Cardiologic and neurologic findings in left ventricular hypertrabeculation/non-compaction related to wall thickness, size and systolic function

Left ventricular hypertrabeculation/noncompaction (LVHT) is a rare cardiac abnormality, diagnosed echocardiographically when >3 left ventricular trabeculations are visible in one image plane apically to the papillary muscles and intertrabecular spaces are perfused from the ventricular cavity. In the majority of the cases, LVHT is associated with neuromuscular disorders (NMD). LVHT occurs in dilated as well as in normally sized ventricles, with or without systolic dysfunction and wall thickening. Aim of the study was to assess whether cardiologic and neurologic findings differ between patients according to echocardiographically determined left ventricular size, systolic function and wall thickness. In 77 patients (19 f, mean age 52 years) LVHT was diagnosed. LVHT was assessed as 'dilative' (enddiastolic diameter >or=60 mm and fractional shortening or=12 mm and fractional shortening >or=26%) and in the remaining 16 patients as 'normally-dimensioned'. Dilative LVHT patients were older than hypertrophic or normally-dimensioned LHVT patients. The prevalence of NMD was 63% in dilative LVHT, 67% in hypertrophic LVHT and 56% in normally-dimensioned LVHT. LHVT is more frequently found in dilated than hypertrophic ventricles. NMD are equally frequent in dilative, hypertrophic and normally-dimensioned LVHT. Cardiac abnormalities may progress with age.     

Right ventricular obstructive hypertrophic cardiomyopathy in primary Myo-Adenylate Deaminase Deficiency

MyoAdenylate Deaminase Deficiency (MADD) is a relatively common metabolic disorder of the skeletal muscle. Patients with MADD usually show an impaired bioenergetic production and a clinical spectrum with either exercise-induced muscle pain, fatigue and/or rhabdomyolysis.Left ventricular hypertrophy as well as other types of cardiac involvement have been reported in patients with primary MADD.We describe herein a case of a 61-year-old woman with biochemical and genetic evidence of Myo-Adenylate Deaminase deficiency, in whom we found a right ventricular hypertrophic cardiomyopathy leading to severe outflow tract dynamic obstruction.Key words: Echocardiography, Myo-Adenylate Deaminase deficiency, neuromuscular disorders, right ventricular disease, right ventricular hypertrabeculation, right ventricular hypertrophic cardiomyopathy     

Non-compaction on autopsy in Duchenne muscular dystrophy

Left ventricular hypertrabeculation (LVHT)/non-compaction is frequently associated with neuromuscular disorders. Recently, LVHT has been detected in a 28-year patient with Duchenne muscular dystrophy. Here, the patho-anatomic findings of this patient are presented, which showed LVHT located within in the apex and the anterior and lateral wall, being the most demanded segments during systole. The septum and the left ventricular outflow tract were not involved. The patho-anatomic specimen also showed aberrant bands and false tendons, a frequent finding in hearts with LVHT. The patho-anatomic findings were in line with those of LVHT patients with or without neuromuscular disorders.     

Diagnosing left ventricular noncompaction by echocardiography and cardiac magnetic resonance imaging and its dependency on neuromuscular disorders

BACKGROUND: Left ventricular hypertrabeculation (LVHT), also termed noncompaction LVHT, is diagnosed by echocardiography or cardiac magnetic resonance imaging (CMRI), and associated with neuromuscular disorders (NMD). The aim of this study was to assess if LVHT can be diagnosed by CMRI applying echocardiographic definitions. METHODS AND RESULTS: The CMRI images of 19 echocardiographically diagnosed LVHT patients were re-evaluated (10 female, 14-67 y of age). Left ventricular hypertrabeculation was diagnosed by CMRI in 9 cases. Patients with CMRI-diagnosed LVHT were more often females (67% versus 40%), experienced heart failure more often (100% versus 50%), had an LV end diastolic diameter > 57 mm (67% versus 40%), had an LV fractional shortening < 25% (89% versus 40%), and had a larger extension of LVHT than patients without CMRI-diagnosed LVHT. The prevalence of NMD (87%) did not differ between both groups. CONCLUSIONS: Echocardiographic definition for CMRI yielded the diagnosis of LVHT in only 47%. When looking for LVHT by CMRI, LV size, function, and extension of LVHT have to be considered. Copyright (c) 2008 Wiley Periodicals, Inc.     

