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Logo of thijTexas Heart Institute JournalSee also Cardiovascular Diseases Journal in PMCSubscribeSubmissionsTHI Journal Website
Tex Heart Inst J. 2009; 36(3): 194–204.
PMCID: PMC2696493

Contemporary Treatment of Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is a fascinating disease that for the past 50 years has captured the interest of clinicians and surgeons alike. It is a primary disease of cardiac myocytes that is characterized by concentric, yet asymmetric, cardiac hypertrophy and by an increased or preserved left ventricular ejection fraction (LVEF). Despite the descriptions of the pathologic phenotype by Liouville in 18691 as cardiac contraction below the aortic valve and by Schmincke in 19072 as diffuse muscular “hyperplasia” at the left ventricular outflow tract (LVOT), the clinical recognition of HCM had to await the development of advanced diagnostic tools in the 2nd half of the 20th century. Accordingly, Braunwald and colleagues, in the 1960s, emphasized the hemodynamic features of HCM and coined the term “idiopathic hypertrophic subaortic stenosis” or “IHSS” to describe the LVOT obstruction.3,4 The recognition of LVOT obstruction as a major characteristic of HCM led to the 1st performance of a surgical transaortic septal myectomy, described by Morrow and colleagues in 1964.5

The asymmetric type of cardiac hypertrophy in HCM was recognized very early, and the finding of asymmetric septal hypertrophy on an echocardiogram became the sine qua non for a diagnosis of HCM.6 The application of Doppler echocardiography to the evaluation of patients with HCM shed further light on the physiology of the LVOT obstruction and helped in the evaluation of diastolic function.7–10 More recently, tissue Doppler imaging (TDI) has been applied to obtain an early diagnosis of HCM (before, and independent of, the development of cardiac hypertrophy) and to further evaluate myocardial function in HCM.11,12 Consequently, echocardiography, including Doppler evaluation, is the most commonly used diagnostic technique in HCM—supplanting cardiac catheterization, which is now reserved for specific indications.

The seminal work of Seidman and associates13 led to the discovery, in 1990, of the 1st causal gene and mutation for HCM, ushering in a new era of molecular genetics in application to the disorder. The discovery had a watershed effect, as it led to partial elucidation of the molecular genetic basis of HCM and to the identification of more than a dozen causal genes that encode sarcomeric proteins.14 Accordingly, HCM is now recognized as a disease of sarcomeric proteins. Advances in the molecular genetics of HCM have raised considerable interest in early diagnosis and in genotype-dependent risk stratification and treatment. These studies, on the other hand, have illustrated the presence of considerable phenotypic variability among subjects with identical causal mutations; hence, they have emphasized the importance of considering the plurality of determinants of clinical phenotypes. Similarly, molecular genetic studies have illustrated the shortcomings of clinical diagnosis in distinguishing between HCM and HCM-phenocopy conditions (conditions that mimic HCM, such as storage diseases).

Despite considerable advances in the clinical recognition and molecular genetics of HCM, the pharmacologic treatment of patients with HCM has remained largely unchanged during the past several decades. However, 2 major non-pharmacologic interventions—percutaneous transcatheter septal ablation (or alcohol septal ablation) and the implantation of internal cardioverter-defibrillators (ICDs)—have changed the landscape significantly. Sigwart15 introduced the catheter-based reduction of septal hypertrophy for the treatment of LVOT obstruction in 1995. The procedure has proved a highly effective method for the reduction of LVOT obstruction and alleviation of symptoms.16–18 The potential for arrhythmogenesis, which can originate from the local site of induced myocardial injury, has somewhat subdued enthusiasm for the routine use of alcohol septal ablation, particularly in consideration of the fact that HCM is an arrhythmogenic phenotype. Indeed, HCM remains the most common discernible cause of sudden cardiac death (SCD) in the young—particularly in competitive athletes.19,20 The advent of implantable defibrillators has provided physicians with an effective option for primary and secondary prevention of SCD in high-risk patients.21,22 However, implantable defibrillators have no substantial effects on the underlying phenotype of cardiac hypertrophy and its accompanying fibrosis, so additional therapies are needed. Experimental data obtained from the study of animal models of HCM have suggested the potential usefulness of various pharmacologic agents—including statins, inhibitors of the renin-angiotensin-aldosterone system (RAAS), and N-acetylcysteine—in the prevention and reversal of the cardiac phenotype in HCM.23–27 The field awaits large-scale randomized clinical studies in human beings who have HCM, in order to determine the potential beneficial effects of these novel therapeutic and preventive interventions.

Overview of Clinical Aspectsof Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy is a primary disease of cardiac myocytes that is diagnosed by the presence of unexplained cardiac hypertrophy: that is, by hypertrophy in the absence of an increased load, by a small left ventricular (LV) cavity size, and by preserved or increased LV systolic function. Pathologically, it is characterized by gross cardiac and myocyte hypertrophy, myocyte disarray, interstitial fibrosis, hypertrophy or hyperplasia of the media of the intramural coronary arteries, and anomalies of the mitral valve leaflets. Cardiac myocyte disarray, often affecting more than 20% of the ventricle, is the pathologic hallmark of HCM.

The quintessential diagnostic feature of HCM is cardiac hypertrophy, which is concentric but commonly asymmetric, with predominant involvement of the interventricular septum. Diagnosed on the basis of an echocardiographic wall thickness of ≥15 mm, HCM is a relatively common disease, the estimated prevalence of which is approximately 1:500 in the general population.28 Most patients with HCM are asymptomatic or minimally symptomatic. Unfortunately, SCD may be the 1st manifestation of the disease.19,20 The most common symptom is dyspnea, primarily due to diastolic dysfunction—particularly during exercise. Chest pain may occur because of myocardial hypoperfusion and increased oxygen demand. Palpitations are common and often are associated with lightheadedness and dizziness, and occasionally with syncope. This last is an infrequent but serious symptom that is associated with increased risk of SCD.29,30 Atrial fibrillation and supraventricular arrhythmias, also common in patients with HCM, are often associated with adverse clinical outcomes.31

Overall, HCM is a relatively benign disease with an annual mortality rate of slightly less than 1% in unselected HCM populations.32,33 Sudden cardiac arrest or death is the most feared event in HCM: it often is the 1st manifestation of the disease in young, apparently healthy, and often athletic individuals.19,20 There is no single reliable predictor of SCD in HCM. However, a few major risk factors have been identified: a history of cardiac arrest, syncope due to cardiac arrhythmias, a strong family history of SCD (indicative of causal and modifier genes), repetitive nonsustained or sustained ventricular tachycardia, and severe cardiac hypertrophy (Table I).30,34–38 Given that none of the known risk factors reliably predicts SCD, a pluralistic approach that includes the above combination of risk factors is necessary for proper identification of those at risk of SCD.

