Publications by authors named "Xavier Waintraub"

36 Publications

External Validation of a Risk Prediction Model for Ventricular Arrhythmias in Arrhythmogenic Right Ventricular Cardiomyopathy.

Can J Cardiol 2021 Mar 3. Epub 2021 Mar 3.

Sorbonne Université, APHP, Groupe Hospitalier Pitié-Salpêtrière, Institut de Cardiologie, Paris, France.

The new 5-years ventricular arrhythmia (VA) occurrence risk model is a major breakthrough for arrhythmic-risk stratification in the challenging ARVC population. In the original study, the model resulted in a 20.6% reduction in implantable cardioverter-defibrillator (ICD) placement as compared with the 2015 consensus, for the same protection level. However, only internal validation was performed, limiting generalization. Here, we externally validated the model in a European tertiary care cohort of 128 ARVC patients with restrictive indications for primary prevention ICD placement. Overall, 74% were men, none had VA history and a single patient had an ICD at baseline. Median age at diagnosis was 38 years (interquartile range [IQR] [28-50]). During a median follow-up of 7.8 years [IQR (6.1-9.7)], 15 (12%) patients experienced VA. The model provided good discrimination, with a C-index for 5-year VA risk prediction of 0.84 [95% confidence interval (0.74-0.93)] (Figure 1). However, the model led to an overestimation of the 5-year VA risk when applying thresholds <50%. With a <10% predicted risk, no patient showed VA. With a 7.5% predicted risk, the ICD:VA ratio was 6.3 versus 3.4 in original study. The model still outperformed the 2015 International Task Force Consensus. Overall, in a relatively large European ARVC cohort with restrictive indications for ICD placement, the ARVC model for VA prediction successfully identified ARVC patients with VA during follow-up. Yet, our study underlines the need for careful threshold selection considering the model's associated risk overestimation in low- to intermediate-risk patients.
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http://dx.doi.org/10.1016/j.cjca.2021.02.018DOI Listing
March 2021

Sexual Dimorphisms, Anti-Hormonal Therapy and Cardiac Arrhythmias.

Int J Mol Sci 2021 Feb 2;22(3). Epub 2021 Feb 2.

INSERM, CIC-1901, AP-HP, Pitié-Salpêtrière Hospital, Regional Pharmacovigilance Center, UNICO-GRECO Cardio-Oncology Program, Department of Pharmacology and Clinical Investigation Center, CLIP2 Galilée, Sorbonne Université, F-75013 Paris, France.

Significant variations from the normal QT interval range of 350 to 450 milliseconds (ms) in men and 360 to 460 ms in women increase the risk for ventricular arrhythmias. This difference in the QT interval between men and women has led to the understanding of the influence of sex hormones on the role of gender-specific channelopathies and development of ventricular arrhythmias. The QT interval, which represents the duration of ventricular repolarization of the heart, can be affected by androgen levels, resulting in a sex-specific predilection for acquired and inherited channelopathies such as acquired long QT syndrome in women and Brugada syndrome and early repolarization syndrome in men. Manipulation of the homeostasis of these sex hormones as either hormonal therapy for certain cancers, recreational therapy or family planning and in transgender treatment has also been shown to affect QT interval duration and increase the risk for ventricular arrhythmias. In this review, we highlight the effects of endogenous and exogenous sex hormones in the physiological and pathological states on QTc variation and predisposition to gender-specific pro-arrhythmias.
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http://dx.doi.org/10.3390/ijms22031464DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7867204PMC
February 2021

Cardiotoxicity Associated with Gemcitabine: Literature Review and a Pharmacovigilance Study.

Pharmaceuticals (Basel) 2020 Oct 21;13(10). Epub 2020 Oct 21.

Department of Pharmacology, Regional Pharmacovigilance Centre, Pitié-Salpêtrière Hospital, INSERM CIC-1901, Sorbonne Université, AP-HP, 75006 Paris, France.

Background: Gemcitabine is a nucleoside analog, widely used either alone or in combination, for the treatment of multiple cancers. However, gemcitabine may also be associated with cardiovascular adverse-drug-reactions (CV-ADR).

Methods: First, we searched for all cases of cardiotoxicity associated with gemcitabine, published in MEDLINE on 30 May 2019. Then, we used VigiBase, the World Health Organization's global database of individual case safety reports, to compare CV-ADR reporting associated with gemcitabine against the full database between inception and 1 April 2019. We used the information component (IC), an indicator value for disproportionate Bayesian reporting. A positive lower end of the 95% credibility interval for the IC (IC) ≥ 0, is deemed significant.

Results: In VigiBase, 46,898 reports were associated with gemcitabine on a total of 18,908,940 in the full database. Gemcitabine was associated with higher reporting for myocardial ischemia (MI, n: 119), pericardial diseases (n: 164), supraventricular arrhythmias (SVA, n: 308) and heart failure (HF, n: 484) versus full database with IC ranging between 0.40 and 2.81. CV-ADR were associated with cardiovascular death in up to 17% of cases.

Conclusion: Treatment with gemcitabine is associated with potentially lethal CV-ADRs, including MI, pericardial diseases, SVA and HF. These events should be considered in patient care and clinical trial design.
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http://dx.doi.org/10.3390/ph13100325DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7594046PMC
October 2020

Factors associated with implantable cardioverter defibrillators appropriate therapy in cardiac sarcoidosis: a meta-analysis.

Sarcoidosis Vasc Diffuse Lung Dis 2020 15;37(1):17-23. Epub 2020 Mar 15.

Sorbonne Université, INSERM UMRS-1135, CIMI, Assistance Publique-Hôpitaux de Paris, Service de Médecine Interne 2, Centre National de Référence Maladies Systémiques Rares, Hôpital Pitié-Salpêtrière, 75013-Paris, France.

Background: Patients with cardiac sarcoidosis (CS) are at increased risk of atrioventricular blocks, ventricular arrhythmias, and sudden cardiac death. Objectives We aimed to investigate the characteristics associated with appropriate therapy in implantable cardiac defibrillator (ICD) -implanted CS patients.

Methods: We performed a PubMed and Web of Science search for studies reporting patients with CS who underwent an ICD implantation. The primary criterion was an appropriate therapy.

Results: We screened 705 studies, of which 5 were included in the final analysis. We conducted a meta-analysis including 464 patients (mean age 55 years, 282 males (60%)). The mean follow-up was 3.5 years. Among the 464 patients, 180 received an appropriate therapy (39%). Patients who received an appropriate therapy were younger (-3.33, 95% confidence interval (CI) -6.42 to -0.23, p=0.004), were more likely to be male (OR 2.06, 95% CI 1.37-3.09, p=0.0005), had a lower left ventricular ejection fraction (LVEF) (-10.5, 95% CI -18.23 to -2.78, p=0.008), had a higher rate of complete heart block (OR 2.19, 95% CI 1.20 to 3.99, p=0.01), and more frequently had ventricular pacing (OR 6.44 95% CI 2.57 to 16.16, p<0.0001).

