Noninvasive electrocardiographic risk factors for sudden cardiac death in dilated ca rdiomyopathy: is ambulatory electrocardiography still relevant?

Risk stratification for sudden cardiac death in dilated cardiomyopathy is a field of constant debate, and the currently proposed criteria have been widely questioned due to their low positive and negative predictive value. In this study, we conducted a systematic review of the literature utilizing the PubMed and Cochrane library platforms, in order to gain insight about dilated cardiomyopathy and its arrhythmic risk stratification utilizing noninvasive risk markers derived mainly from 24 h electrocardiographic monitoring. The obtained articles were reviewed in order to register the various electrocardiographic noninvasive risk factors used, their prevalence, and their prognostic significance in dilated cardiomyopathy. Premature ventricular complexes, nonsustained ventricular tachycardia, late potentials on Signal averaged electrocardiography, T wave alternans, heart rate variability and deceleration capacity of the heart rate, all have both some positive and negative predictive value to identify patients in higher likelihood for ventricular arrhythmias and sudden cardiac death. Corrected QT, QT dispersion, and turbulence slope-turbulence onset of heart rate have yet to establish a predictive correlation in the literature. Although ambulatory electrocardiographic monitoring is frequently used in clinical practice in DCM patients, no single risk marker can be used for the selection of patients at high-risk for malignant ventricular arrhythmic events and sudden cardiac death who could benefit from the implantation of a defibrillator. More studies are needed in order to establish a risk score or a combination of risk factors with the purpose of selecting high-risk patients for ICD implantation in the context of primary prevention.

Angiotensin Regulation of Vascular Homeostasis: Exploring the Role of ROS and RAS Blockers.

Extensive research has been conducted to elucidate and substantiate the crucial role of the Renin-Angiotensin System (RAS) in the pathogenesis of hypertension, cardiovascular disorders, and renal diseases. Furthermore, the role of oxidative stress in maintaining vascular balance has been well established. It has been observed that many of the cellular effects induced by Angiotensin II (Ang II) are facilitated by reactive oxygen species (ROS) produced by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. In this paper, we present a comprehensive overview of the role of ROS in the physiology of human blood vessels, specifically focusing on its interaction with RAS. Moreover, we delve into the mechanisms by which clinical interventions targeting RAS influence redox signaling in the vascular wall.

Comparing efficacy and safety in catheter ablation strategies for atrial fibrillation: a network meta-analysis.

BACKGROUND: There is no consensus on the most efficient catheter ablation (CA) strategy for patients with atrial fibrillation (AF). The objective of this study was to compare the efficacy and safety of different CA strategies for AF ablation through network meta-analysis (NMA). METHODS: A systematic search of PubMed, Web of Science, and CENTRAL was performed up to October 5th, 2020. Randomized controlled trials (RCT) comparing different CA approaches were included. Efficacy was defined as arrhythmia recurrence after CA and safety as any reported complication related to the procedure during a minimum follow-up time of 6 months. RESULTS: In total, 67 RCTs (n = 9871) comparing 19 different CA strategies were included. The risk of recurrence was significantly decreased compared to pulmonary vein isolation (PVI) alone for PVI with renal denervation (RR: 0.60, CI: 0.38-0.94), PVI with ganglia-plexi ablation (RR: 0.62, CI: 0.41-0.94), PVI with additional ablation lines (RR: 0.8, CI: 0.68-0.95) and PVI in combination with bi-atrial modification (RR: 0.32, CI: 0.11-0.88). Strategies including PVI appeared superior to non-PVI strategies such as electrogram-based approaches. No significant differences in safety were observed. CONCLUSIONS: This NMA showed that PVI in combination with additional CA strategies, such as autonomic modulation and additional lines, seem to increase the efficacy of PVI alone. These strategies can be considered in treating patients with AF, since, additionally, no differences in safety were observed. This study provides decision-makers with comprehensive and comparative evidence about the efficacy and safety of different CA strategies. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registry number: CRD42020169494 .

