Stefanos Archontakis

Implantable cardioverter defibrillator therapy activation for high risk patients with relatively well preserved left ventricular ejection fraction. Does it really work

BACKGROUND Current guidelines for the primary prevention of sudden cardiac death have used a left ventricular ejection fraction (LVEF) ≤ 35% as a critical point to justify implantable cardioverter defibrillator (ICD) implantation in post myocardial infarction patients and in those with nonischemic dilated cardiomyopathy. We compared mortality and ICD activation rates among different ICD group recipients using a cut-off value for LVEF ≤ 35%. METHODS We followed up for a mean period of 41.1 months 495 ICD recipients (442 males, 65.6 years old, 68.9% post myocardial infarction patients, 422 with LVEF ≤ 35%). Prevention was considered primary in patients who fulfilled guidelines criteria or had inducible ventricular arrhythmia during programmed ventricular stimulation for patients with LVEF >35%. RESULTS Over the course of the trial, 84 of 495 patients died; 69 experienced cardiac death (6 sudden) and 15 non cardiac death. ICD recipients with LVEF ≤ 35% compared to those with preserved LVEF (mean LVEF=43%) had a greater incidence of total mortality (18% vs. 11%, log rank p=0.028) and cardiac death (15.4% vs. 5.5%, log rank p=0.005). There was no difference in the incidence for appropriate device therapy between patients with LVEF ≤ 35% and those with LVEF >35% (56.9% vs. 65.8%, log rank p=0.93). In the multivariate analysis the presence of advanced New York Heart Association stage predicted both total mortality (HR=2.69, 95% CI 1.771-4.086) and cardiac death (HR=3.437, 95% CI 2.163-5.463). CONCLUSIONS ICD therapy may protect heart failure patients at early stages from arrhythmic morbidity and mortality, based on an electrophysiology-guided risk stratification approach.

Primary prevention of sudden cardiac death in a nonischemic dilated cardiomyopathy population: reappraisal of the role of programmed ventricular stimulation.

Background— We considered the role of programmed ventricular stimulation in primary prevention of sudden cardiac death in an idiopathic dilated cardiomyopathy population. Methods and Results— One hundred fifty-eight patients with idiopathic dilated cardiomyopathy underwent programmed ventricular stimulation. Ventricular tachycardia/ventricular fibrillation was triggered in 44 patients (group I, 27.8%) versus 114 patients (group II), where ventricular tachycardia/ventricular fibrillation was not induced. Sixty-nine patients with idiopathic dilated cardiomyopathy underwent implantable cardioverter-defibrillator (ICD) implantation: 41/44 in group I and 28/114 in group II. The major end points of the study were overall mortality and appropriate ICD activation. Overall mortality during the 46.9 months of mean follow-up was not significantly different between the 2 groups. Patients with left ventricular ejection fraction ≤35% (n=119) demonstrated a higher overall mortality rate compared with the patients with left ventricular ejection fraction >35% (n=39; 16.8% versus 10.3%, log-rank P =0.025). Advanced New York Heart Association class (III and IV versus I and II) was the single independent and strongest prognostic factor of overall mortality (hazard ratio, 11.909; P <0.001; confidence interval, 3.106–45.65), as well as of cardiac mortality (hazard ratio, 14.787; P =0.001; confidence interval, 2.958–73.922). Among ICD recipients, ICD activation rate was significantly higher in group I compared with group II (30 of 41 patients–73.2% versus 5 of 28 patients–17.9%; log-rank P =0.001), either in the form of antitachycardia pacing (68.3% versus 17.9%; log-rank P =0.001) or in the shock delivery form (51.2% versus 17.9%; log-rank P =0.05). Induction of ventricular tachycardia/ventricular fibrillation during programmed ventricular stimulation in contrast to left ventricular ejection fraction was the single independent prognostic factor for future ICD activation (hazard ratio, 4.195; P =0.007; confidence interval, 1.467–11.994). Conclusions— Inducibility of ventricular tachycardia/ventricular fibrillation was associated with an increased likelihood of subsequent ICD activation and sudden cardiac death surrogate.Background—We considered the role of programmed ventricular stimulation in primary prevention of sudden cardiac death in an idiopathic dilated cardiomyopathy population. Methods and Results—One hundred fifty-eight patients with idiopathic dilated cardiomyopathy underwent programmed ventricular stimulation. Ventricular tachycardia/ventricular fibrillation was triggered in 44 patients (group I, 27.8%) versus 114 patients (group II), where ventricular tachycardia/ventricular fibrillation was not induced. Sixty-nine patients with idiopathic dilated cardiomyopathy underwent implantable cardioverter-defibrillator (ICD) implantation: 41/44 in group I and 28/114 in group II. The major end points of the study were overall mortality and appropriate ICD activation. Overall mortality during the 46.9 months of mean follow-up was not significantly different between the 2 groups. Patients with left ventricular ejection fraction ⩽35% (n=119) demonstrated a higher overall mortality rate compared with the patients with left ventricular ejection fraction >35% (n=39; 16.8% versus 10.3%, log-rank P=0.025). Advanced New York Heart Association class (III and IV versus I and II) was the single independent and strongest prognostic factor of overall mortality (hazard ratio, 11.909; P<0.001; confidence interval, 3.106–45.65), as well as of cardiac mortality (hazard ratio, 14.787; P=0.001; confidence interval, 2.958–73.922). Among ICD recipients, ICD activation rate was significantly higher in group I compared with group II (30 of 41 patients–73.2% versus 5 of 28 patients–17.9%; log-rank P=0.001), either in the form of antitachycardia pacing (68.3% versus 17.9%; log-rank P=0.001) or in the shock delivery form (51.2% versus 17.9%; log-rank P=0.05). Induction of ventricular tachycardia/ventricular fibrillation during programmed ventricular stimulation in contrast to left ventricular ejection fraction was the single independent prognostic factor for future ICD activation (hazard ratio, 4.195; P=0.007; confidence interval, 1.467–11.994). Conclusions—Inducibility of ventricular tachycardia/ventricular fibrillation was associated with an increased likelihood of subsequent ICD activation and sudden cardiac death surrogate.

