Alcoholic Cardiomyopathy Research Articles

Metformin alleviates ethanol-induced cardiomyocyte injury by activating AKT/Nrf2 signaling in an ErbB2-dependent manner.

Metformin, a first-line oral anti-diabetic drug, has recently been reported to exert protective effect on various cardiovascular diseases. However, the potential role of metformin in ethanol-induced cardiomyocyte injury is still unknown. Therefore, this study was aimed to investigate the effect of metformin on ethanol-induced cardiomyocyte injury and its underlying mechanism. H9c2 cardiomyocytes were exposed to ethanol for 24h to establish an ethanol-induced cardiomyocyte injury model, and followed by treatment with metformin in the presence or absence of Lapatinib (an ErbB2 inhibition). CCK8 and LDH assays demonstrated that metformin improved cell viability in cardiomyocytes exposed to ethanol. Furthermore, metformin suppressed cardiomyocyte apoptosis and reduced the expressions of apoptosis-related proteins (Bax and C-CAS-3). In addition, our results showed that metformin activated the AKT/Nrf2 pathway, and then promoted Nrf2 nuclear translocation and the transcription of its downstream antioxidant genes (HO-1, CAT and SOD2), thereby inhibiting oxidative stress. Interestingly, we found that ErbB2 protein expression was significantly inhibited in ethanol-treated cardiomyocytes, which was markedly reversed by metformin. In contrast, Lapatinib largely abrogated the activation of AKT/Nrf2 signaling by metformin, accompanied by the increases in oxidative stress and cardiomyocyte apoptosis, indicating that metformin prevented ethanol-induced cardiomyocyte injury in an ErbB2-dependent manner. In summary, our study provides the first evidence that metformin protects cardiomyocyte against ethanol-induced oxidative stress and apoptosis by activating ErbB2-mediated AKT/Nrf2 signaling. Thus, metformin may be a potential novel treatment approach for alcoholic cardiomyopathy.

ХРОНИЧЕСКИЙ АЛКОГОЛИЗМ В СОЧЕТАНИИ С ИЗМЕНЕНИЕМ ВНУТРЕННИХ ОРГАНОВ И АТЕРОСКЛЕРОЗОМ

Objective. Establish frequency of change of internal organs and the atherosclerotic process in patients suffering from chronic alcoholism and determine the causes of death. Material and methods. The results of autopsies of the 94 dead with chronic alcoholism in the Centre of Mental Health for 2005–2014 years. Analysis of the material was carried out on the basis of macroscopic and microscopic examination (histological specimens stained with hematoxylin-eosin, pikrofuksin on Van Gieson, on myelin by Kluver-Barrera). During the autopsy, it drew attention to the presence of atherosclerotic lesions in the aorta, coronary and cerebral arteries. Results. According to the morphological study and pathologic diagnosis all observations are as follows: delirium tremens – 24, encephalopathy Gayet-Wernicke – 13, alcoholic encephalopathy – 10, alcoholic dementia – 3, myelinolysis pontis – 8, disease Marchiafawa-Bignami – 1, alcoholic cirrhosis of the liver – 1. All observations were accompanied by severe morphological changes at least 3–4 of the internal organs. Severe atrophic gastritis occurred in 39 cases (75%), alcoholic dilated cardiomyopathy – 31 (59.6%), sclerosing pancreatitis – 32 (61.5%), morphological changes in the liver (steatosis and alcoholic hepatitis) – 43 (82.7%), two observations – alcoholic cirrhosis of the liver, bronchopneumonia – 23 (44.2%). Signs of atherosclerosis were found in 19 cases (36.5 %). The average age of the deceased in these cases was 53.4 years. Conclusion. Complications of chronic alcoholism accompanied by morphological changes of internal organs, which greatly aggravate the disease. The most significant are the changes in the heart in the form of alcoholic dilated cardiomyopathy with the development of acute or chronic cardiovascular failure. A certain importance is pancreatitis, which can result in the development of pancreatic necrosis and changes in the liver with the development of liver failure. In some cases (especially in patients with alcoholic dementia) a major role in tanatogenesis can play bronchopneumonia. Atherosclerotic process is not significant in tanatogenesis of patients with chronic alcoholism and occurs predominantly in elderly patients.

Inhibition of Ceramide Synthesis Attenuates Chronic Ethanol Induced Cardiotoxicity by Restoring Lysosomal Function and Reducing Necroptosis.

