Left ventricular hypertrabeculation/noncompaction (LVHT) is diagnosed in all ages and is frequently associated with neuromuscular disorders (NMDs). The aim of the study was to compare patients with LVHT depending on age at diagnosis. Included were 232 patients with LVHT (72 women, mean age 52 ± 17 years) diagnosed from 1995 to 2014 at 1 echocardiographic laboratory. In 2014, their survival was assessed. Seventy-six percent of the patients were neurologically investigated, revealing specific NMDs in 18%, unspecific NMDs in 60%, and normal findings in 22%. Forty-five patients (19%) received electronic devices: implantable cardioverter-defibrillators in 26 patients, combined with cardiac resynchronization systems (n = 14) or an antibradycardic pacemaker (n = 1); antibradycardic pacemakers (n = 8); cardiac resynchronization systems (n = 4); implantable loop recorders (n = 4); life vests (n = 2); and a left ventricular assist device as a bridge to transplantation (n = 1). During 72-month follow-up, mortality was 4.9% per year. In younger age groups, more patients were referred for syncope or palpitations, whereas in older age groups, more patients were referred for heart failure. Classic cardiovascular risk factors such as hypertension and diabetes, as well as coronary artery stenosis, were rare in the young age groups but were more prevalent in older age groups. Differences between age groups were found regarding cardiac symptoms, NMDs, electrocardiographic findings, rate of device implantation, and mortality but not in location and extension of LVHT. None of the neurologically investigated patients ≥70 years of age was neurologically normal. Prevalence of heart failure, electrocardiographic abnormalities, and mortality were highest in the oldest age group. In conclusion, LVHT must be considered as an echocardiographic diagnosis in all age groups. The morphologic pattern of LVHT is similar, whereas clinical manifestations and prognosis are variable among age groups.
Left ventricular hypertrabeculation/noncompaction (LVHT) is a cardiac abnormality of unknown origin characterized by prominent trabeculations and intertrabecular recesses within the left ventricle. Different terms, such as “spongy myocardium,” “persisting sinusoids,” and “noncompaction cardiomyopathy,” are used to denote the abnormality. We prefer the term “LVHT” because it is a pure description of the morphology. LVHT is detected mainly by echocardiography but may be occasionally detected by cardiac computed tomography, ventriculography, or magnetic resonance imaging. Initially described in children and young adults, LVHT has subsequently been found in elderly subjects as well ( Table 1 ). If systematically screened, LVHT is associated with neuromuscular disorders (NMDs) in most cases. There are indications that the presence or absence of NMDs influences the prognosis of patients with LVHT. Little is known regarding whether indications for echocardiography, cardiac and neurologic findings, and prognosis differ between young and old age groups. The aim of this study, in the largest reported and longest observed cohort of patients with LVHT to date, was to compare clinical and neurologic findings in patients with LVHT depending on age at diagnosis.
| Author | Kawasaki et al | Murphy et al | Aras et al | Lofiego et al | Caliskan et al | Correia et al | Enriquez et al | Greutmann et al | Habib et al | Kimura et al | Present study |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Year of publication | 2005 | 2005 | 2006 | 2007 | 2011 | 2011 | 2011 | 2011 | 2011 | 2013 | 2014 |
| Cases | 10 | 45 | 67 | 65 | 77 | 20 | 15 | 132 | 105 | 35 | 232 |
| Female | 20% | 38% | 34% | NR | 52% | 35% | 60% | 65% | 34% | 0% | 31% |
| Age (years) | 50 | 37 | 41 | 45 | 40 | 53 | 52 | 41 | 45 | 24 | 52 |
| AF ∗ | 0 | 7% | 12% | 2% | 9% | 25% | 20% | 14% | 6% | 0 | 16% |
| NYHA III/IV | NR | 36% | 30% | 32% | 30% | 10% | 40% | 35% | 47% | NR | 36% |
| LVEDD † (mm) | NR | 58 | 58 | 67 | 60 | 58 | 66 | 34 ∗ | 63 | 51 | 60 |
| Follow up (months) | 26 | 46 | 30 | 46 | 26 | 12 | 19 | 32 | 28 | 46 | 72 |
| Mortality/year | 0 | 0.5% | 6% | 3% | 2% | 5% | 0 | NR | 5% | 10% | 5% |
| Deaths | 0 | 1 | 10 | 7 | 4 | 1 | 0 | 21 | 12 | NR | 68 |
| Heart failure | 0 | 0 | 30% | 43% | 75% | 100% | 0 | 52% | 83% | NR | 28% |
| Sudden death | 0 | 100% | 60% | 43% | 0 | 0 | 0 | 48% | 8% | NR | 13% |
| Others | 0 | 0 | 10% ‡ | 14% § | 25% || | 0 | 0 | NR | 8% ¶ | NR | 59% # |
† left ventricular enddiastolic diameter.
