Moderately reversible dilated cardiomyopathy in a cat with presumptive spontaneous primary hypothyroidism

A retrospective study of 22 Saudi patients with a diagnosis of dilated cardiomyopathy confirmed by cardiac catheterization was undertaken to study the pattern of this disease in Saudi Arab...

Introduction. Dilated cardiomyopathy (DCM) is characterized by global cardiac dilation associated with left ventricular (LV) systolic dysfunction without valvar substrate or ischemic heart disease. Diagnosis of idiopathic DCM can only be sustained after excluding other nongenetic causes. Methods. This study was performed on a cohort of 256 patients who died in Emergency County Hospital of Oradea and had diagnosis of DCM; the study was performed on a period of 2 years, from January 2014 until the end of December 2015. These patients were differentiated according to social criteria, background, department of admission, number of autopsies and co-morbidities. Results and Discussion. Diagnosis of DCM was more common in male patients up to the age of 70; after this age the tendency is towards equalization. In patients aged 61-80 years, DCM played a major role in tanatogenesis. Existing clinical trials have shown that patients with idiopathic DCM have a lower mortality than patients with cardiac ischemic disease. Conclusions. Despite the possibility of diagnosis with increased sensitivity and the large number of therapeutic options, multicentre studies and registries are needed to improve the life expectancy of these patients.

Circulating biomarkers can provide important information for the diagnosis and prognosis of dilated cardiomyopathy (DCM). We explored novel biomarkers for the diagnosis and prognosis of DCM to improve clinical decision-making. A total of 238 DCM patients and 65 control were consecutively enrolled at Zhongshan Hospital between January 2017 and January 2019. In the screening set, four DCM patients and four controls underwent measurements of serum proteomic analysis. Seventy-six differentially expressed circulating proteins were screened by data-independent acquisition proteomics, and three of these proteins (S100A4, S100A8/A9, and S100A12) were validated by multiple-reaction monitoring-mass spectrometry. In the validation set, subsequently, a total of 234 DCM patients and 61 control subjects were evaluated by enzyme-linked immunosorbent assay. Circulating S100A4, S100A8/A9, and S100A12 were significantly increased in DCM patients (P<0.001). These three proteins were significant positively correlated with other parameters, such as Lg (NT-proBNP), IL-1β, TGF-β, CRP, left ventricular end-diastolic diameter, and left ventricular end-systolic diameter, whereas they were negatively correlated with left ventricular ejection fraction, respectively (P<0.05). The receiver operator characteristic curve showed the combination of S100A4, S100A8/A9, and S100A12 [area under curve (AUC) 0.88, 95% confidence interval (CI) 0.84-0.93] was better than single S100A4 (AUC 0.74, 95% CI 0.68-0.81), S100A8/A9 (AUC 0.82, 95% CI 0.77-0.88), or S100A12 (AUC 0.80, 95% CI 0.72-0.88) in the diagnosis of DCM (P<0.01). After a median follow-up period of 33.5months, 110 patients (47.01%) experienced major adverse cardiac events (MACEs), including 46 who had cardiac deaths and 64 who had heart failure rehospitalizations. Kaplan-Meier analysis indicated that the DCM patients with ≥75th percentile level of S100A4 had a significantly higher incidence of MACEs than those with <75th percentile level of S100A4 (61.40% vs. 42.37%, P<0.05). There were no significant differences of MACE rate among DCM patients with different concentrations of S100A8/A9 and S100A12 (P>0.05). Cox proportional hazards regression analysis revealed that S100A4 [≥75th percentile vs. <75th percentile: hazard ratio (HR) 1.65; 95% CI 1.11-2.45] remained significant independent predictors for MACEs (P<0.05); however, S100A8/A9 and S100A12 were not independent factors for predicting MACE (P≥0.05). S100A4, S100A8/A9, and S100A12 may be additional diagnostic tools for human DCM recognition, and the combination of these three indicators helped to improve the accuracy of a single index to diagnose DCM. Additionally, S100A4 was identified as a significant predictor of prognosis in patients with DCM.

