Ten years of subcutaneous defibrillator therapy: Consolidated clinical evidence and future perspectives.

The subcutaneous implantable cardioverter defibrillator (S-ICD) was developed as an alternative to the traditional transvenous implantable cardioverter defibrillator (TV-ICD), aiming to provide easier implantation, simplified detection algorithm of malignant ventricular arrhythmias and prevention from placing components in the cardiovascular system. The S-ICD is implanted subcutaneously or intramuscularly with the generator placed in the left midaxillary line and the lead tunneled subcutaneously in the left para-sternal region. Preimplant electrocardiogram screening is recommended to prevent implantation in patients at high risk of T wave over-sensing. Currently, the S-ICD is unsuitable for patients requiring pacing or cardiac resynchronization. Since the beginning, the S-ICD underwent extensive preclinical investigation until the first prospective multicentre trial demonstrating high efficacy and safety led to market release. While earlier studies focused on younger patients with higher ejection fraction, more recent studies showed favorable outcomes even in patients with comorbidities similar to those typically observed in patients receiving TV-ICD. The development of second and third generation devices has contributed to reduce inappropriate shocks and overcome previous limitations. The aim of this paper is to review the evidence in the literature over the past decade supporting S-ICD as a valid alternative to TV-ICD in terms of safety and efficacy, highlighting the improvements in technology, as well as outcomes.

Efficacy of cryoablation in atrial fibrillation: comparison with antiarrhythmic therapy.

Atrial fibrillation (AF) represents the most common arrhythmia in clinical practice, characterized by irregular atrial electrical activity originating mainly in and around the pulmonary veins. This condition can manifest itself symptomatically or silently but still dangerously. Complications associated with AF include stroke, heart failure, worst clinical outcome in patients with underlying conditions, increased emergency room visits, hospitalizations, and cardiovascular mortality. Currently, according to the main international guidelines, antiarrhythmic therapy is considered the first choice for rhythm control in patients with AF despite modest efficacy and non-negligible side effects. In recent decades, radiofrequency catheter ablation has emerged as an alternative to antiarrhythmic drugs for rhythm control. Cryoablation was developed with the aim of reducing procedural times and reducing complications related to the ablative procedure with radiofrequency without losing efficacy. Recent studies conducted with rigour and scientific solidity have demonstrated on the one hand that the results of this technique are not inferior compare with radiofrequency. This study aims to compare data on the safety and efficacy of cryoablation with those obtained from antiarrhythmic drugs through a review of the most recent scientific evidence.

Prognostic Value of Nonischemic Ringlike Left Ventricular Scar in Patients With Apparently Idiopathic Nonsustained Ventricular Arrhythmias.

BACKGROUND: Left ventricular (LV) scar on late gadolinium enhancement (LGE) cardiac magnetic resonance has been correlated with life-threatening arrhythmic events in patients with apparently idiopathic ventricular arrhythmias (VAs). We investigated the prognostic significance of a specific LV-LGE phenotype characterized by a ringlike pattern of fibrosis. METHODS: A total of 686 patients with apparently idiopathic nonsustained VA underwent contrast-enhanced cardiac magnetic resonance. A ringlike pattern of LV scar was defined as LV subepicardial/midmyocardial LGE involving at least 3 contiguous segments in the same short-axis slice. The end point of the study was time to the composite outcome of all-cause death, resuscitated cardiac arrest because of ventricular fibrillation or hemodynamically unstable ventricular tachycardia and appropriate implantable cardioverter defibrillator therapy. RESULTS: A total of 28 patients (4%) had a ringlike pattern of scar (group A), 78 (11%) had a non-ringlike pattern (group B), and 580 (85%) had normal cardiac magnetic resonance with no LGE (group C). Group A patients were younger compared with groups B and C (median age, 40 vs 52 vs 45 years; P<0.01), more frequently men (96% vs 82% vs 55%; P<0.01), with a higher prevalence of family history of sudden cardiac death or cardiomyopathy (39% vs 14% vs 6%; P<0.01) and more frequent history of unexplained syncope (18% vs 9% vs 3%; P<0.01). All patients in group A showed VA with a right bundle-branch block morphology versus 69% in group B and 21% in group C (P<0.01). Multifocal VAs were observed in 46% of group A patients compared with 26% of group B and 4% of group C (P<0.01). After a median follow-up of 61 months (range, 34-84 months), the composite outcome occurred in 14 patients (50.0%) in group A versus 15 (19.0%) in group B and 2 (0.3%) in group C (P<0.01). After multivariable adjustment, the presence of LGE with ringlike pattern remained independently associated with increased risk of the composite end point (hazard ratio, 68.98 [95% CI, 14.67-324.39], P<0.01). CONCLUSIONS: In patients with apparently idiopathic nonsustained VA, nonischemic LV scar with a ringlike pattern is associated with malignant arrhythmic events.

