Endomyocardial Biopsy in Pediatric Myocarditis and Dilated Cardiomyopathy: A Tool in Search for a Role

Endomyocardial biopsy (EMB) is a well-known diagnostic tool for the investigation and treatment of myocardial diseases and remains the gold standard for the diagnosis of myocarditis. Due to its invasiveness, with a complication rate ranging from 1 to 15%, its role in the diagnostic work-up of pediatric heart failure is not well established. The aim of this review is to define the role of EMB as diagnostic technique in the work up of children presenting with severe left ventricular dysfunction with the support of our center experience.

Biventricular non-compaction cardiomyopathy and tricuspid hypoplasia in a novel non-POU domain-containing octamer-binding gene variant

A maternally inherited novel pathogenic non-POU domain-containing octamer-binding gene variant c.767G>T, p.R256I [NM_001145408], manifested in a male infant as dilated cardiomyopathy with severe left ventricular dysfunction and dilation, biventricular non-compaction, tricuspid hypoplasia, and hydrocephaly. To the best of our knowledge, no previous non-POU domain-containing octamer-binding gene variants with biventricular non-compaction have been associated with tricuspid valve hypoplasia. Hence, this case introduces a new pathogenic variant observed in the non-POU domain-containing octamer-binding gene and adds to the range of cardiac phenotypes identified in non-POU domain-containing octamer-binding gene variants.

Cellular aging and rejuvenation in ischemic heart disease: a translation from basic science to clinical therapy

Ischemic heart disease and heart failure (HF) remain the leading causes of death worldwide. The inability of the adult heart to regenerate itself following ischemic injury and subsequent scar formation may explain the poor prognosis in these patients, especially when necrosis is extensive and leads to severe left ventricular dysfunction. Under physiological conditions, the crosstalk between cardiomyocytes and cardiac interstitial/vascular cells plays a pivotal role in cardiac processes by limiting ischemic damage or promoting repair processes, such as angiogenesis, regulation of cardiac metabolism, and the release of soluble paracrine or endocrine factors. Cardiovascular risk factors are the main cause of accelerated senescence of cardiomyocytes and cardiac stromal cells (CSCs), causing the loss of their cardioprotective and repairing functions. CSCs are supportive cells found in the heart. Among these, the pericytes/mural cells have the propensity to differentiate, under appropriate stimuli in vitro, into adipocytes, smooth muscle cells, osteoblasts, and chondroblasts, as well as other cell types. They contribute to normal cardiac function and have an antifibrotic effect after ischemia. Diabetes represents a condition of accelerated senescence. Among the new pharmacological armamentarium with hypoglycemic effect, gliflozins have been shown to reduce the incidence of HF and re-hospitalization, probably through the anti-remodeling and anti-senescent effect on the heart, regardless of diabetes. Therefore, either reducing the senescence of CSC or removing senescent cells from the infarcted heart could represent future antisenescence strategies capable of preventing the deterioration of heart function leading to HF.

Mitochondrial Metabolism in Myocardial Remodeling and Mechanical Unloading: Implications for Ischemic Heart Disease

Ischemic heart disease refers to myocardial degeneration, necrosis, and fibrosis caused by coronary artery disease. It can lead to severe left ventricular dysfunction (LVEF ≤ 35–40%) and is a major cause of heart failure (HF). In each contraction, myocardium is subjected to a variety of mechanical forces, such as stretch, afterload, and shear stress, and these mechanical stresses are clinically associated with myocardial remodeling and, eventually, cardiac outcomes. Mitochondria produce 90% of ATP in the heart and participate in metabolic pathways that regulate the balance of glucose and fatty acid oxidative phosphorylation. However, altered energetics and metabolic reprogramming are proved to aggravate HF development and progression by disturbing substrate utilization. This review briefly summarizes the current insights into the adaptations of cardiomyocytes to mechanical stimuli and underlying mechanisms in ischemic heart disease, with focusing on mitochondrial metabolism. We also discuss how mechanical circulatory support (MCS) alters myocardial energy metabolism and affects the detrimental metabolic adaptations of the dysfunctional myocardium.