Prognostic value of programmed ventricular stimulation for sudden death in selected high risk patients with structural heart disease and preserved systolic function

No recommendations exist regarding the proper management of pa-tients with structural heart disease and preserved systolic function,namely post-myocardial infarction (MI) patients with left ventricularejection fraction (LVEF) N40% and dilated cardiomyopathy (DCM)patients with LVEF ≥40% [1]. Between January 2004 and March 2011,we assessed the prognostic role of programmed ventricular stimulation(PVS) in 69 post-MI and 42 DCM patients with preserved LVEF (96males, 65.8 years old, mean LVEF 46 ± 4.5). Specifically, we included62 patients with syncope (n = 36) or presyncope (n = 26) andnon-conclusive 12-lead ECG, Holter monitoring, echocardiographicstudy and tilt table testing as well as 49 asymptomatic patients with ≥1episodes ofnonsustained ventriculartachycardia (NSVT)(≥3 consecu-tive beats at a rate ≥120 bpm) or ≥30 premature ventricularcomplexes/hour on 24-h Holter monitoring. Active ischemia wasexcluded in post-MI patients. DCM diagnosis was based on clinical,echocardiographic and angiographic findings. The study was approvedby the Medical Research Ethics Committee of our Institution and wascarried out in accordance with the Declaration of Helsinki. All subjectswere informed in detail, agreed to participate and signed an informedconsent form.Antiarrhythmics,prescribedbythereferringphysiciansin23patients,were discontinued before the study. Stimulation protocol consisted of upto triple extrastimuli (S2S3S4) delivered at two paced cycle lengths(550 ms and 400 ms) at the right ventricular apex and outflow tract.Extrastimuliwereappliedafterasix-beatdrivetrainwitha2-sinterdrivepause. In DCM patients where no sustained ventricular tachyarrhythmiawas triggered, PVS was repeated after intravenous isoproterenoladministration (1–4 μg/kg/min) [2]. The presence of either sinus and/or atrioventricular node disease was ascertained based on abnormalelectrophysiological parameters [3].When sustained monomorphic VT for post-MI patients or sustainedVT/ventricular fibrillation (VF) for DCM patients was triggered duringPVS, an implantable cardioverter–defibrillator (ICD) was offered andprogrammed on two consecutive zones: an antitachycardia pacing(ATP)zone(VTdetectioncyclelengthof375±40msanddetectionin-terval of 16/16 or 24/24 beats), and an initial shock zone (VF detectioncycle length of 300 ± 30 ms and detection interval of 18/24). Themajor end-points were the incidence of cardiac death and SCD, as wellas the appropriate first ICD activation for implanted patients. Recur-rence of syncope was examined in patients with syncope/presyncopeat baseline.Sustained monomorphic VT was induced in 23/69 (33.3%) post-MIpatients, more frequently in those with NSVT in Holter monitoring(42.5%vs. 20.7%, p = 0.058). ICD was implanted in all induced patientswhile a pacemaker was also implanted in 16 symptomatic post-MI pa-tients with sinus node and/or atrio-ventricular node disease (Fig. 1).Sustained monomorphic VT was induced in 8 and polymorphic VT/VFin 5 of the 42 DCM patients (VT/VF induction rate 31%). ICD wasimplanted in 10/13 induced patients (3 asymptomatic patients deniedimplantation) and a pacemaker in 7 symptomatic patients (Fig. 1).Mean follow-up period was 52.3 months. During that period, 1 in-ducible DCM patient, that denied ICD implant, experienced SCD and 3patients experienced non-cardiac death. None of the non-inducible pa-tientsatbaseline(46post-MIand29DCMpatients)referredrecurrenceor new-onset syncope or pre-syncope or experienced SCD or cardiac

