Cardiac sarcoidosis and giant cell myocarditis after COVID-19 infection

Patients infected with SARS-CoV-2 have varying manifestations of cardiac involvement. We report four patients presenting with symptomatic cardiac sarcoidosis (CS) or giant cell myocarditis (GCM) 1-8 months after mild COVID-19. All patients received immunosuppressive therapy and improved gradually within the following months. The possible temporal association between the CS/GCM and COVID-19 infection might suggest that COVID-19 could be a trigger for granulomatous myocarditis.Peer reviewe

Short- and long-term outcomes after heart transplantation in cardiac sarcoidosis and giant-cell myocarditis : a systematic review and meta-analysis

Heart transplantation (HTx) is a valid therapeutic option for end-stage heart failure secondary to cardiac sarcoidosis (CS) or giant-cell myocarditis (GCM). However, post-HTx outcomes in patients with inflammatory cardiomyopathy (ICM) have been poorly investigated. We searched PubMed, Scopus, Science Citation Index, EMBASE, and Google Scholar, screened the gray literature, and contacted experts in the field. We included studies comparing post-HTx survival, acute cellular rejection, and disease recurrence in patients with and without ICM. Data were synthesized by a random-effects meta-analysis. We screened 11,933 articles, of which 14 were considered eligible. In a pooled analysis, post-HTx survival was higher in CS than non-CS patients after 1 year (risk ratio [RR] 0.88, 95% confidence interval [CI] 0.60-1.17; I-2 = 0%) and 5 years (RR 0.72, 95% CI 0.52-0.91; I-2 = 0%), but statistically significant only after 5 years. During the first-year post-HTx, the risk of acute cellular rejection was similar for patients with and without CS, but after 5 years, it was lower in those with CS (RR 0.38, 95% CI 0.03-0.72; I-2 = 0%). No difference in post-HTx survival was observed between patients with and without GCM after 1 year (RR 1.16, 95% CI 0.05-2.28; I-2 = 0%) or 5 years (RR 0.98, 95% CI 0.42-1.54; I-2 = 0%). During post-HTx follow-up, recurrence of CS and GCM occurred in 5% and 8% of patients, respectively. Post-HTx outcomes in patients with CS and GCM are comparable with cardiac recipients with other heart failure etiologies. Patients with ICM should not be disqualified from HTx. [GRAPHICS] .Peer reviewe

Stromal Vascular Fraction Transplantation as an Alternative Therapy for Ischemic Heart Failure: Anti-inflammatory Role

<p>Abstract</p> <p>Background</p> <p>The aims of this study were: (1) to show the feasibility of using adipose-derived stromal vascular fraction (SVF) as an alternative to bone marrow mono nuclear cell (BM-MNC) for cell transplantation into chronic ischemic myocardium; and (2) to explore underlying mechanisms with focus on anti-inflammation role of engrafted SVF and BM-MNC post chronic myocardial infarction (MI) against left ventricular (LV) remodelling and cardiac dysfunction.</p> <p>Methods</p> <p>Four weeks after left anterior descending coronary artery ligation, 32 Male Lewis rats with moderate MI were divided into 3 groups. SVF group (n = 12) had SVF cell transplantation (6 × 10⁶cells). BM-MNC group (n = 12) received BM-MNCs (6 × 10⁶) and the control (n = 10) had culture medium. At 4 weeks, after the final echocardiography, histological sections were stained with Styrus red and immunohistochemical staining was performed for α-smooth muscle actin, von Willebrand factor, CD3, CD8 and CD20.</p> <p>Results</p> <p>At 4 weeks, in SVF and BM-MNC groups, LV diastolic dimension and LV systolic dimension were smaller and fractional shortening was increased in echocardiography, compared to control group. Histology revealed highest vascular density, CD3+ and CD20+ cells in SVF transplanted group. SVF transplantation decreased myocardial mRNA expression of inflammatory cytokines TNF-α, IL-6, MMP-1, TIMP-1 and inhibited collagen deposition.</p> <p>Conclusions</p> <p>Transplantation of adipose derived SVF cells might be a useful therapeutic option for angiogenesis in chronic ischemic heart disease. Anti-inflammation role for SVF and BM transplantation might partly benefit for the cardioprotective effect for chronic ischemic myocardium.</p

