Implantable cardioverter-defibrillators and prevention of sudden cardiac death in hypertrophic cardiomyopathy.
Maron BJ, Spirito P, Shen WK, Haas TS, Formisano F, Link MS, Epstein AE, Almquist AK, Daubert JP, Lawrenz T, Boriani G, Estes NA 3rd, Favale S, Piccininno M, Winters SL, Santini M, Betocchi S, Arribas F, Sherrid MV, Buja G, Semsarian C, Bruzzi P.
JAMA. 2007 Jul 25;298(4):405-12.
Hypertrophic Cardiomyopathy Center of the Minneapolis Heart Institute Foundation, Minneapolis, Minnesota 55407, USA. hcm.maron@mhif.org
CONTEXT: Recently, the implantable cardioverter-defibrillator (ICD) has been promoted for prevention of sudden death in hypertrophic cardiomyopathy (HCM). However, the effectiveness and appropriate selection of patients for this therapy is incompletely resolved. OBJECTIVE: To study the relationship between clinical risk profile and incidence and efficacy of ICD intervention in HCM. DESIGN, SETTING, AND PATIENTS: Multicenter registry study of ICDs implanted between 1986 and 2003 in 506 unrelated patients with HCM. Patients were judged to be at high risk for sudden death; had received ICDs; underwent evaluation at 42 referral and nonreferral institutions in the United States, Europe, and Australia; and had a mean follow-up of 3.7 (SD, 2.8) years. Measured risk factors for sudden death included family history of sudden death, massive left ventricular hypertrophy, nonsustained ventricular tachycardia on Holter monitoring, and unexplained prior syncope. MAIN OUTCOME MEASURE: Appropriate ICD intervention terminating ventricular tachycardia or fibrillation. RESULTS: The 506 patients were predominately young (mean age, 42 [SD, 17] years) at implantation, and most (439 [87%]) had no or only mildly limiting symptoms. ICD interventions appropriately terminated ventricular tachycardia/fibrillation in 103 patients (20%). Intervention rates were 10.6% per year for secondary prevention after cardiac arrest (5-year cumulative probability, 39% [SD, 5%]), and 3.6% per year for primary prevention (5-year probability, 17% [SD, 2%]). Time to first appropriate discharge was up to 10 years, with a 27% (SD, 7%) probability 5 years or more after implantation. For primary prevention, 18 of the 51 patients with appropriate ICD interventions (35%) had undergone implantation for only a single risk factor; likelihood of appropriate discharge was similar in patients with 1, 2, or 3 or more risk markers (3.83, 2.65, and 4.82 per 100 person-years, respectively; P = .77). The single sudden death due to an arrhythmia (in the absence of advanced heart failure) resulted from ICD malfunction. ICD complications included inappropriate shocks in 136 patients (27%). CONCLUSIONS: In a high-risk HCM cohort, ICD interventions for life-threatening ventricular tachyarrhythmias were frequent and highly effective in restoring normal rhythm. An important proportion of ICD discharges occurred in primary prevention patients who had undergone implantation for a single risk factor. Therefore, a single marker of high risk for sudden death may be sufficient to justify consideration for prophylactic defibrillator implantation in selected patients with HCM.
Effect of biventricular pacing on symptoms and cardiac remodelling in patients with end-stage hypertrophic cardiomyopathy.
Rogers DP, Marazia S, Chow AW, Lambiase PD, Lowe MD, Frenneaux M, McKenna WJ, Elliott PM.
Eur J Heart Fail. 2008 May;10(5):507-13
The Heart Hospital, University College London, UK. minirogers@googlemail.com
BACKGROUND: Biventricular (BiV) pacing is an established therapy for heart failure in ischaemic and dilated cardiomyopathy. Its effects in end-stage hypertrophic cardiomyopathy (HCM) are unknown. AIMS: To assess the potential benefits of BiV pacing in patients with symptomatic end-stage HCM. METHODS: Twenty patients with non-obstructive HCM (12 male, mean age 57+/-13 years), left bundle branch block and symptoms of heart failure refractory to medical therapy underwent implantation of a BiV device. NYHA class, echocardiographic parameters and exercise capacity were assessed before and after implantation. RESULTS: At a mean follow-up of 13+/-6 months, an improvement of at least one NYHA class was reported in 8 (40%) patients. A clinical response was associated with an increase in ejection fraction (from 41+/-14% to 50+/-12%, p=0.009), and reductions in left ventricular end-diastolic diameter (from 57+/-6 mm to 52+/-7 mm, p=0.031) and left atrial diameter (from 65+/-8 mm to 57+/-6 mm, p=0.005). Percentage predicted peak oxygen consumption was unchanged in responders but significantly declined in non-responders (p=0.029).
