Treatment of Obstructive Hypertrophic Cardiomyopathy Symptoms and Gradient Resistant to First-Line Therapy With β-Blockade or Verapamil

Sherrid, Mark V.; Shetty, Aneesha; Winson, Glenda; Kim, Bette; Musat, Dan; Alviar, Carlos L.; Homel, Peter; Balaram, Sandhya K.; Swistel, Daniel G.

doi:10.1161/circheartfailure.112.000122

Cited by 135 publications

(97 citation statements)

References 34 publications

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“…Only 2 patients had cardiac events (syncope in both) during 225 patient‐years of treatment. This high safety profile is in concordance with previous publications demonstrating no increase in sudden cardiac death risk in HCM patients treated with higher mean doses (430–500 mg) of this drug 4, 9. Nevertheless, disopyramide does have significant electrophysiological effects.…”

Section: Discussionsupporting

confidence: 91%

“…Furthermore, a recommendation for hospital monitoring for initiation of a drug is likely to limit its utilization significantly. In the case of disopyramide, underutilization may lead to unnecessary interventions given that therapy with this drug may abolish the need for septal reduction procedures in most patients with LVOTO‐related symptoms 4, 9…”

Section: Discussionmentioning

confidence: 99%

“…At that time, and according to the clinical response, increasing the disopyramide dose, discontinuation of the drug, or referral for a septal reduction intervention (as per guideline indications)5, 6 is considered. Pyridostigmine, which has been demonstrated to attenuate the anticholinergic side effects of disopyramide,4 is also considered if patients develop such side effects.…”

Section: Methodsmentioning

confidence: 99%

“…Drugs with a negative inotropic effect are most commonly used as first line and include beta‐blockers (BB) and/or nondihydropyridine calcium‐channel blockers (CCB; primarily verapamil) 3. However, a substantial portion of patients (40% in 1 large study)4 suffer from symptoms that are refractory to these agents. In such patients, an interventional approach for reduction of septal myocardial mass by either surgery (myectomy) or catheterization (alcohol septal ablation) may be recommended 5, 6.…”

Section: Introductionmentioning

confidence: 99%

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Safety of Outpatient Initiation of Disopyramide for Obstructive Hypertrophic Cardiomyopathy Patients

Adler

Fourey

Weissler‐Snir

et al. 2017

JAHA

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BackgroundDisopyramide is effective in ameliorating symptoms in patients with hypertrophic cardiomyopathy; however, its potential for proarrhythmic effect has raised concerns about its use in the ambulatory setting. The risk of initiating disopyramide in this manner has never been evaluated.Methods and ResultsAll charts of patients seen in the outpatient hypertrophic cardiomyopathy clinic between 2010 and 2014 were screened for initiation of disopyramide and data were extracted. Disopyramide in our clinic is usually initiated at a dose of 300 mg daily and titrated during follow‐up. A total of 2015 patients were seen in the clinic, including 168 who were started on disopyramide. There were no cardiac events within 3 months of disopyramide initiation. During long‐term follow‐up (255 patient‐years; mean, 447 days; interquartile range, 201–779), only 2 patients developed cardiac events (syncope of unknown cause in both). Thirty‐eight patients (23%) developed side effects of disopyramide and 18 (11%) stopped the drug because of these side effects. Of the patients continuing disopyramide long term, 63% remained free of septal reduction interventions at end of follow‐up. Disopyramide at a dose of 300 mg prolonged the mean QTc interval by 19±23 ms; however, increasing the dose to 600 mg had no further significant effect.ConclusionsInitiation of disopyramide in the outpatient setting is safe and the risk of subsequent sudden cardiac death is low. Because of its QT‐prolonging effect, precautions may be necessary in patients at higher risk of torsades de pointes.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Safety of Outpatient Initiation of Disopyramide for Obstructive Hypertrophic Cardiomyopathy Patients

