|Year : 2018 | Volume
| Issue : 3 | Page : 871-874
Factors affecting the prognosis of hypertrophic cardiomyopathy disease
Hala Mahfouz1, Ghada M Soltan1, Ahmed Y Salem2
1 Department of Cardiology, Faculty of Medicine, Menoufiya University, Menoufiya, Egypt
2 Department of Cardiology, National Heart Institute, Cairo, Egypt
|Date of Submission||05-Nov-2016|
|Date of Acceptance||02-Dec-2016|
|Date of Web Publication||31-Dec-2018|
Ahmed Y Salem
Department of Cardiology, National Heart Institute, Cairo
Source of Support: None, Conflict of Interest: None
To assess the potential factors affecting the prognosis of hypertrophic cardiomyopathy disease. Medline databases (PubMed, Medscape, HYPERLINK “http://www.sciencedirect.com/”ScienceDirect. EMF-Portal) and all materials available in the Internet from 2000 to 2014, and Topol manual of cardiovascular medicine 4th edition. The initial search presented 30 articles of which 20 met the inclusion criteria. The articles studied the relation between several risk factors and the prognosis of hypertrophic cardiomyopathy. If the studies did not fulfill the inclusion criteria, they were excluded. Study quality assessment included whether ethical approval was gained, eligibility criteria specified, appropriate controls, adequate information, and defined assessment measures. Comparisons were made by structured review with the results tabulated. In total 20 potentially relevant publications were included; They indicate an association between left ventricular outflow tract obstruction, previous cardiac arrest, sustained VT, prolonged or repetitive episodes of nonsustained VT on Holter monitoring , left ventricular wall thickness more than 30mm , family history of sudden cardiac dealth , no change or decrease in the blood pressure with exercise , syncope or near syncope, LA size, occurrence of AF, late gadolinium enhancement by magnetic resonance imaging, and poor prognosis in the terms of morbidity and mortality of hypertrophic cardiomyopathy patients. We found an association between left ventricular outflow tract obstruction, previous cardiac arrest, sustained VT, prolonged or repetitive episodes of nonsustained VT on Holter monitoring, left ventricular wall thickness more than 30mm (thirty millemeters), family history of sudden cardiac death, no change or decrease in the blood pressure with exercise , syncope or near syncope, left atrial size, occurrence of AF, late gadolinium enhancement by magnetic resonance imaging, and poor prognosis in the terms of morbidity and mortality of hypertrophic cardiomyopathy patients.
Keywords: hypertrophic cardiomyopathy, prognosis, risk factors
|How to cite this article:|
Mahfouz H, Soltan GM, Salem AY. Factors affecting the prognosis of hypertrophic cardiomyopathy disease. Menoufia Med J 2018;31:871-4
|How to cite this URL:|
Mahfouz H, Soltan GM, Salem AY. Factors affecting the prognosis of hypertrophic cardiomyopathy disease. Menoufia Med J [serial online] 2018 [cited 2019 Jun 19];31:871-4. Available from: http://www.mmj.eg.net/text.asp?2018/31/3/871/248754
| Introduction|| |
Hypertrophic cardiomyopathy (HCM) is a common inherited heart disease with diverse phenotypic and genetic expression, clinical presentation, and natural history. HCM has been recognized for 55 years, but recently substantial advances in diagnosis and treatment options have evolved, as well as increased recognition of the disease in clinical practice. Nevertheless, most genetically and clinically affected individuals probably remain undiagnosed, largely free from disease-related complications, although HCM may progress along one or more of its major disease pathways [i.e., arrhythmic sudden death risk; progressive heart failure (HF) due to dynamic left ventricular outflow (LVOT) obstruction or due to systolic dysfunction in the absence of obstruction; or atrial fibrillation (AF) with risk of stroke].
Various genetic mutations are included in the pathology of HCM; most mutations occur in MYH7 and MYBPC3 genes.
We reviewed papers on the prognostic factors of HCM from Medline databases, which are PubMed, Medscape, ScienceDirect, and also materials available in the Internet from 2000 to 2014, and Topol manual of cardiovascular medicine, 4th ed.
We used HCM, prognosis, and risk factors as searching terms.
All the studies were independently assessed for inclusion. They were included if they fulfilled the following criteria:
- Published in English language
- Published in peer-reviewed journals or Topol manual of clinical cardiology
- Focused on the prognostic factors of HCM
- Discussed the relation between possible risk factors of HCM and morbidity or mortality
- If a study had several publications on certain aspects, we used the latest publication giving the most relevant data.