Collateral injury of the conduction system during catheter ablation of septal substrate in nonischemic cardiomyopathy.

INTRODUCTION: In patients with nonischemic cardiomyopathy (NICM) little is known about the clinical impact of catheter ablation (CA) of septal ventricular tachycardia (VT) resulting in the collateral injury of the conduction system (CICS). METHODS AND RESULTS: Ninety-five consecutive patients with NICM underwent CA of septal VT. Outcomes in patients with no baseline conduction abnormalities who developed CICS (group 1, n = 28 [29%]) were compared to patients with no CICS (group 2, n = 17 [18%]) and to patients with preexisting conduction abnormalities or biventricular pacing (group 3, n = 50 [53%]). Group-1 patients were younger, had a higher left ventricular ejection fraction and a lower prevalence of New York Heart Association III/IV class compared to group 3 while no significant differences were observed with group 2. After a median follow-up of 15 months, VT recurred in 14% of patients in group 1, 12% in group 2 (P = .94) and 32% in group 3 (P = .08) while death/transplant occurred in 14% of patients in group 1, 18% in group 2 (P = .69) and 28% in group 3 (P = .15). A worsening of left ventricular ejection fraction (LVEF) (median LVEF variation, -5%) was observed in group 1 compared to group 2 (median LVEF variation, 0%; P < .01) but not group-3 patients (median LVEF variation, -4%; P = .08) with a consequent higher need for new biventricular pacing in group 1 (43%) compared to group 2 (12%; P = .03) and group 3 (16%; P < .01). CONCLUSIONS: In patients with NICM and septal substrate, sparing the abnormal substrate harboring the conduction system provides acceptable VT control while preventing a worsening of the systolic function.

Prognostic role of serial quantitative evaluation of 18F-fluorodeoxyglucose uptake by PET/CT in patients with cardiac sarcoidosis presenting with ventricular tachycardia.

BACKGROUND: Positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) has shown to be useful in diagnosis, staging and monitoring of cardiac sarcoidosis (CS) but its interpretation is not standardized. OBJECTIVES: We sought to investigate the clinical impact of serial quantitative FDG uptake analysis in patients with CS presenting with ventricular tachycardia (VT) treated by catheter ablation (CA). METHODS: We followed 20 patients (51 ± 9 years, 70% males) with CS and VT who underwent CA, with 92 serial FDG-PET scans (3-10 per patient). Myocardial FDG-avid lesions were quantified using three parameters: maximum standardized uptake value (SUVmax), partial-volume corrected mean standardized uptake value (SUVmean) and partial-volume corrected volume-intensity product [lesion metabolic activity (LMA)]. The volume-intensity product of the entire heart [global cardiac metabolic activity (gCMA)] and the background cardiac metabolic activity (bCMA: difference between gCMA and LMA) were also calculated. The primary end-point was the occurrence of major adverse cardiac events (MACE), including death, heart transplant, hospitalization for heart failure and implantable cardioverter defibrillator (ICD) appropriate interventions. Evolution of echocardiographic parameters over follow-up was also assessed. RESULTS: During a median follow-up of 35 (20-66) months, 18 MACE (1 death, 2 heart transplants, 12 ICD appropriate interventions, 3 hospitalizations) occurred in 12 (60%) patients. At univariable analysis, lack of PET improvement (defined by decrease in LMA of at least 25%) was the only variable associated with cardiac events during follow-up. In particular, non-responders had a 20-fold higher risk of MACE at follow-up (HR 18.96, 95% CI 2.26-159.27; p = 0.007). Moreover, a significant linear inverse relationship was observed between changes in LMA and changes in left ventricular ejection fraction over follow-up (ß = -20.11; p = 0.003). CONCLUSIONS: In patients with CS and VT, temporal change in FDG uptake evaluated by a quantitative approach is associated with parallel change in systolic function. Moreover, reduction in FDG uptake is strongly associated with fewer MACE at long-term follow-up.

