Anesthetic management of a patient with dilated cardiomyopathy and purpura for interventional thrombectomy of both femoral artery: Case report.

RATIONALE: Anesthesia management of patients with dilated cardiomyopathy (DCM) has always been a challenge for anesthesiologists. Eighty percent of patients with DCM have heart failure as the first symptom, which may be accompanied by arrhythmias, thromboembolism, etc. Thrombosis is a significant contributing factor to adverse cardiovascular and cerebrovascular events, and its risk is severely underestimated in the anesthetic management of DCM. PATIENT CONCERNS: We present a case of a 54-year-old hypersensitive female patient with dilated cardiomyopathy and purpura who underwent an interventional thrombectomy under general anesthesia following a lower limb thromboembolism. DIAGNOSIS: Patient underwent an interventional thrombectomy under general anesthesia, with in situ thrombosis occurring during the surgery. INTERVENTIONS: After maintaining stable hemodynamics, proceed with the intervention to retrieve the embolus. OUTCOME: Patients in the advanced DCM developed acute thrombosis twice during embolization. LESSONS: This case discusses the causes of intraoperative thrombosis and summarizes and reflects on the anesthesia management of this case, which has always been one of the difficult points for anesthesiologists to master. In the anesthesia management of DCM patients, it is also necessary to maintain hemodynamic stability, enhance perioperative coagulation management, use anticoagulants rationally, and avoid the occurrence of thrombotic events.

A mutation that prevents myosin from overcoming its inhibitions.

JGP study (Duno-Miranda et al. https://doi.org/10.1085/jgp.202313522) shows that a mutation linked to dilated cardiomyopathy stabilizes ß-cardiac myosin in its autoinhibited, super-relaxed state.

Cardiac L-type calcium channel regulation by Leucine-Rich Repeat-Containing Protein 10.

L-type calcium channels (LTCCs), the major portal for Ca2+ entry into cardiomyocytes, are essential for excitation-contraction coupling and thus play a central role in regulating overall cardiac function. LTCC function is finely tuned by multiple signaling pathways and accessory proteins. Leucine-rich repeat-containing protein 10 (LRRC10) is a little studied cardiomyocyte-specific protein recently identified as a modulator of LTCCs. LRRC10 exerts a remarkable effect on LTCC function, more than doubling L-type Ca2+ current (ICa,L) amplitude in a heterologous expression system by altering the gating of the channels without changing their surface membrane expression. Genetic ablation of LRRC10 expression in mouse and zebrafish hearts leads to a significant reduction in ICa,L density and a slowly progressive dilated cardiomyopathy in mice. Rare sequence variants of LRRC10 have been identified in dilated cardiomyopathy and sudden unexplained nocturnal cardiac death syndrome, but these variants have not been clearly linked to disease. Nevertheless, the DCM-associated variant, I195T, converted LRRC10 from a ICa,L potentiator to a ICa,L suppressor, thus illustrating the wide dynamic range of LRRC10-mediated ICa,L regulation. This review focuses on the contemporary knowledge of LTCC modulation by LRRC10 and discusses potential directions for future investigations.

Tail length and E525K dilated cardiomyopathy mutant alter human ß-cardiac myosin super-relaxed state.

Dilated cardiomyopathy (DCM) is a condition characterized by impaired cardiac function, due to myocardial hypo-contractility, and is associated with point mutations in ß-cardiac myosin, the molecular motor that powers cardiac contraction. Myocardial function can be modulated through sequestration of myosin motors into an auto-inhibited "super-relaxed" state (SRX), which may be further stabilized by a structural state known as the "interacting heads motif" (IHM). Here, we sought to determine whether hypo-contractility of DCM myocardium results from reduced function of individual myosin molecules or from decreased myosin availability to interact with actin due to increased IHM/SRX stabilization. We used an established DCM myosin mutation, E525K, and characterized the biochemical and mechanical activity of wild-type and mutant human ß-cardiac myosin constructs that differed in the length of their coiled-coil tail, which dictates their ability to form the IHM/SRX state. We found that short-tailed myosin constructs exhibited low IHM/SRX content, elevated actin-activated ATPase activity, and fast velocities in unloaded motility assays. Conversely, longer-tailed constructs exhibited higher IHM/SRX content and reduced actomyosin ATPase and velocity. Our modeling suggests that reduced velocities may be attributed to IHM/SRX-dependent sequestration of myosin heads. Interestingly, longer-tailed E525K mutants showed no apparent impact on velocity or actomyosin ATPase at low ionic strength but stabilized IHM/SRX state at higher ionic strength. Therefore, the hypo-contractility observed in DCM may be attributable to reduced myosin head availability caused by enhanced IHM/SRX stability in E525K mutants.

