Left Ventricular Hypertrabeculation/noncompaction Research Articles

Coronary Angiography in Patients With Left Ventricular Hypertrabeculation/Noncompaction.

Left ventricular hypertrabeculation/noncompaction (LVHT) is a cardiac abnormality of unknown pathogenesis, frequently associated with neuromuscular disorders. The relevance of coronary artery disease (CAD) in LVHT is largely unknown. This study aimed to assess the role of CAD as a prognostic marker in LVHT. Data from patients with LVHT were collected from an echocardiographic laboratory. The hospital information system was retrospectively screened for coronary angiography. The association of CAD with clinical, echocardiographic, and neurologic baseline parameters was assessed. End points were all-cause death and heart transplantation. A total of 154 patients (mean [SD] age, 57 [13.7] years; 31% female) who had undergone coronary angiography between 1995 and 2020 were included in the study. Coronary angiography disclosed CAD in 53 of 154 patients. Patients with CAD were older (mean [SD] age of, 64.2 [12.9] years vs 52.7 [12.4] years; P < .001); more frequently had angina pectoris (P = .05), diabetes (P = .002), and hypertension (P = .03); and more frequently had 3 or more electrocardiographic abnormalities (P = .04) than patients without CAD. During a median (IQR) follow-up period of 6.48 (2.44-11.20) years, 39% of patients reached an end point (death, n = 56; heart transplantation, n = 4). Mortality was 4.5% per year, and the rate of death or heart transplantation did not differ between patients with and without CAD (P = .26). Patients with 3-vessel disease had a worse prognosis than patients with 1- or 2-vessel disease (P = .046). In patients with LVHT, CAD does not appear to be associated with an increased rate of death or heart transplantation.

The relationship between takotsubo syndrome, left ventricular hypertrabeculation/noncompaction, neurologic and neuromuscular disorders.

Takotsubo syndrome (TTS) and left ventricular hypertrabeculation/noncompaction (LVHT) have in common that they are only diagnosed since 1990. Diagnostic criteria and prognosis of affected patients are still debated and the knowledge about etiology and pathogenesis of both disorders is limited. Both abnormalities are associated with neurologic and neuromuscular disorders (NMD). We summarize the data about the relationship between TTS, LVHT and NMD. We identified 8 case reports about the co-incidence of TTS and LVHT (6 females, 2 males, age 0-76 years). In 2/8 cases recurrent TTS occurred after 8 and 10 months. In most of the patients, LVHT was diagnosed together with TTS, thus, it cannot be assessed if LVHT was present since birth or developed during life-time. In one case, LVHT was absent in a previous echocardiogram, developed de novo during TTS, and disappeared after 3 months. In 4/8 patients follow-up were reported, and in all of them, regression or disappearance of LVHT was observed. NMD or psychiatric disorders were reported in 7/8 patients. We conclude -limited by the small number of cases-that patients with LVHT and TTS seem to be frequently associated with NMD and have a high risk of recurrence. LVHT seems to disappear after TTS, but it remains unclear whether trabeculations in fact regress or are still present, but not more visible because of a decrease in left ventricular size resulting in smaller spaces between the trabeculations. Patients with LVHT and TTS require long-term follow-up to assess any changes of these abnormalities over time.

Neuromuscular comorbidity, atrial fibrillation and left bundle branch block predict the prognosis of left ventricular hypertrabeculation/noncompaction

