Use of a taurolidine containing antimicrobial wash to reduce cardiac implantable electronic device infection.

AIMS: TauroPace (Tauropharm, Bavaria Germany), a taurolidine solution for combating cardiac implantable electronic device (CIED) infection, was compared with a historical control of 3% hydrogen peroxide (H2O2) in a prospective observational study. METHODS AND RESULTS: The device pocket was irrigated, and all hardware accessible within (leads, suture sleeves, pulse generator) was wiped with H2O2, TauroPace, or taurolidine in a galenic formulation during any invasive CIED procedure at the study centre. Only CIED procedures covered by TauroPace or H2O2 from 1 January 2017 to 28 February 2022 were included for analysis. Patients who underwent >1 procedure were censored for the last treatment group and reassigned at the next procedure. The primary endpoint was major CIED infection within 3 months. The secondary endpoints were CIED infection beyond 3 months, adverse events potentially related to the antimicrobial solutions, CIED system, procedure, and death, till the end of follow-up. TauroPace covered 654 procedures on 631 patients, and H2O2 covered 551 procedures on 532 patients. The TauroPace group had more patient risk factors for infection than the H2O2 group (P = 0.0058) but similar device and procedure-specific risk factors (P = 0.17). Cardiac implantable electronic device infection occurred in 0/654 (0%) of the TauroPace group and 6/551 (1.1%) of the H2O2 group (P = 0.0075). Death occurred in 23/654 (3.5%) of the TauroPace group and 14/551 (2.5%) of the H2O2 group (P = 0.33). Non-infection related adverse events were rarer in the TauroPace (3.8%) than the H2O2 (6.0%) group (P = 0.0802). CONCLUSION: TauroPace is safe but more effective than H2O2 in reducing CIED infection. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05576194.

A prospective trial of a novel low-dose paclitaxel-coated balloon therapy in patients with restenosis in drug-eluting coronary stents Intracoronary Stenting and Angiographic Results: Optimizing Treatment of Drug Eluting Stent In-stent REstenosis 3A (ISAR-DESIRE 3A).

OBJECTIVES: We investigated the clinical efficacy of a paclitaxel-coated balloon (PCB) with a novel matrix coating and reduced drug concentration in comparison with a widely used PCB with iopromide excipient. METHODS: We prospectively enrolled patients with restenosis in drug-eluting stents. All patients were treated with a novel low-dose PCB with citrate-based excipient (Agent PCB). Angiographic follow-up was scheduled at 6-8 months. Outcomes were compared against those of patients treated with iopromide excipient PCB (SeQuent Please PCB) enrolled in a trial with identical inclusion and exclusion criteria. The primary endpoint was percent diameter stenosis (%DS) at follow-up angiography. The primary hypothesis was that the investigational device would be non-inferior to the control device (ClinicalTrials.gov Identifier: NCT02367495). RESULTS: One hundred twenty-five patients with 151 lesions were enrolled. Mean age was 68.1 ± 10.2 years, 40.8% had diabetes mellitus and 80.1% had focal morphology in-stent restenosis. Follow-up angiography data at 6-8 months was available for 102 (81.6%) patients. The Agent PCB was non-inferior to the SeQuent Please PCB in terms of the primary endpoint (38.9 ± 17.5 vs. 38.1 ± 21.5%; p non-inferiority  = 0.0056). Late lumen loss was also comparable between the groups (0.35 ± 0.55 vs. 0.37 ± 0.59; p = 0.71). There was no difference between the groups in the incidence of TLR (27.7% vs. 22.1%; p = 0.31), death or myocardial infarction (4.2% vs. 4.4%; p = 0.92) or target lesion thrombosis (1.0% vs. 0.7%; p = 0.93). CONCLUSION: In patients with DES restenosis, angioplasty with a novel PCB with citrate-based excipient was non-inferior to PCB with iopromide excipient in terms of angiographic outcome.

Can we rely on Danish? Real-world data on patients with nonischemic cardiomyopathy from the German Device Registry.