Left ventricular hypertrabeculation/noncompaction with and without neuromuscular disorders

BACKGROUND: Left ventricular hypertrabeculation/noncompaction (LVHT) is frequently associated with neuromuscular disorders (NMD). It is unknown, whether LVHT patients differ according to the presence or absence of NMD. Aim of the study was to assess, if clinical, ECG or echocardiographic findings differ between LVHT patients with and without NMD. METHODS: Included were all patients, in whom LVHT was diagnosed between June 1995 and February 2003 in one echocardiographic laboratory. All patients underwent a cardiologic examination and were invited for a neurologic investigation. RESULTS: Of 77 patients with LVHT (19 female, mean age 52 years), 59 were investigated neurologically. Eleven were neurologically normal, 21 had a definite NMD (metabolic myopathy, n=15; Leber's hereditary optic neuropathy, n=3; myotonic dystrophy, n=2 and Becker muscular dystrophy, n=1). The remaining 27 had a NMD of unknown etiology. Neurologically normal patients had more often anginal chest pain than patients with definite NMD (64% vs. 14%, P=0.0042) or NMD of unknown etiology (64% vs. 26%, P=0.0157). Neurologically normal patients were more often in NYHA class 0 or I than patients with NMD of unknown etiology (64% vs. 26%, P=0.0289) and had a thinner interventricular septum than patients with NMD (10.6 mm vs. 12.8 mm, P=0.0253). CONCLUSIONS: Cardiac abnormalities are hardly different between patients with and without NMD.     

Myopathy,Left Ventricular Noncompaction,and Tetralogy of Fallot

Left ventricular hypertrabeculation, also termed noncompaction (LVHT) is a cardiac abnormality characterized by excessive trabeculations of the left ventricular cavity. LVHT may be associated with extracardiac abnormalities, most frequently neuromuscular disorders (NMDs). LVHT associated with tetralogy of Fallot (ToF), so far, has been reported in 2 cases, but no indication for the presence of NMDs are given. We present a 47‐year old female who underwent 2 cardiac surgeries because of ToF, and was admitted because of heart failure. She was diagnosed with echocardiographic LVHT. A myopathy was diagnosed by biopsy. Copyright © 2009 Wiley Periodicals, Inc.     

Familial left ventricular hypertrabeculation in myotonic dystrophy type 1

BACKGROUND: Familial left ventricular hypertrabeculation (LVHT)has not been described in myotonic dystrophy type 1 (MD1).CASE REPORT: Two MD1 patients are described, father and daughter, both presenting with LVHT. The father was a 45-year-old man with the typical MD1 phenotype starting in 1992. DNA analysis revealed a heterozygous expansion of 300 CTG repeats in the myotonic dystrophy protein kinase (DMPK) gene on chromosome 19q13.3. He had a history of successful electrocardioversion of atrial flutter into sinus rhythm. Cardiac history and clinical cardiologic examination were otherwise normal. On ECG, ST elevation was found exclusively. Transthoracic echocardiography revealed LVHT, previously described only in Becker's muscular dystrophy, metabolic myopathy, Barth syndrome, and other rare genetic disorders. In the 13-year-old daughter, occasional muscle cramps since 1998, discrete weakness of the left triceps brachii muscle, and discrete distal wasting of the upper limbs were found. Serum creatine kinase (CK) and electromyography were normal. The daughter carried an expansion of 140 CTG repeats in the DMPK gene. Clinical cardiologic examination as well as the ECG were normal. Echocardiography revealed LVHT,which was also confirmed by cardiac MRI. Neither the father nor the daughter required any cardiac medication. CONCLUSION: This study demonstrates that LVHT in MD1 may bea cardiac manifestation of the underlying skeletal muscle disorder, may show a familial occurrence, or may be associated with other cardiac abnormalities or isolated.     