Conclusions: Appropriate ICD therapy during CS is associated with young age, male sex, low LVEF, history of complete heart block, and ventricular pacing. .
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http://dx.doi.org/10.36141/svdld.v37i1.8271DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7569536PMC
November 2020

Rates and Anticoagulation Treatment of Known Atrial Fibrillation in Patients with Acute Ischemic Stroke: A Real-World Study.

Adv Ther 2020 10 27;37(10):4370-4380. Epub 2020 Aug 27.

Atrial Fibrillation Centre and Department of Cardiovascular Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Introduction: Known atrial fibrillation (AF) rate and appropriate prescription of oral anticoagulants (OACs) in acute ischemic stroke (AIS) patients with AF in China are not as well known as in Western countries.

Methods: Known AF and unknown AF, rate and adequacy of OACs use of AIS patients with AF attending five hospitals from April 2018 to August 2019 in the northwest region of China were investigated.

Results: A total of 344 patients were enrolled. Of these, 237 (AF-known group; 237/344, 68.9%) and 107 patients (AF-unknown group; 107/344, 31.1%) were diagnosed with AF before and after AIS during this hospitalization, respectively. In the AF-known group with echocardiography results (178 patients, including 103 female and 75 male patients), 154 of overall, 88 of female and 66 of male patients, respectively, were indicated to be taking OACs. However, the actual OACs proportion was much lower [overall (30.5%, 47/154); female (31.8%, 28/88) and male (28.8%, 19/66) patients] than indicated. Only one female patient met the guideline-based criteria for OACs. As for patients diagnosed with massive cerebral infraction (MCI; 43.0%, 148/344), the known AF rate was 65.5% (97/148). Among the MCI patients in the AF-known group with echocardiography results (61 patients), 50 patients had an OACs indication. However, only 22.0% (11/50) of these patients took OACs, and none met the guideline-based criteria for OACs.

Conclusions: This study revealed a low known AF rate, low OACs use rate and low rate of meeting the guideline-based criteria for OACs in AIS patients with AF in the northwest region of China. These findings indicated the importance of AF as a public health problem in China.
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http://dx.doi.org/10.1007/s12325-020-01469-wDOI Listing
October 2020

Extracorporeal Membrane Oxygenation to Support Life-Threatening Drug-Refractory Electrical Storm.

Crit Care Med 2020 Oct;48(10):e856-e863

Medical Intensive Care Unit, Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Paris, France.

Objectives: Despite rapid implementation of anti-arrhythmic treatment and sedation and controlling the triggering event, rare patients develop treatment-refractory electrical storm and their hemodynamic instability prevents emergency catheter ablation. In that context, venoarterial extracorporeal membrane oxygenation could rapidly restore hemodynamics and tissue perfusion and reduce myocardial oxygen consumption, until adequate anti-arrhythmic drug levels are reached to safely perform catheter ablation.

Design: Retrospective, multicenter study over an 8-year period.

Setting: Two French tertiary care centers.

Patients: Eighty-three consecutive adults with venoarterial extracorporeal membrane oxygenation-supported treatment-refractory electrical storm (median [interquartile range] age, 55 yr [48-63 yr]).

Measurements And Main Results: Fifty-nine percent of these patients had acute ischemic cardiomyopathy and 66% underwent cardiopulmonary resuscitation prior to venoarterial extracorporeal membrane oxygenation initiation, with 18% cannulated during it. Fifty patients (60%) had ventricular tachycardia and/or ventricular fibrillation alternating with short periods of sinus rhythm and 33 (40%) had refractory ventricular tachycardia and/or ventricular fibrillation. Twelve patients (15%) underwent safe catheter ablation under venoarterial extracorporeal membrane oxygenation. After a median of 3 days (1-13 d) on extracorporeal membrane oxygenation support, 37 patients (45%) were successfully weaned off and 42% were alive 6 months post-ICU admission. Multivariable analysis retained ventricular tachycardia and/or ventricular fibrillation episodes alternating with short periods of sinus rhythm (odds ratio, 0.18; 95% CI, 0.06-0.52; p = 0.002) and age less than 50 years (odds ratio, 0.32; 95% CI, 0.18-0.89; p = 0.002) as being independent protective factors with 6-month survival, regardless of the underlying electrical storm cause.

Conclusions: Among venoarterial extracorporeal membrane oxygenation-supported drug-refractory electrical storm patients, 42% survived 6 months post-ICU admission. Ventricular tachycardia and/or ventricular fibrillation episodes alternating with short periods of sinus rhythm and age less than 50 years were independently associated with better survival.
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http://dx.doi.org/10.1097/CCM.0000000000004490DOI Listing
October 2020

Cardiovascular disease during the COVID-19 pandemic: Think ahead, protect hearts, reduce mortality.

Cardiol J 2020 13;27(5):616-624. Epub 2020 Aug 13.

Department of Cardiovascular Medicine, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Coronavirus disease 2019 (COVID-19) is rapidly spreading globally. As of October 3, 2020, the number of confirmed cases has been nearly 34 million with more than 1 million fatalities. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is accountable for COVID-19. Newly diagnosed and worsening cardiovascular disease are common complications in COVID-19 patients, including acute cardiac injury, hypertension, arrhythmia, myocardial infarction, heart failure and sudden cardiac arrest. The mechanisms contributing to cardiac disease burden include hypoxemia, inflammatory factor storm, dysfunctional angiotensin converting enzyme 2 (ACE2), and drug-induced cardiac toxicity. Notably, the macrophages expressing ACE2 as direct host cells of SARS-CoV-2 secrete chemokine and inflammatory cytokines, as well as a decrease in cellular immune responses to SARS-CoV-2 infection due to elevated exhaustion levels and dysfunctional diversity of T cells, that may be accountable for the "hyperinflammation and cytokine storm syndrome" and subsequently acute cardiac injury and deteriorating cardiovascular disease in COVID-19 patients. However, no targeted medication or vaccines for COVID-19 are yet available. The management of cardiovascular disease in patients with COVID-19 include general supportive treatment, circulatory support, other symptomatic treatment, psychological assistance as well as online consultation. Further work should be concentrated on better understanding the pathogenesis of COVID-19 and accelerating the development of drugs and vaccines to reduce the cardiac disease burden and promote the management of COVID-19 patients, especially those with a severe disease course and cardiovascular complications.
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http://dx.doi.org/10.5603/CJ.a2020.0101DOI Listing
November 2020

Sarcoidosis diagnosed on granulomas in the explanted heart after transplantation: Results of a French nationwide study.

