Form Of Dilated Cardiomyopathy Research Articles

Alcoholic cardiomyopathy: an update.

Alcohol-induced cardiomyopathy (AC) is an acquired form of dilated cardiomyopathy (DCM) caused by prolonged and heavy alcohol intake in the absence of other causes. The amount of alcohol required to produce AC is generally considered as >80 g/day over 5 years, but there is still some controversy regarding this definition. This review on AC focuses on pathogenesis, which involves different mechanisms. Firstly, the direct toxic effect of ethanol promotes oxidative stress in the myocardium and activation of the renin-angiotensin system. Moreover, acetaldehyde, the best-studied metabolite of alcohol, can contribute to myocardial damage impairing actin-myosin interaction and producing mitochondrial dysfunction. Genetic factors are also involved in the pathogenesis of AC, with DCM-causing genetic variants in patients with AC, especially titin-truncating variants. These findings support a double-hit hypothesis in AC, combining genetics and environmental factors. The synergistic effect of alcohol with concomitant conditions such as hypertension or liver cirrhosis can be another contributing factor leading to AC. There are no specific cardiac signs and symptoms in AC as compared with other forms of DCM. However, natural history of AC differs from DCM and relies directly on alcohol withdrawal, as left ventricular ejection fraction recovery in abstainers is associated with an excellent prognosis. Thus, abstinence from alcohol is the most crucial step in treating AC, and specific therapies are available for this purpose. Otherwise, AC should be treated according to current guidelines of heart failure with reduced ejection fraction. Targeted therapies based on AC pathogenesis are currently being developed and could potentially improve AC treatment in the future.

Clinical Trajectories and Long-Term Outcomes of Alcoholic Versus Other Forms of Dilated Cardiomyopathy

Alcoholic cardiomyopathy (ACM) is a form of dilated cardiomyopathy (DCM) occurring secondary to long-standing heavy alcohol use and is associated with poor outcomes, but the cause-specific risks are insufficiently understood. Between 1997 and 2018, we identified all patients with a first diagnosis of ACM or DCM. The cumulative incidence of different causes of hospitalisation and mortality in the two groups was calculated using the Fine-Gray and Kaplan-Meier methods. A Total of 1,237 patients with ACM (mean age 56.3±10.1 years, 89% men) and 17,211 individuals with DCM (mean age 63.6±13.8 years, 71% men) were identified. Diabetes (10% vs 15%), hypertension (22% vs 31%), and stroke (8% vs 10%) were less common in ACM than DCM, whereas obstructive lung disease (15% vs 12%) and liver disease (17% vs 2%) were more prevalent (p<0.05). Cumulative 5-year mortality was 49% in ACM vs 33% in DCM, p<0.0001, multivariable adjusted hazards ratio 2.11 (95% confidence interval 1.97-2.26). The distribution of causes of death was similar in ACM and DCM, with the predominance of cardiovascular causes in both groups (42% in ACM vs 44% in DCM). 5-year cumulative incidence of heart failure hospitalisations (48% vs 54%) and any somatic cause (59% vs 65%) were also similar in ACM vs DCM. At 1 year, the use of beta blockers (55% vs 80%) and implantable cardioverter defibrillators (3% vs 14%) were significantly less often used in ACM vs DCM. Patients with ACM had similar cardiovascular risks and hospitalisation patterns as other forms of DCM, but lower use of guideline-directed cardiovascular therapies and greater mortality.

Alcoholic cardiomyopathy- characterization and outcomes

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Alcoholic cardiomyopathy is a severe consequence of chronic alcohol abuse and causes gradual changes in the structure and function of the heart, being a form of dilated cardiomyopathy. Purpose To characterize the population of patients (pts) with alcoholic cardiomyopathy (AC) in terms of baseline characteristics, echocardiographic parameters, alcohol consumption, medication and outcomes. We also intended to evaluate the impact of alcohol reduction/cessation. Methods We performed a retrospective study of the group of pts with the diagnosis of AC, established after exclusion of other aetiologies, followed in the heart failure consultation between 2018 and 2022. We divided the population into patients who maintained (2), reduced (1) (to an average of 2 drinks in men and 1 in women) or discontinued consumption (0). Results A total of 39 pts with a mean age of 68.13 ± 11 years were included. Of these, 35 were males (89.7%). In terms of cardiovascular risk factors, 64.1% had hypertension, 33.3% had diabetes, 53.5% dyslipidaemia, 10.3% had chronic hepatic disease, 30.8% were smokers and 10.3% ex-smokers. The prevalence of atrial fibrillation (AF) was 46.2%, with a median heart rate of 72.50 ± 20.99 bpm. At the beginning of follow-up, this population had a mean left ventricular ejection fraction (LVEF) of 30.46% ± 9.99, a mean indexed LA volume of 58.5 ml/m2 ± 32.63 and a mean indexed LV volume 87.44% ± 27.73. Concerning the alcohol consumption, during the follow-up, 43.6% of the patients stopped drinking alcohol, 10.3% reduced the habits and 20.5% maintained the consumption. Regarding the medication, at the end of follow-up 24.4% were medicated with sacubitril/valsartan, 51.1% with angiotensin-converting enzyme inhibitors, 71.1% with beta blockers, 51.1% with mineralocorticoid receptor antagonists and 35.6% with SGLT2 inhibitors. In a mean follow-up of 26.62± 11.11 months, there was a significant improvement of the ejection fraction (mean of 9.59% ± 12.97, p&amp;lt; 0.001), with a mean LVEF of 40.59% ± 12.78 at the end of follow-up. In fact, in 17.8% of the patients the final LVEF was more than 50%. Regarding indexed LV volume, there was a significant reduction during follow-up (102.250 ± 43.46 ml/m2, p= 0.018). Concerning alcohol consumption, pts who quit drinking had a mean improvement of LVEF of 13,73% ± 15.83 (p= 0.003), pts who reduced alcohol consumption 8.6% ± 5.81 (p=0.03) and pts that kept the consumption 2.67% ± 3.01 (p= 0.82). The variation of LVEF was statistically significant between the groups (p=0.03). These three groups had no statistically significant differences in medical history of hypertension (p=0.37), diabetes (p=0.22), dyslipidaemia (p=0.17), AF (p=0.70) and medication. Conclusion Pts with alcoholic cardiomyopathy had a high prevalence of atrial fibrillation and cardiovascular risk factors. Improvement and even recovery of cardiac function depends on reduction/extinction of alcohol consumption.