Myocardial B cells have specific gene expression and predicted interactions in dilated cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy.

Introduction: Growing evidence from animal models indicates that the myocardium hosts a population of B cells that play a role in the development of cardiomyopathy. However, there is minimal data on human myocardial B cells in the context of cardiomyopathy. Methods: We integrated single-cell and single-nuclei datasets from 45 healthy human hearts, 70 hearts with dilated cardiomyopathy (DCM), and 8 hearts with arrhythmogenic right ventricular cardiomyopathy (ARVC). Interactions between B cells and other cell types were investigated using the CellChat Package. Differential gene expression analysis comparing B cells across conditions was performed using DESeq2. Pathway analysis was performed using Ingenuity, KEGG, and GO pathways analysis. Results: We identified 1,100 B cells, including naive B cells and plasma cells. Cells showed an extensive network of interactions within the healthy myocardium that included outgoing signaling to macrophages, T cells, endothelial cells, and pericytes, and incoming signaling from endothelial cells, pericytes, and fibroblasts. This niche relied on ECM-receptor, contact, and paracrine interactions; and changed significantly in the context of cardiomyopathy, displaying disease-specific features. Differential gene expression analysis showed that in the context of DCM both naive and plasma B cells upregulated several pathways related to immune activation, including upregulation of oxidative phosphorylation, upregulation of leukocyte extravasation, and, in naive B cells, antigen presentation. Discussion: The human myocardium contains naive B cells and plasma cells, integrated into a diverse and dynamic niche that has distinctive features in healthy, DCM, and ARVC. Naive myocardial-associated B cells likely contribute to the pathogenesis of human DCM.

Magnetic Resonance Imaging Characterization and Clinical Outcomes of Dilated and Arrhythmogenic Left Ventricular Cardiomyopathies.

BACKGROUND: Nondilated left ventricular cardiomyopathy (NDLVC) has been recently differentiated from dilated cardiomyopathy (DCM). A comprehensive characterization of these 2 entities using cardiac magnetic resonance (CMR) and genetic testing has never been performed. OBJECTIVES: This study sought to provide a thorough characterization and assess clinical outcomes in a large multicenter cohort of patients with DCM and NDLVC. METHODS: A total of 462 patients with DCM (227) or NDLVC (235) with CMR data from 4 different referral centers were retrospectively analyzed. The study endpoint was a composite of sudden cardiac death or major ventricular arrhythmias. RESULTS: In comparison to DCM, NDLVC had a higher prevalence of pathogenic or likely pathogenic variants of arrhythmogenic genes (40% vs 23%; P < 0.001), higher left ventricular (LV) systolic function (LV ejection fraction: 51% ± 12% vs 36% ± 15%; P < 0.001) and higher prevalence of free-wall late gadolinium enhancement (LGE) (27% vs 14%; P < 0.001). Conversely, DCM showed higher prevalence of pathogenic or likely pathogenic variants of nonarrhythmogenic genes (23% vs 12%; P = 0.002) and septal LGE (45% vs 32%; P = 0.004). Over a median follow-up of 81 months (Q1-Q3: 40-132 months), the study outcome occurred in 98 (21%) patients. LGE with septal location (HR: 1.929; 95% CI: 1.033-3.601; P = 0.039) was independently associated with the risk of sudden cardiac death or major ventricular arrhythmias together with LV dilatation, older age, advanced NYHA functional class, frequent ventricular ectopic activity, and nonsustained ventricular tachycardia. CONCLUSIONS: In a multicenter cohort of patients with DCM and NDLVC, septal LGE together with LV dilatation, age, advanced disease, and frequent and repetitive ventricular arrhythmias were powerful predictors of major arrhythmic events.

Single-Cell RNA Sequencing Reveals Cardiac Fibroblast-Specific Transcriptomic Changes in Dilated Cardiomyopathy.