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TABLE I. Risk Factors for Sudden Cardiac Death in Patients with Hypertrophic Cardiomyopathy

Overview of the Molecular Genetics of Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy, whether sporadic or familial, is a genetic disease caused by mutations in genes that encode sarcomeric proteins, including the Z-disc proteins.14 The mode of inheritance is autosomal dominant, so every offspring has a 50% chance of inheriting the disease. From the clinician's point of view, then, it is essential that all family members be screened for the disease, particularly because SCD can be the 1st manifestation of this disease in apparently healthy family members.19,20

Since the seminal discovery13 in 1990 of a point missense mutation in the MYH7 gene coding for the β-myosin heavy chain (β-MyHC), more than a dozen causal genes for HCM have been identified (Table II). There are several hundred causal mutations. The frequency of each mutation is low enough that mutations are considered private. The 2 most common genes for HCM are MYH7 and MYBPC3, which encode β-MyHC and myosin binding protein-C (MyBP-C), respectively.39–41 Each accounts for approximately 25% to 30% of HCM cases.39–41 Other relatively common genes are TNNT2, TNNI3, TPM1, and ACTC1, which encode cardiac troponin T, cardiac troponin I, α-tropomyosin, and cardiac α-actin, respectively.42–45 They account, collectively, for about 10% of HCM cases. The rest of the causal genes are low in prevalence. Overall, known causal genes account for about 60% of all HCM cases, so 40% of the causal genes for HCM are unknown.

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TABLE II. Causal Genes for Hypertrophic Cardiomyopathy

Approximately 5% to 10% of clinically diagnosed cases of HCM are not HCM but are phenocopy conditions, such as storage diseases. A prototypic example of an HCM phenocopy is Fabry disease, which is caused by the deficient activity of α-galactosidase A (α-Gal A), also known as ceramide trihexosidase.46–48 Cardiac hypertrophy in Fabry disease is often indistinguishable from true HCM. Another noteworthy phenocopy is a glycogen storage disease due to PRKAG2 mutations; this leads to cardiac hypertrophy, conduction defects, and pre-excitation–type electrocardiograms.49–51

An important aspect of the genetic studies in HCM is the presence of considerable phenotypic variability, which restricts the power of genetic testing in prognostication. Variable phenotypic expression is best illustrated among members of a single family, who share causal mutation and a significant fraction of their genome. Phenotypic variability of HCM occurs in part because the modifier genes, which are neither necessary nor sufficient to cause HCM, have functional variants that can affect the severity of the disease (the degree of cardiac hypertrophy, for example).52–54 Recently, we mapped 5 modifier loci for human HCM and showed that each exerted significant effect on the phenotypic expression of cardiac hypertrophy. The effect sizes of the modifier alleles in the homozygous form were greater than the effect size of the causal mutation (heterozygous only).55,56 The findings illustrate the importance of considering all constituents that contribute to a clinical phenotype.

Contemporary Management of Hypertrophic Cardiomyopathy

Overview. Hypertrophic cardiomyopathy, diagnosed clinically by the presence of primary cardiac hypertrophy and a preserved or enhanced LVEF, is a relatively common disease.28,57 Despite its prevalence, HCM is often undiagnosed, particularly in the early stages of the phenotype and in the presence of concomitant phenotypes, such as hypertension. Therefore, patients with HCM are typically diagnosed when they present with symptoms of heart failure due to diastolic dysfunction, with palpitations and syncope due to supraventricular or ventricular arrhythmias, or with chest pain due to myocardial hypoperfusion. Unfortunately, in a substantial number of individuals, SCD or cardiac arrest is the 1st manifestation of HCM.19 Therefore, an important aspect of the management of HCM is early diagnosis, in order to intervene and prevent SCD.

Most HCM patients are asymptomatic or minimally symptomatic. In such patients, the primary focus is on the assessment of risk of SCD. Those who are at low risk for SCD (discussed below) require only periodic history-taking and physical examination, 12-lead electrocardiography, 2-dimensional and Doppler echocardiography, and 48-hour Holter monitoring. An asymptomatic individual who is at high risk of SCD because of the presence of 2 or more major risk factors (Table I) is a candidate for an ICD implantation, which has been shown to reduce SCD.21 The merit of pharmacologic or nonpharmacologic intervention in an effort to prevent or attenuate the evolving cardiac phenotype in asymptomatic patients or to prevent SCD has not been established.

Treatment options for patients with symptoms of heart failure consist of pharmacologic therapy with β-blockers, verapamil, disopyramide, and (in low doses) diuretic agents. Symptomatic patients who display substantial LVOT gradients are candidates for treatment with a combination of β-blockers and disopyramide, surgical myectomy, and transcatheter septal ablation. Patients who have palpitations require extensive Holter monitoring and, in certain situations, electrophysiologic studies, in order to detect cardiac arrhythmias and to determine their causes, so that proper therapy can be administered. Syncope, a major risk factor for SCD, requires extensive investigation that comprises Holter monitoring, electrophysiologic studies, exercise testing, and, if needed, tilt-table testing to differentiate arrhythmic from autonomic causes and thereby enable the choice of appropriate therapy.

Pharmacologic Therapy. Current pharmacologic treatment of patients who have HCM includes the use of β-blockers (without intrinsic sympathetic activity), calcium-channel blockers (without vasodilating activity), and disopyramide. b-Blockers are the mainstay of therapy and the 1st choice in all patients, unless there is a contraindication. b-Blockers are most useful in patients with exercise-induced symptoms, LVOT obstruction, and chest pain. The beneficial effects of b-blockers are imparted in part through the prevention of catecholaminergic increases in heart rate, in ventricular contractility, and in stiffness. The collective effects of b-blockers lead to improved ventricular relaxation and increased diastolic filling time and, hence, to improved LV end-diastolic pressure and perfusion. In addition, treatment with b-blockers is expected to reduce ventricular and supraventricular arrhythmias. Despite these advantages, the effects of treatment with b-blockers on cardiovascular death and the risk of SCD remain to be established. Retrospective observational data on pediatric populations with HCM (mixed HCM and Noonan's syndrome) suggest that treatment with high doses of β-blockers might yield beneficial effects on total survival.58 Side effects of b-blockers are easy fatigability, excess bradycardia, hypotension, and bronchospasm.

Calcium-channel blockers such as verapamil and diltiazem are also beneficial, in part through their negative inotropic and chronotropic effects and in part through their improvement of myocardial diastolic properties. They should be used whenever b-blockers are not tolerated, or in conjunction with b-blockers, but should be avoided in patients who have LVOT obstruction. Conversely, dihydropyridine calcium-channel blockers, such as nifedipine, should not be used in patients with HCM, because of the possibility that their vasodilatory effects could induce hypotension, syncope, and possibly death. In general, diltiazem and verapamil are well tolerated in HCM patients who do not have LVOT obstruction. The most common side effect of verapamil is constipation.

Disopyramide, which is a class I antiarrhythmic drug, has been used in conjunction with β-blockers to attenuate LVOT obstruction and improve symptoms in patients with HCM.59 The beneficial effects of disopyramide are largely attributable to its negative inotropic effects. Hence, it is most effective in patients with LVOT obstruction. Data from an observational study59 suggest that approximately two thirds of patients with significant LVOT gradients could be managed with disopyramide and β-blocker therapy. The most significant side effects of disopyramide are its anticholinergic effects, such as tachycardia, blurred vision, and dry mucosa.

Diuretics are reserved only for those with evidence of significant volume overload and should be used at low dose to avoid intravascular volume depletion and hypotension. Experimental data suggest that mineralocorticoid-receptor blockade with aldosterone has potential beneficial effects.60 Experimental and clinical data also suggest a potential benefit in using angiotensin-II receptor blockers to treat HCM.27,61 In general, however, drugs with vasodilatory effects, such as inhibitors of the renin-angiotensin system, are not routinely recommended in treating HCM.