Sex and gender differences in myocarditis and dilated cardiomyopathy: An update.

In the past decade there has been a growing interest in understanding sex and gender differences in myocarditis and dilated cardiomyopathy (DCM), and the purpose of this review is to provide an update on this topic including epidemiology, pathogenesis and clinical presentation, diagnosis and management. Recently, many clinical studies have been conducted examining sex differences in myocarditis. Studies consistently report that myocarditis occurs more often in men than women with a sex ratio ranging from 1:2-4 female to male. Studies reveal that DCM also has a sex ratio of around 1:3 women to men and this is also true for familial/genetic forms of DCM. Animal models have demonstrated that DCM develops after myocarditis in susceptible mouse strains and evidence exists for this progress clinically as well. A consistent finding is that myocarditis occurs primarily in men under 50 years of age, but in women after age 50 or post-menopause. In contrast, DCM typically occurs after age 50, although the age that post-myocarditis DCM occurs has not been investigated. In a small study, more men with myocarditis presented with symptoms of chest pain while women presented with dyspnea. Men with myocarditis have been found to have higher levels of heart failure biomarkers soluble ST2, creatine kinase, myoglobin and T helper 17-associated cytokines while women develop a better regulatory immune response. Studies of the pathogenesis of disease have found that Toll-like receptor (TLR)2 and TLR4 signaling pathways play a central role in increasing inflammation during myocarditis and in promoting remodeling and fibrosis that leads to DCM, and all of these pathways are elevated in males. Management of myocarditis follows heart failure guidelines and there are currently no disease-specific therapies. Research on standard heart failure medications reveal important sex differences. Overall, many advances in our understanding of the effect of biologic sex on myocarditis and DCM have occurred over the past decade, but many gaps in our understanding remain. A better understanding of sex and gender effects are needed to develop disease-targeted and individualized medicine approaches in the future.

Peripartum Cardiomyopathy in Emergency Department: A Case Report

Peripartum cardiomyopathy (PPCM) is a form of dilated cardiomyopathy, which is one of the potential life-threatening complications of pregnancy. Peripartum cardiomyopathy is observed between the last 4 weeks of the pregnancy and the postpartum 5th month. It is related to high rate of maternal and infant mortality. Although the underlying factor has not been clearly understood yet, many factors such as infections, myocarditis, immunological factors or oxidative stress caused by prolactin have been attributed. We aimed to discuss the emergency management of postpartum PPCM in our case report.

Variable Presentations of Enteric Fever, beyond Fever and Pain Abdomen: A Case Series

Enteric Fever (Typhoid and Paratyphoid fever) is an illness that presents with marked pyrexia, abdominal pain and other gastrointestinal symptoms. Symptoms and complications primarily involve gut. But sometimes it involves other organ systems like heart, and brain. It thus poses a great diagnostic challenge in diagnosing these extraintestinal manifestations. The three cases depicted in this case series had unusual presentations in the form of dilated cardiomyopathy, non haemophagocytic lymphohistiocytosis (HLH) dyslipidaemia and encephalopathy. The first case is a case of reversible cardiomyopathy in a 26-year-old male presenting with fever for seven days with headache, loose motions and vomiting with audible S3 and bibasal crepitations without oedema. The patient responded to ceftriaxone and azithromycin. On echocardiography dilated cardiomyopathy was diagnosed after which treatment with ramipril and metoprolol was started. The second case was of a 30-year-old female presenting with fever, vomiting, and abdominal pain. There was hypertriglyceridaemia with normal ferritin levels. The patient responded to ceftriaxone. High Density Lipoprotein (HDL) level was low. Statin and fenofibrates were added after which the triglyceride levels came down. This was an interesting case of nonHLH dyslipidaemia which responded to therapy. The third case was of a 40-year-old female presenting with fever for six days with impairment of consciousness. Bilateral plantar responses were extensor and there was no papilledema or any cranial nerve palsy. Magnetic Resonance Imaging (MRI) Brain and Cerebrospinal Fluid (CSF) study were normal. The patient responded to ceftriaxone and dexamethasone proving beneficial effects of steroids in enteric encephalopathy. The purpose of the case series was to make clinicians aware of these uncommon presentations of a common disease so that early diagnosis and treatment with Anti Salmonella antibiotics can be initiated quickly to prevent complications.

