Criteria For Left Ventricular Noncompaction Research Articles

Searching for genetic determinants for left ventricular non-compaction.

Left ventricular non-compaction (LVNC) is still a pathology around which there are numerous controversies regarding the criteria for its diagnosis, presentation, prognosis, and even classification into the appropriate group of diseases. So far, about 190 genes in which mutations may be associated with LVNC have been described, and in each of them, several to several dozen different loci have been discovered. We decided to analyze the frequency of single nucleotide variants (SNVs) in correlation to Petersen's criteria. We retrospectively analyzed the results of cardiac magnetic resonance (CMR) studies. Twenty-three patients who met Petersen's criteria agreed to participate in the research and take blood samples for genetic testing. Next, we prospectively included 24 volunteers who did not meet Petersen's criteria. Petersen's criteria were complied with ratio of non-compacted to compacted myocardium (NC/C) ≥2.3. A total of 47 DNA samples were analyzed based on the selected regions of the following genes: β-myosin heavy chain (MYH7), α-cardiac actin (ACTC1), cardiac troponin T (TNNT2), myosin binding protein-C (MYBPC3), LIM-domain binding protein 3 (LBD3), and taffazin (TAZ). In total, 248 substitutions in exons and introns were obtained for all analyzed samples. No statistically significant differences were detected between the mentioned groups. No significant difference in either downward or upward trends in the number of substitutions in relation to the increasing trabeculation is observed. We indicated differences in the occurrence of the studied SNVs between groups, especially for rs8037241 (3'UTR region of ACTC1) and rs2675686 (LDB3), but they also did not show statistical significance. Although we did not find a significant correlation between the co-occurrence of individual mutations with LVNC, it is worth noting that the presence of one of the four mutations in the range rs8037241 (ACTC1 3'UTR), rs3729998 (TNNT2e. 12), and rs727503240 (MYH7e. 39) increases the risk of LVNC more than 4 times. An inverse association between the number of SNVs and the meeting the Petersen's criteria was demonstrated for studied LDB3 region and rs397516254 in exon 39 of the MYH7 gene. To our knowledge, no studies have been published comparing the prevalence of selected SNVs in a group of healthy subjects and in a group meeting the Petersen criteria for LVNC. Among both completely healthy individuals who did not meet the Petersen criteria for LVNC as well as those with symptoms who met these criteria we found a similar incidence of SNVs in the ACTC1, TNNT2, LDB3 and MYH7 genes segments analyzed. Further studies are required to confirm or exclude "potentially protective" SNV in the 39th exon of MYH7 (rs397516254) and the role of co-occurrence of individual SNVs in rs8037241 (ACTC1 3'UTR), rs3729998 (TNNT2), and rs727503240 (MYH7) for the increase of the risk of LVNC.

Left Ventricular Non-Compaction: Evolving Concepts

Left ventricular non-compaction (LVNC) is a rare heart muscle disease defined by the presence of prominent left ventricular trabeculation, deep intertrabecular recesses, and a thin compact layer. Several hypotheses have been proposed regarding its pathogenesis, with the most recently accepted one being that compact layer and trabeculated layers develop independently according to an “allometric growth”. The current gold-standard diagnostic criteria (in particular, the Petersen index non-compaction/compaction ratio > 2.3) reflect an excess of myocardial trabeculation, which is not a specific morpho-functional feature of LVNC cardiomyopathy but merely a “phenotypic trait”, even described in association with other myocardial disease and over-loading conditions. Accordingly, the European Society of Cardiology (ESC) guidelines have definitively abolished the term ‘LVNC cardiomyopathy’. Recently, evolving perspectives led to the restoration of LVNC cardiomyopathy by distinguishing “hypertrabeculation phenotype” and “non-compaction phenotype”. It has been proposed that the disease-specific pathophysiologic mechanism is a congenitally underdevelopment of the compact layer accounting for an impairment of the left ventricular systolic function. Future prospective research should focus on the clinical and prognostic relevance of compact layer thinning rather than excessive trabeculation, which could significantly influence the management of patients with LVNC. The review aims to update current knowledge on the pathogenesis, genetics, and diagnostic criteria of LVNC, offering modern insights for future perspectives.

