Search

Background: The Subcutaneous-ICD (S-ICD) is emerging as a suitable option for most ICD candidates, however some open issues regarding the sensing algorithm still remain. Objectives: We aimed to examine the performance of the S-ICD sensing algorithm in patients hospitalized for ST elevation myocardial infarction (STEMI), non ST elevation acute coronary syndrome (NSTE-ACS) or chronic coronary syndrome (CCS), before and after revascularization. Methods: We performed a S-ICD automated screening on 75 patients, 21 hospitalized for STEMI, 23 for NSTE-ACS and 31 for CCS, before and after percutaneous revascularization, regardless their eligibility to ICD implantation. Results: Patients did not differ in clinical, electrocardiographic and echocardiographic parameters. Rates of screening pass were significantly lower in STEMI patients compared to NSTE-ACS and CCS (5% vs 56.7% vs 81% respectively, p

Abstract: Cardiogenic shock (CS) is a life-threatening condition. The aim of this study is to evaluate the clinical characteristics, management, and complication rate of patients with CS admitted to a high-volume hospital in Italy. We retrospectively reviewed the clinical, echocardiographic, and laboratory data, therapeutic management, and outcomes of patients with CS admitted to the Policlinico Gemelli (Rome) between January 1, 2020, and January 1, 2023. We included 96 patients [median age 71 years, interquartile range 60-79; 65 (68%) males], of whom 49 patients (51%) presented CS secondary to acute myocardial infarction and 60 (63%) with a de novo presentation of CS. Dobutamine was the most frequently used inotrope and noradrenaline the most frequently used vasopressor (adopted in 56% and 82% of cases, respectively). Forty-five (47%) patients died during the hospitalization. Nonsurvivors were older and had a higher inflammatory burden at admission, elevated lactate levels, a greater increase in lactate levels, higher left ventricular filling pressures, and worse right ventricular function. C-reactive protein levels [odds ratio (OR) 1.03, 95% confidence interval (CI) (1.00-1.04), P = 0.027], lactate levels at admission (OR 3.49, 95% CI, 1.59-7.63, P = 0.02), and increase in lactate levels (OR 2.8, 95% CI, 1.37-5.75, P = 0.005) were independent predictors of in-hospital all-cause death. Our data contribute to the assessment of the regional variations in the management and outcomes of patients with CS. We observed a high mortality and complication rate. Lactate acidosis and C-reactive protein measured at admission may help in identifying patients at higher risk of adverse in-hospital outcomes., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Cardiac implantable electronic devices (CIEDs) offer the benefit of remote monitoring and decision making and find particular applications in special populations such as the elderly. Less transportation, reduced costs, prompt diagnosis, a sense of security, and continuous real-time monitoring are the main advantages. On the other hand, less physician-patient interactions and the technology barrier in the elderly pose specific problems in remote monitoring. CIEDs nowadays are abundant and are mostly represented by rhythm control/monitoring devices, whereas hemodynamic remote monitoring devices are gaining popularity and are evolving and becoming refined. Future directions include the involvement of artificial intelligence, yet disparities of availability, lack of follow-up data, and insufficient patient education are still areas to be improved. This review aims to describe the role of CIED in the very elderly and highlight the merits and possible drawbacks.

Recently, prognosis and survival of cancer patients has improved due to progression and refinement of cancer therapies; however, cardiovascular sequelae in this population augmented and now represent the second cause of death in oncological patients. Initially, the main issue was represented by heart failure and coronary artery disease, but a growing body of evidence has now shed light on the increased arrhythmic risk of this population, atrial fibrillation being the most frequently encountered. Awareness of arrhythmic complications of cancer and its treatments may help oncologists and cardiologists to develop targeted approaches for the management of arrhythmias in this population. In this review, we provide an updated overview of the mechanisms triggering cardiac arrhythmias in cancer patients, their prevalence and management.

Introduction and Objectives: The clinical value of electrocardiogram (ECG) repolarization parameters associated with ventricular arrhythmias (VAs) in tako-tsubo syndrome is still under debate. We aimed to evaluate ECG predictors of subacute VAs, defined as those occurring after the first 48hours from admission., Methods: This single-center observational study enrolled patients admitted to the cardiology department between 2012 and 2018 with a confirmed diagnosis of tako-tsubo syndrome. Data collection included a 12-lead ECG on admission and at 48hours, continuous telemetry monitoring, blood testing, transthoracic echocardiography, and coronary angiography during hospitalization. VAs events were defined as: premature ventricular contractions ≥ 2000 within a 24-hour window of telemetry monitoring, ventricular fibrillation, sustained ventricular tachycardia (VT), polymorphic VT, and non-sustained VT., Results: A total of 87 patients (age 72±12 years) were enrolled. During a median of 8 days of hospitalization, subacute VAs were documented in 22 patients (25%) after a median of 91hours from admission. Subacute VAs were associated with an increase in mortality during hospitalization (P=.030). The corrected global (mean of the 12-lead ECG values) Tpeak-Tend interval at 48hours from admission was an independent predictor of subacute VAs and was statistically superior to the standard corrected QT interval (Z test, P=.040). A cut-off of 108 msec for the corrected global Tpeak-Tend yielded a 71% sensitivity and 72% specificity for subacute VAs., Conclusions: In patients with tako-tsubo syndrome, subacute VAs are associated with repolarization alterations that can be identified on conventional ECG using the Tpeak-Tend interval., (Copyright © 2022. Published by Elsevier España, S.L.U.)