Residual Platelet Reactivity After Clopidogrel Loading in Patients With ST-Elevation Myocardial Infarction Undergoing an Unexpectedly Delayed Primary Percutaneous Coronary Intervention

BACKGROUND Residual platelet reactivity (RPR) after clopidogrel loading, measured by the VerifyNow assay, has been shown to predict 12-month clinical events in patients with acute coronary syndromes. However, links between coronary angiographic findings and outcome in patients with ST-elevation myocardial infarction (STEMI), with RPR have not been reported. We investigated whether RPR is associated with the amount of intracoronary thrombus burden (TB) in patients with STEMI undergoing unexpectedly-delayed primary percutaneous coronary intervention (pPCI). Moreover, we evaluated whether RPR might influence coronary flow and myocardial perfusion immediately post-pPCI. METHODS AND RESULTS The VerifyNow assay was used to determine RPR after clopidogrel loading, expressed in P2Y12-Reaction-Units (PRU). Intracoronary-TB was angiographically estimated and stratified as TB-Grade-A, -B and -C. Thrombolysis In Myocardial Infarction (TIMI) flow and Myocardial Blush (MB) were also estimated post-PCI. A total of 74 consecutive patients who presented with STEMI were enrolled in the study. Patients with greater TB presented significantly higher PRU-levels (174.1 ± 91.5, 196.23 ± 113.4 and 252.8 ± 107.8 for TB-Grade A, B and C, respectively; P=0.044). PRU-levels >251.5 were shown to predict Large-TB (LTB; TB-Grade-C) (sensitivity=57.9%; specificity=77.8%; P=0.014). Impaired TIMI-flow and MB after PCI were significantly associated with higher PRU-levels (P < 0.001). CONCLUSIONS Among the studied patients, those with a higher RPR after clopidogrel loading presented larger intracoronary TB, worse post-PCI myocardial flow and perfusion.

Leadless Pacing System: Initial experience with a novel technology in Greece

lease cite this article in press as: Sid ociety of Cardiology (2017), http:// tp://dx.doi.org/10.1016/j.hjc.2017 09-9666/a 2017 Hellenic Society of ense (http://creativecommons.org/ Leadless pacing systems have recently emerged as a reliable therapeutic alternative to conventional pacemakers in providing therapy for patients with bradyarrhythmias. Initial studies demonstrate favorable efficacy and safety results compared to transvenous pacemakers. We report the first six cases of a leadless pacemaker system (Micra Transcatheter Pacing System, Medtronic, Minneapolis, MN, USA) implantation in Greece that took place in the electrophysiology laboratory of Hippokrateion General Hospital of Athens between April and November 2016. Because of the relatively high cost of leadless pacemakers compared to the conventional ones, the use of this technology is still limited in Greece, and currently such implantations are restricted mostly to patients who present with severe access problems, unlikely to be overcome by conventional transvenous implantation techniques. Data of our patients are presented in Table 1. Procedure: Implantation was performed under fluoroscopy, after obtaining informed consent from the patients, with local anesthesia. After introducing a 24-French sheath into the right femoral vein, a deflectable delivery catheter with the pacemaker adjusted on its distal part was advanced through the inferior vena cava and the right atrium to the right ventricle (RV). Subsequently, the outer sheath was retracted, allowing the device tines to be deployed, fixing the pacemaker in the right ventricular trabeculae. Adequate fixing of the system was confirmed mechanically by the “tug-test” while the pacemaker still

