[SCD-FORUM] 86E RE: Alleged apical hypertrophic cardiomyopathy. Dr. Perez Riera

[SCD INFO]

Dear Luis Wolman: I'm Andres Ricardo Perez Riera from Sao Paulo Brazil, 
and I'll answer your question.
Hypertrophic cardiomyopathy (HCM) is a myocardial disease with variable 
phenotpye and genotype. Non-obstructive hypertrophy localized to the 
cardiac apex (wall thickening is confined to the  most distal region at 
the apex,)  or apical hypertrophic cardiomyopathy (ApHCM) is a specific 
variant of HCM. This disease has been first described in Japan where the 
prevalence is much higher than in the western world.
ApHCM, occurs in only 1 to 2% of the non-Japanese population.
Only a limited number of sarcomere gene defects (eg, cardiac actin 
Glu101Lys) consistently produce ApHCM (1). A single amino acid 
substitution in actin causes either CHF or maladaptive cardiac 
hypertrophy, depending on its effect on actin structure and function.
De novo mutations in cardiac actin gene were identified in two patients 
with sporadic HCM who presented with syncope in early childhood. 
Patients were heterozygous for missense mutations resulting in Pro164Ala 
and Ala331Pro amino acid substitutions, adjacent to regions of 
actin-actin and actin-myosin interaction, respectively. A mutation that 
cosegregated with familial HCM was also found, causing a Glu99Lys 
substitution in a weak actomyosin binding domain. The cardiac phenotype 
in many affected patients was characterized by an ApHCM (2).
 
The typical features of AHC include:
1)       Giant negative T waves in the precordial ECG leads Giant 
negative T waves negativity  mayor or equal 1.0 mV (10 mm). Giant 
negative T waves are more common in Japanese patients than American 
patients: 15% in Japan vs 3% in US (3);
2)       Sometimes R-wave voltage and T-wave negativity progressively 
decreased in magnitude at serial electrocardiograms;
3)       Non-sustained  or sustained VT in patients that developed 
apical aneurysm with normal coronary arteries;
4)       A spade-like configuration of the left ventricle at end-systole 
in the right anterior oblique projection.  Non-spade ApHCM was newly 
identified on cardiac magnetic resonance (CMR) short-axis images, and 
this could be an additional, important underlying cause of moderately to 
severely inverted T waves. The area of hypertrophied myocardium is 
confined to a narrow region of the septum or the anterior or lateral 
wall at the apical level (non-spade apical hypertrophic cardiomyopathy)(4);
5)       The absence of an outflow tract pressure gradient;
6)       Mild symptoms;
7)       The prognosis of ApHCM with regard to SCD is believed to be 
better than that of common HCM.  Patients with the ApHCM had a benign 
clinical course. However, the mutation Arg719Trp in the cardiac 
beta-myosin heavy chain (beta MHC) gene is a high risk factor for sudden 
death and can be associated with an unusual ApHCM(5);
8)       Progressing to myocardial necrosis and aneurysm formation 
because of the chronic myocardial ischemia at the apex eventually is 
observed (6)
9)       123I-MIBG imaging revealed regional sympathetic denervation in 
the inferior and lateral regions.
 
 Recent observations suggest that the risk of SCD might be increased not 
only in common HCM, but also in Japanese-type ApHCM (7).
PES demonstrated reproducible induction of VF in aborted SD and 
presyncopal patients, resulting in the need for an ICD and amiodarone.
Patients with refractory atrial fibrillation with a rapid ventricular 
response suffered from serious congestive heart failure. A prudent 
assessment and strategy in patients with this disease would be 
indispensable in avoiding a disastrous outcome.
To clarify the mechanisms of      ECG abnormalities in hypertrophic 
cardiomyopathy, 102 patients were examined with CMR. Distribution and 
magnitude of hypertrophy and late-enhancement were correlated with ECG 
abnormalities:
1)           Abnormal Q waves reflect the interrelation between upper 
anterior septal thickness and other regions of the left and right 
ventricles, and wider Q waves are associated with late-enhancement;
2)           Conduction disturbances and absent septal Q waves are 
associated with late-enhancement;
3)           The depth of negative T waves is related to craniocaudal 
asymmetry and apical late-enhancement (8)
  As many as 25% of Japanese patients with HCM have predominately apical 
involvement.
Despite its low incidence, physicians caring for patients with chest 
pain need to consider ApHCM, in their differential diagnosis(9).
In ApHCM, sustained cavity obliteration is an important pathophysiologic 
condition as well as hypertrophy, ischemia, and prolonged QTc, which are 
considered jointly related to the development of aneurysm through 
interactions(10).
 
