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Cardiology and Therapy Jun 2022There is limited evidence on therapies for obstructive hypertrophic cardiomyopathy (HCM), and data regarding treatment patterns and cost are scarce. This study assessed...
INTRODUCTION
There is limited evidence on therapies for obstructive hypertrophic cardiomyopathy (HCM), and data regarding treatment patterns and cost are scarce. This study assessed treatment patterns and economic outcomes in patients with symptomatic obstructive HCM.
METHODS
Adults with symptomatic obstructive HCM as per study design and treated with pharmacotherapies [beta blockers (BBs), calcium channel blockers (CCBs), BB + CCB, or disopyramide] or procedures (septal reduction therapy, heart transplantation, implantable cardioverter-defibrillator, and pacemaker implantation) were identified from the IBM® MarketScan® Commercial and Medicare Supplemental database (January 2009-March 2019). Patients had 12-month continuous eligibility before and after (study period) treatment initiation (index treatment). Healthcare resource utilization (HRU), costs, and treatment changes were assessed.
RESULTS
Of the 4883 patients included in the analysis, 85% received pharmacotherapies (BB 52.5%; CCB 11.7%; BB + CCB 17.7%; disopyramide 2.4%) and 15.7% underwent procedures. During the study period, 38, 34, and 100% of all patients had ≥ 1 inpatient stay, emergency room (ER) visit, and outpatient visit, respectively; mean total healthcare costs were US$53,053. Patients undergoing procedures had the highest HRU and costs across groups. Among patients receiving pharmacotherapies, HRU was lowest with BBs and highest with disopyramide. Treatment changes were observed in 43.8% of patients receiving pharmacotherapies.
CONCLUSIONS
Patients experienced high rates of treatment changes, and the economic burden associated with symptomatic obstructive HCM increased as therapy escalated. More effective therapies are needed to stabilize or decrease the economic burden of obstructive HCM.
PubMed: 35230625
DOI: 10.1007/s40119-022-00257-7 -
Current Cardiology Reports Jun 2021Pharmacological treatment options for hypertrophic cardiomyopathy (HCM) are currently limited and comprise non-disease specific therapies such as β-blockers,... (Review)
Review
PURPOSE OF REVIEW
Pharmacological treatment options for hypertrophic cardiomyopathy (HCM) are currently limited and comprise non-disease specific therapies such as β-blockers, non-dihydropyridine calcium channel blockers, and disopyramide. These agents that offer a variable degree of symptomatic relief, often suboptimal, are often limited by side-effects and fail to address the key molecular abnormalities of the disease.
RECENT FINDINGS
Mavacamten is a novel, first-in-class, allosteric inhibitor of cardiac myosin ATPase, which reduces actin-myosin cross-bridge formation, thereby reducing myocardial contractility and improving myocardial energetic consumption in experimental HCM models. Following a successful Phase 2 study, the recently published phase III, placebo-controlled, randomized EXPLORER-HCM trial demonstrated the efficacy and safety of mavacamten in reducing left ventricular outflow tract obstruction and ameliorating exercise capacity, New York Heart Association functional class and health status in patients with obstructive HCM. Mavacamten represents the first agent specifically developed for HCM successfully tested in a Phase III trial, to be registered soon for clinical use, representing a radical change of paradigm in the pharmacological treatment of HCM.
Topics: Benzylamines; Cardiac Myosins; Cardiomyopathy, Hypertrophic; Clinical Trials, Phase III as Topic; Humans; Randomized Controlled Trials as Topic; Uracil
PubMed: 34081217
DOI: 10.1007/s11886-021-01508-0 -
Medicine May 2021Syncope often occurs in patients with advanced head and neck cancers due to the stimulation of the autonomic nervous system by the tumor. Here, we describe a case of...
RATIONALE
Syncope often occurs in patients with advanced head and neck cancers due to the stimulation of the autonomic nervous system by the tumor. Here, we describe a case of frequent syncopal episodes after laryngopharyngectomy for hypopharyngeal cancer. As all syncopal episodes were observed during the forenoon, we also evaluated the heart rate variability using ambulatory electrocardiography to determine why the syncopal episodes occurred during a specified period of the day.