Chronic alcohol misuse could cause alcoholic cardiomyopathy (ACM), and the specific mechanisms remained largely unknown. In this study, we aimed to explore the effects of endogenous ceramides on chronic ethanol-induced myocardial injury or cell loss (e.g. necroptosis). We established chronic alcohol intoxication models in vivo (male C57BL/6 mice) and in vitro (H9c2 cardiomyoblasts). The ceramide profiles were analyzed in mice myocardium and cultured cardiomyocytes. Further research on the role of ceramides and underlying signaling pathways was carried out in H9c2 cells. The ceramide profiles analysis revealed increased long and very long-chain ceramides in alcoholic myocardium and ethanol-treated cardiomyocytes. Next, we proved that endogenous ceramide inhibition could reduce necroptosis and alleviate cardiomyocytes injury as suggested by decreased levels of p-RIPK1, p-RIPK3 and p-MLKL proteins and cardiac injury factors expression. Furthermore, we found that lysosomal dysfunction also contributed to alcohol-induced cardiac damage and inhibiting ceramide biosynthesis could repaired this to some extent. Cells studies with exogenous C6 ceramide confirmed the pleotropic roles of ceramide in myocardial damage by causing both necroptosis and lysosomal dysfunction. Finally, our data suggested that lysosomal dysfunction could sensitize cardiomyocytes to induction of necroptosis due to the restriction on degradation of RIPK1/RIPK3 proteins. In conclusion, chronic ethanol treatment boosted myocardial ceramide synthesis in animal hearts and cultured cardiomyocytes. Moreover, ceramides exerted crucial roles in the intrinsic signaling pathways of alcohol-induced cardiotoxicity. Targeting ceramide biosynthesis to simultaneously attenuate necroptosis and lysosomal dysfunction might be a novel strategy for preventing alcoholic cardiotoxicity.

National, regional, and global cardiomyopathy burden from 1990 to 2019.

To examine the incidence of cardiomyopathy including both alcoholic cardiomyopathy (AC) and other cardiomyopathy (OC) in 204 nations and regions over the 1990-2019 period. The present study was conducted using data derived from the GBD 2019 study coordinated by the Institute for Health Metrics and Evaluation (IHME). The GBD 2019 study included epidemiological data pertaining to 369 diseases/injuries, 286 causes of death, and 87 risk factors in 204 nations and regions. For this study, we adopt published estimates pertaining to the prevalence rates, mortality rates, and disability-adjusted life years (DALYs) associated with cardiomyopathy. The Bayesian mixed-effects DisMod-MR 2.1 meta-regression tool, which was designed to analyze GBD data, was used to estimate the prevalence of OC and AC. The GBD data are subdivided into 21 global regions based on characteristics such as geographical proximity and epidemiological similarity. The overall burden of cardiomyopathy was assessed by combining AC- and OC-related data, 95% confidence intervals were calculated based on standardized error values determined based upon the width of the 95% UI divided by 1.96 × 2. Globally, there were an estimated 0.71 million (95% UI: 0.55-0.92) AC cases and 3.73 million (95% UI: 2.92-4.72) OC cases in 2019. The age-standardized cardiomyopathy, AC, and OC prevalence rates (per 100,000 persons) in 2019 were 56.0 (95% CI: 43.82-71.17), 8.51 (95% UI: 6.6-11.01), and 47.49 (95% UI: 37.22-60.16), respectively. In total, the respective numbers of global deaths attributed to AC and OC were 0.07 million (95% UI: 0.06-0.08) and 0.24 million (95% UI: 0.19-0.26). The age-standardized mortality rate for cardiomyopathy in 2019 was 3.97 (95% CI: 3.29-4.39), with respective mortality rates of 0.86 (95% UI: 0.72-0.99) and 3.11 (95% UI: 2.57-3.4) for AC and OC. At the global level in 2019, 2.44 million (95% UI: 2.04-2.78) DALYs were attributed to AC, while 5.72 million (95% UI: 4.89-6.33) DALYs were attributed to OC. From 1990 to 2019, cardiomyopathy age-standardized prevalence rates declined by -0.49% (95% CI: -0.57 to -0.41), with those for AC and OC having respectively declined by -0.32% (95% UI: -0.36 to -0.28) and -0.17% (95% UI: -0.21 to -0.13). The age-standardized AC and OC mortality rates declined by -0.36% (95% UI: -0.5 to -0.26) and -0.39% (95% UI: -0.44 to -0.29), despite 24.8 and 30.2% increases, respectively, in the numbers of AC- and OC-related deaths during the same period. Previous studies have estimated the risk factors that influence the burden of multiple cardiovascular diseases (CVD). Among them, some studies related to the GBD database on cardiomyopathy data suggest that alcohol intake, gender are factors in the development of AC, and the burden of AC and OC is not limited to developed or less developed countries. Otherwise, this study mainly focused on cardiomyopathy, and analyzed multiple indicators from national, regional, and age-standard dimensions to identify potential risk factors including prevalence, deaths, years lived with Disability-adjusted life years (DALYs) that influence the development of AC and OC. To our knowledge, this study is the first to have systematically assessed the burden of AC and OC as of 2019 at the national, regional, and global levels and calculated DALYs to achieve a better evaluation of disease risk and quality of life of the population. The number of cases, deaths and DALYs of cardiomyopathy showed an overall increasing trend and obvious geographical differences in the past three decades. The burden of cardiomyopathy remains a persistent threat to global public health. These results provide an epidemiological foundation that can guide public health efforts and policymakers.

Prognostic Importance of Atrial Fibrillation and Anticoagulation in Alcoholic Versus Dilated Cardiomyopathy.

