FOCUS ISSUE: HYPERTROPHIC CARDIOMYOPATHY: CLINICAL RESEARCH
Outcome of Mildly Symptomatic or Asymptomatic Obstructive Hypertrophic CardiomyopathyA Long-Term Follow-Up Study
Paul Sorajja, MD*,*,
Rick A. Nishimura, MD*,
Bernard J. Gersh, MB, ChB, DPhil*,
Joseph A. Dearani, MD ,
David O. Hodge, MS ,
Heather J. Wiste, BA and
Steve R. Ommen, MD*
* Division of Cardiovascular Diseases and Internal Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota
Division of Cardiovascular Surgery, Mayo Clinic College of Medicine, Rochester, Minnesota
Department of Biostatistics, Mayo Clinic College of Medicine, Rochester, Minnesota
Manuscript received November 2, 2008;
revised manuscript received January 7, 2009,
accepted January 12, 2009.
* Reprint requests and correspondence: Dr. Paul Sorajja, Mayo Clinic, 200 1st Street SW, Rochester, Minnesota 55905 (Email: paul.sorajja{at}mayo.edu).
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Abstract
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Objectives: The purpose of this study was to characterize the prognosis of minimally symptomatic patients with obstructive hypertrophic cardiomyopathy (HCM).
Background: Recent data have suggested that obstruction may be present in the majority of HCM patients, irrespective of cardiac symptoms. The prognosis of minimally symptomatic obstructive HCM remains poorly defined.
Methods: We examined 544 consecutive adult patients (age 59 ± 16 years; 55% men) with obstructive HCM documented by Doppler echocardiography who were free of severe cardiac symptoms, and we performed clinical follow-up (median 9.3 years).
Results: There was only a slight excess mortality of the cohort in comparison to the expected survival of a similar U.S. general population (10-year observed vs. expected survival, 69.3% vs. 71.9%; p = 0.04) and 46% of the deaths were attributable to noncardiac causes. However, there was a clear relation between increasing severity of the left ventricular outflow tract (LVOT) gradient and outcome. For patients with high resting gradients (Doppler peak velocity >4 m/s), survival was significantly impaired (53% at 10 years; p = 0.001 vs. expected), and death or severe symptoms occurred in 68% of these patients within 10 years after the initial evaluation. Conversely, there was no impairment of long-term survival for patients with less-severe resting obstruction. Independent predictors of mortality in the entire cohort were age, prior stroke, and LVOT gradient severity.
Conclusions: Patients with obstructive HCM and mild or no symptoms have only slight excess mortality. However, patients with markedly elevated resting LVOT gradients are at a high risk of heart failure and death. These findings may have important implications for therapy, including the timing of septal reduction therapy.
Key Words: hypertrophic cardiomyopathy • obstruction • prognosis
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Abbreviations and Acronyms
| | CCS = Canadian Cardiovascular Society | | CI = confidence interval | | HCM = hypertrophic cardiomyopathy | | ICD = implantable cardioverter-defibrillator | | LVOT = left ventricular outflow tract | | NYHA = New York Heart Association |
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Dynamic left ventricular outflow tract (LVOT) obstruction is an important component of the pathophysiology of hypertrophic cardiomyopathy (HCM), arising from an interplay of drag effects, Venturi forces, and systolic anterior motion of the mitral valve (1–4). The prognosis of HCM patients with obstruction is poorer than that of those without obstruction, especially in the patients with severe symptoms (5–8). For patients with obstructive HCM and severe symptoms, surgical myectomy is the therapeutic gold standard and provides hemodynamic and symptom relief with a low operative risk in appropriate candidates (9–11). However, it is unclear as to whether intervention should be performed in patients with mild or no symptoms, because the outcome of minimally symptomatic patients with obstructive HCM has not been delineated. Accordingly, this study was undertaken to evaluate the long-term outcome of patients with minimally symptomatic, obstructive HCM.
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Methods
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Patients.