Rapid advances in DNA sequencing technologies have made it increasingly cost-effective to obtain accurate and timely large-scale genomic sequence data on individuals (short read massively parallel or next generation [next-gen]). A next-gen molecular diagnostic approach that has seen rapid deployment in the clinic over the last year is exome sequencing. Whole exome sequencing covers all protein-coding genes in the genome (≈1.1% of genome), and an exome test for a single patient generates ≈6 gigabases (109 bp) of DNA sequence data. A key challenge facing routine use of next-gen data in patient diagnosis and management is data interpretation. What sequence variant findings are relevant to diagnosis (pathogenic mutations)? What sequence variant findings are relevant to clinical care but not necessarily to patient diagnosis (clinically actionable incidental data)? What sequence information should be stored, and where can it be stored? This review provides a tutorial on current approaches to answering these questions. A recent landmark study showed that application of next-gen sequencing to a large cohort of idiopathic dilated cardiomyopathy patients found ≈27% of patients to show mutations of the titin gene, the most complex gene in the genome (363 exons). We use titin in cardiomyopathy as an exemplar for explaining next-gen sequencing approaches and data interpretation. Decreasing sequencing costs and broad dissemination of next-generation (next-gen) equipment and expertise are increasing availability of massively parallel sequencing of patient DNA samples (short read massively parallel or next-gen sequencing).1,2 Most rapidly expanding is exome sequencing, where all protein-coding sequences (exons) are selected from total genomic DNA and selectively sequenced.3 Alternative approaches to next-gen sequencing include targeted sequencing (TS) and whole genome (complete genome) sequencing. Currently, marketed targeted Sanger sequencing panels using traditional individual exon-by-exon sequencing remain expensive and time consuming, and massively parallel next-gen approaches are beginning to supplant …

DILATED CARDIOMYOPATHY WITH CARDIOGENIC SHOCK SECONDARY TO COVID-19 INFECTION

Dilated cardiomyopathy is a disease of unknown etiology that principally affects the myocardium [1]. The diagnosis of dilated cardiomyopathy is established by the presence of left ventricular dilatation and systolic dysfunction in the absence of congenital, coronary, valvular, or pericardial heart disease [2]. In some patients the development of dilated cardiomyopathy is associated with clinical factors such as alcoholism, pregnancy or a family history of cardiomyopathy [1,2]. However, dilated cardiomyopathy is distinct from specific heart muscle disease (“secondary myocardial disease”), which occurs with a specific systemic disorder that may be metabolic, collagen-vascular, infiltrative, neuromuscular, inflammatory, or neoplastic in origin [1, 2] (see Chap. 1). There are currently no specific gross anatomic, histologic, or ultrastructural morphologic features which can differentiate dilated cardiomyopathy from other causes of heart failure [3]. Since dilated cardiomyopathy is defined clinically, it is likely that several specific etiologies are responsible for this condition. It is therefore not surprising that patients with dilated cardiomyopathy have a heterogeneous clinical presentation and prognosis.

Section 5: Management of Asymptomatic Patients with Reduced Left Ventricular Ejection Fraction

Proposed Guidelines for the Diagnosis of Canine Idiopathic Dilated Cardiomyopathy

Introduction: microRNAs (miRs) are small single stranded RNAs capable of targeting expression of several genes. Circulating miRs can be important biomarkers of disease progression. Children with dilated cardiomyopathy (DCM) experience multiple outcomes including recovered-normalization, stable disease, and progression to death/ need for transplant. We hypothesized that circulating miRs are differentially expressed among these cohorts and may serve as useful prognostic biomarkers in pediatric DCM patients. Methods: RNA-sequencing was used to detect and quantify circulating miRs. Samples were collected within 3 months of a new diagnosis of DCM. Inclusion criteria included &lt;18 years of age at diagnosis of idiopathic or familial DCM (LVEF&lt;50% or left ventricular end-diastolic dimension [LVEDd] z-score ≥+2). Primary outcomes within 1 year of enrollment were defined as: [1] Death, cardiac transplant, or initiation of mechanical circulatory support; [2] Recovered-normalization of LVsize and function (LVEF≥50% and LVEDd z-score &lt;+2) or [3] Stable-persistent DCM with LVEF&lt;50% or LVEDd z-score ≥+2. Statistical analysis included random forest and hierarchical clustering (HC). Results: Sequencing was performed on 76 patients: death/transplant (n=35), recovered (n=20), or stable DCM (n=21). The top three differentially expressed miRs between the death/transplant and recovery group were miR-424-5p, miR-335-5p, and miR-503-5p (Figure A). HC based on expression of these 3 miRs identified an expression pattern associated with death/transplant outcome (Figure B). miR-503-5p was also among the top 3 miRs most differentially expressed between the stable and the recovery group. Conclusions: These results indicate circulating miRs can predict recovery in the pediatric DCM population. Importantly, miR-503-5p was more highly expressed in the recovery group when compared to both the stable and transplant groups, suggesting expression of this miR may be associated with favorable outcomes. A unique biomarker signature of miRs specific to children with DCM who have the potential to recover would improve risk stratification of this population.

