Comparing and contrasting speeches attributed to barbarian leaders by ancient Roman historians, this book offers a systematic examination of the ways in which those historians valorized foreigners ...and presented criticisms of their own society.
Eosinophilic myocarditis (EM) is an acute life-threatening inflammatory disease of the heart. Neither large case series nor clinical trials on this specific myocarditis have been reported.
Based on a ...systematic revision of all published histologically proven cases, this study aimed to describe the clinical presentation, treatment, and outcome of EM.
The study screened 443 manuscripts in MEDLINE and EMBASE on cases of EM published until June 2017. The authors identified 264 patients and included in the main analysis 179 patients admitted to hospital with histologically proven EM.
Median age was 41 years (interquartile range: 27 to 53 years) with similar prevalence in both sexes; pediatric cases (≤16 years of age) accounted for 10.1%. The main symptom at presentation was dyspnea (59.4%), with peripheral eosinophilia observed in 75.9%. Median left ventricular ejection fraction at presentation was 35% (interquartile range: 25% to 50%). The disorders most frequently associated with EM were hypersensitivity and eosinophilic granulomatosis with polyangiitis, which accounted for 34.1% and 12.8% of cases, respectively, whereas idiopathic or undefined forms accounted for 35.7% of cases. Steroids were administered in 77.7% of patients. A temporary mechanical circulatory support (n = 30) was instituted in 16.8% of patients. In-hospital death was 22.3% (n = 40), with the highest occurrence in the hypersensitivity form (36.1%; p = 0.026).
EM has a poor prognosis during the acute phase, despite a publication bias that could have led to an overestimation of mortality. Associated conditions are identified in approximately 65% of cases. Specific trials and multicenter registries are needed to provide evidence-based treatments to improve in-hospital outcome.
Background
Predicting mortality is important in patients with heart failure (HF). However, current strategies for predicting risk are only modestly successful, likely because they are derived from ...statistical analysis methods that fail to capture prognostic information in large data sets containing multi‐dimensional interactions.
Methods and results
We used a machine learning algorithm to capture correlations between patient characteristics and mortality. A model was built by training a boosted decision tree algorithm to relate a subset of the patient data with a very high or very low mortality risk in a cohort of 5822 hospitalized and ambulatory patients with HF. From this model we derived a risk score that accurately discriminated between low and high‐risk of death by identifying eight variables (diastolic blood pressure, creatinine, blood urea nitrogen, haemoglobin, white blood cell count, platelets, albumin, and red blood cell distribution width). This risk score had an area under the curve (AUC) of 0.88 and was predictive across the full spectrum of risk. External validation in two separate HF populations gave AUCs of 0.84 and 0.81, which were superior to those obtained with two available risk scores in these same populations.
Conclusions
Using machine learning and readily available variables, we generated and validated a mortality risk score in patients with HF that was more accurate than other risk scores to which it was compared. These results support the use of this machine learning approach for the evaluation of patients with HF and in other settings where predicting risk has been challenging.
Fulminant myocarditis (FM) is a form of acute myocarditis characterized by severe left ventricular systolic dysfunction requiring inotropes and/or mechanical circulatory support. A single-center ...study found that a patient with FM had better outcomes than those with acute nonfulminant myocarditis (NFM) presenting with left ventricular systolic dysfunction, but otherwise hemodynamically stable. This was recently challenged, so disagreement still exists.
This study sought to provide additional evidence on the outcome of FM and to ascertain whether patient stratification based on the main histologic subtypes can provide additional prognostic information.
A total of 220 patients (median age 42 years, 46.3% female) with histologically proven acute myocarditis (onset of symptoms <30 days) all presenting with left ventricular systolic dysfunction were included in a retrospective, international registry comprising 16 tertiary hospitals in the United States, Europe, and Japan. The main endpoint was the occurrence of cardiac death or heart transplantation within 60 days from admission and at long-term follow-up.