# pneumonia (n = 11), stroke (n = 7), malignancy (n = 7), sepsis (n = 5), liver cirrhosis (n = 4), pulmonary embolism (n = 3), renal failure (n = 2), progressive multifocal leukencephalopathy (n = 1).
Methods
Included were all patients in whom LVHT was diagnosed in the echocardiography laboratory of Krankenanstalt Rudolfstiftung from June 1995 and June 2014. For the diagnosis of LVHT, end-systolic as well as end-diastolic images were used. Two-dimensional and Doppler echocardiographic criteria for the diagnosis of LVHT were >3 trabeculations protruding from the left ventricular wall, apically to the papillary muscles, visible in 1 echocardiographic image plane at end-diastole; trabeculations forming the noncompacted part of a 2-layered myocardial structure, best visible at end-systole; and intertrabecular spaces perfused from the ventricular cavity, as visualized on color Doppler imaging. Trabeculations were defined as structures moving synchronously with the ventricular contractions, which are distinct from ventricular bands, false tendons, and prominent papillary muscles. The location of LVHT was assessed and categorized as apical if it involved the left ventricular apex and as anterior, lateral, or posterior if it involved the anterior, lateral, or posterior part of the left ventricular wall. The diagnostic criteria remained the same during the study period, and all echocardiographic investigations were performed by 3 of the authors (CS, GB, and MG) and jointly reviewed by the same 3 authors.
All patients underwent baseline cardiologic examinations during which they were asked for their medical histories and cardiovascular symptoms and their duration. A clinical examination was carried out, and a 12-lead electrocardiogram was recorded. Systematic family screening was performed only in a subgroup of the patients.
All patients were invited for a neurologic investigation comprising history, a clinical neurologic examination, and instrumental investigations if NMDs were suspected. An NMD was diagnosed if history or clinical or instrumental findings indicated the presence of an NMD. NMDs were assessed as “specific” if a definite diagnosis could be established. In cases in which the neurological investigations suggested the presence of NMDs but could not detect a specific cause, NMDs of unknown origin were diagnosed.
Pharmacotherapy and the decision to implant any cardiac electronic devices or to refer for cardiac transplantation were carried out by the treating physicians and not according to any protocol. In July 2014, patients or their treating physicians were contacted by telephone. Vital status was assessed. If a patient was deceased, the cause of death was registered. Additionally, the computer information system of all community hospitals in Vienna was screened for information about the patients.
For statistical analysis, age-group comparisons for differences of mean values from noncategorical data were carried out using Student’s t tests. Categorical data were analyzed using 2-sided Fisher’s exact tests. All statistical analyses were performed using the statistical software package R version 3.0.3.