According to current guidelines prophylactic implantable cardioverter-defibrillator (ICD) therapy is recommended in patients with significantly impaired left ventricular systolic function. However, the recently published DANISH trial did not find a significantly lower long-term rate of death from any cause compared with usual clinical care in patients with non-ischemic cardiomyopathy. We investigated whether registry data from a multi-center 'real-life' registry on patients with non-ischemic cardiomyopathy are similar to this trial. The German Device Registry (DEVICE) is a nationwide, prospective registry with one-year follow-up investigating 5451 patients receiving device implantations in 50 German centers. The present analysis of DEVICE focused on patients with non-ischemic cardiomyopathy and a left ventricular ejection fraction ≤35% who received a prophylactic ICD. Out of 779 patients with symptomatic heart failure and nonischemic cardiomyopathy, 33.1% received a single chamber ICD (VVI), while 11.0% were implanted with a dual-chamber ICD (DDD), and 55.8% received a defibrillator system for cardiac resynchronization therapy. Median follow-up was 16.1 months. 90.7% were alive at follow-up, 9.3% had died during this period. Overall mortality after one year was 5.4%. Overall mortality one year after implantation was significantly increased in patients 68 years and older(7.9%) as compared to younger patients (59-68 years: 2.5%; < 59 years: 3.8%; p < 0.015). Data from the present registry support the recently published results of the DANISH trial. In particular the influence of an increased age as proven in the DANISH trial might also play a role in the present collective. This limits the potential beneficial effect of ICD therapy in particular in the elderly population.

Zero-fluoroscopy cryothermal ablation of atrioventricular nodal re-entry tachycardia guided by endovascular and endocardial catheter visualization using intracardiac echocardiography (Ice&ICE Trial).

INTRODUCTION: Stochastic damage of the ionizing radiation to both patients and medical staff is a drawback of fluoroscopic guidance during catheter ablation of cardiac arrhythmias. Therefore, emerging zero-fluoroscopy catheter-guidance techniques are of great interest. METHODS AND RESULTS: We investigated, in a prospective pilot study, the feasibility and safety of the cryothermal (CA) slow-pathway ablation in patients with symptomatic atrioventricular-nodal-re-entry-tachycardia (AVNRT) using solely intracardiac echocardiography (ICE) for endovascular and endocardial catheter visualization. Twenty-five consecutive patients (mean age 55.6 ± 12.0 years, 17 female) with ECG-documentation or symptoms suggesting AVNRT underwent an electrophysiology study (EPS) in our laboratory utilizing ICE for catheter navigation. Supraventricular tachycardia was inducible in 23 (92%) patients; AVNRT was confirmed by appropriate stimulation maneuvers in 20 (80%) patients. All EPS in the AVNRT subgroup could be accomplished without need for fluoroscopy, relying solely on ICE-guidance. CA guided by anatomical location and slow-pathway potentials was successful in all patients, median cryo-mappings = 6 (IQR:3-10), median cryo-ablations = 2 (IQR:1-3). Fluoroscopy was used to facilitate the trans-septal puncture and localization of the ablation substrate in the remaining 3 patients (one focal atrial tachycardia and two atrioventricular-re-entry-tachycardias). Mean EPS duration in the AVNRT subgroup was 99.8 ± 39.6 minutes, ICE guided catheter placement 11.9 ± 5.8 minutes, time needed for diagnostic evaluation 27.1 ± 10.8 minutes, and cryo-application duration 26.3 ± 30.8 minutes. CONCLUSIONS: ICE-guided zero-fluoroscopy CA in AVNRT patients is feasible and safe. Real-time visualization of the true endovascular borders and cardiac structures allow for safe catheter navigation during the ICE-guided EPS and might be an alternative to visualization technologies using geometry reconstructions.

Gender based differences in drug eluting stent implantation - data from the German ALKK registry suggest underuse of DES in elderly women.

BACKGROUND: Observational studies suggest there are gender based differences in the treatment of coronary artery disease, with women receiving evidence based therapy less frequently than suggested by current guidelines. The aim of our study was to evaluate gender based differences in the use of DES. METHODS: We analysed prospectively collected data from 100704 stent implantations in the PCI registry of the ALKK between 2005 and 2009. RESULTS: The usage of DES increased from 16.0 to 43.9%. Although women had smaller vessel sizes, they received DES less often compared to men (28.2 vs. 31.3%), with an adjusted odds ratio of 0.93 (95% confidence interval 0.89-0.97) at the age of 75, and an adjusted odds ratio of 0.89 (95% confidence interval 0.84-0.94) at the age of 80. CONCLUSION: Despite having smaller vessels than men, women were treated less often with DES. These findings apply to women above the age of 75 years. These findings support previous reports, that elderly women with coronary artery disease are treated differently to men.