Limited data exist to describe the prognostic impact of atrial fibrillation (AF) and oral anticoagulation on patients with alcoholic cardiomyopathy (ACM) compared with dilated cardiomyopathy (DCM) and were investigated in this study. Using Danish nationwide registries, a cohort analysis was conducted to assess the prognostic differences for patients with a first diagnosis of ACM versus DCM with and without AF 1994-2018 (followed until end 2019). Our study also assessed differences in mortality following initiation of anticoagulation in both populations. Totally, 1237 patients with ACM (33% with AF) and 17,211 individuals with DCM (33% with AF) were included. Those with ACM were more often men (89 versus 71%) and younger than patients with DCM (mean age 56 versus 64years). Cumulative 5-year mortality was greater among patients with ACM, compared with DCM, regardless of AF (ACM with AF 49% [95% CI: 44-54%], ACM without AF 48% [45-53%], DCM with AF 41% [39-42%], DCM without AF 30% [29-31%], P < 0.0001). The prognosis associated with AF was statistically significantly different in people with ACM and DCM (adjusted hazards ratio 0.85 [95% CI: 0.74-0.98] versus 1.04 [1.00-1.09] in ACM and DCM, P < 0.0001). The mortality associated with oral anticoagulation was similar in ACM and DCM (hazards ratio 0.81 [0.61-1.07] versus 0.87 [0.80-0.94], P = 0.49). Patients with ACM had a worse prognosis when compared with patients with DCM, but this did not appear to be driven by AF. Patients with ACM were observed to have similar associated risk benefits of oral anticoagulation as DCM.

Abstract 15276: Polygenic Susceptibility to Dilated Cardiomyopathy Underlies Peripartum, Alcoholic, and Chemotherapy-Induced Cardiomyopathies

Introduction: Rare (monogenic) variants linked to dilated cardiomyopathy (DCM) are enriched among individuals with peripartum (PPCM), alcoholic (ACM), and chemotherapy-induced cardiomyopathies (CCM), but are present in &lt;15% of cases. Whether a common-variant (polygenic) susceptibility to DCM is also shared across these secondary cardiomyopathies is unknown. Methods: Cases of DCM, PPCM, ACM, and CCM were adjudicated using hospital billing codes only (in UK Biobank), or with additional chart reviews conducted by 2 medical doctors blinded to the genetic data (in Mass General Brigham [MGB] Biobank). A DCM polygenic score predicated on imaging-based measures of left ventricular structure and function was tested for association with each condition. In a subset of MGB Biobank participants with whole exome sequencing data, we determined the proportion of cases with a monogenic variant and/or a high (≥90 th percentile) polygenic score. Results: In MGB Biobank (n=30,837) and UK Biobank (n=304,687), 193 cases of PPCM (n=18), ACM (n=127) or CCM (n=48) were identified. A DCM polygenic score comprising 2.3 million common genetic variants associated comparably with DCM and all three secondary cardiomyopathies (meta-analyzed p&lt;0.001 for all) ( Figure ). Among chart-validated phenotypes in MGB Biobank, cases had higher median polygenic score percentiles than controls (Controls=50; DCM=68; PPCM=86; ACM=70; CCM=59), and a high polygenic score conferred 3.3-fold odds of any secondary cardiomyopathy (p&lt;0.001). In the whole exome sequencing subset (N=21,378; n=65 secondary cardiomyopathy cases), 9.2% of secondary cardiomyopathy cases harbored a monogenic variant, while 21.5% had a high polygenic score (including 1.5% who had both). Conclusion: Individuals with PPCM, ACM, and CCM are enriched for a high DCM polygenic score, further suggesting that these conditions arise from unique, extrinsic insults acting in the context of a common, underlying genetic susceptibility.

Increased incidence of alcohol use disorder and alcohol-related psychiatric disorders in patients with obstructive sleep apnea: A nationwide population-based cohort study

BackgroundObstructive sleep apnea (OSA) and alcohol-related diseases (ARDs), including alcohol use disorder, alcohol-related psychiatric disorders, alcoholic liver disease, alcoholic polyneuropathy alcoholic cardiomyopathy, and alcoholic gastritis, are both highly prevalent conditions. Alcohol consumption is associated with a higher risk of sleep apnea. However, whether OSA increases the risk of ARD has not, as yet, been studied comprehensively. Our study aimed to determine whether OSA increases the subsequent risk of ARD. MethodsThis study utilized the data from Taiwan's National Health Insurance Database between 2000 and 2015. We identified 7722 individuals newly diagnosed with OSA and randomly selected sex-, age-, and index date-matched (1:3) 22,166 controls without OSA, with a total of 29,888 subjects. We used the Fine and Gray's survival analysis to estimate the effects of OSA on ARD. ResultsThe OSA cohort had an adjusted hazard ratio of subsequent ARDs as 1.486 (95% Confidence Interval: 1.301–1.698), when comparing the cohort without OSA. The Kaplan-Meier analysis showed that the cumulative incidence of ARDs was significantly higher in the OSA cohort than in the controls in the first year of follow-up, till the end of the follow-up. A post-hoc analysis showed that OSA was associated with alcohol use disorder, alcohol-related psychiatric disorders, and alcoholic liver disease, but not alcoholic polyneuropathy, alcoholic cardiomyopathy, and alcoholic gastritis. The use of psychoactive medication, including the sedative-hypnotics, antidepressants or antipsychotics were associated with a lower risk of ARDs. ConclusionsOur study demonstrates that the OSA patients are at a higher risk of developing ARDs.