References
1)       Arad M, Penas-Lado M, Monserrat L, et al. Gene mutations in 
apical hypertrophic cardiomyopathy.  Circulation. 2005; 112:2805-2811
2)       Olson TM, Doan TO, Kishimoto NY, et al.  Inherited and de novo 
mutations in the cardiac actin gene cause hypertrophic cardiomyopathy. J 
Mol Cell Cardiol. 2000;32:1687-1694.
3)       Kitaoka H, Doi Y,  Casey SA, Comparison of prevalence of apical 
hypertrophic cardiomyopathy in Japan and the United States. Am J 
Cardiol. 2003;92:1183-1186.
4)       Suzuki J, Watanabe F, Takenaka K, et al. New subtype of apical 
hypertrophic cardiomyopathy identified with nuclear magnetic resonance 
imaging as an underlying cause of markedly inverted T waves J Am Coll 
Cardiol. 1993;22:1175-1181;
5)       Dohlemann C, Hebe J, Meitinger T, Apical hypertrophic 
cardiomyopathy due to a de novo mutation Arg719Trp of the beta-myosin 
heavy chain gene and cardiac arrest in childhood. A case report and 
family study.
6)       Marcu CB, Kapoor A, Donohue TJ Apical aneurysm in a patient 
with apical hypertrophic cardiomyopathy. Conn Med. 2006; 70:297-300.
7)       Ridjab D, Koch M, Zabel M, Schultheiss HP, Morguet AJ.Cardiac 
Arrest and Ventricular Tachycardia in Japanese-Type Apical Hypertrophic 
Cardiomyopathy. Cardiology. 2006; 107:81-86.
8)       Dumont CA, Monserrat L, Soler R, et al .Interpretation of 
electrocardiographic abnormalities in hypertrophic cardiomyopathy with 
cardiac magnetic resonance. Eur Heart J. 2006; 27:1725-1731.
9)       Iskandar SB, Dittus K, Merrick D. Uncommon cause of a common 
disease. South Med J. 2003;96:828-831
10)   Matsubara K, Nakamura T, Kuribayashi T, et al.Sustained cavity 
obliteration and apical aneurysm formation in apical hypertrophic 
cardiomyopathy. Am Coll Cardiol. 2003;42:1338.
All the best
Andrés Ricardo Pérez Riera
Chief of Electro-Vectocardiology Sector of the Discipline of  
Cardiology, ABC Faculty of Medicine (FMABC), Foundation of ABC (FUABC) - 
Santo André -  Sao Paulo - Brazil. Rua Sebastiao Afonso  885 - Zip Code: 
044417-100- Jardim Miriam   S.P  Brazil

El 21/10/2006, a las 20:53, SCD Symposium escribió:

> Hello, friends from the cyberspace,
> Congratulations and thank you for this new great event. I would like 
> to ask about the best management to follow in the following clinical 
> case: this is a 56-year-old patient, who consulted 10 years ago as a 
> routine. In that moment he had a very pathological ECG, with negative 
> and huge T waves in all the anterior side. We conducted ergometer 
> test, 2D echo, Holter and coronary angiography, and all of them 
> resulted normal. Since then studies have been repeated annually, and 
> he remains completely asymptomatic. The ECG persists with no changes 
> and the two last echoes report: apical ventricular hypertrophy. A 
> spect gamma camera does not report the alleged apical hypertrophy. We 
> have scheduled a cardiac resonance. The question is: should this 
> patient receive any treatment? For instance, beta blockers?
> At first I had thought that this was a case of genetic hypertrophic 
> cardiomyopathy (troponin?) without phenotype. Now, I'm not sure that's 
> correct. I would like to have your opinion about what management to 
> follow. The father of the patient died when he was 56 years old, 
> suddenly, but he ignores if the father was a coronary patient, and the 
> sons of the patient do not show any pathology to this date. Thank you 
> very much,
> Luis Wolman



--
Dr. Sergio Dubner
President of Scientific Committee

Dr. Edgardo Schapachnik
President of Steering Committee