ISAR-SAFE: a randomized, double-blind, placebo-controlled trial of 6 vs. 12 months of clopidogrel therapy after drug-eluting stenting.

BACKGROUND: In patients receiving aspirin, the optimal duration of clopidogrel therapy after drug-eluting stent (DES) implantation remains unclear. METHODS: This multicentre, randomized, double-blind, placebo-controlled trial tested the hypothesis that in patients undergoing DES implantation, 6 months of clopidogrel is non-inferior to 12 months in terms of clinical outcomes. At 6 months after DES implantation, patients on clopidogrel were randomly assigned to either a 6-month period of placebo or an additional 6-month period of clopidogrel. The primary endpoint was the composite of death, myocardial infarction, stent thrombosis, stroke, and thrombolysis in myocardial infarction major bleeding at 9 months after randomization. RESULTS: Owing to slow recruitment and low event rates, the trial was stopped prematurely after enrolment of 4005 of 6000 planned patients. Of 4000 patients included in the final analysis, 1997 received 6 months of clopidogrel and 2003 received 12 months. The primary endpoint occurred in 29 patients (1.5%) assigned to 6 months of clopidogrel and 32 patients (1.6%) assigned to 12 months, observed difference -0.1%, upper limit of one-sided 95% confidence interval (CI) 0.5%, limit of non-inferiority 2%, Pfor noninferiority <0.001. Stent thrombosis was observed in five patients (0.3%) assigned to 6 months of clopidogrel and three patients (0.2%) assigned to 12 months; hazard ratio (HR) 1.66, 95% CI: 0.40-6.96, P = 0.49. Thrombolysis in myocardial infarction major bleeding was observed in 4 patients (0.2%) assigned to 6 months clopidogrel and 5 patients (0.3%) assigned to 12 months; HR 0.80, 95% CI: 0.21-2.98, P = 0.74. CONCLUSIONS: In the present trial, characterized by low event rates, we did not observe a significant difference in net clinical outcome between 6 and 12 months of clopidogrel therapy after DES implantation. However, the results of the trial must be considered in view of its premature termination and lower than expected event rates. The trial is registered with ClinicalTrials.gov, Identifier: NCT00661206.

Atrial overexpression of angiotensin-converting enzyme 2 improves the canine rapid atrial pacing-induced structural and electrical remodeling. Fan, ACE2 improves atrial substrate remodeling.

The purpose of this study was to investigate whether atrial overexpression of angiotensin-converting enzyme 2 (ACE2) by homogeneous transmural atrial gene transfer can reverse atrial remodeling and its mechanisms in a canine atrial-pacing model. Twenty-eight mongrel dogs were randomly divided into four groups: Sham-operated, AF-control, gene therapy with adenovirus-enhanced green fluorescent protein (Ad-EGFP) and gene therapy with Ad-ACE2 (Ad-ACE2) (n = 7 per subgroup). AF was induced in all dogs except the Sham-operated group by rapid atrial pacing at 450 beats/min for 2 weeks. Ad-EGFP and Ad-ACE2 group then received epicardial gene painting. Three weeks after gene transfer, all animals except the Sham group underwent rapid atrial pacing for another 3 weeks and then invasive electrophysiological, histological and molecular studies. The Ad-ACE2 group showed an increased ACE2 and Angiotensin-(1-7) expression, and decreased Angiotensin II expression in comparison with Ad-EGFP and AF-control group. ACE2 overexpression attenuated rapid atrial pacing-induced increase in activated extracellular signal-regulated kinases and mitogen-activated protein kinases (MAPKs) levels, and decrease in MAPK phosphatase 1(MKP-1) level, resulting in attenuation of atrial fibrosis collagen protein markers and transforming growth factor-ß1. Additionally, ACE2 overexpression also modulated the tachypacing-induced up-regulation of connexin 40, down-regulation of connexin 43 and Kv4.2, and significantly decreased the inducibility and duration of AF. ACE2 overexpression could shift the renin-angiotensin system balance towards the protective axis, attenuate cardiac fibrosis remodeling associated with up-regulation of MKP-1 and reduction of MAPKs activities, modulate tachypacing-induced ion channels and connexin remodeling, and subsequently reduce the inducibility and duration of AF.