Association of non-invasive electrocardiographic risk factors with left ventricular systolic function in post-myocardial infarction patients with mildly reduced or preserved ejection fraction: Insights from the PRESERVE-EF study.

BACKGROUND: Electrocardiographic non-invasive risk factors (NIRFs) have an important role in the arrhythmic risk stratification of post-myocardial infarction (post-MI) patients with preserved or mildly reduced left ventricular ejection fraction (LVEF). However, their specific relation to left ventricular systolic function remains unclear. We aimed to evaluate the association between NIRFs and LVEF in the patients included in the PRESERVE-EF trial. METHODS: We studied 575 post-MI ischemia-free patients with LVEF≥40% (mean age: 57.0 ± 10.4 years, 86.2% men). The following NIRFs were evaluated: premature ventricular complexes, non-sustained ventricular tachycardia (NSVT), late potentials (LPs), prolonged QTc, increased T-wave alternans, reduced heart rate variability, and abnormal deceleration capacity with abnormal turbulence. RESULTS: There was a statistically significant relationship between LPs (Chi-squared = 4.975; p < .05), nsVT (Chi-squared = 5.749, p < .05), PVCs (r= -.136; p < .01), and the LVEF. The multivariate linear regression analysis showed that LPs (p = .001) and NSVT (p < .001) were significant predictors of the LVEF. The results of the multivariate logistic regression analysis indicated that LPs (OR: 1.76; 95% CI: 1.02-3.05; p = .004) and NSVT (OR: 2.44; 95% CI: 1.18-5.04; p = .001) were independent predictors of the mildly reduced LVEF: 40%-49% versus the preserved LVEF: ≥50%. CONCLUSION: Late potentials and NSVT are independently related to reduced LVEF while they are independent predictors of mildly reduced LVEF versus the preserved LVEF. These findings may have important implications for the arrhythmic risk stratification of post-MI patients with mildly reduced or preserved LVEF.

Noninvasive risk factors for the prediction of inducibility on programmed ventricular stimulation in post-myocardial infarction patients with an ejection fraction ≥40% at risk for sudden cardiac arrest: Insights from the PRESERVE-EF study.

BACKGROUND: In the PRESERVE-EF study, a two-step sudden cardiac death (SCD) risk stratification approach to detect post-myocardial infarction (MI) patients with left ventricle ejection fraction (LVEF) ≥40% at risk for major arrhythmic events (MAEs) was used. Seven noninvasive risk factors (NIRFs) were extracted from a 24-h ambulatory electrocardiography (AECG) and a 45-min resting recording. Patients with at least one NIRF present were referred for invasive programmed ventricular stimulation (PVS) and inducible patients received an Implantable Cardioverter - Defibrillator (ICD). METHODS: In the present study, we evaluated the performance of the NIRFs, as they were described in the PRESERVE-EF study protocol, in predicting a positive PVS. In the PRESERVE-EF study, 152 out of 575 patients underwent PVS and 41 of them were inducible. For the present analysis, data from these 152 patients were analyzed. RESULTS: Among the NIRFs examined, the presence of signal averaged ECG-late potentials (SAECG-LPs) ≥ 2/3 and non-sustained ventricular tachycardia (NSVT) ≥1 eposode/24 h cutoff points were important predictors of a positive PVS study, demonstrating in the logistic regression analysis odds ratios 2.285 (p = .027) and 2.867 (p = .006), respectively. A simple risk score based on the above cutoff points in combination with LVEF < 50% presented high sensitivity but low specificity for a positive PVS. CONCLUSION: Cutoff points of NSVT ≥ 1 episode/24 h and SAECG-LPs ≥ 2/3 in combination with a LVEF < 50% were important predictors of inducibility. However, the final decision for an ICD implantation should be based on a positive PVS, which is irreplaceable in risk stratification.

Transvenous extraction of permanent pacemaker and defibrillator leads: Reduced procedural complexity and higher procedural success rates in patients with infective versus noninfective indications.