Dilated cardiomyopathy (DCM) is the most common cause of heart failure, with a complex aetiology involving multiple cell types. We aimed to detect cell-specific transcriptomic alterations in DCM through analysis that leveraged recent advancements in single-cell analytical tools. Single-cell RNA sequencing (scRNA-seq) data from human DCM cardiac tissue were subjected to an updated bioinformatic workflow in which unsupervised clustering was paired with reference label transfer to more comprehensively annotate the dataset. Differential gene expression was detected primarily in the cardiac fibroblast population. Bulk RNA sequencing was performed on an independent cohort of human cardiac tissue and compared with scRNA-seq gene alterations to generate a stratified list of higher-confidence, fibroblast-specific expression candidates for further validation. Concordant gene dysregulation was confirmed in TGFß-induced fibroblasts. Functional assessment of gene candidates showed that AEBP1 may play a significant role in fibroblast activation. This unbiased approach enabled improved resolution of cardiac cell-type-specific transcriptomic alterations in DCM.

Familial dilated cardiomyopathy in a child: a case report.

BACKGROUND: Dilated cardiomyopathy (DCM) commonly leads to heart failure (HF) and represents the most common indication for cardiac transplantation in the pediatric population. Clinical manifestations of DCM are mainly the symptoms of heart failure; it is diagnosed by EKG, chest x-ray and echocardiography. For the idiopathic and familial diseases cases of DCM, there are no definite guidelines for treatment in children as they are treated for prognostic improvement. CASE PRESENTATION: We report the case of a 2-year-old girl diagnosed with dilated cardiomyopathy associated with homozygous mutation in the Myosin Light Chain 3 gene admitted for edema in lower extremities, muscle weakness, lethargy and vomiting, and she was found to be in cardiogenic shock. Chest x-ray showed cardiomegaly and EKG showed first degree atrioventricular block. Echocardiogram showed severe biventricular systolic and diastolic dysfunction. After 70 days of hospitalization, the patient went into cardiac arrest with cessation of electrical and mechanical activity of the heart, despite cardiopulmonary resuscitative efforts. CONCLUSION: Although rare, pediatric DCM carries a high risk of morbidity and mortality and a lack of curative therapy.

Association between dietary selenium and zinc intake and risk of dilated cardiomyopathy in children: a case-control study.

BACKGROUND: Dilated cardiomyopathy (DCMP) is characterized by the enlargement and weakening of the heart and is a major cause of heart failure in children. Infection and nutritional deficiencies are culprits for DCMP. Zinc is an important nutrient for human health due to its anti-oxidant effect that protects cell against oxidative damage. This case-control study aimed to investigate the relationship between dietary intake of zinc and selenium and the risk of DCMP in pediatric patients. METHODS: A total of 36 DCMP patients and 72 matched controls were recruited, and their dietary intakes were assessed via a validated food frequency questionnaire. We used chi-square and sample T-test for qualitative and quantitative variables, respectively. Logistic regression analysis was applied to assess the relationship between selenium and zinc intake with the risk of DCMP. RESULTS: After fully adjusting for confounding factors, analyses showed that selenium (OR = 0.19, CI = 0.057-0.069, P trend < 0.011) and zinc (OR = 0.12, CI = 0.035-0.046, P trend < 0.002) intake were strongly associated with 81% and 88% lower risk of pediatric DCMP, respectively. CONCLUSIONS: This study highlights the protective role of adequate dietary intake of selenium and zinc in decreasing the risk of DCMP in children. Malnutrition may exacerbate the condition and addressing these micronutrient deficiencies may improve the cardiac function. Further studies are recommended to detect the underlying mechanisms and dietary recommendations for DCMP prevention.

Restrictive annuloplasty or replacement on reverse remodeling for nonischemic dilated cardiomyopathy.