Dilated cardiomyopathy (DCM) is one of the most common types of non-ischemic cardiomyopathy. DCM is characterized by left ventricle (LV) dilatation and systolic dysfunction without coronary artery disease or abnormal loading conditions. DCM is not a single disease entity and has a complex historical background of revisions and updates to its definition because of its diverse etiology and clinical manifestations. In cases of LV dilatation and dysfunction, conditions with phenotypic overlap should be excluded before establishing a DCM diagnosis. The differential diagnoses of DCM include ischemic cardiomyopathy, valvular heart disease, burned-out hypertrophic cardiomyopathy, arrhythmogenic cardiomyopathy, and non-compaction. Cardiac magnetic resonance (CMR) imaging is helpful for evaluating DCM because it provides precise measurements of cardiac size, function, mass, and tissue characterization. Comprehensive analyses using various sequences, including cine imaging, late gadolinium enhancement imaging, and T1 and T2 mapping, may help establish differential diagnoses, etiological work-up, disease stratification, prognostic determination, and follow-up procedures in patients with DCM phenotypes. This article aimed to review the utilities and limitations of CMR in the diagnosis and assessment of DCM.

Detection and diagnosis of dilated cardiomyopathy and hypertrophic cardiomyopathy using image processing techniques

Introduction: microRNAs (miRs) are small single stranded RNAs capable of targeting expression of several genes. Circulating miRs are stable and can be important biomarkers of disease progression and diagnosis. Hypothesis: We hypothesized circulating miRs could be a reliable prognostic biomarker of recovery for pediatric dilated cardiomyopathy (DCM). Methods: TaqMan Open Array miR panel (ThermoFisher Scientific) was used to investigate expression of 381 circulating miRs. Samples originated from the Pediatric Cardiomyopathy Registry (PCMR) and were collected within 3 months of a new diagnosis of DCM. Inclusion criteria included &lt;18 years of age at diagnosis of idiopathic or familial DCM (EF&lt;50% or left ventricular end-diastolic dimension [LVEDd] z-score ≥+2). Patients with DCM secondary to musculoskeletal diseases or anthracycline toxicity were excluded. Primary outcomes, occurring within 1 year of enrollment, were defined as: [1] Death, transplant (tx) listing or initiation of mechanical circulatory support; [2] Recovered- normalization of ventricular size and function (EF≥50% and LVEDd z-score &lt;+2) or [3] Stable- persistent DCM with EF&lt;50% or LVEDd z-score ≥+2. Statistical analysis included random forest, hierarchical clustering and area under the receiver operator curve (AUC). Results: N=10 subjects were included in Group 1, of which 70% were female, 6 were white, 2 Hispanic and 3 of other/unknown races, median age 9.5y. N=5 samples were included in Group 2, of which 60% were female, 3 were white, 1 black and 1 native American, median age 1.9y. N=20 samples were included in Group 3, of which 40% were female, 10 were white, 5 black, 1 Pacific islander, 2 Hispanic and 4 of other/unknown races, median age 2.1y. The top 3 miRs differentiating Group 2 (Recovered) from Group 1 (Death/Tx) (AUC of 0.92) were hsa-miR-655, -410 and -636. The top 3 miRs differentiating Group 2 (Recovered) from Group 3 (Stable) were hsa-miR-17, -410 and -345 (AUC of 0.76). Conclusions: These results indicate circulating miRs can predict recovery in the pediatric DCM population. A unique biomarker signature of miRs specific to patients who have the potential to recover would improve risk stratification of this population.