Rhinovirus as a rare cause of acute onset dilated cardiomyopathy due to myocarditis in a newborn: case report and review of the literature

Cardiomyopathies account for 1% of cardiac diseases that mainly originate from myocarditis in the form of dilated cardiomyopathy in the neonatal period. Viruses are the main cause of myocarditis resulting in dilated cardiomyopathy. Rhinovirus is the leading cause of viral respiratory infections though it is rarely severe. We report a 17 day old newborn with acute onset dilated cardiomyopathy due to myocarditis that developed after a viral respiratory infection caused by Rhinovirus who was admitted to the emergency ward with shock due to heart failure and recovered without any complications. This is the first case reporting the causal role of rhinovirus and myocarditis in the neonatal period. A comprehensive approach is needed for the diagnosis of myocarditis in the case of unknown etiology and an extensive respiratory panel may be taken into consideration if there is a history or clinical symptoms of respiratory infection.

Family form of dilated cardiomyopathy

Cardiomyopathy (CMP) is classified into familial and non-familial, which reflects the need to study the genetic basis of the disease. The article describes a clinical case of a familial form of non-compact cardiomyopathy in combination with a dilated form of cardiomyopathy. The article provides data of echocardiographic and MRI studies. The diagnosis was confirmed by genetic research, there was revealed a mutation in the MYH7 gene p.IIe201Thr in a heterozygous state, which is associated with the development of non-compact cardiomyopathy and dilated form of cardiomyopathy.

Abstract 13546: Putative Titin Mutations Associated With Both Long QT Syndrome and Left Ventricular Noncompaction

Introduction: Inherited long QT Syndrome (LQTS) is characterized by prolonged QTc intervals on electrocardiogram (EKG), ventricular arrhythmias and sudden death (SCD), and is caused by mutations in ion channel or ion-channel related genes. Inherited forms of dilated cardiomyopathy (DCM) and left ventricular noncompaction (LVNC), on the other hand, are caused by mutations in sarcomeric and structural genes including titin. Methods: Two unrelated families with histories of SCD presented to us for clinical evaluation of LQTS. Clinical genetic testing covering arrhythmia and cardiomyopathy genes was performed on each proband, with carrier testing on other family members. Results (Figure): The proband of family 1 had a strong family history of SCD, carried the clinical diagnosis of LQTS treated with propranolol, and had normal cardiac function by echocardiography. Following chemotherapy with adriamycin for breast cancer, evaluation showed a QTc of 514 ms on EKG, non-sustained VT on Holter, and LVNC with an LVEF=43% on cardiac MRI (cMRI). Genetic testing identified a likely pathogenic nonsense TTN variant (p.W18202*) along with a benign TTN polymorphism (p.E689K). Her clinically normal daughter did not carry the p.W18202* variant. The proband of family 2 had a strong family history of LQTS and SCD and was diagnosed with LQTS in her 20s after her mother suffered a cardiac arrest. Evaluation showed a QTc of 500 ms on EKG and biventricular LVNC with an LVEF=48% on cMRI. Genetic testing identified a likely pathogenic frameshift TTN variant (p.E18038Rfs*47). Three of her children carried the variant and had borderline or prolonged QTc intervals; one had hypertrabeculation on cMRI. Conclusion: We have identified two truncating TTN variants in close proximity to each other in unrelated families with overlapping LQTS/LVNC/DCM syndromes. Mutations in TTN may play a previously unappreciated role in the pathogenesis of inherited arrhythmia syndromes.