Malfunction of cardiac devices after radiotherapy without direct exposure to ionizing radiation: mechanisms and experimental data.

AIMS: Malfunctions of cardiac implantable electronical devices (CIED) have been described after high-energy radiation therapy even in the absence of direct exposure to ionizing radiation, due to diffusion of neutrons (n) causing soft errors in inner circuits. The purpose of the study was to analyse the effect of scattered radiation on different types and models of CIED and the possible sources of malfunctions. METHODS AND RESULTS: Fifty-nine explanted CIED were placed on an anthropomorphous phantom of tissue-equivalent material, and a high-energy photon (15 MV) radiotherapy course (total dose = 70 Gy) for prostate treatment was performed. All devices were interrogated before and after radiation. Radiation dose, the electromagnetic field, and neutron fluence at the CIED site were measured. Thirty-four pacemakers (PM) and 25 implantable cardioverter-defibrillators (ICD) were analysed. No malfunctions were detected before radiation. After radiation a software malfunction was evident in 13 (52%) ICD and 6 (18%) PM; no significant electromagnetic field or photon radiations were detected in the thoracic region. Neutron capture was demonstrated by the presence of the (198)Au((197)Au + n) or (192)Ir((191)Ir + n) isotope activation; it was significantly greater in ICD than in PM and non-significantly greater in damaged devices. A greater effect in St Jude PM (2/2 damaged), Boston (9/11), and St Jude ICD (3/6) and in older ICD models was observed; the year of production was not relevant in PM. CONCLUSION: High-energy radiation can cause different malfunctions on CIED, particularly ICD, even without direct exposure to ionizing radiation due to scattered radiation of neutrons produced by the linear accelerator.

Long-term outcome of 'super-responder' patients to cardiac resynchronization therapy.

AIMS: To evaluate the long-term changes of clinical and echocardiographic parameters, the incidence of cardiac events and parameters associated with late cardiac events in 'super-responders' to cardiac resynchronization therapy (CRT) with [CRT defibrillator (CRT-D)] or without defibrillator back-up. METHODS AND RESULTS: In all consecutive patients treated with CRT in two Italian centres (Trieste and Udine) with left ventricular ejection fraction (LVEF) ≤0.35 at implantation (Timp) and LVEF > 0.50 1 and/or 2 years (Tnorm) after implantation, the long-term outcome and the evolution of echocardiographic parameters were assessed; factors associated with a higher risk of cardiac events, defined as hospitalization or death for heart failure (HF), sudden death, or CRT-D appropriate interventions, were also analysed. Among the 259 patients evaluated, 62 (24%) had LVEF ≥ 0.50 at Tnorm (n = 44 with at 1 year, n = 18 at 2 years). During a mean follow-up of 68 ± 30 months, one cardiac death (for HF) and eight cardiovascular events (two hospitalization for HF and six appropriate CRT-D interventions) occurred. At the last echo evaluation (Tfup) performed 51 ± 26 months after Timp, LVEF was <0.50 in five patients (>0.45 in four of them). At univariable analysis, only LV end-systolic volume evaluated at Tfup was associated with a higher risk of cardiac events during follow-up. CONCLUSION: In 'super-responders' to CRT long-term outcome is excellent. However, cardiac events, mainly CRT-D appropriate interventions, can occur despite the persistence of LVEF > 0.50. Early identification of these patients is still an unsolved issue.

Correlation of MRI premature ventricular contraction activation pattern in bigeminy with electrophysiology study-confirmed site of origin.