This study was approved by the Mayo Clinic Institutional Review Board. Consecutive patients with the following criteria were enrolled: 1) age  18 years; 2) the presence of obstructive HCM; 3) self-reported mild or no cardiac symptoms; 4) absence of need for cardiac surgery that would lead to concomitant myectomy (e.g., endocarditis, aortic root surgery); 5) absence of prior cardiac arrest; and 6) informed consent for study participation. The presence of both New York Heart Association (NYHA) functional class II or lower and Canadian Cardiac Society (CCS) angina class II or lower were required to define mild or no cardiac symptoms (5,12). Each of these patients was evaluated for obstructive HCM between January 1, 1982, and December 31, 2005, at the Mayo Clinic in Rochester, Minnesota. The selection of this entry date was based upon the initial availability of Doppler echocardiography for calculation of the LVOT gradient at our institution. The diagnosis of HCM was based on typical clinical, electrocardiographic, and echocardiographic features, with ventricular myocardial hypertrophy (end-diastolic wall thickness 15 mm) occurring in the absence of any other cardiac or systemic disease that could have been responsible for the hypertrophy (13,14). The magnitude of myocardial hypertrophy was assessed with M-mode and 2-dimensional transthoracic echocardiography using standard techniques. Patients with peak LVOT velocity  2.7 m/s underwent provocation with either Valsalva strain or amyl nitrite inhalation per standard protocol in the echocardiographic laboratory. In this protocol, Valsalva strain or amyl nitrite (0.3 ml) inhalation is performed to change ventricular load during simultaneous Doppler and 2-dimensional echocardiography. The peak LVOT velocity is averaged from 3 to 5 cardiac cycles recorded at a sweep speed of 50 to 100 mm/s. LVOT obstruction was defined by Doppler echocardiography as a systolic anterior motion of the mitral valve and an LVOT (subaortic) velocity of >2.7 m/s at rest of >3.5 m/s with provocation, which is respectively comparable to an LVOT gradient >30 mm Hg at rest or >50 mm Hg with provocation (5,6,9). In all cases, particular consideration was given to distinguishing the Doppler signal of LVOT obstruction from that of mitral regurgitation. The initial clinical evaluation was defined as the point at which obstructive HCM was first identified at the Mayo Clinic.
Follow-up.
Vital status, cardiac symptoms, and need for septal reduction therapy (e.g., surgical myectomy, percutaneous alcohol septal ablation) were ascertained by follow-up evaluation consisting of mailed questionnaires, telephone contact, and interrogation of the Social Security Death Index (11,15). For deceased patients, procurement of death certificates and interviews with next of kin was performed to determine cause of death. Death due to congestive heart failure was defined as death occurring in the context of long-standing cardiac decompensation with progression of the disease over the preceding year with the development of pulmonary edema or cardiogenic shock. Sudden cardiac death was defined as instantaneous and unexpected death with or without documented ventricular fibrillation within 1 h after a witnessed collapse, in patients who previously were in stable clinical condition, or nocturnal death with no antecedent history of worsening symptoms (11,15). Appropriate discharge of an implantable cardioverter-defibrillator (ICD) device for therapy of a lethal arrhythmia (i.e., sustained ventricular tachycardia or fibrillation) was considered to be sudden cardiac death. HCM-related death was defined as occurrence of death due to either congestive heart failure or stroke, sudden cardiac death or appropriate discharge of an ICD device for treatment of lethal arrhythmia, occurrence of cardiac transplantation, or death in the absence of pre-mortal causative conditions (e.g., malignancy) (16).
Data analysis.
Study end points were all-cause mortality, death due to HCM-related causes, and the combination of all-cause mortality and occurrence of severe symptoms (NYHA functional class III or greater or CCS angina class III or greater) following the initial clinical visit. The Kaplan-Meier method was used to estimate survival of the various end point events with 95% confidence intervals (CIs). Expected survival was calculated using age- and sex-specific mortality rates for the year of entry into the study obtained from the U.S. general population. These rates specified all-cause mortality, were calculated for each individual in the study, and were combined to form an expected summary curve for the population (11,16,17). Observed mortality was compared to expected survival using a 1-sample log-rank test for the entire follow-up period. For purposes of data analysis, patients were grouped according to severity of the LVOT gradient at rest (peak LVOT velocity <3, 3 to 4, and >4 m/s). These categories of severity were chosen on the basis of prior investigations of patients with aortic valvular stenosis that have been used to identify high-risk asymptomatic patients (16,18,19).