Early Identification and Management of Individuals at Risk of Hypertrophic Cardiomyopathy. Hypertrophic cardiomyopathy is a familial disease with an autosomal dominant mode of inheritance in approximately one half to two thirds of all cases.62,63 Consequently, a practical and effective approach to early diagnosis of asymptomatic individuals with HCM lies in obtaining both a detailed family history and clinical evaluation of genetically related family members. In an autosomal dominant disease, approximately half of the offspring will develop HCM at some point in their lives. The typical clinical evaluation includes history-taking, physical examination, and obtaining a 12-lead electrocardiogram, Holter monitoring, and echocardiograms (M-mode, 2-dimensional, and Doppler). Routine screening of asymptomatic family members of patients who have dilated cardiomyopathy has led to the early identification of affected family members (20% of the examined relatives).64

Recent studies have shown the potential usefulness of TDI in the early diagnosis of individuals with HCM-causing mutations.11,12,65 Those with HCM-causing mutations but without cardiac hypertrophy show reduced myocardial Doppler velocities and typically a preserved or enhanced LVEF.12,65 Tissue Doppler imaging is likely to be most useful in familial settings because of the lower prevalence of confounders, in comparison with garden-variety HCM in the general population. Similarly, the detection of subtle myocardial abnormalities by means of magnetic resonance imaging could help to identify mutation-carrying individuals before they develop cardiac hypertrophy.66

The most desirable approach for the early identification of those at risk of HCM is genetic screening. Family members of affected individuals and their physicians share the enthusiasm for early identification of mutation carriers by genetic screening. The obvious benefit of genetic testing is the identification of family members who do not carry the causal mutation and are at extremely low risk of developing HCM (this risk is due to 2nd mutations and technical errors). Family members who carry the causal mutation will develop HCM, albeit the severity of the phenotype could vary considerably. Genetic screening is confounded by marked allelic and nonallelic genetic heterogeneity of HCM that requires extensive resequencing and by the fact that about 40% of the causal genes for HCM have yet to be identified (hence, screening is not possible). The use of massively parallel DNA resequencing instruments—often referred to as the Next Generation Sequencers—is expected to enhance genetic screening significantly by making it possible to screen for a very large number of genes (known causal genes, together with candidates) in a large number of individuals.

Whether by genetic testing or by modern diagnostic imaging or by the use of new biomarkers, early diagnosis of mutation carriers (before, and independent of, the presence of cardiac hypertrophy) attempts, of course, to identify those persons who are at risk of clinical events and to intervene. Through early pharmacologic intervention, we can attempt to prevent or attenuate the evolution of the HCM phenotype in those with mutations but without clinical HCM, as was shown in a transgenic rabbit model of human HCM.25 An important effect of our ability to identify the HCM phenotype early is a higher level of alertness among physicians and affected family members, so that monitoring becomes more vigorous and widespread. Currently, there are insufficient data to recommend pharmacologic intervention or implantation of ICDs in persons who manifest HCM mutations without clinical HCM.

Management of Risk of Sudden Cardiac Death. Not surprisingly, SCD is the most common and important concern in the minds of patients with HCM, their relatives, and their physicians. The problem is compounded by the lack of a strongly reliable predictor of SCD in patients with HCM. This deficiency, along with data suggesting the efficacy of ICDs in the primary prevention of SCD, has led some physicians, in the absence of adequate risk stratification, to recommend the implantation of ICDs in patients with HCM. This approach is extreme, because HCM in its usual form is a relatively benign disease with an annual mortality rate of less than 1%.32,33,67–69 Therefore, risk stratification is crucial to proper use of the ICD for primary prevention of SCD in HCM patients. For secondary prevention (in patients who already have experienced sudden cardiac arrest or sustained ventricular tachycardia or fibrillation), ICDs are highly effective in reducing the risk of SCD and should be implanted.21,70

Clinical phenotypes are highly complex and involve a large number of commonly recognized determinants. So too is the case for the risk of SCD in patients with HCM, because no single factor can reliably predict the risk. Accordingly, a comprehensive approach that considers all putative risk factors is necessary for the proper risk stratification of HCM patients. Table I lists the risk factors for SCD in patients with HCM. Chief among them are a family history of SCD, a personal history of arrhythmic syncope or of recurrent nonsustained ventricular tachycardia, and severe cardiac hypertrophy. The existing data could justify implantation of an ICD in HCM patients who have any one of the above risk factors.21 However, given that adverse events associated with ICD implantation are not negligible and that the positive predictive value of these predictors for SCD is relatively low in patients who have not experienced a prior event, additional risk stratification is warranted when only a single risk factor is present. For example, family history of SCD in only 1 family member of the index case is a weak indication for ICD implantation, because of remarkable phenotypic variability among family members. In contrast, an ICD should be strongly considered in a patient with arrhythmic syncope, whether that person has a family history of SCD or not. Similarly, the cutoff value of a wall thickness of 3 cm or greater (“severe hypertrophy”) as a risk factor for SCD, while substantiated,35,71 is arbitrary. The risk of SCD increases with increasing severity of hypertrophy.34,72 Exercise-induced hypotension and severe LVOT obstruction are likely important risk factors,38 but the potential benefit of ICD implantation in patients with either of these 2 risk factors remains to be established. In addition, the low incidence of the causal mutations has impeded determining their significance in accurately predicting the risk of SCD in association with HCM. Nonetheless, certain mutations are considered high risk—for example, R719Q and R403Q in MYH7, most mutations in TNNT2, and double-causal mutations.40,73–76 Although the significance of causal mutations in determining the severity of the phenotype cannot be overemphasized, it is important to point out that the phenotype is also influenced by modifier genes, microRNAs, post-translational modifications of proteins, epigenetic factors, and environmental factors.14,56 Consequently, the phenotype of SCD in HCM, a single gene disorder, is a complex phenotype, determined by a large number of genetic and nongenetic factors. Accordingly, all constituents that contribute to the phenotype need be considered for an accurate assessment of the global risk of SCD and, hence, of the justification of ICD implantation in patients with HCM.

Management of Left Ventricular Outflow Tract Obstruction. Left ventricular outflow tract obstruction is present at rest in approximately a quarter of patients with HCM and can be provoked in most HCM patients with the Valsalva maneuver, exercise, amyl nitrate inhalation, or dobutamine infusion. Left ventricular outflow tract obstruction is an important determinant of morbidity and death, and probably of SCD, in patients with HCM.35,77 Fortunately, in most patients, LVOT obstruction is relatively mild and the symptoms can be controlled with pharmacologic treatment. About one third of patients with a significant LVOT gradient do not respond adequately to pharmacologic therapy and remain significantly symptomatic. In these patients, it is important to establish that the LVOT obstruction—rather than severe diastolic dysfunction or cavity obliteration—is the major determinant of symptoms. Patients who are symptomatic because of a significant LVOT gradient and whose septal thickness is ≥15 mm are candidates for invasive interventions, which is to say surgical septal myectomy (Morrow's procedure) and transcatheter septal ablation. Both procedures are highly effective in reducing LVOT gradient and improving symptoms. The advantages and disadvantages of these 2 techniques are summarized in Table III.