PATIENT CONCERNS
A 73-year-old Japanese man who underwent laryngopharyngectomy for recurrent hypopharyngeal cancer started experiencing frequent episodes of loss of consciousness that occurred during the same time period (10:00-12:00). He had never experienced syncopal episodes before the operation. From 23 to 41 days postoperatively, he experienced 9 syncopal episodes that occurred regardless of his posture.
DIAGNOSES
Pharyngo-esophagoscopy revealed an anastomotic stricture between the free jejunum graft and the upper esophagus. Swallowing videofluoroscopy confirmed the dilatation of the jejunal autograft and a foreign body stuck on the oral side of the anastomosis. Contrast-enhanced computed tomography revealed that the carotid artery was slightly compressed by the edematous free jejunum. The patient was diagnosed with carotid sinus syndrome (CSS) as the free jejunum was dilated when consuming breakfast, which may have caused carotid sinus hypersensitivity and induced a medullary reflex.
INTERVENTIONS
Administration of disopyramide was effective in preventing syncope. Heart rate variability analysis using ambulatory electrocardiography showed that parasympathetic dominancy shifted to sympathetic dominancy during 10:00 to 12:00. The significant time regularity of the syncopal episodes may have been affected by modified diurnal variation in autonomic tone activity.
OUTCOMES
After the surgical release and re-anastomosis of the pharyngoesophageal stenosis via an open-neck approach, no recurrent episodes of syncope were reported.
LESSONS
We reported a case of frequent syncopal episodes limited to the forenoon due to CSS after surgery for hypopharyngeal carcinoma. The patient was treated with anticholinergics followed by the release and re-anastomosis of the pharyngoesophageal stenosis. When syncope occurs after surgery for head and neck lesions, CSS due to postoperative structural changes should be considered as a differential diagnosis of syncope.
Topics: Aged; Anastomosis, Surgical; Breakfast; Carotid Sinus; Deglutition; Disopyramide; Electrocardiography; Esophageal Stenosis; Esophagus; Humans; Hypopharyngeal Neoplasms; Laryngectomy; Male; Pharyngectomy; Pharynx; Syncope; Syndrome
PubMed: 34011078
DOI: 10.1097/MD.0000000000025959 -
South African Medical Journal =... Mar 2021Extracorporeal life support is the utilisation of advanced techniques to sustain circulatory and/or ventilatory functions in critically ill patients when standard...
Extracorporeal life support is the utilisation of advanced techniques to sustain circulatory and/or ventilatory functions in critically ill patients when standard therapies fail. It is well established in developed countries. There is increasing literature supporting its application in refractory cardiac arrest with a potential reversible cause, a procedure also known as extracorporeal cardiopulmonary resuscitation (eCPR). Two cases where eCPR was successfully utilised in a busy (>30 000 visits per year) private South African emergency department are described here, the first such cases to be reported on the African continent. The first patient had a life-threatening cardiac arrhythmia due to toxin ingestion, and the second a refractory ventricular fibrillation due to acute myocardial infarction. In both these cases the cardiac arrest was witnessed, occurred in the emergency department, and failed to respond to standard advanced resuscitative measures. Both the patients were discharged neurologically intact. Although it is effective, the benefit of this advanced method of resuscitation in a low- to middle-income country is debated.
Topics: Anti-Arrhythmia Agents; Cardiopulmonary Resuscitation; Cardiotoxicity; Disopyramide; Extracorporeal Membrane Oxygenation; Female; Humans; Male; Middle Aged; Myocardial Infarction; South Africa; Ventricular Fibrillation
PubMed: 33944740
DOI: 10.7196/SAMJ.2021.v111i3.15366 -
International Journal of Molecular... Jan 2021Electrical remodelling as a result of homeodomain transcription factor 2 (Pitx2)-dependent gene regulation was linked to atrial fibrillation (AF) and AF patients with...
In Silico Assessment of Class I Antiarrhythmic Drug Effects on -Induced Atrial Fibrillation: Insights from Populations of Electrophysiological Models of Human Atrial Cells and Tissues.