CONCLUSIONS: BiV pacing improved heart failure symptoms in a significant proportion of patients with end-stage HCM. Symptomatic improvement was associated with reverse remodelling of the left atrium and ventricle.
Sudden deaths in young competitive athletes: analysis of 1866 deaths in the United States, 1980-2006.
Maron BJ, Doerer JJ, Haas TS, Tierney DM, Mueller FO.
Circulation. 2009 Mar 3;119(8):1085-92.
Hypertrophic Cardiomyopathy Center, Minneapolis Heart Institute Foundation and Abbott Northwestern Hospital, Minneapolis, Minn., USA. hcm.maron@mhif.org
BACKGROUND: Sudden deaths in young competitive athletes are highly
visible events with substantial impact on the physician and lay
communities. However, the magnitude of this public health issue has
become a source of controversy. METHODS AND RESULTS: To estimate the
absolute number of sudden deaths in US competitive athletes, we have
assembled a large registry over a 27-year period using systematic
identification and tracking strategies. A total of 1866 athletes who
died suddenly (or survived cardiac arrest), 19+/-6 years of age, were
identified throughout the United States from 1980 to 2006 in 38 diverse
sports. Reports were less common during 1980 to 1993 (576 [31%]) than
during 1994 to 2006 (1290 [69%], P<0.001) and increased at a rate of 6%
per year. Sudden deaths were predominantly due to cardiovascular disease
(1049 [56%]), but causes also included blunt trauma that caused
structural damage (416 [22%]), commotio cordis (65 [3%]), and heat
stroke (46 [2%]). Among the 1049 cardiovascular deaths, the highest
number of events in a single year was 76 (2005 and 2006), with an
average of 66 deaths per year (range 50 to 76) over the last 6 years;
29% occurred in blacks, 54% in high school students, and 82% with
physical exertion during competition/training, whereas only 11% occurred
in females (although this increased with time; P=0.023). The most common
cardiovascular causes were hypertrophic cardiomyopathy (36%) and
congenital coronary artery anomalies (17%). CONCLUSIONS: In this
national registry, the absolute number of cardiovascular sudden deaths
in young US athletes was somewhat higher than previous estimates but
relatively low nevertheless, with a rate of <100 per year. These data
are relevant to the current debate surrounding preparticipation
screening programs with ECGs and also suggest the need for systematic
and mandatory reporting of athlete sudden deaths to a national registry.
Prevalence, clinical significance, and natural history of left ventricular apical aneurysms in hypertrophic cardiomyopathy
Maron MS, Finley JJ, Bos JM, Hauser TH, Manning WJ, Haas TS, Lesser JR, Udelson JE, Ackerman MJ, Maron BJ.
Circulation.2008 Oct 7;118(15):1541-9..
Division of Cardiology, Hypertrophic Cardiomyopathy Center, Tufts Medical Center, Boston, Massachussetts 02111, USA. mmaron@tuftsmedicalcenter.org
BACKGROUND: Hypertrophic cardiomyopathy (HCM) is the most common genetic heart disease characterized by a diverse clinical and phenotypic spectrum. This study reports the prevalence, morphology, clinical course, and management of an underrecognized subgroup of HCM patients with left ventricular apical aneurysms. METHODS AND RESULTS: Of 1299 HCM patients, 28 (2%) were identified with left ventricular apical aneurysms, including a pair of identical twins. Aneurysms were recognized at a wide age range (26 to 83 years), including 12 patients (43%) who were <or=50 years of age. Apical aneurysms varied considerably in size (maximum dimension, 10 to 66 mm), were dyskinetic/akinetic with thin rims, and were associated with transmural (and often more extensive) myocardial scarring identified by late gadolinium enhancement cardiovascular magnetic resonance. Apical aneurysms were recognized by echocardiography in only 16 of 28 patients (57%) but by cardiovascular magnetic resonance in the 12 patients undetected by echocardiography. Left ventricular chamber morphology varied; however, 19 patients (68%) showed an "hourglass" contour, with midventricular hypertrophy producing muscular narrowing and intracavitary gradients in 9 patients (74+/-42 mm Hg). Sarcomeric protein missense mutations known to cause other phenotypic expressions of HCM were present in 3 patients. Over 4.1+/-3.7 years of follow-up, 12 patients (43%) with left ventricular apical aneurysms experienced adverse disease complications (event rate, 10.5%/y), including sudden death, appropriate implantable cardioverter-defibrillator discharges, nonfatal thromboembolic stroke, and progressive heart failure and death. CONCLUSIONS: Patients with left ventricular apical aneurysms represent an underappreciated subset in the heterogeneous HCM disease spectrum with important clinical implications, often requiring a high index of suspicion and cardiovascular magnetic resonance for identification. Apical aneurysms in HCM are associated with substantial cardiovascular morbidity and mortality and raise novel treatment considerations.