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TABLE III. Septal Myectomy versus Transcatheter Septal Ablation with Ethanol

Surgical Myectomy (Myomectomy). Surgical myectomy, commonly performed through a transaortic approach described by Morrow and colleagues,5 involves resection of a small portion of the interventricular septum at its base. The procedure is best indicated in symptomatic patients who are refractory to medical therapy and have significant LVOT obstruction. It is the procedure of choice in HCM patients who have concomitant conditions such as coronary artery disease or valvular disorders. Surgical mortality rates are relatively low but vary with the experience of the surgeon and are higher in the elderly and in patients who undergo concomitant surgical procedures such as coronary artery bypass or valve surgery. The overall mortality rate varies from 1% to 5%.78–81 More extensive myectomy, extending to the papillary muscle, is associated with higher morbidity and mortality rates, but with more pronounced relief of the LVOT obstruction.82

Surgical myectomy is highly effective in alleviating symptoms and reducing LVOT obstruction. Fewer than 5% of surgical patients need repeat myectomy, and long-term survival is excellent.78–80,83 Observational studies also suggest that there is a reduced risk of SCD, as it is inferred from the lower number of ICD shocks in those who both have undergone myectomy and have received ICDs.79 For these reasons—together with the potential for arrhythmogenesis in association with myocardial necrosis induced by transcatheter septal ablation84—surgical myectomy is preferred over transcatheter septal ablation in patients who are at high risk for SCD. Similarly, surgical myectomy is preferred over transcatheter septal ablation in young symptomatic patients who have LVOT obstruction, because of a low recurrence rate and a much lower rate of permanent pacemaker implantation. Surgical myectomy is also associated with the regression of cardiac hypertrophy and with favorable LV remodeling.85 Collectively, the observational data support the positive impact of surgical myectomy on the reduction of cardiovascular death in patients with HCM, and specifically the risk of SCD.

Transcatheter Septal Ablation. Since the initial description of percutaneous transcatheter septal ablation by Sigwart in 1995,15 the procedure has been increasingly, and possibly excessively, used to reduce LVOT obstruction in patients with HCM. It is estimated that by the beginning of 2008 more than 5,000 such procedures had been performed in patients with HCM, surpassing the number of surgical myectomies performed during the same period (estimated to be between 3,000 and 4,000).86 The procedure involves the infusion of a small amount of alcohol into the major septal perforator branch of the left anterior descending coronary artery to induce localized myocardial necrosis in the septum and thereby reduce LVOT obstruction. Although septal ablation is highly effective in reducing the LVOT gradient and improving symptoms, suitability of the coronary anatomy is essential to a good outcome. As is true of surgical myectomy, transcatheter septal ablation is best reserved for symptomatic patients who are refractory to medical therapy and have an interventricular septal thickness of ≥15 mm and a substantial resting or provoked LVOT gradient.

Transcatheter septal ablation is associated with progressive LV remodeling and regression of cardiac hypertrophy.87,88 The clinical outcomes of transcatheter septal ablation are favorable, because the procedure is well tolerated, the perioperative complication rate is relatively low, and the long-term effects are sustainable.17,81,89–91 A major complication of transcatheter septal ablation is complete or advanced atrioventricular (AV) block that requires the implantation of a permanent pacemaker. The incidence of this complication has been reduced from more than 30% to about 20%, consequent to recent technical refinements of the procedure, such as the infusion of alcohol at a lesser volume and slower rate.18,92–95 An uncommon but potentially serious risk is that ventricular arrhythmias will originate from the site of alcohol infusion or border regions.18,84,96–98 The overall mortality rate associated with alcohol septal ablation is about 2% to 5% per year.18,89,99

Dual-Chamber Pacing. Dual-chamber pacing may be useful in a subset of symptomatic patients who have substantial LVOT gradients but do not respond to medical therapy and are not candidates for surgical myectomy or transcatheter septal ablation. The rationale for the use of dual-chamber pacing is that the LV excitation pattern can be modified by changing the depolarization synchrony of the LV contraction. Therefore, optimal timing of the AV interval (for reducing the LVOT gradient) is determined in a laboratory. The initial observational studies have shown promising results. However, subsequent randomized clinical studies in patients with HCM have failed to show a significant benefit of dual-chamber pacing.100–103 Hence, it is no longer used, except in rare situations.

Management of Cardiac Arrhythmias. In addition to β-blockers, which are the 1st line of therapy for cardiac arrhythmias in HCM patients, amiodarone and sotalol are used for the treatment of atrial and ventricular arrhythmias. Patients who have HCM are evaluated for cardiac arrhythmias by means of Holter monitoring and, in certain situations, by invasive electrophysiologic procedures. Ventricular ectopic beats are common and may suggest underlying arrhythmogenic substrates; hence, there is need for close monitoring to detect nonsustained and sustained ventricular arrhythmias. Repetitive nonsustained ventricular tachycardia is a risk factor for SCD and merits further evaluation for possible ICD implantation.37 Atrial fibrillation is probably the most common sustained arrhythmia in patients with HCM and is often poorly tolerated, particularly in patients who have severe hypertrophy or LVOT obstruction.31 New-onset atrial fibrillation is best converted to sinus rhythm through electrical cardioversion. To reduce the risk of systemic embolization and stroke, anticoagulation is indicated in patients who display chronic or intermittent atrial fibrillation.

Endocarditis Prophylaxis

Patients with HCM who have substantial valvular regurgitation or LVOT gradients are at increased risk of infective endocarditis. Such individuals should receive antibiotic agents prophylactically whenever undergoing dental or other procedures that place them at high risk of bacteremia.104

Potential New Pharmacologic Therapies

Current pharmacologic treatment of human beings who have HCM is largely empiric, and no such treatment has yet been proved to prevent, attenuate, or reverse the cardiac phenotype in HCM. Experimental data in animal models of human HCM have raised interest in the potential salutary effects of 3-hydroxy-3-methyglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) in preventing the evolving phenotype and in reversing the established phenotype in HCM.25,26 Various mechanisms have the potential for involvement in modulating cardiac hypertrophy and fibrosis by statins, including the blockade of geranylgeranylation of RhoA and Rac1, which are essential mediators of cardiac hypertrophic response.25,26 A preliminary clinical study in human beings with HCM did not show any beneficial effects of atorvastatin on regression of the established phenotype.105

Inhibition of the RAAS—that is, blockade of angiotensin II and mineralocorticoid receptors by losartan and aldosterone, respectively—has shown beneficial effects in animal models of HCM.27,60 Preliminary clinical studies in human beings have suggested beneficial effects of losartan on regression of cardiac hypertrophy and on indices of diastolic function.61,106 Given that angiotensin-II blockers are not recommended in the treatment of human patients with HCM, particularly in those with LVOT obstruction, these findings merit further investigation in patients with nonobstructive HCM before their use in clinical practice.

Another noteworthy experimental pharmacologic agent is N-acetylcysteine, which was recently shown to completely reverse cardiac hypertrophy and fibrosis and prevent deterioration of cardiac systolic function over time in a transgenic rabbit model of human HCM.23,24 The N-acetylcysteine influenced various pathways, including the oxidative stress-responsive signaling mechanisms and thiol modifications of proteins involved in cardiac hypertrophy. These promising results invite testing in human beings who have HCM, a potentially deadly disease for which there is no effective pharmacologic treatment at present.


Address for reprints: Ali J. Marian, MD, Center for Cardiovascular Genetics, 6770 Bertner St., Denton A. Cooley Building 900A, Houston, TX 77030. E-mail: ude.cmt.htu@nairaM.J.ilA

Supported in part by grants from the National Heart, Lung, and Blood Institute; the Burroughs Wellcome Award in Translational Research; the TexGen Fund from the Greater Houston Community Foundation; and the St. Luke's Roderick D. MacDonald Research Fund.