Univariate models were first constructed to determine which variables were associated with the end point of all-cause mortality. Variables considered were age, male sex, known coronary artery disease, atrial fibrillation, prior stroke, diabetes mellitus, hypertension, resting LVOT gradient, maximal left ventricular wall thickness, use of beta-receptor antagonist, left atrial volume index, posterior wall thickness, left ventricular end-diastolic dimension, and left ventricular end-systolic dimension. Variables that were significant at the 0.05 level were then considered for a multivariate model. Forward and backward stepwise techniques using the PHREG procedure in SAS verison 9.1.3 (SAS Institute, Cary, North Carolina) were used to identify which variables were independently associated with each end point at a significance level of p < 0.05 and thus incorporated into a final multivariate model. Left atrial volume index, posterior wall thickness, end-diastolic dimension, and end-systolic dimension were not included in the stepwise model even if univariately significant due to the significant number patients with missing data (17% to 26%). Comparisons of continuous variables were made with the appropriate 2-sample test: a 2-sample t test in cases in which the variable distributions were symmetric, and a Wilcoxon rank sum test otherwise. Variables are reported as mean ± SD. Statistical significance was set a priori at p < 0.05.
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Results
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Baseline characteristics.
Table 1
lists the baseline characteristics of the study population (median age 59 years; 55% men). The majority of patients were completely asymptomatic (NYHA functional class I in 61.6%; CCS angina class I in 79.6%; both NYHA functional class I and CCS angina class I in 54.0%). Massive septal hypertrophy (30 mm in 4.5%), an adverse family history of sudden death (present in 12.0%), and history of ICD (1.0%) were uncommon. The average peak LVOT gradient at rest was 40.9 ± 35.8 mm Hg, with 270 patients (49.6%) having a resting peak LVOT gradient of 30 mm Hg. In the remaining 274 patients (50.4%), the resting peak LVOT gradient was <30 mm Hg at rest and 50 mm Hg following provocation.
Survival.
Median follow-up for the entire cohort was 9.3 years (range 6 days to 23 years). There were 178 deaths (32.7%) during follow-up (Table 2). Noncardiac etiologies were the cause of death in 81 patients (14.9%; 45.5% of all deaths). HCM-related death occurred in 82 patients (46.1% of all deaths). Sudden death occurred in 10 patients, none of whom had previously been implanted with an ICD. Two patients died after septal reduction therapy (1 myectomy, 1 septal ablation) that was performed for severe symptoms that developed during follow-up. Cause of death could not be specified in 15 patients (2.8%).
Overall survival was 85.8% (95% CI: 82.6% to 89.0%) at 5 years and 69.3% (95% CI: 64.6% to 74.3%) at 10 years (Fig. 1). This observed survival was only slightly lower than that of the expected survival of a similar general U.S. population of individuals, whose 5- and 10-year survival estimates were 87.7% and 71.9%, respectively (p = 0.04, observed vs. expected). Of note, 80 deaths (44.9% of all deaths) occurred in patients after 80 years of age. Survival free of HCM-related death in the entire cohort was 94.5% (95% CI: 92.3% to 96.6%) at 5 years and 82.9% (95% CI: 78.7% to 87.4%) at 10 years.
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Figure 1 Observed Versus Expected Survival of Patients With Obstructive Hypertrophic Cardiomyopathy
Expected survival was calculated from age- and sex-matched U.S. general population mortality rates and year of entry.
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There was a strong relation between the severity of the LVOT gradient at rest and the outcome. For patients with high resting LVOT gradients (velocity >4 m/s; n = 111), the 10-year survival free of all mortality was only 52.8% (95% CI: 41.4% to 67.2%) and was significantly lower than the expected survival for this group of patients (69.2%; p < 0.001 for expected vs. observed) (Fig. 2). Conversely, patients with either peak LVOT velocity <3 m/s at rest (n = 293) or peak resting velocity of 3 to 4 m/s (n = 140) had normal survival. The 10-year survival for these 2 groups of patients was 76.5% (95% CI: 70.6% to 82.9%; p = 0.75 vs. expected) and 65.9% (95% CI: 57.2% to 75.9%; p = 0.37 vs. expected), respectively (Fig. 2). Independent predictors of all-cause mortality were age (hazard ratio [HR]: 1.07; 95% CI: 1.05 to 1.08; p < 0.0001), prior stroke (HR: 1.75; 95% CI: 1.06 to 2.88; p = 0.03), and resting LVOT gradient (HR: 1.005; 95% CI: 1.001 to 1.009; p = 0.01) (Table 3). Severity of LVOT obstruction was also related to occurrence of HCM-related death (10-year survival, 70.7% vs. 82.4% vs. 86.8% for peak LVOT velocity at rest of <3 m/s vs. 3 to 4 m/s vs. >4 m/s; p = 0.02 for group comparison) (Fig. 3).