Clinical characteristics and outcomes of patients with hypertrophic cardiomyopathy with latent obstruction.
Vaglio JC Jr, Ommen SR, Nishimura RA, Tajik AJ, Gersh BJ.
Am Heart J. 2008 Aug;156(2):342-7. Epub 2008 Jun 6
Division of Cardiovascular Diseases and Internal Medicine, Mayo Clinic and Mayo Foundation, Rochester, MN, USA. jvaglio@yahoo.com
BACKGROUND: The purpose of this article is to describe the demographic and clinical features of patients with hypertrophic cardiomyopathy (HCM) and latent obstruction, with an emphasis on identifying factors associated with disease progression and survival. The presence of a resting left ventricular outflow obstruction in patients with HCM has been well described and is associated with increased symptoms and adverse long-term outcomes. However, less is known about patients with latent obstruction. METHODS: Four hundred fifteen patients with echocardiographic or catheterization findings of latent obstruction, defined as a left ventricular outflow pressure gradient <30 mm Hg at rest, which increases to > or =30 mm Hg with provocation, were identified and included in the study group. RESULTS: The mean age was 55.0 +/- 17.9, and 226 (54.6%) patients were male. There were 330 (79.5%) patients with New York Heart Association (NYHA) functional class I and II at baseline. Fifty-nine (17.9%) of these patients had symptom progression requiring septal reduction therapy. Eighty-five patients had severe symptoms (NYHA functional class III and IV) at baseline, and 23 (27.1%) underwent septal reduction. Overall survival at 1, 5, and 10 years was 98%, 91%, and 81%, respectively. Survival among patients after undergoing invasive relief of outflow obstruction was equivalent to the general US population. CONCLUSIONS: Latent obstruction in HCM is an important pathophysiologic entity and may cause heart failure symptoms. One-third of patients in this referral series required invasive therapy for relief of symptoms. The evaluation of HCM patients with resting outflow tract gradients <30 mm Hg must include provocative maneuvers to identify this substantial subset of patients, preferably by physiologic exercise.
Prevalence of hypertrophic cardiomyopathy in highly trained athletes: relevance to pre-participation screening
Basavarajaiah S, Wilson M, Whyte G, Shah A, McKenna W, Sharma S.
J Am Coll Cardiol. 2008 Mar 11;51(10):1033-9.
King's College Hospital, London, England.
OBJECTIVES: This study sought to determine the prevalence of hypertrophic cardiomyopathy (HCM) in elite athletes. BACKGROUND: Hypertrophic cardiomyopathy is considered to be the most common cause of exercise-related sudden death in young athletes. The prevalence of HCM in elite athletes has never been reported but has important implications with regard to pre-participation screening for the disorder. METHODS: Between 1996 and 2006, 3,500 asymptomatic elite athletes (75% male) with a mean age of 20.5 +/- 5.8 years (range 14 to 35 years) underwent 12-lead electrocardiography and 2-dimensional echocardiography. None had a known family history of HCM. RESULTS: Of the 3,500 athletes, 53 (1.5%) had left ventricular hypertrophy (mean 13.6 +/- 0.9, range 13 to 16), and of these 50 had a dilated left ventricular cavity with normal diastolic function to indicate physiological left ventricular hypertrophy. Three (0.08%) athletes with left ventricular hypertrophy had a nondilated left ventricular cavity and associated deep T-wave inversion that could have been consistent with HCM. However, none of the 3 athletes had any other phenotypic features of HCM on further noninvasive testing and none had first-degree relatives with features of HCM. One of the 3 athletes agreed to detrain for 12 weeks, which showed resolution of electrocardiography and echocardiographic changes confirming physiologic left ventricular hypertrophy. CONCLUSIONS: The prevalence of HCM in highly trained athletes is extremely rare. Structural and functional changes associated with HCM naturally select out most individuals from competitive sports. Screening athletes with echocardiography is not cost effective. However, electrocardiography is useful in selecting out those individuals who may have pathological left ventricular hypertrophy for subsequent echocardiography.
