Electrogram-guided Endomyocardial Biopsy Yield in Patients with Suspected Cardiac SarcoidosisAbbas Hoteit MD, Marwan M. Refaat, MDDivision of Cardiology, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, LebanonRunning Title: Electrogram-guided Biopsy in Cardiac SarcoidosisWords: 819 (excluding the title page and references)Keywords: Cardiac Sarcoidosis, Heart Diseases, Cardiovascular Diseases, Cardiac ArrhythmiasFunding: NoneDisclosures: NoneCorresponding Author:Marwan M. Refaat, MD, FACC, FAHA, FHRS, FASE, FESC, FACP, FAAMAAssociate Professor of MedicineDirector, Cardiovascular Fellowship ProgramDepartment of Internal Medicine, Cardiovascular Medicine/Cardiac ElectrophysiologyDepartment of Biochemistry and Molecular GeneticsAmerican University of Beirut Faculty of Medicine and Medical CenterPO Box 11-0236, Riad El-Solh 1107 2020- Beirut, LebanonUS Address: 3 Dag Hammarskjold Plaza, 8th Floor, New York, NY 10017, USAOffice: +961-1-350000/+961-1-374374 Extension 5353 or Extension 5366 (Direct)Sarcoidosis is a multisystem disease that is characterized by T-cell mediated formation of noncaseating granulomas in affected organs. The disease commonly might involve hilar lymphadenopathy, lungs, liver, spleen, heart, and other organs. The natural course and prognosis of the disease generally depends on the extent of the disease and the organs affected where spontaneous remission occurs in around two-thirds of patient.1 Involvement of the heart is recognized in around 30% of patients and is associated with poor prognosis.2 The presentation of patients with cardiac sarcoidosis varies significantly; it can range from mild to severe disease such as heart failure and fatal arrhythmias. Patients with cardiomyopathies might require implantable cardiac defibrillators or cardiac resynchronization therapy for sudden death prevention.3,4 Cardiac sarcoidosis can either present alongside extracardiac manifestations or isolated.5Diagnosis of cardiac sarcoidosis presents a particular challenge since there is no gold standard diagnostic tool and the presentation is variable.6 There are no disease-specific biomarkers that can reliably be used for diagnosis. Clinicians typically rely on current published guidelines for diagnostic criteria of cardiac sarcoidosis such as those of Heart Rhythm Society (HRS) and the Japanese Ministry of Health and Welfare (JMHW). The revised JMHW criteria provide a diagnosis either through histological evidence on biopsy or through the fulfillment of major and minor criteria that do not include cardiac PET whereas the HRS criteria provide either a definite pathway for diagnosis through histology or a clinical pathway for diagnosis of probable cardiac sarcoidosis that includes both cardiac PET and CMR as criteria.7,8 A definitive diagnosis of cardiac sarcoidosis can be obtained if endomyocardial biopsy can show noncaseating granulomas in the context of suspected cardiac sarcoidosis and other granulomatous diseases are excluded. However, endomyocardial biopsy has a low sensitivity of 20-30% since it is limited by several factors such as technique, sampling, patchy distribution of granulomas, location of lesions, and stage of the disease at the time of biopsy.5 Areas of inflammation and scarring typically show abnormal electrogram morphology, hence, it is thought that electrogram guidance may help in increasing the yield of endomyocardial biopsies. Electrogram guidance would potentially help avoiding normal myocardium during biopsy leading to increased yield and sensitivity.9In their study, Ezzedine et al. assessed the diagnostic yield of electrogram-guided endomyocardial biopsy and investigated association between positive endomyocardial biopsy and prognosis in patients with suspected cardiac sarcoidosis.10 This retrospective observational study included seventy-nine patients between 2011 and 2019 who had suspected cardiac sarcoidosis based on clinical presentation and findings on late gadolinium-enhancement cardiac magnetic resonance and/or cardiac positron emission tomography-computed tomography with N-13 NH3 perfusion imaging and F-18 fluorodeoxyglucose. Biopsy was done in patients suspicious of cardiac sarcoidosis in patients without extracardiac sarcoidosis or those with extracardiac disease but atypical/equivocal findings of cardiac sarcoidosis on imaging and meeting criteria in HRS guidelines as per the routine practice in Mayo Clinic. Mapping of the heart was performed prior to biopsy with partial guidance based on pre-procedural cardiac imaging. In patients with no identifiable abnormalities on electrogram, biopsies were taken from areas corresponding to those with abnormalities on pre-procedural imaging. Collected specimens were processed according to protocol and assessed by a blinded specialist. These specimens were considered positive if there was a combination