INTRODUCTION: Transvenous lead extraction (TLE) is critical in the long-term management of patients with cardiac implanted electronic devices (CIEDs). The aim of the study is to evaluate the outcomes of TLE and to investigate the impact of infection. METHODS AND RESULTS: Data of patients undergoing extraction of permanent pacemaker and defibrillator leads during October 2014-September 2019 were prospectively analyzed. Overall, 242 consecutive patients (aged 71.0 ± 14.0 years, 31.4% female), underwent an equal number of TLE operations for the removal of 516 leads. Infection was the commonest indication (n = 201, 83.1%). Mean implant-to-extraction duration was 7.6 ± 5.4 years. Complete procedural success was recorded in 96.1%, and clinical procedural success was achieved in 97.1% of attempted lead extractions. Major complications occurred in two (0.8%) and minor complications in seven (2.9%) patients. Leads were removed exclusively by using locking stylets in 65.7% of the cases. In the subgroup of noninfective patients, advanced extraction tools were more frequently required compared to patients with CIED infections, to extract leads (success only with locking stylet: 55.8% vs. 67.8%, p = .032). In addition, patients without infection demonstrated lower complete procedural success rates (90.7% vs. 97.2%, p = .004), higher major complication rates (2.4% vs. 0.5%, p = .31) and longer procedural times (136 ± 13 vs. 111 ± 15 min, p = .001). CONCLUSIONS: Our data demonstrate high procedural efficacy and safety and indicate that in patients with noninfective indications, the procedure is more demanding, thus supporting the hypothesis that leads infection dissolves and/or prohibits the formation of fibrotic adherences.

Syncope associated with supraventricular tachycardia: Diagnostic role of implantable loop recorders.

Syncope represents a relatively uncommon symptom of supraventricular tachycardia (SVT). It is likely that an impaired autonomic vasomotor response to the hemodynamic stress of tachycardia is the determinant of hemodynamic changes leading to cerebral hypoperfusion and syncope. In this regard, tilt-table test may detect abnormalities in the autonomic nervous function and predict the occurrence of syncope during SVT. Electrophysiology studies may reproduce the SVT, distinguish it from other life-threatening ventricular tachyarrhythmias, and exclude other causes of syncope. Not infrequently mixed syncope mechanisms are revealed during the above diagnostic workup raising doubts about the operating mechanism in the clinical setting. In such cases of uncertainty, an implantable loop recorder, providing long-term cardiac monitoring, may play a pivotal role in the establishment of the diagnosis, confirming the association of an arrhythmic event with the symptom. Herein, we present four such cases with recurrent unexplained syncope finally attributed to paroxysmal SVT guiding them to a potentially radical treatment through radiofrequency catheter ablation.

Arrhythmic risk stratification in post-myocardial infarction patients with preserved ejection fraction: the PRESERVE EF study.

AIMS: Sudden cardiac death (SCD) annual incidence is 0.6-1% in post-myocardial infarction (MI) patients with left ventricular ejection fraction (LVEF)≥40%. No recommendations for implantable cardioverter-defibrillator (ICD) use exist in this population. METHODS AND RESULTS: We introduced a combined non-invasive/invasive risk stratification approach in post-MI ischaemia-free patients, with LVEF ≥ 40%, in a multicentre, prospective, observational cohort study. Patients with at least one positive electrocardiographic non-invasive risk factor (NIRF): premature ventricular complexes, non-sustained ventricular tachycardia, late potentials, prolonged QTc, increased T-wave alternans, reduced heart rate variability, abnormal deceleration capacity with abnormal turbulence, were referred for programmed ventricular stimulation (PVS), with ICDs offered to those inducible. The primary endpoint was the occurrence of a major arrhythmic event (MAE), namely sustained ventricular tachycardia/fibrillation, appropriate ICD activation or SCD. We screened and included 575 consecutive patients (mean age 57 years, LVEF 50.8%). Of them, 204 (35.5%) had at least one positive NIRF. Forty-one of 152 patients undergoing PVS (27-7.1% of total sample) were inducible. Thirty-seven (90.2%) of them received an ICD. Mean follow-up was 32 months and no SCDs were observed, while 9 ICDs (1.57% of total screened population) were appropriately activated. None patient without NIRFs or with NIRFs but negative PVS met the primary endpoint. The algorithm yielded the following: sensitivity 100%, specificity 93.8%, positive predictive value 22%, and negative predictive value 100%. CONCLUSION: The two-step approach of the PRESERVE EF study detects a subpopulation of post-MI patients with preserved LVEF at risk for MAEs that can be effectively addressed with an ICD. CLINICALTRIALS.GOV IDENTIFIER: NCT02124018.