Glucosylceramide synthase deficiency in the heart compromises β1-adrenergic receptor trafficking

Aims: Cardiac injury and remodelling are associated with the rearrangement of cardiac lipids. Glycosphingolipids are membrane lipids that are important for cellular structure and function, and cardiac dysfunction is a characteristic of rare monogenic diseases with defects in glycosphingolipid synthesis and turnover. However, it is not known how cardiac glycosphingolipids regulate cellular processes in the heart. The aim of this study is to determine the role of cardiac glycosphingolipids in heart function.Methods and results: Using human myocardial biopsies, we showed that the glycosphingolipids glucosylceramide and lactosylceramide are present at very low levels in non-ischaemic human heart with normal function and are elevated during remodelling. Similar results were observed in mouse models of cardiac remodelling. We also generated mice with cardiomyocyte-specific deficiency in Ugcg, the gene encoding glucosylceramide synthase (hUgcg-/- mice). In 9- to 10-week-old hUgcg-/- mice, contractile capacity in response to dobutamine stress was reduced. Older hUgcg-/- mice developed severe heart failure and left ventricular dilatation even under baseline conditions and died prematurely. Using RNA-seq and cell culture models, we showed defective endolysosomal retrograde trafficking and autophagy in Ugcg-deficient cardiomyocytes. We also showed that responsiveness to β-adrenergic stimulation was reduced in cardiomyocytes from hUgcg-/- mice and that Ugcg knockdown suppressed the internalization and trafficking of β1-adrenergic receptors.Conclusions: Our findings suggest that cardiac glycosphingolipids are required to maintain β-adrenergic signalling and contractile capacity in cardiomyocytes and to preserve normal heart function.</p

Structural, functional and metabolic effects of growth hormone on nomal and failing heart

The growth hormone/insulin-like growth factor I (GH/IGF-I) system plays an important role for cardiac development, structure and function. Recently, data from experimental and clinical studies have suggested the use of GH as treatment after myocardial infarction (MI) affecting cardiac remodeling and development of heart failureThe aim of this thesis was to study the effects of GH on cardiac structure, function and energy metabolism in normal and failing heart.To evaluate the effect of GH treatment on left ventricular (LV) remodeling, we used different experimental models: a rat model of experimental MI, hypophysectomised (hx) rats and transgenic mice overexpressing bovine GH (bGH). Transthoracic echocardiography and 31P magnetic resonance spectroscopy, were used to evaluate geometry, systolic and diastolic function as well as energy metabolism of LV in vivo. Biochemical analysis including high pressure liquid chromatography and histological evaluation were also performed.Three days after MI, LV internal diameter increased significantly compared with control rats. Systolic and diastolic indexes of LV function were significantly deteriorated after MI. Three weeks later a further dilatation of LV and a more spherical shape were observed in MI rats. Phosphocreatine (PCr) to ATP ratio was significantly lower in MI rats three days and three weeks after MI. Short term (9 days) treatment with GH alone or in combination with metoprolol preserved the LV systolic function after MI, whereas three weeks treatment with GH after MI preserved systolic function and attenuated the remodeling. Plasma and myocardium tissue of catecholamines and brain natriuretic peptide levels were significantly decreased after GH treatment. Moreover, three weeks treatment with GH normalized PCr/ATP in MI rats.GH administration in hx rat increase body weight, heart weight, improved LV performance and myocardial energy metabolism. In transgenic bGH mice, hypertrophy of LV with poor systolic performance was observed. Moreover, a decrease in PCr/ATP ratios associated with qualitative changes on mitochondrial structure was detected in LV from bGH mice. GH plays an important role for the maintenance of normal cardiac structure, function and myocardial energy metabolism. Short term treatment with GH after MI attenuated the LV remodeling, preserved systolic function, improved myocardial bioenergetics and decreased neurohormonal activation. Long term exposures to high levels of GH leads to cardiac hypertrophy, poor performance and decreased energy reserve

Inflammatory cardiomyopathies : short- and long-term outcomes after heart transplantation-a protocol for a systematic review and meta-analysis