Background: Adults with congenital heart disease (ACHD) are often affected by cardiac arrhythmias requiring catheter ablation. Catheter ablation in this setting represents the treatment of choice but is flawed by frequent recurrencies. Predictors of arrhythmia relapse have been identified, but the role of cardiac fibrosis in this setting has not been investigated. The aim of this study was to determine the role of the extension of cardiac fibrosis, detected by electroanatomical mapping, in predicting arrhythmia recurrencies after ablation in ACHD., Materials and Methods: Consecutive patients with congenital heart disease and atrial or ventricular arrhythmias undergoing catheter ablation were enrolled. An electroanatomical bipolar voltage map was performed during sinus rhythm in each patient and bipolar scar was assessed according to the current literature data. During follow-up, arrhythmia recurrences were recorded. The relationship between the extent of myocardial fibrosis and arrhythmia recurrence was assessed., Results: Twenty patients underwent successful catheter ablation of atrial (14) or ventricular (6) arrhythmias, with no inducible arrhythmia at the end of the procedure. During a median follow-up period of 207 weeks (IQR 80 weeks), eight patients (40%; five atrial and three ventricular arrhythmias) had arrhythmia recurrence. Of the five patients undergoing a second ablation, four showed a new reentrant circuit, while one patient had a conduction gap across a previous ablation line. The extension of the bipolar scar area (HR 1.049, CI 1.011-1.089, p = 0.011) and the presence of a bipolar scar area >20 cm 2 (HR 6.101, CI 1.147-32.442, p = 0.034) were identified as predictors of arrhythmia relapse., Conclusion: The extension of the bipolar scar area and the presence of a bipolar scar area >20 cm 2 can predict arrhythmia relapse in ACHD undergoing catheter ablation of atrial and ventricular arrhythmias. Recurrent arrhythmias are often caused by circuits other than those previously ablated.

Introduction: Monomorphic ventricular tachycardia (VT) is a life-threatening condition often observed in patients with structural heart disease. Ventricular tachycardia ablation through radiation therapy (VT-ART) for sustained monomorphic ventricular tachycardia seems promising, effective, and safe. VT-ART delivers focused, high-dose radiation, usually in a single fraction of 25 Gy, allowing ablation of VT by inducing myocardial scars. The procedure is fully non-invasive; therefore, it can be easily performed in patients with contraindications to invasive ablation procedures. Definitive data are lacking, and no direct comparison with standard procedures is available., Discussion: The aim of this multicenter observational study is to evaluate the efficacy and safety of VT-ART, comparing the clinical outcome of patients undergone to VT-ART to patients not having received such a procedure. The two groups will not be collected by direct, prospective accrual to avoid randomization among the innovative and traditional arm: A retrospective selection through matched pair analysis will collect patients presenting features similar to the ones undergone VT-ART within the consortium (in each center independently). Our trial will enroll patients with optimized medical therapy in whom endocardial and/or epicardial radiofrequency ablation (RFA), the gold standard for VT ablation, is either unfeasible or fails to control VT recurrence. Our primary outcome is investigating the difference in overall cardiovascular survival among the group undergoing VT-ART and the one not exposed to the innovative procedure. The secondary outcome is evaluating the difference in ventricular event-free survival after the last procedure (i.e., last RFA vs. VT-ART) between the two groups. An additional secondary aim is to evaluate the reduction in the number of VT episodes comparing the 3 months before the procedure to the ones recorded at 6 months (from the 4th to 6th month) following VT-ART and RFA, respectively. Other secondary objectives include identifying the benefits of VT-ART on cardiac function, as evaluated through an electrocardiogram, echocardiographic, biochemical variables, and on patient quality of life. We calculated the sample size (in a 2:1 ratio) upon enrolling 149 patients: 100 in the non-exposed control group and 49 in the VT-ART group. Progressively, on a multicentric basis supervised by the promoting center in the VT-ART consortium, for each VT-ART patient enrollment, a matched pair patient profile according to the predefined features will be shared with the consortium to enroll a patient that has not undergone VT-ART., Conclusion: Our trial will provide insight into the efficacy and safety of VT-ART through a matched pair analysis, via an observational, multicentric study of two groups of patients with or without VT-ART in the multicentric consortium (with subgroup stratification into dynamic cohorts)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Cellini, Narducci, Pavone, Bencardino, Perna, Pinnacchio, Chiesa, Massaccesi, Gambacorta, Manfrida, Longo, Mannocci, Di Gregorio, Boldrini, Tagliaferri, Indovina, Placidi, Stimato, Spera, Scacciavillani, Crea, Valentini and Pelargonio.)

Abstract: Wearable cardioverter defibrillator has revealed a crucial device both in patients with a clear indication of ICD implantation but with temporary contraindications or in expectation of a diagnosis, considering that its use should be individualized.

Introduction: Unrecognized incomplete pulmonary vein (PV) isolation during the index procedure, can be a major cause of clinical recurrences of atrial fibrillation (AF) after cryoballoon (CB) ablation. We aimed to characterize the extension of the lesions produced by CB ablation and to assess the value of using an ultra-high resolution electroanatomic mapping (UHDM) system to detect incomplete CB lesions., Materials and Methods: Twenty-nine consecutive patients from the CHARISMA registry undergoing AF ablation at four Italian centers were prospectively evaluated. The Rhythmia™ mapping system and the Orion™ (Boston Scientific) mapping catheter were used to systematically map the left atrium and PVs before and after cryoablation., Results: A total of 116 PVs were targeted and isolated. Quantitative assessment of the lesions revealed a significant reduction of the antral surface area of the PV, resulting in an ablated area of 5.7 ± 0.7 cm 2 and 5.1 ± 0.8 cm 2 for the left PV pair and right PV pair, respectively ( p = 0.0068). The mean posterior wall (PW) area was 22.9 ± 2 cm 2 and, following PV isolation, 44.8 ± 6% of the PW area was ablated. After CB ablation, complete isolation of each PV was documented by the POLARMap™ catheter in all patients. By contrast, confirmatory UHDM and the Lumipoint™ tool unveiled PV signals in 1 out of 114 of the PVs (0.9%). Over 30-day follow-up, no major procedure-related adverse events were reported. After a mean follow-up of 333 days, 89.7% of patients were free from arrhythmia recurrence., Conclusion: The lesion extension achieved by the new CB ablation system involved the PV antrum, with less than 50% of the PW remaining untouched. The new system, with short tip and circular mapping catheter, failed to achieve PV isolation in only 0.9% of all PVs treated., Clinical Trial Registration: [http://clinicaltrials.gov/], identifier [NCT03793998]., Competing Interests: Authors MM and FPi were salaried Boston Scientific employees. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Spera, Narducci, Bencardino, Perna, Bisignani, Pinnacchio, Tondo, Maggio, Stabile, Iacopino, Tundo, Ferraro, De Simone, Malacrida, Pintus, Crea and Pelargonio.)