Abstract Background The prognosis of patients with left ventricular hypertrabeculation/noncompaction (LVHT) is controversially assessed. LVHT is frequently associated with neuromuscular disorders (NMDs). Aim of the study was to assess cardiac and neurological findings as predictors of mortality in LVHT-patients. Methods Included were patients with LVHT diagnosed between June 1995 and December 2019 in one echocardiographic laboratory. They underwent a baseline cardiologic examination and were invited for a neurological investigation. In January 2020, their survival status was assessed. Results LVHT was diagnosed in 310 patients (93 female, aged 53±18 years) with a prevalence of 0.4%/year. A neurologic investigation was performed in 205 patients (67%). A specific NMD was found in 33 of the investigated patients (16%), NMDs of unknown etiology in 123 (60%) and the neurological investigation was normal in 49 (24%) patients. During 86 months of follow-up, 59 patients received implanted electronic devices (cardioverter/defibrillator n=21, antibradycardic pacemakers n=11, cardiac resynchronization device/defibrillator n=22, cardiac resynchronization device n=4). During follow-up 105 patients died and 6 patients underwent heart transplantation. The mortality was 4.7%/year. By multivariate analysis, the following baseline parameters were identified as predictors of mortality: increased age (p=0.0005), inpatient-status when LVHT was diagnosed (p=0.0050), presence of a specific NMD (p=0.0187) or NMD of unknown etiology (p=0.0052), atrial fibrillation (p=0.0007) and left bundle branch block (p=0.0168). Conclusions LVHT patients should be systematically investigated neurologically since neurological comorbidity has a prognostic impact. Electrocardiographic abnormalities like atrial fibrillation and left bundle branch block should be considered when planning pharmacotherapy and device-therapy. It has to be assessed by prospective studies, which measures improve the prognosis of LVHT. Funding Acknowledgement Type of funding source: None

NT-pro-BNP in patients with left ventricular hypertrabeculation/non-compaction.

AimsLeft ventricular hypertrabeculation/non‐compaction (LVHT) is a cardiac abnormality of unknown pathogenesis and frequently associated with neuromuscular disorders. The N‐terminal fragment of the pro brain natriuretic peptide (NT‐pro‐BNP) is a prognostic marker in heart failure whose relevance in LVHT patients is largely unknown. The aim of the study was to assess the role of NT‐pro‐BNP levels as prognostic markers in LVHT.Methods and resultsData of LVHT patients were collected in a database from one echocardiographic laboratory since 1996. The hospital information system was screened for measurements of NT‐pro‐BNP levels, and their association with clinical and echocardiographic baseline parameters was retrospectively assessed. During follow‐up, the endpoints were death and heart transplantation. In 113 patients (median age 57 years, 24% women), data about NT‐pro‐BNP measurements were found, ranging from 8 to 121 152 (median 2029) ng/L. High NT‐pro‐BNP levels were associated with heart failure, valvular abnormalities, diabetes mellitus, hypertension, angina pectoris, number of LVHT‐affected segments, end‐diastolic diameter, and systolic dysfunction. During a follow‐up of 73 (±64; 0–237) months, 35% of the patients reached an endpoint. High NT‐pro‐BNP levels were associated with the occurrence of an endpoint (P < 0.001). By multivariate analysis, predictors for endpoints were increased age (P = 0.0025), atrial fibrillation (P = 0.0023), natural logarithm of NT‐pro‐BNP levels (P = 0.0073), diabetes mellitus (P = 0.014), and thromboembolic events before diagnosis (P = 0.0347).ConclusionsAlso in LVHT patients, high NT‐pro‐BNP levels are indicators for death and heart transplantation.

Usefulness of Neuromuscular Co-morbidity, Left Bundle Branch Block, and Atrial Fibrillation to Predict the Long-Term Prognosis of Left Ventricular Hypertrabeculation/Noncompaction

The prognosis of patients with left ventricular hypertrabeculation/noncompaction (LVHT) is assessed controversially. LVHT is associated with other cardiac abnormalities and with neuromuscular disorders (NMD). Aim of the study was to assess cardiac and neurological findings as predictors of mortality rate in adult LVHT-patients. Included were patients with LVHT diagnosed between 1995 and 2019 in 1 echocardiographic laboratory. Patients underwent a baseline cardiologic examination and were invited for a neurological investigation. In January 2020, their survival status was assessed. End points were death or heart transplantation. LVHT was diagnosed by echocardiography in 310 patients (93 female, aged 53 ± 18 years) with a prevalence of 0.4%/year. A neurologic investigation was performed in 205 patients (67%). A specific NMD was found in 33 (16%), NMD of unknown etiology in 123 (60%) and the neurological investigation was normal in 49 (24%) patients. During follow-up of 84 ± 71 months, 59 patients received electronic devices, 105 patients died, and 6 underwent heart transplantation. The mortality was 4.7%/year, the rate of heart transplantation/death 5%/year. By multivariate analysis, the following parameters were identified to elevate the risk of mortality/heart transplantation: increased age (p = 0.005), inpatient (p = 0.001), presence of a specific NMD (p = 0.0312) or NMD of unknown etiology (p = 0.0365), atrial fibrillation (p = 0.0000), ventricular premature complexes (p = 0.0053), exertional dyspnea (p = 0.0023), left bundle branch block (p = 0.0201), and LVHT of the posterior wall (p = 0.0158). In conclusion, LVHT patients should be systematically investigated neurologically since neurological co-morbidity has a prognostic impact.

