Pascal F.H.M. van Dessel

An Entirely Subcutaneous Implantable Cardioverter–Defibrillator

BACKGROUND Implantable cardioverter-defibrillators (ICDs) prevent sudden death from cardiac causes in selected patients but require the use of transvenous lead systems. To eliminate the need for venous access, we designed and tested an entirely subcutaneous ICD system. METHODS First, we conducted two short-term clinical trials to identify a suitable device configuration and assess energy requirements. We evaluated four subcutaneous ICD configurations in 78 patients who were candidates for ICD implantation and subsequently tested the best configuration in 49 additional patients to determine the subcutaneous defibrillation threshold in comparison with that of the standard transvenous ICD. Then we evaluated the long-term use of subcutaneous ICDs in a pilot study, involving 6 patients, which was followed by a trial involving 55 patients. RESULTS The best device configuration consisted of a parasternal electrode and a left lateral thoracic pulse generator. This configuration was as effective as a transvenous ICD for terminating induced ventricular fibrillation, albeit with a significantly higher mean (+/-SD) energy requirement (36.6+/-19.8 J vs. 11.1+/-8.5 J). Among patients who received a permanent subcutaneous ICD, ventricular fibrillation was successfully detected in 100% of 137 induced episodes. Induced ventricular fibrillation was converted twice in 58 of 59 patients (98%) with the delivery of 65-J shocks in two consecutive tests. Clinically significant adverse events included two pocket infections and four lead revisions. After a mean of 10+/-1 months, the device had successfully detected and treated all 12 episodes of spontaneous, sustained ventricular tachyarrhythmia. CONCLUSIONS In small, nonrandomized studies, an entirely subcutaneous ICD consistently detected and converted ventricular fibrillation induced during electrophysiological testing. The device also successfully detected and treated all 12 episodes of spontaneous, sustained ventricular tachyarrhythmia. (ClinicalTrials.gov numbers, NCT00399217 and NCT00853645.)

Diagnostic yield in sudden unexplained death and aborted cardiac arrest in the young: the experience of a tertiary referral center in The Netherlands.

BACKGROUND In sudden unexplained death (SUD) in the young (age 1-50 years), cardiologic and genetic examination in surviving relatives may unmask the cause of death in a significant proportion. The causes of aborted cardiac arrest (ACA) in this age group likely are similar to those in sudden cardiac death. However, there is a paucity of recent data on this topic. OBJECTIVE The purpose of this study was to gain insight into the yield of current diagnostic strategies used in relatives of SUD victims and in ACA victims aged 1-50 years in our dedicated tertiary referral center. METHODS We studied (1) all consecutive families who presented to the cardiology department for examination because of ≥1 first-degree related SUD victim aged 1-50 years and (2) all consecutive ACA victims aged 1-50 years who presented to the cardiology department from 1996 to 2009. Comprehensive cardiologic and genetic examination was performed in both populations. RESULTS A certain or probable diagnosis was made in 47 (33%) of 140 SUD families, including 45 (96%) cases of inherited cardiac diseases. Long QT syndrome (19%) was the most prevalent diagnosis. In 42 (61%) of 69 ACA victims, the cause of the event was determined (inherited in 31 [74%]). Hypertrophic cardiomyopathy was most prevalent (17%). CONCLUSION The yield of the current diagnostic workup in relatives of young SUD victims is 33% and is almost twice as high in young ACA victims. Inherited cardiac diseases are predominantly causative in both groups.

Local depolarization abnormalities are the dominant pathophysiologic mechanism for type 1 electrocardiogram in brugada syndrome a study of electrocardiograms, vectorcardiograms, and body surface potential maps during ajmaline provocation.