Int J Cardiol 2020 May 17;307:94-100. Epub 2020 Jan 17.

Sorbonne Université, Assistance Publique-Hôpitaux de Paris, Hôpital De la Pitié-Salpêtrière, Service de Médecine Interne 2, Centre de Référence National Maladies Systémiques Rares, 75013 Paris, France. Electronic address:

Background: Cardiac sarcoidosis (CS) is a challenging diagnosis. Patients may progress to end-stage congestive heart failure and require cardiac transplantation without ever having been diagnosed. Characteristics and outcomes of patients with granulomas in the explanted hearts are unknown.

Methods: All French heart transplantation centers were contacted to participate in the study. Each center searched through local databases for the cases of non-caseating granuloma in the explanted hearts between 2000 and 2017. Data before and after transplantation were recorded from medical charts. Survival of CS and all- cause heart transplantation patients were compared.

Results: Fifteen patients (10 men, 5 women) received a diagnosis of CS based on pathologic data of the explanted heart and were recruited for the study. All patients were diagnosed as non-ischemic dilated or hypertrophic cardiomyopathy and presented congestive heart failure. Eight patients (53%) had ventricular rhythm disturbances, and 3 (20%) a complete heart block. Ten out of 13 patients (77%) had extracardiac radiological signs compatible with sarcoidosis on chest computed tomography (CT) scans. One patient died 3 months after transplantation from infectious complications. The 14 remaining patients were still alive at the end of the study (median follow-up of 28.8 months). One patient had a second heart transplantation 5 years later because of chronic allograft vasculopathy. One patient presented a relapse of CS confirmed by myocardial biopsies 9 years after transplantation, requiring an escalation of immunosuppressive therapy.

Conclusion: CS may be undiagnosed before heart transplantation. In 77% of cases, sarcoidosis could have been detected before transplantation with non-invasive imaging techniques.
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http://dx.doi.org/10.1016/j.ijcard.2019.12.066DOI Listing
May 2020

My approach to ventricular tachycardia ablation in patient with arrhythmogenic right ventricular cardiomyopathy/dysplasia.

HeartRhythm Case Rep 2020 Feb 14;6(2):51-59. Epub 2020 Feb 14.

Cardiology Institute, Pitié-Salpêtrière Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.

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http://dx.doi.org/10.1016/j.hrcr.2019.09.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7026538PMC
February 2020

A novel gain-of-function mutation in SCN5A responsible for multifocal ectopic Purkinje-related premature contractions.

Hum Mutat 2020 04 25;41(4):850-859. Epub 2020 Jan 25.

Faculté de Médecine, Sorbonne Université, Paris, France.

Recently, four SCN5A mutations have been associated with Multifocal Ectopic Purkinje-related Premature Contractions (MEPPC), a rare cardiac syndrome combining polymorphic ventricular arrhythmia with dilated cardiomyopathy (DCM). Here, we identified a novel heterozygous mutation in SCN5A (c.611C>A, pAla204Glu) in a young woman presenting with polymorphic premature ventricular contractions (PVCs) and DCM. After failure of antiarrhythmic drugs and an attempt of radiofrequency catheter ablation showing three exit-sites of PVCs, all with presystolic Purkinje potentials, a treatment by hydroquinidine was tried, leading to an immediate and spectacular disappearance of all PVCs and normalization of cardiac function. Electrophysiological studies showed that Na 1.5-A204E mutant channels exhibited a significant leftward shift of 8 mV of the activation curve, leading to a larger hyperpolarized window current when compared to wild-type. Action potential modeling using Purkinje fiber and ventricular cell models predicted an arrhythmogenic effect predominant in Purkinje fibers for the A204E mutation. Comparison with other MEPPC-associated Na 1.5 mutations revealed a common electrophysiological pattern of abnormal voltage-dependence of activation leading to a larger hyperpolarized window current as a shared biophysical mechanism of this syndrome. These features of the mutant sodium channels are likely to be responsible for the hyperexcitability of the fascicular-Purkinje system observed in patients with MEPPC.
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http://dx.doi.org/10.1002/humu.23981DOI Listing
April 2020

Management of sustained arrhythmias for patients with cardiogenic shock in intensive cardiac care units.

Arch Cardiovasc Dis 2019 Dec 13;112(12):781-791. Epub 2019 Nov 13.

LIRYC institute, Bordeaux university, Bordeaux university hospital, 33000 Bordeaux, France.

Cardiac arrhythmias that occur in patients referred to intensive care units worsen symptoms and outcomes and need urgent correction, especially in patients admitted for refractory heart failure. Electrical storm is a frequent reason for referral to an intensive care unit. Specific, efficient and rapid management of patients presenting with various arrhythmias is therefore mandatory and procedures should be known by any physician involved in an intensive care unit. This article reviews the current knowledge on the management of supraventricular and ventricular arrhythmias in this setting, from medications and sedation to ablation and more exceptional therapy. It also covers the occasional indications of resynchronization in refractory heart failure and the interest for haemodynamic assistance when specific therapy fails.
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http://dx.doi.org/10.1016/j.acvd.2019.10.002DOI Listing
December 2019

Clinical characterization of men with long QT syndrome and torsades de pointes associated with hypogonadism: A review and pharmacovigilance study.

Arch Cardiovasc Dis 2019 Nov 30;112(11):699-712. Epub 2019 Aug 30.

Inserm, UNICO-GRECO Cardio-Oncology Programme, Department of Pharmacology, CIC-1421, Pharmacovigilance Unit, Pitié-Salpêtrière Hospital, Sorbonne Université, AP-HP, 75013 Paris, France.

Background: Long QT syndrome (LQTS) can cause the potentially fatal ventricular tachycardia torsades de pointes (TdP). QT interval corrected for heart rate (QTc) is shorter in men than in women, with testosterone contributing to shorten QTc. We recently described male hypogonadism as a reversible risk factor for acquired LQTS and TdP, but the clinical characteristics of such patients have not been characterized.

Aims: To describe the clinical characteristics of men with acquired LQTS or TdP associated with hypogonadism caused by endocrine conditions or androgen deprivation therapy (ADT), and to evaluate the relationship between testosterone concentrations and electrocardiographic changes.

Methods: We searched MEDLINE (to 04 January 2019) and the French pharmacovigilance database (to 09 August 2018) to identify male cases of acquired LQTS and TdP associated with endocrine hypogonadism or ADT; their narratives were gathered from reporting collaborators.