Left Ventricular Trabeculation: Arrhythmogenic and Clinical Significance in Elite Athletes

Left ventricular (LV) trabeculations (LVTs) are common findings in athletes. Limited information exists regarding clinical significance, management, and outcome. The purpose of this study is to examine the prevalence and morphologic characteristics of LVTs in elite athletes, with a focus on clinical correlates and prognostic significance. We enrolled 1,492 Olympic elite athletes of different sports disciplines with electrocardiogram, echocardiogram, and exercise stress test. Individuals with a definite diagnosis of LV noncompaction (LVNC) were excluded; we focused on athletes with LVTs not meeting the criteria for LVNC. Four hundred thirty-five (29.1%) athletes presented with LVTs, which were more frequent in male athletes (62.1% vs 53.5%, P=.002) and Black athletes compared with Caucasian (7.1% vs 2.4%, P<.0001) and endurance athletes (P=.0005). No differences were found with relation to either the site or extent of trabeculations. Endurance athletes showed a higher proportion of LVTs and larger LV volumes (end-diastolic and end-systolic, respectively, 91.5±19.8mL vs 79.3±29.9mL, P=.002; and 33.1±10mL vs 28.6±11.7mL, P=.007) and diastolic pattern with higher E wave (P=.01) and e' septal velocities (P=.02). Ventricular arrhythmias were found in 14% of LVTs versus 11.6% of athletes without LVTs (P=.22). Neither the location nor the LVTs' extension were correlated to ventricular arrhythmias. At 52±32months of follow-up, no differences in arrhythmic burden were observed (11.1% in LVT athletes vs 10.2%, P=.51). Left ventricular trabeculations are quite common in athletes, mostly male, Black, and endurance, likely as the expression of adaptive remodeling. In the absence of associated clinical abnormalities, such as LV systolic and diastolic impairment, electrocardiogram repolarization abnormalities, or family evidence of cardiomyopathy, athletes with LVTs have benign clinical significance and should not require further investigation.

Impact of Cardiac Magnetic Resonance on the Diagnosis of Left Ventricular Noncompaction-A 15-Year Experience.

The aim of this study was to assess the impact of cardiac magnetic resonance (CMR) on the diagnosis in patients with known or suspected left ventricular noncompaction (LVNC). We retrospectively reviewed the medical charts of 12,811 consecutive patients who had CMR studies between 2008 and 2022 in a large tertiary center. We included patients referred for CMR because of known or suspected LVNC. The study sample consisted of 333 patients, 193 (58.0%) male, median age 39.0 (26.8-51.0) years. Among 74 patients fulfilling the echocardiographic LVNC criteria, the diagnosis was confirmed in 54 (73.0%) cases. In 259 patients with ultrasound-based suspicion of LVNC, CMR led to an LVNC diagnosis in 82 (31.7%) patients. In both groups, CMR led to a new diagnosis in 89 cases (10 (13.5%) and 79 (30.5%)). A quantity of 38 (5.4%) patients were diagnosed with dilated cardiomyopathy, 11 (1.4%) patients were diagnosed with hypertrophic cardiomyopathy, and 21 (4.1%) patients were diagnosed with unclassified cardiomyopathy. In four patients with suspected LVNC, a myocardial trabeculation was a secondary result of dilatation due to coronary heart disease. In five cases, valvular heart disease was found. Four patients were diagnosed with athlete's heart. Other diagnoses (arrhythmogenic right ventricular cardiomyopathy, peripartum cardiomyopathy, hypokinetic non-dilated cardiomyopathy, sarcoidosis, amyloidosis, and ventricular septum defect) were found in six patients. CMR is a valuable tool in the evaluation of cardiac muscle and in differentiating LVNC and other cardiac diseases.

Entropy as a novel predictor of cardiovascular events in patients with left ventricular noncompaction

BackgroundThe risk stratification of left ventricular noncompaction (LVNC) remains ambiguous. LV entropy derived from late gadolinium enhancement (LGE) in cardiac magnetic resonance (CMR) as a novel measurement of myocardial heterogeneity may serve as the substrate of major adverse cardiovascular events (MACEs). This retrospective study aimed to investigate the value of LV entropy for predicting MACEs in LVNC patients. MethodsConsecutive patients who underwent CMR and met the diagnosis criteria of LVNC were included. All patients were follow-up for MACEs (cardiac death, ventricular arrhythmia requiring therapy or heart failure hospitalization), and their LV entropy derived from the distribution of pixel signal intensities in the LGE of the LV myocardium was analyzed. ResultsOne hundred and forty-three patients (mean age 40 years, 64.3% male) were followed for a median of 3.2 years, and forty-two (29.4%) experienced MACEs. Presenting of symptoms, left ventricular end-diastolic diameter (LVEDD), LV end-diastolic volume (LVEDV) index, LV end-systolic volume (LVESV) index, LV ejection fraction (LVEF), LGE extent, and LV entropy showed association with MACEs. LV entropy maintained independent association with MACEs (HR: 4.76, 95%CI 3.68–5.15, p < 0.001) in multivariable analysis. Entropy was also strong independent predictor of MACEs in patients with and without LGE (HR: 5.89, 95% CI4.18–7.73, p < 0.001; HR: 3.06, 95% CI:1.53–4.80, p = 0.013, respectively). ConclusionsLV entropy can predict MACEs in LVNC patients and provide incremental prognostic value on top of LVEF and LGE. Also, LV entropy may help risk stratification in LGE-negative LVNC patients.