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Figure 2 Relation of Survival to Severity of the Resting Peak LVOT Velocity
(A) Observed versus expected survival for patients with resting peak left ventricular outflow tract (LVOT) velocity <3 m/s. (B) Observed versus expected survival for patients with resting peak LVOT velocity 3 to 4 m/s. (C) Observed versus expected survival for patients with resting peak LVOT velocity >4 m/s. Overall survival was significantly poorer for patients with high peak LVOT gradients (velocity >4 m/s), but not for patients with lower gradient thresholds.
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Figure 3 Survival Free of Definite or Probable HCM-Related Death and Severe Cardiac Symptoms According to Severity of the Peak LVOT Velocity
Increasing severity of the peak left ventricular outflow tract (LVOT) velocity was directly related to occurrence of hypertrophic cardiomyopathy (HCM)-related death and occurrence of severe cardiac symptoms (i.e., New York Heart Association functional class III or IV dyspnea or Canadian Cardiac Society class III or IV angina). Occurrence of severe symptoms includes need for septal reduction therapy (i.e., surgical septal myectomy or percutaneous alcohol septal ablation) during the follow-up period.
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Heart failure and septal reduction therapy.
One hundred fourteen patients (21.0%) developed severe cardiac symptoms (NYHA functional class III/IV dyspnea or CCS class III/IV angina) in follow-up, including 104 patients whose severe symptoms occurred within 10 years after the initial evaluation. Fifty-one of these patients (9.2%) underwent either surgical myectomy (n = 47) or alcohol septal ablation (n = 4) at the onset of severe symptoms. Forty-eight of the procedures were undertaken within 10 years after the initial evaluation. The 10-year survival free of death and severe symptoms (including those requiring septal reduction therapy) in the overall population was 50.3% (95% CI: 45.3% to 55.8%). For the end point of HCM-related death and severe symptoms, this survival was 59.4% (95% CI: 54.2% to 65.0%).
Survival free of severe symptoms was related to the severity of LVOT obstruction. For patients with peak LVOT velocity at rest of >4 m/s, the 10-year survival free of death and severe symptoms was only 31.7% (95% CI: 21.5% to 46.7%), and was significantly lower than patients with either peak LVOT velocity of <3 m/s (58.1%; 95% CI: 51.5% to 65.6%) or peak LVOT velocity of 3 to 4 m/s (46.7%; 95% CI: 38.0% to 57.5%; p < 0.0001 for 3-group comparison) (Fig. 3). Severity of the resting LVOT gradient was an independent predictor of survival free of death and severe symptoms in a multivariate model, which also identified age, male sex, and prior stroke as independent covariates of this end point (Table 4).
Development of severe symptoms in follow-up (entered as a time-dependent variable) also was significantly associated with poorer survival in the multivariate model (HR: 1.71; 95% CI: 1.11 to 2.65; p = 0.02). Of note, the 10-year survival of the 430 patients who continued to remain free of severe symptoms at follow-up was 66.5% (95% CI: 61.0% to 72.5%), which was not different than the expected survival of these 430 patients (p = 0.18) (Fig. 4). However, the relation between the magnitude of the resting LVOT gradient and death persisted even among patients who avoided the development of severe symptoms in follow-up (p < 0.0001) (Fig. 4). Excess mortality was present among patients with peak LVOT velocity >4 m/s (p = 0.007 vs. observed), but not among the patients with less severe obstruction (Fig. 5).
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Figure 4 Survival of Patients With Obstructive HCM Who Remained Free of Severe Cardiac Symptoms During the Follow-Up
(A) Expected versus observed survival. (B) Survival according to peak left ventricular outflow tract (LVOT) velocity. There was no survival impairment for patients who remained free of severe symptoms during follow-up. However, the relation between the magnitude of the LVOT gradient to survival persisted in patients who avoided the development of severe symptoms.
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Figure 5 Observed Versus Expected Survival of Patients With Obstructive Hypertrophic Cardiomyopathy Who Remained Free of Severe Symptoms in Follow-Up
Expected survival was calculated from age- and sex-matched U.S. general population mortality rates and year of entry. (A) Expected versus observed survival for patients with peak left ventricular outflow tract (LVOT) velocity <3 m/s. (B) Expected versus observed survival for patients with peak LVOT velocity 3 to 4 m/s. (C) Expected versus observed survival for patients with peak LVOT velocity >4 m/s.