1. Liouville H. Retrecissement cardiaque, sous-aortique. Gazette Medicale de Paris 1869;24:161–5.
2. Schmincke A. Ueber linkseitige muskulose conusstenosen. Dtsch Med Wochenschr 1907;33:2082–3.
3. Braunwald E, Ebert PA. Hemodynamic alterations in idiopathic hypertrophic subaortic stenosis induced by sympathomimetic drugs. Am J Cardiol 1962;10:489–95. [PubMed]
4. Braunwald E, Lambrew CT, Rockoff SD, Ross J Jr, Morrow AG. Idiopathic hypertrophic subaortic stenosis. I. A description of the disease based upon an analysis of 64 patients. Circulation 1964;30:Suppl 4:3–119. [PubMed]
5. Morrow AG, Lambrew CT, Braunwald E. Idiopathic hypertrophic subaortic stenosis. II. Operative treatment and the results of pre- and postoperative hemodynamic evaluations. Circulation 1964;30:Suppl 4:120–51. [PubMed]
6. Henry WL, Clark CE, Epstein SE. Asymmetric septal hypertrophy. Echocardiographic identification of the pathognomonic anatomic abnormality of IHSS. Circulation 1973; 47(2):225–33. [PubMed]
7. Boughner DR, Schuld RL, Persaud JA. Hypertrophic obstructive cardiomyopathy. Assessment by echocardiographic and Doppler ultrasound techniques. Br Heart J 1975;37(9):917–23. [PMC free article] [PubMed]
8. Joyner CR, Harrison FS Jr, Gruber JW. Diagnosis of hypertrophic subaortic stenosis with a Doppler velocity flow detector. Ann Intern Med 1971;74(5):692–6. [PubMed]
9. Maron BJ, Gottdiener JS, Arce J, Rosing DR, Wesley YE, Epstein SE. Dynamic subaortic obstruction in hypertrophic cardiomyopathy: analysis by pulsed Doppler echocardiography. J Am Coll Cardiol 1985;6(1):1–18. [PubMed]
10. Takenaka K, Dabestani A, Gardin JM, Russell D, Clark S, Allfie A, Henry WL. Left ventricular filling in hypertrophic cardiomyopathy: a pulsed Doppler echocardiographic study. J Am Coll Cardiol 1986;7(6):1263–71. [PubMed]
11. Nagueh SF, McFalls J, Meyer D, Hill R, Zoghbi WA, Tam JW, et al. Tissue Doppler imaging predicts the development of hypertrophic cardiomyopathy in subjects with subclinical disease. Circulation 2003;108(4):395–8. [PMC free article] [PubMed]
12. Nagueh SF, Bachinski LL, Meyer D, Hill R, Zoghbi WA, Tam JW, et al. Tissue Doppler imaging consistently detects myocardial abnormalities in patients with hypertrophic cardiomyopathy and provides a novel means for an early diagnosis before and independently of hypertrophy. Circulation 2001;104(2): 128–30. [PMC free article] [PubMed]
13. Geisterfer-Lowrance AA, Kass S, Tanigawa G, Vosberg HP, McKenna W, Seidman CE, Seidman JG. A molecular basis for familial hypertrophic cardiomyopathy: a beta cardiac myosin heavy chain gene missense mutation. Cell 1990;62(5):999–1006. [PubMed]
14. Marian AJ. Genetic determinants of cardiac hypertrophy. Curr Opin Cardiol 2008;23(3):199–205. [PMC free article] [PubMed]
15. Sigwart U. Non-surgical myocardial reduction for hypertrophic obstructive cardiomyopathy. Lancet 1995;346(8969): 211–4. [PubMed]
16. Seggewiss H. Current status of alcohol septal ablation for patients with hypertrophic cardiomyopathy. Curr Cardiol Rep 2001;3(2):160–6. [PubMed]
17. Talreja DR, Nishimura RA, Edwards WD, Valeti US, Ommen SR, Tajik AJ, et al. Alcohol septal ablation versus surgical septal myectomy: comparison of effects on atrioventricular conduction tissue. J Am Coll Cardiol 2004;44(12):2329–32. [PubMed]
18. Sorajja P, Valeti U, Nishimura RA, Ommen SR, Rihal CS, Gersh BJ, et al. Outcome of alcohol septal ablation for obstructive hypertrophic cardiomyopathy. Circulation 2008;118(2): 131–9. [PubMed]
19. Maron BJ, Doerer JJ, Haas TS, Tierney DM, Mueller FO. Sudden deaths in young competitive athletes: analysis of 1866 deaths in the United States, 1980-2006. Circulation 2009;119 (8):1085–92. [PubMed]
20. Maron BJ, Shirani J, Poliac LC, Mathenge R, Roberts WC, Mueller FO. Sudden death in young competitive athletes. Clinical, demographic, and pathological profiles. JAMA 1996; 276(3):199–204. [PubMed]
21. Maron BJ, Spirito P, Shen WK, Haas TS, Formisano F, Link MS, et al. Implantable cardioverter-defibrillators and prevention of sudden cardiac death in hypertrophic cardiomyopathy [published erratum appears in JAMA 2007;298(13):1516]. JAMA 2007;298(4):405–12. [PubMed]
22. Maron BJ, Shen WK, Link MS, Epstein AE, Almquist AK, Daubert JP, et al. Efficacy of implantable cardioverter-defibrillators for the prevention of sudden death in patients with hypertrophic cardiomyopathy. N Engl J Med 2000;342(6):365–73. [PubMed]
23. Lombardi R, Rodriguez G, Chen SN, Ripplinger CM, Li W, Chen J, et al. Resolution of established cardiac hypertrophy and fibrosis and prevention of systolic dysfunction in a transgenic rabbit model of human cardiomyopathy through thiol-sensitive mechanisms. Circulation 2009;119(10):1398–407. [PMC free article] [PubMed]
24. Marian AJ, Senthil V, Chen SN, Lombardi R. Antifibrotic effects of antioxidant N-acetylcysteine in a mouse model of human hypertrophic cardiomyopathy mutation. J Am Coll Cardiol 2006;47(4):827–34. [PMC free article] [PubMed]
25. Senthil V, Chen SN, Tsybouleva N, Halder T, Nagueh SF, Willerson JT, et al. Prevention of cardiac hypertrophy by atorvastatin in a transgenic rabbit model of human hypertrophic cardiomyopathy. Circ Res 2005;97(3):285–92. [PMC free article] [PubMed]
26. Patel R, Nagueh SF, Tsybouleva N, Abdellatif M, Lutucuta S, Kopelen HA, et al. Simvastatin induces regression of cardiac hypertrophy and fibrosis and improves cardiac function in a transgenic rabbit model of human hypertrophic cardiomyopathy. Circulation 2001;104(3):317–24. [PMC free article] [PubMed]
27. Lim DS, Lutucuta S, Bachireddy P, Youker K, Evans A, Entman M, et al. Angiotensin II blockade reverses myocardial fibrosis in a transgenic mouse model of human hypertrophic cardiomyopathy. Circulation 2001;103(6):789–91. [PMC free article] [PubMed]
28. Maron BJ, Gardin JM, Flack JM, Gidding SS, Kurosaki TT, Bild DE. Prevalence of hypertrophic cardiomyopathy in a general population of young adults. Echocardiographic analysis of 4111 subjects in the CARDIA Study. Coronary Artery Risk Development in (Young) Adults. Circulation 1995;92(4):785–9. [PubMed]