Use and outcome of radial versus femoral approach for primary PCI in patients with acute ST elevation myocardial infarction without cardiogenic shock: results from the ALKK PCI registry.

OBJECTIVES: This study sought to compare the use and outcome of radial versus femoral access in patients treated with primary percutaneous coronary intervention (PCI) for acute ST elevation myocardial infarction (STEMI) in clinical practice. BACKGROUND: The radial approach for PCI in patients with STEMI has been suggested to have a lower rate of complications and bleeding and to improve prognosis compared with the femoral approach. However, there still is a large regional and national variation in its use. METHODS: Between 2008 and 2012 a total of 17,865 patients with STEMI without cardiogenic shock undergoing primary PCI were prospectively enrolled in the observational German PCI registry of the Arbeitsgemeinschaft leitende kardiologische Krankenhausärzte (ALKK). Transfemoral (TF) access was used in 15,270 (85.5%), transradial (TR) access in 2,530 (14.2%), and other access in 65 (0.3%) patients. In this analysis, 10,264 patients from 20 centers that had performed at least 5 TR-PCI for STEMI were included. This study compared TR-PCI (n = 2,454 23.9%) with TF-PCI (n = 7,810, 76.1%). RESULTS: Procedural success was high in both cohorts. Hospital mortality (1.8 vs. 5.1%, P < 0.001) and vascular access complications (0.3 vs. 1.8%, P < 0.001%) were lower in the TR group. In the multivariate analysis radial access was associated with an improved in-hospital survival rate (OR 0.47, 95% CI 0.35-0.65). CONCLUSIONS: The radial approach for PCI can be performed with excellent procedural success in selected STEMI patients and is associated with a lower rate of vascular access complications and hospital mortality.

Angiotensin-(1-7) attenuates angiotensin II-induced signalling associated with activation of a tyrosine phosphatase in Sprague-Dawley rats cardiac fibroblasts.

BACKGROUND INFORMATION: Angiotensin-(1-7) [ANG-(1-7)] mediates vasodilation, antiproliferation, anti-apoptosis and antifibrosis, therefore, it opposes the effects of angiotensin II (ANG II). However, the detailed signal transduction mechanism following the Mas receptor activated by ANG-(1-7) is still poorly understood. Src homology2-containing inositol phosphatase 1 (SHP-1), a redoxsensitive protein tyrosine phosphatase, negatively influences downstream signalling molecules, such as mitogen-activated protein kinases (MAPKs), through dephosphorylation, thereby inhibiting proliferative and profibrotic signalling induced by ANG II. Therefore, we hypothesised that SHP-1 may mediate the antiproliferative signalling of ANG-(1-7) through the regulation of the dynamic balance of MAPKs and SHP-1 in isolated cardiac fibroblasts. Primary culture of neonatal Sprague-Dawley rats cardiac fibroblasts was treated separately with different interventions to investigate this issue. RESULTS: Our data revealed that ANG II increased the phosphorylation of extracellular signal-related kinase (p-ERK1/2) and the ratio of (p-ERK1/2)/(ERK1/2), but ANG-(1-7) decreased them. The effects of ANG-(1-7) on the phosphorylation p-ERK1/2 were blocked by the Mas receptor antagonist A-779. Unlike ANG II, which decreased the activity of SHP-1, ANG-(1-7) increased its activity. Overexpression of SHP-1 attenuated the ANG II-stimulated phosphorylation of c-Src, its downstream molecules ERK1/2, α-smooth muscle actin and transforming growth factor-ß1 (TGF-ß1). These effects were also inhibited by the specific inhibitor of SHP-1, sodium stibogluconate. ANG-(1-7) had no significant effects on the gene expression of TGF-ß1, collagen I or collagen III, but was found to antagonise the stimulatory effects of ANG II on them. CONCLUSIONS: ANG-(1-7), through Mas receptor, activates SHP-1 in cardiac fibroblasts, which can negatively modulate ANG II-induced phosphorylation of c-Src and MAPKs, and inhibits profibrotic factors TGF-ß1 and collagen production. ANG-(1-7) can thereby serve as a protective role by counteracting the effects of ANG II.