Results
During the study period, 63,364 transthoracic echocardiographic examinations were carried out in the echocardiographic laboratory of Krankenanstalt Rudolfstiftung. LVHT was diagnosed in 232 patients (72 women, mean age 52 ± 17 years, range 13 to 93). The prevalence of LVHT was 0.37%. Data from this cohort have been published previously. Four patients were African blacks, 5 were from Asia (Japan, Vietnam, India, and the Philippines) and the remaining were Caucasians. Echocardiographic diagnoses of LVHT were established in 56% of patients during their hospitalizations; in the remaining patients, diagnoses were established on an outpatient basis. In all age groups, we found a preponderance of men ( Table 2 ). The referral pattern varied between age groups ( Table 2 ): in younger age groups, more patients were referred for syncope or palpitations, whereas in older age groups, more patients were referred for heart failure. The high frequency of “other” referral reasons for echocardiography in the youngest age group was due to cases referred for to family screening because of relatives with LVHT or evaluation of heart murmurs.
| Characteristic | All patients (n=232) | <30 years (n=24) | 30-39 years (n=33) | 40-49 years (n=42) | 50-59 years (n=53) | 60-69 years (n=42) | 70+ years (n=38) |
|---|---|---|---|---|---|---|---|
| Age (years) mean | 52±17 | 24±5 | 35±3 | 44±3 | 54±3 | 64±3 | 77±5 |
| Female | 72 (31%) | 8 (33%) | 10 (30%) | 17 (41%) | 10 (19%)* | 14 (33%) | 13 (34%) |
| Outpatients | 101 (44%) | 15 (63%) | 17 (52%) | 21 (50%) | 30 (57%)* | 13 (31%) | 5 (13%)*** |
| Referral reasons for echocardiography | |||||||
| Angina pectoris | 39 (17%) | 4 (16%) | 4 (12%) | 7 (17%) | 15 (28%)* | 6 (13%) | 3 (8%) |
| Heart failure | 126 (54%) | 4 (17%)*** | 13 (39%) | 18 (43%) | 27 (51%) | 32 (76%)** | 32 (84%)*** |
| Myopathy | 13 (6%) | 3 (13%) | 3 (9%) | 3 (7%) | 3 (6%) | 0 | 1 (3%) |
| Syncope | 23 (10%) | 5 (21%) | 7 (21%)* | 8 (19%)* | 1 (2%)* | 1 (2%) | 1 (3%) |
| Others ∗ | 31 (13%) | 8 (33%)** | 6 (18%) | 6 (14%) | 7 (13%) | 3 (7%) | 1 (3%)* |
| Neurologic diagnosis | |||||||
| Specific NMD | 31 (13%) | 4 (17%) ‡ | 6 (18%) § | 9 (21%) || | 5 (9%) ¶ | 3 (7%) # | 4 (11%) ∗∗ |
| NMD of unknown etiology | 106 (46%) | 8 (33%) | 10 (30%) | 12 (29%)* | 31 (59%)* | 19 (45%) | 26 (68%)** |
| Neurologically normal | 39 (17%) | 5 (21%) | 7 (21%) | 7 (17%) | 9 (17%) | 11 (26%) | 0*** |
| Neurol. not investigated | 56 (24%) | 7 (29%) | 10 (30%) | 14 (33%) | 8 (15%) | 9 (21%) | 8 (21%) |
| Exertional dyspnea | 140 (60%) | 7 (29%)** | 15 (46%) | 23 (55%) | 31 (59%) | 32 (76%)* | 32 (84%)*** |
| Angina pectoris | 58 (25%) | 4 (17%) | 9 (27%) | 11 (26%) | 12 (23%) | 16 (38%)* | 6 (16%) |
| Edema | 49 (21%) | 1 (4%)* | 7 (21%) | 6 (14%) | 10 (19%) | 8 (19%) | 17 (45%)*** |
| Palpitations/vertigo/syncope | 68 (29%) | 7 (29%) | 13 (39%) | 17 (41%) | 9 (17%)* | 12 (29%) | 10 (26%) |
| Diabetes mellitus | 41 (18%) | 1 (4%) | 1 (3%)* | 3 (7%) | 12 (23%) | 13 (31%)* | 11 (29%) |
| Arterial hypertension | 96 (41%) | 3 (13%)** | 4 (12%)*** | 13 (31%) | 30 (56%)* | 25 (60%)** | 21 (55%) |