29. Nienaber CA, Hiller S, Spielmann RP, Geiger M, Kuck KH. Syncope in hypertrophic cardiomyopathy: multivariate analysis of prognostic determinants. J Am Coll Cardiol 1990;15(5):948–55. [PubMed]
30. Kofflard MJ, Ten Cate FJ, van der Lee C, van Domburg RT. Hypertrophic cardiomyopathy in a large community-based population: clinical outcome and identification of risk factors for sudden cardiac death and clinical deterioration. J Am Coll Cardiol 2003;41(6):987–93. [PubMed]
31. Robinson K, Frenneaux MP, Stockins B, Karatasakis G, Poloniecki JD, McKenna WJ. Atrial fibrillation in hypertrophic cardiomyopathy: a longitudinal study. J Am Coll Cardiol 1990;15(6):1279–85. [PubMed]
32. Kofflard MJ, Waldstein DJ, Vos J, ten Cate FJ. Prognosis in hypertrophic cardiomyopathy observed in a large clinic population. Am J Cardiol 1993;72(12):939–43. [PubMed]
33. Cannan CR, Reeder GS, Bailey KR, Melton LJ 3rd, Gersh BJ. Natural history of hypertrophic cardiomyopathy. A population-based study, 1976 through 1990. Circulation 1995;92 (9):2488–95. [PubMed]
34. Spirito P, Bellone P, Harris KM, Bernabo P, Bruzzi P, Maron BJ. Magnitude of left ventricular hypertrophy and risk of sudden death in hypertrophic cardiomyopathy. N Engl J Med 2000;342(24):1778–85. [PubMed]
35. Elliott PM, Gimeno Blanes JR, Mahon NG, Poloniecki JD, McKenna WJ. Relation between severity of left-ventricular hypertrophy and prognosis in patients with hypertrophic cardiomyopathy. Lancet 2001;357(9254):420–4. [PubMed]
36. Marian AJ. On predictors of sudden cardiac death in hypertrophic cardiomyopathy. J Am Coll Cardiol 2003;41(6):994–6. [PMC free article] [PubMed]
37. Monserrat L, Elliott PM, Gimeno JR, Sharma S, Penas-Lado M, McKenna WJ. Non-sustained ventricular tachycardia in hypertrophic cardiomyopathy: an independent marker of sudden death risk in young patients. J Am Coll Cardiol 2003; 42(5):873–9. [PubMed]
38. Frenneaux MP. Assessing the risk of sudden cardiac death in a patient with hypertrophic cardiomyopathy. Heart 2004; 90(5):570–5. [PMC free article] [PubMed]
39. Niimura H, Patton KK, McKenna WJ, Soults J, Maron BJ, Seidman JG, Seidman CE. Sarcomere protein gene mutations in hypertrophic cardiomyopathy of the elderly. Circulation 2002;105(4):446–51. [PubMed]
40. Watkins H, Rosenzweig A, Hwang DS, Levi T, McKenna W, Seidman CE, Seidman JG. Characteristics and prognostic implications of myosin missense mutations in familial hypertrophic cardiomyopathy. N Engl J Med 1992;326(17):1108–14. [PubMed]
41. Watkins H, Conner D, Thierfelder L, Jarcho JA, MacRae C, McKenna WJ, et al. Mutations in the cardiac myosin binding protein-C gene on chromosome 11 cause familial hypertrophic cardiomyopathy. Nat Genet 1995;11(4):434–7. [PubMed]
42. Thierfelder L, Watkins H, MacRae C, Lamas R, McKenna W, Vosberg HP, et al. Alpha-tropomyosin and cardiac troponin T mutations cause familial hypertrophic cardiomyopathy: a disease of the sarcomere. Cell 1994;77(5):701–12. [PubMed]
43. Olson TM, Doan TP, Kishimoto NY, Whitby FG, Ackerman MJ, Fananapazir L. Inherited and de novo mutations in the cardiac actin gene cause hypertrophic cardiomyopathy. J Mol Cell Cardiol 2000;32(9):1687–94. [PubMed]
44. Mogensen J, Murphy RT, Kubo T, Bahl A, Moon JC, Klausen IC, et al. Frequency and clinical expression of cardiac troponin I mutations in 748 consecutive families with hypertrophic cardiomyopathy. J Am Coll Cardiol 2004;44(12): 2315–25. [PubMed]
45. Watkins H, McKenna WJ, Thierfelder L, Suk HJ, Anan R, O'Donoghue A, et al. Mutations in the genes for cardiac troponin T and alpha-tropomyosin in hypertrophic cardiomyopathy. N Engl J Med 1995;332(16):1058–64. [PubMed]
46. Arad M, Maron BJ, Gorham JM, Johnson WH Jr, Saul JP, Perez-Atayde AR, et al. Glycogen storage diseases presenting as hypertrophic cardiomyopathy. N Engl J Med 2005;352(4): 362–72. [PubMed]
47. Chimenti C, Pieroni M, Morgante E, Antuzzi D, Russo A, Russo MA, et al. Prevalence of Fabry disease in female patients with late-onset hypertrophic cardiomyopathy. Circulation 2004;110(9):1047–53. [PubMed]
48. Sachdev B, Takenaka T, Teraguchi H, Tei C, Lee P, McKenna WJ, Elliott PM. Prevalence of Anderson-Fabry disease in male patients with late onset hypertrophic cardiomyopathy. Circulation 2002;105(12):1407–11. [PubMed]
49. Gollob MH, Seger JJ, Gollob TN, Tapscott T, Gonzales O, Bachinski L, Roberts R. Novel PRKAG2 mutation responsible for the genetic syndrome of ventricular preexcitation and conduction system disease with childhood onset and absence of cardiac hypertrophy. Circulation 2001;104(25):3030–3. [PubMed]
50. Gollob MH, Green MS, Tang AS, Gollob T, Karibe A, Ali Hassan AS, et al. Identification of a gene responsible for familial Wolff-Parkinson-White syndrome. N Engl J Med 2001; 344(24):1823–31. [PubMed]
51. Blair E, Redwood C, Ashrafian H, Oliveira M, Broxholme J, Kerr B, et al. Mutations in the gamma(2) subunit of AMP-activated protein kinase cause familial hypertrophic cardiomyopathy: evidence for the central role of energy compromise in disease pathogenesis. Hum Mol Genet 2001;10(11):1215–20. [PubMed]
52. Marian AJ. Modifier genes for hypertrophic cardiomyopathy. Curr Opin Cardiol 2002;17(3):242–52. [PMC free article] [PubMed]
53. Patel R, Lim DS, Reddy D, Nagueh SF, Lutucuta S, Sole MJ, et al. Variants of trophic factors and expression of cardiac hypertrophy in patients with hypertrophic cardiomyopathy. J Mol Cell Cardiol 2000;32(12):2369–77. [PubMed]
54. Brugada R, Kelsey W, Lechin M, Zhao G, Yu QT, Zoghbi W, et al. Role of candidate modifier genes on the phenotypic expression of hypertrophy in patients with hypertrophic cardiomyopathy. J Investig Med 1997;45(9):542–51. [PubMed]
55. Daw EW, Lu Y, Marian AJ, Shete S. Identifying modifier loci in existing genome scan data. Ann Hum Genet 2008;72(Pt 5):670–5. [PubMed]
56. Daw EW, Chen SN, Czernuszewicz G, Lombardi R, Lu Y, Ma J, et al. Genome-wide mapping of modifier chromosomal loci for human hypertrophic cardiomyopathy. Hum Mol Genet 2007;16(20):2463–71. [PMC free article] [PubMed]