Electrical remodelling as a result of homeodomain transcription factor 2 (Pitx2)-dependent gene regulation was linked to atrial fibrillation (AF) and AF patients with single nucleotide polymorphisms at chromosome 4q25 responded favorably to class I antiarrhythmic drugs (AADs). The possible reasons behind this remain elusive. The purpose of this study was to assess the efficacy of the AADs disopyramide, quinidine, and propafenone on human atrial arrhythmias mediated by Pitx2-induced remodelling, from a single cell to the tissue level, using drug binding models with multi-channel pharmacology. Experimentally calibrated populations of human atrial action po-tential (AP) models in both sinus rhythm (SR) and Pitx2-induced AF conditions were constructed by using two distinct models to represent morphological subtypes of AP. Multi-channel pharmaco-logical effects of disopyramide, quinidine, and propafenone on ionic currents were considered. Simulated results showed that Pitx2-induced remodelling increased maximum upstroke velocity (dVdtmax), and decreased AP duration (APD), conduction velocity (CV), and wavelength (WL). At the concentrations tested in this study, these AADs decreased dVdtmax and CV and prolonged APD in the setting of Pitx2-induced AF. Our findings of alterations in WL indicated that disopyramide may be more effective against Pitx2-induced AF than propafenone and quinidine by prolonging WL.
Topics: Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Atrial Fibrillation; Computer Simulation; Disopyramide; Heart Atria; Homeodomain Proteins; Humans; Mice; Propafenone; Quinidine; Transcription Factors; Homeobox Protein PITX2
PubMed: 33514068
DOI: 10.3390/ijms22031265 -
Frontiers in Pharmacology 2020Short QT syndrome (SQTS) is associated with tachyarrhythmias and sudden cardiac death. So far, only quinidine has been demonstrated to be effective in patients with SQTS...
Ionic Mechanisms of Disopyramide Prolonging Action Potential Duration in Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes From a Patient With Short QT Syndrome Type 1.
Short QT syndrome (SQTS) is associated with tachyarrhythmias and sudden cardiac death. So far, only quinidine has been demonstrated to be effective in patients with SQTS type 1(SQTS1). The aim of this study was to investigate the mechanisms of disopyramide underlying its antiarrhythmic effects in SQTS1 with the N588K mutation in HERG channel. Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from a patient with SQTS1 and a healthy donor, patch clamp, and calcium imaging measurements were employed to assess the drug effects. Disopyramide prolonged the action potential duration (APD) in hiPSC-CMs from a SQTS1-patient (SQTS1-hiPSC-CMs). In spontaneously beating SQTS1-hiPSC-CMs challenged by carbachol plus epinephrine, disopyramide reduced the arrhythmic events. Disopyramide enhanced the inward L-type calcium channel current (I), the late sodium channel current (late I) and the Na/Ca exchanger current (I), but it reduced the outward small-conductance calcium-activated potassium channel current (I), leading to APD-prolongation. Disopyramide displayed no effects on the rapidly and slowly activating delayed rectifier and ATP-sensitive potassium channel currents. In hiPSC-CMs from the healthy donor, disopyramide reduced peak I, I, I, and I but enhanced late I and I. The results demonstrated that disopyramide may be effective for preventing tachyarrhythmias in SQTS1-patients carrying the N588K mutation in HERG channel by APD-prolongation enhancing I, late I, I, and reducing I.
PubMed: 33154722
DOI: 10.3389/fphar.2020.554422 -
Journal of Atrial Fibrillation 2020The presence of both sympathetic activation-mediated triggers and parasympathetic activation-mediated substrates are required to initiate and maintain some forms of...
OBJECTIVE
The presence of both sympathetic activation-mediated triggers and parasympathetic activation-mediated substrates are required to initiate and maintain some forms of atrial fibrillation (AF). AF predominantly precipitated by parasympathetic stimulation is known as vagally-mediated AF (VM-AF). The role of novel drugs and molecular targeted gene therapy that modulate the autonomic nervous system are therapeutic options in this unique population with VM-AF. Here, we review the role of the sympatho-vagal balance in the genesis of AF and consider drug therapy for VM-AF.
METHODS
In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement, literature search was conducted using the keywords "vagal", "vagal nerve", "vagus", "vagus nerve", and "atrial fibrillation". Retrieved citations were first screened independently by 2 reviewers for inclusion and exclusion criteria.
RESULTS
A total of 14 studies and 3 practice guidelines from 1986-2017 were included. Only two clinical investigations evaluated the effectiveness of disopyramide and sotalol in human subjects with VM-AF. The potential role of antiarrhythmic drugs has been studied in animal models.