Noncompact myocardium with dilated phenotype: differences in comparison with other forms of dilated cardiomyopathy

Abstract Introduction Noncompact myocardium (NCM) is a cardiomyopathy with various genetic causes and clinical manifestations; its relationship with other forms of dilated cardiomyopathy (DCM) and its impact on prognosis are unclear. Objective To study the place of NCM in the structure of DCM, its clinical features and influence on prognosis in comparison with other forms of DCM syndrome. Methods The NCM registry includes 125 patients, mean age 46.4±15.1 years, 74 men and 51 women, mean follow-up 14 [4.0; 41.0] months. The DCM registry included 365 patients, mean age 46.4±15.1 years, 253 men and 112 women, mean follow-up 14 [5; 43.75] months. The examination included ECG, ECG Holter monitoring, echocardiography, blood anti-heart antibody level evaluation, and additionally cardiac CT, MRI, DNA diagnostics (in the MYH7, MYBPC3, TPM1, TNNI3, TNNT2, ACTC1, TAZ, ZASP (LDB3), MYL2, MYL3, DES, LMNA, EMD, TTR gene panel), coronary angiography, right ventricular endomyocardial biopsy. Results The proportion of patients with DCM phenotype in the NCM registry was 40% (n=49), another 11% (n=15) had DCM syndrome diagnosed simultaneously with acute/subacute myocarditis. Lethality in these subgroups was 12.2% and 33.3%, respectively, and was significantly higher than in asymptomatic, ischemic and arrhythmic variants of DCM. In the DCM registry, the proportion of patients with NCM was 21% (n=78), and increased left ventricular (LV) trabecularity was detected in another 18% (n=64). DCM patients with and without NCM did not differ by baseline echocardiographic parameters, heart failure class, and cardiotropic therapy. Pathogenic mutations were detected in 14% of DCM patients with NCM and only 3% of other patients with DCM (p&amp;lt;0.001). Only in patients without NCM the presence of mutations had a significant effect on lethality. The patients with NCM compared with the others DCM patients showed significantly lower increase in EF in early and late period (from 31.0±10.2 to 34.8±11.0 and 37.1±10.9% vs from 31.8±9.7 to 38.8±11.3 and 42.3±12.4%, p&amp;lt;0.05 vs 05 and &amp;lt;0.01, respectively), a greater incidence of PVBs (1568 [105; 7000] vs 543.5 [77.75; 3194], p&amp;lt;0.05), appropriate defibrillator shocks and sudden deaths (17.9 vs 5.9%, p&amp;lt;0.001), intracardiac thrombosis (21.8 vs 13.5%, p=0.069) despite a greater frequency of anticoagulants (73.1 vs 57.4%, p&amp;lt;0&amp;lt;05). There were no significant differences in death (19.2 vs 18.5%) and transplantation (7.7 vs 3.8%) between patients with and without NCM. There were no cases of NCM regression. Conclusion NCM is an independent form of DCM syndrome, which is characterized by higher frequency of pathogenic mutations, arrhythmic events, worse response to cardiotropic therapy, higher frequency of intracardiac thrombosis. The absence of mortality differences can be explained by the higher frequency of preventive interventions in this category of patients with DCM (prescription of anticoagulants, defibrillator implantation, heart transplantation). Funding Acknowledgement Type of funding sources: None.

Effectiveness of implanted cardiac rhythm recorders with electrocardiographic monitoring for detecting arrhythmias in peripartum cardiomyopathy (PPCM)

Abstract Introduction Peripartum cardiomyopathy (PPCM) is a form of dilated cardiomyopathy that occurs within the last months of pregnancy or up to 5 months postpartum. Previous studies have shown that up to 30% of deaths in PPCM are related to sudden cardiac death (SCD). However, little is known about the burden of arrythmias in PPCM and their contribution to SCD. Purpose We aimed to compare implantable loop recorder (ILR) plus 24-hour Holter monitoring to 24h Holter monitoring alone to assess its utility in the detection of arrhythmias in PPCM. Methods In this single-centre, prospective clinical trial, 20 consecutive patients with PPCM were randomized to either standard care (SC cohort: ECG &amp; 24-hour Holter) or SC plus ILR (SC-ILR cohort: ECG, 24-hour Holter, ILR). Follow-up included the first six months after ILR implantation. Results The median age of this cohort was 31.7 years with a parity of 2 (IQR 1–4). They presented with a median left ventricular ejection fraction (LVEF) of 28% (IQR 24–35) and LVEDD of 60mm (IQR 55–66). The 12-lead ECG recorded sinus tachycardia in half of the patients, with median heart rate of 90bpm (IQR 79–106) compared to 94.5bpm (IQR 85–99) on 24h-Holter-monitoring. The median QTc-interval was 464ms (IQR 424–494). Ambulatory ECG monitoring detected major arrhythmias in three women (one in SC cohort, two in SC-ILR cohort). One patient (5%) died shortly after ILR implantation. Her ILR detected sinus arrest with an escape rhythm (figure 1A) that failed and resulted in an out of hospital cardiac arrest. Non-sustained ventricular tachycardia (nsVT) occurred in two women (10%), one of which was detected by Holter monitoring and the other on ILR (figure 1B, 1C). Both women presented with acute heart failure with severely impaired systolic function (LVEF 12% and 21% respectively). One of these patients had persistent LV systolic dysfunction despite optimal medical therapy and received an implantable cardioverter-defibrillator (ICD). The other patient had intractable heart failure requiring recurrent intensive-care treatment and underwent heart transplantation. There was no atrial fibrillation or atrioventricular block detected in any patient by ECG, Holter or ILR monitoring throughout the study period. Conclusion This study on ambulatory ECG monitoring in PPCM showed a high prevalence of potentially fatal arrhythmias, which occurred predominantly in the acute phase of the disease. One patient had sinus arrest and asystole detected by ILR as the terminal arrhythmia. Both Holter monitoring and ILR played an important role in ventricular arrhythmia detection, which in two cases had a direct influence on clinical decision making. ILR is more effective than 24-hour Holter monitoring in paroxysmal arrhythmia detection because of extended monitoring. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Medtronic South Africa Ambulatory ECG monitoring in PPCM

Endocardial fibroelastosis and dilated cardiomyopathy - the past and future of the interface between histology and genetics.

