Response to cardiac resynchronization therapy (CRT) is well-established in patients with typical left bundle branch block (LBBB) but modest or even negative in those with intraventricular conduction delay (IVCD). However, IVCD pattern is heterogeneous, and it is possible that QRS patterns may also respond to CRT. Consecutive baseline ECGs of 239 patients implanted between 2007 and 2010 with CRT were analyzed. ECGs were classified into the following three groups: (a) typical LBBB (TLBBB) according to accepted guidelines (n = 67); (b) IVCD with LBBB pattern criteria in V1, 1, and aVL but with QS or rS in V5–V6 which we defined as atypical LBBB (ALBBB) (n = 74); and (c) all other IVCD (OIVCD) patterns (n = 98). Endpoints were 2 years mortality and echocardiographic response, defined as a decrease of ≥ 10% in indexed LVESV or an increase of ≥ 5% in left ventricular ejection fraction at 1 year of follow-up. Baseline clinical characteristics were similar among all the three groups. Rates of echocardiographic response were lower among those with OIVCD compared to those with LBBB and ALBBB (50% vs. 75% and 72%, respectively, p = 0.01 for both comparisons). A multivariable model showed a lower likelihood of echocardiographic response in OIVCD [HR = 0.40; (0.16–0.98)] and a similar likelihood in ALBBBB [HR = 0.98; (0.40–2.40)] compared to TLBBB. Cumulative 2-year survival was 88% in ALBBB, 86% in TLBBB, and 76% in OIVCD (p value = 0.011). Patients with ALBBB may have a favorable echocardiographic response to CRT and display similar survival rates to typical LBBB. This subgroup of IVCD should be considered for CRT. Atypical left bundle branch morphology defined as QS or rS in lead V1, broad R waves in lead I, and aVL but with QS or rS in V5–V6 is associated with favorable echocardiographic response to CRT and displays similar survival rates to typical LBBB patients.

Invagination is an innovative technique for closing the left atrial appendage (LAA) to reduce the risk of thrombi formation. The influence of LAA invagination on the flow fields in the atria was investigated based on a computational fluid dynamics. The simulation results demonstrated that the novel invagination process can eliminate low velocities (blood stasis) and low shear rate and thus decrease the risk of thrombus formation during atrial fibrillation. This innovative technique may enhance the clinical treatment of patients with atrial fibrillation by improving the atrial flow field while lowering the risk of creating emboli.

OBJECTIVESThe phosphodiesterase-5 inhibitor sildenafil was developed for the treatment of pulmonary hypertension. The authors investigated the efficacy and safety of sildenafil in the early postoperative period after mitral valve surgery in patients with pulmonary hypertension.DESIGNA double-blind, placebo-controlled randomized trial was performed.SETTINGThe trial was performed in a single tertiary referral center.PARTICIPANTSFifty consecutive patients who experienced pulmonary hypertension and underwent mitral valve surgery.INTERVENTIONSPatients were randomly assigned to the following 2 groups: 25 patients received 20 mg sildenafil every 8 hours, and the remaining 25 patients received placebo during the same period. Hemodynamic parameters were studied by using a pulmonary artery catheter at baseline and every 6 hours up to 36 hours.RESULTSPatients who received sildenafil showed a decrease in mean pulmonary pressure, from 32 ± 7 mmHg at baseline to 26 ± 3 mmHg after 36 hours, whereas no change was seen in patients who received placebo (mean pulmonary pressure 34 ± 6 mmHg at baseline and 35 ± 5 mmHg after 36 h) (p < 0.001). No significant changes in systemic hemodynamic and oxygenation were observed. Patients who received sildenafil compared with those who received placebo had a median mechanical lung ventilation time of 16 (10-31) hours versus 19 (13-41) hours (p = 0.431), intensive care unit stay of 74 (44-106) hours versus 91 (66-141) hours (p = 0.410), and a total hospitalization stay of 7 (5-10) days versus 11 (7-15) days (p = 0.009).CONCLUSIONSThe immediate postoperative administration of sildenafil after mitral valve surgery is safe. Sildenafil demonstrates a favorable decreasing effect on pulmonary vascular pressure without systemic hypotension and ventilation-perfusion mismatch.

