BP (not significant) at 12 months (n=10). The results are shown in Fig. 1. In six patients the number of different drugs could be reduced (−1 in five patients, −2 in one patient) and in one patient the medication increased from 5 to 6 different drugs at 6-month FU. All other patients received unchanged doses of antihypertensive drugs. Serum creatinine and proteinuria as markers of renal function remained stable in the FUperiod. Renal duplex sonography performed at 3 and at 12 months revealed no renal artery stenosis or other abnormalities in all patients. The blood-pressure-lowering in our study was a little less than described in the Symplicity HTN trials that found a reduction in officebased BP of −32/−12 mmHg after 6 months [8] and −27/−17 mmHg after 12 months [3]. However, these differences might be due to methodical aspects. In contrast to the measurement of office-based BP by the Symplicity HTN-1 and HTN-2 investigators, we used 24-h ambulatory BP measurements for our analysis, possibly depicting more real life proportions of blood-pressure-lowering. In fact, the 24-h BP monitoring, which was available in 20 patients of the Symplicity HTN-2 trial at 6 months, showed only a decrease of −11/−7 mmHg from baseline to 6 months follow-up [8], underscoring the efficacy of our approach. Furthermore, after 6 months, 80% of our patients were responders to our treatment, defined by a reduction in BP of 10 mm Hg ormore, which is comparable with the response rate of 84% in the HTN-2 trial. However, we recognize that the small number of patients, especially

Survival does not improve when therapeutic hypothermia is added to post-cardiac arrest care.

BACKGROUND We investigated whether the use of therapeutic hypothermia improves the outcome after cardiac arrest (CA) under routine clinical conditions. METHOD In a retrospective study, data of CA survivors treated from 2003 to 2010 were analysed. Of these, 143 patients were treated with hypothermia at 33 ± 0.5°C for 24h according to predefined inclusion criteria, while 67 who did not fulfil these criteria received comparable therapy without hypothermia. RESULTS 210 patients were included, 143 in the hypothermia group (HG) and 67 in the normothermia group (NG). There was no significant difference in mortality between the groups; 69 (48.2%) in the HG died in the first four weeks, compared to 30 patients (44.8%) in the NG (p=0.659). Patients in the NG were older and more seriously ill, and CA occurred more often in-hospital. Binary logistic regression revealed ventricular fibrillation (p=0.044), NSE serum level < 33 ng ml⁻¹ (p<0.001), age (p=0.035) and witnessed cardiac arrest (p=0.043) as independent factors significantly improving survival after CA, whereas hypothermia was not (p=0.69). The target temperature was maintained for a significantly longer time (19.5h vs. 15.2h; p=0.003) in hypothermia patients with a favourable outcome than in those with an unfavourable outcome. CONCLUSION There was no improvement in survival rates when hypothermia was added to standard therapy in this case series, as compared to standard therapy alone. The time at target temperature may be of relevance. We need better evidence in order to expand the recommendations for hypothermia after CA.

Multidimensional ECG-based analysis of cardiac autonomic regulation predicts early AF recurrence after electrical cardioversion.

BACKGROUND Heart rate turbulence, deceleration capacity (DC), and symbolic dynamics (SD) are promising novel domains of autonomic indices representing the multidimensional qualities of autonomic heart rate dynamics. PURPOSE The aim of this study was to test the impact of these novel indices in predicting early AF recurrence within the first month after electrical cardioversion (CV). METHODS In 45 patients with AF, standard Holter recordings were commenced immediately after CV. Holter-based indices were retrospectively analyzed using computerized algorithms. The best indices were applied in a multivariate model to select the optimal combination set that correctly classified patients who developed early AF recurrence. RESULTS Early AF recurrence occurred in 25 vs 20 patients with stable sinus rhythm. The set with the highest predictive power consisted of DC, turbulence onset, VLF/P, and PTH19 as a parameter of SD. The receiver operating curve analysis applied to this optimum set produced an area under the curve of 0.86, thus correctly classifying patients with 95.0% specificity and 76.0% sensitivity. CONCLUSION The analysis of novel multidimensional Holter-based autonomic indices after CV appears of clinical value because the procedure identifies patients with high risk of early AF recurrence. Furthermore, it indicates a substantial alteration of autonomic regulation.

