Herz 2012 · 38:313–316DOI 10.1007/s00059-012-3696-8Received: 20 June 2012Revised: 11 September 2012Accepted: 18 September 2012Published online: 23 December 2012© Urban & Vogel 2012

M. Sunbul · B. Ozben · B. MutluFaculty of Medicine, Department of Cardiology, Marmara University, Besiktas/Istanbul

Two different cardiomyopathies in a single patientHypertrophic cardiomyopathy and left ventricular noncompaction

Introduction

Hypertrophic cardiomyopathy is a rel-atively common genetic disease of the cardiac sarcomere with a Mendelian au-tosomal dominant pattern of inherence (about 1:500 in the general adult popu-lation; [1]). It is characterized by the left ventricular (LV) hypertrophy (typically asymmetric in distribution) with a non-dilated and hyperdynamic chamber. It is associated with a heterogeneous pheno-typic expression and clinical course, in-cluding sudden cardiac death (SCD) and heart failure symptoms [1]. LV wall thick-ness, family history for SCD, nonsus-tained or sustained ventricular tachycar-dia (VT), syncope, hypotensive response to exercise testing were all shown to be as-sociated with increased risk for SCD.

Left ventricular noncompaction, first described in 1990, is an uncommon car-diomyopathy characterized by the per-sistence of fetal myocardium with exces-sive prominence of trabecular meshwork and deep intertrabecular recesses, systolic dysfunction, and LV dilatation [2]. With a prevalence of 0.014%, men are more af-fected than women. Although LV non-compaction has been classified as a pri-mary cardiomyopathy of genetic origin, its definition, diagnostic criteria, and treatment modalities are still being de-bated. It has been postulated to be caused by an arrest of the normal process of in-

trauterine endomyocardial and myocar-dial morphogenesis [2]. Clinical manifes-tations are highly variable, ranging from no symptoms to a progressive deterio-ration in cardiac function that results in congestive heart failure, systemic throm-boemboli, arrhythmias, and SCD.

We report a 29-year-old man with these two different inherent conditions manifesting in a single patient. Our aim is to draw attention to the possibility of underlying common genetic mutations associated with these two clinical entities.

Case

A 29-year-old man was admitted to our clinic with exertional chest pain. His past medical history was not significant for heart failure or syncope. His sister had hypertrophic cardiomyopathy compli-cated with SCD at the age of 18. Physi-cal examination revealed a systolic ejec-tion murmur with normal heart sounds. Blood pressure was 110/80 mmHg and heart rate was 72/min. The 12-lead elec-trocardiogram (ECG) demonstrated si-nus rhythm with left bundle-branch block. Chest X-ray showed an enlarged heart with double outline of the large left atrium. The patient underwent 2-dimen-sional echocardiography, which revealed asymmetrical LV hypertrophy with a maximum LV wall thickness of 24 mm in the basal anterior septum. LV cavity

size was normal with no evidence of rest-ing LV outflow tract obstruction. There was widespread LV hypokinesis with an ejection fraction (LVEF) of 40%, restric-tive type diastolic filling pattern with mitral E/E’ ratio of 17, moderate mitral regurgitation,and pulmonary hyperten-sion (estimated systolic pulmonary artery pressure: 45 mm Hg). In addition, heavy trabeculations were noted at the LV api-cal and lateral walls (. Fig. 1). The right ventricle was normal in size and func-tion. Basal and contrast-enhanced car-diac magnetic resonance imaging (MRI) confirmed the presence of asymmetrical LV hypertrophy in the basal anterior and inferior septum, with prominent trabecu-lation and intertrabecular recesses, with a two-layered structure of the myocardium with an increased noncompacted to com-pacted ratio (>2.0) in the LV apex and lat-eral wall, as well as global hypokinesis, which were all compatible with LV non-compaction (. Fig. 2). The myocardium in the hypertrophic basal anterior and in-ferior septum was compact, which distin-guished it from LV noncompaction. Ge-netic analysis included screening of the two major genes responsible for hyper-trophic cardiomyopathy. In the mybpc3-gene coding for the myosin binding pro-tein C protein, only one base substitution in intron 19–20 was found. However, in the myh7 gene coding for beta (β) myo-sin heavy chain, a single nucleotide poly-

e-Herz: Case study

e-Herz

313Herz 3 · 2013  | 

morphism was found in exon 19 c.2155C >T resulting in an amino acid substitu-tion from arginine to tryptophan at posi-tion 719 (p.R719 W), which was described as a β-cardiac myosin heavy chain gene mutation causing familial hypertrophic cardiomyopathy [3].