Percutaneous lead extraction and repositioning: An effective and safe therapeutic strategy for early ventricular lead perforation with dislocation both inside and outside the pericardial sac following a cardiac device implantation.

INTRODUCTION: Cardiac perforation of the right ventricle associated with pacemaker or implantable cardioverter defibrillator (ICD) leads' implantation is uncommon, albeit potentially life-threatening, complication. The aim of this study is to further identify the optimal therapeutic strategy, especially when lead dislocation has occurred outside the pericardial sac. METHODS AND RESULTS: The study population included 10 consecutive patients (six female, mean age: 66.5 years old) diagnosed with early ventricular lead perforation following a pacemaker or ICD implantation, with significant protrusion inside the pericardial sac (n = 2) or migration of the lead at the pleural space ( n = 3), the diaphragm ( n = 1), or the abdominal cavity ( n = 4), during the period 2013-2017. All patients were symptomatic; however, individuals presenting with hemodynamic instability were excluded. The outcome of the percutaneous therapeutic approach was retrospectively assessed. All patients underwent a successful removal of the perforating lead percutaneously at the electrophysiology lab, by direct traction, and repositioning in another location of the right ventricle. The operation was performed by a multidisciplinary team, under continuous hemodynamic and transesophageal echocardiographic monitoring and cardiac surgical backup. The periprocedural period was uneventful. Subjects were followed up for at least 1 year. Interestingly, all patients developed a type of postcardiac injury syndrome, successfully treated with a 3-month regimen of ibuprofen and colchicine. CONCLUSION: Percutaneous traction and repositioning of the perforating ventricular lead are effective, safe, and less invasive compared with the thoracotomy method in hemodynamically stable patients when dislocation has occurred outside the pericardial sac provided that there is no visceral organs injury.

T wave alternans extracted from 30-minute short resting Holter ECG recordings predicts mortality in heart failure.

BACKGROUND: We extracted T Wave Alternans (TWA) from a 30 minute Short Resting Holter ECG (SRH ECG) in the supine position, as a Total Mortality (TM) predictor in Heart Failure (HF). METHODS: Signals from 146 HF patients (LVEF = 33 ±â€¯10%), were analyzed with Modified Moving Average method. After 42.1 months, 26 patients died. RESULTS: (Deceased vs Living group): TWA:31 ±â€¯18 µV vs 25 ±â€¯13 µV(p = 0.05), LVEF:32 ±â€¯10% vs 34 ±â€¯9% (p = 0.5), Heart Rate:73 ±â€¯11 bpm vs 69 ±â€¯12 bpm (p = 0.2), SDNN/HRV:45 ±â€¯42 ms vs 41 ±â€¯29 ms (p = 0.4), QRS:123 ±â€¯26 ms vs 119 ±â€¯29 ms (p = 0.5).Cox regression model adjusted for TWA, LVEF and QRS, revealed that the TWA was an independent TM predictor (H.R.: 1.022, 95% C.I.: 0.999-1.046, p = 0.05).The TWA ≥ 42 µV demonstrated HR: 2.521, (95% C.I.: 0.982-6.472, p = 0.05). CONCLUSIONS: In severely affected HF patients, TWA from a SRH ECG may be present even during slow resting heart rates and proved to be an important and independent TM predictor. The SRH ECG recording is an efficient and fast method for mortality risk evaluation in HF patients.