Dynamics of Regional Mortality Rates From Cardiac Causes in Russia 2019-2020.

Aim To analyze the dynamics of standardized mortality ratios (SMR) (2019-2020) for the cardiological causes indicated as the primary (original) cause of death, in regions of the Russian Federation, based on the RF State Statistics Service Brief Nomenclature of Causes of Death (RFSSS BNCD). Reports have indicated substantial changes in the indexes and structure of mortality since the beginning of the COVID-19 pandemic in many countries.Material and methods RFSSS data on numbers of deaths were analyzed according to BNCD and mid-year population in single year of age groups in 2019 and 2020. SMRs were determined for 23 cardiological causes of death listed in the BNSD in a separate line; the average regional SMR value and the standard deviation were provided; and SMRs were compared both among 4 groups (with a previously described method) and by 23 RFSSS BNCD causes using the Wilcoxon test.Results In 2020 vs. 2019, the mean regional SMR for cardiological causes increased by 12.07±9.86 % (from 301.02±77.67 to 336.15±84.5 %; р&lt;0.0001). Decreases in SMR were found in 9 of 82 regions; however, only in two of them (the Republic of Ingushetia and the Sakhalin Region), SMR was decreased for all 4 groups of causes. In both 2019 and 2020 (60.9±13.8 and 62.5±12.8 %, respectively), the highest proportion of deaths was related with the 1st group of causes (chronic ischemic heart disease, IHD), with an increase in SMR of 18.66±33.28 % (р&lt;0.0001). Increases in SMR were found in 75 regions while in the other regions, decreases in SMRs were observed. For the 2nd group of causes (myocardial infarction, other acute forms of IHD, sudden cardiac death), the mean regional SMR increased in 2020 by 3.2±18.1 % (р=0.3). Increased SMRs were noted in 54 regions. The proportion of the 2nd group in cardiological mortality was 17.3±9.7 % in 2019 and 16.1±9.6 % in 2020. The mean regional SNR for the 3rd group of causes (heart defects, myocardial diseases, etc.) increased in 2020 by 11.6±23.1 % (р=0.006). The mean regional proportion of causes for this group did not significantly changed compared to 2019 (17.5±8.2 and 17.1±7.3 %, respectively); however, the contribution of this group was greater than the contribution of the 2nd group. Increases in SMR were observed in 65 regions, while the contribution of causes related with arterial hypertension did not significantly change. Significant mid-regional differences in SMR values, dynamics of SMRs for different causes, and increases in the coefficient of variation were noted for almost all causes of death. Significant differences between 2019 and 2020 were found for 3 of 23 causes: other forms of chronic IHD (decreased SMRs in 15 regions and increased SMRs in the others), atherosclerotic heart disease (decreased SMRs in 38 regions), and alcoholic cardiomyopathy (decreased SMRs in 28 regions).Conclusion During the COVID-19 pandemic, the SMR for cardiological causes was increased. Considerable regional differences in values and dynamics of SMR for individual causes call for attention to the unification of the criteria for clinical diagnosis.

Comprehensive analysis of transcriptomics and metabolomics to understand chronic ethanol induced murine cardiotoxicity.

Alcohol abuse has attracted public attention and long-term alcohol exposure can lead to alcohol-featured non-ischemic dilated cardiomyopathy. However, the precise underlying mechanisms of alcoholic cardiomyopathy remain to be elucidated. This study aimed to comprehensively characterize alcohol abuse-mediated effects on downstream metabolites and genes transcription using a multi-omics strategy. We established chronic ethanol intoxication model in adult male C57BL/6 mice through 8weeks of 95% alcohol vapor administration and performed metabolomics analysis, mRNA-seq and microRNA-seq analysis with myocardial tissues. Firstly, ethanol markedly induced ejection fraction reductions, cardiomyocyte hypertrophy, and myocardial fibrosis in mice with myocardial oxidative injury. In addition, the omics analysis identified a total of 166 differentially expressed metabolites (DEMs), 241 differentially expressed genes (DEGs) and 19 differentially expressed microRNAs (DEmiRNAs), respectively. The results highlighted that alcohol abuse mainly interfered with endogenous lipids, amino acids and nucleotides production and the relevant genes transcription in mice hearts. Based on KEGG database, the affected signaling pathways are primarily mapped to the antigen processing and presentation, regulation of actin cytoskeleton, AMPK signaling pathway, tyrosine metabolism and PPAR signaling pathway, etc. Furthermore, 9 hub genes related to oxidative stress from DEGs were selected based on function annotation, and potential alcoholic cardiotoxic oxidative stress biomarkers were determined through establishing PPI network and DEmiRNAs-DEGs cross-talk. Altogether, our data strongly supported the conclusion that ethanol abuse characteristically affected amino acid and energy metabolism, nucleotide metabolism and especially lipids metabolism in mice hearts, and underlined the values of lipids signaling and oxidative stress in the treatment strategies.