Left Ventricular Non-compaction Cardiomyopathy and Polycystic Kidney Disease Revealed by Inappropriate Polycythemia: A Fortuitous Association? Case Report

Abstract We present the case of a patient with heart failure with reduced left ventricular (LV) ejection fraction, diagnosed in the first instance by echocardiography and further on by more accurate cardiac magnetic resonance imaging with LV non-compaction (LVNC). Blood tests showed high erythrocyte and hematocrit levels, inappropriate in this setting, whilst Janus Kinase 2V617F mutation was absent, erythropoietin level was slightly increased, and arterial O2 pressure level was normal. At the time of diagnosis, the patient had mild renal impairment, and abdominal echography revealed bilateral polycystic kidney disease (PKD). The patient had one son who fulfilled the echocardiographic criteria for LVNC and had bilateral renal cysts revealed by abdominal ultrasound. The genes responsible for autosomal dominant PKD (ADPKD) development are PKD1, on chromosome 16, coding for polycystin 1 and PKD2, on chromosome 4, coding for polycystin 2. There are some experimental data which suggest that polycystins might play an important role in cardiac development and hence PKD1 and PKD2 mutations may be involved in primary cardiomyopathies. These data could explain this particular association between LVNC and ADPKD. To date, there are only a few isolated cases reported, and only one shows this association in more than one member of the same family. Further genetic testing in the few reported cases would presumably elucidate whether this finding is the result of complex genetic synergy or just a simple coincidence.

Abstract 12506: Assessment of the Left Ventricular Trabeculation Phenotype Contributes to Risk Stratification in Hypertrophic Cardiomyopathy Patients

Aims: To investigate clinical values associated with the “left ventricular (LV) trabeculation phenotype” that did not meet the diagnostic criteria of LV noncompaction (LVNC) in hypertrophic cardiomyopathy (HCM). Hypothesis: The presence of left ventricular trabeculation phenotype was associated with a poor prognosis in HCM patients. Genetic factors contributed to this particular phenotype. Methods: A total of 940 HCM patients were recruited. The primary endpoint was cardiovascular death; the secondary endpoints were sudden cardiac death (SCD) and all-cause death. The LV trabeculation phenotype was assessed by cardiac magnetic resonance. Baseline and survival analyses regarding the LV trabeculation phenotype were conducted in general HCM patients and obstructive subset. A combination model was constructed by adding the LV trabeculation phenotype to the HCM risk-SCD model. The whole exome sequencing was used for genetic analysis. Results: The LV trabeculation phenotype was recognized in 34.5% HCM patients and was mostly observed at the apex and free wall. Patients with the LV trabeculation phenotype were younger, had a higher prevalence of family history of SCD and more frequent presence of late gadolinium enhancement. Cox proportional hazards regression analysis showed that the LV trabeculation phenotype increased the risk of cardiovascular death (P=0.031), SCD (P=0.008), and all-cause death (P=0.047) in obstructive HCM patients. Furthermore, the LV trabeculation phenotype-combined model improved risk stratification for SCD. The genetic analysis showed that DTNA variants were more frequently identified in patients with the LV trabeculation phenotype. Conclusions: The LV trabeculation phenotype contributes to risk stratification in obstructive HCM, thus this parameter should be assessed in obstructive HCM patients even if the degree of trabeculation does not fulfil the LVNC criteria. DTNA mutation underlies the cause of this phenotype.

Prognostic Value of Late Gadolinium Enhancement in Left Ventricular Noncompaction: A Multicenter Study.

Current diagnostic criteria for left ventricular noncompaction (LVNC) may be poorly related to adverse prognosis. Late gadolinium enhancement (LGE) is a predictor of major adverse cardiovascular events (MACE), but risk stratification of LGE in patients with LVNC remains unclear. We retrospectively analyzed the clinical and cardiovascular magnetic resonance (CMR) data of 75 patients from three institutes and examined the correlation between different LGE types and MACE based on the extent, pattern (including a specific ring-like pattern), and locations of LGE in LVNC. A total of 51 patients (68%) presented LGE. A specific ring-like pattern was observed in 9 (12%). MACE occurred in 29 (38.7%) at 4.3 years of follow-up (interquartile range: 2.1–5.7 years). The adjusted hazard ratio (HR) for patients with ring-like LGE were 6.10 (95% CI, 1.39–26.75, p < 0.05). Free-wall or mid-wall LGE was associated with an increased risk of MACE after adjustment (HR 2.85, 95% CI, 1.31–6.21; HR 4.35, 95% CI, 1.23–15.37, respectively, p < 0.05). The risk of MACE in LVNC significantly increased when the LGE extent was greater than 7.5% and ring-like, multiple segments, and free-wall LGE were associated with MACE. These results suggest the value of LGE risk stratification in patients with LVNC.