Unproven genotype/phenotype correlation in any genetic defect associated with non-compaction

We appreciated to read the report by Klaassen et al. [1] about the detection of MYH7, ACTC, and TNNT2-mutations in 11 of 63 patients and 13 relatives with left-ventricular hypertrabeculation/noncompaction (LVHT). The study raises a number of comments and concerns. Though LVHT is associated with a large number of different genetic defects [2,3codorn18], a causal relation between any of these genetic defects and LVHT has never been proven. A strong argument against a causal relation is rare segregation of LVHT together with a mutation in a single family. To date LVHT has been associated with mutations in at least 30 different genes and &gt;20 different chromosomal abnormalities. To regard LVHT as only autosomal dominantly inherited [1] is not justified given its heterogeneous genetic background and the report of autosomal dominant, X-chromosomal, and maternal traits of inheritance.

New oral anticoagulants for thromboembolic risk from noncompaction?

With interest we read the article by Cevik et al. about a 62 years-old female who was diagnosed with left ventricular hypertrabeculation / noncompaction (LVHT) and multiple intra-ventricular thrombi, for which she received oral anticoagulation but died from multiorgan failure due to unknown cause [1]. We have the following concerns: Which was the cause of death in this patient? Were ventricular arrhythmias recorded before decease? Did systolic function deteriorate shortly before decease? Was there clinical evidence for cardioembolism? Did she develop an infectious disease before death? LVHT is not congenital in each case. A number of patients with acquired LVHT have been reported [2]. Were previous echocardiographies reviewed to confirm that LVHT was present already before diagnosis? Did the patient undergo cardiac MRI to confirm the diagnosis of LVHT?.

Unproven causal relation between a de novo NKX2.5 insertion and left ventricular noncompaction

In their article, Ouyong et al. reported about a three-generation family, of which three members carried a heterozygous 2bp insertion at c.512 from the translation start point in exon 2 of the NKX2.5 gene [1]. Mutations in the NKX2.5 have been shown to be associated with atrial septal defects (ASDs), congenital heart disease (CHD), and occasionally left-ventricular hypertrabeculation / noncompaction (LVHT) [2-4]. We have the following comments and concerns. Though three family members carried the mutation only one of them (III/2) presented with (LVHT). How do the authors explain this finding particularly with regard to the proposed causal relation between LVHT and the mutation? How to explain the interfamilial heterogeneity? Were family members not carrying the mutation also screened for LVHT? Since LVHT frequently occurs familiarly and since a causal relation between the mutation and LVHT remains unproven, LVHT might have been due to other causes. Since LVHT is frequently associated with neuromuscular disorders (NMDs) [5], it is worthwhile to investigate affected and non-affected family members for clinically manifesting or subclinical NMD. There is no comprehensive clinical description of the presented cases. Were there any indications for an extra-cardiac disease?

QT-prolongation and noncompaction

In a recent article, Szulik et al. reported about a 22 years old female with ventricular fibrillation, QT-prolongation, and left ventricular hypertrabeculation/noncompaction (LVHT) who died from hypoxic cerebral damage 5 days after admission [1]. We have the following comments and concerns. Patients with LVHT have a disposition for any type of cardiac arrhythmia [2,3]. This is why ventricular fibrillation not only could be due to hereditary long-QT syndrome but also due to LVHT. Ventricular fibrillation was either due to LVHT or a consequence of QT-prolongation. QT-prolongation is not unusual in LVHT and has been reported in several cases (table 1) [3-7]. LVHT has been also reported in association with long-QT-syndrome due to mutations in the KCNQ1 gene [8], in the KCNH2 gene [9], or due to an unidentified genetic defect (table 1) [10]. In a study of 105 patients with LVHT, the QT-interval increased during a mean follow up of 3.6y in 15 patients and normalized in 21 patients [11]. The increase was associated with the extension of LVHT and the presence of a neuromuscular disorder (NMD) [11].