Relationship between GDF-15, urinary sodium and markers of renal function in patients with chronic heart failure

Abstract Background Patients with heart failure (HF) often have altered renal function. Urinary sodium is a marker of diuretic resistance and is associated with a worse prognosis in HF. Growth differentiation factor-15 (GDF-15) is a marker of oxidative stress and inflammation and is a prognostic predictor in HF. Objectives We sought to assess the relationship of GDF-15 with renal function parameters and with urinary sodium in patients with chronic HF. Methods We undertook a cross-sectional study of patients with HF from specialized outpatient clinic. Patients with signs and symptoms of HF and LVEF &amp;lt;50% were included. An echocardiogram was performed and blood samples were collected, which were frozen for the final study, where the performance of GDF-15 in the prediction of renal outcomes in HF will be evaluated. The dosage of NT-proBNP was performed using the Elecsys® system (Roche, Basel, Switzerland) and GDF-15 by the sandwich immunoassay method with monoclonal antibodies (Elecsys®, Roche, Basel, Switzerland). Analysis of the relationship between GDF-15 and baseline renal parameters was performed. Correlation analysis was performed between GDF-15 and continuous variables, using the Spearman method. Results Sixty-seven patients were included. The etiologies of HF were hypertension, diabetes mellitus, alcoholic cardiomyopathy and idiopathic cardiomyopathy. Forty-one (61.2%) individuals were male, with a mean age of 61±13 years. Median GDF-15 values were 1413 pg/mL (interquartile range 1044–2554). Patients with GDF-15 values above the median had lower urinary sodium values (88 mEq/L [53–121] vs 112 [76–171], p=0.06), lower glomerular filtration rate (GFR) (63.9±29.1 vs 91.2±25 mL/min/1.73 m2, p=0.001) and higher creatinine levels (1.32 mg/dL [0.85–1.71] vs 0.91 [0.78–1.08], p&amp;lt;0.001). There was no significant difference in relation to urinary albumin (21 mg/L [7–126] vs 15.1 [5.8–41], p=0.30). The urinary albumin/creatinine ratio was higher in the group above the median, but did not reach statistical significance (38 mg/g [11–110] vs 12.5 [4.9–29], p=0.13). There was a direct correlation between GDF-15 and creatinine (r=0.56, p&amp;lt;0.001) and an inverse correlation with urinary sodium (r=−0.39, p=0.005) and with GFR (r=−0.55, p&amp;lt;0.001). Conclusion GDF-15 correlated with lower urinary sodium levels and worse kidney function in patients with chronic HF. Future studies should address whether GDF-15 is a predictor of worsening renal function overtime. Funding Acknowledgement Type of funding sources: None.

Lower rate limit in cardiac resynchronization therapy defibrillators

Abstract Background There is few data about programmed lower rate limit (LRL) in real world heart failure (HF) patients with cardiac resynchronization therapy–defibrillators (CRT-Ds) and its influence in clinical outcomes. Heart rate score (HRS) is the percentage of all atrial-paced and sensed events in the single tallest 10 beats/min device histogram bin and may indicate impaired heart rate variability. Purpose We hypothesized that higher LRL programming is associated with worse clinical outcomes as arrhythmic events and HF decompensations in chronic HF patients with CRT-Ds. Methods LRL was evaluated and HRS was calculated from remote monitoring in 126 HF patients with CRT-D. Primary outcome was defined as HF hospitalizations and related admissions to the emergency department and secondary outcome as number of device therapies, sustained ventricular tachycardia (VT) and ventricular fibrillation (VF). Results Mean age was 69,03±10,39 years, 81 (64,3%) were males and mean follow-up was 53,72±46,13 months. Mean left ventricular ejection fraction was 30,31±8,33% and 29 (23,0%) were in NYHA III–IV. HF aetiology was idiopathic in 39 (43,3%), ischemic in 32 (25,4%) and alcoholic cardiomyopathy in 8 (6,3%). Thirty-seven (29,4%) patients had atrial fibrillation and 33 (26,2%) coronary disease. LRL ranged from to 40 to 80 bpm and mean LRL was 52,64±9,64 and mean HRS 49,60±23,17%. Programmed LRL was higher in women (p=0,014), patients with atrial fibrillation (AF) (p=0,012) and coronary disease (p=0,015). Higher LRL correlated with HF hospitalizations and related admissions to the emergency department (ED) (r=0,541, p=0,001), VT or VF episodes (r=0,337, p=0,005) and CRT-D number of therapies (r=0,342, p=0,004) and higher HRS (r=0,547, p&amp;lt;0,05). Conclusion Higher LRL programming was associated with higher HRS, HF decompensations with hospitalization or admission to the emergency department, VT or VF episodes and CRT-D therapies in a real world population. More studies are required but lower LRL may be preferred in HF patients. Funding Acknowledgement Type of funding sources: None.