Patients with FM (n = 165) had significantly higher rates of cardiac death and heart transplantation compared with those with NFM (n = 55), both at 60 days (28.0% vs. 1.8%, p = 0.0001) and at 7-year follow-up (47.7% vs. 10.4%, p < 0.0001). Using Cox multivariate analysis, the histologic subtype emerged as a further variable affecting the outcome in FM patients, with giant cell myocarditis having a significantly worse prognosis compared with eosinophilic and lymphocytic myocarditis. In a subanalysis including only adults with lymphocytic myocarditis, the main endpoints occurred more frequently in FM compared with in NFM both at 60 days (19.5% vs. 0%, p = 0.005) and at 7-year follow up (41.4% vs. 3.1%, p = 0.0004).
This international registry confirms that patients with FM have higher rates of cardiac death and heart transplantation both in the short- and long-term compared with patients with NFM. Furthermore, we provide evidence that the histologic subtype of FM carries independent prognostic value, highlighting the need for timely endomyocardial biopsy in this condition.
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Acute myocarditis (AM), a recent-onset inflammation of the heart, has heterogeneous clinical presentations, varying from minor symptoms to high-risk cardiac conditions with severe heart failure, ...refractory arrhythmias, and cardiogenic shock. AM is moving from being a definitive diagnosis based on histological evidence of inflammatory infiltrates on cardiac tissue to a working diagnosis supported by high sensitivity troponin increase in association with specific cardiac magnetic resonance imaging (CMRI) findings. Though experts still diverge between those advocating for histological definition versus those supporting a mainly clinical definition of myocarditis, in the real-world practice the diagnosis of AM has undoubtedly shifted from being mainly biopsy-based to solely CMRI-based in most of clinical scenarios. It is thus important to clearly define selected settings where EMB is a must, as information derived from histology is essential for an optimal management. As in other medical conditions, a risk-based approach should be promoted in order to identify the most severe AM cases requiring appropriate bundles of care, including early recognition, transfer to tertiary centers, aggressive circulatory supports with inotropes and mechanical devices, histologic confirmation and eventual immunosuppressive therapy. Despite improvements in recognition and treatment of AM, including a broader use of promising mechanical circulatory supports, severe forms of AM are still burdened by dismal outcomes. This review is focused on recent clinical studies and registries that shed new insights on AM. Attention will be paid to contemporary outcomes and predictors of prognosis, the emerging entity of immune checkpoint inhibitors-associated myocarditis, updated CMRI diagnostic criteria, new data on the use of temporary mechanical circulatory supports in fulminant myocarditis. The role of viruses as etiologic agents will be reviewed and a brief update on pediatric AM is also provided. Finally, we summarize a risk-based approach to AM, based on available evidence and clinical experience.
Myocarditis is an inflammatory disease of the heart that may occur because of infections, immune system activation, or exposure to drugs. The diagnosis of myocarditis has changed due to the ...introduction of cardiac magnetic resonance imaging. We present an expert consensus document aimed to summarize the common terminology related to myocarditis meanwhile highlighting some areas of controversies and uncertainties and the unmet clinical needs. In fact, controversies persist regarding mechanisms that determine the transition from the initial trigger to myocardial inflammation and from acute myocardial damage to chronic ventricular dysfunction. It is still uncertain which viruses (besides enteroviruses) cause direct tissue damage, act as triggers for immune-mediated damage, or both. Regarding terminology, myocarditis can be characterized according to etiology, phase, and severity of the disease, predominant symptoms, and pathological findings. Clinically, acute myocarditis (AM) implies a short time elapsed from the onset of symptoms and diagnosis (generally <1 month). In contrast, chronic inflammatory cardiomyopathy indicates myocardial inflammation with established dilated cardiomyopathy or hypokinetic nondilated phenotype, which in the advanced stages evolves into fibrosis without detectable inflammation. Suggested diagnostic and treatment recommendations for AM and chronic inflammatory cardiomyopathy are mainly based on expert opinion given the lack of well-designed contemporary clinical studies in the field. We will provide a shared and practical approach to patient diagnosis and management, underlying differences between the European and US scientific statements on this topic. We explain the role of histology that defines subtypes of myocarditis and its prognostic and therapeutic implications.
Mitochondrial quality control is critical for cardiac homeostasis as these organelles are responsible for generating most of the energy needed to sustain contraction. Dysfunctional mitochondria are ...normally degraded via intracellular degradation pathways that converge on the lysosome. Here, we identified an alternative mechanism to eliminate mitochondria when lysosomal function is compromised. We show that lysosomal inhibition leads to increased secretion of mitochondria in large extracellular vesicles (EVs). The EVs are produced in multivesicular bodies, and their release is independent of autophagy. Deletion of the small GTPase Rab7 in cells or adult mouse heart leads to increased secretion of EVs containing ubiquitinated cargos, including intact mitochondria. The secreted EVs are captured by macrophages without activating inflammation. Hearts from aged mice or Danon disease patients have increased levels of secreted EVs containing mitochondria indicating activation of vesicular release during cardiac pathophysiology. Overall, these findings establish that mitochondria are eliminated in large EVs through the endosomal pathway when lysosomal degradation is inhibited.
Danon disease (DD) is a rare X-linked autophagic vacuolar myopathy, characterized by high penetrance and severe cardiomyopathy. Because of its rarity, the natural history (NH) is uncertain.
We aimed ...to describe disease variability and outcomes through a systematic review of all published DD cases.
Among 83 manuscripts in MEDLINE and EMBASE on DD cases published until October 2017, we identified 146 patients with positive genetic testing for DD or positive muscle biopsy in a relative of a genetically diagnosed proband.
56 females and 90 males were identified. 92.5% of patients had cardiac abnormalities. Females presented with either hypertrophic cardiomyopathy (HCM, 70.3%) or dilated cardiomyopathy (DCM, 29.3%) whereas males presented with HCM 96.2% of the time. The composite outcome of death, heart transplant or ventricular assist devices occurred equally in both sexes (32% of females and 37% of males, p = 0.60) but later in females (median age 38 years) than in males (median age 21 years, p < 0.001). Whereas women present with isolated cardiac disease 73% of the time, in males DD was frequently multisystemic and presented as a triad of cognitive impairment, skeletal myopathy, and HCM in 42% of patients.
In this first systematic review of DD, we confirmed the severe morbidity and mortality associated with disease in both sexes. Women presented with both HCM and DCM and generally with isolated cardiac disease, whereas in men DD usually presented as HCM and was frequently multi-systemic. Further prospective NH studies will be required to confirm these findings.
•The study reviewed all the case report/case series published on Danon Disease (DD).•DD may be devastating in both genders.•DD Males present with a triad of skeletal myopathy and cardiac and cognitive impairment.•DD Females present as an isolated cardiomyopathy.•DD should be considered in both sexes with clinical manifestations or positive family history.
Purpose of Review
To review the clinical features of acute myocarditis, including its fulminant presentation, and present a pragmatic approach to the diagnosis and treatment, considering indications ...of American and European Scientific Statements and recent data derived by large contemporary registries.
Recent Findings
Patients presenting with acute uncomplicated myocarditis (i.e., without left ventricular dysfunction, heart failure, or ventricular arrhythmias) have a favorable short- and long-term prognosis: these findings do not support the indication to endomyocardial biopsy in this clinical scenario. Conversely, patients with complicated presentations, especially those with fulminant myocarditis, require an aggressive and comprehensive management, including endomyocardial biopsy and availability of advanced therapies for circulatory support. Although several immunomodulatory or immunosuppressive therapies have been studied and are actually prescribed in the real-world practice, their effectiveness has not been clearly demonstrated. Patients with specific histological subtypes of acute myocarditis (i.e., giant cell and eosinophilic myocarditis) or those affected by sarcoidosis or systemic autoimmune disorders seem to benefit most from immunosuppression. On the other hand, no clear evidence supports the use of immunosuppressive agents in patients with lymphocytic acute myocarditis, even though small series suggest a potential benefit.
Summary
Acute myocarditis is a heterogeneous condition with distinct pathophysiological pathways. Further research is mandatory to identify factors and mechanisms that may trigger/maintain or counteract/repair the myocardial damage, in order to provide a rational for future evidence-based treatment of patients affected by this condition.
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