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Discussion
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The principal findings of this investigation are: 1) there is only a slight excess mortality in patients with obstructive HCM who self-report mild or no symptoms in comparison to the expected survival for a similar general U.S. population of individuals; 2) approximately one-half of the deaths can be attributed to non–HCM-related causes in these patients; 3) even in the absence of severe cardiac symptoms, the magnitude of the resting LVOT gradient is directly and independently associated with increasing risk of adverse clinical outcome; and 4) mildly symptomatic or asymptomatic patients with high LVOT gradients at rest (peak velocity >4 m/s) have poorer than expected survival and are at higher risk for severe heart failure.
Knowledge about the prognostic significance of LVOT obstruction in patients with HCM is important as obstruction may be present in >65% of these patients, irrespective of cardiac symptoms (20,21). Although the prognostic significance of LVOT obstruction in HCM has been debated, recent analyses confirm that obstruction is associated with poorer survival (5–8). It has been shown that septal myectomy in patients with obstruction and severe symptoms has a highly favorable long-term outcome (11). These reports have spurred consideration about a possible role for relief of LVOT obstruction in the absence of significant cardiac symptoms, especially since surgical myectomy can now be performed with low risk (<1%), particularly in younger patients without comorbidities (11,22).
The present investigation examined the long-term survival of minimally symptomatic patients with obstructive HCM who were initially treated without surgical myectomy. Comparison to the expected survival of a similar age- and sex-matched cohort from the U.S. general population was performed to gain insight into whether or not these patients have excess mortality (11,16,19). Overall, there was only a slight excess in observed mortality (10-year estimate, 69% vs. 72%). Although it can be difficult to determine the contribution of HCM to death in individuals with other morbid conditions, approximately one-half of the deaths in this population were attributable to noncardiac causes. Based on these findings, prophylactic relief of LVOT obstruction, either via surgical myectomy or percutaneous methods, is unlikely to significantly impact the longevity of these patients.
Patients with obstructive HCM and minimal symptoms, however, are at risk for developing heart failure. In this study, severe cardiac symptoms developed in 114 (21.0%) patients, and 48 of these underwent septal reduction therapy within 10 years after their initial evaluation. These frequencies are similar to prior reports on the natural history of other unselected HCM populations (1,23–26). Nonetheless, an important finding of the present study was a direct, independent relation between the severity of the LVOT gradient and both death and long-term occurrence of severe symptoms. In particular, for patients with high LVOT gradients (peak velocity >4 m/s), there was a significantly increased incidence of heart failure and death that was not present at lower gradient thresholds. Among patients with peak LVOT velocity at rest of >4 m/s, survival was 53%, and only 32% remained free of death and severe symptoms at 10 years after the initial evaluation. Although these data may not be persuasive enough to make the case for surgery or ablation in the absence of severe symptoms, they do strongly support the need for frequent and close surveillance of patients with HCM and severe LVOT gradients, even when symptoms are mild or not present at the initial evaluation. In this regard, particular attention to differentiating the Doppler signal of LVOT obstruction from mitral regurgitation is needed.
The present investigation was a nonrandomized, retrospective analysis with known limitations of such studies. A randomized trial of septal reduction versus medical therapy would be the optimal method for examining the most appropriate treatment of these patients. Of note, in this study, there was a survival difference of 2.0% at 5 years of follow-up. In order to have 80% power to detect this difference in a 5-year prospective study, 4,436 patients would need to be randomized into each therapeutic arm. Such a study would require screening of >30,000 HCM patients if the trial was able to enroll 20% of patients screened (27). This high number of patients significantly reduces the feasibility of a prospective treatment trial that would address the study aims of the present investigation. A treatment trial that restricted enrollment to patients with high LVOT gradients might require enrollment of fewer study patients. In the absence of such data, consensus about the management of these patients will continue to rely on observational studies such as the present investigation (27).
For asymptomatic patients with valvular heart disease, early surgery increasingly is being advocated in an effort to avoid detrimental, irreversible ventricular remodeling due to increased ventricular load (28). With the advent of modern surgical techniques, the risk of surgery has become lower and more favorable to this approach in appropriately selected patients. For example, in low-risk asymptomatic patients with severe aortic stenosis (operative mortality <1%), early surgery may be considered because of the high frequency of subsequent adverse clinical events that have been observed in recent analyses of these patients (16,19).