Left ventricular hypertrabeculation/noncompaction, cardiac phenotype, and neuromuscular disorders.

The prognosis of patients with left ventricular hypertrabeculation/noncompaction (LVHT) and its association with neuromuscular disorders (NMDs) is acontroversial topic. The aim of this study was to assess whether the prognosis of LVHT patients is dependent on cardiac phenotype and the presence of NMDs. Consecutive patients who were diagnosed with LVHT between 1995 and 2016 were included in the study. Cardiac phenotype was classified according to the recommendations of the European Society of Cardiology as: "dilated" if the left ventricular end-diastolic diameter (LVEDD) was >57 mm and left ventricular fractional shortening (FS) was ≤25%; "hypertrophic" if LVEDD was ≤57 mm, FS > 25%, and left ventricular posterior wall (LVPWT) and interventricular septal thickness (IVST) were both >13 mm; "intermediate" if LVEDD was >57 mm and FS > 25% or if LVEDD was ≤57 mm and FS ≤ 25%; and "normal" if LVEDD was ≤57 mm, FS > 25%, and IVST and LVPWT ≤ 13 mm. Therapy was carried out by the treating physicians. LVHT was diagnosed in 273 patients (80females, 53 ± 16years). The phenotype was assessed as dilated in 46%, hypertrophic in 8%, intermediate in 17%, and normal in 29% of the patients. Of these patients, 72% underwent neurological examinations, and anNMD was found in 76%. Over aperiod of 7.4years (±5.7), 84patients died and sixunderwent cardiac transplantation. The highest mortality rate was observed in the dilated and the lowest in the hypertrophic cardiac phenotype groups. Among the dilated phenotype, mortality was higher in patients with than without NMDs. Patients with LVHT and dilated cardiac phenotype have aworse prognosis than patients with ahypertrophic or intermediate/normal cardiac phenotype, especially if they suffer from NMDs.

Revision of Echocardiographic Indications and Findings in Neurologically Ill Patients.

Background and Objective:Little is known about the general indications for echocardiography and the prevalence of abnormalities detected by echocardiography in patients who are referred from a neurological department. Left ventricular hypertrabeculation/noncompaction (LVHT) is associated with neuromuscular disorders and embolism. The aim of the study was to assess the indications for echocardiography in patients from a neurological department and to review the cine-loops of the examinations in order to assess the frequency of abnormal echocardiographic findings with special regard to LVHT.Methods and Results:Included were 126 patients, 58 females (mean age 65 years). Indications were stroke (84%), heart failure (6%), endocarditis (6%) and arrhythmia (3%). The most frequent abnormalities were impaired relaxation (71%) and left ventricular wall thickening (63%). Females were older (68 vs. 62 years, p = 0.0214) and more frequently had normally sized left ventricles than males (98 vs. 88%, p = 0.0376). Patients ≥66 years more frequently had stroke as an indication (91 vs. 77%, p = 0.05), showed a thickened myocardium (72 vs. 53%, p = 0.0272), valvular abnormalities (52 vs. 13%, p = 0.0000) and impaired relaxation (86 vs. 54%, p = 0.0001) than patients <66 years.LVHT was diagnosed in 3 patients; in one of them the diagnosis was already known. In 45% LVHT and in 38% left ventricular thrombus could neither be excluded nor established since the image quality was poor.Conclusion:Care should be taken to visualize the left ventricular apical regions when investigating patients referred from a neurologic department in order not to overlook LVHT and thrombi within the left ventricular apex.