Permanent pacemaker implantation (PPI) represents a frequent complication after transcatheter aortic valve implantation (TAVI) due to atrio-ventricular (AV) node injury. Predictors of early AV function recovery were investigated. We analyzed 50 consecutive patients (82 ± 6 years, 58% males, EuroSCORE: 7.8 ± 3.3%, STS mortality score: 5 ± 2.8%). Pacemaker interrogations within 4−6 weeks from PPI were performed to collect data on AV conduction. The most common indication of PPI was persistent third-degree (44%)/high-degree (20%) AV block/atrial fibrillation (AF) with slow ventricular conduction (16%) after TAVI. At follow-up, 13 patients (26%) recovered AV conduction (i.e., sinus rhythm with stable 1:1 AV conduction/AF with a mean ventricular response >50 bpm, associated with a long-term ventricular pacing percentage < 5%). At multivariate analysis, complete atrio-ventricular block independently predicted pacemaker dependency at follow-up (p = 0.019). Patients with persistent AV dysfunction showed a significant AV conduction time prolongation after TAVI (PR interval from 207 ± 50 to 230 ± 51, p = 0.02; QRS interval from 124 ± 23 to 147 ± 16, p < 0.01) compared to patients with recovery, in whom AV conduction parameters remained unchanged. Several patients receiving PPI after TAVI have recovery of AV conduction within a few weeks. Longer observation periods prior to PPI might be justified, and algorithms to minimize ventricular pacing should be utilized whenever possible.

Background: Atrioventricular (AV) conduction disturbances requiring permanent pacemaker implantation (PPI) are a common complication after transcatheter aortic valve implantation (TAVI). However, a significant proportion of patients might recover AV conduction at follow-up., Objectives: The aim of our study was to evaluate the recovery of AV conduction by determination through Wenckebach point in patients with PPI and therefore identify patients who could benefit from device reprogramming to avoid unnecessary RV pacing., Methods: We enrolled 43 patients that underwent PM implantation after TAVI at our Department from January 2018 to January 2021. PM interrogation was performed at follow-up and patients with native spontaneous rhythm were further assessed for AV conduction through WP determination., Results: A total of 43 patients requiring a PM represented the final study population, divided in patients with severely impaired AV conduction (no spontaneous valid rhythm or WP < 100; 26) and patients with valid AV conduction (WP ≥ 100; 17). In the first group patients had a significantly higher number of intraprocedural atrioventricular block (AVB) (20 vs. 1, p < 0.005), showed a significant higher implantation depth in LVOT (7.7 ± 2.2 vs. 4.4 ± 1.1, p < 0.05) and lower ΔMSID (-0.28 ± 3 vs. -3.94 ± 2, p < 0.05)., Conclusion: AV conduction may recover in a significant proportion of patients. In our study, valve implantation depth in the LVOT and intraprocedural AV block are associated with severely impaired AV conduction. Regular PM interrogation and reprogramming are required to avoid unnecessary permanent right ventricular stimulation in patients with AV conduction recovery., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Pelargonio, Scacciavillani, Donisi, Narducci, Aurigemma, Pinnacchio, Bencardino, Perna, Spera, Comerci, Ruscio, Romagnoli, Crea, Burzotta and Trani.)

Background: Sleep apnea syndrome (SAS) has been reported to be associated with a higher incidence of ventricular arrhythmias. The aim of this study was twofold: (1) to investigate whether in SAS patients receiving an implantable cardioverter defibrillator (ICD) the severity of SAS was associated with the occurrence of ventricular arrhythmias; (2) to assess whether changes in nocturnal apnoic/hypopnoic episodes may favor the occurrence of life-threatening arrhythmias, that is, sustained ventricular tachycardia (VT)/fibrillation (VF), requiring ICD intervention., Methods: We enrolled 46 patients with documented SAS at polysomnography (apnea/hypopnea index [AHI] > 5) who also had a left ventricle ejection fraction (LVEF) < 35% and, according to primary prevention indications, implanted an ICD (Boston Scientific Incepta) able to daily monitor apnoic/hypopnoic episodes occurring during sleep. Patients were followed at 3-month intervals., Results: At a mean follow-up of 18 months, 21 episodes of sustained VT/FV requiring ICD intervention were documented in eight patients (17.4%). Baseline AHI was significantly higher in patients with compared to those without ICD intervention. ICD interventions, however, were not preceded by any worsening of apnoic/hypopnoic episodes. The respiratory disturbance index (RDI) of the week during the event, indeed, was not different from that recorded during the previous 2 weeks (25.4 ± 11, 25.6 ± 10 and 25.1 ± 10, respectively; p = .9)., Conclusions: In patients with SAS who received an ICD for primary prevention of sudden death, those with ICD interventions showed a more severe form of the disease at baseline. ICD interventions, however, were not preceded by any significant changes in SAS severity., (© 2021 Wiley Periodicals LLC.)

Background: The Subcutaneous-ICD (S-ICD) is emerging as a suitable option for most ICD candidates, however some open issues regarding the sensing algorithm still remain., Objectives: We aimed to examine the performance of the S-ICD sensing algorithm in patients hospitalized for ST elevation myocardial infarction (STEMI), non ST elevation acute coronary syndrome (NSTE-ACS) or chronic coronary syndrome (CCS), before and after revascularization., Methods: We performed a S-ICD automated screening on 75 patients, 21 hospitalized for STEMI, 23 for NSTE-ACS and 31 for CCS, before and after percutaneous revascularization, regardless their eligibility to ICD implantation., Results: Patients did not differ in clinical, electrocardiographic and echocardiographic parameters. Rates of screening pass were significantly lower in STEMI patients compared to NSTE-ACS and CCS (5% vs 56.7% vs 81% respectively, p < .0001). The viability of the primary vector was lower in STEMI patients compared to NSTE-ACS and CCS (33% vs 56% vs 71%, p .027 respectively). After revascularization, there were no more significant differences between groups. Pairing subjects at baseline and after revascularization, STEMI subjects percentages of screening success were respectively 5% and 81% (p < .001) and the rates of primary vector viability were 33% and 81% (p .002). STEMI was the only independent predictor of screening failure at multivariate logistic regression analysis (odds ratio 10.68 confidence interval 2.77-41.38, p = .001)., Conclusion: The performance of the S-ICD and possible malfunction detections in the context of an acute ischemic event deserve further evaluation. Adequate patient selection and the development of dynamic device programming are warranted., Competing Interests: The authors report no relationships that could be construed as a conflict of interest., (© 2021 The Authors.)