Endocardial fibroelastosis (EFE) signifies the pathological process by which collagen and elastin are focally or diffuse deposited in the endocardium of the left ventricle. The new layer causes left ventricular dysfunction sometimes with fulminant progression to heart failure. EFE is a major component in many congenital heart abnormalities but can also occur in the absence of heart malformations, either as a primary process or in response to cardiac injury. The endothelial–mesenchymal transition (EndMT) abnormalities seem to be main pathogenic factor in fibroelastosis development. The “gold standard” for diagnosis of primary EFE (pEFE) is the histological examination. Additionally, genetic studies may help to establish the natural course of the disease and to communicate prophylactic measures to family members of the affected child. Moreover, in the newborn, EFE takes the form of dilated cardiomyopathy (DCM) with unfavorable evolution. The proper management should be established considering negative prognostic factors, involving early transplantation, drug therapy and long-term follow-up.

Undiagnosed Peripartum Cardiomyopathy for emergency Caesarean section: Lessons learnt

Peripartum cardiomyopathy is a form of dilated cardiomyopathy. It is a systolic heart failure of unknown aetiology and poorly understood pathophysiology. The prognosis of patients with PPCM is generally good with 70-80% recovering with ejection fraction &gt;50% at the end of 6 months. However, the intrapartum period, especially in case of operative delivery, is fraught with danger

The Broad Spectrum of LMNA Cardiac Diseases: From Molecular Mechanisms to Clinical Phenotype.

Mutations of Lamin A/C gene (LMNA) cause laminopathies, a group of disorders associated with a wide spectrum of clinically distinct phenotypes, affecting different tissues and organs. Heart involvement is frequent and leads to cardiolaminopathy LMNA-dependent cardiomyopathy (LMNA-CMP), a form of dilated cardiomyopathy (DCM) typically associated with conduction disorders and arrhythmias, that can manifest either as an isolated event or as part of a multisystem phenotype. Despite the recent clinical and molecular developments in the field, there is still lack of knowledge linking specific LMNA gene mutations to the distinct clinical manifestations. Indeed, the severity and progression of the disease have marked interindividual variability, even amongst members of the same family. Studies conducted so far have described Lamin A/C proteins involved in diverse biological processes, that span from a structural role in the nucleus to the regulation of response to mechanical stress and gene expression, proposing various mechanistic hypotheses. However, none of those is per se able to fully justify functional and clinical phenotypes of LMNA-CMP; therefore, the role of Lamin A/C in cardiac pathophysiology still represents an open question. In this review we provide an update on the state-of-the-art studies on cardiolaminopathy, in the attempt to draw a line connecting molecular mechanisms to clinical manifestations. While investigators in this field still wonder about a clear genotype/phenotype correlation in LMNA-CMP, our intent here is to recapitulate common mechanistic hypotheses that link different mutations to similar clinical presentations.

Bi-allelic missense disease-causing variants in RPL3L associate neonatal dilated cardiomyopathy with muscle-specific ribosome biogenesis

Dilated cardiomyopathy (DCM) belongs to the most frequent forms of cardiomyopathy mainly characterized by cardiac dilatation and reduced systolic function. Although most cases of DCM are classified as sporadic, 20–30% of cases show a heritable pattern. Familial forms of DCM are genetically heterogeneous, and mutations in several genes have been identified that most commonly play a role in cytoskeleton and sarcomere-associated processes. Still, a large number of familial cases remain unsolved. Here, we report five individuals from three independent families who presented with severe dilated cardiomyopathy during the neonatal period. Using whole-exome sequencing (WES), we identified causative, compound heterozygous missense variants in RPL3L (ribosomal protein L3-like) in all the affected individuals. The identified variants co-segregated with the disease in each of the three families and were absent or very rare in the human population, in line with an autosomal recessive inheritance pattern. They are located within the conserved RPL3 domain of the protein and were classified as deleterious by several in silico prediction software applications. RPL3L is one of the four non-canonical riboprotein genes and it encodes the 60S ribosomal protein L3-like protein that is highly expressed only in cardiac and skeletal muscle. Three-dimensional homology modeling and in silico analysis of the affected residues in RPL3L indicate that the identified changes specifically alter the interaction of RPL3L with the RNA components of the 60S ribosomal subunit and thus destabilize its binding to the 60S subunit. In conclusion, we report that bi-allelic pathogenic variants in RPL3L are causative of an early-onset, severe neonatal form of dilated cardiomyopathy, and we show for the first time that cytoplasmic ribosomal proteins are involved in the pathogenesis of non-syndromic cardiomyopathies.