He was considered for a possible im-plantable cardioverter–defibrillator (ICD) implantation for primary preven-tion of SCD. The 24-h ECG Holter mon-itoring showed no sustained VT. Dur-ing hospitalization, no VT episode was observed on ECG monitoring. Exercise testing did not reveal any hypotensive re-sponse. ICD implantation was considered on the basis of the young age of the pa-tient, the family history of SCD, and the LV systolic dysfunction. However, the patient declined ICD implantation and was discharged with medical therapy in-cluding a β-blocking agent (carvedilol 12.5 mg/day) and warfarin.

Discussion

Hypertrophic cardiomyopathy is a well-known genetic disease of the cardiac sar-comere; >900 associated mutations from 11 sarcomeric genes have been identified so far [1]. LV noncompaction may be spo-radic or familial and is linked to muta-tions in mitochondrial, cytoskeletal, Z-line, and sarcomeric proteins [4]. Recent-ly, mutations in genes previously impli-cated in the pathogenesis of hypertrophic cardiomyopathy have been identified in patients with LV noncompaction without hypertrophy [5]. Antonio et al. [6] iden-tified the R495Q (G10931A) mutation in exon 17 of the MYBPC3 gene, which is as-sociated with hypertrophic cardiomyop-athy.

The coexistence of LV noncompaction and hypertrophic cardiomyopathy in the same patient is extremely rare. However, there are several reports suggesting that these cardiomyopathies may have a sim-ilar genetic origin. Ramineni et al. [7] re-ported a patient with LV noncompac-tion, hypertrophic obstructive cardio-myopathy, and polycystic kidney disease and posed the possibility of genetic mu-tation common to these three clinical en-tities or two different gene mutations ex-isting in the same individual. Another re-

Fig. 2 8 Cardiac magnetic resonance imaging (a short axis and b 4- chamber bright blood balanced FFE sequence) showing a markedly hypertrophic left ventricle (LV, asterisks) and prominent trabecula-tion (arrow heads) in the apical and lateral wall (compatible with hypertrophic cardiomyopathy and LV noncompaction)

Fig. 1 8 a Two dimensional echocardiography in the parasternal long axis, b, c apical 4-chamber views, and d short axis at the enddiastole showing hypertrophy of the ventricular septum (arrow in a) with trabeculated myocardium (arrows,b, c) involving the apex and the lateral wall of the left ventri-cle (LV). LA left atrium

314 |  Herz 3 · 2013

e-Herz: Case study

port from Spain pointed out that a baby who was initially diagnosed with severe hypertrophic cardiomyopathy by fetal echocardiography showed regression of LV hypertrophy and development of heavy trabeculations achieving noncom-paction criteria at the follow-up, during the first year of life [8]. Contrarily, there is a case of LV noncompaction with initial dilatation that evolved gradually to a hy-pertrophic pattern during follow-up [6]. Such cases have been described as “un-dulating phenotypes” [9]. Our case dem-onstrated certain features of both hyper-trophic cardiomyopathy and LV noncom-paction. The LV was highly hypertrophic with no identifiable cause for the hyper-trophy. Heavy trabeculations with deep intertrabecular recesses were also noted at the LV apical and lateral walls. Cardi-ac MRI confirmed the features compati-ble with both hypertrophic cardiomyop-athy and LV noncompaction (a noncom-pacted-to-compacted ratio at enddiasto-le of ≥2:1). The myocardium in the hyper-trophic segments of septum was compact, while the apex and lateral walls showed typical two-layered structure. In addi-tion, the genetic analysis also revealed the presence of a single nucleotide poly-morphism in exon 19, namely c.2155C >T, which was described as a β-cardiac myo-sin heavy chain gene mutation causing fa-milial hypertrophic cardiomyopathy [3].