Although PVCs commonly lead to degraded cine cardiac MRI (CMR), patients with PVCs may have relatively sharp cine images of both normal and ectopic beats ("double beats") when the rhythm during CMR is ventricular bigeminy, and only one beat of the pair is detected for gating. MRI methods for directly imaging premature ventricular contractions (PVCs) are not yet widely available. Localization of PVC site of origin with images may be helpful in planning ablations. The contraction pattern of the PVCs in bigeminy provides a "natural experiment" for investigating the potential utility of PVC imaging for localization. The purpose of this study was to evaluate the correlation of the visually assessed site of the initial contraction of the ectopic beats with the site of origin found by electroanatomic mapping. Images from 7 of 86 consecutive patients who underwent CMR prior to PVC ablation were found to include clear cine images of bigeminy. The visually apparent site of origin of the ectopic contraction was determined by three experienced, blinded CMR readers and correlated with each other, and with PVC site of origin determined by 3D electroanatomic mapping during catheter ablation. Blinded ascertainment of visually apparent initial contraction pattern for PVC localization was within 2 wall segments of PVC origin by 3D electroanatomic mapping 76% of the time. Our data from patients with PVCs with clear images of the ectopic beats when in bigeminy provide proof-of-concept that CMR ectopic beat contraction patterns analysis may provide a novel method for localizing PVC origin prior to ablation procedures. Direct imaging of PVCs with use of newer cardiac imaging methods, even without the presence of bigeminy, may thus provide valuable data for procedural planning.

Effect of Prolonged and Substantial Weight Loss on Incident Atrial Fibrillation: A Systematic Review and Meta-Analysis.

Background. Overweight and obesity are associated with atrial fibrillation (AF), and bariatric surgery (BS), able to induce sustained and prolonged weight loss, might represent the ideal treatment in the prevention of AF. Previous studies could not definitely establish a role for weight loss and BS in preventing incident AF so far. During the last few years, several studies on the effect of bariatric surgery on cardiovascular diseases have been published, and we performed a systematic review and meta-analysis to evaluate the role of weight loss through BS in the prevention of incident AF in obesity. Methods. This meta-analysis followed the PRISMA guideline. Eligible studies were controlled trials evaluating the appearance of atrial fibrillation in patients undergoing weight loss through BS as compared with patients receiving medical treatment. Quality of studies was assessed according to the Newcastle-Ottawa Quality Assessment Scale, and risk-of-bias was evaluated employing the Egger's test. All analyses were run by a random-effects model according to Hartung and Knapp and sensitivity analyses were performed. Heterogeneity was assessed through Q and I2 statistics for each comparison, and potential publication bias was formally investigated. Results. Ten studies were included in the meta-analysis, and the overall result was statistically significant [OR = 0.665 (0.475-0.929), p = 0.017], with significant heterogeneity (Q = 48.98, p < 0.001; I2 = 81.6%), but with no publication bias. In sensitivity analyses, the amount of weight loss, percentage of patients with diabetes and value of the Newcastle-Ottawa Quality Assessment Scale, were all associated with significance of effect. Since age was different in one study, a sensitivity analysis was performed by excluding this study; OR was similar [OR = 0.608 (0.454-0.814), p < 0.001]; heterogeneity was reduced but still significant (Q = 35.74, p < 0.001, I2 = 77.6%) and again no publication bias was detected. Conclusions. Bariatric surgery as compared to medical treatment is associated with reduced appearance of incident AF.

Polycomb Bodies Detection in Murine Fibromuscular Stroma from Skin, Skeletal Muscles, and Aortic Tissues.

The regulation of chromatin structure depends on a dynamic, multiple mechanisms that modulate gene expression and constitute the epigenome. The Polycomb group (PcG) of proteins are epigenetic factors involved in the transcriptional repression. Among their multilevel, chromatin-associated functions, PcG proteins mediate the establishment and maintenance of higher-order structures at target genes, allowing the transmission of transcriptional programs throughout the cell cycle.In the nucleus, PcG proteins localize close to the pericentric heterochromatin forming microscopically foci, called Polycomb bodies. Here, to visualize the tissue-specific PcG distribution in the aorta, dorsal skin and hindlimb muscles, we combine a fluorescence-activated cell sorter (FACS)-based method with an immunofluorescence staining.

Cardiac electrical instability in Erdheim-Chester disease: a case report.