P1385 Mechanical dispersion of the right atrium in dilated cardiomyopathy: does the etiology matter?

Abstract Funding Acknowledgements This work was supported by CREDO Project - ID: 49182, financed through the SOP IEC -A2-0.2.2.1-2013-1 cofinanced by the ERDF Background Mechanical dispersion assessed by myocardial strain reflects a susceptibility for arrhythmia development. While the contractile heterogeneity of both ventricles has been assessed in different clinical settings, the incidence and significance of right atrial (RA) dyssynchrony in dilated cardiomyopathy (DCM) are unknown. Methods 50 consecutive patients with DCM were divided in 2 groups according to the etiology: group I had 26 patients with ischemic DCM (68 ± 10 years, 23 men), group N had 24 patients with non-ischemic DCM (52 ± 12 years, 18 men). We assessed the RA strain by 2D speckle-tracking analysis, and we calculated RA mechanical dispersion as the standard deviation of the time-to-peak contraction strain in 6 RA segments. 20 healthy individuals served as controls. Data were compared between groups with one-way analysis of variance and using a post-hoc Bonferroni correction. Results The RA strain was reduced in DCM patients, both in group I and in group N. All three components of the RA strain were most reduced in group I (p &amp;lt; 0.001 for reservoir and conduit strain, p = 0.001 for contraction strain) (Table). The RA mechanical dispersion was highest in group I (56.8 ± 21.6 ms), followed by group N (39.9 ± 15.3 ms) and controls (23.8 ± 7.7 ms)(p &amp;lt; 0.001). Patients with DCM and documented supraventricular arrhythmias (either atrial fibrillation, atrial flutter or premature atrial contractions) had higher RA mechanical dispersion (57.5 ± 19.7 ms) than DCM patients with no documented atrial rhythm disturbances (44.9 ± 19.9 ms, p = 0.04). Conclusion Mechanical dispersion of the RA is pronounced in patients with DCM and it is higher in patients with documented supraventricular arrhythmias. Patients with ischemic DCM have a more pronounced mechanical dispersion of the RA than patients with non-ischemic DCM, reflecting a more heterogenous RA contraction in ischemic heart disease when compared to other forms of DCM. The prognostic significance of RA dyssynchrony in a disease primarily involving the left heart warrants further studies. Group I Group N Controls P value Reservoir RA strain (%) 12.9 ± 7.4§ 17.6 ± 12.9§ 30.1 ± 9.9 &amp;lt;0.001 Conduit RA strain (%) -6 ± 5.5§ -8 ± 8.9§ -15.2 ± 6.4 &amp;lt;0.001 Contraction RA strain (%) 6.9 ± 6§ 9.6 ± 8.1 14.9 ± 6.1 0.001 RA mechanical dispersion (ms) 56.8 ± 21.6§ 39.±15.3§* 23.8 ± 7.7 &amp;lt;0.001 § significant difference with controls; * significant difference with group I

P4138Clinical differences between methamphetamine and non-methamphetamine associated non-ischemic dilated cardiomyopathy

Abstract Background Methamphetamine associated cardiomyopathy (MACM) is an increasingly recognized form of dilated cardiomyopathy around the globe which remains poorly characterized. Purpose To compare the clinical characteristics of MACM to those of non-MA associated dilated CM (NMACM). Methods Consecutive patients with MACM presenting to our institution between Jun 2018 and Jan 2019 were prospectively studied and compared to an age and gender-matched cohort of dilated non-ischemic CM cases. Results Seventy patients were studied (35 MACM and 35 NMACM). Mean age was similar between groups (49±9 vs. 48±10 years, p=0.465) and 97% of patients were male. Median duration of MA use prior to cardiomyopathy diagnosis was 5 years (range 0–30). Patients were predominantly Hispanic in both groups (48% vs. 62%, p=0.229), but with a greater proportion of Caucasians in the MACM group compared to NMACM (26% vs 6%, p=0.045).MACM was characterized by lower left ventricular ejection fraction (LVEF) and greater left ventricular end diastolic volume (LVEDV) compared to NMACM. RV dilation was present more often in MACM cases (Table). Years of MA use was associated with greater LA volumes (R2= 0.13, p=0.048). Association with larger LVEDV and incidence of RV dilation were borderline significant (R2= 0.11, p=0.054 and p=0.058 respectively). The amount of MA used per week correlated with higher RVSP (R2=0.317, p=0.004). Polysubstance abuse was associated with greater LVEF (p=0.028), lower LVEDV (p=0.037) and lower LV mass (p=0.004). Echocardiographic parameters MACM Non-MACM p-value LVEDV (ml) 215 (62) 181 (40) 0.009* LVESV (ml) 166 (63) 133 (41) 0.017* LVEF (%) 20 (8) 26 (10) 0.006* LV Mass (g) 311 (109) 285 (81) 0.286 LA Volume (ml) 88 (26) 85 (29) 0.670 RV Dilation (no.) 23 (65.7%) 14 (40.0%) 0.027* Reduced RV Function (no.) 21 (60.0%) 21 (60.0%) 0.596 RVSP (mmHg) 40 (14) 44 (12) 0.671 RAP (mmHg) 9 (5) 10 (5) 0.682 Intracardiac Thrombus (no.) 3 (8.6%) 2 (5.7%) 0.500 Mean values are reported with standard deviation. *p&lt;0.05. Conclusion MACM is associated with higher degree of LV and RV dilatation as well as LV systolic dysfunction when compared to matched NMACM cases. Years of MA use and amount of MA consumed appear to influence severity of disease. Acknowledgement/Funding None