Simple SummaryDilated cardiomyopathy is a cardiac disorder most commonly observed in specific dog breeds and is characterized by diffuse left ventricular systolic dysfunction and left ventricular enlargement. Recent studies have reported a potential connection between diet and dilated cardiomyopathy, and some studies have shown a positive effect of diet change on cardiac function and prognosis in dogs with diet-related dilated cardiomyopathy. However, these reports were from large-breed dogs and did not include detailed assessments of myocardial function, such as two-dimensional speckle-tracking echocardiography. We report an overview of our experience in a small-breed dog with a clinical diagnosis of dilated cardiomyopathy, in which dietary modification resulted in improved cardiac enlargement and myocardial dysfunction evaluated by two-dimensional speckle-tracking echocardiography. We suggest that it is necessary to suspect a dietary association with dilated cardiomyopathy, even in small-breed dogs. Furthermore, the prognosis for diet-related dilated cardiomyopathy in small-breed dogs may also be as good as in previous reports of large-breed dogs when changing to appropriate diets.An 11-year-old intact female Papillion weighing 2.1 kg was referred to our institution with the main complaint of shallow, rapid breathing. At the first visit (day 0), although clinical signs improved due to the use of medication from the primary hospital, transthoracic radiography and echocardiography revealed left heart enlargement and left ventricular dysfunction. A clinical diagnosis of dilated cardiomyopathy (DCM) was made and oral administration of pimobendan, temocapril, and taurine was initiated. However, on day 10, the respiratory status worsened and furosemide was prescribed. On day 54, no significant improvement in heart size was observed. Additionally, the diet that this patient received met the recommendation for diet-related DCM by the U.S. Food and Drug Administration, and the patient’s diet was changed from a grain-free diet to a grain-containing diet. On day 1191, the patient’s respiratory status was stable and no clinical signs were observed. Transthoracic radiography and echocardiography revealed an improvement in left heart size. Additionally, improvements in the left and right ventricular myocardial strains were observed after changing the diet. We suggest that it may be necessary to suspect a dietary association with dilated cardiomyopathy, and a good prognosis might be expected by dietary modification, even in small-breed dogs.

Echocardiography has crucial importance in the diagnosis of dilated cardiomyopathy (DCM). Echocardiographic features of DCM are left ventricular (LV) dilation and systolic dysfunction with impaired global contractility and normal LV wall thickness and LV diastolic dysfunction with elevation in LV filling pressure. Other frequent characteristics are LV dyssynchrony, right ventricular (RV) dysfunction, atrial dilation, functional mitral and tricuspid regurgitation, and secondary pulmonary hypertension. New echocardiographic technologies can be helpful, i.e., three-dimensional (3D) echocardiography for more accurate assessment of LV volumes and ejection fraction (EF) and speckle tracking for analysis of strain particularly for early diagnosis. Of note, many echocardiographic parameters have demonstrated important prognostic value in DCM.

This survey investigates natriuretic peptide (NP) testing in community and hospital settings, assessing awareness, accessibility, and utilization. This investigator-initiated survey, conceived within the HFA of the European Society of Cardiology, comprised 14 questions. It underwent validation and pilot testing to ensure question readability and online system functionality. The survey was accessible for 87days, from 5 April 2023 to 1 July 2023 via a web platform. There were 751 healthcare professionals across 99 countries who responded. Of them, 92.5% had access to NPs testing in hospital whereas 34.3% had no access to NTproBNP in community settings. Access to point of care NP testing was uncommon (9.6%). Public insurance fully covered NPs testing in 31.0% of cases, with private insurance providing coverage in 37.9%. The majority (84.0%) of participants believed that the medical evidence supporting NPs testing was strong, and 54.7% considered it cost-effective. Also, 35.8% found access, awareness, and adoption to be in favour of NPs testing both in hospital and community settings. Strategies to optimize NP testing involved regular guideline updates (57.9%), prioritizing NPs testing for dyspnoea assessment (36.4%), and introducing clinician feedback mechanisms (21.2%). Notably, 40% lacked a community-based HF diagnostic pathway for referring high-NP patients for echocardiography and cardiology evaluation. This survey reveals NP awareness, access, and adoption across several countries. Highlighting the importance of community-based early heart failure diagnosis and optimizing HF diagnostic pathways remains a crucial, unmet opportunity to improve patient outcomes.