Reviewer 1 mentions the need for further mechanistic insight into how SK4 channel block rescues the electrical properties of cardiac cells, to strengthen the findings and increase their impact. S/he also points to a number of deficiencies in data processing and presentation, which are also shared in part by reviewers 2 and 3. I wish to add that during our reviewer cross-commenting exercise, #2 agreed that the concerns raised by #1 and 3 required appropriate action.

potential inversion was recorded in 9 (39%) patients (inversion group).Pacing threshold are significantly lower in inversion group compared to non-inversion group (implant: 1.06 6 0.8 V vs 1.86 6 0.8 V; P < 0.05, 1 week: 1.22 6 1.3 V vs 2.84 6 2.3 V; P ¼ 0.08, 1 month: 0.97 6 0.9 V vs 2.73 6 2.1 V; P < 0.05).Conclusions: HB potential inversion could be recorded during permanent HBP in 39% of patients and is associated with significantly lower pacing thresholds compared to patients in whom inversion was not recorded.HB potential inversion may be a predictor for superior short-term HB pacing thresholds.

The aim of this study was to evaluate the effects of fish oils, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), on ventricular tachyarrhythmic episodes (VTEs) in implantable cardioverter defibrillator (ICD) recipients with ischemic cardiomyopathy.

This study sought to determine the feasibility of using noninvasive cardiac hemodynamics (NICHE), a new noninvasive Doppler-based device, to monitor real-time, simultaneous tissue and blood-flow Doppler measurements in a clinical setting, and to obtain preliminary performance data compared to a commercially available system. Doppler-based measurements have been shown to correlate well with invasive hemodynamic data and diastolic function, but their use in clinical applications has been limited by various technical issues. The NICHE device was developed to obtain simultaneous tissue and blood-flow Doppler measurements automatically, in real-time and in a hands-free manner. Thirty participants (ten normal volunteers and 20 patients in a cardiac rehab program) underwent standard echocardiographic/Doppler studies followed immediately by NICHE monitoring. Early diastolic transmitral blood-flow velocity (E) and tissue Doppler myocardial wall velocity during early relaxation (E′) were acquired using a standard echo device; and E/E′ was derived post hoc. NICHE measurements included E, E′, and directly measured instantaneous E/E′. NICHE was successfully used in 28 participants. Measurements of ENICHE ranged from 40 cm/s to over 120 cm/s and correlated well with Eecho (R = 0.93). ENICHE′ ranged from 2 to 23 cm/s and correlated well with the averaged Eecho′ (R = 0.91). Directly measured E/ENICHE′ ratios ranged from 3 to 23 and correlated well with derived E/Eecho′ (R = 0.91). The NICHE device can monitor patients in a hands-free manner and can supply real-time Doppler derived measurements of hemodynamic parameters and diastolic function that correlate well with measurements from standard echo devices.

BACKGROUND The recessive form of catecholaminergic polymorphic ventricular tachycardia 2 (CPVT2) is caused by mutations in cardiac calsequestrin (CASQ2), leading to protein deficiency. OBJECTIVES The aims of this study were to develop a viral-delivered gene therapy for CPVT2 and to determine the relationship between CASQ2 expression and antiarrhythmic efficacy in a murine model.METHODS We used a murine model of CPVT2 caused by the D307H human mutation (CASQ2(D307H)) or CASQ2 knockout (CASQ2(Delta/Delta)). Adeno-associated virus (AAV) particles containing the CASQ2 gene (AAV(CASQ2)) were injected into the heart or intraperitoneally to 12-week-old mice. A telemetry device was implanted, and mice underwent provocation testing 7-8 weeks after gene therapy.RESULTS CASQ2(Delta/Delta) mice injected intracardiacally with AAVCASQ2 expressed 40% +/- 25% of the normal CASQ2 protein level, which was increased compared to untreated CASQ2(Delta/Delta) mice (n 5 10; P,.05). Intraperitoneal therapy led to a significantly elevated expression of the CASQ2 protein, which was comparable in CASQ2(D307H) (n = 12) and CASQ2(Delta/Delta) (n = 4) mice. All control mice with CPVT2 had nonsustained ventricular tachycardia (VT) and 8 of 13 had sustained VT on provocation. Expressing >= 33% of the normal CASQ2 level was needed to protect from nonsustained VT as well as stress-induced premature ventricular contractions. Lower levels of expression prevented sustained VT in AAVCASQ2-treated mice (0 of 26; P,. 001 vs controls).CONCLUSION AAV(CASQ2) displays a long-lasting capacity to attenuate and potentially cure CPVT2. Systemic delivery is feasible and convenient, reproducibly providing adequate levels of transgene expression. Antiarrhythmic efficacy depends on the CASQ2 level: >= 33% of the normal CASQ2 level is needed to prevent arrhythmia. However, even lower levels of protein protect from sustained VT, thereby potentially reducing the risk of sudden death.