Heart transplantation (HTx) for patients with "giant cell myocarditis" (GCM) or "cardiac sarcoidosis" (CS) is still controversial. However, no single center has accumulated enough experience to investigate post-HTx outcome. The primary aim of this systematic review is to identify, appraise, and synthesize existing literature investigating whether patients who have undergone HTx because of GCM or CS have worse outcomes as compared with patients transplanted because of other etiologies. A systematic and comprehensive search will be performed using PubMed, Scopus, Web of Science, EMBASE, and Google Scholar, for studies published up to December 2019. Observational and interventional population-based studies will be eligible for inclusion. The quality of observational studies will be assessed using the Newcastle-Ottawa scale, while the interventional studies will be assessed using the Cochrane Effective Practice Organization of Care tool. The collected evidence will be narratively synthesized; in addition, we will perform a meta-analysis to pool estimates from studies considered to be homogenous. Reporting of the systematic review and meta-analysis will be in accordance with the Meta-analysis of Observational Studies in Epidemiology Preferred Reporting Items for Systematic reviews and Meta-Analysis guidelines. To our knowledge, this will be the first synthesis of outcomes, including survival, acute cellular rejection, and disease recurrence, in patients with either GCM or CS treated with HTx. Reviewing the suitability of HTx in this population and highlighting areas for further research will benefit both patients and healthcare providers. Trial registration: CRD42019140574.Peer reviewe

Temporal trends in outcome and patient characteristics in dilated cardiomyopathy, data from the Swedish Heart Failure Registry 2003–2015

Abstract Background Temporal trends in clinical composition and outcome in dilated cardiomyopathy (DCM) are largely unknown, despite considerable advances in heart failure management. We set out to study clinical characteristics and prognosis over time in DCM in Sweden during 2003–2015. Methods DCM patients (n = 7873) from the Swedish Heart Failure Registry were divided into three calendar periods of inclusion, 2003–2007 (Period 1, n = 2029), 2008–2011 (Period 2, n = 3363), 2012–2015 (Period 3, n = 2481). The primary outcome was the composite of all-cause death, transplantation and hospitalization during 1 year after inclusion into the registry. Results Over the three calendar periods patients were older (p = 0.022), the proportion of females increased (mean 22.5%, 26.4%, 27.6%, p = 0.0001), left ventricular ejection fraction was higher (p = 0.0014), and symptoms by New York Heart Association less severe (p < 0.0001). Device (implantable cardioverter defibrillator and/or cardiac resynchronization) therapy increased by 30% over time (mean 11.6%, 12.3%, 15.1%, p < 0.0001). The event rates for mortality, and hospitalization were consistently decreasing over calendar periods (p < 0.0001 for all), whereas transplantation rate was stable. More advanced physical symptoms correlated with an increased risk of a composite outcome over time (p = 0.0043). Conclusions From 2003 until 2015, we observed declining mortality and hospitalizations in DCM, paralleled by a continuous change in both demographic profile and therapy in the DCM population in Sweden, towards a less affected phenotype

Prognostic impact over time of ischaemic heart disease vs. non-ischaemic heart disease in heart failure

Aims The aim of this study is to investigate the prognostic impact of ischaemic heart disease (IHD) in heart failure (HF) and its association to age, sex, left ventricular ejection fraction (EF), and HF duration, and furthermore, to evaluate if the impact of IHD has changed over time, in light of improved therapy. Methods and results We studied 30 946 patients with non-valvular HF, by accessing the Swedish Heart Failure Registry, from years 2000 to 2012. The mortality in 17 778 patients with clinical IHD was compared with 13 168 patients without IHD (non-IHD). There was a significantly worse outcome in IHD, with the crude mortality of 41.1% and the event rate per 100 person-years [95% confidence interval (CI)] of 14.8 (14.4-15.1), compared with 28.2% and 9.7 (9.4-10.0) in non-IHD. After multivariable adjustment, the hazard ratio (HR) (95% CI) for mortality, IHD vs. non-IHD, was 1.16 (1.11-1.22; P amp;lt; 0.0001). Subgroup analyses showed significantly increased mortality in IHD, in all age subgroups, in all subgroups with EF amp;lt; 50%, in both men and women, and regardless of heart failure duration more or less than 6 months. Analyses for the combination of age and EF showed the highest HR for time to death in the youngest with the lowest EF, HR (95% CI) 2.05 (1.59-2.64) for patients amp;lt;60 years of age with EF amp;lt; 30%. Although a numerical reduction of the HR for mortality was seen over time, the risk for mortality in IHD, compared with the non-IHD group, was greater throughout the study period. Conclusions In non-valvular heart failure, IHD was associated with significantly increased mortality, compared with non-IHD, in groups of EF below 50%, in all age groups, and regardless of sex or HF duration. The risk increase associated with EF reduction diminished with increasing age. The mortality in IHD, compared with non-IHD, remained significantly higher throughout the 13 year study period.Funding Agencies|Swedish Heart-Lung FoundationSwedish Heart-Lung Foundation [20170453]; Region Vastra Gotaland [ALFGBG-721961]; University of Gothenburg [ALFGBG-721961]; Swedish National Board of Health and Welfare; Swedish Association of Local Authorities and Regions; Swedish Society of Cardiology</p