Conversely, for patients with HCM, estimating the clinical burden of the systolic contraction load due to LVOT obstruction poses unique challenges. Heterogeneity characterizes the phenotypic expression and natural history of HCM. The LVOT gradient is labile due to its sensitivity to ventricular loading conditions (20,21,29). Although relief of LVOT obstruction can result in regression of myocardial hypertrophy, severity of hypertrophy is a primary phenomenon that occurs independently of LVOT obstruction and thus does not accurately reflect adverse ventricular load in HCM. The present study relied on patient self-reporting of symptoms. Exercise testing may reveal previously unrecognized functional limitation, leading to septal reduction therapy in some instances. The present study did not examine patients who had mild symptoms (NYHA functional class II or lower) and underwent septal reduction therapy for lifestyle impairment (9).
Nonetheless, onset of severe symptoms independently predicted poorer survival and was frequent in patients with high LVOT gradients. Although these data do not support surgical relief of LVOT obstruction for minimally symptomatic patients, such patients should be followed with awareness of the potential for symptoms to progress and the development of heart failure. Few (<2%) patients had documented sudden cardiac death in this study, although uncertainty about the specific cause of death was present in a number of patients.
Although all patients in this study had evidence of dynamic LVOT obstruction, the present analyses focused on the relation between long-term outcome and severity of the LVOT gradient under basal conditions (i.e., at rest). The present study demonstrates a relation between magnitude of the resting LVOT gradient and prognosis, which has not been evident in previous analyses. The present observation may be due to differences in unique clinical characteristics of the study population such as a relatively older age (median 59 years) as well as inclusion of patients with lower LVOT gradients (mean 41 mm Hg). Severity of LVOT gradients observed with provocation were not examined due to the different methods (e.g., Valsalva strain, amyl nitrite inhalation) used to determine latent obstruction. Currently, comparison data for these methods and their prognostic implications are limited (30,31). Further analyses of the clinical significance of the different methods for evaluating latent obstruction and the potential impact of agents used to lessen its severity (i.e., beta-receptor antagonists, calcium-channel antagonists, disopyramide) are warranted (32). These data would be of particular relevance for minimally symptomatic patients with obstructive HCM, for whom septal reduction therapy currently is not advised.
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Footnotes
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Bernard J. Gersh is an advisory board member for AstraZeneca, Boston Scientific, Bristol-Myers Squibb, and Abbott Laboratories; and has stock options with CV Therapeutics.
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References
|
|---|
1. Maron BJ. Hypertrophic cardiomyopathy: a systematic review JAMA 2002;287:1308-1320.[Abstract/Free Full Text]2. Levine RA, Vlahakes GJ, Lefebvre X, et al. Papillary muscle displacement causes systolic anterior motion of the mitral valve. Experimental validation and insights into the mechanism of subaortic obstruction. Circulation 1995;91:1189-1195.[Abstract/Free Full Text] 3. Braunwald E, Lambrew CT, Rockoff SD, et al. Idiopathic hypertrophic subaortic stenosis. I. A description of the disease based upon an analysis of 64 patients. Circulation 1964;30(Suppl IV):IV3-IV119. 4. Wigle ED, Sasson Z, Henderson MA, et al. Hypertrophic cardiomyopathy. The importance of the site and the extent of hypertrophy. A review. Prog Cardiovasc Dis 1985;28:1-83.[CrossRef][Web of Science][Medline] 5. Maron MS, Olivotto I, Betocchi S, et al. Effect of left ventricular outflow tract obstruction on clinical outcome in hypertrophic cardiomyopathy N Engl J Med 2003;348:295-303.[CrossRef][Web of Science][Medline] 6. Elliott PM, Gimeno JR, Tome MT, et al. Left ventricular outflow tract obstruction and sudden death risk in patients with hypertrophic cardiomyopathy Europ Heart J 2006;27:1933-1941.[Abstract/Free Full Text] 7. Maki S, Ideda H, Muro A, et al. Predictors of sudden cardiac death in hypertrophic cardiomyopathy Am J Cardiol 1998;82:774-778.[CrossRef][Web of Science][Medline] 8. 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;45:1076-1080.[Abstract/Free Full Text] 9. Maron BJ, McKenna WJ, Danielson GK, et al. ACC/ESC clinical expert consensus document on hypertrophic cardiomyopathy: a report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents and the European Society of Cardiology Committee for Practice Guidelines (Committee to Develop an Expert Consensus Document on Hypertrophic Cardiomyopathy) J Am Coll Cardiol 2003;42:1687-1713.