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International Journal of Cardiology Jan 2023Left ventricular outflow tract obstruction (LVOTO) is present in 1/3 of children with Hypertrophic Cardiomyopathy (HCM). Disopyramide improves symptoms associated with...
BACKGROUND
Left ventricular outflow tract obstruction (LVOTO) is present in 1/3 of children with Hypertrophic Cardiomyopathy (HCM). Disopyramide improves symptoms associated with LVOTO and delays surgical intervention in adults, but it is not licensed in children.
AIM
To describe a single-centre thirty-year experience of using disopyramide to treat LVOTO-related symptoms in a paediatric HCM cohort.
METHODS
Clinical data were collected for all patients meeting diagnostic criteria for HCM (<18 years) at the time of initiation, 6 months after, and last follow-up or end of disopyramide treatment. It included demographics, clinical history, 12‑lead electrocardiography, and echocardiography. Comparisons between baseline and 6 month follow up, and end of follow up respectively were performed.
RESULTS
Fifty-one patients with HCM were started on disopyramide at a mean age 10.2±5.3 years. At 6 months, of those previously symptomatic, 33(86.8%) reported an improvement of symptoms and 12(31.6%) were asymptomatic. PR interval, corrected QT interval and maximal LVOT gradient had not significantly changed, but fewer participants were noted to have systolic anterior motion of the mitral valve 31 (72.1%) vs. 26 (57.80%). Patients were followed up for a median of 1.9 years (IQR 0.83-4.5). Nine patients (17.6%) reported side effects, and eleven patients (33.3%) with initial improvement in symptoms reported a return or worsening of symptoms requiring a change in medication (n = 4, 12.1%) or left ventricular septal myomectomy (n = 7, 21.2%) during follow up.
CONCLUSION
Disopyramide is a safe and effective treatment for LVOTO-related symptoms in childhood obstructive HCM. Any delay in the need for invasive intervention, particularly during childhood, is of clear clinical benefit.
Topics: Adult; Humans; Child; Child, Preschool; Adolescent; Disopyramide; Ventricular Outflow Obstruction; Cardiomyopathy, Hypertrophic; Echocardiography; Heart Ventricles
PubMed: 36174821
DOI: 10.1016/j.ijcard.2022.09.044 -
The Annals of Pharmacotherapy Apr 2023To assess mavacamten's role in hypertrophic cardiomyopathy treatment. (Review)
Review
OBJECTIVE
To assess mavacamten's role in hypertrophic cardiomyopathy treatment.
DATA SOURCES
In addition to clinical guidelines, package inserts, and general reviews, we searched PubMed using the term mavacamten from inception to June 11, 2022.
STUDY SELECTION AND DATA EXTRACTION
English language studies describing mavacamten's mechanism of action, pharmacokinetics, drug interactions, clinical and economic outcomes, and adverse events.
DATA SYNTHESIS
Mavacamten reduces left ventricular outflow obstruction and New York Heart Association functional class while improving Kansas City Cardiomyopathy Questionnaire-Clinical Summary Scores in patients with obstructive hypertrophic cardiomyopathy. With an acquisition cost of $245.20 per capsule, it would cost $1.2 million for every additional quality-adjusted life year. In those with unobstructive hypertrophic cardiomyopathy, there were improvements in -terminal probrain natriuretic peptide and high-sensitivity cardiac troponin biochemical markers. Mavacamten is a substrate for CYP2C19 and CYP3A4, and a CYP enzyme inducer.
RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE
Patients with obstructive hypertrophic cardiomyopathy and an ejection fraction ≥55% have a new option if they remain symptomatic despite maximally tolerated β-blocker or non-dihydropyridine calcium channel blocker therapy. It is an alternative to disopyramide therapy, which has poor patient tolerance, or septal reduction therapies, which are invasive. However, mavacamten is not cost-effective and its role in nonobstructive hypertrophic cardiomyopathy is not well established.
CONCLUSIONS
Mavacamten is a new option for patients with refractory obstructive hypertrophic cardiomyopathy and an ejection fraction ≥55% but its pricing makes therapy not cost-effective. Final health outcomes are not fully elucidated and additional studies are needed to determine long-term effects.
Topics: Humans; Benzylamines; Cardiomyopathy, Hypertrophic; Cytochrome P-450 CYP3A; Drug Tolerance
PubMed: 35950315
DOI: 10.1177/10600280221117812 -
Yakugaku Zasshi : Journal of the... 2022The management of syncope is clinically important for heart failure (HF) patients. We herein describe a case on the efficacy of disopyramide for refractory syncope in HF...