Randomized Trial of COBRA PzF Stenting to Reduce the Duration of Triple Therapy: The COBRA-REDUCE Trial.

BACKGROUND: Patients with an indication for oral anticoagulation who undergo percutaneous coronary intervention require a combination of oral anticoagulation and antiplatelet therapy. The use of a coronary stent with a thromboresistant and pro-healing coating may allow an abbreviated duration of dual antiplatelet therapy (DAPT) without an increase in the risk of thromboembolic events. METHODS: Patients with an indication for oral anticoagulation undergoing percutaneous coronary intervention were randomized to treatment with the COBRA polyzene F (PzF) stent followed by 14 days of DAPT or a Food and Drug Administration-approved new-generation drug-eluting stent followed by 3 or 6 months of DAPT. The bleeding coprimary end point was Bleeding Academic Research Consortium type ≥2 beyond 14 days (or after hospital discharge) until 6 months. The thromboembolic coprimary end point was the composite of all-cause death, myocardial infarction, definite or probable stent thrombosis, or ischemic stroke at 6 months. The trial hypothesis was that the COBRA PzF stent strategy would be superior with respect to bleeding events and noninferior with respect to thromboembolic events. RESULTS: A total of 996 patients underwent randomization. The bleeding end point occurred in 37 of 475 patients (7.8%) in the COBRA PzF group and 47 of 482 patients (9.8%) in the control group (difference, -2.0 [95% CI, -5.6 to 1.6]; P=0.14). The thromboembolic end point occurred in 37 of 492 patients (7.5%) in the COBRA PzF group and 24 of 490 patients (4.9%) in the control group (difference, 2.6%; prespecified noninferiority margin 5%, upper limit of 1-sided 95% CI of the difference, 5.2%; Pnoninferiority=0.07). CONCLUSIONS: In patients with an indication for oral anticoagulation undergoing percutaneous coronary intervention, treatment with the COBRA PzF stent plus 14 days of DAPT was not superior with respect to bleeding events and was not noninferior with respect to thromboembolic events at 6 months compared with treatment with standard Food and Drug Administration-approved drug-eluting stent plus 3 to 6 months of DAPT. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02594501.

Are plasma natriuretic peptide levels influenced by automatic pacemaker algorithms for ventricular pacing minimization?

BACKGROUND: Automatic atrioventricular search hysteresis (AVSH) is designed to reduce the cumulative percentage of potentially deleterious right ventricular apical pacing (VP%) in dual-chamber pacemakers. We investigated whether minimizing VP% by AVSH can, in turn, reduce ventricular wall stretching/stress, as assessed by plasma concentrations of the amino-terminal fragment of the pro-B-type natriuretic peptide (NT-proBNP). METHODS: After dual-chamber pacemaker implantation in 81 patients (age: 69 ± 11 years; males: 55.6%), the fixed atrioventricular delay of 225 ms was programmed and AVSH was turned off for 1 month. The patients were thereafter randomly assigned to standard AVSH for 1 month, followed by an enhanced AVSH for another month, or vice versa. At the 1-, 2-, and 3-month follow-ups, VP% values were retrieved from the pacemaker memory, and venous blood samples were taken for NT-proBNP measurements. RESULTS: Both standard and enhanced AVSH reduced the median VP% value from 38.5% (for the fixed atrioventricular delay) to 2.1% (P < 0.001). However, plasma NT-proBNP concentrations for the fixed atrioventricular delay (median, 253 pg/mL), standard AVSH (225 pg/mL), and enhanced AVSH (276 pg/mL) did not differ significantly on the intrapatient basis (paired Wilcoxon tests) between any pair of these modalities. CONCLUSION: Minimizing ventricular pacing by AVSH during 1 month had no influence on plasma NT-proBNP levels (i.e., ventricular wall stretching/stress) compared with a constant, moderately prolonged atrioventricular delay.

Cryoablation versus radiofrequency energy for the ablation of atrioventricular nodal reentrant tachycardia (the CYRANO Study): results from a large multicenter prospective randomized trial.