Results: We identified seven cases of TdP (one fatal) with endocrine hypogonadism, abnormally long QTc and morphologically abnormal T-wave notches. After reversion of low testosterone concentrations in the surviving patients (N=6), QTc shortened, T-wave morphology normalized and there was no TdP recurrence. Among these cases, none had mutation in the LQTS genes, three men required testosterone and three had reversible hypogonadism after resolution of a concurrent acute severe illness. We found an additional 27 reports of men with LQTS (N=6), TdP (N=9; 2/9 fatal) or sudden death (N=12; 10/12 fatal) suspected to be induced or favoured by ADT (24/27 for prostate cancer). Generally, after ADT withdrawal, QTc shortened and no TdP recurred.

Conclusion: We propose seeking for hypogonadism caused by endocrine conditions or ADT in men presenting with TdP. Caution is warranted when ADT is used in situations at risk of TdP. Testosterone may be useful to treat or prevent TdP.
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http://dx.doi.org/10.1016/j.acvd.2019.06.008DOI Listing
November 2019

Androgenic Effects on Ventricular Repolarization: A Translational Study From the International Pharmacovigilance Database to iPSC-Cardiomyocytes.

Circulation 2019 09 5;140(13):1070-1080. Epub 2019 Aug 5.

Department of Medicine (J-E.S., T.Y., J.J.M., B.C.K., A.M.G., D.M.R.), Vanderbilt University Medical Center, Nashville, TN.

Background: Male hypogonadism, arising from a range of etiologies including androgen-deprivation therapies (ADTs), has been reported as a risk factor for acquired long-QT syndrome (aLQTS) and torsades de pointes (TdP). A full description of the clinical features of aLQTS associated with ADT and of underlying mechanisms is lacking.

Methods: We searched the international pharmacovigilance database VigiBase for men (n=6 560 565 individual case safety reports) presenting with aLQTS, TdP, or sudden death associated with ADT. In cardiomyocytes derived from induced pluripotent stem cells from men, we studied electrophysiological effects of ADT and dihydrotestosterone.

Results: Among subjects receiving ADT in VigiBase, we identified 184 cases of aLQTS (n=168) and/or TdP (n=68; 11% fatal), and 99 with sudden death. Of the 10 ADT drugs examined, 7 had a disproportional association (reporting odds ratio=1.4-4.7; <0.05) with aLQTS, TdP, or sudden death. The minimum and median times to sudden death were 0.25 and 92 days, respectively. The androgen receptor antagonist enzalutamide was associated with more deaths (5430/31 896 [17%]; <0.0001) than other ADT used for prostate cancer (4208/52 089 [8.1%]). In induced pluripotent stem cells, acute and chronic enzalutamide (25 µM) significantly prolonged action potential durations (action potential duration at 90% when paced at 0.5 Hz; 429.7±27.1 (control) versus 982.4±33.2 (acute, <0.001) and 1062.3±28.9 ms (chronic; <0.001), and generated afterdepolarizations and/or triggered activity in drug-treated cells (11/20 acutely and 8/15 chronically). Enzalutamide acutely and chronically inhibited delayed rectifier potassium current, and chronically enhanced late sodium current. Dihydrotestosterone (30 nM) reversed enzalutamide electrophysiological effects on induced pluripotent stem cells.

Conclusions: QT prolongation and TdP are a risk in men receiving enzalutamide and other ADTs.

Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03193138.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.119.040162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6756939PMC
September 2019

Catheter ablation of electrical storm in patients with arrhythmogenic right ventricular cardiomyopathy.

Heart Rhythm 2020 01 5;17(1):41-48. Epub 2019 Jul 5.

Sorbonne Université, AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Institut de Cardiologie, Paris, France.

Background: Therapeutic strategies for electrical storm (ES) in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) are not well defined.

Objective: The purpose of this study was to report the acute and long-term results of ventricular tachycardia (VT) radiofrequency catheter ablation (RFCA) as a treatment of ES in patients with ARVC.

Methods: This multicenter study retrospectively enrolled 23 consecutive patients with ARVC (mean age 43.6 ± 16.7 years; all men) who underwent 24 RFCA procedures for ES between 2003 and 2015.

Results: Thirteen patients (57%) had a previous VT RFCA procedure; 14 (61%) had right ventricular dysfunction and 7 (30%) left ventricular ejection fraction ≤ 50%. The clinical VT was inducible in 19 procedures (79%). Epicardial ablation was performed in 4 procedures (17%). The median number of targeted VTs was 1 (range 1-6). Complete acute success (no VT inducible) was achieved in 11 procedures (46%) and partial acute success (clinical VT nor inducible) in 11 (46%). After a median follow-up of 3.9 years (range 1 month-10 years), ES recurred in 2 patients and end-stage heart failure developed in 4 (17%), leading to 1 death and 3 heart transplantations. At 1-year follow-up, the probability of freedom from VT recurrence was 75% and did not significantly predict long-term survival. At the last evaluation, 8 patients (35%) were free of non-β-blocker antiarrhythmic drugs as compared with 1 (4%) at baseline (P = .02).

Conclusion: Catheter ablation was efficient to prevent ES recurrence in patients with ARVC. However, these patients were at high risk of evolution toward ARVC-related heart failure that was not associated with VT recurrence.
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http://dx.doi.org/10.1016/j.hrthm.2019.06.022DOI Listing
January 2020

Development and Validation of a New Risk Prediction Score for Life-Threatening Ventricular Tachyarrhythmias in Laminopathies.