Previous studies have shown that an acute coronary syndrome (ACS) may be triggered by external activities; however, their frequency, predictors, and significance are uncertain. We evaluated data from the National Israel Survey of Acute Coronary Syndromes, which was conducted in 2004 (February to March) in all 25 coronary care units and cardiac wards in Israel. Demographic and clinical data were recorded for consecutive participants, including potential triggers and time of symptom onset of ACS. Among the 1,849 patients who completed the trigger question, 1/4 (25.9%) reported a possible trigger, comprising heavy physical exertion (15.2%), emotional stress (8.3%), anger (1.1%), heavy meal (1.3%), and sexual activity (0.5%). Predictors of a triggered ACS were age <65 years, previous angina, no previous angiotensin-converting enzyme inhibitors/angiotensin 2 receptor blockers, impaired functional class, not having typical chest pain on admission, and a final diagnosis of unstable angina. The highest proportion of triggered ACS was between noon and 6 P.M. Physical exertion as a trigger was associated with reduced in-hospital mortality (0.4% vs 2.8%, p <0.05) and 1-year mortality. Emotional stress as a trigger did not influence in-hospital or 1-year mortality; however among those discharged from hospital, it was associated with increased 30-day rehospitalization (27.6% vs 19.3%, p <0.05) and a trend toward increased mortality (4.1% vs 2.0%, p = 0.10). (C) 2017 Elsevier Inc. All rights reserved.

HomeCirculationVol. 133, No. 4Response to Letters Regarding Article, "Clinical Management of Catecholaminergic Polymorphic Ventricular Tachycardia: The Role of Left Cardiac Sympathetic Denervation" Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBResponse to Letters Regarding Article, "Clinical Management of Catecholaminergic Polymorphic Ventricular Tachycardia: The Role of Left Cardiac Sympathetic Denervation" Gaetano M. De Ferrari, MD Veronica Dusi, MD Carla Spazzolini, DVM, MS J. Martijn Bos, MD, PhD Dominic J. Abrams, MD, MRCP Charles I. Berul, MD, FAHA Lia Crotti, MD, PhD Michael Eldar, MD, FAHA Maria Kharlap, MD Asaad Khoury, MD Andrew D. Krahn, MD Antoine Leenhardt, MD Christopher R. Moir, MD Attilio Odero, MD Louise Olde Nordkamp, MD Thomas Paul, MD Ferran Rosés i Noguer, MD Maria Shkolnikova, MD Jan Till, MD Arthur A.M. Wilde, MD, FAHA Michael J. Ackerman, MD, PhD Peter J. Schwartz, MD, FAHA Gaetano M. De FerrariGaetano M. De Ferrari Department of Cardiology and Cardiovascular Clinical Research Center, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy Veronica DusiVeronica Dusi Department of Cardiology and Cardiovascular Clinical Research Center, Fondazione IRCCS Policlinico San Matteo, Department of Molecular Medicine, University of Pavia, Pavia, Italy Carla SpazzoliniCarla Spazzolini Center for Cardiac Arrhythmias of Genetic Origin, IRCCS Istituto Auxologico Italiano, Milano, Italy J. Martijn BosJ. Martijn Bos Departments of Medicine, Pediatrics, and Molecular Pharmacology & Experimental Therapeutics, Divisions of Cardiovascular Diseases and Pediatric Cardiology Windland Smith Rice Sudden Death Genomics Laboratory, Mayo Clinic, Rochester, MN Dominic J. AbramsDominic J. Abrams Cardiac Arrhythmia Service, Department of Cardiology, Children's Hospital, Boston, MA Charles I. BerulCharles I. Berul Division of Cardiology, Children's National Heart Institute, George Washington University, Washington, DC Lia CrottiLia Crotti Department of Molecular Medicine, University of Pavia, Pavia, ItalySan Luca Hospital, IRCCS Istituto Auxologico Italiano, Milano, Italy Michael EldarMichael Eldar Heart Institute Leviev Heart Center, Sheba Medical Center, Sackler School of Medicine, Tel Aviv University, Tel Hashomer, Israel Maria KharlapMaria Kharlap Department of Clinical Cardiology and Molecular Genetics, National Center for Preventive Medicine, Ministry of