BACKGROUND: Cryoablation has emerged as an alternative to radiofrequency catheter ablation (RFCA) for the treatment of atrioventricular (AV) nodal reentrant tachycardia (AVNRT). The purpose of this prospective randomized study was to test whether cryoablation is as effective as RFCA during both short-term and long-term follow-up with a lower risk of permanent AV block. METHODS AND RESULTS: A total of 509 patients underwent slow pathway cryoablation (n=251) or RFCA (n=258). The primary end point was immediate ablation failure, permanent AV block, and AVNRT recurrence during a 6-month follow-up. Secondary end points included procedural parameters, device functionality, and pain perception. Significantly more patients in the cryoablation group than the RFCA group reached the primary end point (12.6% versus 6.3%; P=0.018). Whereas immediate ablation success (96.8% versus 98.4%) and occurrence of permanent AV block (0% versus 0.4%) did not differ, AVNRT recurrence was significantly more frequent in the cryoablation group (9.4% versus 4.4%; P=0.029). In the cryoablation group, procedure duration was longer (138±54 versus 123±48 minutes; P=0.0012) and more device problems occurred (13 versus 2 patients; P=0.033). Pain perception was lower in the cryoablation group (P<0.001). CONCLUSIONS: Cryoablation for AVNRT is as effective as RFCA over the short term but is associated with a higher recurrence rate at the 6-month follow-up. The risk of permanent AV block does not differ significantly between cryoablation and RFCA. The potential benefits of cryoenergy relative to ablation safety and pain perception are counterbalanced by longer procedure times, more device problems, and a high recurrence rate. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00196222.

Effect of depression on mortality in implantable cardioverter defibrillator recipients--findings from the prospective LICAD study.

INTRODUCTION: Depression predicts mortality in patients with coronary artery disease and heart failure. However, its effect on patient outcome in the presence of an implantable cardioverter defibrillator (ICD) has not been investigated. METHODS: A total of 236 ICD patients (76 females, 58.6 ± 14.0 years) were screened for depressive symptoms using the Hospital Anxiety and Depression Scale (HADS). The outcome measure was all-cause mortality and the prognostic effect of depression was evaluated with Cox proportional hazards regression analysis. RESULTS: Fifty (21%) patients reported depressive symptoms (HADS score ≥ 8). Renal failure (odds ratio [OR]= 4.0, 95% confidence intervals [CI]= 1.47-10.87, P = 0.007), prior angina (OR = 2.1, 95% CI = 1.07-4.12, P = 0.03), but not the experience of ICD shocks were associated with baseline depressive symptoms. In a mean follow-up period of 6.1 ± 2.5 years, 74 patients (31%) died. Mortality significantly increased from 45.1 deaths per 1,000 person-years among patients without depression to 80.3 deaths per 1,000 person-years in patients with depressive symptoms (P = 0.039). In the univariate model, depression (HADS score ≥8) was a significant predictor of mortality (OR = 1.81, 95% CI = 1.1-3.0, P = 0.02). However, in the multivariate model, depression lost its prognostic significance. CONCLUSIONS: In our prospective patient cohort, one-fifth of ICD recipients reported depressive symptoms. Depression increased the absolute mortality risk but was not an independent predictor of mortality.

Reduction of right ventricular pacing with advanced atrioventricular search hysteresis: results of the PREVENT study.

BACKGROUND: Right ventricular pacing predisposes to the development of heart failure and atrial fibrillation. Automatic atrioventricular search hysteresis (AVSH) is a commonly used strategy to decrease the percentage of right ventricular pacing (%VP) in patients without permanent AV block, but the results have not been optimal. METHODS: The randomized, crossover PREVENT study evaluated whether an enhanced AVSH with two new features can reduce %VP compared with standard AVSH. The new features are the repetitive hysteresis [switch from extended to basic AV delay after a consistent loss of intrinsic AV conduction (IAVC) lasting for six consecutive atrial cycles] and the scan hysteresis (periodic IAVC search extension over six consecutive atrial cycles). Both standard AVSH and enhanced AVSH performed a periodic IAVC search every 180 cardiac cycles and operated with a basic AV-delay of 225 ms and a rate-independent maximum AV-delay of 300 ms for paced and sensed atrial events. RESULTS: Among 178 patients, 53.4% had no evidence of AV block at enrollment and 46.6% had history of intermittent AV block. The median %VP was decreased by enhanced AVSH compared to standard AVSH (4.0% vs 5.5%, P < 0.001), particularly in patients with a history of AV block (21.4% vs 25.5%, P < 0.001). The primary study hypothesis that 25% of all patients would experience > 20% relative %VP reduction was not met as 46 (25.8%) patients (95% confidence interval, 20.5-31.8%) presented such relative reduction. CONCLUSION: The enhanced AVSH algorithm reduces %VP compared with standard AVSH in patients with intermittent AV block.