of non-necrotizing granulomas, interstitial fibrosis, and scatted eosinophils. The study showed that electrogram-guided endomyocardial biopsy was associated with an adequate negative predictive value but low positive predictive value. A diagnosis of probable cardiac sarcoidosis can be made in patients with extracardiac manifestations according to established guidelines whereas in patients with suspected isolated cardiac sarcoidosis this is more difficult and as such biopsies play a more major role here. This study showed that, when guided by electrograms, endomyocardial biopsies had a higher diagnostic yield (41%) than that established in literature around 20-25%. Utilizing both abnormalities seen on both electrograms and on CMR or PET showed the highest diagnostic yield in endomyocardial biopsies. This acts as an important point of consideration for further research because accurate and timely diagnosis is paramount due to the diagnostics challenges and poor prognosis seen in cardiac sarcoidosis.10Previous evidence had shown that a positive endomyocardial biopsy for sarcoidosis was associated with poor prognosis.11However, LVAD and transplantation-free survival was found to be similar regardless of status of endomyocardial biopsy in this study.10 The authors explained that this could be explained by earlier detection of disease, differences in treatment, or more subtle detection of areas of involvement through electrograms. This study was well conducted but has been limited by its nature of being a retrospective observational study. Also, mapping was mostly limited to the right ventricle which may have underestimated the diagnostic yield of biopsies. This study represents the management done in a single tertiary care center which may not represent the same practice in other institutions with different facilities. Further multicenter and prospective studies are warranted to corroborate the data here and assess diagnostic and therapeutic modalities and long-term outcomes in patients.ReferencesStatement on sarcoidosis. Joint Statement of the American Thoracic Society (ATS), the European Respiratory Society (ERS) and the World Association of Sarcoidosis and Other Granulomatous Disorders (WASOG) adopted by the ATS Board of Directors and by the ERS Executive Committee, February 1999. Am J Respir Crit Care Med Aug 1999 ;160(2):736-55.Sekhri V, Sanal S, Delorenzo LJ, Aronow WS, Maguire GP. Cardiac sarcoidosis: a comprehensive review. Arch Med Sci Aug 2011; 7(4):546-54.AlJaroudi WA, Refaat MM, Habib RH, Al-Shaar L, Singh M, Gutmann R, Bloom HL, Dudley SC, Ellinor PT, Saba SF, Shalaby AA, Weiss R, McNamara DM, Halder I, London B; for the Genetic Risk Assessment of Defibrillator Events (GRADE) Investigators. Effect of Angiotensin Converting Enzyme Inhibitors and Receptor Blockers on Appropriate Implantable Cardiac Defibrillator Shock: Insights from the GRADE Multicenter Registry. Am J Cardiol Apr 2015; 115 (7): 115(7):924-31.Refaat M, Mansour M, Singh JP, Ruskin JN, Heist EK: Electrocardiographic Characteristics in Right Ventricular Versus Biventricular Pacing in Patients With Paced Right Bundle Branch Block QRS Pattern. J Electrocardiol Mar-Apr 2011; 44 (2): 289-95.Isobe M, Tezuka D. Isolated cardiac sarcoidosis: Clinical characteristics, diagnosis and treatment. Int J Cardiol Mar 2015; 182:132-40.Ahmed AI, Abebe AT, Han Y, Alnabelsi T, Agrawal T, Kassi M, Aljizeeri A, Taylor A, Tleyjeh IM, Al-Mallah MH. The prognostic role of cardiac positron emission tomography imaging in patients with sarcoidosis: A systematic review. J Nucl Cardiol Jul 2021; doi: 10.1007/s12350-021-02681-z. Online ahead of print.Sharma A, Okada DR, Yacoub H, Chrispin J, Bokhari S. Diagnosis of cardiac sarcoidosis: an era of paradigm shift. Ann Nucl Med Feb 2020;34(2):87-93.Ha FJ, Agarwal S, Tweed K, Palmer SC, Adams HS, Thillai M, Williams L. Imaging in Suspected Cardiac Sarcoidosis: A Diagnostic Challenge. Curr Cardiol Rev 2020;16(2):90-97.Liang JJ, Hebl VB, DeSimone CV, Madhavan M, Nanda S, Kapa S, Maleszewski JJ, Edwards WD, Reeder G, Cooper LT , Asirvatham SJ. Electrogram guidance: a method to increase the precision and diagnostic yield of endomyocardial biopsy for suspected cardiac sarcoidosis and myocarditis. JACC Heart Fail Oct 2014;2(5):466-73.Ezzedine FM, Kapa S, Rosenbaum A, Blauwet L, Deshmukh AJ, AbouEzzeddine OF, Maleszewski JJ, Asirvatham SJ, Bois JP, Schirger JA, Chareonthaitawee P, Siontis KC. Electrogram-guided Endomyocardial Biopsy Yield in Patients with Suspected Cardiac Sarcoidosis and Relation to Outcome. J Cardiovasc Electrophysiol Jul 2021; In Press.Ardehali H , Howard DL, Hariri A, Qasim A, Hare JM, Baughman KL, Kasper EK. A positive endomyocardial biopsy result for sarcoid is associated with poor prognosis in patients with initially unexplained cardiomyopathy. Am Heart J Sep 2005 ;150(3):459-63.