57. Maron BJ. Hypertrophic cardiomyopathy: a systematic review. JAMA 2002;287(10):1308–20. [PubMed]
58. Ostman-Smith I, Wettrell G, Riesenfeld T. A cohort study of childhood hypertrophic cardiomyopathy: improved survival following high-dose beta-adrenoceptor antagonist treatment. J Am Coll Cardiol 1999;34(6):1813–22. [PubMed]
59. Sherrid MV, Barac I, McKenna WJ, Elliott PM, Dickie S, Chojnowska L, et al. Multicenter study of the efficacy and safety of disopyramide in obstructive hypertrophic cardiomyopathy. J Am Coll Cardiol 2005;45(8):1251–8. [PubMed]
60. Tsybouleva N, Zhang L, Chen S, Patel R, Lutucuta S, Nemoto S, et al. Aldosterone, through novel signaling proteins, is a fundamental molecular bridge between the genetic defect and the cardiac phenotype of hypertrophic cardiomyopathy. Circulation 2004;109(10):1284–91. [PMC free article] [PubMed]
61. Araujo AQ, Arteaga E, Ianni BM, Buck PC, Rabello R, Mady C. Effect of Losartan on left ventricular diastolic function in patients with nonobstructive hypertrophic cardiomyopathy. Am J Cardiol 2005;96(11):1563–7. [PubMed]
62. Maron BJ, Nichols PF 3rd, Pickle LW, Wesley YE, Mulvihill JJ. Patterns of inheritance in hypertrophic cardiomyopathy: assessment by M-mode and two-dimensional echocardiography. Am J Cardiol 1984;53(8):1087–94. [PubMed]
63. Greaves SC, Roche AH, Neutze JM, Whitlock RM, Veale AM. Inheritance of hypertrophic cardiomyopathy: a cross sectional and M mode echocardiographic study of 50 families. Br Heart J 1987;58(3):259–66. [PMC free article] [PubMed]
64. Michels VV, Moll PP, Miller FA, Tajik AJ, Chu JS, Driscoll DJ, et al. The frequency of familial dilated cardiomyopathy in a series of patients with idiopathic dilated cardiomyopathy. N Engl J Med 1992;326(2):77–82. [PubMed]
65. Ho CY, Sweitzer NK, McDonough B, Maron BJ, Casey SA, Seidman JG, et al. Assessment of diastolic function with Doppler tissue imaging to predict genotype in preclinical hypertrophic cardiomyopathy. Circulation 2002;105(25):2992–7. [PubMed]
66. Germans T, Wilde AA, Dijkmans PA, Chai W, Kamp O, Pinto YM, van Rossum AC. Structural abnormalities of the inferoseptal left ventricular wall detected by cardiac magnetic resonance imaging in carriers of hypertrophic cardiomyopathy mutations. J Am Coll Cardiol 2006;48(12):2518–23. [PubMed]
67. Eriksson MJ, Sonnenberg B, Woo A, Rakowski P, Parker TG, Wigle ED, Rakowski H. Long-term outcome in patients with apical hypertrophic cardiomyopathy. J Am Coll Cardiol 2002;39(4):638–45. [PubMed]
68. Cecchi F, Olivotto I, Montereggi A, Santoro G, Dolara A, Maron BJ. Hypertrophic cardiomyopathy in Tuscany: clinical course and outcome in an unselected regional population. J Am Coll Cardiol 1995;26(6):1529–36. [PubMed]
69. Spirito P, Chiarella F, Carratino L, Berisso MZ, Bellotti P, Vecchio C. Clinical course and prognosis of hypertrophic cardiomyopathy in an outpatient population. N Engl J Med 1989;320(12):749–55. [PubMed]
70. Begley DA, Mohiddin SA, Tripodi D, Winkler JB, Fananapazir L. Efficacy of implantable cardioverter defibrillator therapy for primary and secondary prevention of sudden cardiac death in hypertrophic cardiomyopathy. Pacing Clin Electrophysiol 2003;26(9):1887–96. [PubMed]
71. Maron MS, Zenovich AG, Casey SA, Link MS, Udelson JE, Aeppli DM, Maron BJ. Significance and relation between magnitude of left ventricular hypertrophy and heart failure symptoms in hypertrophic cardiomyopathy. Am J Cardiol 2005;95(11):1329–33. [PubMed]
72. Olivotto I, Gistri R, Petrone P, Pedemonte E, Vargiu D, Cecchi F. Maximum left ventricular thickness and risk of sudden death in patients with hypertrophic cardiomyopathy. J Am Coll Cardiol 2003;41(2):315–21. [PubMed]
73. Jeschke B, Uhl K, Weist B, Schroder D, Meitinger T, Dohlemann C, Vosberg HP. A high risk phenotype of hypertrophic cardiomyopathy associated with a compound genotype of two mutated beta-myosin heavy chain genes. Hum Genet 1998; 102(3):299–304. [PubMed]
74. Anan R, Greve G, Thierfelder L, Watkins H, McKenna WJ, Solomon S, et al. Prognostic implications of novel beta cardiac myosin heavy chain gene mutations that cause familial hypertrophic cardiomyopathy. J Clin Invest 1994;93(1):280–5. [PMC free article] [PubMed]
75. Abchee A, Marian AJ. Prognostic significance of beta-myosin heavy chain mutations is reflective of their hypertrophic expressivity in patients with hypertrophic cardiomyopathy. J Investig Med 1997;45(4):191–6. [PubMed]
76. Richard P, Isnard R, Carrier L, Dubourg O, Donatien Y, Mathieu B, et al. Double heterozygosity for mutations in the beta-myosin heavy chain and in the cardiac myosin binding protein C genes in a family with hypertrophic cardiomyopathy. J Med Genet 1999;36(7):542–5. [PMC free article] [PubMed]
77. Autore C, Bernabo P, Barilla CS, Bruzzi P, Spirito P. The prognostic importance of left ventricular outflow obstruction in hypertrophic cardiomyopathy varies in relation to the severity of symptoms. J Am Coll Cardiol 2005;45(7):1076–80. [PubMed]
78. Maron BJ, Dearani JA, Ommen SR, Maron MS, Schaff HV, Gersh BJ, Nishimura RA. The case for surgery in obstructive hypertrophic cardiomyopathy. J Am Coll Cardiol 2004; 44(10):2044–53. [PubMed]
79. McLeod CJ, Ommen SR, Ackerman MJ, Weivoda PL, Shen WK, Dearani JA, et al. Surgical septal myectomy decreases the risk for appropriate implantable cardioverter defibrillator discharge in obstructive hypertrophic cardiomyopathy. Eur Heart J 2007;28(21):2583–8. [PubMed]
80. Woo A, Williams WG, Choi R, Wigle ED, Rozenblyum E, Fedwick K, et al. Clinical and echocardiographic determinants of long-term survival after surgical myectomy in obstructive hypertrophic cardiomyopathy. Circulation 2005;111(16): 2033–41. [PubMed]
81. Firoozi S, Elliott PM, Sharma S, Murday A, Brecker SJ, Hamid MS, et al. Septal myotomy-myectomy and transcoronary septal alcohol ablation in hypertrophic obstructive cardiomyopathy. A comparison of clinical, haemodynamic and exercise outcomes. Eur Heart J 2002;23(20):1617–24. [PubMed]
82. Ommen SR, Shah PM, Tajik AJ. Left ventricular outflow tract obstruction in hypertrophic cardiomyopathy: past, present and future. Heart 2008;94(10):1276–81. [PubMed]