CONCLUSIONS
Growing evidence suggests that the autonomic nervous system is integral in the development of VM-AF. Novel medications and genetic targets are undergoing investigation with promising results.
PubMed: 33024510
DOI: 10.4022/jafib.2410 -
The American Journal of Cardiology Aug 2020Highly reliable identification of adults with hypertrophic cardiomyopathy (HC) at risk for sudden death (SD) has been reported. A significant controversy remains,...
Highly reliable identification of adults with hypertrophic cardiomyopathy (HC) at risk for sudden death (SD) has been reported. A significant controversy remains, however, regarding the most reliable risk stratification methodology for children and adolescents with HC. The present study assesses the accuracy of SD prediction and prevention with prophylactic implantable cardioverter-defibrillators (ICDs) in young HC patients. The study group is comprised of 146 HC patients <20 years of age evaluated consecutively over 17 years with prospective risk stratification and ICD decision-making. We relied on ≥1 established individual risk markers considered major within each patient's clinical profile, based on an enhanced American College of Cardiology /American Heart Association (ACC/AHA) guidelines algorithm. Of the 60 largely asymptomatic patients implanted with primary prevention ICDs at age 15 ± 4 years, 9 (15%) experienced device therapy terminating potentially lethal ventricular tachyarrhythmias and restoring sinus rhythm at 19 ± 6 years (range 9 to 29), 5.1 ± 6.0 years after implant; 3 patients had multiple appropriate ICD discharges. The individual risk marker algorithm was associated with 100% sensitivity in predicting SD events (95%CI: 69, 100) and 63% specificity for identifying patients without events (95%CI: 54, 71). Of these patients with device therapy, massive left ventricular hypertrophy (absolute wall thickness ≥30 mm) was the most common predictor, present in 70% of patients either alone or in combination with other risk markers. Each of the 146 study patients have survived to date at 22 ± 5 years, including all 86 without ICD recommendations. In conclusion, an enhanced ACC/AHA risk stratification strategy, based on established individual risk markers, was highly reliable in prospectively predicting SD events in children and adolescents with HC, and preventing arrhythmia-based catastrophes in this susceptible high risk population.
Topics: Adolescent; Adrenergic beta-Antagonists; Adult; Anti-Arrhythmia Agents; Calcium Channel Blockers; Cardiac Resynchronization Therapy Devices; Cardiomyopathy, Hypertrophic; Child; Death, Sudden, Cardiac; Defibrillators, Implantable; Disopyramide; Female; Humans; Male; Primary Prevention; Risk Assessment; Syncope; Tachycardia, Ventricular; Young Adult
PubMed: 32650928
DOI: 10.1016/j.amjcard.2020.04.042 -
Anales de Pediatria Apr 2021
Topics: Anti-Arrhythmia Agents; Cardiomyopathy, Hypertrophic; Disopyramide; Humans
PubMed: 32646796
DOI: 10.1016/j.anpedi.2020.04.028 -
Journal of Pharmacological Sciences Aug 2020The effects of class I antiarrhythmic drugs on the automaticity of isolated guinea pig pulmonary vein myocardia were investigated using microelectrode and voltage clamp...
Differential effects of class I antiarrhythmic drugs on the guinea pig pulmonary vein myocardium: Inhibition of automatic activity correlates with blockade of a diastolic sodium current component.
The effects of class I antiarrhythmic drugs on the automaticity of isolated guinea pig pulmonary vein myocardia were investigated using microelectrode and voltage clamp methods. All of the drugs examined reduced the maximum rate of rise of automatic action potentials. The firing frequency and rate of diastolic depolarization were decreased by aprindine, flecainide and propafenone, but not by cibenzoline, disopyramide and pilsicainide, which correlated with blockade of the sodium current component induced by ramp depolarization mimicking the diastolic depolarization. In conclusion, class I antiarrhythmic drugs which block the diastolic sodium current component inhibit the automaticity of the pulmonary vein myocardium.
Topics: Action Potentials; Animals; Anti-Arrhythmia Agents; Guinea Pigs; In Vitro Techniques; Microelectrodes; Patch-Clamp Techniques; Pulmonary Veins; Sodium
PubMed: 32487451
DOI: 10.1016/j.jphs.2020.05.004