Peripartum anesthetic management in patients with left ventricular noncompaction: a case series and review of the literature

BackgroundThis retrospective review focuses on peripartum anesthetic management and outcome of a series of five pregnant women with left ventricular noncompaction (LVNC). MethodsThe Mayo Clinic Advanced Cohort Explorer medical database was utilized to identify women diagnosed with LVNC who had been admitted for delivery at the Mayo Clinic in Rochester, Minnesota, between January 2001 and September 2021. Echocardiograms were independently reviewed by two board-certified echocardiographers, and those determined by both to meet the Jenni criteria and/or having compatible findings on magnetic resonance imaging (MRI) were included. Electronic medical records were reviewed for information pertaining to cardiac function, labor, delivery, and postpartum management. ResultsWe identified 44 patients whose medical record included the term “noncompaction” or “hypertrabeculation” and who had delivered at our institution during the study period. Upon detailed review of the medical records, 36 did not meet criteria for LVNC, and three additional patients did not receive the diagnosis until after delivery, leaving five patients with confirmed LVNC who had undergone six deliveries during the study interval. All five patients had a history of arrhythmias or had developed arrhythmias during pregnancy. One patient underwent emergency cesarean delivery due to sustained ventricular tachycardia requiring three intra-operative cardioversions. ConclusionsThis case series adds new evidence to that already available about pregnancies among women with LVNC. Favorable obstetrical outcomes were achievable when multidisciplinary teams were prepared to manage the maternal and fetal consequences of intrapartum cardiac arrhythmias and hemodynamic instability.

Left Ventricular Noncompaction in Children: The Role of Genetics, Morphology, and Function for Outcome.

Left ventricular noncompaction (LVNC) is a ventricular wall anomaly morphologically characterized by numerous, excessively prominent trabeculations and deep intertrabecular recesses. Accumulating data now suggest that LVNC is a distinct phenotype but must not constitute a pathological phenotype. Some individuals fulfill the morphologic criteria of LVNC and are without clinical manifestations. Most importantly, morphologic criteria for LVNC are insufficient to diagnose patients with an associated cardiomyopathy (CMP). Genetic testing has become relevant to establish a diagnosis associated with CMP, congenital heart disease, neuromuscular disease, inborn error of metabolism, or syndromic disorder. Genetic factors play a more decisive role in children than in adults and severe courses of LVNC tend to occur in childhood. We reviewed the current literature and highlight the difficulties in establishing the correct diagnosis for children with LVNC. Novel insights show that the interplay of genetics, morphology, and function determine the outcome in pediatric LVNC.

Imaging Features of Pediatric Left Ventricular Noncompaction Cardiomyopathy in Echocardiography and Cardiovascular Magnetic Resonance.

Background: Left ventricular noncompaction (LVNC) is a distinct cardiomyopathy characterized by the presence of a two-layer myocardium with prominent trabeculation and deep intertrabecular recesses. The diagnosis of LVNC can be challenging because the diagnostic criteria are not uniform. The aim of our study was to evaluate echocardiographic and CMR findings in a group of children with isolated LVNC. Methods: From February 2008 to July 2021, pediatric patients under 18 years of age at the time of diagnosis with echocardiographic evidence of isolated LVNC were prospectively enrolled. The patients underwent echocardiography and contrast-enhanced cardiovascular magnetic resonance (CMR) with late gadolinium enhancement to assess myocardial noncompaction, ventricular size, and function. Results: A total of 34 patients, with a median age of 11.9 years, were recruited. The patients were followed prospectively for a median of 5.1 years. Of the 31 patients who met Jenni’s criteria in echocardiography, CMR was performed on 27 (79%). Further comprehensive analysis was performed in the group of 25 patients who met the echocardiographic and CMR criteria for LVNC. In echocardiography, the median NC/C ratio in systole was 2.60 and in diastole 3.40. In 25 out of 27 children (93%), LVNC was confirmed by CMR, according to Petersen’s criteria, with a median NC/C ratio of 3.27. Conclusions: (1) Echocardiography precisely identifies patients with LVNC. (2) Echocardiography is a good method for monitoring LV systolic function, but CMR is indicated for the precise assessment of LV remodeling and RV size and function, as well as for the detection of myocardial fibrosis.

Clinical Characteristics and Prognosis of Fetal Left Ventricular Noncompaction in Japan.