| Heart failure | 144 (62%) | 6 (25%)*** | 15 (46%) | 22 (52%) | 34 (64%) | 35 (83%)** | 32 (84%)** |
| NYHA I | 15 (7%) | 0 (0) | 1 (3%) | 3 (7%) | 6 (11%) | 4 (10%) | 1 (3%) |
| NYHA II | 45 (19%) | 3 (13%) | 8 (24%) | 6 (14%) | 10 (19%) | 9 (21%) | 9 (24%) |
| NYHA III | 47 (20%) | 3 (13%) | 2 (6%)* | 6 (14%) | 9 (17%) | 12 (29%) | 15 (40%)** |
| NYHA IV | 37 (16%) | 0* | 4 (12%) | 7 (14%) | 9 (17%) | 10 (24%) | 7 (18%) |
| Asymptomatic † | 29 (13%) | 9 (38%)*** | 6 (18%) | 3 (7%) | 8 (15%) | 2 (5%) | 1 (3%) |
| Coronary angiography performed | 102 (44%) | 2 (8%)*** | 9 (27%)* | 23 (55%) | 30 (57%)* | 21 (50%) | 17 (45%) |
| Coronary artery stenoses | 27 (12%) | 0 *** | 3 (9%) | 0** | 8 (15%) | 6 (14%) | 10 (26%)** |
| Neither coronary artery stenosis nor hypertension | 42 (18%) | 1 (4%) | 6 (18%) | 16 (38%)*** | 12 (23%) | 5 (12%) | 3 (8%) |
∗ family screening, source for embolism, heart murmur.
† asymptomatic = absence of the following symptoms: dyspnea, angina pectoris, palpitations, syncope, vertigo and edema.
‡ Lebers hereditary optic neuropathy (n = 1), myotonic dystrophy (n = 1), Duchenne muscular dystrophy (n = 1), Becker muscular dystrophy (n = 1).
§ Becker muscular dystrophy (n = 1), metabolic myopathy (n = 5).
|| Lebers hereditary optic neuropathy (n = 2), myotonic dystrophy (n = 3), metabolic myopathy (n = 3), MYH7 myopathy (n = 1).
∗∗ metabolic myopathy (n = 3), post-poliomyelitis syndrome (n = 1).
One hundred seventy-six patients (76%) were neurologically investigated. The remaining 56 patients (24%) refused or were not investigated for organizational reasons. Of the investigated patients, specific NMDs were diagnosed in 31 patients (18%): metabolic myopathy (n = 19), Leber’s hereditary optic neuropathy (n = 3), myotonic dystrophy (n = 4), Becker muscular dystrophy (n = 2), postpoliomyelitis syndrome (n = 1), Duchenne muscular dystrophy (n = 1), and MYH7 myopathy (n = 1). In patients with metabolic myopathy, muscle biopsy results were indicative for that disease, but no further diagnostic measures were carried out. In 106 patients (60%), the neurologic findings were indicative of neuropathy or myopathy, but no specific diagnosis could be obtained and thus NMDs of unknown origin were diagnosed. The severity of symptoms of the patients’ NMDs was variable and ranged from asymptomatic to severely disabled and wheelchair bound. The neurologic results were normal in 39 patients (22%). LVHT was familial in 10 patients (specific NMDs, n = 6; NMDs of unknown origin, n = 2; neurologically normal, n = 2).
Whereas specific NMDs were evenly distributed between the age groups, more patients among the elderly were diagnosed with NMDs of unknown origin ( Table 2 ). Of note, none of the neurologically investigated patients ≥70 years of age was neurologically normal.
Arterial hypertension and diabetes were found more frequently in elderly than in young patients ( Table 2 ). Whereas the prevalence of angina pectoris was similar, heart failure was more frequent in elderly than younger patients.