BACKGROUND: For patients with nonischemic dilated cardiomyopathy (NIDCM), the indications for and results of mitral surgery remain controversial. We reviewed a strategy of mitral repair and replacement for clinically relevant secondary mitral regurgitation (MR) in patients with NIDCM. METHODS: We retrospectively reviewed 65 patients with advanced NIDCM (LVEF < 40%) who underwent mitral surgery. Of them, 47 (72%) underwent mitral annuloplasty and 18 (28%) replacement for secondary MR. The primary endpoint was postoperative reduction in indexed LV end-systolic volume (LVESVI). RESULTS: At baseline, there was no intergroup difference in LVESVI (123 ± 47 vs. 147 ± 37 ml/m2, P = 0.055), LVEF (27 ± 8% vs. 25 ± 6%, P = 0.41), incidence of severe MR (57% (27/47) vs. 72% (13/18), P = 0.40), or EuroSCORE II score (6.2% vs. 7.6%, P = 0.90). At 6 months, the annuloplasty group reduced LVESVI to a greater degree than the replacement group (P < 0.001), yielding significantly smaller postoperative LVESVI (96 ± 59 vs. 154 ± 61 ml/m2, P < 0.001) and better LVEF (P < 0.001). The rates of moderate/severe recurrent MR were 17% (8/47) and 0%, respectively. Multivariable analysis demonstrated that mitral annuloplasty (OR 6.10, 95% CI 1.14-32.8, P = 0.035) was significantly associated with postoperative LV reverse remodeling. Cumulative survival was not different between the groups (P = 0.26). CONCLUSIONS: In patients with NIDCM, mitral annuloplasty reduced LV volume to a greater degree than did mitral replacement. These findings may assist with surgical options for secondary MR associated with NIDCM.

[Analysis of long-term prognosis and risk factors in patients with dilated cardiomyopathy].

Objective: To investigate the risk factors and long-term prognosis of major adverse cardiovascular events(MACEs) in patients with dilated cardiomyopathy (DCM). Methods: This study was a single-center retrospective cohort study. Clinical information from 300 patients with DCM hospitalized in Peking Union Medical College Hospital from April 2013 to April 2023 was collected. Based on echocardiography results, the patients were divided into two groups: isolated DCM and DCM with left ventricular non-compaction cardiomyopathy (LVNC). The MACEs, including major heart failure events, severe ventricular arrhythmias, and cardiovascular death, were recorded by outpatient or telephone follow-up. Univariate and multivariate Cox proportional hazard regression models were used to analyze the risk factors affecting the prognosis of patients with DCM. Kaplan-Meier curve and log-rank were used for survival analysis to compare the difference in the incidence of cardiovascular events between the two groups. Results: The included 300 DCM patients were (47.8±16.8) years old, with 197 males (65.7%), of which 237 (79.0%) were isolated DCM and 63 (21.0%) were DCM with LVNC. The follow-up time was 4.0 (1.9, 6.2) years. A total of 142 (47.3%) MACEs occurred, including 117 (39.0%) major heart failure events, 20 (6.7%) severe ventricular arrhythmia events, and 53 (17.7%) cardiovascular death events. Multivariate Cox proportional hazard regression analysis showed that increased left ventricular end-diastolic diameter (HR=1.21, 95%CI: 1.01-1.44, P=0.042), moderate or severe mitral regurgitation (HR=1.71, 95%CI: 1.19-2.47, P=0.004), increased ln (N-terminal pro-B-type natriuretic peptide) (HR=1.30, 95%CI: 1.10-1.54, P=0.002) were independent risk factors for dverse cardiovascular events in DCM patients, and angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB)/angiotensin receptor neprilysin inhibitor (ARNI) treatment (HR=0.45, 95%CI: 0.26-0.78, P=0.004) was independent protective factor. Kaplan-Meier survival analysis found no significant difference in the risk of MACEs between isolated DCM and DCM with LVNC (P=0.22). Similarly, there were no significant differences in the incidence of major heart failure, severe ventricular arrhythmia, and cardiovascular death between the two groups (all P>0.05). Conclusion: An increase in left ventricular end-diastolic diameter, moderate or severe mitral regurgitation, elevated N-terminal pro-B-type natriuretic peptide, and non use of ACEI/ARB/ARNI are independent predictors of cardiovascular events in DCM patients. There was no significant risk of MACEs in patients with isolated DCM and DCM with LVNC, and suggested that LVNC may be a unique phenotype and should be accurately managed in combination with genetic background.

Prognosis value of galectin-3 in patients with dilated cardiomyopathy: a meta-analysis.