Left ventricular noncompaction (LVNC) is morphologically characterized by numerous prominent trabeculations and a severely thickened, two-layered myocardium. The fetal onset of LVNC has rarely been described. We conducted nationwide retrospective surveys on fetal cardiomyopathy (CM) in Japan from 2010 to 2016, from which 38 fetal patients with CM were enrolled, including 16 patients with LVNC. The rate of diagnostic concordance was 56.3% between fetal and postnatal visits in LVNC patients. The increase in the ratio of noncompacted to compacted (N/C) myocardium was time-dependent throughout the fetal period till birth (LV lateral: 1.6±0.1 to 2.8±0.2; LV apex: 2.0±0.1 to 3.2±0.2). Of all fetuses, 16 (42.1%) died or underwent heart transplantation (HT), with 3 intrauterine deaths. Lower fetal cardiovascular profile score (odds ratio, 26.9; P=0.0266) was a risk factor for death or HT. N/C ratio ≥1.6 at the apex at the first visit was a significant predictor of LVNC (odds ratio, 47.8; P=0.0113). This is the first study to reveal the etiology of fetal CM based on results from a nationwide survey in Japan, highlighting the difficulty of diagnosing LVNC in fetal patients. To better understand and manage fetal CM, novel diagnostic criteria of LVNC in fetus should be established.

Abstract 12229: Left Ventricular Non-Compaction in Childhood: Echocardiographic Follow-Up and Prevalence in First-Degree Relatives

Introduction: Left ventricular non-compaction (LVNC) is characterized by excessive trabeculations of the left ventricular wall and may be associated with reduced systolic function. It is debated whether LVNC is congenital or may develop later as part of other cardiomyopathies. The clinical importance and heredity of LVNC with normal systolic function is unclear. We aimed to describe the cardiac development in children with LVNC from birth to 2-4 years of age, compared to matched controls. Additionally, we aimed to describe the prevalence of LVNC in first-degree relatives. Methods: A follow-up transthoracic echocardiography was performed in children at 2-4 years of age diagnosed with LVNC at birth (&lt;30 days) in the Copenhagen Baby Heart Study. Cases were matched to controls on mothers age at delivery, parity, and age of child at follow-up. First-degree relatives (parents, siblings and half-siblings) were also included. LVNC was defined as a non-compact to compact ratio of myocardium of ≥2 in at least one left ventricular segment, measured in 24 segments in end-diastole perpendicular to the left ventricular cavity as previously suggested. Results: Of the 16 children diagnosed with LVNC at birth, 10 have been reevaluated (age 3.5 (interquartile range (IQR) 3, 4) years, 80% male) together with 20 matched controls (age 4 (IQR 3, 4) years, 70% male), 29 first-degree relatives in case group (age 29 (IQR 4, 35) years, 45% male) and 55 first-degree relatives in control group (age 32 (IQR 11, 36) years, 51% male). In probands, the extent of trabeculation (13% vs. 12%, p=0.97) and fractional shortening (FS) (29% vs. 31%, p=0.24) were unchanged from birth to follow-up. At follow-up, the median left ventricular FS was significantly lower in probands compared to matched controls (31% vs. 33%, p=0.03). Ten (35%) first-degree relatives to probands fulfilled criteria for LVNC compared to 0 (0%) of first-degree relatives to controls (p&lt;0.001). Conclusions: Children with LVNC diagnosed neonatally as part of a population study had no further progression of left ventricular dysfunction or extent of trabeculation at the age of 2-4 years, but systolic function was reduced compared to matched controls. One third of first-degree relatives to children with LVNC fulfilled criteria for LVNC.

Abstract 9686: Stroke and Thrombosis Risk in Left Ventricular Non-Compaction

Introduction: Left ventricular non-compaction (LVNC) is a rare genetic condition affecting 1 in 5000 people in which the myocardium of the left ventricle fails to adequately compact, forming deep recesses within the muscle wall. These recesses have been theorized to contribute to thrombus formation and embolic stroke, though the association has never been firmly established in the limited literature over the last 20 years. Hypothesis: We assessed the hypothesis that patients with LVNC, as well as those with hypertrabeculation not meeting LVNC criteria, would have increased rates of lifetime incidence of CVA, LV thrombus diagnosis, and distal arterial embolic events. Methods: We performed a retrospective control-matched cohort study assessing patients at Loyola University Medical Center diagnosed with LVNC, as well as those with hypertrabeculated left ventricles not meeting LVNC criteria, assembling the largest cohort of adult patients in the literature to date. We matched our study patients to controls based on age, HTN, DM, smoking status, history of atrial fibrillation, and history of DVT/PE. Results: Compared to matched controls, neither the LVNC group (n=98) nor the hypertrabeculation group (n=119) showed an increased risk of CVA, but both were associated with an increase in diagnosis of LV thrombus by TTE, TEE, or cMRI (p=0.045, p=0.003, respectively). Furthermore, in the LVNC group, each 10% increase in EF was found to reduce the risk of a composite endpoint of arterial thromboembolism (CVA, LV thrombus, distal arterial embolus) by 50%, while in the hypertrabeculation group, each 10% increase in EF reduced total arterial thromboembolism by 37%. Conclusions: These findings suggest that patients with hypertrabeculated left ventricles are either more likely to have LV thrombi that do not result in CVA events, or that due to the ventricle morphology, LV thrombi are being diagnosed when none are actually present. Furthermore, our study supports the existing literature that more severe systolic dysfunction increases risk for CVA and thromboembolic events, though that association seems largely multifactorial. Based on these results we cannot advocate for or against a particular anticoagulation strategy in patients with LVNC.