OBJECTIVES We sought to obtain new insights into the pathophysiologic basis of Brugada syndrome (BrS) by studying changes in various electrocardiographic depolarization and/or repolarization variables that occurred with the development of the signature type 1 BrS electrocardiogram (ECG) during ajmaline provocation testing. BACKGROUND BrS is associated with sudden cardiac death. Its pathophysiologic basis, although unresolved, is believed to reside in abnormal cardiac depolarization or abnormal repolarization. METHODS Ajmaline provocation was performed in 269 patients suspected of having BrS with simultaneous recording of ECGs, vectorcardiograms, and 62-lead body surface potential maps. RESULTS A type 1 ECG was elicited in 91 patients (BrS patients), 162 patients had a negative test result (controls), and 16 patients had an abnormal test result. Depolarization abnormalities were more prominent in BrS patients and were mapped to the right ventricle (RV) by longer right precordial filtered QRS complex durations (142 +/- 23 ms vs. 125 +/- 14 ms, p < 0.01) and right terminal conduction delay (60 +/- 11 ms vs. 53 +/- 9 ms, p < 0.01). Repolarization abnormalities remained concordant with depolarization abnormalities as indicated by steady low nondipolar content (12 +/- 8% vs. 8 +/- 4%, p = NS), lower spatial QRS-T integrals (33 +/- 12 mV.ms vs. 40 +/- 16 mV.ms, p < 0.05), similar spatial QRS-T angles (92 +/- 39 degrees vs. 87 +/- 31 degrees , p = NS), similar T(peak)-T(end) interval (143 +/- 36 ms vs. 138 +/- 25 ms, p = NS), and similar T(peak)-T(end) dispersion (47 +/- 37 ms vs. 45 +/- 27 ms, p = NS). CONCLUSIONS The type 1 BrS ECG is characterized predominantly by localized depolarization abnormalities, notably (terminal) conduction delay in the RV, as assessed with complementary noninvasive electrocardiographic techniques. We could not define a separate role for repolarization abnormalities but suggest that the typical signs of repolarization derangements seen on the ECG are secondary to these depolarization abnormalities.

Slow and Discontinuous Conduction Conspire in Brugada Syndrome A Right Ventricular Mapping and Stimulation Study

Background—Brugada syndrome (BrS) is associated with lethal arrhythmias, which are linked to specific ST-segment changes (type-1 BrS-ECG) and the right ventricle (RV). The pathophysiological basis of the arrhythmias and type-1 BrS-ECG is unresolved. We studied the electrophysiological characteristics of the RV endocardium in BrS. Methods and Results—RV endocardial electroanatomical mapping and stimulation studies were performed in controls (n=12) and BrS patients with a type-1 (BrS-1, n=10) or type-2 BrS-ECG (BrS-2, n=12) during the studies. BrS-1 patients had prominent impairment of RV endocardial impulse propagation when compared with controls, as represented by: (1) prolonged activation-duration during sinus rhythm (86±4 versus 65±3 ms), (2) increased electrogram fractionation (1.36±0.04 versus 1.15±0.01 deflections per electrogram), (3) longer electrogram duration (83±3 versus 63±2 ms), (4) activation delays on premature stimulation (longitudinal: 160±26 versus 86±9 ms; transversal: 112±5 versus 58±6 ms), and (5) abnormal transversal conduction velocity restitution (42±8 versus 18±2 ms increase in delay at shortest coupling intervals). Wider and more fractionated electrograms were also found in BrS-2 patients. Repolarization was not different between groups. Conclusions—BrS-1 and BrS-2 patients are characterized by wide and fractionated electrograms at the RV endocardium. BrS-1 patients display additional conduction slowing during sinus rhythm and premature stimulation along with abnormal transversal conduction velocity restitution. These patients may thus exhibit a substrate for slow and discontinuous conduction caused by abnormal active membrane processes and electric coupling. Our findings support the emerging notion that BrS is not solely attributable to abnormal electrophysiological properties but requires the conspiring effects of conduction slowing and tissue discontinuities.