Complex fractionated atrial electrogram or linear ablation in patients with persistent atrial fibrillation--a prospective randomized study.

BACKGROUND: Catheter ablation of complex fractionated atrial electrograms (CFAE) for persistent atrial fibrillation (AF) is a promising treatment strategy. We tested the hypothesis that CFAE ablation is superior to linear ablation in patients with persistent or long-standing persistent AF. METHODS: In this study, 116 patients with persistent AF were randomly assigned to undergo circumferential PVI plus additional lines (linear ablation group; 59 patients) or CFAE ablation plus ostial pulmonary vein isolation (PVI) (spot ablation group; 57 patients). Primary endpoint was freedom from atrial tachyarrhythmia after a single ablation procedure (clinical and repeat 7-day Holter), 12 months after ablation without antiarrhythmic medication. RESULTS: The primary endpoint was reached in 22 of 59 (37%) patients of the linear ablation group and in 22 of 57 (39%) patients of the spot ablation group (P = 0.9). Freedom from atrial tachyarrhythmias, including reablations, was achieved in 54% of patients (linear ablation group) versus 56% of patients (spot ablation group; P = 0.8). The incidence of recurrent persistent AF was higher after linear ablation than after spot ablation (21/37 vs 11/35 patients; P = 0.03); atrial tachycardia (AT) was seen more often after spot ablation (10/35 vs 4/37 patients; P = 0.03). CONCLUSION: In patients with persistent AF, CFAE ablation plus PVI reaches the same results as circumferential PVI plus lines, in terms of freedom from symptomatic atrial tachyarrhythmias within the first year after a single ablation procedure. Arrhythmia recurrences in patients after spot ablation were caused more often by AT, whereas recurrent persistent AF was more prevalent after the linear ablation approach.

Does electrogram guided substrate ablation add to the success of pulmonary vein isolation in patients with paroxysmal atrial fibrillation? A prospective, randomized study.

INTRODUCTION: Pulmonary vein isolation (PVI) is an established treatment for paroxysmal atrial fibrillation (AF). The ablation of complex fractionated atrial electrograms (CFAE) has emerged as a novel treatment approach. We sought to evaluate the additional effect of CFAE ablation to PVI in paroxysmal AF. METHODS AND RESULTS: Ninety-eight patients with paroxysmal AF (57 +/- 10 years, 74 male) were randomized to the PVI (n = 48) or PVI + CFAE group (n = 50). After PVI, CFAE ablation was performed in patients with inducible AF in the PVI + CFAE group. The primary endpoint was combined objective (7-day Holter ECG) and subjective (symptoms) freedom of atrial tachyarrhythmia 3 months after ablation. Long-term follow-up (19 +/- 8 months) was available in 94 of 98 patients. CFAE ablation was performed in 30 of 50 patients of the PVI + CFAE group. After 3 months, 36 of 48 patients (75%) in the PVI group and 38 of 50 patients (76%) in the PVI + CFAE group were in stable sinus rhythm (P = NS). During long-term follow-up (19 +/- 8 months), 34 of 46 patients (74%) in the PVI group and 40 of 48 patients (83%) in the PVI + CFAE group were in sinus rhythm (P = 0.08). In a subgroup analysis, a significantly better long-term outcome was achieved if inducible AF after PVI had been treated by additional CFAE ablation as compared with PVI only (sinus rhythm in 25/28 patients; 89% vs 22/30 patients 73%; P = 0.003). CONCLUSION: In the intention-to-treat analysis, additional CFAE ablation did not improve the success rate of PVI in patients with paroxysmal AF. However, during long-term follow-up, patients with still inducible AF after PVI seemed to profit from additional CFAE ablation.

Defibrillation threshold testing: tradition or necessity?