Healthcare, Russian Federation, Moscow, Russia Asaad KhouryAsaad Khoury The Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel Andrew D. KrahnAndrew D. Krahn Division of Cardiology, University of British Columbia, Vancouver, Canada Antoine LeenhardtAntoine Leenhardt AP-HP, Hôpital Bichat, Service de Cardiologie et Centre de Référence des Maladies, Cardiaques Héréditaires, ParisUniversité Paris Diderot, Sorbonne Paris Cité, Paris, France Christopher R. MoirChristopher R. Moir Departments of Medicine, Pediatrics, and Molecular Pharmacology & Experimental Therapeutics, Divisions of Cardiovascular Diseases and Pediatric Cardiology Windland Smith Rice Sudden Death Genomics Laboratory, Mayo Clinic, Rochester, MN Attilio OderoAttilio Odero Division of Vascular Surgery, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy Louise Olde NordkampLouise Olde Nordkamp Heart Centre AMC, Department of Cardiology, Academic Medical Centre, Amsterdam, The Netherlands Thomas PaulThomas Paul Department of Pediatric Cardiology and Intensive Care Medicine, University Hospital, Georg-August-University, Göttingen, Germany Ferran Rosés i NoguerFerran Rosés i Noguer Royal Brompton Hospital, London, UK Maria ShkolnikovaMaria Shkolnikova Research Clinical Institute for Pediatrics of the Pirogov National, Research Medical University, Moscow, Russia Jan TillJan Till Royal Brompton Hospital, London, UK Arthur A.M. WildeArthur A.M. Wilde Heart Centre AMC, Department of Cardiology, Academic Medical Centre, Amsterdam, The NetherlandsPrincess Al Jawhara Albrahim Centre of Excellence in Research of Hereditary Disorders, King Abdulaziz University, Jeddah, Saudi Arabia Michael J. AckermanMichael J. Ackerman Departments of Medicine, Pediatrics, and Molecular Pharmacology & Experimental Therapeutics, Divisions of Cardiovascular Diseases and Pediatric Cardiology Windland Smith Rice Sudden Death Genomics Laboratory, Mayo Clinic, Rochester, MN Peter J. SchwartzPeter J. Schwartz Center for Cardiac Arrhythmias of Genetic Origin, IRCCS Istituto Auxologico Italiano, Milano, Italy Originally published26 Jan 2016https://doi.org/10.1161/CIRCULATIONAHA.115.019465Circulation. 2016;133:e366–e367We are glad to have the opportunity to respond to the points kindly raised by Drs Patanè and Gow in reference to our recent article on catecholaminergic polymorphic ventricular tachycardia (CPVT).1We are obviously aware of the article by Faggioni et al,2 which includes 1 of the coauthors of our article, Dr Wilde. We also have direct experience with a few CPVT patients who had a reduction or disappearance of the ventricular arrhythmias induced by exercise when heart rate increased further (usually to >140 bpm). We have not discussed atrial overdrive pacing simply because we do not believe that these data and observations have direct relevance to the ongoing clinical management of CPVT patients in everyday life. The concept of atrial high-rate pacing (>120 bpm) may be of potential value in the in-hospital management of emergencies, but we find it difficult to recommend that heart rate should be increased permanently, or during exercise, to >140 bpm. In addition, how would it be possible to exclude that such an intervention, activated in the out-of-hospital setting, would not precipitate ventricular tachycardia or ventricular fibrillation? Our article was focused on how to reduce the incidence of life-threatening arrhythmias in the safest way. Rate support of CPVT patients who have symptomatic bradycardia in response to therapeutic β-blockade is always a consideration in CPVT.We acknowledge the comments concerning the possibility of anatomic variations in the cervicothoracic ganglion. Dr Gow has downplayed the statements by a recognized expert in the field (Andrew Armour),3 who wrote that "all major cardiopulmonary nerves were found to arise from the stellate ganglia" and focused on the conclusions by Marcer et al4 