Programmed ventricular stimulation predicts arrhythmic events and survival in hypertrophic cardiomyopathy

BACKGROUND Sudden cardiac death (SCD) risk stratification in hypertrophic cardiomyopathy (HCM) in the context of primary prevention remains suboptimal. The purpose of this study was to examine the additional contribution of programmed ventricular stimulation (PVS) on established risk assessment. METHODS Two-hundred-and-three consecutive patients with diagnosed HCM and ≥1 noninvasive risk factors were prospectively enrolled over 19years. Patients were risk stratified, submitted to PVS and received an implantable cardioverter-defibrillator (ICD) according to then-current American Heart Association (AHA) guidelines and inducibility. Participants were prospectively followed-up for primary endpoint occurrence (appropriate ICD therapy or SCD). Contemporary (2015) AHA and European Society of Cardiology (ESC) guidelines were retrospectively assessed. RESULTS During a median follow-up period of 60months the primary endpoint occurred in 20 patients, 19 of whom were inducible and received an ICD. Overall, 79 patients (38.9%) were inducible and 92 patients (45.3%) received an ICD (PVS sensitivity=95%, specificity=67.2%, positive predictive value=24%, negative predictive value=99.2%). AHA and ESC guidelines application misclassified 3 and 9 primary endpoint-meeting patients, respectively. Inducibility was the most important determinant of event-free survival in multivariate Cox regression (hazard ratio=33.3). A combined approach of ESC score≥6% or AHA indication for ICD with PVS inducibility yielded absolute sensitivity and negative predictive value, the former at a more cost-effective and specific way. CONCLUSIONS Inducibility at PVS predicts SCD or appropriate device therapy in HCM. Non-inducibility is associated with prolonged event-free survival, while the procedure was proven safe. Reintegration of PVS into established risk stratification models in HCM may improve patient assessment.

The subcutaneous ICD as an alternative to the conventional ICD system: Initial experience in Greece and a review of the literature

The introduction of an implantable cardioverter defibrillator (ICD) in clinical practice has revolutionized our therapeutic approach for both primary and secondary prevention of sudden cardiac death (SCD), as it has proven to be superior to medical therapy in treating potentially life-threatening ventricular arrhythmias and has resulted in reduced mortality rates. However, implantation of a conventional ICD carries a non-negligible risk of periprocedural and long-term complications associated with the transvenous ICD leads. The entirely subcutaneous implantable cardioverter defibrillator (S-ICD) has recently emerged as a therapeutic alternative to the conventional ICD for patients with various cardiopathies and who are at high risk of SCD. The main advantage is the avoidance of vascular access and thus avoidance of complications associated with transvenous leads. Patients without pacing indications, such as bradycardia, a need for antitachycardia pacing or cardiac resynchronization, as well as those at higher risk of complications from transvenous lead implantation are perfect candidates for this novel technology. The subcutaneous ICD has proven to be equally safe and effective compared to transvenous ICD systems in early clinical trials. Further technical improvements of the system will likely lead to the expansion of indications and widespread use of this technology. In the present review, we discuss the indications for this system, summarize early clinical experiences and highlight the advantages and disadvantages of this novel technology. In addition, we present the first two cases of subcutaneous cardioverter defibrillator system implantation in Greece.

Leadless pacing systems: A valuable alternative for patients with severe access problems

In the last decades, the expanding use of pacemakers has contributed to a significant improvement in the prognosis of patients with bradyarrhythmias. Resembling the two faces of Janus, however, pacemaker therapy may occasionally be associated with significant periand/or post-procedural complications, which in most of the cases are related to the presence of the transvenous leads, e.g. pneumothorax, lead dislodgment, cardiac perforation and tamponade, venous thromboses, regurgitation of the tricuspid valve, pacemaker pocket-related complications, chronic lead failure and, most importantly, infections occurringwith an incidence of 1-2%.1,2Moreover, in a non-insignificant number of patients, the implantation of conventional transvenous systems is restricted by severe venous access problems of the superior caval system due to thromboses, venous obstruction, anatomical variations, malignant superior vena cava syndrome, etc. Alternatively, implantation of an epicardiac pacemakermay be reasonable; however, because this procedure is surgical, it is related to a risk for potential complications. Subsequently, the recent introduction in clinical practice of a new generation of leadless pacemakers, completely implantable on the right ventricular wall, marks the start of a new era in pacing.3e5 A 72-year-old Caucasian male patient was referred to the Cardiology Department of our hospital because of fatigue and deterioration of his functional status to New York Heart Association class III since the last few months. In addition, in the last 3 months prior to referral, he had experienced three syncoptic episodes and several episodes of presyncope. The patient had a history of a coronary artery by-pass grafting operation 20 years ago (Fig. 3a, black arrow head) and rheumatic mitral and aortic valvular heart disease that resulted in a double replacement with bioprosthetic valves 4 years before the present assessment (Figs. 1a and 3a, black and white arrows). Additionally, he had a history of superior vena cava (SVC) syndrome of non-malignant cause, diagnosed 4 years before the present assessment and treated by a venous stent placement that was, however, thrombosed soon after the operation (Fig. 1a, white arrow and 3a, white arrow head). Moreover, arterial hypertension, chronic