Erdheim-Chester disease (ECD) is a rare multisystemic disorder of non-Langerhans histiocytic cells with a pleomorphic clinical presentation. It affects bones, skin, central nervous system, pituitary gland, ocular tissue, kidneys and perirenal tissue and lungs. Cardiac involvement presents usually with pericardial effusion and right atrial masses, but rarely with conduction system infiltration and subsequent arrhythmic events. Following the discovery of mutations of activating signaling kinase proteins (BRAF, MEK, ALK), the therapeutic landscape has changed to a more precise targeted treatment. Currently vemurafenib is approved for patient with end-organ dysfunction and BRAF-V600E mutation and the prognosis has dramatically improved. Here we present a case of ECD with electrical instability as main clinically relevant manifestation of cardiac involvement.

Comparative evaluation of seven resistance interpretation algorithms and their derived genotypic inhibitory quotients for the prediction of 48 week virological response to darunavir-based salvage regimens.

BACKGROUND: the darunavir genotypic inhibitory quotient (gIQ) has been suggested as one of the predictors of virological response to darunavir-containing salvage regimens. Nevertheless, which resistance algorithm should be used to optimize the calculation of gIQ is still debated. The aim of our study was to compare seven different free-access resistance algorithms and their derived gIQs as predictors of 48 week virological response to darunavir-based salvage therapy in the clinical setting. METHODS: patients placed on two nucleoside reverse transcriptase inhibitors + 600/100 mg of darunavir/ritonavir twice daily  ±â€Š enfuvirtide were prospectively evaluated. Virological response was assessed at 48 weeks. Darunavir resistance interpretation was performed according to seven different algorithms, of which two were weighted algorithms. Analysis of other factors potentially associated with virological response at 48 weeks was performed. RESULTS: fifty-six treatment-experienced patients were included. Overall, 35 patients (62.5%) had a virological response at 48 weeks. Receiver operator characteristic curve analysis showed that De Meyer's weighted score (WS) and its derived gIQ (gIQ WS) were the most accurate parameters defining virological response, and related cut-offs showed the best sensitivity/specificity pattern. In univariate logistic regression analysis, baseline log viral load (P = 0.028), optimized background score ≥ 2 (P = 0.048), WS >5 (P = 0.001) and WS gIQ ≥ 600 (P < 0.0001) were independently associated with virological response. In multivariate analysis, only baseline log viral load (P = 0.008) and WS gIQ ≥ 600 (P < 0.0001) remained in the model. CONCLUSIONS: in our study, although different resistance interpretation algorithms and derived gIQs were associated with virological response, gIQ WS was the most accurate predictive model for achieving a successful virological response.

Echocardiographic evaluation of systolic and mean pulmonary artery pressure in the follow-up of patients with pulmonary hypertension.

AIMS: To identify a correction of the modified Bernoulli formula used to estimate systolic and mean pulmonary artery pressure [sPAP and mPAP; respectively: sPAP = 4 × TRv (tricuspid regurgitation velocity)(2)+ RAP (right atrial pressure); and mPAP = 0.61sPAP + 2], applicable in the follow-up of pulmonary hypertension (PH) patients. METHODS AND RESULTS: From January 1979 to December 2009, 60 patients with precapillary (class I and IV) and 'out of proportion' PH were consecutively enrolled in the PH Registry of Trieste. All patients underwent both echocardiographic and right heart catheter evaluation. We used a simple-linear-regression method in order to compare sPAP and mPAP Doppler-estimated values with the respective right-heart catheterization invasive variables. The comparison of the estimated with the traditional modified Bernoulli formula echo-Doppler data and the effective invasive values confirmed a significant association between them (for sPAP P< 0.001; for mPAP P= 0.006). Simple-linear-regression-derived formulas were sPAP = 1.07 × (4TRv(2)+ RAP) + 7.4 (1) and mPAP = 1.1 × (0.61sPAP + 2) + 2.5 (2). These regression-corrected formulas were validated in an external population of PH patients. CONCLUSION: Our data suggest that formulas (1) and (2) could be more reliable with respect to the traditional modified Bernoulli equation, when estimating echocardiographically sPAP and mPAP in patients with PH confirmed by right-heart catheterization.

Role of cardiac imaging in patients undergoing catheter ablation of ventricular tachycardia.