Catheter-based radiofrequency ablation therapy of the renal sympathetic-nerve system for drug resistant hypertension in a patient with end-stage renal disease

Sympathetic overactivity is a major contributor to the pathogenesis and progression of human hypertension [1]. Especially, renal sympathetic activation is combined with renal vasoconstriction, increased renin secretion, and enhanced sodium and water reabsorption, contributing to the development of systemic hypertension [1]. Two recent reports of a novel catheter-based technique for renal sympathetic denervation offer a promising new therapeutic option for patients with resistant hypertension [2,3]. Percutaneous catheterbased radiofrequency ablation therapy can modify renal nerves that carry either efferent sympathetic and also afferent sensory fibers. Since hypertension is present in the vast majority of patients with chronic and end-stage renal failure [4] and sympathetic overactivity is a hallmark of patients with chronic renal disease and renal failure, this catheter-based technique may be also used in patients with chronic kidney disease. Here we report for the first time the successful treatment of hypertension with this novel technique in a patient with endstage renal disease. A 36-year old male patient with end-stage renal disease caused by a hereditary Alport syndrome and drug resistant hypertension was admitted to our university hospital. The mean blood pressure was 186/117 mm Hg proven by a 24-h ambulatory blood pressure monitoring despite medical therapy with six different antihypertensive

Successful use of a wearable cardioverter-defibrillator in myocarditis with normal ejection fraction

Sudden cardiac death (SCD) is generally defined as an unexpected death due to cardiovascular causes. In the majority of cardiac arrest patients, a structural or functional abnormality can be identified. Coronary artery disease is the most common cause of SCD [1]. In younger individuals, SCD often occurs during exercise, where hypertrophic cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy accounts for most of these cases [2]. Myocarditis comprises 5–11% of SCD in individuals less than 40 years of age [3]. In these cases, symptoms before the fatal event are rare [4]. Secondary prevention of SCD needs ICD therapy after documented cardiac arrest unless a transient or correctable cause of the arrhythmic trigger can be identified [5]. The treatment strategy for patients with ventricular fibrillation associated with a ‘‘transient’’ or ‘‘correctable’’ cause is not clear. These patients have a similar mortality rate as the survivors of ventricular fibrillation arrest in the observational registry of the AVID trial [6]. In myocarditis complicated by ventricular tachycardia (VT) or ventricular fibrillation (VF), antiarrhythmic drugs or an ICD implantation have not yet been studied in controlled trials. Because acute myocarditis often represents a transient condition from which recovery is common, the implantation of a permanent ICD should not be routine. Current guidelines do not recommend ICD therapy in a patient with acute myocarditis [5]. The debatable content of this statement is demonstrated with this presented case.

Transesophageal left ventricular posterior wall potential in heart failure patients with biventricular pacing / Transösophageales linksventrikuläres Potenzial der posterioren Wand bei Patienten mit Herzinsuffizienz und biventrikulärer Stimulation