Authors:
Karim Wahbi Rabah Ben Yaou Estelle Gandjbakhch Frédéric Anselme Thomas Gossios Neal K Lakdawala Caroline Stalens Frédéric Sacher Dominique Babuty Jean-Noel Trochu Ghassan Moubarak Kostantinos Savvatis Raphaël Porcher Pascal Laforêt Abdallah Fayssoil Eloi Marijon Tanya Stojkovic Anthony Béhin Sarah Leonard-Louis Guilhem Sole Fabien Labombarda Pascale Richard Corinne Metay Susana Quijano-Roy Ivana Dabaj Didier Klug Marie-Christine Vantyghem Philippe Chevalier Pierre Ambrosi Emmanuelle Salort Nicolas Sadoul Xavier Waintraub Khadija Chikhaoui Philippe Mabo Nicolas Combes Philippe Maury Jean-Marc Sellal Usha B Tedrow Jonathan M Kalman Jitendra Vohra Alexander F A Androulakis Katja Zeppenfeld Tina Thompson Christine Barnerias Henri-Marc Bécane Eric Bieth Franck Boccara Damien Bonnet Françoise Bouhour Stéphane Boulé Anne-Claire Brehin Françoise Chapon Pascal Cintas Jean-Marie Cuisset Jean-Marc Davy Annachiara De Sandre-Giovannoli Florence Demurger Isabelle Desguerre Klaus Dieterich Julien Durigneux Andoni Echaniz-Laguna Romain Eschalier Ana Ferreiro Xavier Ferrer Christine Francannet Mélanie Fradin Bénédicte Gaborit Arnaud Gay Albert Hagège Arnaud Isapof Isabelle Jeru Raul Juntas Morales Emmanuelle Lagrue Nicolas Lamblin Olivier Lascols Vincent Laugel Arnaud Lazarus France Leturcq Nicolas Levy Armelle Magot Véronique Manel Raphaël Martins Michèle Mayer Sandra Mercier Christophe Meune Maud Michaud Marie-Christine Minot-Myhié Antoine Muchir Aleksandra Nadaj-Pakleza Yann Péréon Philippe Petiot Florence Petit Julien Praline Anne Rollin Pascal Sabouraud Catherine Sarret Stéphane Schaeffer Frederic Taithe Céline Tard Vincent Tiffreau Annick Toutain Camille Vatier Ulrike Walther-Louvier Bruno Eymard Philippe Charron Corinne Vigouroux Gisèle Bonne Saurabh Kumar Perry Elliott Denis Duboc

Circulation 2019 07 3;140(4):293-302. Epub 2019 Jun 3.

APHP, Cochin Hospital, Cardiology Department, FILNEMUS, Centre de Référence de Pathologie Neuromusculaire Nord/Est/Ile de France, Paris-Descartes, Sorbonne Paris Cité University (K.W., D.D.).

Background: An accurate estimation of the risk of life-threatening (LT) ventricular tachyarrhythmia (VTA) in patients with LMNA mutations is crucial to select candidates for implantable cardioverter-defibrillator implantation.

Methods: We included 839 adult patients with LMNA mutations, including 660 from a French nationwide registry in the development sample, and 179 from other countries, referred to 5 tertiary centers for cardiomyopathies, in the validation sample. LTVTA was defined as (1) sudden cardiac death or (2) implantable cardioverter defibrillator-treated or hemodynamically unstable VTA. The prognostic model was derived using the Fine-Gray regression model. The net reclassification was compared with current clinical practice guidelines. The results are presented as means (SD) or medians [interquartile range].

Results: We included 444 patients, 40.6 (14.1) years of age, in the derivation sample and 145 patients, 38.2 (15.0) years, in the validation sample, of whom 86 (19.3%) and 34 (23.4%) experienced LTVTA over 3.6 [1.0-7.2] and 5.1 [2.0-9.3] years of follow-up, respectively. Predictors of LTVTA in the derivation sample were: male sex, nonmissense LMNA mutation, first degree and higher atrioventricular block, nonsustained ventricular tachycardia, and left ventricular ejection fraction (https://lmna-risk-vta.fr). In the derivation sample, C-index (95% CI) of the model was 0.776 (0.711-0.842), and the calibration slope 0.827. In the external validation sample, the C-index was 0.800 (0.642-0.959), and the calibration slope was 1.082 (95% CI, 0.643-1.522). A 5-year estimated risk threshold ≥7% predicted 96.2% of LTVTA and net reclassified 28.8% of patients with LTVTA in comparison with the guidelines-based approach.

Conclusions: In comparison with the current standard of care, this risk prediction model for LTVTA in laminopathies significantly facilitated the choice of candidates for implantable cardioverter defibrillators.

Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03058185.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.118.039410DOI Listing
July 2019

Crossroads or "Flyovers" novel insights into ventricular tachycardia mechanisms: The path is twisting.

Pacing Clin Electrophysiol 2018 11 23;41(11):1564-1567. Epub 2018 Jul 23.

University Hospital La Pitié Salpétrière, Paris, France.

Diverging channels of activation may be observed in some ventricular tachycardia (VT) using ultra-high-density mapping. We present here cases of such diverging activation patterns as observed from 60 consecutive VT activation maps using the Rhythmia system™ (Boston Scientific, Marlborough, MA, USA). Diverging directions of activation in the same area with "crossroads" or "flyover" pattern can be traced, implying recording of independent multilayer channels. Adaptation of current automated recording by the 3D mapping system is mandatory for better investigating this phenomenon.
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http://dx.doi.org/10.1111/pace.13433DOI Listing
November 2018

Risk Stratification in Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia Without an Implantable Cardioverter-Defibrillator.

JACC Clin Electrophysiol 2018 06;4(6):757-768

AP-HP, Groupe Hospitalier Pitié-Salpêtrière, L'institut de Cardiométabolisme et Nutrition, Département de Cardiologie, Paris, France; Centre de Référence des Maladies Cardiaques Héréditaires, Paris, France; Sorbonne Universités, UPMC Univ Paris 06, Paris, France. Electronic address:

Objectives: The purpose of this study was to identify clinical factors associated with arrhythmic events and sudden cardiac death (SCD), and to evaluate the prognostic value of electrophysiological study (EPS) in arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) patients without implantable cardioverter-defibrillators (ICDs).

Background: ARVC/D is an inherited cardiomyopathy characterized by a risk of SCD. Few studies have evaluated predictive factors of ventricular arrhythmias (VAs) in patients without ICDs.

Methods: Between 2000 and 2010, all consecutive patients with ARVC/D without ICDs and with EPS at diagnosis were enrolled. Patients that received an ICD during follow-up were censored at the date of implantation, and in that case, only VAs that occurred before ICD implantation were analyzed. Risk factors for any VA event were determined by Cox regression. Patients that only experienced SCD or aborted cardiac arrest (ACA) were reported.

Results: A total of 137 consecutive patients (78% male) diagnosed with ARVC/D without ICD were enrolled. 31% had sustained ventricular tachycardia at diagnosis. After mean follow-up of 42 ± 31 months, 19 patients experienced an episode of sustained VA and 5 patients experienced a SCD/ACA. No event occurred in asymptomatic patients. Left ventricular ejection fraction ≤50% (p = 0.024), positive EPS (p = 0.017), and physical activity >6 h/week (p = 0.025) were independently associated with occurrence of VAs. SCD/ACA exclusively occurred in male probands with definite diagnosis and syncope.