Background: Life-threatening ventricular tachyarrhythmias (VAs) represent a significant cause of death in myocarditis., Objective: The purpose of this study was to identify predictors of sustained VAs in patients with myocarditis and ventricular phenotype diagnosed by workflow including endomyocardial biopsy (EMB) guided by 3D electroanatomic mapping (3D-EAM)., Methods: We prospectively enrolled patients with suspected myocarditis and VAs, undergoing cardiac magnetic resonance imaging, coronary angiography, 3D-EAM, and EMB guided by 3D-EAM. At follow-up, sustained VAs were detected by device interrogation and 24-hour electrocardiographic Holter monitoring., Results: We enrolled 54 consecutive patients (mean age 41 ± 14 years; 32(59%) men) with normal ventricular function; left ventricular and right ventricular (RV) late gadolinium enhancement was present, respectively, in 21 (46%) and 6 (13%) of the 46 patients who underwent cardiac magnetic resonance. In 31 patients, the histological diagnosis was myocarditis, while in 14 patients, focal replacement myocardial fibrosis (FRMF); in 9 patients, specimens were inadequate (diagnostic yield of EMB 83%). 3D-EAM showed a larger endocardial scar area for both ventricles in myocarditis than in FRMF (RV bipolar mean scar area 22 ± 16 cm 2 vs 3 ± 2 cm 2 ; P = .02; left ventricular bipolar mean scar area 13 ± 5 cm 2 vs 4 ± 2 cm 2 ; P = .02, respectively). At a follow-up of 21 months, freedom from sustained VAs was 58% in myocarditis and 92% in FRMF (log-rank, P = .008). Histological diagnosis of myocarditis and RV endocardial scar were independent predictors of sustained VAs (P = .02 for both)., Conclusion: Our data highlight the need for 3D-EAM-guided EMB in apparently healthy young patients with suspected myocarditis and VAs., (Copyright © 2021 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Aims: To investigate predictors of the occurrence of subacute ventricular arrhythmias (VAs), defined as any VAs presenting after 48 h from admission in patients with Takotsubo Syndrome (TTS), and to evaluate the related in-hospital mortality., Methods: This is a retrospective single-center study enrolling patients admitted between 2012 and 2017 with TTS according to International Takotsubo diagnostic criteria. Data collection included ECG on admission and at 48 h, telemetry monitoring and transthoracic echocardiogram., Results: We enrolled 93 patients; during in-hospital stay (mean 14 ± 16 days) subacute VAs occurred in 25% of patients (VAs group). Life-threatening VAs occurred in 6% of patients (3 sustained ventricular tachycardia, 1 torsade de pointes, 1 ventricular fibrillation) and not life-threatening VAs in 19% (6 non-sustained ventricular tachycardia and 12 premature ventricular contractions > 2000 in 24 h). Mortality was higher in the VAs than in the non-VAs group (P = 0.03), without differences in terms of life-threatening and not life-threatening subacute VAs (P = 0.65) and VAs on admission (P = 0.25). Logistic regression identified the following independent predictors of subacute VAs occurrence: VAs on admission {odds ratio [OR] 22.5 (3.9-131.8), P = 0.001]}, New York Heart Association (NYHA) class III-IV on admission [OR 6.7 (1.3- 34.0), P = 0.021] and QTc at 48 h [OR 1.01 (1.00-1.03), P = 0.046]., Conclusion: TTS patients with VAs and NYHA class III-IV on admission and higher QTc at 48 h are at increased risk of subacute VAs occurrence, associated with higher in-hospital mortality. Awareness of this potential complication is critical for proper patients management., (Copyright © 2020 Italian Federation of Cardiology - I.F.C. All rights reserved.)

The diagnosis of structural heart disease in athletes with ventricular arrhythmias (VAs) and an apparently normal heart can be very challenging. Several pieces of evidence demonstrate the importance of an extensive diagnostic work-up in apparently healthy young patients for the characterization of concealed cardiomyopathies. This study shows the various diagnostic levels and tools to help identify which athletes need deeper investigation in order to unmask possible underlying heart disease.