The management of syncope is clinically important for heart failure (HF) patients. We herein describe a case on the efficacy of disopyramide for refractory syncope in HF with preserved ejection fraction (HFpEF). An 82-year-old man was hospitalized for respiratory distress and lower limb edema and was subsequently diagnosed with HFpEF. The use of diuretics improved HF symptoms; however, on day 10 after hospitalization, a rapid decrease in blood pressure and transient loss of consciousness developed. After neurologic examination, he was diagnosed with pure autonomic failure. Although he was administered midodrine 8 mg/d, fludrocortisone 0.1 mg/d, and droxidopa 300 mg/d, syncope was observed once a day on average. According to the Holter electrocardiogram, the patient's heart rate and coefficient of variation of R-R intervals (CVRR) during the day were unstable. In addition, high frequency power (parasympathetic nerve activity) was significantly higher than low frequency power (both sympathetic and parasympathetic nerves activity), suggesting that the parasympathetic nerves may have been highly active while the sympathetic nerves would have been blocked. On day 29, a pharmacist proposed disopyramide 300 mg/d, which blocks parasympathetic nerves and improves neural-mediated syncope, to the attending doctor. After the initiation of disopyramide, transient loss of consciousness was not observed. Furthermore, the diurnal variation in the heart rate and CVRR completely disappeared. In conclusion, disopyramide would be effective for refractory syncope in patients with HFpEF, and the Holter electrocardiogram may be a useful tool for the assessment of drug efficacy by pharmacists.
Topics: Aged, 80 and over; Disopyramide; Electrocardiography, Ambulatory; Heart Failure; Humans; Male; Stroke Volume; Syncope
PubMed: 35908952
DOI: 10.1248/yakushi.22-00047 -
Journal of Thoracic Disease Jun 2022The prevalence of hypertrophic cardiomyopathy (HCM) is estimated to be 1 in 200 to 500 individuals, with systolic anterior motion (SAM) of the mitral valve (MV) and left... (Review)
Review
BACKGROUND AND OBJECTIVE
The prevalence of hypertrophic cardiomyopathy (HCM) is estimated to be 1 in 200 to 500 individuals, with systolic anterior motion (SAM) of the mitral valve (MV) and left ventricular outflow tract (LVOT) obstruction present in 60% to 70%. In this narrative review, we aim to elucidate the pathophysiology of SAM-septal contact and LVOT obstruction in HCM by presenting a detailed review on the anatomy of the MV apparatus in HCM, examining the various existing theories pertaining to the SAM phenomenon as supported by cardiac imaging, and providing a critical assessment of management strategies for SAM in HCM.
METHODS
A literature review was performed using PubMed, EMBASE, Ovid, and the Cochrane Library, of all scientific articles published through December 2021. A focus was placed on descriptive studies, reports correlating echocardiographic findings with pathologic diagnosis, and outcomes studies.
KEY CONTENT AND FINDINGS
The pathophysiology of SAM involves the complex interplay between HCM morphology, MV apparatus anatomic abnormalities, and labile hemodynamic derangements. Echocardiography and cardiac magnetic resonance (CMR) vector flow mapping have identified drag forces, as opposed to the "Venturi effect", as the main hydraulic forces responsible for SAM. The degree of mitral regurgitation with SAM is variable, and its severity is correlated with degree of LVOT obstruction and outcomes. First line therapy for the amelioration of SAM and LVOT obstruction is medical therapy with beta-blockers, non-dihydropyridine calcium-channel blockers, and disopyramide, in conjunction with lifestyle modifications. In refractory cases septal reduction therapy is performed, which may be combined with a 'resect-plicate-release' procedure, anterior mitral leaflet extension, surgical edge-to-edge MV repair, anterior mitral leaflet retention plasty, or secondary chordal cutting.
CONCLUSIONS
Recent scientific advances in the field of HCM have allowed for a maturation of our understanding of the SAM phenomenon. Cardiac imaging plays a critical role in its diagnosis, treatment, and surveillance, and in our ability to apply the appropriate therapeutic regimens. The increasing prevalence of HCM places an emphasis on continued basic and clinical research to further improve outcomes for this challenging population.
PubMed: 35813751
DOI: 10.21037/jtd-22-182 -
Journal of Clinical Medicine Jul 2022Obstructive hypertrophic cardiomyopathy (oHCM) has been studied primarily in comprehensive centers of excellence. Broadening the understanding of patients with oHCM in...