Implantable cardioverter defibrillators (ICDs) have become an essential tool for primary and secondary prevention of sudden cardiac death. Traditionally, defibrillation threshold (DFT) testing is part of the "lege artis" ICD implantation. Taking into consideration that the absolute mortality reduction in primary prevention trials is estimated around 8% and in secondary prevention trials around 7%, it is only in these patients that an acceptable DFT is expected to affect survival. Using a high-energy ICD, the likelihood of obtaining an inadequate DFT is about 2.5%. Thus, the number of patients needed to be subjected to DFT testing in order to avert one potential death is about 500. Application of antitachycardia pacing for rapid ventricular tachycardias further reduces the percentage of patients dependent on reliable ICD defibrillation capability. Thus, the mortality rate that can be prevented by DFT testing is below 0.2%. This contrasts a 0.4% risk of life-threatening complications and a low but not negligible mortality risk owed to the procedure. Although in light of these data the balance between DFT-related risk and benefit seems to tilt toward the former, insights gained from prospective randomized trials will clarify whether the abandonment of routine DFT testing can be claimed on a rightful basis.

Combined Rotational Atherectomy and Intravascular Lithotripsy for the Treatment of Severely Calcified in-Stent Neoatherosclerosis: A Mini-Review.

Coronary calcifications remain associated to increased rate of complications and worse clinical outcomes, particularly in the setting of in-stent restenosis. We present the first reported case of combined rotational atherectomy and intravascular lithotripsy for the treatment of heavily calcified neoatherosclerosis.

Selective Renal Denervation Guided by Renal Nerve Stimulation in Canine.

Renal nerve stimulation (RNS) can result in substantial blood pressure (BP) elevation, and the change was significantly blunted when repeated stimulation after ablation. However, whether RNS could provide a meaningful renal nerve mapping for identification of optimal ablation targets in renal denervation (RDN) is not fully clear. Here, we compared the antihypertensive effects of selective RDN guided by two different BP responses to RNS and explored the nerve innervations at these sites in Kunming dogs. Our data indicated that ablation at strong-response sites showed a more systolic BP-lowering effect than at weak-response sites (P=0.002), as well as lower levels of tyrosine hydroxylase and norepinephrine in kidney and a greater reduction in plasma norepinephrine (P=0.004 for tyrosine hydroxylase, P=0.002 for both renal and plasma norepinephrine). Strong-response sites showed a greater total area and mean number of renal nerves than weak-response sites (P=0.012 for total area and P<0.001 for mean number). Systolic BP-elevation response to RNS before RDN and blunted systolic BP-elevation to RNS after RDN were correlated with systolic BP changes at 4 weeks follow-up (R=0.649; P=0.012 and R=0.643; P=0.013). Changes of plasma norepinephrine and renal norepinephrine levels at 4 weeks were also correlated with systolic BP changes at 4 weeks (R=0.837, P<0.001 and R=0.927, P<0.001). These data suggest that selective RDN at sites with strong BP-elevation response to RNS could lead to a more efficient RDN. RNS is an effective method to identify the nerve-enriched area during RDN procedure and improve the efficacy of RDN.

Acute effects and long-term outcome of pulmonary vein isolation in combination with electrogram-guided substrate ablation for persistent atrial fibrillation.

Complex fractionated atrial electrographic (CFAE) catheter ablation is a new approach for the treatment of atrial fibrillation (AF). It is unclear if acute results of this approach correspond to long-term outcome. The purpose of this study was to prospectively assess acute and long-term successes of an ablation approach combining pulmonary vein isolation (PVI) and ablation of CFAE areas for treatment of persistent AF. PVI and ablation of CFAE areas were performed in 35 patients with persistent AF (30 men, 57+/-9 years of age). At the end of the ablation procedure AF had terminated in 23 of 35 patients (66%) by conversion to sinus rhythm (8 of 23 patients, 35%) or organization to atrial tachycardia (15 of 23 patients, 65%). AF persisted in 12 of 35 patients (34%). At the end of the follow-up period (19+/-12 months), sinus rhythm was present in 26 of 35 patients (74%), including 9 patients with a repeat procedure. This group of 26 patients consisted of 7 of 8 patients (88%) with acute sinus rhythm after the first ablation, 11 of 15 patients (73%) with organization, and 8 of 12 patients (66%) with ongoing AF (p=0.32). In conclusion, a combined approach of PVI and CFAE ablation in persistent AF leads to acute AF termination in 66% and long-term maintenance of sinus rhythm in 74% of cases. However, long-term outcome was not predictable by acute results of the ablation procedure.