Conclusions: In this cohort of ARVC/D patients without ICD, left ventricular ejection fraction ≤50%, positive EPS, and physical activity >6 h/week were independent predictors of VAs, whereas asymptomatic patients at diagnosis were at low risk. EPS predicted all VAs but had limited value to predict SCD/ACA.
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http://dx.doi.org/10.1016/j.jacep.2018.04.017DOI Listing
June 2018

Catheter ablation of organized atrial arrhythmias in orthotopic heart transplantation.

J Heart Lung Transplant 2017 Jul 21. Epub 2017 Jul 21.

Unité de Rythmologie, Institut de Cardiologie, Hôpital Pitié-Salpêtrière, Paris, France.

Background: Organized atrial arrhythmias (OAAs) are common after orthotopic heart transplantation (OHT). Some controversies remain about their clinical presentation, relationship with atrial anastomosis and electrophysiologic features. The objectives of this retrospective study were to determine the mechanisms of OAAs after OHT and describe the outcomes of radiofrequency catheter ablation (RFCA).

Methods: Thirty consecutive transplanted patients (mean age 48 ± 17 years, 86.6% male) underwent 3-dimensional electroanatomic mapping and RFCA of their OAA from 2004 to 2012 at our center.

Results: Twenty-two patients had biatrial anastomosis and 8 had bicaval anastomosis. Macro-reentry was the arrhythmia mechanism for 96% of patients. The electrophysiologic diagnoses were: cavotricuspid isthmus (CTI)-dependent atrial flutter (AFL) in 93% of patients (n = 28); perimitral AFL in 3% (n = 1); and focal atrial tachycardia (FAT) in 3% (n = 1). In 5 patients with biatrial anastomosis, a right FAT was inducible. Primary RFCA success was obtained in 93% of patients. Mean follow-up time was 39 ± 26.8 months. Electrical repermeation between recipient and donor atria, present in 20% of patients (n = 6), did not account for any of the OAAs observed. Survival without OAA relapse at 12, 24 and 60 months was 93%, 89% and 79%, respectively.

Conclusions: CTI-dependent AFL accounted for most instances of OAA after OHT, regardless of anastomosis type. Time from transplantation to OAA was shorter with bicaval than with biatrial anastomosis. RFCA was safe and provided good long-term results.
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http://dx.doi.org/10.1016/j.healun.2017.07.022DOI Listing
July 2017

Ten-year outcomes of monomorphic ventricular tachycardia catheter ablation in repaired tetralogy of Fallot.

Arch Cardiovasc Dis 2017 May 25;110(5):292-302. Epub 2017 Mar 25.

Unité de Rythmologie, Institut de Cardiologie, Hôpital Pitié-Salpêtrière, Paris, France. Electronic address:

Background: Monomorphic ventricular tachycardia (MVT) is common in adults with repaired tetralogy of Fallot (TOF), and is associated with sudden cardiac death. Management of MVT is not defined, and results of catheter ablation (CA) are limited.

Aims: To evaluate long-term outcomes of MVT CA in repaired TOF.

Methods: Thirty-four patients (mean age 32±10.3 years; 59% male) with repaired TOF underwent CA for symptomatic MVT between 1990 and 2012 in our centre; direct-current ablation (DCA) was used in 6%, radiofrequency followed by DCA in 29% and radiofrequency alone in 65%.

Results: Right ventricular (RV) dysfunction was present in 35% and left ventricular (LV) dysfunction in 21%. Mean numbers of clinical and induced MVTs were 1 and 2, respectively. Mean VT rate was 225±95bpm. Ablation targeted a single site (range 1-2), which was RV outflow tract in 85%. Primary success, defined as ventricular tachycardia (VT) termination during CA and final non-inducibility, was obtained in 82%. Seven patients (21%) required redo ablation in the first 3 months (before 2004; DCA). No death related to CA occurred. Mean follow-up time was 9.5±5.2 years. Antiarrhythmic therapy was discontinued in 71%. There were two cases of sudden cardiac death and four VT recurrences. Freedom from death and arrhythmia recurrence was 94% at 5 years, 81% at 10 years and 70% at 20 years. Global survival was 91% at 20 years. Baseline LV ejection fraction<60% was significantly associated with ventricular arrhythmia recurrence (hazard ratio 16.4, 95% confidence interval 1.8-147; P=0.01).

Conclusions: CA can safely address macroreentrant MVT in repaired TOF patients with an acceptable long-term rate of recurrence in this high-risk population. Anatomical classification of isthmuses with electroanatomical mapping provides reproducible endpoints for CA. Attention should be given to LV systolic function in risk assessment and selection of candidates for implantable cardioverter-defibrillator.
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http://dx.doi.org/10.1016/j.acvd.2017.01.009DOI Listing
May 2017

Long-Term Arrhythmic and Nonarrhythmic Outcomes of Lamin A/C Mutation Carriers.

J Am Coll Cardiol 2016 11;68(21):2299-2307

Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts. Electronic address:

Background: Mutations in LMNA are variably expressed and may cause cardiomyopathy, atrioventricular block (AVB), or atrial arrhythmias (AAs) and ventricular arrhythmias (VA). Detailed natural history studies of LMNA-associated arrhythmic and nonarrhythmic outcomes are limited, and the prognostic significance of the index cardiac phenotype remains uncertain.

Objectives: This study sought to describe the arrhythmic and nonarrhythmic outcomes of LMNA mutation carriers and to assess the prognostic significance of the index cardiac phenotype.

Methods: The incidence of AVB, AA, sustained VA, left ventricular systolic dysfunction (LVD) (= left ventricular ejection fraction ≤50%), and end-stage heart failure (HF) was retrospectively determined in 122 consecutive LMNA mutation carriers followed at 5 referral centers for a median of 7 years from first clinical contact. Predictors of VA and end-stage HF or death were determined.

Results: The prevalence of clinical manifestations increased broadly from index evaluation to median follow-up: AVB, 46% to 57%; AA, 39% to 63%; VA, 16% to 34%; and LVD, 44% to 57%. Implantable cardioverter-defibrillators were placed in 59% of patients for new LVD or AVB. End-stage HF developed in 19% of patients, and 13% died. In patients without LVD at presentation, 24% developed new LVD, and 7% developed end-stage HF. Male sex (p = 0.01), nonmissense mutations (p = 0.03), and LVD at index evaluation (p = 0.004) were associated with development of VA, whereas LVD was associated with end-stage HF or death (p < 0.001). Mode of presentation (with isolated or combination of clinical features) did not predict sustained VA or end-stage HF or death.