and Pather et al,5 largely based on embalmed cadavers and on fetuses, that in ≈20% of cases the inferior cervical ganglion and the first thoracic ganglion were separate. In our personal experience of >40 years in hundreds of patients in whom we performed left (and sometimes right) cardiac sympathetic denervation, we have always found the stellate ganglion to be the fusion of the last cervical and first thoracic ganglia. The current video-assisted thoracoscopic approach allows a clear and comprehensive visualization of the anatomy and excludes the possibility of missing a significant anatomic variant.Another part of Dr Gow's letter is clinically relevant. He suggests a correlation between the possibility of anatomic variations of the stellate ganglion and the recurrence of syncope, and very seldom of cardiac arrest, in CPVT patients (and in patients with long QT syndrome) treated with left cardiac sympathetic denervation. Although we consider the issue of anatomic variability of minor importance in favoring the occurrence of arrhythmia recurrences, the deliberate lack of removal of either T4 or of the lower part of the stellate ganglion (T1), to exclude any risk of Horner syndrome, is a true concern. Patients with intentionally incomplete denervation did show a much higher risk of recurrences than patients with complete denervation in our study.1 Should a functionally incomplete denervation be frequent because of anatomic variability, one would expect a higher frequency of recurrences. Be that as it may, an arrhythmia recurrence does not necessarily imply that the left-sided denervation was incomplete. The right cardiac sympathetic nerves also release norepinephrine in the ventricles, and their contribution may be important in some patients; in addition, circulating catecholamines released by the adrenal glands may play a role. Thus, to explain incomplete arrhythmia protection, there is no need to invoke anatomic variability. The suggested possibility of a "further surgical exploration of the same side" does not consider the growth of connective tissue after surgery.Thanks to the current use of video-assisted thoracoscopic surgery, we will closely monitor the real occurrence of significant anatomic variations in our cohort of patients. To treat our patients with CPVT and long QT syndrome, we will continue, as we have always done, to remove the lower half of the left stellate ganglion together with the first 4 thoracic ganglia, and, in the case of failure, we will attempt right cardiac sympathetic denervation. Taking into account that the currently reported recurrence rate does include cases of deliberate incomplete denervation, we consider a reduction of events close to 90% quite gratifying.Gaetano M. De Ferrari, MDDepartment of Cardiology and Cardiovascular Clinical Research CenterFondazione IRCCS Policlinico San MatteoPavia, ItalyVeronica Dusi, MDDepartment of Cardiology and Cardiovascular Clinical Research CenterFondazione IRCCS Policlinico San MatteoDepartment of Molecular MedicineUniversity of PaviaPavia, ItalyCarla Spazzolini, DVM, MSCenter for Cardiac Arrhythmias of Genetic OriginIRCCS Istituto Auxologico ItalianoMilano, ItalyJ. Martijn Bos, MD, PhDDepartments of Medicine, Pediatrics, and Molecular Pharmacology & Experimental TherapeuticsDivisions of Cardiovascular Diseases and Pediatric CardiologyWindland Smith Rice Sudden Death Genomics LaboratoryMayo ClinicRochester, MNDominic J. Abrams, MD, MRCPCardiac Arrhythmia ServiceDepartment of CardiologyChildren's HospitalBoston, MACharles I. Berul, MD, FAHADivision of CardiologyChildren's National Heart InstituteGeorge Washington UniversityWashington, DCLia Crotti, MD, PhDDepartment of MolecularMedicine University of PaviaPavia, ItalySan Luca HospitalIRCCS Istituto Auxologico ItalianoMilano, ItalyMichael Eldar, MD, FAHAHeart Institute, Leviev Heart CenterSheba Medical CenterSackler School of MedicineTel