Objectives: This study sought to assess long-term arrhythmic risk in patients with myocarditis who received an implantable cardioverter-defibrillator (ICD)., Background: The arrhythmic risk of patients with myocarditis overtime remains poorly known., Methods: The study enrolled 56 patients with biopsy-proven myocarditis who received an ICD for either primary (57%) or secondary prevention (43%) according to current guidelines. Clinical characteristics, biopsy findings, electrophysiological data from endocardial 3-dimensional electroanatomic voltage mapping, and device interrogation data were analyzed to detect arrhythmic events overtime. Coronary angiography excluded significant coronary artery disease in all patients., Results: At a mean follow-up of 74 ± 60 months (median 65 months), 25 (45%) patients had major ventricular arrhythmias treated by ICD intervention (76% being terminated by ICD shock and 24% by antitachyarrhythmia burst pacing). At multivariable analysis, the presence of sustained ventricular tachycardia on admission (hazard ratio: 13.0; 95% confidence interval: 2.0 to 35.0; p = 0.032) and the extension of the areas of low potentials at the bipolar endocardial mapping (hazard ratio: 1.19; 95% confidence interval: 1.04 to 1.37; p = 0.013) were the only independent predictors of appropriate ICD interventions. A cutoff value of 10% of abnormal bipolar area at electroanatomical ventricular mapping discriminated patients with appropriate ICD interventions with a sensitivity of 89% and a specificity of 85%., Conclusions: The study demonstrates that the prevalence of life-threatening ventricular arrhythmias in patients with myocarditis receiving an ICD according to current guidelines is high and the arrhythmic risk persists late overtime. Electroanatomical ventricular mapping may be a useful tool to identify patients at greater arrhythmic risk., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Ventricular arrhythmias (VAs) are the most common cause of death in athletes. The differences in the electroanatomic substrate in athletes and nonathletes with complex VA are unknown., Objective: The purpose of this study was to compare the electroanatomic substrate of complex VA in athletes vs nonathletes., Methods: The study prospectively enrolled young athletes and nonathletes with VA. Patients underwent 2-dimensional echocardiography, cardiac magnetic resonance (CMR) imaging, coronary angiography, 3-dimensional electroanatomic mapping (3D-EAM), and 3D-EAM-guided endomyocardial biopsy (EMB). Follow-up included 24-hour electrocardiographic Holter or implantable cardioverter-defibrillator/loop recorder interrogation for VA recurrence., Results: Thirty-three patients were enrolled: 18 competitive athletes (56%) and 15 nonathletes (44%). Left ventricular and right ventricular (RV) findings by echocardiography and CMR did not show structural disease. Nine athletes (50%) were asymptomatic compared to 1 nonathlete (7%; P <.05). Unifocal origin of VA was reported in 14 athletes (93%) and 17 nonathletes (94%). Athletes showed a larger RV unipolar than bipolar scar (18 ± 17 cm 2 vs 3 ± 3.8 cm 2 ; P = .04). Diagnostic yield of EMB was 50% in athletes and 40% in nonathletes. Among athletes, the final diagnosis was myocarditis in 2, arrhythmogenic ventricular right cardiomyopathy in 1, and focal replacement fibrosis in 1. Among nonathletes, EMB revealed focal replacement fibrosis in 4 cases. At median follow-up of 18.7 months, Kaplan-Meier curves showed lower VA recurrence in detrained athletes than nonathletes (53% vs 6%; P = .02)., Conclusion: This study showed the need for extensive diagnostic workup in apparently healthy young patients with complex VA in order to characterize concealed cardiomyopathies., (Copyright © 2019 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Little is known about the prognostic significance of non-sustained ventricular tachycardia (NS-VT) in outpatients scheduled for routine pacemaker controls. We therefore sought to investigate the prognostic significance of non-sustained ventricular tachycardia on stored electrograms in pacemaker recipients., Methods: We enrolled patients implanted with dual chamber pacemaker for atrioventricular block or sinus node dysfunction from 2010 to 2016, with LVEF> 45%, older than 18 years, with at least 3 device interrogations at follow-up. Data were collected about medical history, pharmacological therapy at implantation, pacemaker programming, NS-VT occurrence, long-term survival., Results: A total of 308 patients were included in the final analysis, with median follow-up time of 56 months. No ventricular arrhythmic episodes were documented in 221 patients (Group 1), whereas 87 had at least 1 episode of NS-VT during follow-up (Group 2). As a whole, 282 episodes of NS-VT were documented. There was a higher prevalence of previous myocardial infarction and slightly lower left ventricular ejection fraction (LVEF) in Group 2. The primary endpoint (all-cause mortality) occurred in 50 patients (22%) of Group 1 and 12 (14%) patients of Group 2 (p = 0.07). Clinical predictors of all-cause mortality at univariate analysis included age, LVEF and coronary artery disease (CAD). Only age and CAD, however, remained as predictors of mortality at multivariable analysis. A sizeable, but not statistically significant, portion of patients who died had a de novo occurrence of NS-VT at the last pacemaker check., Conclusion: Our data do not support a prognostic role for the detection of NS-VT during pacemaker controls., Competing Interests: The authors have declared that no competing interests exist.

Aims: Microvolt T-wave alternans (MTWA) has been found to predict fatal events in patients with coronary artery disease (CAD). In a previous study, we found that MTWA values are higher in patients with CAD, compared with apparently healthy individuals. In this study, we assessed the relation between CAD and MTWA in patients with a diagnosis based on coronary angiography results., Methods: We studied 98 consecutive patients undergoing coronary angiography for suspected CAD. All patients underwent a maximal exercise stress test (EST), and MTWA was measured in the precordial ECG leads. Patients were divided into three groups: 40 patients without any significant (>50%) stenosis (group 1); 47 patients with significant stenosis (group 2); and 11 patients with a previous percutaneous coronary intervention (PCI) who had no evidence of restenosis (group 3). EST was repeated after 1 month in 24 group 2 patients who underwent PCI and in 17 group 1 patients., Results: MTWA was significantly higher in group 2 (58.7 ± 24 μV) compared with group 1 (34.2  ± 15 μV, P < 0.01) and group 3 (43.2 ± 24 μV, P < 0.05). An MTWA greater than 60 μV had 95% specificity and 82% positive predictive value for obstructive CAD. At 1-month follow-up, MTWA decreased significantly in patients treated with PCI (from 61.3 ± 22 to 43.5 ± 17 μV; P < 0.001), but not in group 1 patients (from 50.5 ± 22 to 44.3 ± 19 μV, P = 0.19)., Conclusion: MTWA is increased in patients with obstructive CAD and is reduced by coronary revascularization. An assessment of MTWA can be helpful in identifying which patients with suspected CAD are likely to show obstructive CAD on angiography.