[Free Full Text] 10. Maron BJ, Dearani JA, Ommen SR, et al. The case for surgery in obstructive hypertrophic cardiomyopathy J Am Coll Cardiol 2004;44:2044-2053.[Abstract/Free Full Text] 11. Ommen SR, Maron BJ, Olivotto I, et al. Long-term effects of surgical septal myectomy on survival in patients with obstructive hypertrophic cardiomyopathy J Am Coll Cardiol 2005;46:470-476.[Abstract/Free Full Text] 12. Lucien C. Grading of angina pectoris Circulation 1976;54:522-523. 13. Report of the World Health Organization/International Society and Federation of Cardiology Task Force on the definition and classification of cardiomyopathies Circulation 1996;93:841-842.[Free Full Text] 14. Maron BJ, Epstein SE. Hypertrophic cardiomyopathy: a discussion of nomenclature Am J Cardiol 1979;43:1242-1244.[CrossRef][Web of Science][Medline] 15. Sorajja P, Nishimura RA, Ommen SR, et al. Utility of echocardiography in patients with hypertrophic cardiomyopathy: clinical implications of massive hypertrophy J Am Soc Echocardiogr 2006;19:788-795.[CrossRef][Web of Science][Medline] 16. Pellikka PA, Sarano ME, Nishimura RA, et al. Outcome of 622 adults with asymptomatic hemodynamically significant aortic stenosis during prolonged follow-up Circulation 2005;111:3290-3295.[Abstract/Free Full Text] 17. Therneau T, Offord J. Expected Survival Based on Hazard Rates (update). Technical Report 63. Rochester, MN: Section of Biostatistics, Mayo Clinic; 19991–26. 18. Otto C, Burwash I, Legget M, et al. Prospective study of asymptomatic valvular aortic stenosis: clinical, echocardiographic, and exercise predictors of outcome Circulation 1997;95:2262-2270.[Abstract/Free Full Text] 19. Pellikka P, Nishimura R, Bailey K, et al. The natural history of adults with asymptomatic, hemodynamically significant aortic stenosis J Am Coll Cardiol 1990;15:1012-1017.[Abstract] 20. Maron MS, Olivotto I, Zenovich AG, et al. Hypertrophic cardiomyopathy is predominantly a disease of left ventricular outflow tract obstruction Circulation 2006;115:2232-2239. 21. Nishimura RA, Ommen SR. Hypertrophic cardiomyopathy. The search for obstruction. Circulation 2006;114:2200-2202.[Free Full Text] 22. McCully RB, Nishimura RA, Tajik AJ, et al. Extent of clinical improvement after surgical treatment of hypertrophic cardiomyopathy Circulation 1996;94:467-471.[Abstract/Free Full Text] 23. Maron BJ, Olivotto I, Spirito P, et al. Epidemiology of hypertrophic cardiomyopathy-related death: revisited in a large non-referral-based patient population Circulation 2000;102:858-864.[Abstract/Free Full Text] 24. Cecchi F, Olivotto I, Montereggi A, et al. Hypertrophic cardiomyopathy in Tuscany: clinical course and outcome in an unselected regional population J Am Coll Cardiol 1995;26:1529-1536.[Abstract] 25. Maron BJ, Casey SA, Poliac LC, et al. Clinical course of hypertrophic cardiomyopathy in a regional United States cohort JAMA 1999;281:650-655.[Abstract/Free Full Text] 26. Cannan CR, Reeder GS, Bailey KR, et al. Natural history of hypertrophic cardiomyopathy: a population-based study, 1976 through 1990 Circulation 1995;92:2488-2495.[Abstract/Free Full Text] 27. Olivotto I, Ommen SR, Maron MS, et al. Surgical myectomy versus alcohol septal ablation for obstructive hypertrophic cardiomyopathy: will there ever be a randomized trial? J Am Coll Cardiol 2007;50:831-834.[Abstract/Free Full Text] 28. Bonow RO, Carabello B, Chatterjee K, et al. ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1998 Guidelines for the Management of Patients With Valvular Heart Disease) J Am Coll Cardiol 2006;48:e1-e148.[Free Full Text] 29. Kizilbash AM, Heinle SK, Grayburn PA. Spontaneous variability of left ventricular outflow tract gradient in hypertrophic obstructive cardiomyopathy Circulation 1998;97:461-466.[Abstract/Free Full Text] 30. Elesber A, Nishimura RA, Rihal CS, et al. Utility of isoproterenol to provoke outflow tract gradients in patients with hypertrophic cardiomyopathy Am J Cardiol 2008;101:516-520.[CrossRef][Web of Science][Medline] 31. Vaglio Jr. JC, Ommen SR, Nishimura RA, et al. Clinical characteristics and outcomes of patients with hypertrophic cardiomyopathy with latent obstruction Am Heart J 2008;156:342-347.[CrossRef][Web of Science][Medline] 32. Sherrid MV, Pearle G, Gunsburg DZ. Mechanism of benefit of negative inotropes in obstructive hypertrophic cardiomyopathy Circulation 1998;97:41-47.[Abstract/Free Full Text]
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B. J. Gersh, B. J. Maron, R. O. Bonow, J. A. Dearani, M. A. Fifer, M. S. Link, S. S. Naidu, R. A. Nishimura, S. R. Ommen, H. Rakowski, et al.