Aviv UniversityTel Hashomer, IsraelMaria Kharlap, MDDepartment of Clinical Cardiology and Molecular GeneticsNational Center for Preventive MedicineMinistry of HealthcareRussian FederationMoscow, RussiaAsaad Khoury, MDThe Bruce Rappaport Faculty of MedicineTechnionHaifa, IsraelAndrew D. Krahn, MDDivision of CardiologyUniversity of British ColumbiaVancouver, CanadaAntoine Leenhardt, MDAP-HP, Hôpital BichatService de Cardiologie et Centre de Référence des MaladiesCardiaques Héréditaires, ParisUniversité Paris DiderotSorbonne Paris CitéParis, FranceChristopher R. Moir, MDDepartments of Medicine, Pediatrics, and Molecular Pharmacology & Experimental TherapeuticsDivisions of Cardiovascular Diseases and Pediatric CardiologyWindland Smith Rice Sudden Death Genomics LaboratoryMayo Clinic, Rochester, MNAttilio Odero, MDDivision of Vascular SurgeryFondazione IRCCS Policlinico San MatteoPavia, ItalyLouise Olde Nordkamp, MDHeart Centre AMCDepartment of CardiologyAcademic Medical CentreAmsterdam, The NetherlandsThomas Paul, MDDepartment of Pediatric Cardiology and Intensive Care MedicineUniversity HospitalGeorg-August-UniversityGöttingen, GermanyFerran Rosés i Noguer, MDRoyal Brompton HospitalLondon, UKMaria Shkolnikova, MDResearch Clinical Institute for Pediatrics of the Pirogov NationalResearch Medical UniversityMoscow, RussiaJan Till, MDRoyal Brompton HospitalLondon, UKArthur A.M. Wilde, MD, FAHAHeart Centre AMCDepartment of CardiologyAcademic Medical CentreAmsterdam, The NetherlandsPrincess Al Jawhara Albrahim Centre of Excellence in Research of Hereditary DisordersKing Abdulaziz UniversityJeddah, Saudi ArabiaMichael J. Ackerman, MD, PhDDepartments of Medicine, Pediatrics, and Molecular Pharmacology & Experimental TherapeuticsDivisions of Cardiovascular Diseases and Pediatric CardiologyWindland Smith Rice Sudden Death Genomics LaboratoryMayo Clinic, Rochester, MNPeter J. Schwartz, MD, FAHACenter for Cardiac Arrhythmias of Genetic OriginIRCCS Istituto Auxologico ItalianoMilano, ItalyDisclosuresDr Wilde is a member of the Sorin Scientific Advisory Board. Dr Ackerman is a consultant for Boston Scientific, Gilead Sciences, Medtronic, and St. Jude Medical. In addition, Dr Ackerman and Mayo Clinic receive sales-based royalties from Transgenomic's FAMILION-CPVT genetic test. The other authors report no conflicts.References1. De Ferrari GM, Dusi V, Spazzolini C, Bos JM, Abrams DJ, Berul CI, Crotti L, Davis AM, Eldar M, Kharlap M, Khoury A, Krahn AD, Leenhardt A, Moir CR, Odero A, Olde Nordkamp L, Paul T, Rosés I Noguer F, Shkolnikova M, Till J, Wilde AA, Ackerman MJ, Schwartz PJ.Clinical management of catecholaminergic polymorphic ventricular tachycardia: the role of left cardiac sympathetic denervation.Circulation. 2015; 131:2185–2193. doi: 10.1161/CIRCULATIONAHA.115.015731.LinkGoogle Scholar2. Faggioni M, Hwang HS, van der Werf C, Nederend I, Kannankeril PJ, Wilde AA, Knollmann BC.Accelerated sinus rhythm prevents catecholaminergic polymorphic ventricular tachycardia in mice and in patients.Circ Res. 2013; 112:689–697. doi: 10.1161/CIRCRESAHA.111.300076.LinkGoogle Scholar3. Janes RD, Brandys JC, Hopkins DA, Johnstone DE, Murphy DA, Armour JA.Anatomy of human extrinsic cardiac nerves and ganglia.Am J Cardiol. 1986; 57:299–309.CrossrefMedlineGoogle Scholar4. Marcer N, Bergmann M, Klie A, Moor B, Djonov V.An anatomical investigation of the cervicothoracic ganglion.Clin Anat. 2012; 25:444–451. doi: 10.1002/ca.21266.CrossrefMedlineGoogle Scholar5. Pather N, Partab P, Singh B, Satyapal KS.Cervico-thoracic ganglion: its clinical implications.Clin Anat. 2006; 19:323–326. doi: 10.1002/ca.20214.CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Roston T, Cunningham T and Sanatani S (2017) Advances in the diagnosis and treatment of catecholaminergic polymorphic ventricular tachycardia, Cardiology in the Young, 10.1017/S1047951116002237, 27:S1, (S49-S56), Online publication date: 1-Jan-2017. January 26, 2016Vol 133, Issue 4 Advertisement Article InformationMetrics © 2016 American Heart Association, Inc.https://doi.org/10.1161/CIRCULATIONAHA.115.019465PMID: 26811283 Originally publishedJanuary 26, 2016 PDF download Advertisement SubjectsArrhythmiasGenetics