Biventricular or left univentricular pacing in heart failure patients: is there a better strategy

Abstract Background Cardiac resynchronization therapy (CRT) is a cornerstone in treatment of heart failure (HF) with reduced left ventricular ejection fraction (LVEF) and ventricular dyssynchrony. Biventricular (BiV) pacing is often the preferred method and corrects electrical and mechanical dyssynchrony but Left ventricular (LV) preferential pacing is may preserve conduction via the right bundle branch, preventing deleterious effects from right ventricular. The evidence is sparse and there is doubts whether which programming strategy is better. Purpose We hypothesized that BiV is non-inferior to preferential LV pacing in HF patients with reduced LVEF and CRT devices in cardiovascular death and HF hospitalizations. Methods We retrospectively evaluated 147 patients with HF patients with reduced LVEF and CRT devices. Two groups were defined: LV pacing (group 1) and BiV pacing (group 2). Primary outcome was defined as cardiovascular death and secondary outcome as HF hospitalizations and NYHA class after CRT. Results Mean age was 70,26±10,6 years, 68,1% were males and follow-up was 52,22±44,51 months. One hundred and twenty six (85,7%) patients had implantable cardiac resynchronization therapy (CRT) defibrillator (CRT-D) and 21 (14,3%) CRT pacemaker (CRT-P). Mean LVEF was 31,1±8,5% and mean QRS duration before CRT implantation was 149,5±48,6 ms. Thirty-nine (36,4%) patients were in NYHA III–IV. HF aetiology was idiopathic in 51 (47,2%), ischemic in 36 (33,3%) and alcoholic cardiomyopathy in 9 (8,3%). Forty-five (40,5%) patients had atrial fibrillation and 37 (35,6%) coronary disease. Patients in group 2 were more frequently males than group 1 patients (46 (78,0%) vs 32 (56,1%) respectively, p=0,012). There were no differences in regard to age, LVEF, HF aetiology or other comorbidities between groups. In 57 (49,1%) CRT was programming in preferential LV pacing and 50 (50,9%) in BiV pacing. There were 2 deaths in group 1 and 3 in group 2 (OR 0.80, 95% CI 0.27–2.40). There were 0,98±3,17 hospitalizations per patient and there were no differences in HF hospitalizations between groups (OR 1.01, 95% CI 0.92–1.18) or NYHA after 6 months of CRT (p=0,364). Conclusion BiV pacing was not inferior to LV-only pacing in regard to cardiovascular death, HF hospitalizations and NYHA class improvement. There was no clear advantage for one pacing strategy over the other but more studies are still required. Funding Acknowledgement Type of funding sources: None.

Alcohol abstinence vs. persistent alcohol consumption in alcoholic cardiomyopathy: impact on long-term prognosis

Abstract Background Alcoholic Cardiomyopathy (ACM) remains a prevalent form of toxic-induced heart damage. Whether ACM prognosis depends on the persistence of alcohol consumption is a matter of debate. Purpose We sought to determine predictors of adverse events during long-term follow-up and left ventricular ejection fraction (LVEF) changes between abstainers and non-abstainers. Methods Consecutive patients admitted to a HF clinic from 2001 to 2020 with ACM were included. The primary endpoint was the composite of all-cause death or HF hospitalization. HF hospitalization was analyzed as a secondary outcome. Changes in LVEF at 1- and 3-years follow-up according to discontinuation of alcohol consumption was also analyzed. Multivariable Cox regression analyses were performed using the competing risk strategy for the secondary endpoint. Results A total of 122 patients were included with a mean age of 57.8±10.0 years and 95.1% (n=116) of males. The mean LVEF was 27.5% ± 10.6 and 11.5% (n=14) exhibited NYHA functional class 3. A total of 92 (75.4%) patients remained abstinent during follow-up; the rest continued with at least moderate alcohol intake. After a median follow-up of 6.8 years (interquartile range: 3.2 to 11.3 years), 59 (48.4%) presented the primary endpoint (45 [36.9%] died and 34 [27.9%] experienced HF readmission). Independent predictors of the primary outcome were age (hazard ratio [HR]: 1.03; 95% confidence interval [CI]: 1.00–1.06; p=0.042), hemoglobin (HR: 0.68; 95% CI: 0.56–0.82; p&amp;lt;0.001) and alcohol abstinence (HR: 0.35; 95% CI: 0.20–0.61; p&amp;lt;0.001). Predictors of HF readmission were hemoglobin (HR: 0.65; 95% CI: 0.50–0.83; p=0.001) and alcohol abstinence (HR: 0.39; 95% CI: 0.17–0.92; p=0.032). Improvement in LVEF was higher in abstainers (27.5±10.6% from baseline to 46.7±13.1% and 49.1±14.3% at 1- and 3-years respectively) than in non-abstainers (27.8±10.3% to 40.3±14.0% and 39.2±16.3% at 1- and 3-years respectively), being these changes in LVEF significantly different between both groups (p=0.004). Conclusions Patients with ACM and who remain abstainers during follow-up exhibit better outcomes and higher LVEF improvement in comparison to non-abstainers. These findings should help to inform lifestyle modification for patients with ACM. Funding Acknowledgement Type of funding sources: None.