Background: Accurate prediction and assessment of myocardial fibrosis (MF) and adverse cardiovascular events (MACEs) are crucial in patients with dilated cardiomyopathy (DCM). Several studies indicate that galectin-3 (gal-3) as a promising prognostic predictor in patients with DCM. Methods: A comprehensive search was conducted in PubMed, EMBASE, the Cochrane Library, and Web of Science for relevant studies up to August 2023. The hazard ratios (HRs) of gal-3 for MACEs in DCM patients, and for MACEs in LGE(+) versus LGE(-) groups, were evaluated. Statistical analysis was performed using STATA SE 14.0 software. Results: Seven studies, encompassing 945 patients, met the eligibility criteria. In DCM patients, abnormally elevated gal-3 levels were indicative of an increased MACEs risk (HR = 1.10, 95% CI [1.00-1.21], I2 = 65.7%, p = 0.008). Compared with the LGE(-) group, the level of gal-3 in LGE(+) group was higher (HR = 1.12, 95% CI [1.05-1.19], I2 = 31.4%, p = 0.233), and the combination of gal-3 and LGE significantly improved the prediction of MACEs. Sensitivity analysis confirmed the robustness of all results. Conclusions: This study's findings suggest that elevated gal-3 levels significantly correlate with increased MACE risk in DCM, highlighting its potential as a biomarker. However, significant heterogeneity among studies necessitates further research to ascertain gal-3's predictive and diagnostic value in DCM prognosis, particularly in conjunction with LGE. PROSPERO ID: CRD42023471199.

Cardiac MRI for clinical dilated cardiomyopathy: Improved diagnostic power via combined T1, T2, and ECV.

INTRODUCTION: Early diagnosis of patients with dilated cardiomyopathy (DCM) remains challenging. Cardiac MR can correlate myocardial changes with their pathological basis. There have been some previous studies on the effect of T1 mapping in DCM, but there is limited data on the incremental value of T2 mapping for DCM in routine clinical practice. This study will examine whether the combination of MRI T1 and T2 mapping offers greater advantages in the diagnosis of DCM. METHODS: The study included 28 patients with DCM and 21 healthy controls. CMR evaluation included late gadolinium enhancement (LGE), T1 mapping, extracellular volume (ECV) fraction and T2 mapping. The DCM group was divided into LGE (+) and LGE (-) subgroups. The main modes of LGE are subendocardial, midwall, subepicardial, or transmural. T1 values, T2 values, and ECV in the 16 segments myocardial levels were measured by post-processing software. Student's t-tests or Mann-Whitney U test was used to compare between two groups, and one-way ANOVA or Kruskal-Wallis H test was used to compare between multiple groups, with p values corrected by Bonferroni. The difference was considered statistically significant at P < 0.05. ROC curve analysis was used to compare the area under the curve (AUC) of each index and its combined value, and the cut-off value, sensitivity and specificity were determined by Jordan's index. RESULTS: Mean native myocardial T1, ECV and T2 were significantly higher in the DCM group compared to controls (p ≤ 0.001, respectively). The best cut-off values for T1, T2 and ECV to discriminate DCM from controls were 1184 ms, 40.9 ms and 29.2%, respectively. The AUC of T1, ECV and T2 were 0.87, 0.89, and 0.83, respectively. The combined AUC of the three values was 0.96. CONCLUSION: Native T1 value and ECV overcome some of the limitations of LGE, and the T2 helps to understand the extent of myocardial damage. The combination of T1 and T2 mapping techniques can reveal fibrotic and oedematous changes in the early stages of DCM, providing a more comprehensive assessment of DCM and better guidance for individualised clinical management of patients. IMPLICATIONS FOR PRACTICE: We suggest that the addition of T2 mapping to the routine CMR examination of patients with suspected DCM, and the combined assessment of T1mapping and T2 mapping can provide complementary information about the disease and improve the early diagnosis of DCM.

Association of uncertain significance genetic variants with myocardial mechanics and morphometrics in patients with nonischemic dilated cardiomyopathy.

BACKGROUND: Careful interpretation of the relation between phenotype changes of the heart and gene variants detected in dilated cardiomyopathy (DCM) is important for patient care and monitoring. OBJECTIVE: We sought to assess the association between cardiac-related genes and whole-heart myocardial mechanics or morphometrics in nonischemic dilated cardiomyopathy (NIDCM). METHODS: It was a prospective study consisting of patients with NIDCM. All patients were referred for genetic testing and a genetic analysis was performed using Illumina NextSeq 550 and a commercial gene capture panel of 233 genes (Systems Genomics, Cardiac-GeneSGKit®). It was analyzed whether there are significant differences in clinical, two-dimensional (2D) echocardiographic, and magnetic resonance imaging (MRI) parameters between patients with the genes variants and those without. 2D echocardiography and MRI were used to analyze myocardial mechanics and morphometrics. RESULTS: The study group consisted of 95 patients with NIDCM and the average age was 49.7 ± 10.5. All echocardiographic and MRI parameters of myocardial mechanics (left ventricular ejection fraction 28.4 ± 8.7 and 30.7 ± 11.2, respectively) were reduced and all values of cardiac chambers were increased (left ventricular end-diastolic diameter 64.5 ± 5.9 mm and 69.5 ± 10.7 mm, respectively) in this group. It was noticed that most cases of whole-heart myocardial mechanics and morphometrics differences between patients with and without gene variants were in the genes GATAD1, LOX, RASA1, KRAS, and KRIT1. These genes have not been previously linked to DCM. It has emerged that KRAS and KRIT1 genes were associated with worse whole-heart mechanics and enlargement of all heart chambers. GATAD1, LOX, and RASA1 genes variants showed an association with better cardiac function and morphometrics parameters. It might be that these variants alone do not influence disease development enough to be selective in human evolution. CONCLUSIONS: Combined variants in previously unreported genes related to DCM might play a significant role in affecting clinical, morphometrics, or myocardial mechanics parameters.