Catecholaminergic Polymorphic Ventricular Tachychardia (CPVT) is a stressed-provoked ventricular arrhythmia triggered by diastolic intracellular calcium leak, which can lead to sudden death. While many studies have focused on ventricular tachyarrhythmia, very little is known about the pathological pacemaker of this disease. Recently, we identified the calcium-activated potassium channel SK4 as a new player involved in the pacemaker of cardiomyocytes derived from human embryonic stem cells. Here we used human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs) from healthy and CPVT2 (CASQ2 D307H) patients, mouse sinoatrial node (SAN) cells as well as knock-in (CASQ2 D307H) and knock-out mice to investigate the pacemaker arrhythmogenic properties of this disease. Using TRAM-34, a selective blocker of SK4 channels, we could isolate SK4 currents in both wild-type and CPVT2-derived hiPS-CMs. Delayed afterdepolarizations in CPVT2-derived hiPS-CMs cells were observed following application of the beta-adrenergic agonist isoproterenol (Iso). Interestingly, the iso-provoked arrhythmias were markedly reduced by adding TRAM-34 (2-5 μM). Like in hiPS-CMs, we also identified TRAM34-sensitive SK4 currents in mouse SAN. Under continuous ECG recording, we found that intraperitoneal injection of the SK4 blockers TRAM 34 or clotrimazole (20 mg/kg) produced a bradycardic effect in WT, knock-in and knock-out mice, thereby increasing the PP and PR intervals. Remarkably, TRAM 34 or clotrimazole dramatically reduced the ECG arrhythmia features of knock-in and knock-out mice like ventricular tachycardia, ventricular premature contractions or bigeminy. These results suggest that SK4 Ca2+ activated K+ channels play a critical role in normal and diseased pacemaker dysfunction and notably that found in CPVT2. Our data also indicate that SK4 channel blockers could open new horizons in the management of CPVT rhythm disorders.

BACKGROUND Transvenous lead extraction can lead to tricuspid valve damage. OBJECTIVES To assess the incidence, risk factors and clinical outcome of tricuspid regurgitation (TR) following lead extraction. METHODS We prospectively collected data on patients who underwent lead extraction at the Sheba Medical Center prior to laser use (i.e., before 2012). Echocardiography results before and following the procedure were used to confirm TR worsening, defined as an echocardiographic increase of at least one TR grade. Various clinical and echocardiographic parameters were analyzed as risk factors for TR. Clinical and echocardiographic follow-up was conducted to assess the clinical significance outcome of extraction-induced TR. RESULTS Of 152 patients who underwent lead extraction without laser before 2012, 86 (56%) (192 electrodes) had echocardiography results before and within one week following the procedure. New or worsening TR was discovered in 13 patients (15%). Use of mechanical tools and younger age at extraction were found on multivariate analysis to be factors for TR development (P = 0.04 and P = 0.03 respectively). Average follow-up was 22.25 ± 21.34 months (range 8-93). There were no significant differences in the incidence of right-sided heart failure (50% vs. 23%, P = 0.192) or hospitalizations due to heart failure exacerbations (37.5% vs. 11%, P = 0.110). No patient required tricuspid valve repair or replacement. Death rates were similar in the TR and non-TR groups (20% vs. 33%). CONCLUSIONS TR following lead extraction is not uncommon but does not seem to affect survival or outcomes such as need for valve surgery. Its long-term effects remain to be determined.