Heart failure therapy in new onset heart failure versus chronic heart failure: an analysis of 90,383 patients from the Swedish Heart Failure Registry (SwedeHF)

Abstract Background The period after newly diagnosed heart failure (HF) presents challenges in HF management. Although recent HF guidelines recommend immediate initiation of HF therapies, little is known about real life HF therapy. Purpose We analyzed differences in treatment management in patients with new onset and chronic HF across the ejection fraction (EF) spectrum in the large nationwide Swedish HF registry. Methods In patients enrolled 2000–2018 in the Swedish HF registry, clinical characteristics, co-morbidities, laboratory values and use of therapy were analyzed in all HF patients with new onset HF (HF duration &amp;lt;3 months from diagnosis) and chronic HF (HF duration ≥3 months from diagnosis). Additionally, therapy use was studied separately for patients with HFrEF (defined as EF &amp;lt;40%). Results Of 90,383 patients, 40% had new onset and 60% had chronic HF. Patients with new onset HF were more likely females (42 vs. 37%) compared to chronic HF. They had lower NYHA class, with higher EF, less often had atrial fibrillation (46 vs. 60%) and left bundle branch block (14 vs. 21%). They more often had hypertension (31 vs. 24%), and less often ischemic heart disease (34 vs. 44%), dilated cardiomyopathy (4.1 vs. 8.1%) and known alcoholic cardiomyopathy (0.6 vs. 0.8) as cause of HF. Chronic HF was associated with worse renal function (eGFR 58 [41, 77] vs. 69 [51, 87] mL/min/1.73 m2) and higher co-morbidity burden. Overall, new onset HF were less often on beta-blockers (85 vs. 88%) and MRAs (26 vs. 40%), whereas patients with chronic HF more often received HF medication and HF related device therapy. Patients with new onset HFrEF and thus with an indication for guidelines directed medical therapies were more often treated with beta-blockers (93 vs. 92%), ACE/ARB (91 vs. 83%), but less often ARNi (2.5 vs. 16%) and device therapy. Conclusions In this large HF population, patients with new onset HF were more often females, with less severe HF symptoms, and with fewer co-morbidities; New onset HF was associated with less MRA use. Our findings implies that faster and concomitant HF therapy initiation as recommended in 2021 ESC HF/HFA guidelines should occur in new onset HF patients. Funding Acknowledgement Type of funding sources: None.

UNIQUE CASE OF ISOLATED CONGESTIVE SPLENOMEGALY DUE TO ALCOHOLIC CARDIOMYOPATHY RESULTING IN PANCYTOPENIA

UNIQUE CASE OF ISOLATED CONGESTIVE SPLENOMEGALY DUE TO ALCOHOLIC CARDIOMYOPATHY RESULTING IN PANCYTOPENIA

Percutaneous Coronary Intervention Outcomes Among Patients With Alcoholic Cardiomyopathy: An Analysis of the National Inpatient Sample.

IntroductionHigh consumption of alcohol has an enormous toll on the health status of individuals. A direct affectation of cardiac integrity concerns cardiologists, primary care physicians, and the healthcare system because this increases the disease burden. Alcoholic cardiomyopathy (ACM) results from the enormous consumption of alcohol over a long period of time. The prevalence varies between regions and sex and ranges between 4% and 40%. Viewing the entire spectrum of cardiomyopathies, ACM makes up about 4% of all cardiomyopathies. However, it causes dilated-type cardiomyopathy and is the second most common cause of dilated cardiomyopathy. We sought to explore the outcomes of percutaneous coronary intervention (PCI) among patients with ACM.MethodsThis was a retrospective, cross-sectional study of the National Inpatient Sample (NIS) for hospital discharges in the United States between 2012 and 2014. We identified the number of patients with a primary or secondary diagnosis of ACM using the International Classification of Diseases, Ninth Revision (ICD-9) code of 4.255. Using the ICD-9 codes for PCI (00.66, 36.01, 36.02, 36.05, 36.06, 36.07, and 17.55), we identified patients diagnosed with ACM who underwent a PCI (ACPCI). The racial and sexual prevalence, hospital length of stay (LOS), mortality, cost of hospitalization, and cardiovascular outcomes (ventricular fibrillation (VF) and atrial fibrillation (AF)) were compared between patients with and without ACM who underwent a PCI.ResultsA total of 2,488,293 PCIs were performed between 2012 and 2014. Of these, there were a total of 161 admissions for ACM. About 93% (151) of the ACM PCI group were men. Ethnic distribution revealed a majority of Caucasians with 69% (98), and blacks and Asians at 13.4% (19) and 11.3% (16), respectively. The mean age was 59.8 (SD = 9). The patients with ACPCI were likely to stay longer in the hospital, with an average stay of 6.6 days (SD = 6.2) compared to patients without ACM undergoing PCI (NOACPCI) (3.7 days; SD = 5.0) (p = 0.0001). The mean cost of hospital admission for patients with ACPCI was $120,225 (SD = 101,044), while that of those without ACM who underwent PCI (NOACPCI) was $87,936 (SD = 83,947) (p = 0.0001). A higher death rate during hospitalization (3.7%) was recorded in the ACPCI category vs. 2.3% in patients without ACM who underwent PCI (p = 0.0001). Patients with ACPCI had a higher prevalence of AF (30.4%) than VF (7.5%).ConclusionThe ACPCI group had overall poorer hospital outcomes. The majority affected were older Caucasian men with an increased prevalence of AF, higher cost of hospitalization, and longer hospital stays. Further studies are needed to explore the burden of long-term alcohol consumption on cardiovascular disease treatment outcomes.