The most frequent electrocardiographic (ECG) abnormalities in all age groups were ST/T-wave abnormalities. Elderly patients had more frequent left bundle branch block, atrial fibrillation, a larger number of ECG abnormalities, broader QRS complexes, and longer corrected QT intervals than younger patients ( Table 3 ).
| Characteristic | All patients (n=232) | <30 years (n=24) | 30-39 years (n=33) | 40-49 years (n=42) | 50-59 years (n=53) | 60-69 years (n=42) | 70+ years (n=38) |
|---|---|---|---|---|---|---|---|
| Tall QRS complex | 70 (30%) | 6 (25%) | 14 (42%) | 14 (33%) | 19 (36%) | 10 (24%) | 7 (18%) |
| ST/T wave abnormality | 115 (50%) | 10 (41%) | 14 (42%) | 19 (45%) | 23 (43%) | 21 (50%) | 21 (55%) |
| Left bundle branch block | 38 (16%) | 1 (4%) | 4 (12%) | 8 (19%) | 2 (4%)** | 9 (21%) | 14 (37%)*** |
| Ventricular ectopic beats | 19 (8%) | 1 (4%) | 3 (9%) | 4 (10%) | 3 (6%) | 5 (12%) | 3 (8%) |
| Pathologic Q waves | 27 (12%) | 1 (4%) | 1 (3%) | 7 (17%) | 8 (15%) | 2 (5%) | 8 (21%) |
| Pathologic Q waves without coronary artery stenosis | 7 (3%) | 0 | 1 (3%) | 4 (10%) | 1 (2%) | 0 | 1 (2,6%) |
| Atrial fibrillation | 38 (16%) | 2 (8%) | 0** | 4 (10%) | 7 (13%) | 10 (24%) | 15 (40%)*** |
| Left anterior hemiblock | 25 (11%) | 1 (4%) | 0* | 6 (14%) | 6 (11%) | 6 (14%) | 6 (16%) |
| Right bundle branch block | 12 (5%) | 2 (8%) | 1 (3%) | 2 (5%) | 2 (4%) | 2 (5%) | 3 (8%) |
| Wolff-Parkinson-White-syndrome | 4 (2%) | 0 | 2 (6%) | 2 (5%) | 0 | 0 | 0 |
| Low voltage | 11 (5%) | 1 (4%) | 2 (6%) | 2 (5%) | 3 (6%) | 2 (5%) | 1 (3%) |
| Sinustachycardia | 18 (8%) | 2 (8%) | 2 (6%) | 6 (14%) | 5 (9%) | 1 (2%) | 2 (5%) |
| Number of ECG abnormalities, mean | 1.7±1.4 | 1.3±1.3 | 1.2±1.0** | 1.8±1.3 | 1.8±1.5 | 1.8±1.3 | 2.4±1.4** |
| No ECG abnormality | 54 (23%) | 11 (46%)** | 11 (33%) | 8 (19%) | 13 (25%) | 7 (16%) | 4 (11%) |
| 1 ECG abnormality | 45 (19%) | 1 (4%) | 6 (18%) | 9 (21%) | 9 (17%) | 13 (31%) | 7 (18%) |
| 2 ECG abnormalities | 75 (32%) | 8 (33%) | 14 (42%) | 16 (38%) | 20 (38%) | 9 (21%) | 8 (21%) |
| 3+ ECG abnormalities | 58 (25%) | 4 (17%) | 2 (6%)** | 9 (21%) | 11 (21%) | 13 (31%) | 19 (50%)*** |
| PQ interval (ms), mean | 174±42 | 174±51 | 172±30 | 166±39 | 175±34 | 175±47 | 188±51 |
| QRS width (ms), mean | 93±38 | 82±38 | 80±27* | 93±46 | 81±25** | 108±39* | 110±38** |
| QTC interval (ms), mean | 426±54 | 401±50* | 403±44** | 443±66 | 420±45 | 445±57* | 433±48 |
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