Spectrum of Clinical Features and Genetic Profile of Left Ventricular Noncompaction Cardiomyopathy in Children

Background: Left ventricular noncompaction (LVNC) is a genetically determined cardiomyopathy that occurs following a disruption of endomyocardial morphogenesis. The purpose of this study was to identify the clinical characteristics and genetic profile of children with LVNC. Methods: From February 2008 to July 2020, a total of 32 children (median 11.5 years) with LVNC were prospectively enrolled and followed up for a median of 4.02 years. Diagnosis was made based on characteristic features of LVNC in echocardiography and cardiovascular magnetic resonance (CMR). Patients’ clinical symptoms, family history, ECG, Holter ECG, and genetic tests were also evaluated. Results: The most common presenting symptom was heart failure (31% of children). ECG abnormalities were noted in 56% of patients. The most prominent features were ventricular arrhythmias, sinus bradycardia, and paroxysmal third-degree atrioventricular block. Most of the patients (94%) met the criteria for LVNC and CMR confirmed this diagnosis in 82% of cases. The molecular etiology was found in 53% of children. Conclusion: Although heart failure and arrhythmias were very frequent in our study group, thromboembolic events and genetic syndromes were rare. For the accurate and reliable assessment of children with LVNC, it is necessary to get to know their family history and detailed clinical profile.

Left ventricular noncompaction: the importance of identifying high-risk patients within the scope of left ventricular hypertrabeculation

Abstract Introduction Prominent left ventricular (LV) trabeculation is frequently encountered, however LV noncompaction (LVNC) criteria are not always fulfilled. The clinical and prognostic significance of these findings remains unclear. Objectives To characterize the patients (P) with echocardiographic suspicion of LVNC and to assess clinical outcomes. Methods Retrospective single-centre study that included all echocardiograms between January 2018 and June 2020 perceiving LV hypertrabeculation. The cohort underwent diagnostic assessment for LVNC by Chin and Jenni criteria. Baseline characteristics were evaluated. Composite endpoint of cardiovascular death, heart failure (HF) hospitalization, ventricular arrythmias (VA) and nonfatal stroke was considered. Results 51P, 75% male, mean age 50±18 years. 35P (69%) had associated heart conditions, of which 57% had other known cardiomyopathy (mainly dilated cardiomyopathy), 14% congenital, 26% ischemic and 3% valvular heart disease. 2P were in postpartum period and 1P was an athlete. Family history of cardiomyopathy was present in 8P (16%). 12P underwent genetic testing, with TTN and MYH7 mutations being the most frequently detected. Prior clinical HF was reported in 53%, previous stroke in 14%, and non-sustained and sustained VA in 24% and 4%, respectively. Mean NYHA classification was 1.8±0.7, with 31% being asymptomatic. The prevalence of LVNC by Chin criteria was 31% and by Jenni criteria was 55%. 32P (63%) met at least one LVNC criteria. This group was younger (45±18 vs 59±15, p=0.004), had higher NT-proBNP levels (3644±2819 vs 389±640, p=0.048) and QRS fragmentation (59% vs 21%, p=0.027). Significantly higher LV end-diastolic volume (84 (41) vs 64 (28)ml/m2, p=0.008) and end-systolic volume (51 (37) vs 35 (20)ml/m2, p=0.004), along with lower LV ejection fraction (39±12 vs 49±13%, p=0.009) and global longitudinal strain (−11±5 vs −17±4%, p=0.003) were noticed. P who met LVNC criteria also had higher number of affected LV segments (6.4±1.8 vs 4.2±1.6, p&amp;lt;0.001). Over a mean follow-up of 18±9 months, the incidence of composite endpoint was 35%. Univariate Cox analysis showed a significant association between the presence of LVNC criteria and adverse outcomes (HR: 5.108, 95% CI: 1.682–11.236, p=0.030) (Fig. 1). Conclusion LV hypertrabeculation can be encountered in a variety of clinical scenarios and often overlaps with other heart diseases. P satisfying criteria for LVNC had more impairment in LV performance and worse clinical outcomes. Funding Acknowledgement Type of funding sources: None. Figure 1

Left ventricular characteristics of noncompaction phenotype patients with good ejection fraction measured with cardiac magnetic resonance.

