The application of brief high voltage electrical pulses to tissue can lead to an irreversible or reversible electroporation effect in a cell-specific manner. In the management of ventricular ...arrhythmias, the ability to target different tissue types, specifically cardiac conduction tissue (His-Purkinje System) vs. cardiac myocardium would be advantageous. We hypothesize that pulsed electric fields (PEFs) can be applied safely to the beating heart through a catheter-based approach, and we tested whether the superficial Purkinje cells can be targeted with PEFs without injury to underlying myocardial tissue.
In an acute (n = 5) and chronic canine model (n = 6), detailed electroanatomical mapping of the left ventricle identified electrical signals from myocardial and overlying Purkinje tissue. Electroporation was effected via percutaneous catheter-based Intracardiac bipolar current delivery in the anesthetized animal. Repeat Intracardiac electrical mapping of the heart was performed at acute and chronic time points; followed by histological analysis to assess effects.
PEF demonstrated an acute dose-dependent functional effect on Purkinje, with titration of pulse duration and/or voltage associated with successful acute Purkinje damage. Electrical conduction in the insulated bundle of His (n = 2) and anterior fascicle bundle (n = 2), was not affected. At 30 days repeat cardiac mapping demonstrated resilient, normal electrical conduction throughout the targeted area with no significant change in myocardial amplitude (pre 5.9 ± 1.8 mV, 30 days 5.4 ± 1.2 mV, p = 0.92). Histopathological analysis confirmed acute Purkinje fiber targeting, with chronic studies showing normal Purkinje fibers, with minimal subendocardial myocardial fibrosis.
PEF provides a novel, safe method for non-thermal acute modulation of the Purkinje fibers without significant injury to the underlying myocardium. Future optimization of this energy delivery is required to optimize conditions so that selective electroporation can be utilized in humans the treatment of cardiac disease.
Arrhythmogenic cardiomyopathy (ACM) is an arrhythmogenic disorder of the myocardium not secondary to ischemic, hypertensive, or valvular heart disease. ACM incorporates a broad spectrum of genetic, ...systemic, infectious, and inflammatory disorders. This designation includes, but is not limited to, arrhythmogenic right/left ventricular cardiomyopathy, cardiac amyloidosis, sarcoidosis, Chagas disease, and left ventricular noncompaction. The ACM phenotype overlaps with other cardiomyopathies, particularly dilated cardiomyopathy with arrhythmia presentation that may be associated with ventricular dilatation and/or impaired systolic function. This expert consensus statement provides the clinician with guidance on evaluation and management of ACM and includes clinically relevant information on genetics and disease mechanisms. PICO questions were utilized to evaluate contemporary evidence and provide clinical guidance related to exercise in arrhythmogenic right ventricular cardiomyopathy. Recommendations were developed and approved by an expert writing group, after a systematic literature search with evidence tables, and discussion of their own clinical experience, to present the current knowledge in the field. Each recommendation is presented using the Class of Recommendation and Level of Evidence system formulated by the American College of Cardiology and the American Heart Association and is accompanied by references and explanatory text to provide essential context. The ongoing recognition of the genetic basis of ACM provides the opportunity to examine the diverse triggers and potential common pathway for the development of disease and arrhythmia.