Epicardial right ventricular lipoma presenting with sustained ventricular tachycardia

Cardiac lipomas are benign tumors but can be associated with septal infiltration, arrhythmias, and superior vena cava stenosis. We present images of an epicardial right ventricular lipoma presentingwith sustained ventricular tachycardia (VT). A 59-year-old female, with no previous medical history, presented with syncope and was found to have sustained VT with left bundle branch block morphology, which was successfully cardioverted to normal sinus rhythm (NSR). A transthoracic echocardiogram revealed a 6 × 4-cm mass compressing the right ventricle (RV), resulting in significant tricuspid regurgitation (Figure 1A). Cardiac magnetic resonance imaging confirmed these findings (Figure 1B). A coronary angiogram revealed no coronary stenosis. At the time of surgery, cardiopulmonary bypass (CPB) was established via a mediansternotomy and ascending aortic and bicaval cannulation. The aorta was crossclamped and the heart arrested with cold antegrade blood cardioplegia. The tumor was located on the anterior surface of the RV and extended from the atrioventricular groove to the tricuspid annulus (Figures 2A and 2B). The tumor, with its surrounding capsule, was resected (Figure 2C). The tricuspid annulus was repaired with a #30 annuloplasty ring (Carpentier-Edwards Physio Annuloplasty Ring, Edwards Lifesciences LLC, Irvine, CA) and the defect in the RV was reconstructed with a pericardial patch reinforced with pericardial strips (Figure 2D). The patient was weaned off CPB in NSR; the CPB and crossclamp times were 114 and 102min, respectively. The patient had an uncomplicated postoperative course and the histology was consistent with a benign lipoma. A month following surgery, a follow-up electrophysiology study showed sustained monomorphic VT associated with hemodynamic compromise. Therefore, an implantable cardioverterdefibrillator (EveraTM ICD, Medtronic, Minneapolis, MN) was inserted. She is now 2 years postsurgery and has had no further VT on beta-blocker therapy. Follow-up echocardiography showed no recurrent tumor development (Figure 3).

Biomarkers Associated with Bleeding Risk in the Setting of Atrial Fibrillation

BACKGROUND Prevention of thromboembolic disease, mainly stroke, with oral anticoagulants remains a major therapeutic goal in patients with atrial fibrillation. Unfortunately, despite the high efficacy, anticoagulant therapy is associated with a significant risk of, frequently catastrophic, and hemorrhagic complications. Among different clinical and laboratory parameters related to an increased risk of bleeding, several biological markers have been recognized and various risk scores for bleeding have been developed. OBJECTIVES/METHODS The aim of the present study is to review current evidence regarding the different biomarkers associated with raised bleeding risk in atrial fibrillation. RESULTS Data originating from large cohorts or the recent large-scale trials of atrial fibrillation have linked numerous individual biomarkers to an increased bleeding risk. Such a relation was revealed for markers of cardiac physiology, such as troponin, BNP and NT-proBNP, markers of renal function, such as GFR and Cystatin or hepatic function, markers involving the system of coagulation, such as D-dimer and Von Willebrand factor, hematologic markers, such as low haemoglobin or low platelets, inflammatory markers, such as interleukin-6, other factors such as GDF-15 and vitamin-E and finally genetic polymorphisms. Many such biomarkers are incorporated in the bleeding risk schemata developed for the prediction of the hemorrhagic risk. CONCLUSIONS Biomarkers were introduced in clinical practice in order to better estimate the potential risk of haemorrhage in these patients and increase the prognostic impact of clinical risk scores. In the last years this concept is gaining significant importance.