Although mainly described in the con-text of dilated and hypokinetic LV, it is unclear whether isolated LV noncompac-tion is a distinct cardiomyopathy, a sub-type of dilated cardiomyopathy, or a mor-phogenetic disorder. Biagini et al. [10] re-viewed 73 patients with LV noncompac-tion and found that 65 patients had dilat-ed cardiomyopathy, 2 adults had clear-cut hypertrophic cardiomyopathy, 1 adult had restrictive cardiomyopathy, and 5 pa-tients had normal LV morphology and function. They concluded that LV non-compaction is a morphologic trait rath-er than a distinct cardiomyopathy based on the knowledge that it can co-exist with restrictive and hypertrophic cardiomyop-athy.

LV noncompaction may also be ob-served in families with hypertrophic or dilated cardiomyopathy, casting doubt on its acceptance as a distinct disease en-

tity. Stöllberger et al. [11] reported three brothers suffering from a neuromuscular disorder, two of who had LV hypertrabec-ulation and the last one had apical-type hypertrophic cardiomyopathy. They con-cluded that apical-type hypertrophic car-diomyopathy might occur together with LV noncompaction in the same family and might represent an abortive form of LV noncompaction.

Risk stratification and management of these patients are extremely impor-tant. Both diseases are associated with increased risk for malignant arrhythmias and SCD. An appreciation of the risk of overall mortality and sudden death is an important component of the identifica-tion of patients who are at risk for ad-verse events. Current guidelines recom-

mend that patients with such cardiomy-opathies be implanted with an ICD in cases of aborted cardiac arrest, sustained VT, syncope related to ventricular ar-rhythmias, family history of SCD, or se-verely impaired LVEF. First-degree rela-tives should also be screened for familial forms of LV noncompaction and hyper-trophic cardiomyopathy.

Conclusions

Hypertrophic cardiomyopathy is the most common genetic heart disease, whereas LV noncompaction is an ex-tremely rare disorder. The phenotypic expression of both diseases in the same patient is even far more rare. However, 

Abstract · Zusammenfassung

Herz 2012 · 38:313–316   DOI 10.1007/s00059-012-3696-8© Urban & Vogel 2012

M. Sunbul · B. Ozben · B. Mutlu

Two different cardiomyopathies in a single patient. Hypertrophic cardiomyopathy and left ventricular noncompaction

AbstractHypertrophic cardiomyopathy is a complex and relatively common genetic disorder char-acterized by left ventricular (LV) hypertrophy, usually associated with a nondilated and hy-perdynamic chamber with heterogeneous phenotypic expression and clinical course. On the other hand, LV noncompaction is an un-common cardiomyopathy characterized by the persistence of fetal myocardium with a pattern of prominent trabecular meshwork and deep intertrabecular recesses, systol-

ic dysfunction, and LV dilatation. We report a 29-year-old man with these two different in-herent conditions. Our case raises the possi-bility of a genetic mutation common to these two clinical entities or different gene muta-tions existing in the same individual.

KeywordsCardiomyopathy · Hypertrophic cardiomyopathy · Left ventricular noncompaction

Zwei verschiedene Kardiomyopathien in ein und demselben Patienten. Hypertrophe Kardiomyopathie und linksventrikuläre Non-Compaction

ZusammenfassungDie hypertrophe Kardiomyopathie ist eine komplexe und relativ häufige genetische Er-krankung, die von linksventrikulärer (LV) Hypertrophie gekennzeichnet ist, welche gewöhnlich mit einer nichtdilatierten und hyperdynamen Kammer unter heteroge-nem phänotypischen Erscheinungsbild und klinischem Verlauf einhergeht. Auf der an-deren Seite ist LV-Non-Compaction eine sel-tene Kardiomyopathie, welche durch Fort-bestehen des fetalen Myokards mit einem Muster von prominenten Trabekelwerk und tiefen intertrabekulären Aussparungen, sys-tolische Dysfunktion und LV-Dilatation cha-

rakterisiert ist. Wir berichten über einen 29-jährigen männlichen Patienten mit beiden genannten unterschiedlichen inhärenten Be-dingungen. Aus unserem Fall ergibt sich die Möglichkeit einer einzelnen genetischen Mu-tation, die diesen beiden klinischen Entitäten gemeinsam ist, oder aber unterschiedlicher Genmutationen, die nebeneinander im sel-ben Individuum existieren.