If the studies did not fulfill the above criteria, they were excluded.
The analyzed publications were evaluated according to evidence-based medicine (EBM) criteria using the classification of the US Preventive Services Task Force and UK National Health Service protocol for EBM in addition to the evidence pyramid.
US Preventive Services Task Force classification is as follows:
- Level I: evidence obtained from at least one properly designed randomized controlled trial
- Level II-1: evidence obtained from well-designed controlled trials without randomization
- Level II-2: evidence obtained from well-designed cohort or case–control analytic studies, preferably from more than one center or research group
- Level II-3: evidence obtained from multiple time series with or without the intervention. Significant results in uncontrolled trials might also be regarded as this type of evidence
- Level III: opinions of respected authorities, based on clinical experience, descriptive studies, or reports of expert committees.
The quality of all the studies was assessed. Important factors included study design, attainment of ethical approval, evidence of a power calculation, specified eligibility criteria, appropriate controls, adequate information, and specified assessment measures. It was expected that confounding factors would be reported and controlled for and appropriate data analysis made in addition to an explanation of missing data.
A structured systematic review was performed with the results tabulated.
| Results|| |
Study selection and characteristics
In a total of 30 potentially relevant publications that were identified, 10 articles were excluded, as they did not meet our inclusion criteria. A total of 20 studies were included in the review, as they were deemed eligible by fulfilling the inclusion criteria. The studies were analyzed with respect to the study design using the classification of the US Preventive Services Task Force and UK National Health Service protocol for EBM.
Risk factors affecting the prognosis of hypertrophic cardiomyopathy
Risk factors for sudden cardiac death (SCD) include previous cardiac arrest, sustained ventricular tachycardia (SVT), prolonged or repetitive episodes of nonsustained ventricular tachycardia (NSVT) on holter monitoring, left ventricular (LV) wall thickness more than 30 mm, family history of SCD, no change or decrease in the blood pressure (BP) with exercise, and syncope or near syncope.
Some studies included left atrium size as a prognostic factor in HCM (from the Italian registry for HCM) and concluded that left atrial size is an independent novel prognostic factor particularly relevant to the identification of patients at risk for death related to HF.
Another study assessed the occurrence of AF as a prognostic influence in HCM and has proven a strong correlation with prognosis and concluded that AF was associated with substantial risk for HF-related mortality, stroke, and severe functional disability, particularly in patients with outflow obstruction, those lower to 50 years of age, or those developing chronic AF, and was, nevertheless, compatible with benign outcome in 35% of patients.
Risk of sudden cardiac death
SCD is the most significant complication of HCM. Although primary estimates of the SCD rate emanating from tertiary center-based cohorts have been as high as 6% per year, true prevalence based on data coming from large-scale community registries is significantly lower, ~0.7% annually,. It is evident that the prevalence of SCD is higher in younger people, approximately before 35 years of age, although according to other studies longevity is not synonymous with immunity,. HCM-related SCD is the leading cause of mortality among competitive athletes following different sport disciplines,. The vast majority of SD (85%) occurs during daily activities (walking, rest, driving, or during sleep), whereas 70% of patients dying suddenly are asymptomatic or have few symptoms (functional class Ior II). Despite the fact that SCD objectively affects a small minority of HCM patients, early recognition of predisposing factors and concomitant prevention still remains a major clinical challenge, as SCD and associated lethal arrhythmic events may be fully prevented, either primarily or secondarily, by means of implantable intracardiac devices (ICDs).
Apart from personal history of ventricular fibrillation, SVT, or resuscitated cardiac arrest, which has been found to represent the highest risk predisposing to new potentially lethal arrhythmic events (secondary prevention),,, five noninterventional clinical factors have been identified up to now to represent risk markers for SCD in HCM: (a) family history of SCD affecting at least one first-degree relative less than 40 years; (b) syncope, without a known causal factor occurring in the recent past (<6 months); (c) extreme LV hypertrophy, as this is represented by a maximum wall thickness of any myocardial segment greater than 30 mm; (d) abnormal BP response to exercise, defined as either a failure of systolic BP to increase by at least 20 mmHg or a drop below baseline resting values during effort and even a drop of systolic pressure during maximal exercise; and (e) NSVT, defined as recording on ambulatory 24 h Holter of more than or equal to three consecutive ventricular ectopic beats at a rate of greater than or equal to 120 beats lasting less than 30 s,,,,. NSVT is considered a risk factor for SCD, primarily in patients under the age of 30 years,.