Introduction: Cases of ventricular tachycardia (TV) with hemodynamic compromise present a challenge in achieving non-inducibility by radiofrequency catheter ablation (RFCA). We report our experience of VT RFCA facilitated by elective mechanical circulatory support. Methods and results: Five patients with hemodynamically unstable, recurrent ventricular arrhythmias that were unresponsive to medical therapy underwent extracorporeal membrane oxygenation (ECMO) assisted RFCA of scar related VT. All underwent RFCA under general anesthesia and were connected to an ECMO circuit maintained at minimum flow of 1.5 L /min. In case of VT or VF the blood flow of the ECMO circuit was increased to 4 L/min to allow hemodynamic stability and adequate systemic organ perfusion. A total of 8 VTs were observed. In 4 cases, we mapped during VT the critical isthmus was found and ablated. Four VTs were targeted by substrate mapping only. Complete success, defined as non-inducibility with aggressive program stimulation of any VT, was achieved in 4 patients. In a single patient, a non-clinical VT was still inducible. He died of septic shock 24 hour after the procedure. The remaining 4 were free of ventricular arrhythmia as proven by implanted defibrillator interrogation, over a median follow up of 16 months. Conclusion: ECMO implantation for VTRFCA is safe and assists in reaching the desired endpoint of noninducibility. This approach should be considered in high risk patients who may not otherwise tolerate such procedures.

Background: Patients with coronary heart disease demonstrate changes in skin microcirculation and a decrease in cutaneous blood mass.Objective: The goal of this study was to assess the feasibility of diagnosing myocardial ischemia based on peripheral microcirculatory variables.Methods: The skin microcirculatory measurements were monitored using an LPT system comprising a Laser Doppler Flowmeter (LDF), a photoplethysmograph (PPG) and a transcutaneous oxygen tension device (tc-PO2). Concurrently, heart rate and blood pressure were monitored. Measurements were performed before and after exercise stress test. Subjects were divided into ischemic (20) and nonischemic (27) patients based on myocardial perfusion imaging (MPI).Results: The results indicate differences in LPT variables between ischemic and nonischemic patients following exercise, while no differences in the central variable values were observed between the two groups.Conclusions: Peripheral microcirculatory variables may be useful for non-invasive assessment of myocardial ischemia. The system has clinical potential for sensitive and noninvasive monitoring of vital variables during medical procedures in clinics, as well as in home care for patients who suffer from ischemic cardiac diseases. (C) 2015 Elsevier Masson SAS. All rights reserved.

BACKGROUNDCatecholaminergic polymorphic ventricular tachycardia (CPVT) is a genetic disorder causing life-threatening arrhythmias whenever sympathetic activity increases. β-Βlockers are the mainstay of therapy; when they fail, implantable cardioverter-defibrillators (ICDs) are used but often cause multiple shocks. Preliminary results with flecainide appear encouraging. We proposed left cardiac sympathetic denervation (LCSD) as useful additional therapy, but evidence remains anecdotal.METHODS AND RESULTSWe report 63 patients with CPVT who underwent LCSD as secondary (n=54) or primary (n=9) prevention. The median post-LCSD follow-up was 37 months. The 9 asymptomatic patients remained free of major cardiac events. Of the 54 patients with prior major cardiac events either on (n=38) or off (n=16) optimal medical therapy, 13 (24%) had at least 1 recurrence: 0 patients had an aborted cardiac arrest, 2 patients had syncope only, 10 patients had ≥1 appropriate ICD discharges, and 1 patient died suddenly. The 1- and 2-year cumulative event-free survival rates were 87% and 81%. The percentage of patients with major cardiac events despite optimal medical therapy (n=38) was reduced from 100% to 32% (P<0.001) after LCSD, and among 29 patients with a presurgical ICD, the rate of shocks dropped by 93% from 3.6 to 0.6 shocks per person per year (P<0.001). Patients with an incomplete LCSD (n=7) were more likely to experience major cardiac events after LCSD (71% versus 17%; P<0.01) than those with a complete LCSD.CONCLUSIONSLCSD is an effective antifibrillatory intervention for patients with CPVT. Whenever syncope occurs despite optimal medical therapy, LCSD could be considered the next step rather than an ICD and could complement ICDs in patients with recurrent shocks.