Abstract Introduction: Biventricular (BV) pacing is an established therapy for heart failure (HF) patients with intraventricular conduction delay, but not all patients improved clinically. We investigated the interventricular delay (IVD) by means of the transesophageal left ventricular posterior wall potential (LVPWP). Materials and methods, and Results: A total of 18 HF patients (age 62±9 years; 15 males) with NYHA class 3.1±0.3, LV ejection fraction 22±7%, left bundle branch block and a QRS duration (QRSD) of 171±27 ms were analyzed using transesophageal LVPWP before implantation of a BV pacing device. The median follow up was 14±14 months. In 14 responders, IVD was 81±25 ms with a QRSD/IVD ratio of 2.2±0.3 with reclassification of NYHA class 3.1±0.3 to 2.0±0.5 (p<0.001) and an increase in LV ejection fraction from 22±7% to 36±11% (p=0.001) during long-term BV pacing. In four non-responders, transesophageal IVD was significantly smaller at 30±11 ms (p=0.001). Conclusion: Transesophageal IVD may be a useful method to detect responders to BV pacing. Transesophageal LVPWP may be a simple and useful technique to detect clinical responders to BV pacing in HF patients. Zusammenfassung Einleitung: Die biventrikuläre (BV) Stimulation ist eine etablierte Therapie bei Patienten mit Herzinsuffizienz (HF) und intraventrikulärem Leitungsdelay, aber nicht alle Patienten verbessern sich klinisch. Wir haben das interventrikuläre Delay (IVD) mit dem transösophagealen linksventrikulären Potenzial der posterioren Wand (LVPWP) untersucht. Material und Methode und Ergebnisse: Elf HF-Patienten (Alter 62±9 Jahre; 15 Männer) mit NYHA Klasse 3,1±0,3, LV Ejektionsfraktion 22±7%, Linksschenkelblock und QRS-Dauer (QRSD) 171±27 ms wurden mit dem transösophagealen LVPWP vor Implantation eines BV Schrittmachers analysiert. Der Median der Nachuntersuchung betrug 14±14 Monate. Bei 14 Respondern betrug das IVD 81±25 ms mit einem QRSD/IVD Verhältnis von 2,2±0,3. Es verbesserte sich die NYHA Klasse von 3,1±0,3 auf 2,0±0,5 (p<0,001) und erhöhte sich die LV Ejektionsfraktion von 22±7 auf 36±11% (p=0,001) während der BV Stimulation über lange Zeit. Bei 4 Nonrespondern war das transösophageale IVD signifikant geringer mit 30±11 ms (p=0,001). Schlussfolgerung: Das transösophageale IVD stellt möglicherweise eine brauchbare Methode zur Erkennung von Respondern für die BV Stimulation dar. Das transösophageale LVPWP ist möglicherweise eine einfache und brauchbare Technik zur Erkennung von klinischen Respondern für die BV Stimulation bei HF-Patienten.

Renal denervation with cryoenergy as second-line option is effective in the treatment of resistant hypertension in non-responders to radiofrequency ablation.

AIMS Renal denervation (RDN) with radiofrequency (RF) is being used to treat resistant hypertension (rHTN). As 15-30% of treated patients are non-responders to RDN, we investigated whether RDN with cryoenergy can serve as a second-line option. METHODS AND RESULTS Ten non-responder patients (mean age 55 years, six male) with rHTN were treated with cryoenergy for RDN. In order to qualify as non-responders, patients had to show systolic 24 hr ambulatory BP (ABP) ≥150 mmHg (median ABP 183/102 mmHg, median office- based BP [OBP] 191/108 mmHg) despite treatment with ≥4 different antihypertensive drugs (mean 6), and further not show a reduction of systolic ABP ≥10 mmHg at ≥3 months after RDN with RF. The three/six/12-month follow-up (FU) comprised clinical and biochemical evaluation, OBP and ABP measurement. Additionally, at six months, duplex sonography was performed. Cryoablation with a 7 Fr cryoablation catheter (Freezor® Xtra; Medtronic, Minneapolis, MN, USA) was performed in all patients without complications (four applications in both renal arteries, every four minutes, temperature -75°C). At three, six, and 12 months we found a reduction in systolic OBP of -41/-47/-61 mmHg (n=10/7/6; p=0.044 for all), diastolic OBP of -18/-14/-34 mmHg, systolic ABP of -38/-35/-52 mmHg (n=9/7/6, p=0.014 for all), and diastolic ABP of -20/-13/-18 mmHg (p=0.043 for all), respectively. During FU, no complications occurred and the renal function remained unchanged. CONCLUSIONS The significant reduction in systolic OBP and ABP observed qualifies RDN with cryoenergy as an effective second-line therapeutic option in non- responders to RDN with RF.