SchlüsselwörterKardiomyopathie · Hypertrophe Kardiomyopathie · Linksventrikuläre Non-Compaction

315Herz 3 · 2013  | 

there may be a shared molecular etiolo-gy of different cardiomyopathic pheno-types and LV noncompaction can co-ex-ist with either hypertrophic or restrictive cardiomyopathy. Our case has demon-strated that the phenotypic expression of both diseases can occur in the same patient suggesting that they may have a similar genetic origin such as sarco-mere protein gene defects. Whether the phenotypic expression of both diseas-es in the same patient might worsen the prognosis is to be elucidated.

Corresponding address

Assoc. Prof. B. OzbenFaculty of Medicine, Department of Cardiology, Marmara UniversityYildiz Caddesi Konak Apartmani No: 43/16, 34353 Besiktas/IstanbulTurkeybesteozben@yahoo.com

Acknowledgment.  Prof. Dr. Volker Ruppert per-formed the genetic analysis in the Experimental Cardi-ology Laboratory of the Department of Internal Medi-cine and Cardiology of Philipps University of Marburg Heart Center (Marburg, Germany). We thank Dr. Rup-pert for his excellent work and cooperation.

Funding status.  No grant received.

Conflict of interest.  On behalf of all authors, the cor-responding author states that there are no conflicts of interest.

References

  1.  Maron BJ (2002) Hypertrophic cardiomyopathy: a systematic review. JAMA 287:1308–1320

  2.  Chin TK, Perloff JK, Williams RG et al (1990) Iso-lated noncompaction of left ventricular myocar-dium. A study of eight cases. Circulation 82:507–513

  3.  Anan R, Greve G, Thierfelder L et al (1994) Prog-nostic implications of novel beta cardiac myo-sin heavy chain gene mutations that cause fa-milial hypertrophic cardiomyopathy. J Clin Invest 93:280–285

  4.  Sen-Chowdhry S, McKenna WJ (2008) Left ventric-ular noncompaction and cardiomyopathy: cause, contributor, or epiphenomenon? Curr Opin Cardi-ol 23:171–175

  5.  Klaassen S, Probst S, Oechslin E et al (2008) Muta-tions in sarcomere protein genes in left ventricu-lar noncompaction. Circulation 117:2893–2901

  6.  António M, Costa C, Venâncio M et al (2011) Left ventricular noncompaction: analysis of a pediatric population. Rev Port Cardiol 30:295–311

  7.  Ramineni R, Merla R, Chernobelsky A (2010) Non-compaction of ventricular myocardium associated with hypertrophic cardiomyopathy and polycystic kidney disease. Am J Med Sci 339:383–386

  8.  Betrián Blasco P, Albert Brotóns DC, Menduña QF et al (2010) Severe foetal hypertrophic cardiomy-opathy evolving to left ventricular non-compac-tion. Eur J Echocardiogr 11:E36

  9.  Pignatelli RH, McMahon CJ, Dreyer WJ et al (2003) Clinical characterization of left ventricular non-compaction in children: a relatively common form of cardiomyopathy. Circulation 108:2672–2678

10.  Biagini E, Ragni L, Ferlito M et al (2006) Different types of cardiomyopathy associated with isolated ventricular noncompaction. Am J Cardiol 98:821–824

11.  Stöllberger C, Hamedanchi A, Finsterer J (2009) Myopathy, apical hypertrophic cardiomyopathy and left ventricular noncompaction within the same family. Acta Cardiol 64:35–40

316 |  Herz 3 · 2013

e-Herz: Case study