Prognostic differences in long-standing vs. recent-onset dilated cardiomyopathy

Aims This study aimed to evaluate the outcome and prognostic factors in patients with dilated cardiomyopathy (DCM) and long-standing heart failure (LDCM) vs. recent-onset heart failure (RODCM). Methods and results We compared 2019 patients with RODCM (duration &amp;lt;6 months, mean age 58.6 years, 70.7% male) with 1714 patients with LDCM (duration &amp;gt;= 6 months, median duration 3.5 years, mean age 62.5 years, 73.7% male) included in the Swedish Heart Failure Registry in the years 2003-16. Outcome measures were all-cause, cardiovascular (CV), and non-CV death and hospitalizations; heart transplantation; and a combined outcome of all-cause death, heart transplantation, or heart failure (HF) hospitalization. Multivariable risk factor analyses were performed for the combined endpoint. All outcomes were more frequent in LDCM than in RODCM. The multivariable-adjusted hazard ratios (HRs) (95% confidence interval) for LDCM vs. RODCM were 1.56 (1.34-1.82), P &amp;lt; 0.0001, for all-cause death over a median follow-up of 4.2 and 5.0 years, respectively; 1.67 (1.36-2.05), P &amp;lt; 0.0001, for CV death; 2.12 (1.14-3.91), P &amp;lt; 0.0001, for heart transplantation; 1.36 (1.21-1.53), P &amp;lt; 0.0001, for HF hospitalization; and 1.37 (1.24-1.52), P &amp;lt; 0.0001, for the combined outcome. A propensity score-matched analysis yielded similar results. CV death was the main cause of mortality in LDCM and was higher in LDCM than in RODCM (P &amp;lt; 0.0001). Almost all co-morbidities were significantly more frequent in LDCM than in RODCM, and the mean number of co-morbidities increased significantly with increased duration of disease, also after age adjustment. Age, New York Heart Association functional class, ejection fraction, and left bundle branch block were prognostically adverse. The only co-morbidity associated with the combined outcome regardless of HF duration was diabetes, in LDCM [HR 1.34 (1.15-1.56), P = 0.0002] and in RODCM [HR 1.29 (1.04-1.59), P = 0.018]. Male sex [HR 1.38 (1.18-1.63), P &amp;lt; 0.0001] and aspirin use [HR 1.33 (1.14-1.55), P = 0.0004] carried increased risk only in RODCM. Heart rate &amp;gt;= 75 b.p.m. [HR 1.20 (1.04-1.37), P = 0.01], atrial fibrillation [HR 1.24 (1.08-1.42), P = 0.0024], musculoskeletal or connective tissue disorder [HR 1.36 (1.13-1.63), P = 0.0014], and diuretic therapy [HR 1.40 (1.17-1.67), P = 0.0002] were prognostically adverse only in LDCM. Conclusions This nationwide study of patients with DCM demonstrates that longer disease duration is associated with worse prognosis. Co-morbidities are more common in long-standing HF than in recent-onset HF and are associated with worse outcome. With the increased survival seen in the last decades, our results highlight the importance of careful attention to co-morbid conditions in patients with DCM.Funding Agencies|Swedish Heart Lung Foundation (Hjart-Lungfonden) [20170453]; Swedish government [ALFGBG-721961]; Swedish county councils, the ALF-agreement [ALFGBG-721961]; Swedish National Board of Health and Welfare; Swedish Association of Local Authorities and Regions; Swedish Society of Cardiology</p