We describe left ventricular (LV) volumes, myocardial and trabeculated muscle mass and strains with Cardiac magnetic resonance of a large cohort (n=81) who fulfilled the morphologic criteria of left ventricular noncompaction (LVNC) and had good ejection fraction (EF >55%) and compare them with healthy controls (n=81). Male and female patients were compared to matched controls and to each other. We also investigated the LV trabeculated muscle mass cutoff in male and female patients with LVNC. 81 participants with LVNC and 81 healthy controls were included. Male and female patients were compared to matched controls and to each other. We also investigated the left ventricular trabeculated muscle mass cut-off in male and female LVNC patients. The LV parameters of the LVNC population were normal, but they had significantly higher volumes, myocardial and trabeculated muscle mass, and a significantly smaller EF than the controls. Similar differences were observed after stratifying by sex. The optimal LV trabeculated muscle mass cutoffs were 25.8 g/m2 in men (area under the curve: 0.81) and 19.0 g/m2 in women (area under the curve: 0.87). The patients had normal global strains but a significantly worse global circumferential strain (patients vs controls: -29.9±4.9 vs. -35.8±4.7%, p<0.05) and significantly higher circumferential mechanical dispersion than the controls (patients vs. controls: 7.6±4.2 vs. 6.1±2.8%; p<0.05). No disease-related strain differences were noted between men and women. The LV functional and strain characteristics of the LVNC cohort differed significantly from those of healthy participants; this might be caused by increased LV trabeculation, and its clinical relevance might be questionable. The LV trabeculated muscle mass was very different between men and women; thus, the use of sex-specific morphologic diagnostic criteria should be considered.

Diagnostic value of standard and modified echocardiographic criteria for left ventricular noncompaction

Aim. To assess the diagnostic value of standard and modified ultrasound criteria for left ventricular noncompaction (LVNC).Material and methods. The study included 37 patients. All patients underwent echocardiography and magnetic resonance imaging (MRI). Patients with any of the standard echocardiographic criteria for LVNC (Chin, Jenni, Stollberger) were included in the study. We studied modified echocardiographic criteria of LVNC in 4 and 3-chamber apical views in systole and diastole in the anterolateral (ALsist and ALdiast) and posterolateral (PLsist and PLdiast) walls with the non-compact to compact layer ratio (NC/C) &gt;2. To assess the diagnostic value of the echocardiographic LVNC criteria, the specificity (SP) and sensitivity (SN), the likelihood ratio for positive (LR+) and negative (LR-) test results were calculated, and the operating characteristic curve (ROC) was analyzed.Results. The study included 19 women (51,4%) and 18 men (48,6%), aged 18 to 69 years. The mean age of the patients was 37,7±12,6 years. Relative to the Petersen's MRI-criterion for the Chin's criterion, SN was 55%, SP — 53% (LR+ =1,2, LR- =0,9); for the Jenni's criterion, SN — 55%, SP — 35% (LR+ =0,9, LR- =1,3); for the Stollberger's criterion, SN — 70%, SP — 18% (LR+ =0,9, LR- =1,7); for PLsyst criterion, SP — 82%, SN — 50% (LR+ =2,8, LR- =0,6). Relative to the Grothoff's MRI-criterion, which determined the LVNC mass as a percentage, for the Chin's criterion, SN was 69%, SP — 58% (LR+ =of 1,7, LR- =0,5); for the Jenni's criterion, SN — 85%, SP — 54% (LR+ =1,9, LR- =0,3); for the Stollberger's criterion, SN — 77%, SP — 25% (LR+ =1,0, LR- =0,9); for PLdiast criterion SP — 79%, SN — 62% (LR+ =3,0, LR- =0,5); for PLsyst criterion SP — 63%, SN — 84% (LR+ of 2,2, LR- =0,3); for ALdiast criterion, SP — 83%, SN — 69% (LR+ =4,1, LR- =0,4); for ALsyst criterion, SP — 71%, SN — 92% (LR+ =3,1, LR- =0,1). Relative to the Grothoff's MRI-criterion, which determined the LVNC mass index, for the Chin's criterion, SN was 59%, SP — 70% (LR+ =2,0, LR- =0,6); for the Jenni's criterion, SN — 67%, SP — 60% (LR+ =1,7, LR- =0,6); for the Stollberger's criterion SN — 78%, SP — 30% (LR+ =1,1, LR- =0,7); for the PLdiast criterion, SN — 33%, SP — 60% (LR+ =0,7, LR- =1,3); for PLsist criterion, SN — 59%, SP — 60% (LR+ =1,5, LR- =0,7); for ALdiast criterion, SN — 41%, SP — 80% (LR+ =2,0, LR- =0,7); for ALsist criterion, SN — 67%, SP — 90% (LR+ =6,7, LR- =0,4). Using ROC analysis with NC/C ratio of 2,3 for the ALsyst criterion, SN was 62%, SP — 92%; with NC/C ratio of 2,2 for PLsyst criteria in a posterolateral view in systole, SN — 62%, SP — 83%; with NC/C ratio of 2,1 for ALdiast criterion in an anterolateral view in diastole, SN — 54%, SP — 88%; with NC/C ratio of 2,1 for PLdiast criterion in a posterolateral view in diastole, SN — 46%, SP — 96%.Conclusion. Standard echocardiographic criteria are characterized by moderate sensitivity and low specificity. To improve the diagnostic accuracy of LVNC, the combined use of modified echocardiographic criteria is possible. As a screening of LVNC, using NC/C of 2,2 for the PLsist and NC/C of 2,3 for the PLsist to improve the specificity of the study should be useful.