Conclusions: LMNA-related heart disease was associated with a high incidence of phenotypic progression and adverse arrhythmic and nonarrhythmic events over long-term follow-up. The index cardiac phenotype did not predict adverse events. Genetic diagnosis and subsequent follow-up, including anticipatory planning for therapies to prevent sudden death and manage HF, is warranted.
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http://dx.doi.org/10.1016/j.jacc.2016.08.058DOI Listing
November 2016

Multicenter Experience With Catheter Ablation for Ventricular Tachycardia in Lamin A/C Cardiomyopathy.

Circ Arrhythm Electrophysiol 2016 08;9(8)

From the Cardiovascular Division, Brigham and Women's Hospital, Boston, MA (S.K., S.H.B., B.A.K., R.M.J., G.F.M., N.K.L., W.G.S., U.B.T.); Department of Cardiology, Leiden University Medical Centre, The Netherlands (A.F.A.A., K.Z.); Hôpital Cardiologique du Haut-Lévêque (CHU), Bordeaux-Pessac & L'Institut de RYthmologie et Modélisation Cardiaque (LIRYC), Institut Hospitalo-Universitaire (IHU), Bordeaux, France (J.-M.S., F.S.); Centre Hospitalier Universitaire de Nancy (J.-M.S.); Toulouse University Hospital, Rangueil, Toulouse (P.M., A.R.); Département de Cardiologie, Hôpital Pitié-Salpêtrière, AP-HP (J.-M.S., F.S., E.G., X.W.); Cardio-myogenetic, Department of Biochimie and INSERM U582, University Hospital Pitié-Salpêtrière, AP-HP (P.R.); Centre de Référence Maladies Cardiaques Héréditaires, ICAN, Hôpital Pitié-Salpêtrière, Paris (P.C.); and Université de Versailles-Saint Quentin, Hôpital Ambroise Paré, AP-HP, Boulogne-Billancourt, France (P.C.).

Background: Lamin A/C (LMNA) cardiomyopathy is a genetic disease with a proclivity for ventricular arrhythmias. We describe the multicenter experience with percutaneous catheter ablation of sustained monomorphic ventricular tachycardia (VT) in LMNA cardiomyopathy.

Methods And Results: Twenty-five consecutive LMNA mutation patients from 4 centers were included (mean age, 55±9 years; ejection fraction, 34±12%; VT storm in 36%). Complete atrioventricular block was present in 11 patients; 3 patients were on mechanical circulatory support for severe heart failure. A median of 3 VTs were inducible per patient; in 82%, mapping was consistent with origin from scar in the basal left ventricle, particularly the septum, but also basal inferior wall and subaortic mitral continuity. After multiple procedures (median 2/patient; transcoronary alcohol in 6 and surgical cryoablation in 2 patients), acute success (noninducibility of any VT) was achieved in only 25% of patients. Partial success (inducibility of a nonclinical VT only: 50%) and failure (persistent inducibility of clinical VT: 12.5%) was attributed to intramural septal substrate in 13 of 18 patients (72%). Complications occurred in 25% of patients. After a median follow-up of 7 months after the last procedure, 91% experienced ≥1 VT recurrence, 44% received or were awaiting mechanical circulatory support or transplant for end-stage heart failure, and 26% died.

Conclusions: Catheter ablation of VT associated with LMNA cardiomyopathy is associated with poor outcomes including high rate of arrhythmia recurrence, progression to end-stage heart failure, and high mortality. Basal septal scar and intramural VT origin makes VT ablation challenging in this population.
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http://dx.doi.org/10.1161/CIRCEP.116.004357DOI Listing
August 2016

Implantable cardioverter-defibrillators in end-stage heart failure patients listed for heart transplantation: Results from a large retrospective registry.

Arch Cardiovasc Dis 2016 Aug-Sep;109(8-9):476-85. Epub 2016 Jun 22.

Département de Cardiologie, AP-HP, Hôpital Pitié-Salpêtrière, 47-83, boulevard de l'Hôpital, 75013 Paris, France.

Background: Implantable cardioverter-defibrillators (ICDs) are recommended in patients with low ejection fraction. However, the survival benefit of ICDs in patients with end-stage heart failure listed for heart transplantation is unclear.

Aim: To evaluate the ICD benefit on mortality in this population.

Methods: Three hundred and eighty consecutive patients listed for heart transplantation between 2005 and 2009 in one tertiary heart transplant centre were enrolled in a retrospective registry; 122 patients received an ICD before or within 3 months after being listed for heart transplantation (ICD group). Predictors of death on the waiting list were assessed by Cox regression.

Results: Overall, 15.6% of patients died while awaiting heart transplantation. Non-ICD patients presented more often haemodynamic compromise requiring mechanical circulatory support (29.1% vs. 9.8%; P<0.001), and were more likely to die while on the waiting list (19.0% vs. 8.3%; log-rank P=0.001). However, in the multivariable model, ICD did not remain an independent predictor of death. Need for mechanical circulatory support (P<0.001), low ejection fraction (P=0.001) and registration on the regular list (P=0.008) were the only independent predictors of death. Death was mainly caused by haemodynamic compromise (76.3% of deaths), which occurred more frequently in the non-ICD group (14.7% vs. 5.8%; log-rank P=0.002). Unknown/arrhythmic deaths did not differ significantly between the two groups (3.9% vs. 1.7%; log-rank P=0.21). ICD-related complications occurred in 21.4% of patients, mainly as a result of postoperative worsening of heart failure (11.9%).

Conclusion: Haemodynamic failure appears as the main determinant of mortality in patients with end-stage heart failure awaiting heart transplantation. ICD seems to have little benefit on survival in this population.
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http://dx.doi.org/10.1016/j.acvd.2016.02.005DOI Listing
January 2017

Substrate-based strategies for paroxysmal refractory VT catheter ablation: coming of age?

Arch Cardiol Mex 2014 Jan-Mar;84(1):55-6. Epub 2014 Mar 2.

Cardiology Institute, Rhythmology Unit, Pitié-Salpêtrière Hospital, Paris, France. Electronic address:

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http://dx.doi.org/10.1016/j.acmx.2013.11.002DOI Listing
January 2015

Post-ablation prolongation of atrioventricular nodal refractory period is correlated with long-term success of cryoablation for atrioventricular nodal reentrant tachycardia in the case of the persistence of a residual jump.

J Interv Card Electrophysiol 2012 Oct 5;35(1):63-9. Epub 2012 May 5.

Cardiology Institute, Rhythmology Unit, Pitié-Salpêtrière Hospital, 47-83, boulevard de l'Hôpital, 75651 Paris, France.

Purpose: A residual slow pathway after successful cryoablation for atrioventricular nodal reentrant tachycardia (AVNRT) is correlated with a higher recurrence rate. We described determinants of recurrence in subjects with a residual jump.