Acquired left ventricular hypertrabeculation/noncompaction in myotonic dystrophy type 1

Congenital left ventricular hypertrabeculation/noncompaction (LVHT) is a common feature of neuromuscular disorders (NMDs). Most commonly LVHT is located in the apex and the lateral wall. Acquired LVHT has been only occasionally reported. In myotonic dystrophy type 1 (MD1) acquired LVHT has not been described. In a 48-year-old female with MD1 due to a CTG-repeat expansion of 700-800 repeats in blood lymphocytes echocardiography at the age of 48 years revealed LVHT in the apex and the mid-ventricular septum. LVHT was interpreted as acquired since none of the previous echocardiograms, carried out to assess cardiac involvement in MD1, showed LVHT. Cardiac history and clinical cardiologic examination were normal. On ECG, non-specific ST-abnormalities and supraventricular ectopic beats were recorded. The AECG showed episodic sinus-bradycardia, ventricular ectopic beats, and was indicative of a sleep-apnea syndrome. This case is unique for the association of MD1 with acquired LVHT located in the apex and the mid-ventricular septum. In the absence of significant additional cardiac abnormalities no cardiac therapy was indicated.     

Left ventricular non-compaction and its cardiac and neurologic implications

Left ventricular non-compaction, also known as left ventricular hypertrabeculation (LVHT), is a morphological abnormality of the left ventricular myocardium, characterised by a meshwork of myocardial strings, interlacing, and orderless in arrangement. LVHT is most frequently located in the apex and the lateral wall and may occur with or without other congenital or acquired cardiac abnormalities. LVHT is believed to be congenital in the majority of the cases but may develop during life in single cases (acquired LVHT). Congenital LVHT is believed to result from defective late-stage embryonic development of the myocardial architecture. The pathogenesis of acquired LVHT remains speculative. LVHT is most frequently found on transthoracic echocardiography and cardiac MRI but may be visualised also with other imaging techniques. In the majority of the cases, LVHT is associated with hereditary cardiac, neuromuscular, non-cardiac/non-muscle disease, or chromosomal aberrations. In the majority of the cases, LVHT is complicated by ventricular arrhythmias, systolic dysfunction, cardiac embolism, or sudden cardiac death. LVHT per se does not require a specific treatment. Only in case of complications, such as ventricular arrhythmias, cardioembolism, or systolic dysfunction, adequate therapy is indicated. Though initially assessed as poor, the prognosis of LVHT has meanwhile improved, most likely due to the increased awareness for the abnormality and the timely administration of adequate therapy.     

Wolff-Parkinson-White syndrome and isolated left ventricular abnormal trabeculation as a manifestation of Leber's hereditary optic neuropathy

Myocardial thickening and isolated left ventricular abnormal trabeculation (ILVAT) have not been described in patients with Leber's hereditary optic neuropathy (LHON) before. Wolff-Parkinson-White syndrome, myocardial thickening and ILVAT were found by electrocardiogram, echocardiography and cardiac magnetic resonance imaging in a 48-year-old man with bilateral, severely reduced visual acuity since age 24 years, palpitations since age 43 years and lower limb muscle cramps since age 47 years. Because ILVAT is frequently associated with respiratory chain disorders, neurological investigations were initiated, revealing the primary LHON mutation G3460A in lymphocytic mitochondrial DNA. On the basis of the clinical and genetic data, LHON was diagnosed in the index patient, but also in the patient's brother who showed ILVAT as well. Wolff-Parkinson-White syndrome, myocardial thickening and ILVAT may be rare manifestations of LHON.     

Neuromuscular implications in left ventricular hypertrabeculation/noncompaction

This review focuses on recent advances in the association between left ventricular hypertrabeculation/noncompaction (LVHT), a form of unclassified cardiomyopathy, and neuromuscular disorders (NMD). So far, LVHT has been found in single patients with dystrophinopathy, dystrobrevinopathy, laminopathy, zaspopathy, myotonic dystrophy, infantile glycogenosis type II (Pompe's disease), myoadenylate-deaminase deficiency, mitochondriopathy, Barth syndrome, Friedreich ataxia, and Charcot–Marie–Tooth disease. Most frequently LVHT is found in patients with Barth syndrome and mitochondrial disorders. The prevalence of LVHT in NMD patients is not known. On the contrary, NMD can be detected in up to four fifths of the patients with LVHT. Because LVHT is associated with an increased risk of rhythm abnormalities and heart failure, it is essential to detect LVHT as soon as possible. Because of adequate therapeutic options, all patients with NMD should undergo a comprehensive cardiological examination as soon as their neurological diagnosis is established. In reverse, all patients with LVHT should undergo a comprehensive neurological investigation following the detection of LVHT.     