Impact of Pre-ablation Weight Loss on the Success of Catheter Ablation for Atrial FibrillationAbdul Hafiz Al Tannir BS, Marwan M. Refaat MDDepartment of Internal Medicine, Division of Cardiology, American University of Beirut Medical Center, Beirut, LebanonRunning Title: Pre-ablation Weight Loss and Success of AF AblationDisclosures: NoneFunding: NoneKeywords: Cardiac Arrhythmias, Cardiovascular Diseases, Heart Diseases, Weight Loss, Catheter Ablation, Atrial FibrillationWords: 621 (excluding references)Correspondence:Marwan M. Refaat, MD, FACC, FAHA, FHRS, FASE, FESC, FACP, FRCPAssociate Professor of MedicineDirector, Cardiovascular Fellowship ProgramDepartment of Internal Medicine, Cardiovascular Medicine/Cardiac ElectrophysiologyDepartment of Biochemistry and Molecular GeneticsAmerican University of Beirut Faculty of Medicine and Medical CenterPO Box 11-0236, Riad El-Solh 1107 2020- Beirut, LebanonFax: +961-1-370814Clinic: +961-1-759616 or +961-1-355500 or +961-1-350000/+961-1-374374 Extension 5800Office: +961-1-350000/+961-1-374374 Extension 5353 or Extension 5366 (Direct)Email: email@example.comIn the United States, the prevalence of obese individuals has risen 3-fold since 1960, with 1 in every 3 persons being obese. The effect of weight changes on the progression on atrial fibrillation is well-established but the effect of pre-ablation weight loss on the recurrence of atrial fibrillation is not well-studied. Atrial fibrillation is the most frequently encountered cardiac arrhythmia ; it currently affects around 2.7 million people in the United States of America and is estimated that 6-12 million people will suffer from this condition by 2050 [2, 3]. Pulmonary vein isolation is the primary target for cardiac ablation; it can be achieved either by radiofrequency (RF) or cryoballoon ablation (CBA) [4, 5]. The FIRE and ICE trial conducted by Kuck et al showed that CBA therapy was associated with significantly fewer recurrence, rehospitalization, and cardioversion rates . Several studies suggest the preferred use of CBA in treating atrial fibrillation in obese patients due to the increased surface area for ablation .Obesity has adverse effects on the structure and hemodynamics of the heart and it is a well-established risk factor for the development of atrial fibrillation . A prospective cohort study performed by Pathak et al showed that progressive weight loss in obese and overweight patients resulted in dose-dependent effects on freedom from atrial fibrillation (FFAF) . Similarly, Middeldrop et al, concluded that obesity is associated with the progression of the disease while weight loss is associated with reversal of the progression . Limited data is available regarding the effect of weight loss on the recurrence of atrial fibrillation post-ablation. Current guidelines recommend lifestyle modifications, including a healthy diet and exercise, for overweight and obese patients before ablation [8, 9].The study of Peigh et al. is a retrospective cohort study from 2012-2017; 607 patients met the inclusion criteria. The aim of the study is to assess the impact of patient-directed weight loss 1 year before CBA on FFAP 15 months after ablation. The authors addressed an important topic that is poorly understood. Obese patients have a significantly lower FFAF rate 40-50% than the overall population 60-80%. The study selectively included patients undergoing CBA therapy. The follow-up time was 1-year post-ablation. The study concluded that, with the exception of non-obese patients with persistent atrial fibrillation, weight loss is associated with a significantly increased FFAF while weight gain led to a decrease in FFAF. A similar study assessed the impacted of physician-mediated risk control in patients undergoing RF ablation for atrial fibrillation . A total of 149 patients were included in the prospective cohort study. The study showed a positive association between physician-directed weight loss (≥ 10%) and FFAF in symptomatic obese patients. The study performed by Peigh et al, included though a larger subject group (607) than LEGACY (141); however, the LEGACY is a prospective cohort study that is more suitable to monitor the fluctuation in patients’ variables before ablation.This study was well conducted but has the limitations of retrospective studies; a prospective cohort study would better monitor the variations in patients’ variables pre-ablation. In addition, as the authors stated, asymptomatic atrial fibrillation episodes may go unnoticed.Patients with atrial fibrillation, particularly those who are obese, should be advised to lose weight prior to catheter ablation. Lifestyle modifications should not be limited to patients undergoing ablation; the effect of weight loss on disease progression is well-established. Due to the overgrowing prevalence of atrial fibrillation and obesity worldwide, more studies are encouraged to better understand the ideal lifestyle management in patients. Larger prospective cohort studies should be conducted in order to validate the results. There is also an ongoing randomized clinical trial BAROS (Bariatric Atrial Return of Sinus Trial) [NCT 04050969] which will provide more data on this topic.