Methods: We analyzed the data of subjects with acute successful slow pathway cryoablation for AVNRT using a 6-mm-tip cryocatheter. Success was defined as AVNRT non-inducibility. Patients with no baseline elicitable jump, no inducible AVNRT, and transient first atrioventricular (AV) block at the last site were excluded.

Results: From 371 patients who underwent cryoablation from May 2002 to March 2011, 303 fulfilled the entry criteria (mean age, 41 ± 16; 222 women). Baseline AV nodal effective refractory period (ERP) was 272 ± 57 ms, postprocedural 331 ± 64 (P < 0.001), and the mean of the difference (Δ ERP) 60 ± 41. At the end of the procedure, 64 patients (21 %) had a residual jump, of whom 22 with a single echo. At 12 months follow-up, the actuarial recurrence-free rate was 70.3 % in patients with a residual jump and 86 % in those without (P = 0.01). In patients with a jump, only Δ AV nodal ERP was correlated with recurrence (37 ± 41 vs. 68 ± 47 ms; P < 0.04) while a single echo was not. The actuarial rate of recurrence was 60.8 % in patients with a Δ AV nodal ERP ≤ 30 ms and 18.8 % in those with a Δ AV nodal ERP >30 ms (P < 0.01).

Conclusions: Suppression of slow pathway conduction is the optimal endpoint for AVNRT cryoablation. A residual jump can be tolerated if AV nodal ERP postcryoablation is prolonged >30 ms.
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http://dx.doi.org/10.1007/s10840-012-9680-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3435514PMC
October 2012

Temporary transvenous VDD pacing as a bridge to permanent pacemaker implantation in patients with sepsis and haemodynamically significant atrioventricular block.

Europace 2012 Jul 2;14(7):981-5. Epub 2012 Jan 2.

Service de Cardiologie, Hôpital Européen Georges Pompidou, 20 rue Leblanc 75015, Paris, France.

Aims: Permanent pacemaker (PM) implantation is temporarily contraindicated in patients (pts) with sepsis. In patients with symptomatic atrioventricular (AV) block and infection, prolonged VVI pacing is therefore usually ensured by a ventricular pacing lead (PL) connected to an external PM generator. In patients with normal sinus function and heart failure, the VVI mode can exacerbate haemodynamic dysfunction. A single AV PL can be attractive to achieve physiological pacing. This study was designed to assess the efficacy and safety of temporary VDD pacing as a bridge to permanent PM implantation in patients with complete AV block until control of infection.

Methods And Results: This study included eight patients with complete AV block and sepsis with negative blood culture. Due to the presence of congestive heart failure, a single bipolar AV PL connected to an external VDD PM generator. At VDD implantation, P-wave amplitude was 1.9 ± 1.6 mV and R-wave was 11.3 ± 5.2 mV. The ventricular pacing threshold was 0.53 ± 0.1 V for a 0.5 ms pulse. Antibiotic therapy was instituted in all patients. A permanent VDD or DDD PM was implanted after 8 ± 2.5 days of temporary VDD pacing. At permanent PM implantation, the mean brain natriuretic peptide level had decreased and sepsis was controlled in all patients. No recurrence of sepsis was observed with a mean follow-up of 15.8 ± 5.3 months.

Conclusion: Temporary VDD pacing is a safe and effective method to achieve prolonged AV physiological pacing in patients with AV block until infection has been controlled.
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http://dx.doi.org/10.1093/europace/eur403DOI Listing
July 2012

[Treatment of atrial fibrillation in heart failure].

Therapie 2009 Mar-Apr;64(2):115-9. Epub 2009 Aug 11.

Service de Cardiologie A et Rythmologie, Hôpital Européen Georges Pompidou, Université Paris 5, Paris, France.

Treatment of patients with both atrial fibrillation and heart failure remains uneasy. In theory maintenance of sinus rhythm is desirable but the only pharmacological intervention able to do it safely is amiodarone. A trial of strategy randomisation, restoration of sinus rhythm or slowing of atrial fibrillation, has been done in patients with both atrial fibrillation and heart failure. This trial, named AF-CHF has shown neutral results, the 2 strategies, rhythm control or simple rate control were similar in terms of mortality. Dronedarone is an innovative drug bringing new possibilities in the treatment of atrial fibrillation but it is contra-indicated in case of severe heart failure. Another possible approach is that of non pharmacological techniques. Sinus rhythm maintenance may be obtained by pulmonary vein isolation. The other possibility is the ablation of atrio-ventricular node with implantation of a pacemaker, technique which is reserved to selected patients.
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http://dx.doi.org/10.2515/therapie/2009011DOI Listing
October 2009

Rates and predictors of appropriate implantable cardioverter-defibrillator therapy delivery: results from the EVADEF cohort study.

Am Heart J 2009 Aug;158(2):230-237.e1

Université Paris-Descartes, Hôpital Européen Georges Pompidou, AP-HP, Service de Cardiologie A, 20 rue Leblanc, 75908 Paris Cedex 15, France.

Background: The implantable cardioverter defibrillator (ICD) is the therapy of choice in patients at risk for sudden cardiac death in both primary and secondary prevention indication. There are no recent data concerning the delivery rate and etiology of appropriate ICD therapies in routine medical care.

Methods: The EVADEF study was a French multicenter, prospective, observational cohort study of ICD patients with a 2-year follow-up. Every 6 months we recorded patients' survival status and evaluated appropriate ICD therapies-antitachycardia pacing or shocks. Causes of ICD activation were also recorded from among ventricular tachycardia (VT), fast VT and ventricular fibrillation (VF).

Results: From 2001 to 2003, 2296 unselected patients were implanted and followed until 2005. During a mean follow-up of 20.5 months, 274 deaths occurred. In 2009 patients with cardiopathy, 22 patients per 100 person-years had at least one appropriate therapy. Twenty-four and 11 patients per 100 person-years had at least one therapy in secondary and primary prevention, respectively. Age >65 years, left ventricular ejection fraction <30% and secondary prevention were independently associated with appropriate therapy. Besides, 5 patients per 100 person-years had at least 1 episode of life-threatening arrhythmia (fast VT or VF). Left ventricular ejection fraction <30% and secondary prevention were independently associated with life-threatening arrhythmia. In 287 patients without cardiopathy, the rate of appropriate therapy was twice as less, whereas the rate of life-threatening arrhythmia was similar.

Conclusion: Over a 24-month follow-up, the rate of appropriate therapy was substantial while few patients had life-threatening arrhythmia. Appropriate therapies and life-threatening arrhythmia were more frequent in patients with secondary prevention indication.
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http://dx.doi.org/10.1016/j.ahj.2009.05.019DOI Listing
August 2009