Clinical Characteristics and Healthcare Resource Utilization among Patients with Obstructive Hypertrophic Cardiomyopathy Treated in a Range of Settings in the United States.
Obstructive hypertrophic cardiomyopathy (oHCM) has been studied primarily in comprehensive centers of excellence. Broadening the understanding of patients with oHCM in the general population may improve identification and treatment in other settings. This retrospective cohort study identified adults with oHCM from a large electronic medical record database comprising data from 39 integrated delivery networks (IBM Explorys; observational period: January 2009-July 2019). Clinical characteristics, healthcare resource utilization (HCRU), and outcomes were reported. Of 8791 patients, 53.0% were female and the mean index age was 61.8 years. Cardiovascular drugs prescribed included beta-blockers (80.5%), calcium channel blockers (46.0%), and disopyramide (2.4%). Over time, heart failure, atrial fibrillation, and ventricular arrhythmias increased. Surgical procedures included septal myectomy (22.0%), alcohol septal ablation (0.6%), and heart transplantation (0.3%). Implantable cardioverter defibrillators were present in 11.2% of patients. After initial septal reduction therapy (SRT), HCRU increased and 550 patients (27.7%) required a reintervention. Of the overall group, 2.7% experienced sudden cardiac arrest by end of study. In conclusion, this cohort of patients with oHCM had guideline-recommended drug therapy and procedures. Despite this, heart failure, atrial fibrillation, and ventricular arrhythmias increased, and more than a quarter of patients undergoing SRT required reintervention. These unresolved issues emphasize the unmet need for new, effective therapies for patients with oHCM.
PubMed: 35807183
DOI: 10.3390/jcm11133898 -
Journal of Pharmacological Sciences Aug 2022Since information is still limited whether atrial I may become a potential therapeutic target to terminate persistent atrial fibrillation (AF), we assessed it by using...
Roles of I for perpetuating atrial fibrillation: Effects of atrial-selective K channel inhibitor AVE0118 and class I drugs on the persistent atrial fibrillation canine model.
Since information is still limited whether atrial I may become a potential therapeutic target to terminate persistent atrial fibrillation (AF), we assessed it by using the persistent AF canine model with representative I inhibitor AVE0118 and class I drugs. AVE0118 (6 mg/kg, n = 7), disopyramide (3 mg/kg, n = 7) and cibenzoline (3 mg/kg, n = 6) terminated the AF in 3/7, 1/7 and 2/6 animals, respectively, whereas aprindine (3 mg/kg, n = 6) did not suppress it. These findings suggest that I inhibition in addition to open-state I suppression with slow dissociation kinetics can synergistically exert potent antiarrhythmic action against persistent AF.
Topics: Action Potentials; Animals; Anti-Arrhythmia Agents; Atrial Fibrillation; Biphenyl Compounds; Dogs; Heart Atria
PubMed: 35717070
DOI: 10.1016/j.jphs.2022.05.004 -
Drugs Jun 2022Hypertrophic cardiomyopathy (HCM), the most common inherited heart disease, is still orphan of a specific drug treatment. The erroneous consideration of HCM as a rare... (Review)
Review
Hypertrophic cardiomyopathy (HCM), the most common inherited heart disease, is still orphan of a specific drug treatment. The erroneous consideration of HCM as a rare disease has hampered the design and conduct of large, randomized trials in the last 50 years, and most of the indications in the current guidelines are derived from small non-randomized studies, case series, or simply from the consensus of experts. Guideline-directed therapy of HCM includes non-selective drugs such as disopyramide, non-dihydropyridine calcium channel blockers, or β-adrenergic receptor blockers, mainly used in patients with symptomatic obstruction of the outflow tract. Following promising preclinical studies, several drugs acting on potential HCM-specific targets were tested in patients. Despite the huge efforts, none of these studies was able to change clinical practice for HCM patients, because tested drugs were proven to be scarcely effective or hardly tolerated in patients. However, novel compounds have been developed in recent years specifically for HCM, addressing myocardial hypercontractility and altered energetics in a direct manner, through allosteric inhibition of myosin. In this paper, we will critically review the use of different classes of drugs in HCM patients, starting from "old" established agents up to novel selective drugs that have been recently trialed in patients.
Topics: Adrenergic beta-Antagonists; Cardiomyopathy, Hypertrophic; Humans
PubMed: 35696053
DOI: 10.1007/s40265-022-01728-w -
European Journal of Preventive... Aug 2022Several studies have reported excess female mortality in patients with hypertrophic cardiomyopathy, but the cause is unknown.