Ventricular tachycardia (VT) normally occurs from an abnormal structural substrate. We report a case in which VT was caused by a large tumor in the interventricular septum. Surgical intervention was not an option due to the location of the tumor and its proximity to the coronary arteries. The patient underwent ablation and upgrade to CRT before ultimately receiving a heart transplant.
Automatic identification of VT substrate in the era of ultra-high-density mapping: Do Humans or Machines emerge victorious?Richard G. Bennett, BSc, MBChB,a Timothy G. Campbell, BSc,a Saurabh Kumar, BSc(Med)/MBBS, PhDaaDepartment of Cardiology, Westmead Hospital, Westmead Applied Research Centre, University of Sydney, Australia.Correspondence: Associate Professor Saurabh Kumar, Department of Cardiology, Westmead Hospital, Westmead Applied Research Centre, University of Sydney, Darcy Road, Westmead, New South Wales, Australia, 2145. Phone +612 8890 8140; Fax: +612 8890 8323; email: firstname.lastname@example.orgDisclosures: Timothy Campbell has received speakers’ honoraria for Biosense Webster, Inc. in the last 12 monthsFunding: Dr Saurabh Kumar is supported by the NSW Early-mid Career FellowshipKeywords: Ventricular tachycardia, local abnormal ventricular activities, electroanatomic mapping, catheter ablation, structural heart disease
Introduction: Human atria comprise distinct epicardial layers, which can bypass endocardial layers and lead to downstream centrifugal propagation at the “epi-endo” connection. We sought to characterize anatomical substrates, electrophysiological properties, and ablation outcomes of “pseudo-focal” atrial tachycardias (ATs), defined as macroreentrant ATs mimicking focal ATs. Methods and Results: We retrospectively analyzed ATs showing centrifugal propagation with post-pacing intervals (PPIs) after entrainment pacing suggestive of a macroreentry. A total of 26 patients had pseudo-focal ATs consisting of 15 perimitral, 7 roof-dependent, and 5 cavotricuspid isthmus (CTI)-dependent flutters. A low-voltage area was consistently found at the collision site and co-localized with epicardial layers like the: (1) coronary sinus-great cardiac vein bundle (22%); (2) vein of Marshall bundle (15%); (3) Bachmann bundle (22%); (4) septopulmonary bundle (15%); (5) fossa ovalis (7%); and (6) low right atrium (19%). The mean missing tachycardia cycle length (TCL) was 67 ± 29 ms (22%) on the endocardial activation map. PPI was 9 [0-15] ms and 10 [0-20] ms longer than TCL at the breakthrough site and the opposite site, respectively. While feasible in 25 pseudo-focal ATs (93%), termination was better achieved by blocking the anatomical isthmus than ablating the breakthrough site [24/26 (92%) vs. 1/6 (17%); p < 0.001]. Conclusion: Perimitral, roof-dependent, and CTI-dependent flutters with centrifugal propagation are favored by a low-voltage area located at well-identified epicardial bundles. Comprehensive entrainment pacing maneuvers are crucial to distinguish pseudo-focal ATs from true focal ATs. Blocking the anatomical isthmus is a better therapeutic option than ablating the breakthrough site.
Background: Transvenous lead extraction (TLE) is standard of care for the management of patients with cardiac implantable electronic device infection or lead related complications. Currently, objective data on TLE in Latin America is lacking. Objective: To describe the current practice standards in Latin American centers performing TLE. Methods: An online survey was sent through the mailing list of the Latin American Heart Rhythm Association (LAHRS). Online reminders were sent through the mailing list; duplicate answers were discarded. The survey was available for one month, after which no more answers were accepted. Results: A total of 48 answers were received, from 44 different institutions (39.6% from Colombia, 27,1% from Brazil), with most respondents (83%) being electrophysiologists. Twenty-nine institutions (66%) performed less than 10 lead extractions/year, with 7 (15%) institutions not performing lead extraction. Although most institutions in which lead extraction is performed reported using several tools, mechanical rotating sheaths were cited as the main tool (73%), 13.5% reported the use of mechanical extraction sheaths and only 13.5% reporting the use of laser sheaths. Management of infected leads was performed according to current guidelines. Conclusion: This survey is the first attempt to provide information on TLE procedures in Latin America and could provide useful information for future prospective registries. According to our results, the number of centers performing high volume lead extraction in Latin America is smaller than that reported in other continents, with most interventions performed using mechanical tools. Future prospective registries assessing acute and long-term success are needed.