Ventricular tachycardia is a major health issue in patients with structural heart disease (SHD). Implantable cardioverter defibrillator (ICD) therapy has significantly reduced the risk of sudden cardiac death (SCD) in such patients, but on the other hand, it has led to frequent ICD shocks as an emerging problem, being associated with poor quality of life, frequent hospitalizations and increased mortality. Myocardial scar plays a central role in the genesis and maintenance of re-entrant arrhythmias, as the coexistence of surviving myocardial fibres within fibrotic tissue leads to the formation of slow conduction pathways and to a dispersion of activation and refractoriness that constitutes the milieu for ventricular tachycardia circuits. Catheter ablation has repeatedly proven to be well tolerated and highly effective in treating VT and in the last two decades has benefited from continuous efforts to determine ventricular tachycardia mechanisms by integration with a wide range of invasive and noninvasive imaging techniques such as intracardiac echocardiography, cardiac magnetic resonance, multidetector computed tomography and nuclear imaging. Cardiovascular imaging has become a fundamental aid in planning and guiding catheter ablation procedures by integrating structural and electrophysiological information, enabling the ventricular tachycardia arrhythmogenic substrate to be characterized and effective ablation targets to be identified with increasing precision, and allowing the development of new ablation strategies with improved outcomes. In this review, we provide an overview of the role of cardiac imaging in patients undergoing catheter ablation of ventricular tachycardia.

Myocardial Substrate Characterization by CMR T1 Mapping in Patients With NICM and No LGE Undergoing Catheter Ablation of VT.

OBJECTIVES: The goal of this study was to characterize the relationship between DF, the electroanatomic mapping (EAM) substrate, and outcomes of catheter ablation of VT in NICM. BACKGROUND: A substantial proportion of patients with nonischemic dilated cardiomyopathy (NICM) and ventricular tachycardia (VT) do not have scar detectable by cardiac magnetic resonance late gadolinium enhancement (LGE) imaging. In these patients, the significance of diffuse fibrosis (DF) detected with T1 mapping has not been previously investigated. METHODS: This study included 51 patients with NICM and VT undergoing catheter ablation (median age 55 years; 77% male subjects) who had no evidence of LGE on pre-procedural cardiac magnetic resonance. Post-contrast T1 relaxation time determined on the septum was assessed as a surrogate of DF burden. The extent of endocardial low-voltage areas (LVAs) at EAM was correlated with T1 mapping data. RESULTS: Bipolar LVAs were present in 22 (43%) patients (median extent 15 cm2 [8 to 29 cm2]) and unipolar LVA in all patients (median extent 48 cm2 [26 to 120 cm2]). A significant inverse correlation was found between T1 values and both unipolar-LVA (R2 = 0.64; ß = -0.85; p < 0.01) and bipolar-LVA (R2 = 0.16; ß = -1.63; p < 0.01). After a median follow-up of 45 months (22 to 57 months), 2 (4%) patients died, 3 (6%) underwent heart transplantation, and 8 (16%) experienced VT recurrence. Shorter post-contrast T1 time was associated with an increased risk of VT recurrence (hazard ratio: 1.16; 95% confidence interval: 1.03 to 1.33 per 10 ms decrease; p = 0.02). CONCLUSIONS: In patients with NICM and no evidence of LGE undergoing catheter ablation of VT, DF estimated by using post-contrast T1 mapping correlates with the voltage abnormality at EAM and seems to affect post-ablation outcomes.

Acquired neurogenic foreign accent syndrome after right-hemisphere lesion with left cerebellar diaschisis: A longitudinal study.

Patients affected by acquired neurogenic foreign accent syndrome (ANFAS) start speaking with a new accent that resembles that of a foreign language. ANFAS has been reported following left-hemisphere damage, but it is extremely rare after right-hemisphere damage. We described KKE, a right-hemisphere-damaged patient. His cognitive functions were largely intact and he was not aphasic. Nonetheless, KKE showed a marked foreing accent which was mainly judged as Slavic. Positron emission tomography revealed left cerebellar diaschisis, even if the cerebellum did not appear lesioned, on MRI scans. Remarkably, KKE still showed ANFAS three years after lesion onset. We propose that this very rare variant of ANFAS, after right-hemisphere lesion, can be due to the damage of a complex cerebral network involving supra- and infra-tentorial structures.

Pseudopolymorphic Wide Complex Tachycardia in a Child With Long QT Syndrome.