Letter by Finsterer and Zarrouk-Mahjoub Regarding Article, “Combination of Whole Genome Sequencing, Linkage, and Functional Studies Implicates a Missense Mutation in Titin as a Cause of Autosomal Dominant Cardiomyopathy With Features of Left Ventricular Noncompaction”

With interest, we read the article by Hastings et al1 about a 3-generation family in whom 7 members carried the titin mutation p.A178D , and 5 (3 on echocardiography and 2 on cardiac magnetic resonance imaging [MRI]) had left ventricular hypertrabeculation/noncompaction (LVHT). We have the following comments and concerns. To date, a causal relation between mutations in any of the >40 genes and many chromosomal defects associated with LVHT and LVHT has never been proven. Arguments against a causal relation are that only a small number of patients with a certain mutation in any of these genes regarded as causative truly develop LVHT; …

Interdisciplinary management of left ventricular noncompaction in pregnancy using a wearable defibrillator

Introduction: Left ventricular hypertrabeculation/noncompaction (LVHT) is a cardiac abnormality of unknown etiology, characterized by extensive trabeculations of the left ventricular cavity and a two-layered structure of the left ventricular myocardium. LVHT is diagnosed in children and adults, mainly by echocardiography, and may be associated with heart failure, arrhythmias and embolic events. LVHT is no contraindication for pregnancy, however worsening of cardiac function and development of malignant arrhythmias has been described. Protection against malignant arrhythmias can be provided by implanted defibrillators (ICDs) or wearable defibrillators (Lifevest Firma Zoll). We present the first LVHT case with a lifevest during pregnancy.

Prevent Sudden Death in Carvajal Syndrome With Left Ventricular Hypertrabeculation/Noncompaction.

Dear Editor, With interest we read the article by Mohammadpour Ahranjani et al. about a nine-year-old girl with heart failure due to systolic dysfunction and left ventricular hypertrabeculation/noncompaction (LVHT) in whom the association with skin abnormalities led to the diagnosis of Caravajal syndrome (CS) (1). We have the following questions and concerns: mutations in the desmoplakin genes have been identified in some patients with CS. However, there are also CS-cases in whom no mutations of the desmoplakin gene have been found thus indicating genetic heterogeneity (2). It would be interesting to know if genetic studies were carried out in the presented patient. In the case report we miss information about the family history of the patient. It is only indicated that two cousins suffered also from skin lesions and it remains unclear if they were investigated by a cardiologist and dermatologist. Since CS seems to be autosomal recessively inherited it would be of interest if the patient’s parents were consanguineous and if other family members showed any cardiac, skin or hair anomalies. CS may also be inherited as an autosomal dominant disease. In these cases, dental anomalies have been found (2-6). Thus, information about dental anomalies in the presented patient or in her family would be of interest. Regarding the patient’s history, we would like to know if there were any other health problems during pregnancy or early childhood except the skin problems and about her intellectual development. It is mentioned that she was diagnosed with anemia at age 8 years, but the type of anemia and the therapy are not indicated. CS is characterized by woolly hair. We miss the description of the patient’s hair. CS manifests frequently with arrhythmias, even leading to sudden death (4-6). Thus, it would be of interest to get information about any electrocardiographic abnormalities and whether she had a history of syncope, vertigo or spells suggesting arrhythmia which are reported to precede sudden death (7). If carried out, results of 24-hour Holter monitoring and bicycle stress testing are of interest. Implantation of a defibrillator (ICD) is reported in patients with CS and we miss information if this was considered in the presented patient (3, 6). Application of a wearable defibrillator (live vest) could be an alternative to protect her from sudden death and to defer placement of an ICD, or implantation of a loop recorder to more effectively assess the risk of ventricular arrhythmias and sudden death and to support the indication for an ICD. The patient suffered from systolic dysfunction of the left ventricle. It would be of interest if the right ventricle did also show any abnormalities. CS associated with LVHT has been reported in only 3 cases (2, 5, 8). The location of LVHT within the left ventricle should be described more precisely and how it was differentiated from thrombi, papillary muscles, or aberrant bands. Since the presented echocardiograms date from the year 2012, recent follow-up data could be useful. It would be interesting to know if LVHT changed in size and degree, if left ventricular function improved and left ventricular diameter decreased after successful heart failure therapy. Since LVHT is frequently associated with neuromuscular disorders it would be of interest to know if the patient was investigated neurologically and if she had a family history of a neuromuscular disorder (9). In the end of the discussion, the authors state that “we need much more time for the follow-up, cannot conclude clearly about the prognosis...” (1). Although CS as well as LVHT are rare disorders, there are sufficient data which indicate that both diagnoses in children and young adults are associated with a high risk for sudden death (10). Thus, careful follow-up and protection from sudden death seem mandatory in the presented patient.