Hypertrophic cardiomyopathy: the genetic determinants of clinical disease expression.
Keren A, Syrris P, McKenna WJ.
Heart. 2008 Oct;94(10):1288-94. Epub 2007 Nov 21.
Department of Cardiology, Hadassah University Hospital, Jerusalem, Israel.
Hypertrophic cardiomyopathy (HCM), defined clinically by the presence of unexplained left ventricular hypertrophy, is the most common inherited cardiac disorder. This condition is the major cause of sudden death in the young (<30 years of age) and in athletes. The clinical phenotype is heterogeneous, and mutations in a number of sarcomeric contractile-protein genes are responsible for causing the disease in approximately 60% of individuals with HCM. Other inherited syndromes, as well as metabolic and mitochondrial disorders, can present as clinical phenocopies and can be distinguished by their associated cardiac and noncardiac features and on the basis of their unique molecular genetics. The mode of inheritance, natural history and treatment of phenocopies can differ from those of HCM caused by mutations in sarcomere genes. Detailed clinical evaluation and mutation analysis are, therefore, important in providing an accurate diagnosis in order to enable genetic counseling, prognostic evaluation and appropriate clinical management. This Review summarizes current knowledge on the genetics, disease mechanisms, and correlations between phenotype and genotype in patients with HCM, and discusses the implications of genetic testing in routine clinical practice.
Mitral valve abnormalities in hypertrophic cardiomyopathy: echocardiographic features and surgical outcomes.
Kaple RK, Murphy RT, DiPaola LM, Houghtaling PL, Lever HM, Lytle BW,
Blackstone EH, Smedira NG.
Ann Thorac Surg. 2008 May;85(5):1527-35, 1535.e1-2.
Department of Thoracic and Cardiovascular Surgery, The Cleveland Clinic,
Cleveland, Ohio 44195, USA.
BACKGROUND: Functional and intrinsic mitral valve (MV) abnormalities are
common in hypertrophic cardiomyopathy (HCM); however, morphologic
characteristics constituting indications for surgical intervention are
incompletely defined. This study was conducted to define the
echocardiographic features of MV pathology in patients with HCM and
relate these to repairability of the MV, MV procedures performed,
durability of repair, and survival. METHODS: From 1986 to 2003, 851
patients with HCM underwent operation, and 115 had a concomitant MV
procedure. Detailed analysis of their 784 transthoracic and
transesophageal echocardiograms, performed intraoperatively and
postoperatively, was conducted. Outcomes were assessed by
cross-sectional follow-up. RESULTS: Sixty-seven patients (58%) underwent
MV repair, and 48 (42%) had MV replacement. The mean left ventricular
outflow tract peak gradient was 70 +/- 50 mm Hg. Systolic anterior
motion was present in 95%. Valve abnormalities were degenerative in 36
(31%), myxomatous in 23 (20%), papillary muscle in 23 (20%), restrictive
chordal in 22 (19%), restrictive leaflet in 80 (70%), and long leaflet
in 64 (56%). Patients undergoing MV repair had higher prevalence of long
leaflets and degenerative MV pathology. The anterior mitral leaflet was
3.0 +/- 0.49 cm in the repair group vs 2.5 +/- 0.40 cm in the
replacement group (p = 0.0001). MV replacement patients were older, more
symptomatic, and had more renal dysfunction and lower hematocrits. By 3
years, 91% of patients with a repair were free of reoperation.
CONCLUSIONS: Intrinsic MV pathology is frequently observed in HCM
patients with symptomatic obstruction who undergo myectomy.
Echocardiography can identify MV features predictive of successful valve
repair. Repair, although durable, is feasible in only about half of
patients.
Hypertrophic cardiomyopathy is predominantly a disease of left ventricular outflow tract obstruction.
Maron MS. Olivotto I. Zenovich AG. Link MS. Pandian NG. Kuvin JT. Nistri S. Cecchi F. Udelson JE. Maron BJ.
Circulation. 114(21):2232-9, 2006 Nov 21.
Evidence for efficacy of the Italian national pre-participation screening programme for identification of hypertrophic cardiomyopathy in competitive athletes.
Pelliccia A. Di Paolo FM. Corrado D. Buccolieri C. Quattrini FM. Pisicchio C. Spataro A. Biffi A. Granata M. Maron BJ.
European Heart Journal. 27(18):2196-200, 2006 Sep.