P339The factors associated with death, transplantation and appropriate defibrillators shocks in patients with dilated cardiomyopathy depending on its etiology

Abstract Purpose To study the predictors of death, transplantation and appropriate shocks (AS) of defibrillators in patients with dilated cardiomyopathy (DCM) depending on its etiology. Methods In 300 patients with DCM syndrome (206 males, 47.6±12.7 years, the average left ventricle (LV) end-diastolic diameter 6.4 [5.9; 7.1] cm, LV ejection fraction (EF) 32 [25; 40] %) were performed viral genome (real-time PCR) and anti-heart antibodies investigation, ECG, Holter, Echo-CG, cardiac CT, MRI, coronary angiography, and also morphological study of myocardium in 103 (34%) patients. Defibrillators were implanted in 80 (26.7%) patients: 47 ICD, 33 CRTD. The follow-up was 15 [6; 42] months. Results The following causes of DCM syndrome have been identified: the isolated myocarditis (n=164, 54.7%), the primary/genetic DCM (n=58, 19.3%), the genetic DCM with myocarditis (n=71, 23.7%), peripartum (n=1, 0.3%) and chemotherapy-induced cardiomyopathy (n=5, 1.7%), arteriovenous malformation (n=1, 0.3%). Genetic forms of DCM were represented by noncompact myocardium (n=64), ARVC (n=12), TTR-amyloidosis (n=1), myopathy (n=6). The pathogenic mutations in the genes LMNA (n=1), DES (n=2), DSP (n=2), EMD (n=2), PKP2 (n=1), MUH7+MyBPC3 (n=2), MyBPC3 (n=4) were detected. The AS rate was 23.8%. The only predictor of AS was identified the genetic/primary nature of DCM, that is diagnosed in 100% of patients with AS in comparison with 57% in patients without AS, p&lt;0.001 (AUC 0.716, RR 1.76, 95% CI 1.43–2.17). The patients with AS had higher LVEF (35.7±10.3 vs 28.3±9.7%, p&lt;0.01), smaller LV end-diastolic diameter (6.2±0.6 vs 6.8±0.9 cm, p&lt;0.01), low QRS voltage (39 vs 13%, p=0.077), absence of LV hypertrophy on ECG (79 vs 52%, p&lt;0.05), underuse of beta-blockers (74 vs 92%), sustained VT (32 vs 4%, p&lt;0.05), but not isolated unsustained VT (54 vs 70%, p&gt;0.05). The mortality in patients with DCM was 19.7%, rate of transplantation 4.3%, death + transplantation 23.0%, SCD 2.7%. There were no differences depending on devises implantation due to adequate selection to procedure. The following factors were associated with mortality: high NYHA class and severe heart dysfunction, absence of improvement after start of therapy, acute debut of symptoms, viral genome in the myocardium, absence of anti-heart antibodies, absence of immunosuppressive therapy, beta-blockers and ACE inhibitors and MRA. The predictors of transplantation were genetic/primary DCM, younger age (38.3±10.3 vs 48.0±12.7, p&lt;0.05), low QRS voltage, more frequent PVBs and unsustained VT, severe restrictive dysfunction, absence of immunosuppressive therapy, beta-blockers, and sustained reduction of EF. Conclusions The etiology of DCM syndrome plays a key role in the prognosis and should be considered when selecting patients for ICD and heart transplantation. The genetic nature of DCM is the more important predictor of shocks than EF. The total mortality is clearly associated with resistant myocardial dysfunction.