Postnatal Outcome of Fetal Left Ventricular Hypertrabeculation/Noncompaction.

Left ventricular hypertrabeculation/noncompaction (LVHT) is a cardiac abnormality of unknown etiology. Prenatal diagnosis of LVHT can be established by fetal echocardiography. A review of 106 published cases showed that 46 cases with prenatally diagnosed LVHT were alive 0.5-120months after birth. Since the course of cases with prenatally LVHT after publication is unknown, we aimed to collect follow-up-information. Information regarding vital status, cardiac and extracardiac morbidity was gathered by contacting the authors of the 46 cases. Fourteen of the 28 authors answered and gave information about 18 cases (six females, seven males, five gender-unknown, age 18months to 10years, mean follow-up 60months). No differences were found between the 18 cases with follow-up and the 28 cases without follow-up regarding age, gender, cardiac or extracardiac comorbidities, and interventions. Three of the 18 cases had died subsequently from heart failure, osteosarcoma, and enterocolitis, respectively. Mutations or chromosomal abnormalities were found in six of the seven examined patients, extracardiac abnormalities in nine patients. Three patients received a pacemaker because of complete AV block, and two patients underwent heart transplantation. Cardiac surgical or interventional procedures were carried out in four patients. None suffered from malignant arrhythmias or had a cardioverter-defibrillator implanted. Based on the limited information, there are indications that cases with fetal diagnosis of LVHT have a continuing morbidity and mortality, even if they receive appropriate care. Since fetal LVHT is frequently associated with genetic abnormalities, further research about survival and underlying genetic causes is needed.

Comment on "A Rare Case of Renal Infarct due to Noncompaction Cardiomyopathy: A Case Report and Literature Review".

With interest we read the article by Wats et al. about a 53-year-old female with left ventricular hypertrabeculation/noncompaction (LVHT) in whom renal infarction was attributed to LVHT [1]. We have the following comments and concerns.

Interobserver Agreement of the Echocardiographic Diagnosis of LV Hypertrabeculation/Noncompaction

ObjectivesThe aim of the study was to assess interobserver agreement (IOA) between 3 observers from 2 laboratories. BackgroundIOA of left ventricular hypertrabeculation/noncompaction (LVHT) in adults has only been studied within single echocardiographic laboratories. MethodsEchocardiographic recordings with and without LVHT were selected and anonymized. The “not-LVHT” cases were matched for age and systolic function. Each observer reviewed the recordings, blinded to the initial diagnosis and the other observers’ results. Pre-defined criteria for LVHT were: 1) >3 prominent trabeculae at end-diastole, distinct from papillary muscles, false tendons, or aberrant bands; 2) a noncompacted part of a 2-layered myocardial structure formed by these trabeculations; 3) a ratio of >2:1 of noncompacted to compacted layer at end-systole; and 4) perfusion of the intertrabecular spaces from the ventricular cavity. IOA was estimated using the kappa measure of concordance. ResultsCine-loops of 100 patients (42 women, ages 16 to 92 years), 50 from each center, and 51 with LVHT as the initial diagnosis, were reviewed. The left ventricular end-diastolic diameter was 32 to 78 mm, and ejection fraction, 4% to 88%. The observers agreed about presence (n = 29) or absence (n = 36) of LVHT and disagreed in 35 cases. Agreement was higher among the 2 observers from the same laboratory (kappa 0.793 [95% confidence interval (CI): 0.672 to 0.915]) than from different laboratories (kappa 0.628 [95% CI: 0.472 to 0.784], kappa 0.669 [95% CI: 0.521 to 0.818]). The observers agreed with the initial report of LVHT-presence in 53% and of absence in 67%. By reviewing the discordant cases, consensus was achieved about LVHT presence (n = 8) or absence (n = 16); in 11 cases, the diagnosis remained questionable. Discordance was due to poor image quality, lack of views in different apical planes, aberrant bands and chordae tendineae, abnormally sized or inserting papillary muscles, and localized calcifications of the endocardium. ConclusionsIOA was substantial for diagnosing LVHT. However, even the application of pre-defined criteria yielded disagreement in 35% of cases; and after mutual review, there were still 11% questionable cases.