2011 ACCF/AHA Guideline for the Diagnosis and Treatment of Hypertrophic Cardiomyopathy: Executive Summary: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines Developed in Collaboration With the American Association for Thoracic Surgery, American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Failure Society of America, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons
J. Am. Coll. Cardiol.,
December 13, 2011;
58(25):
2703 - 2738.
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B. J. Gersh, B. J. Maron, R. O. Bonow, J. A. Dearani, M. A. Fifer, M. S. Link, S. S. Naidu, R. A. Nishimura, S. R. Ommen, H. Rakowski, et al.
2011 ACCF/AHA Guideline for the Diagnosis and Treatment of Hypertrophic Cardiomyopathy: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines Developed in Collaboration With the American Association for Thoracic Surgery, American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Failure Society of America, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons
J. Am. Coll. Cardiol.,
December 13, 2011;
58(25):
e212 - e260.
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Writing Committee Members, B. J. Gersh, B. J. Maron, R. O. Bonow, J. A. Dearani, M. A. Fifer, M. S. Link, S. S. Naidu, R. A. Nishimura, S. R. Ommen, et al.
2011 ACCF/AHA Guideline for the Diagnosis and Treatment of Hypertrophic Cardiomyopathy: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines
Circulation,
December 13, 2011;
124(24):
e783 - e831.
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Writing Committee Members, B. J. Gersh, B. J. Maron, R. O. Bonow, J. A. Dearani, M. A. Fifer, M. S. Link, S. S. Naidu, R. A. Nishimura, S. R. Ommen, et al.
2011 ACCF/AHA Guideline for the Diagnosis and Treatment of Hypertrophic Cardiomyopathy: Executive Summary: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines
Circulation,
December 13, 2011;
124(24):
2761 - 2796.
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Writing Committee Members:*, B. J. Gersh, B. J. Maron, R. O. Bonow, J. A. Dearani, M. A. Fifer, M. S. Link, S. S. Naidu, R. A. Nishimura, S. R. Ommen, et al.
2011 ACCF/AHA guideline for the diagnosis and treatment of hypertrophic cardiomyopathy: Executive summary: A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines
J. Thorac. Cardiovasc. Surg.,
December 1, 2011;
142(6):
1303 - 1338.
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Writing Committee Members:*, B. J. Gersh, B. J. Maron, R. O. Bonow, J. A. Dearani, M. A. Fifer, M. S. Link, S. S. Naidu, R. A. Nishimura, S. R. Ommen, et al.
2011 ACCF/AHA guideline for the diagnosis and treatment of hypertrophic cardiomyopathy: A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines
J. Thorac. Cardiovasc. Surg.,
December 1, 2011;
142(6):
e153 - e203.
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W. Ball, J. Ivanov, H. Rakowski, E. D. Wigle, M. Linghorne, A. Ralph-Edwards, W. G. Williams, L. Schwartz, A. Guttman, and A. Woo
Long-Term Survival in Patients With Resting Obstructive Hypertrophic Cardiomyopathy: Comparison of Conservative Versus Invasive Treatment
J. Am. Coll. Cardiol.,
November 22, 2011;
58(22):
2313 - 2321.
[Abstract]
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A. N. DeMaria, J. J. Bax, O. Ben-Yehuda, G. K. Feld, B. H. Greenberg, J. Hall, M. Hlatky, W. Y.W. Lew, J. A.C. Lima, A. S. Maisel, et al.
Highlights of the Year in JACC 2009
J. Am. Coll. Cardiol.,
January 26, 2010;
55(4):
380 - 407.
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Abstract
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