The prognostic role of CMR using global planimetric criteria in patients with excessive left ventricular trabeculation.

Although cardiovascular magnetic resonance (CMR) is widely used in the assessment of left ventricular non-compaction (LVNC), there are no universally accepted diagnostic criteria and limited data regarding their prognostic value. We assessed the long-term prognostic role of the planimetric global Grothoff's criteria and of the CMR findings in predicting adverse cardiovascular events (CE). We prospectively enrolled 78 patients (46.7 ± 18.7 years, 33.3% females) with documented positive Jenni's echocardiographic criteria for LVNC. Cine images were used to quantify function parameters and to assess for the presence of all four quantitative Grothoff's criteria (global Grothoff's criteria). Late gadolinium enhancement (LGE) images were acquired to detect the presence of replacement myocardial fibrosis. Petersen's CMR criterion for LVNC (NC/C ratio > 2.3 in at least one myocardial segment) was fulfilled in the whole population. Twenty-six patients fulfilled the global Grothoff's criteria (four out of four). The mean duration of the follow-up was 44.2 ± 27.4 months and 28 CE were registered: 10 ventricular tachycardias, 12 episodes of heart failure (HF), four strokes, and two cardiac deaths. In the multivariate analysis, the independent predictive factors for CE were positive global Grothoff's criteria (hazard ratio, HR = 3.33, 95% CI = 1.52-7.29; p = 0.003) and myocardial fibrosis (HR = 2.41, 95% CI = 1.08-5.36; p = 0.032). Positive global Grothoff's criteria and myocardial fibrosis were powerful predictors of CE in patients with a diagnosis of LVNC by CMR Petersen's criterion. Thus, we strongly suggest a step approach confirming the diagnosis of LVNC by using the global planimetric Grothoff's criteria, which showed a prognostic impact. • Positive global Grothoff's criteria and replacement myocardial fibrosis were powerful predictors of cardiovascular events in patients with a diagnosis of LVNC by CMR Petersen's criterion. • Positive global Grothoff's criteria were associated with a higher frequency of ventricular arrhythmias in patients with a diagnosis of LVNC by CMR Petersen's criterion.

Report of a new case of saw-tooth cardiomyopathy: Clinical presentation and genetic analysis

Saw-tooth Cardiomyopathy is a very rare disease, that should not be confused with left ventricular non compaction, and only few cases have been described. We describe the case of a 33-year-old man who presented with atypical chest pain. The ECG showed left posterior fascicular block. Left ventricular non-compaction (LVNC) was initially suspected by echocardiography. Cardiac MRI found no criteria for LVNC but typical protrusions of muscular bridges in the left ventricle with dense compacted myocardium leading to the diagnosis of Saw-Tooth Cardiomyopathy. No arrhythmic event nor heart failure were noticed. In the family there was no cardiac history nor sudden death. We performed genetic analysis by sequencing a large panel of 71 genes associated with cardiomyopathies [Roche Nimblegen capture probes, sequencing on Miseq (Illumina)]. No pathogenic variant was found according to ACMG criteria ( Fig. 1 ). Less than ten cases of Saw-Tooth Cardiomyopathy (ST-CMP) were previously reported in literature and ST-CMP was initially reported as a variant of LVNC. In fact, myocardial features of ST-CMP are very different from LVNC and ST-CMP should be considered as a separate entity. Some cases were discovered during infancy suggesting prenatal development. Our case first illustrates this distinct entity since none of LVNC criteria were met but typical Saw-tooth muscular bridges that were better exhibited on MRI. Second, our case is the first to report on genetic testing and familial investigations. We did not observed other cardiomyopathy in the family and we did not identify any pathogenic mutation in known cardiomyopathy genes. Although we cannot exclude a non-genetic cause, this result may suggest a genetic cause outside the genes usually related to cardiomyopathies and suggest the search for a new gene through exome or genome sequencing.