Fetal Ventricular Hypertrabeculation/Noncompaction: Clinical Presentation, Genetics, Associated Cardiac and Extracardiac Abnormalities and Outcome.

Left ventricular hypertrabeculation/noncompaction (LVHT) is a cardiac abnormality of unknown etiology. Aim of the review was to summarize the current knowledge about fetal LVHT, including clinical presentation, associated cardiac and extracardiac abnormalities and outcome. In 88 cases, LVHT was diagnosed by fetal echocardiography. In 36 %, no additional cardiac abnormalities were reported; in the remaining 64 %, one or more cardiac abnormalities were reported. Eight cases died prenatally, 17 were electively terminated, and 24 patients died after birth. Six patients were lost to follow-up, and 33 patients are alive at a mean age of 26 months. Surviving cases presented less frequently with fetal hydrops (13 vs. 62 %, p = 0.0004), complete heart block (27 vs. 78 %, p = 0.0076), more than three associated cardiac abnormalities (9 vs. 47 %, p = 0.0008) and more frequently with isolated LVHT (52 vs. 19 %, p = 0.009) than cases who died. Of the surviving patients, 16 received pharmacotherapy, three received pacemakers, eight underwent surgical procedures and four underwent heart transplantation. Postnatal regression of left ventricular hypertrophy and development of LVHT was found in four cases, improvement in cardiac function in two, and regression of right VHT in two. At autopsy, endocardial fibrosis was the most frequent abnormality in 92 %. Thirty-eight percentage of cases with fetal LVHT survived. Fetal and postnatal echocardiographic findings challenge the "embryonic pathogenetic" hypothesis of LVHT. Furthermore, fetal pathoanatomic findings like endocardial fibrosis might play a role in clarifying the still unsolved pathogenesis of LVHT.

Neuromuscular comorbidity, heart failure, and atrial fibrillation as prognostic factors in left ventricular hypertrabeculation/noncompaction

There is some controversy concerning the prognosis of patients with left ventricular hypertrabeculation/noncompaction (LVHT). LVHT is frequently associated with neuromuscular disorders (NMDs). The aim of this study was to assess cardiac and neurological findings as predictors of mortality in patients with LVHT. The study included patients with LVHT diagnosed between June 1995 and January 2014 in one echocardiographic laboratory. They underwent a baseline cardiologic examination and were invited for a neurological examination. Between January and February 2014, their survival status was assessed. LVHT was diagnosed in 220 patients (68 female, aged 52 ± 17years) with a prevalence of 0.35 %/year. During a follow-up of 72 ± 61months, 65 patients died. The mortality was 5 %/year. A neurological investigation was performed on 173 patients (79 %) and revealed specific NMDs in 31 (14 %), NMD of unknown etiology in 103 (47 %), and normal findings in 39 (18 %) patients. In multivariate analysis, the predictors of mortality were increased age (p = 0.0001), presence of a specific NMD (p = 0.0062) or NMD of unknown etiology (p = 0.0062), heart failure NYHA III (p = 0.0396), atrial fibrillation (p = 0.0022), and sinus tachycardia (p = 0.0395). LVHT patients should undergo systematic neurological examinations. Whether an optimal therapy of heart failure and atrial fibrillation will improve the prognosis of LVHT patients needs to be addressed in further studies.

Noncompaction in Healthy Subjects, Dilated and Hypertrophic Cardiomyopathy, and Neuromuscular Disorders Is the Same Entity.

With interest we read the article by Khosroshahi et al. about a novel method for quantification of left ventricular hypertrabeculation/noncompaction (LVHT) using two-dimensional echocardiography in children (1). We appreciate their efforts to contribute to an improvement and unification of echocardiographic diagnostic criteria for LVHT, which is urgently needed. Concerning their proposed method, we have the following questions and concerns: