Diagnosis and treatment of cardiac amyloidosis: a position statement of the ESC Working Group on Myocardial and Pericardial Diseases.

Cardiac amyloidosis is a serious and progressive infiltrative disease that is caused by the deposition of amyloid fibrils at the cardiac level. It can be due to rare genetic variants in the hereditary forms or as a consequence of acquired conditions. Thanks to advances in imaging techniques and the possibility of achieving a non-invasive diagnosis, we now know that cardiac amyloidosis is a more frequent disease than traditionally considered. In this position paper the Working Group on Myocardial and Pericardial Disease proposes an invasive and non-invasive definition of cardiac amyloidosis, addresses clinical scenarios and situations to suspect the condition and proposes a diagnostic algorithm to aid diagnosis. Furthermore, we also review how to monitor and treat cardiac amyloidosis, in an attempt to bridge the gap between the latest advances in the field and clinical practice.

Heat Shock Protein 70 Is Associated With Cardioversion Outcome and Recurrence of Symptomatic Recent Onset Atrial Fibrillation in Hypertensive Patients.

ABSTRACT: Accumulating evidence indicates that heat shock proteins (HSPs) may represent a suitable biomarker to predict atrial fibrillation (AF). We investigated the relation of circulating serum HSP70 (sHSP70) with inflammatory cytokines and recurrence of symptomatic recent onset AF (ROAF). We enrolled 90 patients with ROAF (the duration from onset of symptoms ≤24 hours) and 30 controls. Patients received amiodarone for cardioversion and rhythm control. The association of serum HSP70, serum interleukin-2 (sIL-2), and serum interleukin-4 (sIL-4) with the presence of cardioversion and AF recurrence within a year was investigated. Toll-like receptor 4 (TLR4) signaling dependence for IL-2 and IL-4 induction in response to stimulation with HSP70 was tested in rat aortic vascular smooth muscle cell cultures. Patients had higher sHSP70 and sIL-2 and lower sIL-4 compared with controls. Serum HSP70 was independently associated with ROAF (P = 0.005) and correlated with sIL-2 (r = 0.494, P < 0.001) and sIL-4 (r = -0.550, P < 0.001). By 48 hours, 71 of the 90 patients were cardioverted, with noncardioverted patients having higher sHSP70 and sIL-2 and lower sIL-4, which were the only independent factors associated with cardioversion. AF recurred in 38 of the 71 cardioverted patients in 1 year. A cutoff value of sHSP70 ≥0.65 ng/mL and sIL-2 ≥0.21 pg/mL was the only independent factor associated with AF recurrence (hazard ratio: 3.311, 95% confidence interval: 1.503-7.293, P = 0.003 and hazard ratio: 3.144, 95% confidence interval: 1.341-7.374, P = 0.008, respectively). The exposure of smooth muscle cell to HSP70 in vitro increased the expression of IL-2 (5×) and IL-4 (1.5×) through TLR4-dependent and receptor-independent mechanisms. In conclusion, sHSP70 and sIL-2 might constitute a prognostic tool for determining the cardioversion and recurrence likelihood in ROAF.

Cardiogenic shock with highly complicated course after influenza A virus infection treated with vva-ECMO and Impella CP (ECMELLA): a case report.

BACKGROUND: The value of mechanical circulatory support (MCS) in cardiogenic shock, especially the combination of the ECMELLA approach (Impella combined with ECMO), remains controversial. CASE PRESENTATION: A previously healthy 33-year-old female patient was submitted to a local emergency department with a flu-like infection and febrile temperatures up to 39 °C. The patient was tested positive for type-A influenza, however negative for SARS-CoV-2. Despite escalated invasive ventilation, refractory hypercapnia (paCO2: 22 kPa) with severe respiratory acidosis (pH: 6.9) and a rising norepinephrine rate occurred within a few hours. Due to a Horovitz-Index < 100, out-of-centre veno-venous extracorporeal membrane oxygenation (vv-ECMO)-implantation was performed. A CT-scan done because of anisocoria revealed an extended dissection of the right vertebral artery. While the initial left ventricular function was normal, echocardiography revealed severe global hypokinesia. After angiographic exclusion of coronary artery stenoses, we geared up LV unloading by additional implantation of an Impella CP and expanded the vv-ECMO to a veno-venous-arterial ECMO (vva-ECMO). Clinically relevant bleeding from the punctured femoral arteries resulted in massive transfusion and was treated by vascular surgery later on. Under continued MCS, LVEF increased to approximately 40% 2 days after the initiation of ECMELLA. After weaning, the Impella CP was explanted at day 5 and the vva-ECMO was removed on day 9, respectively. The patient was discharged in an unaffected neurological condition to rehabilitation 25 days after the initial admission. CONCLUSIONS: This exceptional case exemplifies the importance of aggressive MCS in severe cardiogenic shock, which may be especially promising in younger patients with non-ischaemic cardiomyopathy and potentially reversible causes of cardiogenic shock. This case impressively demonstrates that especially young patients may achieve complete neurological restoration, even though the initial prognosis may appear unfavourable.

Cytoprotective Mechanisms of DJ-1: Implications in Cardiac Pathophysiology.

DJ-1 was originally identified as an oncogene product while mutations of the gene encoding DJ-1/PARK7 were later associated with a recessive form of Parkinson's disease. Its ubiquitous expression and diversity of function suggest that DJ-1 is also involved in mechanisms outside the central nervous system. In the last decade, the contribution of DJ-1 to the protection from ischemia-reperfusion injury has been recognized and its involvement in the pathophysiology of cardiovascular disease is attracting increasing attention. This review describes the current and gaps in our knowledge of DJ-1, focusing on its role in regulating cardiovascular function. In parallel, we present original data showing an association between increased DJ-1 expression and antiapoptotic and anti-inflammatory markers following cardiac and vascular surgical procedures. Future studies should address DJ-1's role as a plausible novel therapeutic target for cardiovascular disease.

Rationale and design of the MULTISTARS AMI Trial: A randomized comparison of immediate versus staged complete revascularization in patients with ST-segment elevation myocardial infarction and multivessel disease.

About half of patients with acute ST-segment elevation myocardial infarction (STEMI) present with multivessel coronary artery disease (MVD). Recent evidence supports complete revascularization in these patients. However, optimal timing of non-culprit lesion revascularization in STEMI patients is unknown because dedicated randomized trials on this topic are lacking. STUDY DESIGN: The MULTISTARS AMI trial is a prospective, international, multicenter, randomized, two-arm, open-label study planning to enroll at least 840 patients. It is designed to investigate whether immediate complete revascularization is non-inferior to staged (within 19-45 days) complete revascularization in patients in stable hemodynamic conditions presenting with STEMI and MVD and undergoing primary percutaneous coronary intervention (PCI). After successful primary PCI of the culprit artery, patients are randomized in a 1:1 ratio to immediate or staged complete revascularization. The primary endpoint is a composite of all-cause death, non-fatal myocardial infarction, ischemia-driven revascularization, hospitalization for heart failure, and stroke at 1 year. CONCLUSIONS: The MULTISTARS AMI trial tests the hypothesis that immediate complete revascularization is non-inferior to staged complete revascularization in stable patients with STEMI and MVD.

The pivotal role of cardiovascular imaging in the identification and risk stratification of non-compaction cardiomyopathy patients.

Non-compaction cardiomyopathy (NCM) is a heterogeneous myocardial disease that can finally lead to heart failure, arrhythmias, and/or embolic events. Therefore, early diagnosis and treatment is of paramount importance. Furthermore, genetic assessment and counseling are crucial for individual risk assessment and family planning. Echocardiography is the first-line imaging modality. However, it is hampered by interobserver variability, depends among others on the quality of the acoustic window, cannot assess reliably the right ventricle and the apex, and cannot provide tissue characterization. Cardiovascular magnetic resonance (CMR) provides a 3D approach allowing imaging of the entire heart, including both left and right ventricle, with low operator variability or limitations due to patient's body structure. Furthermore, tissue characterization, using late gadolinium enhancement (LGE), allows the detection of fibrotic areas possibly representing the substrate for potentially lethal arrhythmias, predicts the severity of LV systolic dysfunction, and differentiates apical thrombus from fibrosis. Conversely, besides being associated with high costs, CMR has long acquisition/processing times, lack of expertise among cardiologists/radiologists, and limited availability. Additionally, in cases of respiratory and/or cardiac motion artifacts or arrhythmias, the cine images may be blurred. However, CMR cannot be applied to patients with not CMR-compatible implanted devices and LGE may be not available in patients with severely reduced GFR. Nevertheless, native T1 mapping can provide detailed tissue characterization in such cases. This tremendous potential of CMR makes this modality the ideal tool for better risk stratification of NCM patient, based not only on functional but also on tissue characterization information.

Meta-analysis on the immunohistological detection of inflammatory cardiomyopathy in endomyocardial biopsies.

Meta-analysis on immunohistological (IHC) concepts for the detection of inflammatory cardiomyopathy (InfCM) in endomyocardial biopsies (EMB). We included 61 publications, with 10,491 patients (mean age 47.1 years; men 66%) who underwent EMB and IHC evaluation. The 460 control patients were devoid of IHC proof of InfCM. The mean IHC detection rate of InfCM was 50.8% (95% CI 47.7-53.8%; range 18.4-91.7%). A publication bias was excluded (Funnel Plot p = 0.4264). This IHC detection rate was significantly (p < 0.0001) higher compared to the histological detection of myocarditis according to the Dallas criteria (mean 8.04%; 95% CI 5.08-12.5%; subset of 3274 patients in 30 publications). However, 13 different diagnostic IHC criteria were described in the publications, with various thresholds of diverse phenotypes of quantified infiltrates, and endothelial expression of diverse cell adhesion molecules (CAM), quantified either visually or by digital image analysis (DIA). The comparison of IHC with cardiac magnetic resonance (CMR) data available in a subset of 13 publications with 1185 patients revealed a sensitivity for CMR of 69% (95% CI 58-79%), a specificity of 73% (95% CI 59-84%), and a ROC-AUC of 0.77 (95% CI 0.73-0.81). This meta-analysis encompassing 10,491 patients confirms a mean detection rate of InfCM in 50.8% of EMB, being significantly more sensitive compared to the histological Dallas criteria. IHC cannot be fully substituted by CMR. However, standardization of the diverse IHC markers and protocols seems pertinent, especially considering the published adverse prognostic impact of IHC-confirmed InfCM and its published suitability for the selection of candidates responding favorably to immunosuppression.

Advancements in the diagnostic workup, prognostic evaluation, and treatment of takotsubo syndrome.

Takotsubo syndrome (TTS) is an acute and mostly reversible cardiomyopathy that mimics an acute coronary syndrome with left ventricular (LV) systolic dysfunction without relevant obstructive coronary artery disease. Its prevalence is probably underestimated and reaches 1.2-2% in patients with acute coronary syndrome undergoing coronary catheterization. Although supraphysiological epinephrine levels have been associated with TTS, the detailed pathophysiology is incompletely understood. Chest pain is the most common clinical presentation; however, cardiac decompensation, cardiogenic shock, and sudden cardiac death due to ventricular fibrillation may also be the first clinical manifestations. Patients are mostly postmenopausal women, in whom the condition is commonly associated with emotional triggers; however, men have a higher prevalence of TTS being associated with physical triggers, which has a worse prognosis compared with TTS associated with emotional triggers. As a diagnosis of exclusion, TTS has no single definitive diagnostic test. According to the distribution of LV wall motion abnormalities, various morphological subtypes have been identified. The final diagnosis depends on cardiac imaging with left ventricular angiography during acute heart catheterization, as well as on echocardiography and cardiac magnetic resonance. Most patients recover completely, albeit several factors have been associated with worse prognosis. Management is based on observational data, while randomized multicenter studies are still lacking. This review provides a general overview of TTS and focuses on the hypothesized pathophysiology, and especially on current practices in diagnosis, prognosis, and treatment.

Systematic review on left atrial appendage closure with the LAmbre device in patients with non-valvular atrial fibrillation.

BACKGROUND: Percutaneous closure (LAAC) of the left atrial appendage (LAA) is an efficacious preventive procedure for patients with non-valvular atrial fibrillation (NVAF) and considerable bleeding risk. We sought to systematically review the available LAAC data on the novel occluder device LAmbre™. METHODS: For this systematic review, a search of the literature was conducted by 3 independent reviewers, reporting the safety and therapeutic success of LAAC in patients being treated with a LAmbre™. Publications reporting the safety and therapeutic success of LAAC using LAmbre™ in n > 5 patients were included. RESULTS: The literature search retrieved n = 10 publications, encompassing n = 403 NVAF patients treated with a LAmbre™ LAAC, with relevant data regarding safety and therapeutic success of the procedure. The mean CHA2DS2-VASc Score was 4.0 + 0.9, and the mean HAS-BLED score was 3.4 + 0.5. The implantation success was 99.7%, with a mean procedure time of 45.4 ± 18.7 min, and a fluoroscopy time of 9.6 ± 5.9 min, and a contrast agent volume of 96.7 ± 0.7 ml. The anticoagulation regimen was switched to DAPT post procedure in the majority of the patients (96.8%). Partial and full recapture were done in 45.5% and in 25.6%, respectively. Major complications were reported in 2.9%, with 0.3% mortality, 1.7% pericardial tamponade, 0.3% stroke, and 0.6% major bleeding complications; no device embolization was observed. During follow up at 6 or 12 months, major adverse cardiovascular events were reported in 3.3%: Stroke or TIA in 1.7%, thrombus formation on the device in 0.7%, and residual flow > 5 mm in 1.0%. In some publications, the favorable implantion properties of the LAmbre™ for difficult anatomies such as shallow or multilobular LAA anatomies were described. CONCLUSIONS: This systematic review on the LAmbre™ LAA-occluder including n = 403 NVAF patients demonstrates an excellent implantion success rate, promising follow-up clinical data, and favorable properties for also challenging LAA anatomies,. While its design seems to be helpful in preventing device embolization, pericardial tamponade may not be substantially reduced by the LAmbre™ as compared with other established LAAC devices. Further larger prospective multicenter registries and randomized trials are needed to scrutinize the value of the LAmbre™ compared with established LAAC devices.

Cardiopulmonary Exercise Test Parameters at Three Months After Alcohol Septal Ablation in Hypertrophic Obstructive Cardiomyopathy Are Associated With Late Clinical Outcome.

BACKGROUND: Alcohol septal ablation (ASA) is an established interventional treatment for hypertrophic obstructive cardiomyopathy (HOCM) patients with drug refractory symptoms. This study investigated the prognostic value of cardiopulmonary exercise test (CPET) in relation to the late clinical outcome. METHODS: Twenty-one (21) HOCM patients underwent CPET before and 3 months after ASA and were followed yearly thereafter. Clinical success was considered to be a decrease of ≥1 (New York Heart Association or Canadian Cardiovascular Society) functional class. Cardiopulmonary exercise test parameters [maximal oxygen uptake (PeakVO2), % predicted VO2 (PeakVO2%), oxygen uptake at anaerobic threshold (AT), maximal workload (W), % predicted W (W%), ventilation (VE), % predicted VE (VE%), ventilation to maximal carbon dioxide production slope (VE/VCO2), % predicted maximal heart rate (HR%), and maximal systolic blood pressure (SBP)] were compared before and 3 months after ASA. RESULTS: After follow-up of 29 ± 13 months, 16 patients had a good clinical results (clinical responders), while five did not improve (clinical non-responders). The CPET parameters did not change in non-responders, while clinical responders showed significant improvement in VO2, VO2%, W, VE/VCO2, VE, VE%, as well as an increase in HR% and SBP at 3 months. CONCLUSIONS: The data confirmed a good association between the improvement in CPET parameters and the clinical results 3 months after ASA. This may therefore serve as an early marker of HOCM-ASA treatment success.

Circulating Ligands of the Receptor for Advanced Glycation End Products and the Soluble Form of the Receptor Modulate Cardiovascular Cell Apoptosis in Diabetes.

We determined whether plasma concentrations of the receptor for advanced glycation end products (RAGE) and the soluble (s) form of RAGE (sRAGE) in healthy individuals and patients with type 2 diabetes (T2D) modulate vascular remodeling. Healthy individuals and patients with T2D were divided into two age groups: young = <35 years old or middle-aged (36-64 years old) and stratified based on normal glucose tolerance (NGT), impaired (IGT), and T2D. Plasma titers of sRAGE, the RAGE ligands, AGEs, S100B, S100A1, S100A6, and the apoptotic marker Fas ligand Fas(L) were measured by enzyme-linked immunosorbent assay (ELISA). The apoptotic potential of the above RAGE ligands and sRAGE were assessed in cultured adult rat aortic smooth muscle cells (ASMC). In NGT individuals, aging increased the circulating levels of AGEs and S100B and decreased sRAGE, S100A1 and S100A6. Middle-aged patients with T2D presented higher levels of circulating S100B, AGEs and FasL, but lower levels of sRAGE, S100A1 and S100A6 than individuals with NGT or IGT. Treatment of ASMC with either AGEs or S100B at concentrations detected in T2D patients increased markers of inflammation and apoptosis. Responses attenuated by concomitant administration of sRAGE. In middle-aged patients with T2D, lower circulating plasma levels of sRAGE may limit decoy and exogenous trapping of deleterious pro-apoptotic/pro-inflammatory RAGE ligands AGEs and S100B, increasing the risk for diabetic complications.

Hypertrophic cardiomyopathy: an updated review on diagnosis, prognosis, and treatment.

Hypertrophic cardiomyopathy (HCM) represents a phenotype of left ventricular hypertrophy unexplained by abnormal loading conditions. The definition is based on clinical criteria; however, there are numerous underlying etiologic factors. The MOGE(S) classification provides a standardized approach for multimodal characterization of HCM. HCM is associated with increased morbidity and mortality, and especially the assessment of the risk of sudden cardiac death is of paramount importance. In this review, we summarize essential knowledge and recently published data on clinical presentation, diagnosis, genetic analyses, differential diagnosis, prognosis, and treatment options that are necessary for understanding and management of HCM.

Review on sudden death risk reduction after septal reduction therapies in hypertrophic obstructive cardiomyopathy.

Treatment of left ventricular outflow tract (LVOT) obstruction in hypertrophic obstructive cardiomyopathy (HOCM) with septal reduction, either with myectomy or alcohol septal ablation, is aiming to reduce the LVOT gradient and improve symptoms in patients who are refractory to or do not tolerate medical treatment. Apart from contributing to the evolution to heart failure, LVOT obstruction is considered a risk factor for sudden cardiac death (SCD). Both septal reduction treatments have been proven effective in reducing symptoms and seem to improve survival, which has been shown equal to the expected in the normal population. SCD is probably reduced after septal reduction, implying that LVOT obstruction is a major factor predisposing to ventricular tachyarrhythmias. Although available algorithms for SCD stratification have not been tested in patients after septal reduction treatments, effective treatment improves SCD risk profile substantially. Furthermore, high-risk patients with already implanted implantable cardioverter defibrillators (ICDs) before septal reduction show very low appropriate ICD shock rate after effective treatment. It should be noted, however, that the best outcomes for septal myectomy or ablation have been reported in HOCM patients treated in high-volume centres, which substantiates the need to refer patients to centres with high procedural expertise.

Advances in the diagnosis and treatment of transthyretin amyloidosis with cardiac involvement.

Amyloidosis is caused by extracellular deposition of insoluble abnormal fibrils constituted by misfolded proteins, which can modify tissue anatomy and hinder the function of multiple organs including the heart. Amyloidosis that can affect the heart includes mostly systemic amyloidosis (amyloid light chain, AL) and transthyretin amyloidosis (ATTR). The latter can be acquired in elderly patients (ATTRwt), or be inherited in younger individuals (ATTRm). The diagnosis is demanding given the high phenotypic heterogeneity of the disease. Therefore, "red flags," which are suggestive features giving support to diagnostic suspicion, are extremely valuable. However, the lack of broad awareness among clinicians represents a major obstacle for early diagnosis and treatment of ATTR. Furthermore, recent implementation of noninvasive diagnostic techniques has revisited the need for endomyocardial biopsy (EMB). In fact, unlike AL amyloidosis, which requires tissue confirmation and typing for diagnosis, ATTR can now be diagnosed noninvasively with the combination of bone scintigraphy and the absence of a monoclonal protein. Securing the correct diagnosis is pivotal for the newly available therapeutic options targeting both ATTRm and ATTRwt, and are directed to either stabilization of the abnormal protein or the reduction of the production of transthyretin. The purpose of this article is to review the contemporary aspects of diagnosis and management of transthyretin amyloidosis with cardiac involvement, summarizing also the recent therapeutic advances with tafamidis, patisiran, and inotersen.

Correction to: Meta-analysis for the value of colchicine for the therapy of pericarditis and of postpericardiotomy syndrome.

After publication of the original article [1], we were notified that an author's name is not complete.

Meta-analysis for the value of colchicine for the therapy of pericarditis and of postpericardiotomy syndrome.

BACKGROUND: Colchicine has been used as anti-inflammatory agent in pericardial effusion (PE). We sought to perform a meta-analysis of randomized trials assessing the efficacy and safety of colchicine in patients with pericarditis or postpericardiotomy syndrome (PPS). METHODS: In the systematic literature search following the PRISMA statement, 10 prospective randomized controlled studies with 1981 patients with an average follow-up duration of 13.6 months were identified. RESULTS: Colchicine reduced the recurrence rate of pericarditis in patients with acute and recurrent pericarditis and reduced the incidence of PPS (RR: 0.57, 95% CI: 0.44-0.74). Additionally, the rate of rehospitalizations as well as the symptom duration after 72 h was significantly decreased in pericarditis (RR 0.33; 95% CI 0.18-0.60; and RR 0.43; 95% CI 0.34-0.54; respectively), but not in PPS. Treatment with colchicine was associated with significantly higher adverse event (AE) rates (RR 1.42; 95% CI 1.05-1.92), with gastrointestinal intolerance being the leading AE. The reported number needed to treat (NNT) for the prevention of recurrent pericarditis ranged between 3 and 5. The reported NNT for PPS prevention was 10, and the number needed to harm (NNH) was 12, respectively. Late colchicine administration > 7 days after heart surgery did not reduce postoperative PE. CONCLUSIONS: Our meta-analysis confirms that colchicine is efficacious and safe for prevention of recurrent pericarditis and PPS, while it reduces rehospitalizations and symptom duration in pericarditis. The clinical use of colchicine for the setting of PPS and postoperative PE after heart surgery should be investigated in further multicenter RCT.

Transcatheter septal ablation in hypertrophic obstructive cardiomyopathy: a technical guide and review of published results.

Transcatheter alcohol septal ablation (ASA) treatment of symptomatic patients with hypertrophic obstructive cardiomyopathy (HOCM) is based on the existence and degree of intraventricular obstruction. Patients with significant gradient and symptoms who do not respond to optimal medical therapy are eligible to gradient reduction through a surgical (septal myectomy) or a transcatheter (alcohol septal ablation) septal reduction. The latter encompasses occlusion of a septal branch perfusing the hypertrophied septum, which is involved in the generation of obstruction, by injecting ethanol into the supplying septal branch(es). ASA has been established as a highly effective and safe method and has outnumbered the surgical gold standard. Although the technique is straightforward, patient selection and some technical details may influence the efficacy and safety of the procedure. The technique is based on echocardiographic contrast guidance, which allows accurate target septal branch selection and optimisation of the result. Published long-term results from high-volume centres have confirmed the effectiveness of ASA and have shown excellent survival, which is comparable to that in the general population. Choice and performance of the surgical or interventional treatment should be implemented in highly specialised centres in terms of a heart-team approach, taking notice of anatomic characteristics as well as comorbidities. Involvement of all cases in international registries may reveal the individual merits and indications for the surgical and interventional treatment in HOCM.

Antiapoptotic Effect of ß1 Blockers in Ascending Thoracic Aortic Smooth Muscle Cells: The Role of HSP70 Expression.

Heat shock proteins (HSPs) play an important role in the cellular adaptation to stress, a requisite for cell survival. The aortic wall appears to be a target for increased expression of HSPs during surgical stress. We aimed to define the expression and function of aortic HSP70 in 31 patients with normal ascending thoracic aortic diameter who underwent aortic valve replacement due to aortic valve stenosis and in 35 patients with dilated ascending thoracic aorta who underwent replacement of an ascending thoracic aortic aneurysm. To elucidate responsible signaling mechanisms we used an in vitro model of rat hypoxic aortic vascular smooth muscle cell (AVSMC) cultures. We demonstrated an increase in AVSMC HSP70 and an attenuation of the apoptotic markers (TUNEL-positive nuclei, caspase-3 activity, Bax/Bcl2 ratio) in aortic wall tissue specimens from both aortic valve stenosis and ascending thoracic aortic aneurysm patients on ß1 blockade with metoprolol. In vitro, metoprolol treatment of hypoxic rat AVSMCs increased nitric oxide (NO) production, induced heat shock factor 1 transport to the nucleus, upregulated HSP70, decreased p53 phosphorylation and attenuated apoptosis. Blockade of NO production, resulted in decreased HSP70 and prevented the metoprolol-induced anti-apoptotic response of hypoxic AVSMCs. We demonstrate an anti-apoptotic effect of metoprolol dependent on NO-induced HSP70 expression, and thus augmentation of HSP70 expression should be considered as a therapeutic approach to limit apoptosis in the human ascending thoracic aorta of patients undergoing cardiac surgery.

The MOGE(S) classification for cardiomyopathies: current status and future outlook.

Cardiomyopathies are complex diseases of multifactorial pathogenesis and have a high morbidity and mortality. Over the past decades, several revisions of classifications and definitions of cardiomyopathies have been proposed, primarily focusing on the phenotypic characterization of cardiomyopathies. The MOGE(S) classification system published in 2013 encompasses the classification of rapidly growing knowledge on genetic mutations, acquired causes (i.e., intramyocardial inflammation, viral infections), and further conditions involved in the induction of cardiomyopathies (e.g., storage diseases, toxicity). It is based on five attributes, including morphofunctional characteristics (M), organ involvement (O), genetic or familial inheritance pattern (G), etiological annotation (E), and optional information about the heart failure functional status (S). This review summarizes the development, the cornerstones of the MOGE(S) classification, and the published data on the clinical relevance of the MOGE(S) classification. We furthermore discuss new issues which might be considered for future updates of the MOGE(S) classification of cardiomyopathies.