Rationale and design of the PRAETORIAN trial: A Prospective, RAndomizEd comparison of subcuTaneOus and tRansvenous ImplANtable cardioverter-defibrillator therapy

BACKGROUND Implantable cardioverter-defibrillators (ICDs) are widely used to prevent fatal outcomes associated with life-threatening arrhythmic episodes in a variety of cardiac diseases. These ICDs rely on transvenous leads for cardiac sensing and defibrillation. A new entirely subcutaneous ICD overcomes problems associated with transvenous leads. However, the role of the subcutaneous ICD as an adjunctive or primary therapy in patients at risk for sudden cardiac death is unclear. STUDY DESIGN The PRAETORIAN trial is an investigator-initiated, randomized, controlled, multicenter, prospective 2-arm trial that outlines the advantages and disadvantages of the subcutaneous ICD. Patients with a class I or IIa indication for ICD therapy without an indication for bradypacing or tachypacing are included. A total of 700 patients are randomized to either the subcutaneous or transvenous ICD (1:1). The study is powered to claim noninferiority of the subcutaneous ICD with respect to the composite primary endpoint of inappropriate shocks and ICD-related complications. After noninferiority is established, statistical analysis is done for potential superiority. Secondary endpoint comparisons of shock efficacy and patient mortality are also made. CONCLUSION The PRAETORIAN trial is a randomized trial that aims to gain scientific evidence for the use of the subcutaneous ICD compared with the transvenous ICD in a population of patients with conventional ICD with respect to major ICD-related adverse events. This trial is registered at ClinicalTrials.gov with trial ID NCT01296022.

The ICD for Primary Prevention in Patients With Inherited Cardiac Diseases Indications, Use, and Outcome: A Comparison With Secondary Prevention

Background— Indications for prophylactic implantable cardioverter-defibrillator (ICD) therapy in patients with inherited cardiac diseases stem from observational studies and are uncertain. This study evaluates the efficacy and harm rate of ICD implantations for primary prevention compared with secondary prevention in inherited cardiac diseases. Methods and Results— Between January 1, 1993, and April 1, 2011, 354 patients with inherited cardiac diseases were treated with ICDs. Incidence rates of appropriate shocks in primary prevention patients with arrhythmogenic right ventricular cardiomyopathy and hypertrophic cardiomyopathy were 4.2 to 6.7/100 patient-years, whereas the risk for appropriate shocks in primary prevention patients with Brugada syndrome, long QT syndrome, or carrying the DPP6 haplotype approached zero. Conversely, in secondary prevention patients there was a considerably higher incidence rate of appropriate shocks. None of the indications for primary prevention were associated with appropriate shock therapy. One hundred twenty-three patients (35%) experienced ICD-related adverse events. Conclusions— For Brugada syndrome, long QT syndrome, and DPP6 the efficacy of an ICD for primary prevention contrasts with the amount of harm, and factors that formed the indication for ICD implantation do not relate to the occurrence of appropriate shocks. The higher appropriate discharge rates in arrhythmogenic right ventricular cardiomyopathy and hypertrophic cardiomyopathy compared with primary electric diseases might result from a more advanced risk stratification scheme in these inherited cardiomyopathies.Background—Indications for prophylactic implantable cardioverter-defibrillator (ICD) therapy in patients with inherited cardiac diseases stem from observational studies and are uncertain. This study evaluates the efficacy and harm rate of ICD implantations for primary prevention compared with secondary prevention in inherited cardiac diseases. Methods and Results—Between January 1, 1993, and April 1, 2011, 354 patients with inherited cardiac diseases were treated with ICDs. Incidence rates of appropriate shocks in primary prevention patients with arrhythmogenic right ventricular cardiomyopathy and hypertrophic cardiomyopathy were 4.2 to 6.7/100 patient-years, whereas the risk for appropriate shocks in primary prevention patients with Brugada syndrome, long QT syndrome, or carrying the DPP6 haplotype approached zero. Conversely, in secondary prevention patients there was a considerably higher incidence rate of appropriate shocks. None of the indications for primary prevention were associated with appropriate shock therapy. One hundred twenty-three patients (35%) experienced ICD-related adverse events. Conclusions—For Brugada syndrome, long QT syndrome, and DPP6 the efficacy of an ICD for primary prevention contrasts with the amount of harm, and factors that formed the indication for ICD implantation do not relate to the occurrence of appropriate shocks. The higher appropriate discharge rates in arrhythmogenic right ventricular cardiomyopathy and hypertrophic cardiomyopathy compared with primary electric diseases might result from a more advanced risk stratification scheme in these inherited cardiomyopathies.

Implantable cardioverter defibrillator therapy in adults with congenital heart disease: who is at risk of shocks?

Background— The value of implantable cardioverter defibrillators (ICDs) in adults with congenital heart disease (CHD) is unknown. We investigated the long-term outcome after ICD implantation and developed a simple risk stratification score for ICD therapy. Methods and Results— A total of 136 adults with CHD and ICD (mean age±SD, 41±13 years; 67% male) were identified from 10 tertiary referral centers in the Netherlands and Belgium. The indication for ICD implantation was primary prevention in 50% of patients. Diagnoses included tetralogy of Fallot (51%), septal defects (20%), (congenitally corrected) transposition of the great arteries (13%), and other (16%). Thirty-nine patients (29%) received appropriate ICD shocks during a median follow-up of 4.6 years. Secondary prevention indication (hazard ratio [HR], 3.6; 95% CI, 1.3–9.5; P=0.009), coronary artery disease (HR, 2.7; 95% CI, 1.0–7.2; P=0.042), and symptomatic nonsustained ventricular tachycardia (NSVT; HR, 9.1; 95% CI, 2.8–29.2; P=0.001) were associated with appropriate ICD shocks. A risk score was developed to evaluate the likelihood of appropriate ICD shocks. The 8-year survival curve to first appropriate shocks was 94%, 57%, and 26% for low-, intermediate-, and high-risk patients, respectively. In primary prevention, symptomatic NSVTs (HR, 8.0; 95% CI, 2.3–27.1; P=0.001) and subpulmonary ventricular dysfunction (HR, 3.0; 95% CI, 1.2–12.6; P=0.02) were associated with appropriate shocks in univariable analysis. Inappropriate shocks occurred in 41 patients (30%). In addition, 40 patients (29%) experienced 45 implantation-related complications. Conclusions— Adults with CHD and ICDs receive high rates of appropriate and effective shocks. Patients with secondary prevention indication, coronary artery disease, and symptomatic NSVT are at highest risk of receiving appropriate ICD shocks. ICD implantation is accompanied by considerable morbidity, including inappropriate shocks and procedure- related complications.

Implantable Cardioverter-Defibrillators Have Reduced the Incidence of Resuscitation for Out-of-Hospital Cardiac Arrest Caused by Lethal Arrhythmias

Background— Over the last decades, a gradual decrease in ventricular fibrillation (VF) as initial recorded rhythm during resuscitation for out-of-hospital cardiac arrest (OHCA) has been noted. We sought to establish the contribution of implantable cardioverter-defibrillator (ICD) therapy to this decline. Methods and Results— Using a prospective database of all OHCA resuscitation in the province North Holland in the Netherlands (Amsterdam Resuscitation Studies [ARREST]), we collected data on all patients in whom resuscitation for OHCA was attempted in 2005–2008. VF OHCA incidence (per 100 000 inhabitants per year) was compared with VF OHCA incidence data during 1995–1997, collected in a similar way. We also collected ICD interrogations of all ICD patients from North Holland and identified all appropriate ICD shocks in 2005–2008; we calculated the number of prevented VF OHCA episodes, considering that only part of the appropriate shocks would result in avoided resuscitation. VF OHCA incidence decreased from 21.1/100 000 in 1995–1997 to 17.4/100 000 in 2005–2008 (P<0.001). Non-VF OHCA increased from 12.2/100 000 to 19.4/100 000 (P<0.001). VF as presenting rhythm declined from 63% to 47%. In 2005–2008, 1972 ICD patients received 977 shocks. Of these shocks, 339 were caused by a life-threatening arrhythmia. We estimate that these 339 shocks have prevented 81 (minimum, 39; maximum, 152) cases of VF OHCA, corresponding with 33% (minimum, 16%; maximum, 63%) of the observed decline in VF OHCA incidence. Conclusions— The incidence of VF OHCA decreased over the last 10 years in North Holland. ICD therapy explained a decrease of 1.2/100 000 inhabitants per year, corresponding with 33% of the observed decline in VF OHCA.

Efficacy and safety of percutaneous treatment of iatrogenic femoral artery pseudoaneurysm by biodegradable collagen injection

UNLABELLED OBJECTIVES; The goal of this study was to assess the safety and efficacy of femoral artery pseudoaneurysm (FAP) closure by collagen injection. BACKGROUND; The FAP is an infrequent but troublesome complication after percutaneous transfemoral catheter procedures. If ultrasound-guided compression repair (UGCR) fails, vascular surgery is indicated. We have developed a less invasive method to close FAPs percutaneously by injecting collagen and, thus, inducing clotting within the aneurysm. METHODS Via a 9F needle or 11F sheath, a biodegradable adhesive bovine collagen is injected percutaneously into the FAP, guided by angiography from the contralateral site. RESULTS From 1993 to 2000, compression and UGCR had failed to obliterate 110 FAPs. These patients have been treated by collagen injection. Mean age of the patients was 65.6 +/- 10.2 years (range: 32 to 85 years), and 50% were women. Immediate closure of the FAP was achieved in 107/110 patients (97.3%) without any complication or adverse effect. In one patient the collagen could not be applied due to unfavorable anatomy. One patient needed a second session of collagen injection. In one patient too much collagen was inserted, which resulted in external compression of the artery, and surgical intervention was required. The overall success rate was 108/110 (98%, 95% confidence interval: 93.5% to 99.8%). Among the patients with successful procedures, there were no recurrences during six months follow-up. CONCLUSIONS The percutaneous treatment of iatrogenic FAP, by injection with collagen, is an effective and safe strategy. This method provides an excellent therapeutic alternative to the traditional surgical management.

Incremental prognostic value of an abnormal baseline spatial QRS-T angle in chronic dialysis patients.

AIMS In order to improve the abysmal outcome of dialysis patients, it is critical to identify patients with a high mortality risk. The spatial QRS-T angle, which can be easily calculated from the 12 lead electrocardiogram (ECG), might be useful in the prognostication in dialysis patients. The objective of this study was to establish the prognostic value of the spatial QRS-T angle. METHODS AND RESULTS All patients who initiated dialysis therapy between 2002 and 2009 in the hospitals of Leiden (LUMC) and Amsterdam (AMC) at least 3 months on dialysis were included. The spatial QRS-T angle was calculated, from a routinely acquired ECG, and its relationship with mortality was assessed. An abnormal spatial QRS-T angle was defined as ≥ 130° in men and ≥ 116° in women. In total, 277 consecutive patients (172 male, mean age 56.3 ± 17.0) were included. An abnormal spatial QRS-T angle was associated with a higher risk of death from all causes [hazard ratio (HR) 2.33; 95% confidence interval (CI) 1.46-3.70] and especially a higher risk of sudden cardiac death (HR 2.99; 95% CI 1.04-8.60). Furthermore, an abnormal spatial QRS-T angle was of incremental prognostic value, when added to a risk model consisting of known risk factors. CONCLUSION In chronic dialysis patients the spatial QRS-T angle is a significant and independent predictor of all-cause and especially sudden cardiac death. It implies that this parameter can be used to identify high risk patients.