Aims: To assess the characteristics and determinants of heart rate turbulence (HRT) in individuals without any apparent heart disease and in patients with coronary artery disease (CAD)., Methods and Results: Heart rate turbulence parameters, turbulence onset (TO), and turbulence slope (TS) were calculated on 24 h electrocardiogram recordings in 209 individuals without any heart disease (group 1) and in 157 CAD patients (group 2). In group 1, only age independently predicted abnormal TO (≥0%) [odds ratio (OR), 1.05; P<0.001], while predictors of abnormal TS (≤2.5 ms/RR) were age (OR, 0.85; P < 0.001) and hypertension (OR, 0.19; P = 0.028). In group 2 patients, only age independently predicted TO (OR, 1.03; P = 0.038), while age (OR, 0.90; P = 0.001) and left ventricular ejection fraction (LVEF; OR, 1.07; P = 0.008) predicted TS. Heart rate turbulence values were different in groups 1 and 2. Turbulence onset was (mean, standard deviation) -1.80 ± 2.24 vs. -0.73 ± 1.61%, respectively (P < 0.001), whereas TS was (median, interquartile interval) 5.83 (3.25-10.55) vs. 2.93 (1.73-5.81) ms/RR, respectively (P < 0.001). Coronary artery disease group, however, did not predict abnormal HRT parameters in multivariable analyses, both in the whole population and when comparing two subgroups matched for age and gender. Age and (for TS) LVEF, indeed, were the only independent predictors of abnormal HRT., Conclusions: Age is a major HRT determinant both in subjects without any apparent heart disease and in stable CAD patients. Hypertension and LVEF contribute independently to HRT in these two groups, respectively. Coronary artery disease group was not by itself associated with abnormal HRT parameters in multivariable analyses., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)

Background: Circulating endothelial progenitor cells (EPCs) might limit endothelial dysfunction in patients with microvascular angina (MVA). Endothelial colony-forming cells (ECFCs; displaying the CD34+/KDR+/CD45- phenotype) are currently regarded as true EPCs. The aim of this study was to evaluate exercise-induced ECFC mobilization and platelet reactivity in patients with MVA or with obstructive coronary artery disease (CAD)., Methods and Results: Exercise stress test (EST) was performed in 20 MVA patients, 20 CAD patients and 20 controls. Platelet reactivity was assessed before and after EST as formation of monocyte-platelet aggregates (MPAs) and CD41 platelet expression, without and with adenosine diphosphate (ADP) stimulation. ECFC number was measured before and 24h after EST. At rest, MPAs and CD41 platelet expression increased more with ADP in MVA patients (+71±11.0% and +37±7.5%, respectively), than in CAD patients (+37±8.6% and +19±4.5%, respectively) and controls (+29±3.5% and +21±3.1%, respectively; P<0.001 for both). At rest, ECFCs tended to be lower in CAD patients, compared to MVA patients and controls (4.1±5.0%, 7.2±6.0% and 7.3±7.0% cells/10(5), respectively; P=0.056). After EST, ECFCs increased less in MVA patients (+2.8±11) compared to CAD patients (+3.3±15; P<0.05) and controls (+7.4±24; P<0.01)., Conclusions: In MVA patients, EST is able to blunt the peculiar increase of platelet reactivity to ADP present at rest; in contrast, no potential protective response of ECFCs to exercise was seen in these patients.

Objectives: The aim of our study was to assess the prognostic value of heart rate variability (HRV) in ST-segment elevation acute myocardial infarction (STEMI) patients treated by percutaneous transluminal coronary angioplasty (PTCA) and optimal medical therapy., Methods: We enrolled 182 consecutive patients with a first STEMI (59.1 ± 11 years; 82.4% men) treated by primary PTCA. HRV was assessed on 24-hour Holter ECG recordings before discharge and 1 and 6 months after discharge. The primary end point was the occurrence of major clinical events (MCE), defined as death or new acute myocardial infarction (AMI)., Results: At a follow-up of 42 ± 23 months, MCE occurred in 14 patients (7.6%; 3 deaths and 11 re-AMIs). HRV parameters before discharge were significantly lower in patients with MCE, with standard deviation of all RR intervals (SDNN) and very low frequency and low frequency (LF) amplitude being the most predictive variables. HRV assessed at follow-up instead did not significantly predict MCE. At multivariate analysis, only SDNN (HR 0.97; p = 0.02) and LF (HR 0.90; p = 0.04) remained significantly associated with MCE. Lower tertile SDNN and LF values were associated with a multivariate HR of 3.91 (p = 0.015) and of 2.92 (p = 0.048), respectively. Similar results were observed considering re-AMI only as the end point., Conclusions: In STEMI patients treated by PTCA, HRV assessed before discharge was an independent predictor of MCE and re-AMI., (Copyright © 2013 S. Karger AG, Basel.)

Background: Recent studies have suggested that early repolarization (ER) is associated with increased risk of ventricular tachyarrhythmias. Early repolarization in these studies, however, was defined as J-wave (terminal QRS slurring or notching) or J-point elevation rather than typical ST-segment elevation (STE). Prevalence and characteristics of these different findings in the general population are poorly known. In this study, we assessed prevalence and correlates of STE typical of ER and of J wave in a large population of noncardiac subjects., Methods: We prospectively collected electrocardiograms of 4176 consecutive subjects without heart disease at our hospital., Results: Early repolarization was found in 84 subjects (2.0%) and J wave in 663 (15.9%). Among ER subjects, a J wave was present in 60 (71.4%). Variables independently associated with both ER and J wave included young age, male sex, and lower heart rate. There was no increased history of symptoms (palpitations and syncope) possibly related to arrhythmias in STE or J-wave subjects., Conclusions: Typical ER pattern and J wave are common in noncardiac subjects, particularly in young people, and are not associated with symptoms potentially related to arrhythmias., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Aims: Microvolt T-wave alternans (TWA) predicts arrhythmic risk in patients with ischaemic heart disease (IHD). While TWA has widely been assessed by the spectral method, it has been poorly characterized in healthy people as well as in IHD patients by the modified moving average (MMA) method., Methods and Results: We enrolled 729 consecutive subjects, referred for exercise stress test (EST). T-wave alternans was assessed by the MMA method, considering all 12 electrocardiogram (ECG) leads (TWA&#95;tot) or the 6 ECG pre-cordial leads only (TWA&#95;prec). Patients were divided into five groups: (i) no history of IHD and normal EST (Group 1); (ii) no history of IHD but positive EST (Group 2); (iii) ischaemic heart disease without any acute myocardial infarction [AMI (Group 3)]; (iv) old AMI (Group 4); (v) recent AMI (Group 5). T-wave alternans values >95th percentile of those measured in Group 1 were considered 'abnormal'. The 95th percentile of TWA values in Group 1 was 75 µV for TWA&#95;tot and 65 µV for TWA&#95;prec. T-wave alternans values and prevalence of abnormal TWA increased from Groups 1-2 to Group 5 (P< 0.00001 for both). Group 4 and Group 5, compared with Group 1, showed a significant higher prevalence of abnormal values of TWA&#95;tot [odds ratio (OR) 1.70 (P= 0.002), and 2.07 (P= 0.01), respectively] and TWA&#95;prec [OR 1.51 (P= 0.02) and 2.37 (P= 0.003), respectively] at multivariable analysis. In IHD patients EST-induced ischaemia did not influence TWA; in AMI patients, impaired left ventricular function was associated with higher TWA values., Conclusions: In healthy people, TWA&#95;tot and TWA&#95;prec were ≤75 and ≤65 µV, respectively, in 95% of subjects. In IHD patients TWA values were higher compared with healthy individuals; a history of AMI was independently associated with abnormal TWA values.