Recent HCM guidelines have suggested an escalation in risk stratification, suggesting that personal history of SVT or ventricular fibrillation is class I indication for ICD implantation. Existing literature suggests that these patients have 33% mortality in 7 years and that in 5 years 41% will experience SD or ICD discharge. The presence of a family history of SCD, syncope, or a maximal wall thickness greater than 30 mm confers a Class IIa indication for ICDs, whereas NSVT or abnormal BP response alone probably could not justify ICD implantation needing reassessment of risk profile based on the remaining risk factors or potential arbitrators. Several clinical or laboratory aspects of HCM have been studied as potential risk modifiers for SCD, as shown in [Table 1]. Among them, three certain features of HCM may affect our decision in favor of ICD implantation based on evidence from published trials,: the presence of late gadolinium enhancement (LGE) on MRI; certain mutations, especially coexistence of more than 1 sarcomere mutation; and marked LVOT tract obstruction at rest,,.
|Table 1: Risk factors for sudden cardiac death in hypertrophic cardiomyopathy|
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All of the above-mentioned factors describe the very same phenomenon from a different point of view: extent of replacement and interstitial fibrosis leading to different conduction pathways in the myocardium, thus facilitating re-entry events and finally malignant ventricular tachyarrhythmias,. On the basis of the previous assumptions, detection of LGE by MRI could be the main pillar of SCD risk stratification, as it reflects the extent of fibrosis, the main determinant of malignant arrhythmias. However, a recent meta-analysis concluded that LGE showed a trend toward significance for predicting SCD/aborted SCD (pooled odds ratio = 2.39; 95% confidence interval: 0.87–6.58; P = 0.091), failing to accurately define individual patients with HCM reaching this end point. To date, there is no compelling published evidence that the extent is more important than just the presence of LGE for risk prediction. Moreover, the 2011 current guidelines emphasize that it is the presence and not the extent of LGE that relates to adverse cardiovascular events. However, this is an interesting, controversial topic that should be addressed by future research [an ongoing multicenter trial with over 1000 HCM patients will probably show that the extent of LGE is also relevant (Martin Maron, ACC 2013)].
Patients with HCM are at an increased risk of AF compared with age-matched cohorts, whereas AF is an important cause of symptoms, morbidity, and even mortality in patients with HCM,.
| Discussion|| |
Although most of the previously mentioned prognostic factors were agreed to be of significant value by most authors, and even were included in recent guidelines, there has been some controversy about LVOT gradient (obstruction) as a poor prognostic factor, as few authors in their studies found this factor to be insignificant as regards mortality results and also found that diagnosis at a younger age is of poor prognosis only at large tertiary referral centers but not in general population studies; however, this controversy can be understood upon agreeing that diagnosis at a younger age because of development of symptoms and seeking medical advice carried worse prognosis and taking into consideration the limited number of cases (37 cases) for the study, which had different results. Other novel risk factors have been studied on a limited scale and require further assessment.
| Conclusion|| |
Risk factors for SCD and/or poor prognosis in terms of morbidity and mortality of HCM include LVOT obstruction, previous cardiac arrest, SVT, prolonged or repetitive episodes of NSVT on holter monitoring, LV wall thickness more than 30 mm, family history of SCD, no change or decrease in the BP with exercise, and syncope or near syncope.
Other novel risk factors that were found recently and still require further studies include the following: left atrium size, occurrence of AF, LGE by MRI, severe systolic or diastolic impairment, severe concomitant coronary artery disease, and severe or multiple sarcomeric mutations.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Maron BJ, Ommen SR, Semsarian C, Spirito P, Olivotto I, Maron MS. Hypertrophic Cardiomyopathy: Present and Future, With Translation Into Contemporary Cardiovascular Medicine. J Am Coll Cardiol 2014; 64
Maron BJ. Hypertrophic cardiomyopathy: a systematic review. JAMA 2002; 287
Gersh BJ, Maron BJ, Bonow RO, Dearani JA, Fifer MA, Link MS, 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 2011; 124
Soullier C, Obert P, Doucende G, Nottin S, Cade S, Perez-Martin A, et al.
Exercise response in hypertrophic cardiomyopathy: blunted left ventricular deformational and twisting reserve with altered systolic-diastolic coupling. Circ Cardiovasc Imaging. 2012; 5
Maron BJ. Hypertrophic cardiomyopathy: a systematic review. JAMA 2002; 287
Gersh BJ, Maron BJ, Bonow RO, Dearani JA, Fifer MA, Link MS, 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 Am Coll Cardiol 2011; 58
Maron BJ, Olivotto I, Spirito P, Casey SA, Bellone P, Gohman TE, et al.
Epidemiology of hypertrophic cardiomyopathy-related death: revisited in a large non-referral-based patient population. Circulation 2000; 102
Colan SD, Lipshultz SE, Lowe AM, Sleeper LA, Messere J, Cox GF, et al.
Epidemiology and cause-specific outcome of hypertrophic cardiomyopathy in children: findings from the Pediatric Cardiomyopathy Registry. Circulation 2007; 115
Maron BJ, Pelliccia A. The heart of trained athletes: cardiac remodeling and the risks of sports, including sudden death. Circulation 2006; 114
Pagourelias ED, Efthimiadis GK, Kouidi E, Fragakis N, Athyros VG, Geleris P. Athlete's heart or hypertrophic cardiomyopathy: the dilemma is still there. Am J Cardiol 2011; 108
Cecchi F, Maron BJ, Epstein SE. Long-term outcome of patients with hypertrophic cardiomyopathy successfully resuscitated after cardiac arrest. J Am Coll Cardiol 1989; 13
Elliott PM, Sharma S, Varnava A, Poloniecki J, Rowland E, McKenna WJ. Survival after cardiac arrest or sustained ventricular tachycardia in patients with hypertrophic cardiomyopathy. J Am Coll Cardiol 1999; 33
Maron BJ, Haas TS, Shannon KM, Almquist AK, Hodges JS. Long-term survival after cardiac arrest in hypertrophic cardiomyopathy. Heart Rhythm 2009; 6
Maron BJ. Contemporary insights and strategies for risk stratification and prevention of sudden death in hypertrophic cardiomyopathy. Circulation 2010; 121
Elliott PM, Poloniecki J, Dickie S, Sharma S, Monserrat L, Varnava A, et al.
Sudden death in hypertrophic cardiomyopathy: identification of high risk patients. J Am Coll Cardiol 2000; 36
Spirito P, Rapezzi C, Autore C, Bruzzi P, Bellone P, Ortolani P, et al.
Prognosis of asymptomatic patients with hypertrophic cardiomyopathy and nonsustained ventricular tachycardia. Circulation 1994; 90
Gimeno JR, Tomé-Esteban M, Lofiego C, Hurtado J, Pantazis A, Mist B, et al.
Exercise-induced ventricular arrhythmias and risk of sudden cardiac death in patients with hypertrophic cardiomyopathy. Eur Heart J 2009; 30
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
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
Elliott PM, Anastasakis A, Borger MA. ESC guidelines on diagnosis and management of hypertrophic cardiomyopathy: The task force for the diagnosis and management of hypertrophic cardiomyopathy of the European society of cardiology (ESC). Eur Heart J 2014;35:2733-79.
Green JJ, Berger JS, Kramer CM, Salerno M. Prognostic value of late gadolinium enhancement in clinical outcomes for hypertrophic cardiomyopathy. JACC Cardiovasc Imaging 2012; 5
Girolami F, Ho CY, Semsarian C, Baldi M, Will ML, Baldini K, et al.
Clinical features and outcome of hypertrophic cardiomyopathy associated with triple sarcomere protein gene mutations. J Am Coll Cardiol 2010; 55
Maron MS, Olivotto I, Betocchi S, Casey SA, Lesser JR, Losi MA, et al.
Effect of left ventricular outflow tract obstruction on clinical outcome in hypertrophic cardiomyopathy. N Engl J Med 2003; 348
Elliott PM, Gimeno JR, Tomé MT, Shah J, Ward D, Thaman R, et al.
Left ventricular outflow tract obstruction and sudden death risk in patients with hypertrophic cardiomyopathy. Eur Heart J 2006; 27
Marian AJ, Roberts R The molecular genetic basis for hypertrophic cardiomyopathy. J Mol Cell Cardiol 2001; 33
Frey N, Luedde M, Katus HA. Mechanisms of disease: hypertrophic cardiomyopathy. Nat Rev Cardiol 2012; 9
Romeo F, Cianfrocca C, Pelliccia F, Colloridi V, Cristofani R, Reale A. Long-term prognosis in children with hypertrophic cardiomyopathy: an analysis of 37 patients aged less than 14 years at diagnosis. Clin Cardiol 1990; 13