A Case Report on Application of Multimodal Imaging to an Alcoholic Cardiomyopathic Patient Undergoing Heart Transplantation

Alcoholic cardiomyopathy (ACM) is a dilated cardiomyopathy induced by excessive alcohol consumption that causes progressive cardiac dysfunction and chamber dilatation, leading to arrhythmias, heart failure, and death. Cardiac transplantation is the final measure for end-stage ACM. In this case, we used multimodal imaging for ACM diagnosis in a patient with refractory heart failure. The patient received a heart transplant with a good prognosis, and his pathological results after the transplant confirmed our suspected diagnosis. End-stage ACM may lead to refractory heart failure and multimodal imaging may play an important role in the diagnosis, prognosis prediction, and follow-up study of suspected ACM.

Alcohol Intake in Patients With Cardiomyopathy and Heart Failure: Consensus and Controversy.

Alcohol is often cited to be a common cause of cardiomyopathy and heart failure. However, in most available population-based studies, a modest-to-moderate alcohol consumption has been associated with favorable effects on the cardiovascular system, including a lowered risk of heart failure, compared with no alcohol consumption. Available genetic epidemiological data have not supported a causal association between alcohol consumption and heart failure risk, suggesting that alcohol may not be a common cause of heart failure in the community. Data linking alcohol intake with cardiomyopathy risk are sparse, and the concept of alcoholic cardiomyopathy stems mainly from case series of selected patients with dilated cardiomyopathy, where a large proportion reported a history of excessive alcohol intake. This state-of-the-art paper addresses the current knowledge of the epidemiology of alcoholic cardiomyopathy and the role of alcohol intake in patients with non-alcohol-related heart failure. It also offers directions to future research in the area. The review questions the validity of current clinical teaching in the area. It is not well known how much alcohol is needed to cause disease, and the epidemiological pathways linking alcohol consumption to cardiomyopathy and heart failure are not well understood. Until more evidence becomes available, caution is warranted before labeling patients as having alcoholic cardiomyopathy due to a risk of neglecting other contributors, such as genetic causes of cardiomyopathy. In non-alcohol-related heart failure, it is unknown whether total abstinence is improving outcomes (compared with moderate drinking). Ideally, randomized clinical trials are needed to answer this question.

The burden of alcoholic cardiomyopathy in China and different regions around the world.

BackgroundAlcoholic cardiomyopathy (ACM) remains a significant public health issue with a growing global burden. The burden of ACM in China and different regions remains poorly understood.MethodsData on ACM deaths, disability-adjusted life years (DALYs), the corresponding global age-standardized death rate (ASDR), age-standardized DALY rate and estimated annual percentage change (EAPC) were analysed based on age, sex, socio-demographic index (SDI) quintiles, different regions and in China from the Global Burden of Disease (GBD) study 2019.ResultsGlobally, the death rate and DALYs due to ACM were 71 723 and 2 441 108 in 2019, 33.06% and 38.79% increase from 1990, respectively. The corresponding ASDR and age-standardized DALY rate decreased with EAPC of -1.52 (95% uncertainty interval (UI) = -2.39, -0.65) and -1.12 (95% UI = -2.14, -0.10). The high-middle SDI regions, especially Eastern Europe, showed the highest number of ACM-related deaths and DALYs. The ACM-related deaths and DALYs were 2545 and 87823 in China in 2019, 171.03% and 147.17% increase from 1990, respectively. Unlike the world level, ASDR and age-standardized DALY rate also increased in China. The ACM burden is higher in men, and people with 50 to 69 years old accounted for the most.ConclusionsACM burden in China and across the world increased substantially from 1990 to 2019. The greatest burden was borne by the high-middle SDI regions, especially by men aged 50-69 years old. Geographically and gender-age tailored strategies were needed to prevent ACM.

Aortic saddle embolism just after Impella CP removal in a patient withalcoholic cardiomyopathy.

Aortic saddle embolism just after Impella CP removal in a patient withalcoholic cardiomyopathy.