Left ventricular hypertrabeculation/noncompaction and neuromuscular disorders in idiopathic dilated cardiomyopathy

OBJECTIVE: Our aim was to assess 1) the association of idiopathic dilative cardiomyopathy (IDC) and left ventricular hypertrabeculation/noncompaction (LVHT), 2) the use of cardiac magnetic resonance imaging (CMRI) in IDC and 3) the association of IDC and neuromuscular disorders (NMD). METHODS: Patients in whom coronary heart disease had been excluded by coronary angiography and whose left ventricular end diastolic diameter was > 59 mm and fractional shortening < 25% with no other causes of cardiac dysfunction, were invited to participate. RESULTS: Among 25 patients, 18 refused CMRI (claustrophobia n = 13, inability to lie flat n = 5), thus 7 patients (2 female, 47-66 years) were included. LVHT was found in 5/7 cases. In 4/5 patients who were neurologically investigated, a NMD was found. In 2/7 cases echocardiography failed to visualise the ventricular apex. CONCLUSIONS: Patients with IDC should be investigated neurologically. In IDC patients with poor echocardiographic quality CMRI should be applied.     

Age-dependency of cardiac and neuromuscular findings in left ventricular noncompaction

BACKGROUND: Left ventricular hypertrabeculation/noncompaction (LVHT) is a cardiac abnormality characterized by prominent trabeculations and intertrabecular recesses, and frequently associated with neuromuscular disorders (NMD). Initially described in children and young adults, LVHT has been found also in elderly. Aim of the study was to assess the age-dependency of clinical, electrocardiographic (ECG) and echocardiographic findings, and whether they differ according to the neurologic diagnosis. METHODS AND RESULTS: In 86 patients LVHT was diagnosed echocardiographically between June 1995 and December 2004 (65 male, median age 52 years, range 14-94). All patients underwent a baseline cardiologic investigation and were invited for a neurologic investigation. A specific NMD was diagnosed in 21 (metabolic myopathy, n = 14; Leber's hereditary optic neuropathy, n = 3; myotonic dystrophy, n = 2; Becker muscular dystrophy, n = 1; Duchenne muscular dystrophy, n = 1), a NMD of unknown etiology in 32. The neurologic investigation was normal in 13 and was refused by 20 patients. Patients above median age had more often heart failure (43% versus 95%, p < 0.02) and valvular abnormalities (71% versus 36%, p < 0.02) than below median age. Patients >71 years had more often exertional dyspnoea (39% versus 81%, p < 0.02), left bundle branch block (9% versus 38%, p = 0.031), larger left-ventricular enddiastolic diameters (68 versus 60 mm, p < 0.02) and a lower left-ventricular fractional shortening than patients <34 years (18% versus 29%, p < 0.02). No age-dependency was detected regarding location and extension of LVHT and the neurologic diagnosis. CONCLUSION: There is no age-dependent typical pattern of LVHT regarding clinical, echocardiographic and neurologic findings. Echocardiographers should be aware of this cardiac abnormality when investigating patients of any age.     

Cardiac involvement in facioscapulohumeral muscular dystrophy

Cardiac involvement (CI) in form of myocardial thickening in a patient with genetically confirmed facioscapulohumeral muscular dystrophy (FSHMD) has not been reported. The patient is a 50-year-old male with a tandem repeat size of 17 and 14 kb in the D4Z4 locus on chromosome 4q35. The clinical cardiologic investigation was normal. Blood pressure was 150/90 mm Hg. Funduscopy, 24-hour ambulatory ECG, and 24-hour blood pressure monitoring were normal. ECG showed incomplete right bundle branch block, ST elevation in V2-V4, tall T waves in V3-V5, and hypertrophy signs. Echocardiography revealed left ventricular myocardial thickening of the posterior wall (11.7 mm) and the septum (15.5 mm). In conclusion, CI in genetically confirmed FSHMD may manifest not only as ECG abnormalities but also as left ventricular myocardial thickening.     

Cardiac and neuromuscular implications of left bundle branch block in left ventricular hypertrabeculation/noncompaction

BACKGROUND:

Left bundle branch block (LBB) is frequently found in left ventricular hypertrabeculation/noncompaction (LVHT).

OBJECTIVES:

To compare LVHT patients with and without LBB regarding LVHT location and extension, left ventricular function, symptoms, electrocardiographic findings, prevalence of neuromuscular disorders (NMDs) and mortality during follow-up.