Adler

Fourey

Weissler‐Snir

et al. 2017

JAHA

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“…Presentation is highly variable even within families, and although the majority of affected individuals lead a normal life, some develop severe, progressive heart failure symptoms, angina, or arrhythmia, and others die suddenly, either with or without previous symptoms. Left ventricular outflow tract (LVOT) obstruction occurs in two-thirds of patients either at rest or after provocation and can be improved by negatively inotropic drugs, surgical septal myectomy, or alcohol septal ablation 1 . Patients judged to be at high risk of sudden death (SCD) from ventricular fibrillation can be treated with an implanted defibrillator, most often as primary prevention, or for secondary prevention after surviving a potentially lethal ventricular arrhythmia 2,3 .…”

mentioning

confidence: 99%

Myocardial energy depletion and dynamic systolic dysfunction in hypertrophic cardiomyopathy

2016

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Evidence indicates that anatomical and physiological phenotypes of hypertrophic cardiomyopathy (HCM) stem from genetically mediated, inefficient cardiomyocyte energy utilization, and subsequent cellular energy depletion. However, HCM often presents clinically with normal left ventricular (LV) systolic function or hyperkinesia. If energy inefficiency is a feature of HCM, why is it not manifest as resting LV systolic dysfunction? In this Perspectives article, we focus on an idiosyncratic form of reversible systolic dysfunction provoked by LV obstruction that we have previously termed the 'lobster claw abnormality' — a mid-systolic drop in LV Doppler ejection velocities. In obstructive HCM, this drop explains the mid-systolic closure of the aortic valve, the bifid aortic pressure trace, and why patients cannot increase stroke volume with exercise. This phenomenon is characteristic of a broader phenomenon in HCM that we have termed dynamic systolic dysfunction. It underlies the development of apical aneurysms, and rare occurrence of cardiogenic shock after obstruction. We posit that dynamic systolic dysfunction is a manifestation of inefficient cardiomyocyte energy utilization. Systolic dysfunction is clinically inapparent at rest; however, it becomes overt through the mechanism of afterload mismatch when LV outflow obstruction is imposed. Energetic insufficiency is also present in nonobstructive HCM. This paradigm might suggest novel therapies. Other pathways that might be central to HCM, such as myofilament Ca2+ hypersensitivity, and enhanced late Na+ current, are discussed

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How Hypertrophic Cardiomyopathy Became a Contemporary Treatable Genetic Disease With Low Mortality

et al. 2016

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Hypertrophic cardiomyopathy (HCM) is a relatively common genetic heart disease encumbered throughout much of its almost 60-year history by a large measure of misunderstanding and the perception of a grim outcome without effective treatment options. However, it is now apparent that the majority of patients affected with HCM can achieve normal or near-normal life expectancy without disability, and usually do not require major treatment interventions. Nevertheless, for those patients with HCM who are at risk for (or experience) disease-related complications, a constellation of comprehensive nonpharmacologic management strategies have evolved over the last 15 years, altering the natural history and disease course for many, including implantable defibrillators, heart transplant, external defibrillation/therapeutic hypothermia, advances in surgical myectomy, and alcohol ablation. In particular, expanded contemporary risk stratification strategies have led to a more reliable selection of patients likely to achieve primary prevention of sudden death with implantable defibrillators. Most recently, large cohort studies using current management strategies and therapeutic measures have shown that it is now possible to achieve significantly improved survival with a low HCM-related mortality of 0.5% per year across all ages, and including children and young adults characteristically with the most aggressive disease course. These clinical management initiatives, instituted by the practicing cardiology community, have succeeded in preserving life and restoring an active lifestyle for thousands of patients with HCM, while providing many with a measure of reassurance and a reasonable expectation for an extended (if not normal) life span.

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Treatment of Obstructive Hypertrophic Cardiomyopathy Symptoms and Gradient Resistant to First-Line Therapy With β-Blockade or Verapamil

Cited by 135 publications

References 34 publications

Safety of Outpatient Initiation of Disopyramide for Obstructive Hypertrophic Cardiomyopathy Patients

Safety of Outpatient Initiation of Disopyramide for Obstructive Hypertrophic Cardiomyopathy Patients

Myocardial energy depletion and dynamic systolic dysfunction in hypertrophic cardiomyopathy

How Hypertrophic Cardiomyopathy Became a Contemporary Treatable Genetic Disease With Low Mortality

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