Arrhythmic risk stratification in heart failure: Time for the next step?

BACKGROUND: Primary prevention of sudden cardiac death by means of implantable cardioverter-defibrillators constitutes the holy grail of arrhythmology. However, current risk stratification algorithms lead to suboptimal outcomes, by both allocating ICDs to patients not deriving any meaningful survival benefit and withholding them from those erroneously considered as low-risk for arrhythmic mortality. METHODS: In the present review article we will attempt to present shortcomings of contemporary guidelines regarding sudden death prevention in ischemic and dilated cardiomyopathy patients and present available data suggesting encouraging results following implementation of multifactorial approaches, by using multiple modalities, both noninvasive and invasive. Invasive electrophysiological testing, namely programmed ventricular stimulation, will be discussed in greater length to highlight both its potential usefulness and currently ongoing multicenter studies aiming to provide evidence necessary to make the next step in sudden death risk stratification. RESULTS: Promising findings have been reported by multiple study groups regarding novel strategies for both negative selection of low and positive selection of relatively preserved ejection fraction patients as candidates for ICD implantation. CONCLUSIONS: The era of ejection fraction as the sole risk stratifier for arrhythmic risk in heart failure appears to be drawing to an end, especially if current underway large studies validate previous findings.

Infection control in implantation of cardiac implantable electronic devices: current evidence, controversial points, and unresolved issues.

A significant increase in the implantation of cardiac implantable electronic devices (CIEDs) is evident over the past years, while there is evidence for a disproportionate increase in CIED-related infections. The cumulative probability of device infection seems to be higher in implantable cardioverter defibrillator and in cardiac resynchronization therapy patients compared with permanent pacemaker patients. Given that more than a half of CIED infections are possibly related to the operative procedure, there is a need for effective periprocedural infection control. However, many of the current recommendations are empirical and not evidence-based, while questions, unresolved issues, and conflicting evidence arise. The perioperative systemic use of antibiotics confers significant benefit in prevention of CIED infections. However, there are no conclusive data regarding the specific value of each agent in different clinical settings, the value of post-operative antibiotic treatment as well as the optimal duration of therapy. The merit of local pocket irrigation with antibiotic and/or antiseptic agents remains unproved. Of note, recent evidence indicates that the application of antibacterial envelopes into the device pocket markedly decreases the infection risk. In addition, limited reports on strict integrated infection control protocols show a dramatic reduction in infection rates in this setting and therefore deserve further attention. Finally, the relative impact of particular factors on the infection risk, including the type of the CIED, patients' individual characteristics and comorbidities, should be further examined since it may facilitate the development of tailored prophylactic interventions for each patient.

Left Ventricular Pacing through Coronary Sinus Is Feasible and Safe for Patients with Prior Tricuspid Valve Intervention.

BACKGROUND: In the presence of tricuspid valve intervention, right ventricular lead implantation is associated with the potential risk of tricuspid valve malfunction leading to a tricuspid regurgitation. Few cases have been reported with successful left ventricular pacing via the coronary sinus (CS) after tricuspid valve replacement or repair. In this retrospective study, we present the long-term clinical outcomes of 17 patients who underwent CS lead implantation and left ventricular pacing. METHODS: Seventeen consecutive patients referred to our institution with an indication of postprocedural pacemaker (PM) implantation after tricuspid valve intervention were retrospectively included in the study. The indication for device implantation in all patients was atrial fibrillation with a symptomatic pause ≥ 3.0 seconds. Thus, all devices implanted were ventricular rate responsive (VVIR). RESULTS: All device implantations were successful and uncomplicated. Mean operation time was 60 ± 8 minutes. Mean fluoroscopy time was 8.3 ± 2.1 minutes. Mean R-wave sensing was 7.5 ± 2.0 mV with a mean slew rate of 2.2 V/s. A mean pacing threshold of 1.9 ± 0.3 V/0.4 ms was accepted as patients were not PM-dependent. The pacing impedance was 743.5 ± 109.71 Ohm. At 2-year follow-up, pacing sensing, threshold, and impedance values were unchanged and no lead dislodgement has been noted. CONCLUSIONS: In patients with tricuspid valve intervention, left ventricular pacing might be the treatment of choice for permanent ventricular pacing, with all the advantages of the endovenous route as a minimally invasive approach.