Interpreting Complex Atrial Tachycardia Maps Using Global Atrial VectorsEditorial on: The Utility of a Novel Mapping Algorithm Utilizing Vectors and Global Pattern of Propagation for Scar-Related Atrial TachycardiasMiguel Rodrigo, PhD1-2Sanjiv M. Narayan MD, PhD11Stanford University, Stanford, CA, USA2Electronic Engineering Department, Universitat de Valencia, Spain1500 words excluding title and references12 or less references1-3 tables/figures
Introduction. Atrial Fibrillation and Atrial Flutter (AF/AFL), the most common atrial arrhythmias, have never been examined in combat casualties. In this study, we investigated the impact of traumatic injury on AF/AFL among service members with deployment history. Methods. Sampled from the Department of Defense (DoD) Trauma Registry (n=10,000), each injured patient in this retrospective cohort study was matched with a non-injured service member drawn from the Veterans Affairs/DoD Identity Repository. The primary outcome was AF/AFL diagnosis identified using ICD-9-CM and ICD-10-CM codes. Competing risk regressions based on Fine and Gray subdistribution hazards model with were utilized to assess the association between injury and AF/AFL. Results. There were 130 reported AF/AFL cases, 90 of whom were injured and 40 were non-injured. The estimated cumulative incidence rates of AF/AFL for injured was higher compared to non-injured patients (HR = 2.04; 95% CI = 1.44, 2.87). After adjustment demographics and tobacco use, the association did not appreciably decrease (HR = 1.90; 95% CI = 1.23, 2.93). Additional adjustment for obesity, hypertension, diabetes, and vascular disorders, the association between injury and AF/AFL was no longer statistically significant (HR: 1.51; 95% CI = 0.99, 2.52). Conclusion. Higher AF/AFL incidence rate was observed among deployed service members with combat injury compared to servicemembers without injury. The association did not remain significant after adjustment for cardiovascular-related covariates. These findings highlight the need for combat casualties surveillance to further understand the AF/AFL risk within the military population and to elucidate the potential underlying pathophysiologic mechanisms.
Background: Despite a proven mortality benefit in primary prevention (PP) patients, the utilization of implantable cardioverter-defibrillators (ICD) and cardiac resynchronization therapy-defibrillators (CRT-D) remains low in many geographies. Purpose: The objective of this analysis was to examine the mortality benefit in PP patients by guideline-indicated device type: implantable cardioverter-defibrillator (ICD) and cardiac resynchronization therapy-defibrillator (CRT-D). Methods: Improve SCA was a prospective, non-randomized, non-blinded multicenter trial that enrolled patients from regions where ICD utilization is low. PP patient’s CRT-D or ICD eligibility was based upon the 2008 ACC/AHA/HRS and 2006 ESC guidelines. Mortality was assessed according to guideline-indicated device type comparing implanted and non-implanted patients. Cox proportional hazards methods were used, adjusting for known factors affecting mortality risk. Results: Among 2,618 PP patients followed for a mean of 20.8 ± 10.8 months, 1,073 were indicated for a CRT-D, and 1,545 were indicated for an ICD. PP CRT-D-indicated patients who received CRT-D therapy had a 58% risk reduction in mortality compared to those without implant (adjusted HR 0.42, 95% CI: 0.28-0.61, P<0.0001). PP patients with an ICD indication had a 43% risk reduction in mortality with an ICD implant compared with no implant (adjusted HR 0.57, 95% CI: 0.41-0.81, P=0.002). Conclusions: This analysis confirms the mortality benefit of adherence to guideline-indicated implantable defibrillation therapy for PP patients in geographies where ICD therapy was underutilized. These results affirm that medical practice should follow clinical guidelines when choosing therapy for PP patients who meet the respective defibrillator device implant indication.
Significant changes or cancellation of MCIT could result in limiting access to breakthrough medical technologies that could improve the health and well-being of Medicare beneficiaries. For these reasons, we encourage federal agencies to work together and CMS to implement the MCIT rule without delay to ensure timely access to breakthrough technologies