Recommendations (New Section)258 Aortic Stenosis259 Aortic Stenosis259 Choice of Intervention: Recommendations259 Mitral Regurgitation261 Stages of Chronic MR261 Chronic Primary MR262 Intervention: ...Recommendations262 Chronic Secondary MR264 Intervention: Recommendations264 Prosthetic Valves265 Evaluation and Selection of Prosthetic Valves265 Intervention: Recommendations265 Antithrombotic Therapy for Prosthetic Valves267 Diagnosis and Follow-Up267 Medical Therapy: Recommendations267 Bridging Therapy for Prosthetic Valves269 Diagnosis and Follow-Up269 Medical Therapy: Recommendations269 Acute Mechanical Prosthetic Valve Thrombosis270 Diagnosis and Follow-Up: Recommendation270 Intervention: Recommendation271 Prosthetic Valve Stenosis271 Intervention: Recommendation272 Prosthetic Valve Regurgitation273 Intervention: Recommendations273 Infective Endocarditis274 Infective Endocarditis274 Intervention: Recommendations274 References276 Appendix 1 Author Relationships With Industry and Other Entities (Relevant)283 Appendix 2 Reviewer Relationships With Industry and Other Entities (Comprehensive)284 Appendix 3 Abbreviations289 Preamble Since 1980, the American College of Cardiology (ACC) and American Heart Association (AHA) have translated scientific evidence into clinical practice guidelines (guidelines) with recommendations to improve cardiovascular health. Criteria for commissioning an ERC and formal systematic review include: a) the absence of a current authoritative systematic review, b) the feasibility of defining the benefit and risk in a time frame consistent with the writing of Vilacosta, Aorto-cavitary fistulous tract formation in infective endocarditis: clinical and echocardiographic features of 76 cases and risk factors for mortality, Eur Heart J, Vol. 26, 2005, 288-297 270 K.L. Chan, Early clinical course and long-term outcome of patients with infective endocarditis complicated by perivalvular abscess, CMAJ, Vol. 167, 2002, 19-24 271 F. Jault, I. Gandjbakhch, J.C. Chastre, Prosthetic valve endocarditis with ring abscesses. Surgical management and long-term results, J Thorac Cardiovasc Surg, Vol. 105,...
Advances in cardiac surgery toward the mid-20th century created a need for an artificial means of stimulating the heart muscle. Initially developed as large external devices, technological advances ...resulted in miniaturization of electronic circuitry and eventually the development of totally implantable devices. These advances continue to date, with the recent introduction of leadless pacemakers. In this first part of a 2-part review, we describe indications, implant-related complications, basic function/programming, common pacemaker-related issues, and remote monitoring, which are relevant to the practicing cardiologist. We provide an overview of magnetic resonance imaging and perioperative management among patients with cardiac pacemakers.
Direct administration of chemotherapeutic drugs to the lungs significantly enhances drug exposure to lung resident cancers and may improve chemotherapy when compared to intravenous administration. ...Direct inhalation of uncomplexed or unencapsulated cytotoxic drugs, however, leads to bolus release and unacceptable lung toxicity. Here, we explored the utility of a 56kDa PEGylated polylysine dendrimer, conjugated to doxorubicin, to promote the controlled and prolonged exposure of lung-resident cancers to cytotoxic drug. After intratracheal instillation to rats, approximately 60% of the dendrimer was rapidly removed from the lungs (within 24h) via mucociliary clearance and absorption into the blood. This was followed by a slower clearance phase that reflected both absorption from the lungs (bioavailability 10–13%) and biodegradation of the dendrimer scaffold. After 7days, approximately 15% of the dose remained in the lungs. A syngeneic rat model of lung metastasised breast cancer was subsequently employed to compare the anticancer activity of the dendrimer with a doxorubicin solution formulation after intravenous and pulmonary administration. Twice weekly intratracheal instillation of the dendrimer led to a >95% reduction in lung tumour burden after 2weeks in comparison to IV administration of doxorubicin solution which reduced lung tumour burden by only 30–50%. Intratracheal instillation of an equivalent dose of doxorubicin solution led to extensive lung-related toxicity and death withinseveral days of a single dose. The data suggest that PEGylated dendrimers have potential as inhalable drug delivery systems to promote the prolonged exposure of lung-resident cancers to chemotherapeutic drugs and to improve anti-cancer activity.