Outcomes of Same Day Pacemaker Implantation after TAVI.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) is often associated with conduction disturbances, followed by permanent pacemaker (PPM) implantation. Because of the potential reversibility of these conduction disorders, controversy exists regarding the right timing of PPM implantation. TAVI is routinely performed under dual-antiplatelet and antithrombotic therapy, which poses an additional hemorrhagic risk on a same-day procedure. The aim of the present study was to evaluate the safety and effectiveness of same-day PPM implantation in patients undergoing TAVI. METHODS: Consecutive patients undergoing TAVI with Medtronic Corevalve bioprosthesis (Medtronic Inc., Minneapolis, MN, USA) in a tertiary center were divided into two study groups. Group A included patients undergoing PPM implantation the same day with TAVI, and Group B patients were implanted with a PPM later after TAVI and before hospital discharge. The two study groups were compared for all complications associated with PPM implantation. RESULTS: In total, 168 patients were included in the study. PPM was implanted in 65 patients (38.7%). In 23 patients, a PPM was implanted the same day with TAVI (Group A) and in 42 patients PPM implantation was postponed at least 1 day (Group B). Cephalic vein was the access used for the leads in the majority of cases. There was only one case of pneumothorax in Group B. There were no differences in the incidence of pocket hematomas between the study groups. CONCLUSIONS: Same-day PPM implantation after TAVI is safe and feasible. Strategies reducing pocket hematomas are essential in such patients of high hemorrhagic risk.

Wireless Device Therapy in Hypertrophic Cardiomyopathy Using the Combination of a Leadless Pacemaker and a Subcutaneous Defibrillator: A Report with 2-year Follow-up of Two Patients.

Cardiac implantable electronic devices (CIEDs) are essential tools in cardiology for tackling rhythm disturbances and have come a long way over the last decades. Technology is shifting toward leadless devices that spare the complications and limitations of traditional intravascular CIEDs. Herein, we report the simultaneous implantation of a leadless pacemaker (LP) and a subcutaneous implantable cardioverter-defibrillator (S-ICD) in two patients with hypertrophic cardiomyopathy, as well as their 2-year follow-up results, while explaining the preventive measures taken to steer around unwanted device interaction. Implantation of an S-ICD with an LP is reserved for unique cases but is a feasible approach when there is a contraindication for intravascular CIED implantation. Furthermore, this technique may be used in younger patients with cardiomyopathies in whom multiple generator replacements are expected, along with their known adverse effects.

Ischemia testing and revascularization in patients with monomorphic ventricular tachycardia: A relic of the past?

Testing for myocardial ischemia in patients presenting with sustained monomorphic Ventricular Tachycardia(VT) even without evidence of acute myocardial infarction is a tempting strategy that is frequently utilized in clinical practice. Monomorphic VT is mainly caused by re-entry around chronic myocardial scar and active ischemia has no role in its pathogenesis, thus making testing for ischemia futile, at least in theory. This systematic literature review sought to address the usefulness of ischemia testing (mainly coronary angiography) in patients presenting with monomorphic VT through 8 selected studies after evaluating a total of 130 published manuscripts. Particularly, we sought to unveil whether coronary angiography and possibly concomitant revascularization leads to lesser tachycardia recurrence. Our conclusion can be summarized as follows: this approach whether combined with revascularization or not, does not seem to reduce VT recurrence nor does it affect mortality in such patients. Even though most of the published literature points at this direction, validation from randomized controlled trials is imperative.