Dirk Prochnau

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.

Paclitaxel-eluting stents for the treatment of chronic total coronary occlusions: A strategy of extensive lesion coverage with drug-eluting stents

The recanalization of a chronic total coronary occlusion (CTO) is hampered by a high rate of lesion recurrence. The goal of the present study is to assess the effect of paclitaxel‐eluting stents in CTOs in a strategy of extensive stent coverage and the optional use of additional bare metal stents (BMSs). In 82 consecutive patients, a CTO (duration > 2 weeks) was successfully recanalized with implantation of one or more Taxus stents. These patients underwent a repeat angiography after 5.0 ± 1.5 months and were assessed by quantitative angiography. The patients were compared with 82 clinically and lesion‐matched patients from a consecutive series of 148 patients with CTOs treated by BMS in the preceding time period. In 21 of the 82 patients, additional lesions in the target artery not directly related to the original occlusion site were treated with BMSs (hybrid approach). The history of diabetes, extent of coronary artery disease, clinical symptoms, and angiographic features were similar in the Taxus and BMS group. Periprocedural adverse events were 3.3% with Taxus and 3.3% with BMS, but 12 months MACE was significantly lower in the group with exclusive use of Taxus (13.3% vs. 56.7%; P < 0.001), mainly due to a lower target lesion revascularization of 10.0% as compared to 53.4% (P < 0.001). There was only one late reocclusion with Taxus (1.7%) as compared to 21.7% with BMS (P < 0.05). However, in the hybrid group, the MACE rate was considerably higher, with 33.3%. Our data of a 80% reduction of target vessel failure as compared to BMS, with a lower risk of late reocclusions without increased acute adverse events, demonstrate the benefit of paclitaxel‐eluting stents in CTOs. However, diffuse atherosclerosis in CTOs should be covered completely by the drug‐eluting stents.

Increased production of matrix metalloproteinases 1 and 3 by smooth muscle cells upon infection with Chlamydia pneumoniae

Atherosclerosis has been linked to Chlamydia pneumoniae infection. In atherosclerotic arteries chlamydiae infect macrophages, endothelial cells, and smooth muscle cells (SMC). It has been suggested that the proteolysis of the extracellular matrix by matrix metalloproteinases (MMPs) is involved in the destabilisation and rupture of atherosclerotic plaques. In this study we investigated the expression of several MMPs and tissue inhibitors of MMP (TIMPs) in C. pneumoniae-infected SMC using reverse transcription-polymerase chain reaction analysis. Chlamydial infection of SMC up-regulated the mRNA levels of MMP-1 (interstitial collagenase) and MMP-3 (stromelysin) but did not affect the expression of MMP-2 and -9 (gelatinases). Additionally, the levels of TIMP-1 and -2 mRNA remained unchanged upon infection. Cells infected with C. pneumoniae secreted increased quantities of MMP-1 and -3 proteins as demonstrated by enzyme-linked immunosorbent assays. The ability of C. pneumoniae to stimulate the production of MMP-1 and -3 by SMC may be important for its pathogenic role in the progression of atherosclerotic disease.

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

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

Improvement of the primary success rate of recanalization of chronic total coronary occlusions with the Safe-Cross system after failed conventional wire attempts

BackgroundIn view of the improved long-term patency with drug-eluting stents, the challenge with chronic total coronary occlusion (CTO) remains the low primary success rate. Improved guide wires have increased this rate, but alternative devices may be of additional value. The goal of the present study was to determine the additional benefit of a new penetration device in CTOs after an extensive conventional wire approach.Methods and ResultsIn 148 consecutive patients the recanalization of a CTO of >3 months was attempted. A conventional wire approach was used with recent dedicated recanalization wires, which was successful in 104 patients (70%). If after at least 20 min of fluoroscopic time no crossing of the wire was achieved, the Safe-Cross wire (SC) (Intralumina) was used which enables verification of the intraluminal wire position via optical reflectometry, and crossing of resistent occlusion caps by radiofrequency ablation. Due to severe dissections after the conventional approach, the SC was not used in 10 patients. In 34 patients the SC wire was applied, leading to successful lesion crossing in 14 patients (41%). Thus, the primary success rate was improved from 70.2% to 79.7%. No periprocedural major adverse events were observed with the SC wire. The successful attempts with the SC wire were predominantly in blunt occlusions. All patients with successful wire passage could be treated with one or more stents.ConclusionsIn a real world cohort of patients with CTO, the SC wire could increase the primary success rate after failed extensive conventional wire attempt. In these worst case patients the SC success rate was 41%. This new wire appears to have additional potential in failures of a conventional wire approach.

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.