Background: Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is associated with an increased risk of sudden cardiac death (SCD). Risk stratification of ARVC/D patients, however, remains an unresolved issue. In this study we investigated whether heart rate variability (HRV) can be helpful in identifying ARVC/D patients with increased risk of arrhythmic events., Methods and Results: We studied 30 consecutive patients (17 males; 45.4 ± 18 years) with ARVC/D, diagnosed according to guideline criteria; 15 patients (50%) had received an implantable cardioverter defibrillator (ICD) for primary SCD prevention. HRV was assessed on 24-h ECG Holter monitoring. The primary endpoint was the occurrence of major arrhythmic events (SCD, sustained ventricular tachycardia (VT), ICD therapy for sustained VT or ventricular fibrillation (VF)). During the follow-up period (19 ± 7 months), no deaths occurred, but 5 patients (17%) experienced arrhythmic events (4 VTs and 1 VF, all in the ICD group). All HRV parameters were significantly lower in patients with, compared with those without, arrhythmic events. Low-frequency amplitude was the most significant HRV variable associated with arrhythmic events in univariate Cox regression analysis (P=0.017), and was the only significant predictor of arrhythmic events in multivariable regression analysis (hazard ratio 0.88, P=0.047), together with unexplained syncope (hazard ratio 16.1, P=0.039)., Conclusions: Our data show that among ARVC/D patients HRV analysis might be helpful in identifying those with increased risk of major arrhythmic events.

Background: Endothelial dysfunction, reduced coronary flow reserve and increased markers of inflammation are detectable in cardiac syndrome X (CSX). In this study we investigated the relation between inflammation and systemic endothelial function in CSX patients., Methods: We studied 42 CSX patients (55 +/- 6 years, 14 men) and 20 healthy subjects (52 +/- 7 years, 9 men). Systemic endothelial function was assessed by flow-mediated dilation (FMD) of the brachial artery after 5-minute of forearm cuff inflation. Serum C-reactive protein (CRP) was measured by a high-sensitivity method., Results: FMD was significantly lower in CSX patients compared to controls (4.8 +/- 4.4 vs. 13.7 +/- 4%, p < 0.001), whereas CRP levels were higher in CSX patients than in controls (2.7 +/- 2.4 vs. 0.7 +/- 0.4 mg/L, p = 0.001). In CSX patients FMD showed a significant inverse correlation with CRP levels, even after adjustment for potentially confounding variables (r = -0.34, p = 0.006)., Conclusion: An impaired FMD is detectable in CSX patients, suggesting a generalized abnormality in vascular function. Subclinical inflammation se is to play a significant role in the impairment of endothelium-dependent vasodilator function of these patients.

Introduction: Platelets play a crucial role in the pathogenesis of acute coronary syndromes. Accordingly, previous studies showed increased platelet reactivity on admission in these patients. In this study we assessed platelet reactivity at short-medium term follow-up in patients with ST-segment elevation acute myocardial infarction (STEMI)., Materials and Methods: Fifty-nine patients (58 ± 11 years, 45 men), treated with primary angioplasty, were studied 1 month after STEMI. Thirty-five patients were retested at 6 months. Twenty matched patients with stable coronary artery disease served as controls. Platelet reactivity was assessed by flow cyometry at rest and at peak exercise, with and without adenosine diphosphate (ADP) stimulation, by measuring monocyte-platelet aggregates (MPAs) and glycoprotein IIb/IIIa (CD41) expression in the MPA gate, and CD41 and fibrinogen receptor (PAC-1) expression in the platelet gate., Results: Compared to controls, basal MPAs and CD41 in the MPA gate were higher in STEMI patients both at 1 month (p = 0.001 and p = 0.002, respectively) and at 6 months (p = 0.03 and p = 0.01, respectively). Basal CD41 and PAC-1 expression was also higher in STEMI patients at the two assessments compared to controls (P<0.001 for both). Exercise induced a similar increase in platelet reactivity in patients and controls. ADP induced a higher increase in CD41 platelet expression in STEMI patients compared to controls both at 1 and 6 months (P < 0.001)., Conclusion: Platelet reactivity is increased in the first 6 months after STEMI. The persistence of increased platelet reactivity in this time period may play a role in the early recurrence of coronary events after STEMI., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: The causes of coronary microvascular dysfunction (CMVD) in patients with cardiac syndrome X (CSX) are largely unknown. Common cardiovascular risk factors (CVRFs) and increased markers of inflammation have been associated with CMVD in some studies, but their role in determining CMVD in CSX patients remains poorly known., Methods and Results: We studied 71 CSX patients (56 ± 9 years, 23 men) and 20 healthy volunteers (52 ± 7 years, nine men). Using transthoracic Doppler echocardiography, coronary microvascular vasodilator function was assessed in the left anterior descending coronary artery as the ratio of diastolic coronary blood flow (CBF) velocity at peak intravenous adenosine administration and during cold pressor test (CPT) to the respective basal CBF velocity values. Common CVRFs tended to be more frequent and C-reactive protein (CRP) levels were higher (P < 0.001) in CSX patients than in controls. Both CBF responses to adenosine (2.05 ± 0.6 vs. 2.92 ± 0.9, P < 0.001) and to CPT (1.71 ± 0.6 vs. 2.42 ± 0.7, P < 0.001) were lower in CSX patients than in controls. The differences between the two groups in CBF response to adenosine and in CBF response to CPT remained highly significant (P < 0.01 for both) after adjustment for all CVRFs, including serum CRP levels., Conclusion: In CSX patients, both endothelium-dependent and endothelium-independent CMVD cannot be reliably predicted by CVRFs (including serum CRP levels), alone or in combination.