Dilated cardiomyopathy due to hypocalcaemia: a case report.

BACKGROUND: Hypocalcaemia is a rare, but reversible, cause of dilated cardiomyopathy causing heart failure. Several case reports have been reported on reversible cardiomyopathy secondary to hypocalcaemia. CASE PRESENTATION: We report a case of 54-year-old female Sri Lankan patient who presented with shortness of breath and was diagnosed with heart failure with reduced ejection fraction due to dilated cardiomyopathy. The etiology for dilated cardiomyopathy was identified as hypocalcemic cardiomyopathy, secondary to primary hypoparathyroidism, which was successfully treated with calcium and vitamin D replacement therapy. CONCLUSION: This adds to literature of this rare cause of reversible cardiomyopathy secondary to hypocalcemia reported from the South Asian region of the world. This case highlights the impact of proper treatment improving the heart failure in patients with hypocalcemic cardiomyopathy.

Penetrance of Dilated Cardiomyopathy in Genotype-Positive Relatives.

BACKGROUND: Disease penetrance in genotype-positive (G+) relatives of families with dilated cardiomyopathy (DCM) and the characteristics associated with DCM onset in these individuals are unknown. OBJECTIVES: This study sought to determine the penetrance of new DCM diagnosis in G+ relatives and to identify factors associated with DCM development. METHODS: The authors evaluated 779 G+ patients (age 35.8 ± 17.3 years; 459 [59%] females; 367 [47%] with variants in TTN) without DCM followed at 25 Spanish centers. RESULTS: After a median follow-up of 37.1 months (Q1-Q3: 16.3-63.8 months), 85 individuals (10.9%) developed DCM (incidence rate of 2.9 per 100 person-years; 95% CI: 2.3-3.5 per 100 person-years). DCM penetrance and age at DCM onset was different according to underlying gene group (log-rank P = 0.015 and P <0.01, respectively). In a multivariable model excluding CMR parameters, independent predictors of DCM development were: older age (HR per 1-year increase: 1.02; 95% CI: 1.0-1.04), an abnormal electrocardiogram (HR: 2.13; 95% CI: 1.38-3.29); presence of variants in motor sarcomeric genes (HR: 1.92; 95% CI: 1.05-3.50); lower left ventricular ejection fraction (HR per 1% increase: 0.86; 95% CI: 0.82-0.90) and larger left ventricular end-diastolic diameter (HR per 1-mm increase: 1.10; 95% CI: 1.06-1.13). Multivariable analysis in individuals with cardiac magnetic resonance and late gadolinium enhancement assessment (n = 360, 45%) identified late gadolinium enhancement as an additional independent predictor of DCM development (HR: 2.52; 95% CI: 1.43-4.45). CONCLUSIONS: Following a first negative screening, approximately 11% of G+ relatives developed DCM during a median follow-up of 3 years. Older age, an abnormal electrocardiogram, lower left ventricular ejection fraction, increased left ventricular end-diastolic diameter, motor sarcomeric genetic variants, and late gadolinium enhancement are associated with a higher risk of developing DCM.

Implementing a New Algorithm for Reinterpretation of Ambiguous Variants in Genetic Dilated Cardiomyopathy.