A-41 years old male with alcoholic cardiomyopathy at Tabanan General Hospital, Bali-Indonesia: a case report

Background: Alcoholic cardiomyopathy is a form of toxic cardiomyopathy which develops as a result of long-standing chronic ingestion of alcohol. Its clinical findings share similar features to other forms of dilated cardiomyopathy. Diagnosis can be made based on the history of long term alcohol abuse, clinical findings, and supporting diagnostic studies. This case report aims to overview alcoholic cardiomyopathy; from establishing the initial diagnosis to the treatment given for the condition.Case Description: A 41 years old male came to the emergency department unit with shortness of breath since last few days. Shortness of breath was said to be getting worse over time and progressed to breathlessness at rest. Other complaints were palpitations, fatigue, and long-standing cough. The patient was found to have a history of drinking alcohol in large quantities since 27 years ago. The blood pressure was 110/70 mm Hg, pulse rate 105 beats/min, and respiratory rate was 20 breaths/min. Slight edemas on both legs were also found. From auscultation examination, bibasilar crepitation on both lungs was found. Cardiac examination showed systolic murmur of mitral regurgitation (MR) and tricuspid regurgitation (TR). On supporting investigation, a chest x-ray showed cardiomegaly (cardiothoracic ratio; 57%). ECG examination showed sinus tachycardia and left atrial (LA) and left ventricular (LV) enlargement. Trans-thoracal echocardiographic (TTE) examination revealed; RWMA: global hypokinetic-akinetic, multi-chamber dilated and severe LV systolic dysfunction (EF 29%) and diastolic function (Grade IV (E/A Ratio&gt;4)). Valve examination showed moderate-severe MR and moderate TR (TVG 40 mmHg).Conclusion: Alcohol cardiomyopathy is one of the most common causes of heart failure in young age and carries a poor prognosis if not treated properly. Treatment of alcoholic cardiomyopathy mainly includes total alcohol abstinence along with drugs used to treat systolic heart failure to reverse the condition and correct any nutritional deficiencies.

INDICATIONS FOR IMPLANTATION AND EFFICIENCY OF CARDIOVERTER-DEFIBRILLATORS IN PATIENTS WITH DILATED CARDIOMYOPATHY

Purpose. To assess the frequency and predictors of appropriate shocks of cardioverter-defibrillators in patients with dilated cardiomyopathy (DCM) syndrome and the impact on the total mortality and sudden cardiac death (SCD).Material and Methods. A total of 275 patients with DCM syndrome (average age of 46.8 ± 12.5 years; 185 males and 90 females) were observed. Inclusion criteria were left ventricular (LV) end-diastolic diameter (EDD) more than 5.5 cm and LV ejection fraction (EF) less than 50%. Patients with coronary artery stenosis more than 50% were excluded. Implantable cardioverter-defibrillator (ICD) (n=44) and cardiac resynchronization therapy defibrillator (CRT-D) (n=32) were implanted in 76 (27.6%) patients (53 males and 23 females, average age of 48.9±12.9 years, LV EDD of 6.7±0.8 cm, and LV EF of 28.2±9.9%). A comparison group comprised 199 patients (72.4%) without devices (132 males and 67 females, average age of 46.0±12.3 years, LV EDD of 6.5±0.8 cm, and LV EF of 32.0±10.2%). The average follow-up was 27 (24; 30) months.Results. SCD in patients with DCM syndrome was recorded in 2.9% of cases; the total mortality rate was 18.9%; the rate of death + transplantation was 22.6%. The SCD, total mortality, and death+transplantation rates were 2.6% (4.6/0%), 23.7% (22.7/25.0%), and 32.9% (34.1/31.3%) in patients with devices (ICD/CRT-D) and 3.0%, 17.1%, and 16.6% in patients without devices, respectively. The rate of SCD+appropriate shocks (ASR) was significantly higher in study group: 26.3 vs 3.0% in comparison group (p&lt;0.001). The nature of DCM syndrome was predominantly inflammatory (53%), primary (genetic) (19.6%), and multifactorial (25.1%). Genetic forms of DCM were represented by non-compaction cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy (ARVC), myopathies, and amyloidosis. The pathogenic mutations in the genes LMNA (n=1), DES (n=2), DSP (n=2), EMD (n=2), PKP2 (n=1), TTR (n=1), MUH7+MyBPC3 (n=1), and MyBPC3 (n=4) were detected. The ASR (ICD/CRT-D) rate was 23.7% (n=13/5). The only reliable predictor of ASR was the generic nature of DCM syndrome, identified in 100% of patients with shocks (in the presence of myocarditis in 77.8%/isolated in 22.2%) in comparison with 51.7% (29.3/22.4%) in patients without ASR (p&lt;0.002, AUC 0.747, RR 1.66, 95% CI 0.711-3.885). Ventricular tachycardia (VT) was registered in 84% of patients with shocks (stable/unstable VT rates of 17/67%) vs 1.7/72%, in patients without shocks (р=0.06). In patients with shocks, low QRS voltage (39 vs 6.9%, р&lt;0.05) and the absence of LV hypertrophy signs on the ECG (77.6 vs 58.6%, р&gt;0.05) were registered more often. The average LV EF was higher in patients with ASR (34.4±9.7%) in comparison with patients without ASR (25.9±8.8%), р&lt;0.005. Conclusions. The genetic nature of DCM syndrome is an important predictor of appropriate shocks and an independent selection criterion for ICD/CRT-D implantation. Age, NYHA class, and LV EF did not show prognostic significance. Additional predictors of appropriate shocks were sustained/unsustained VT, low QRS voltage, and the absence of LV hypertrophy signs on the ECG.