Patients with cardiac syndrome X (CSX) have an excellent long-term prognosis, but a significant number show worsening angina over time. Previous studies have found a significant impairment of cardiac uptake of iodine-123-meta-iodobenzylguanidine (MIBG) on myocardial scintigraphy, indicating abnormal function of cardiac adrenergic nerve fibers. The aim of this study was to assess whether cardiac MIBG results can predict symptomatic outcome in patients with CSX. Cardiac MIBG scintigraphy was performed in 40 patients with CSX (mean age 58 ± 5 years, 14 men). Cardiac MIBG uptake was measured by the heart/mediastinum uptake ratio and a single photon-emission computed tomographic regional uptake score (higher values reflected lower uptake). Clinical findings, exercise stress test parameters, sestamibi stress myocardial scintigraphy, and C-reactive protein serum levels were also assessed. At an average follow-up of 79 months (range 36 to 144), no patient had died or developed acute myocardial infarction. Cardiac MIBG defect score was significantly lower in patients with worsening versus those without worsening of angina status (13 ± 7 vs 38 ± 28, p = 0.001), in those with versus those without hospital readmission because of recurrent chest pain (15 ± 9 vs 35 ± 29, p = 0.01), and in those who underwent versus those who did not undergo repeat coronary angiography (11 ± 7 vs 36 ± 27, p = 0.001). Significant correlations were found between quality of life (as assessed by the EuroQoL scale) and heart/mediastinum ratio (r = 0.48, p = 0.002) and cardiac MIBG uptake score (r = -0.69, p <0.001). No other clinical or laboratory variable showed a significant association with clinical end points. In conclusion, in patients with CSX, abnormal function of cardiac adrenergic nerve fibers, as assessed by an impairment of cardiac MIBG uptake, identifies those with worse symptomatic clinical outcomes., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Aims: Low left ventricular ejection fraction (LVEF) is the main indication of implantable cardioverter defibrillators (ICD) in patients with dilated cardiomyopathy (DCM) for the primary prevention of sudden cardiac death, but ICD therapy at follow-up occurs in a minority of patients. We investigated whether heart rate variability (HRV) may improve risk stratification in DCM patients., Methods and Results: We studied 42 patients (age 67.3 ± 3.5; 37 males) who had undergone ICD implant for either idiopathic or ischaemic DCM (LVEF <40%) 34.6 ± 19.7 months prior to the study (range 6-84). Patients underwent 24 h electrocardiographic Holter monitoring, and HRV was assessed over 2 hours in the afternoon showing stable sinus rhythm. Left ventricular ejection fraction was measured by two-dimensional echocardiography. The serum levels of C-reactive protein and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were also obtained. The primary endpoint was the occurrence of appropriate ICD shocks in the 6 months preceding the study. The occurrence of appropriate ICD discharge from ICD implant was considered as a secondary endpoint. In the last 6 months, appropriate ICD shocks had occurred in seven patients (17%). There were no differences between patients with and without ICD shocks in clinical variables, as well as in LVEF and in C-reactive protein and NT-proBNP serum levels. In contrast, most HRV parameters were significantly depressed in patients with, compared with those without, ICD shocks; the most significant difference was shown for the average of the standard deviations of RR intervals in all consecutive 5 min segments (n ¼ 12) within the 2 h (26.7 ± 9 vs. 39.7 ± 14 ms; P = 0.02) in the time domain and for LF amplitude (8.4 ± 3 vs. 14.8 ± 7 ms; P = 0.02) in the frequency domain. Implantable cardioverter defibrillator discharge had occurred in 11 patients (26%) since ICD implant (average 35 months). No clinical or laboratory variable showed significant differences between patients with or without ICD discharge, except very low-frequency (VLF) amplitude (23.8 ± 7 vs. 30.8 ± 10.6 ms, respectively; P = 0.049)., Conclusion: In ICD patients with reduced LVEF, several depressed HRV indices were significantly associated with appropriate ICD shocks in the previous 6 months, and VLF amplitude was the only variable significantly associated with ICD shocks recorded since ICD implant. These data suggest that full HRV analysis might be helpful for improving risk stratification for life-threatening ventricular arrhythmias and ICD indication in patients with DCM.

Background: Drug-eluting stents (DES) have reduced restenosis following percutaneous coronary intervention (PCI), but they seem to be associated with increased coronary endothelial dysfunction compared to bare metal stents (BMS). No data are available about the prognostic value of exercise stress test (EST) in PCI patients in the DES era., Methods and Results: The 160 patients with coronary artery disease (CAD) who underwent PCI with either BMS (n=86) or DES (n=74) were studied. EST was performed 1 month after PCI. DES patients had a higher rate of positive EST compared to BMS patients (49% vs 32%; P=0.03). At a median follow-up of 18 months DES showed a lower rate of target vessel revascularization (TVR) (hazard ratio (HR) 0.37, P=0.07), but a higher rate of acute myocardial infarction (AMI) (HR 3.33, P=0.08). At multivariate Cox-regression time to 1 mm ST and low-workload ischemia were independent predictors of AMI (HR 0.96, P=0.03; and HR 6.24, P=0.009, respectively), as well as of TVR (HR 0.96, P=0.007; and HR 6.43, P=0.001, respectively)., Conclusions: DES implantation is associated with a higher rate of positive EST, compared to BMS, 1 month after PCI, likely due to a higher prevalence of endothelial dysfunction. EST seems to be helpful in predicting clinical outcome in patients with coronary stent implantation.