83. Ommen SR, Maron BJ, Olivotto I, Maron MS, Cecchi F, Betocchi S, et al. Long-term effects of surgical septal myectomy on survival in patients with obstructive hypertrophic cardiomyopathy. J Am Coll Cardiol 2005;46(3):470–6. [PubMed]
84. McGregor JB, Rahman A, Rosanio S, Ware D, Birnbaum Y, Saeed M. Monomorphic ventricular tachycardia: a late complication of percutaneous alcohol septal ablation for hypertrophic cardiomyopathy. Am J Med Sci 2004;328(3):185–8. [PubMed]
85. Deb SJ, Schaff HV, Dearani JA, Nishimura RA, Ommen SR. Septal myectomy results in regression of left ventricular hypertrophy in patients with hypertrophic obstructive cardiomyopathy. Ann Thorac Surg 2004;78(6):2118–22. [PubMed]
86. Sigwart U. Catheter treatment for hypertrophic obstructive cardiomyopathy: for seniors only? Circulation 2008;118(2): 107–8. [PubMed]
87. Flores-Ramirez R, Lakkis NM, Middleton KJ, Killip D, Spencer WH 3rd, Nagueh SF. Echocardiographic insights into the mechanisms of relief of left ventricular outflow tract obstruction after nonsurgical septal reduction therapy in patients with hypertrophic obstructive cardiomyopathy. J Am Coll Cardiol 2001;37(1):208–14. [PubMed]
88. Kitaoka H, Kubo T, Okawa M, Hitomi N, Furuno T, Doi YL. Left ventricular remodeling of hypertrophic cardiomyopathy: longitudinal observation in rural community. Circ J 2006;70 (12):1543–9. [PubMed]
89. Kuhn H, Lawrenz T, Lieder F, Leuner C, Strunk-Mueller C, Obergassel L, et al. Survival after transcoronary ablation of septal hypertrophy in hypertrophic obstructive cardiomyopathy (TASH): a 10 year experience. Clin Res Cardiol 2008; 97(4):234–43. [PubMed]
90. Buell HE, Stables RH, DeLong ER, Shuping KB, Killip DM, Lever HM, et al. Percutaneous transluminal septal reduction for hypertrophic obstructive cardiomyopathy: report from an international pilot study. J Med Syst 2002;26 (4):293–300. [PubMed]
91. Knight C, Kurbaan AS, Seggewiss H, Henein M, Gunning M, Harrington D, et al. Nonsurgical septal reduction for hypertrophic obstructive cardiomyopathy: outcome in the first series of patients. Circulation 1997;95(8):2075–81. [PubMed]
92. Nagueh SF, Ommen SR, Lakkis NM, Killip D, Zoghbi WA, Schaff HV, et al. Comparison of ethanol septal reduction therapy with surgical myectomy for the treatment of hypertrophic obstructive cardiomyopathy. J Am Coll Cardiol 2001; 38(6):1701–6. [PubMed]
93. Reinhard W, Ten Cate FJ, Scholten M, De Laat LE, Vos J. Permanent pacing for complete atrioventricular block after nonsurgical (alcohol) septal reduction in patients with obstructive hypertrophic cardiomyopathy. Am J Cardiol 2004; 93(8):1064–6. [PubMed]
94. El-Jack SS, Nasif M, Blake JW, Dixon SR, Grines CL, O'Neill WW. Predictors of complete heart block after alcohol septal ablation for hypertrophic cardiomyopathy and the timing of pacemaker implantation. J Interv Cardiol 2007;20(1):73–6. [PubMed]
95. Qin JX, Shiota T, Lever HM, Asher CR, Popovic ZB, Greenberg NL, et al. Conduction system abnormalities in patients with obstructive hypertrophic cardiomyopathy following septal reduction interventions. Am J Cardiol 2004;93(2):171–5. [PubMed]
96. Seggewiss H, Gleichmann U, Faber L, Fassbender D, Schmidt HK, Strick S. Percutaneous transluminal septal myocardial ablation in hypertrophic obstructive cardiomyopathy: acute results and 3-month follow-up in 25 patients. J Am Coll Cardiol 1998;31(2):252–8. [PubMed]
97. Boltwood CM Jr, Chien W, Ports T. Ventricular tachycardia complicating alcohol septal ablation. N Engl J Med 2004; 351(18):1914–5. [PubMed]
98. Hori Y, Ueda M, Nakayama T, Saegusa N, Uehara M, Lee K, et al. Occurrence of de novo sustained monomorphic ventricular tachycardia induced after percutaneous transluminal alcohol septal myocardial ablation for hypertrophic obstructive cardiomyopathy. Int J Cardiol 2007;119(3):403–7. [PubMed]
99. Fernandes VL, Nagueh SF, Wang W, Roberts R, Spencer WH 3rd. A prospective follow-up of alcohol septal ablation for symptomatic hypertrophic obstructive cardiomyopathy–the Baylor experience (1996-2002). Clin Cardiol 2005;28(3): 124–30. [PubMed]
100. Ommen SR, Nishimura RA, Squires RW, Schaff HV, Danielson GK, Tajik AJ. Comparison of dual-chamber pacing versus septal myectomy for the treatment of patients with hypertrophic obstructive cardiomyopathy: a comparison of objective hemodynamic and exercise end points. J Am Coll Cardiol 1999;34(1):191–6. [PubMed]
101. Maron BJ, Nishimura RA, McKenna WJ, Rakowski H, Josephson ME, Kieval RS. Assessment of permanent dual-chamber pacing as a treatment for drug-refractory symptomatic patients with obstructive hypertrophic cardiomyopathy. A randomized, double-blind, crossover study (M-PATHY). Circulation 1999;99(22):2927–33. [PubMed]
102. Fananapazir L, Epstein ND, Curiel RV, Panza JA, Tripodi D, McAreavey D. Long-term results of dual-chamber (DDD) pacing in obstructive hypertrophic cardiomyopathy. Evidence for progressive symptomatic and hemodynamic improvement and reduction of left ventricular hypertrophy. Circulation 1994;90(6):2731–42. [PubMed]
103. Kappenberger L, Linde C, Daubert C, McKenna W, Meisel E, Sadoul N, et al. Pacing in hypertrophic obstructive cardiomyopathy. A randomized crossover study. PIC Study Group. Eur Heart J 1997;18(8):1249–56. [PubMed]
104. Seggewiss H, Rigopoulos A. Management of hypertrophic cardiomyopathy in children. Paediatr Drugs 2003;5(10):663–72. [PubMed]
105. Bauersachs J, Stork S, Kung M, Waller C, Fidler F, Hoyer C, et al. HMG CoA reductase inhibition and left ventricular mass in hypertrophic cardiomyopathy: a randomized placebo-controlled pilot study. Eur J Clin Invest 2007;37(11):852–9. [PubMed]
106. Yamazaki T, Suzuki J, Shimamoto R, Tsuji T, Ohmoto-Sekine Y, Ohtomo K, Nagai R. A new therapeutic strategy for hypertrophic nonobstructive cardiomyopathy in humans. A randomized and prospective study with an angiotensin II receptor blocker. Int Heart J 2007;48(6):715–24. [PubMed]

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