Left ventricular outflow tract obstruction and sudden death risk in patients with hypertrophic cardiomyopathy
Elliott PM. Gimeno JR. Tome MT. Shah J. Ward D. Thaman R. Mogensen J. McKenna WJ.
European Heart Journal. 27(16):1933-41, 2006 Aug.
Prevalence, clinical profile, and significance of left ventricular remodeling in the end-stage phase of hypertrophic cardiomyopathy.
Harris KM. Spirito P. Maron MS. Zenovich AG. Formisano F. Lesser JR. Mackey-Bojack S. Manning WJ. Udelson JE. Maron BJ.
Circulation. 114(3):216-25, 2006 Jul 18.
Significance and Relation Between Magnitude of Left Ventricular Hypertrophy and Heart Failure Symptoms in Hypertrophic Cardiomyopathy.
Maron MS, Zenovich AG, Casey SA, Link MS, Udelson JE, Aeppli DM, Maron BJ
Am J Cardiol 95; 2005: 1329-1333.
Long-Term Follow-Up of Patients With Obstructive Hypertrophic Cardiomyopathy Treated With Dual-Chamber Pacing.
Megevand A, Ingles J, Richmond DR, Semsarian C
Am J Cardiol 95; 2005: 991-993.
Hypertrophic obstructive cardiomyopathy: Comparison of outcomes after myectomy or alcohol ablation adjusted by propensity score.
Ralph-Edwards A, Woo A, McCrindle BW, Shapero JL, Schwartz L, Rakowski H, Wigle ED, Williams WG
The Journal of Thoracic and Cardiovascular Surgery 129, 2005: 351-8.
The Prognostic Importance of Left Ventricular Outflow Obstruction in Hypertrophic Cardiomyopathy Varies in Relation to Severity of Symptoms.
Autore C, Bernabo P, Barilla CS, Bruzzi P, Spirito P
J Am Coll Cardiol 45; 2005: 1076-80 .
Apical myocardial injury caused by collateralisation of a septal artery during ethanol septal ablation.
Agarwal SC , Purcell IF, Furniss SS
Heart 91: 2005:e2, 2005.
Yield of Genetic Testing in Hypertrophic Cardiomyopathy
Van Driest SL, Ommen SR, Tajik J, Gersh BJ, Ackerman MJ
Mayo Clinic Proceedings 80; 2005: 739-44.
Glycogen Storage Diseases Presenting as Hypertrophic Cardiomyopathy.
Arad M, Maron BJ, Gorham JM, Johnson, Jr WH, Saul JP, Perez-Atayde AR, Spirito P, Wright GB, Kanter RJ, Seidman CE, Seidman JG
New England Journal of Medicine 352; 2005: 326-72.
Effect of left ventricular outflow tract obstruction on clinical outcome in hypertrophic cardiomyopathy
Maron MS, Olivotto I, Betocchi S, Casey SA, Lesser JR, Losi MA, Cecchi F, Maron BJ.
New England Journal of Medicine. 348(4):295-303, 2003 Jan 23.
Comparison of dual-chamber pacing with nonsurgical septal reduction effect in patients with hypertrophic obstructive cardiomyopathy.
Dimitrow PP. Podolec P. Grodecki J. Plazak W. Dudek D. Pieniazek P.
Bacior B. Legutko J.
Olszowska M. Kostkiewicz M. Kawecka-Jaszcz K. Tracz W. Dubiel JS.
International Journal of Cardiology. 94(1):31-4, 2004 Mar.
Progressive left ventricular remodeling in patients with hypertrophic cardiomyopathy and severe left ventricular hypertrophy.
Thaman R. Gimeno JR. Reith S. Esteban MT. Limongelli G. Murphy RT. Mist B. McKenna WJ. Elliott PM.
Journal of American College of Cardiology. 44(2):398-405, 2004 Jul
Long-term follow-up of implantable cardioverter defibrillator therapy for hypertrophic cardiomyopathy.
Jayatilleke I. Doolan A. Ingles J. McGuire M. Booth V. Richmond DR. Semsarian C.
American Journal of Cardiology. 93(9):1192-4, 2004 May 1.
Predictors of outcome after alcohol septal ablation therapy in patients with hypertrophic obstructive cardiomyopathy
Chang SM. Lakkis NM. Franklin J. Spencer WH 3rd. Nagueh SF.
Circulation. 109(7):824-7, 2004 Feb 24.
Clinical course of hypertrophic cardiomyopathy with survival to advanced age.
Maron BJ. Casey SA. Hauser RG. Aeppli DM
Journal of the American College of Cardiology. 42(5):882-8, 2003 Sep