METHODS:

The charts of patients who underwent transthoracic echocardiographic examination at the Krankenanstalt Rudolfstiftung (Wien, Austria) between June 1995 and November 2006 were examined.

RESULTS:

LVHT was diagnosed in 102 patients (30 women) with a mean (± SD) age of 53±16 years (range 14 to 94 years). A specific NMD was diagnosed in 21 patients and an NMD of unknown etiology was diagnosed in 47. The neurological investigation was normal in 14 patients and 20 patients refused the investigation. The 24 patients with LBB were older (61 versus 51 years of age; P<0.01), and suffered from exertional dyspnea (96% versus 59%; P<0.01) and heart failure (79% versus 46%; P<0.01) more often than patients without LBB. LBB patients had less frequent tall QRS complexes (8% versus 47%; P<0.01) and ST-T wave abnormalities (4% versus 50%; P<0.01) than patients without LBB. Patients with LBB had a larger left ventricular end-diastolic diameter (73 mm versus 61 mm; P<0.01), worse left ventricular fractional shortening (15% versus 26%; P<0.01) and more extensive LVHT (1.8 versus 1.5 ventricular segments; P<0.05). The prevalence of NMDs did not differ between patients with and without LBB. Survival did not differ between patients with and without LBB during follow-up.

CONCLUSIONS:

LBB is associated with increased age, decreased systolic function and increased extension of LVHT. Whether LBB is a prognostic factor in LVHT remains speculative.     

Noncompaction and neuromuscular disease with positive troponin-T in a nonagenerian

In a 94-year-old male with a history of atrial fibrillation, aortic stenosis, heart failure, apical thrombus, arterial hypertension, aneurysm of the abdominal aorta, and a urinary bladder carcinoma, cardiologic investigations revealed pulmonary rales, enlarged heart, absolute arrhythmia, and positive troponin-, myocardial thickening, enlarged cardiac cavities, hypocontractility, aortic stenosis, slight aortic insufficiency, severe mitral insufficiency, and surprisingly left ventricular hypertrabeculation. Upon neurological investigations, a polyneuropathy was suspected but a myopathy not completely excluded. The presented case shows that LVHT occurs also in nonagenarians and is associated with neuromuscular disease and positive troponin-T, in the absence of ischemic heart disease or severe renal failure. The cause of troponin-T-positivity remains multi-factorial.     

Severe dilated cardiomyopathy and quadriceps myopathy due to lamin A/C gene mutation: a phenotypic study

This study reports a family affected by a new phenotype associated with dilated cardiomyopathy and quadriceps myopathy. METHODS: 29 family members underwent a physical and neurological examination, including an electromyogram and biopsy of muscle abnormalities. A cardiac examination was performed in all subjects. RESULTS: The family pedigree (n=72) demonstrated that transmission was autosomal dominant. Eleven subjects had cardiac involvement, only four had quadriceps muscle involvement. Cardiac impairment preceded neurological involvement. The mean age for neurological involvement was 44+/-0.8 years (range 43-45) and cardiac involvement was 37+/-7.9 years (range: 24-45). Cardiac involvement consisted of: hypokinetic dilated cardiomyopathy (64%); atrial fibrillation (100%); ventricular arrhythmias (64%); impaired conduction with bundle branch or complete atrio ventricular block (73%). Four patients required pacemakers and anti arrhythmic therapies. Four patients died: two of refractory heart failure and two of sudden death; two patients were resuscitated following cardiac arrest. Three patients required a prophylactic implantable cardiac defibrillator (ICD). Muscle morphological abnormalities were characterized by a variable number of fibers with rimmed vacuoles. The quadriceps deteriorated progressively without impairment of other muscles. Genotypic study showed a lamin A/C gene mutation. CONCLUSIONS: This family was affected by a new phenotype composed of an autosomal dominant severe dilated cardiomyopathy with conduction defects or arrhythmias and quadriceps myopathy. Cardiac abnormalities preceded neuromuscular disorders and defined the prognosis of this disease.     