Dilated cardiomyopathy is a heterogeneous entity that leads to heart failure and malignant arrhythmias. Nearly 50% of cases are inherited; therefore, genetic analysis is crucial to unravel the cause and for the early identification of carriers at risk. A large number of variants remain classified as ambiguous, impeding an actionable clinical translation. Our goal was to perform a comprehensive update of variants previously classified with an ambiguous role, applying a new algorithm of already available tools. In a cohort of 65 cases diagnosed with dilated cardiomyopathy, a total of 125 genetic variants were classified as ambiguous. Our reanalysis resulted in the reclassification of 12% of variants from an unknown to likely benign or likely pathogenic role, due to improved population frequencies. For all the remaining ambiguous variants, we used our algorithm; 60.9% showed a potential but not confirmed deleterious role, and 24.5% showed a potential benign role. Periodically updating the population frequencies is a cheap and fast action, making it possible to clarify the role of ambiguous variants. Here, we perform a comprehensive reanalysis to help to clarify the role of most of ambiguous variants. Our specific algorithms facilitate genetic interpretation in dilated cardiomyopathy.

Pronóstico del trasplante cardiaco en pacientes con miocardiopatía hipertrófica y restrictiva. Análisis de un registro nacional / Prognosis after heart transplant in patients with hypertrophic and restrictive cardiomyopathy. A nationwide registry analysis

Introducción y objetivos: Existe controversia acerca de los resultados del trasplante cardiaco en pacientes con miocardiopatía hipertrófica (MCH) o restrictiva (MCR). Métodos: Análisis retrospectivo de receptores adultos de un primer trasplante cardiaco entre 1984 y 2021 incluidos en un registro nacional. La mortalidad al primer y quinto año postrasplante en receptores con MCH y MCR se comparó con la de receptores con miocardiopatía dilatada (MCD). Resultados: Se incluyó a 3.703 pacientes (3.112 MCD; 331 MCH y 260 MCR) con seguimiento mediano de 5,0 años (3,1-5,0). En comparación con la MCD, el riesgo ajustado de mortalidad a 1 año fue: MCH: hazard ratio (HR)=1,38; intervalo de confianza del 95% (IC95%), 1,07-1,78; p=0,01, MCR: HR=1,48; IC95%, 1,14-1,93; p=0,003. El riesgo ajustado a 5 años fue: MCH: HR=1,17; IC95%, 0,93-1,47; p=0,18; MCR: HR=1,52; IC95%, 1,22-1,89; p<0,001. En los últimos 20 años, la MCR mejoró significativamente la supervivencia a 1 año (R2 ajustada=0,95) y a 5 años (R2=0,88); la MCH mejoró la supervivencia a 5 años (R2=0,59) y a 1 año permaneció estable (R2=0,16). Conclusiones: Se asoció la MCR y la MCH a peor pronóstico precoz postrasplante que la MCD. La diferencia desfavorable se mantuvo para la supervivencia a 5 años solo para la MCR. Se observa una tendencia temporal a mejor pronóstico precoz y tardío para la MCR, y solo para el tardío en la MCH. (AU)

Introduction and objectives: Posttransplant outcomes among recipients with a diagnosis of hypertrophic cardiomyopathy (HCM) or restrictive cardiomyopathy (RCM) remain controversial. Methods: Retrospective analysis of a nationwide registry of first-time recipients undergoing isolated heart transplant between 1984 and 2021. One-year and 5-year mortality in recipients with HCM and RCM were compared with those with dilated cardiomyopathy (DCM). Results: We included 3703 patients (3112 DCM; 331 HCM; 260 RCM) with a median follow-up of 5.0 [3.1-5.0] years. Compared with DCM, the adjusted 1-year mortality risk was: HCM: HR, 1.38; 95%CI, 1.07-1.78; P=.01, RCM: HR, 1.48; 95%CI, 1.14-1.93; P=.003. The adjusted 5-year mortality risk was: HCM: HR, 1.17; 95%CI, 0.93-1.47; P=.18; RCM: HR, 1.52; 95%CI, 1.22-1.89; P<.001. Over the last 20 years, the RCM group showed significant improvement in 1-year survival (adjusted R2=0.95) and 5-year survival (R2=0.88); the HCM group showed enhanced the 5-year survival (R2=0.59), but the 1-year survival remained stable (R2=0.16). Conclusions: Both RCM and HCM were linked to a less favorable early posttransplant prognosis compared with DCM. However, at the 5-year mark, this unfavorable difference was evident only for RCM. Notably, a substantial temporal enhancement in both early and late mortality was observed for RCM, while for HCM, this improvement was mainly evident in late mortality. (AU)