BACKGROUND
Several studies have reported excess female mortality in patients with hypertrophic cardiomyopathy, but the cause is unknown.
AIMS
To compare risk-factors for disease-related death in both sexes in a geographical cohort of patients with obstructive hypertrophic cardiomyopathy (oHCM).
METHODS AND RESULTS
Data-bases in all ten hospitals within West Götaland Region yielded 250 oHCM-patients (123 females, 127 males). Mean follow-up was 18.1 y. Risk-factors for disease-related death were evaluated by Cox-hazard regression and Kaplan-Meier survival-curves, with sex-comparisons of distribution of risk-factors and therapy in total and age-matched (n = 166) groups. At diagnosis females were older, median 62 y vs. 51 y, (P < 0.001), but not different in outflow-gradients and median NYHA-class. However, septal hypertrophy was more advanced: 10.6 [IQR = 3.2] vs. 9.6 [2.5] mm/m2 BSA; P = 0.002. Females had higher disease-related mortality than males (P = <0.001), with annual mortality 2.9% vs. 1.5% in age-matched groups (P = 0.010 log-rank). For each risk-category identified (NYHA-class ≥ III, outflow-gradient ≥50 mmHg), a higher proportion of females died (P = 0.0004; P = 0.001). Calcium-blocker therapy was a risk-factor (P = 0.005) and was used more frequently in females (P = 0.034). A beta-blocker dose above cohort-median reduced risk for disease-related death in both males (HR = 0.32; P = 0.0040) and in females (HR = 0.49; P = 0.020). Excess female deaths occurred in chronic heart-failure (P = 0.001) and acute myocardial infarctions (P = 0.015). Fewer females received beta-blocker therapy after diagnosis (64% vs. 78%, P = 0.018), in a smaller dose (P = 0.007), and less frequently combined with disopyramide (7% vs. 16%, P = 0.048).
CONCLUSION
Addressing sex-disparities in the timing of diagnosis and pharmacological therapy has the potential to improve the care of females with oHCM.
Topics: Male; Humans; Female; Treatment Outcome; Kaplan-Meier Estimate; Echocardiography; Risk Factors; Cardiomyopathy, Hypertrophic
PubMed: 35512246
DOI: 10.1093/eurjpc/zwac078 -
International Journal of Cardiology May 2022To evaluate the role of bisoprolol to control symptoms and left ventricular outflow tract obstruction (LVOTO) in a consecutive cohort of adults with hypertrophic...
AIMS
To evaluate the role of bisoprolol to control symptoms and left ventricular outflow tract obstruction (LVOTO) in a consecutive cohort of adults with hypertrophic cardiomyopathy (HCM).
METHODS AND RESULTS
In this retrospective study, patients with HCM with an LVOT gradient ≥50 mmHg after Valsalva manoeuvre and New York Heart Association (NYHA) class II-III symptoms were assigned to receive bisoprolol (starting at 1.25 mg daily). The initial dose was increased every two weeks to achieve the target in LVOT gradient <30 mmHg or the maximum tolerated dose. The primary endpoint was the achievement of a LVOT gradient <30 mmHg and ≥ 1 NYHA class improvement. The secondary endpoints were proportion of patients with LVOT gradient <30 mmHg or < 50 mmHg, proportion of patients with ≥1 NYHA class improvement, and change from baseline in LVOT gradient. Between December 2001 and December 2020, 92 patients were enrolled into the study. Sixteen (17%) patients on bisoprolol met the primary endpoint. Bisoprolol reduced the LVOT gradient to less than 30 mmHg in 33 (36%) patients, to less than 50 mmHg in 57 (62%), and improved NYHA class in 30 (33%). The mean reduction of LVOT gradient on bisoprolol was 28 (±14) mmHg and the percentage reduction was 42 (±21) %. In 35 (38%) patients, bisoprolol did not reduce the gradient to less than 50 mmHg requiring disopyramide and/or myectomy to achieve this goal.
CONCLUSION
Treatment with bisoprolol was well-tolerated and effective in relieving obstruction and improving symptoms in a significant proportion of patients with symptomatic obstructive HCM.
Topics: Adult; Bisoprolol; Cardiomyopathy, Hypertrophic; Disopyramide; Humans; Retrospective Studies; Ventricular Outflow Obstruction
PubMed: 35278578
DOI: 10.1016/j.ijcard.2022.03.013