Implantable loop recorders (ILRs) can be a valuable tool in monitoring patients with inherited arrhythmia. This paper reports on a family with long QT syndrome (type 2 [LQT2]) in which a pseudopolymorphic wide complex tachycardia detected by ILR was ultimately diagnosed as a supraventricular aberrant rhythm, facilitated by noncompliance with beta-blocker therapy. (Level of Difficulty: Intermediate.).

QT interval prolongation and torsade de pointes in patients with COVID-19 treated with hydroxychloroquine/azithromycin.

Background: There is no known effective therapy for patients with coronavirus disease 2019 (COVID-19). Initial reports suggesting the potential benefit of hydroxychloroquine/azithromycin (HY/AZ) have resulted in massive adoption of this combination worldwide. However, while the true efficacy of this regimen is unknown, initial reports have raised concerns about the potential risk of QT interval prolongation and induction of torsade de pointes (TdP). Objective: The purpose of this study was to assess the change in corrected QT (QTc) interval and arrhythmic events in patients with COVID-19 treated with HY/AZ. Methods: This is a retrospective study of 251 patients from 2 centers who were diagnosed with COVID-19 and treated with HY/AZ. We reviewed electrocardiographic tracings from baseline and until 3 days after the completion of therapy to determine the progression of QTc interval and the incidence of arrhythmia and mortality. Results: The QTc interval prolonged in parallel with increasing drug exposure and incompletely shortened after its completion. Extreme new QTc interval prolongation to >500 ms, a known marker of high risk of TdP, had developed in 23% of patients. One patient developed polymorphic ventricular tachycardia suspected as TdP, requiring emergent cardioversion. Seven patients required premature termination of therapy. The baseline QTc interval of patients exhibiting extreme QTc interval prolongation was normal. Conclusion: The combination of HY/AZ significantly prolongs the QTc interval in patients with COVID-19. This prolongation may be responsible for life-threatening arrhythmia in the form of TdP. This risk mandates careful consideration of HY/AZ therapy in light of its unproven efficacy. Strict QTc interval monitoring should be performed if the regimen is given.

Risk Stratification of Patients With Apparently Idiopathic Premature Ventricular Contractions: A Multicenter International CMR Registry.

OBJECTIVES: This study investigated the prevalence and prognostic significance of concealed myocardial abnormalities identified by cardiac magnetic resonance (CMR) imaging in patients with apparently idiopathic premature ventricular contractions (PVCs). BACKGROUND: The role of CMR imaging in patients with frequent PVCs and otherwise negative diagnostic workup is uncertain. METHODS: This was a multicenter, international study that included 518 patients (age 44 ± 15 years; 57% men) with frequent (>1,000/24 h) PVCs and negative routine diagnostic workup. Patients underwent a comprehensive CMR protocol including late gadolinium enhancement imaging for detection of necrosis and/or fibrosis. The study endpoint was a composite of sudden cardiac death, resuscitated cardiac arrest, and nonfatal episodes of ventricular fibrillation or sustained ventricular tachycardia that required appropriate implantable cardioverter-defibrillator therapy. RESULTS: Myocardial abnormalities were found in 85 (16%) patients. Male gender (odds ratio [OR]: 4.28; 95% confidence interval [CI]: 2.06 to 8.93; p = 0.01), family history of sudden cardiac death and/or cardiomyopathy (OR: 3.61; 95% CI: 1.33 to 9.82; p = 0.01), multifocal PVCs (OR: 11.12; 95% CI: 4.35 to 28.46; p < 0.01), and non-left bundle branch block inferior axis morphology (OR: 14.11; 95% CI: 7.35 to 27.07; p < 0.01) were all significantly related to the presence of myocardial abnormalities. After a median follow-up of 67 months, the composite endpoint occurred in 26 (5%) patients. Subjects with myocardial abnormalities on CMR had a higher incidence of the composite outcome (n = 25; 29%) compared with those without abnormalities (n = 1; 0.2%; p < 0.01). CONCLUSIONS: CMR can identify concealed myocardial abnormalities in 16% of patients with apparently idiopathic frequent PVCs. Presence of myocardial abnormalities on CMR predict worse clinical outcomes.