Left ventricular remodelling: common process in patients with different primary myocardial disorders

Currently the problem of left ventricular remodelling in the early and late stages after myocardial infarction are under intense study. Studies of the role of remodelling of the left ventricle in patients with long-term arterial hypertension have been recently initiated. The purpose of this investigation was to study whether left ventricular remodelling is common for different primary myocardial disorders. The study population consisted of 212 patients with primary myocardial lesions (121 with dilated cardiomyopathy, 45 with chronic myocarditis and 46 with prolonged damage of the myocardium with alcohol; 196 male and 16 female, mean age 42.6+/-11.3 years) and 32 age matched normal subjects (24 male and eight female). Cardiac catheterization for ventriculography and coronary angiography was performed in all subjects for detection of left ventricular haemodynamics, including chamber volume and shape at end-systole and end-diastole. Worsening of heart failure was associated with a progressive enlargement of the left ventricle, with increases in end-systolic left ventricular wall stress, that lead to increases in left ventricular muscle mass, alteration of left ventricular geometry from a more ellipsoid to a more spherical shape and a progressive decrease of relative wall thickness index that reflects inadequate enlargement of the ventricular chamber in comparison with the increase in muscle mass. This process of left ventricular remodelling was common to all the primary myocardial disorders studied. Thus, regardless of the different etiological nature, most primary myocardial disorders show a similar left ventricular remodelling process suggesting common mechanisms for the development of chronic heart failure.     

Cardiologic and neuromuscular co-morbidity influences mortality of patients with left ventricular hypertrabeculation/noncompaction: comparison with the Austrian general population

OBJECTIVE: Left ventricular hypertrabeculation/noncompaction (LVHT) is characterized by prominent trabeculations and intertrabecular recesses. LVHT patients suffer from heart failure, arrhythmias, chest pain and neuromuscular disorders (NMD). Data about long-term prognosis of LVHT are controversial. The aim of the study was to compare the mortality of LVHT patients with that of the Austrian general population and to assess which clinical and echocardiographic parameters influence mortality, and if mortality differs between patients with and without NMD. METHODS AND RESULTS: In 86 patients LVHT was diagnosed echocardiographically between June 1995 and December 2004 (21 women, mean age 52 +/- 14, range 14 - 94 years). A specific NMD was diagnosed in 21, a NMD of unknown aetiology in 33, the neurologic investigation was normal in 13 and 19 patients refused examination. During a mean follow-up of 51 months (range 3 - 106 months) the mortality rate was 5.3%/year. Compared with the lifetable from the Austrian general population and considering the sex, the standardized mortality ratio (SMR) of LVHT patients was 5.584 (95% CI 3.562-8.754, p = 0.000). The SMR was high in LVHT patients with NMD of unknown aetiology, who refused the neurologic investigation, with heart failure, diabetes mellitus, syncope, ventricular ectopic beats, pathologic Q waves, left anterior hemiblock, atrial fibrillation and low-voltage ECG. Patients with more extensive LVHT had a high SMR. CONCLUSIONS: Mortality in LVHT patients is higher than in the general population and cardiac and neurologic morbidity is the presumed cause for the increased mortality.     

Cardiac resynchronization therapy in left ventricular hypertrabeculation/non-compaction and myopathy.

AIMS: Little is known how patients with left ventricular hypertrabeculation/non-compaction (LVHT) and heart failure respond to cardiac resynchronization therapy (CRT). METHODS AND RESULTS: Included in this retrospective study were 8/102 patients (3 female, age range 43-78 years), in whom LVHT was diagnosed and in whom a CRT system was implanted. All eight patients were investigated neurologically and in seven of them a myopathy was found. The mean follow-up after CRT implantation was 39 (4-68) months. All patients improved by one or more New York Heart Association (NYHA) classes, and two by two NYHA classes. The left ventricular end-diastolic diameter decreased by < or =5% in 2 patients, by 6-10% in 3 patients, by 12% in 1 patient, and by >30% in 2 patients. The left ventricular systolic function, as assessed by the fractional shortening, did not change in 2 patients, increased by 10% in 2 patients, by 59% in 1 patient, doubled in 2 patients, and showed a five-fold increase in 1 patient. Two patients died during follow-up. CONCLUSION: CRT by biventricular pacing in LVHT, heart failure, and myopathy leads to improvement in functional capacity in all patients and improvement of systolic function in half of the patients. The weak response of LVHT patients to CRT may be due to inappropriate selection or comorbidities, in particular, neuromuscular disorders.