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ACC/AHA Task Force Members Glenn N. Levine, MD, FACC, FAHA, Chair Patrick T. O’Gara, MD, MACC, FAHA, Chair-Elect Jonathan L. Halperin, MD, FACC, FAHA, Immediate Past Chair‡‡ Sana M. Al-Khatib, MD, ...MHS, FACC, FAHA Joshua A. Beckman, MD, MS, FAHA Kim K. Birtcher, PharmD, MS, AACC Biykem Bozkurt, MD, PhD, FACC, FAHA‡‡ Ralph G. Brindis, MD, MPH, MACC‡‡ Joaquin E. Cigarroa, MD, FACC Lesley H. Curtis, PhD, FAHA‡‡ Anita Deswal, MD, MPH, FACC, FAHA Lee A. Fleisher, MD, FACC, FAHA Federico Gentile, MD, FACC Samuel Gidding, MD, FAHA‡‡ Zachary D. Goldberger, MD, MSc, FACC, FAHA Mark A. Hlatky, MD, FACC, FAHA John Ikonomidis, MD, PhD, FAHA‡‡ José A. Joglar, MD, FACC, FAHA Laura Mauri, MD, MSc, FAHA‡‡ Mariann R. Piano, RN, PhD, FAHA Susan J. Pressler, PhD, RN, FAHA‡‡ Barbara Riegel, PhD, RN, FAHA‡‡ Duminda N. Wijeysundera, MD, PhD‡‡Former Task Force member; current member during the writing effort.Table of Contents Top 10 Take-Home Messages For the Management of Bradycardia and Cardiac Conduction Delaye53 Preamblee54 Introductione55 1.1.Methodology and Evidence Reviewe55 1.2.Organization of the Writing Committeee55 1.3.Document Review and Approvale55 1.4.Scope of the Guidelinee56 1.5.Class of Recommendation and Level of Evidencee56 1.6.Abbreviationse56 2. General Evaluation of Patients With Documented or Suspected Bradycardia or Conduction Disorderse61 4.1.History and Physical Examination of Patients With Documented or Suspected Bradycardia or Conduction Disorderse61 4.2.Noninvasive Evaluatione66 4.2.1.Resting ECG in Patients With Documented or Suspected Bradycardia or Conduction Disorderse66 4.2.2.Exercise Electrocardiographic Testing in Patients With Documented or Suspected Bradycardia or Conduction Disorderse66 4.2.3.Ambulatory Electrocardiography in Patients With Documented or Suspected Bradycardia or Conduction Disorderse67 4.2.4.Imaging in Patients With Documented or Suspected Bradycardia or Conduction Disorderse69 4.2.5.Laboratory Testing in Patients With Documented or Suspected Bradycardia or Conduction Disorderse70 4.2.6.Genetic Testing in Patients With Documented or Suspected Bradycardia or Conduction Disorderse71 4.2.7.Sleep Apnea Evaluation and Treatment in Patients With Documented or Suspected Bradycardia or Conduction Disorderse72 4.3. In patients with a left ventricular ejection fraction between 36% to 50% and atrioventricular block, who have an indication for permanent pacing and are expected to require ventricular pacing >40% of the time, techniques that provide more physiologic ventricular activation (e.g., cardiac resynchronization therapy, His bundle pacing) are preferred to right ventricular pacing to prevent heart failure. Because conduction system abnormalities are common after transcatheter aortic valve replacement, recommendations on postprocedure surveillance and pacemaker implantation are made in this guideline. Using the principles of shared decision-making and informed consent/refusal, patients with decision-making capacity or his/her legally defined surrogate has the right to refuse or request withdrawal of pacemaker therapy, even if the patient is pacemaker dependent, which should be considered palliative, end-of-life care, and not physician-assisted suicide.
Arrhythmogenic cardiomyopathy (ACM) is an arrhythmogenic disorder of the myocardium not secondary to ischemic, hypertensive, or valvular heart disease. ACM incorporates a broad spectrum of genetic, ...systemic, infectious, and inflammatory disorders. This designation includes, but is not limited to, arrhythmogenic right/left ventricular cardiomyopathy, cardiac amyloidosis, sarcoidosis, Chagas disease, and left ventricular noncompaction. The ACM phenotype overlaps with other cardiomyopathies, particularly dilated cardiomyopathy with arrhythmia presentation that may be associated with ventricular dilatation and/or impaired systolic function. This expert consensus statement provides the clinician with guidance on evaluation and management of ACM and includes clinically relevant information on genetics and disease mechanisms. PICO questions were utilized to evaluate contemporary evidence and provide clinical guidance related to exercise in arrhythmogenic right ventricular cardiomyopathy. Recommendations were developed and approved by an expert writing group, after a systematic literature search with evidence tables, and discussion of their own clinical experience, to present the current knowledge in the field. Each recommendation is presented using the Class of Recommendation and Level of Evidence system formulated by the American College of Cardiology and the American Heart Association and is accompanied by references and explanatory text to provide essential context. The ongoing recognition of the genetic basis of ACM provides the opportunity to examine the diverse triggers and potential common pathway for the development of disease and arrhythmia.
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