682 Cardioncology: is it time to spread the need for dedicated management?

Case report A 56-year-old man affected by micromolecular multiple myeloma was treated by several cycles of different chemotherapy drugs from September 2015 to December 2020. The chemotherapy regimen included 4-cycle first-line therapy with Bortezomib, Thalidomide, and Dexamethasone; 19-cycle second-line therapy with Carfilzomib, Revlimid, and Dexamethasone; 8-cycle third-line therapy with Daratumumab, Revlimid, and Dexamethasone; finally, he was started on therapy with Pomalidomide and Endoxan. During the various treatments, the patient did not follow a dedicated cardiological follow-up programme. In November 2020, he was hospitalized in the Intensive Care Unit for acute pulmonary oedema and subsequently discharged with a diagnosis of mild left ventricular systolic dysfunction (LVEF 50%). One month later, due to the worsening of dyspnoea, the patient was finally referred to our Cardioncology Unit for the medical assessment. The echocardiographic examination revealed a global and severe left ventricular dysfunction (FE 40%) with significant reduction in left ventricular global longitudinal strain (GLS −10%). For these reasons, we referred the patient to coronary angiography. Conclusions This case report wants to underline how important a dedicated cardiological follow-up is in patients undergoing chemotherapy drugs, especially if used at high doses and for many cycles.

Advances in Biomarkers for Detecting Early Cancer Treatment-Related Cardiac Dysfunction

With the gradual prolongation of the overall survival of cancer patients, the cardiovascular toxicity associated with oncology drug therapy and radiotherapy has attracted increasing attention. At present, the main methods to identify early cancer treatment-related cardiac dysfunction (CTRCD) include imaging examination and blood biomarkers. In this review, we will summarize the research progress of subclinical CTRCD-related blood biomarkers in detail. At present, common tumor therapies that cause CTRCD include: (1) Chemotherapy—The CTRCD induced by chemotherapy drugs represented by anthracycline showed a dose-dependent characteristic and most of the myocardial damage is irreversible. (2) Targeted therapy—Cardiovascular injury caused by molecular-targeted therapy drugs such as trastuzumab can be partially or completely alleviated via timely intervention. (3) Immunotherapy—Patients developed severe left ventricular dysfunction who received immune checkpoint inhibitors have been reported. (4) Radiotherapy—CTRCD induced by radiotherapy has been shown to be significantly associated with cardiac radiation dose and radiation volume. Numerous reports have shown that elevated troponin and B-type natriuretic peptide after cancer treatment are significantly associated with heart failure and asymptomatic left ventricular dysfunction. In recent years, a few emerging subclinical CTRCD potential biomarkers have attracted attention. C-reactive protein and ST2 have been shown to be associated with CTRCD after chemotherapy and radiation. Galectin-3, myeloperoxidas, placental growth factor, growth differentiation factor 15 and microRNAs have potential value in predicting CTRCD. In this review, we will summarize CTRCD caused by various tumor therapies from the perspective of cardio-oncology, and focus on the latest research progress of subclinical CTRCD biomarkers.

Late-Term Complications of COVID-19: Retropharyngeal Infection and Myocarditis in a 26-Year-Old Patient

Deep neck space infection and viral myocarditis related to coronavirus disease 2019 (COVID-19) have both been described in the medical literature. However, there are only three reported cases of retropharyngeal infection as a presenting pathology in the setting of COVID-19. A 26-year-old woman presented to the emergency room with fever and neck swelling and pain 1 month after COVID-19 infection. A computed tomography scan of the neck demonstrated tonsillitis with retropharyngeal infection. She was also found to have heart failure with an ejection fraction (EF) of <20% due to acute myocarditis. Her infection resolved and the EF improved to 40% prior to discharge. Our case is the first to describe retropharyngeal infection as a late complication in an adult with a history of COVID-19 several weeks previously. It also presented a clinical challenge in terms of tailoring goal-directed medical therapy to manage severe left ventricular dysfunction caused by myocarditis.

Cardiac resynchronisation therapy in a pace-dependent infant with tetralogy of Fallot

We present the case of a 5-month-old infant with tetralogy of Fallot and congenital atrio-ventricular block that developed severe left ventricular dysfunction during apical left ventricular pacing, in which cardiac resynchronisation therapy was used as an emergency procedure due to persistent low cardiac output syndrome.

A Case Report on Ischaemic Cardiomyopathy with Severe Left Ventricular Dysfunction

Ischaemic cardiomyopathy is a condition that arises when heart muscle is weakened because of coronary artery disease or a heart attack. Left ventricular (LV) dysfunction occurs when the left ventricle is either defective or damaged, thus disrupting healthy function. Normal LV function can be perturbed because of several causes. Some cardiac defects such as valvular malformations or conditions block the passage of blood into the body. Effective and cost-effective treatment is available for such patients that can reduce both morbidity and mortality. Herein, the authors present the case of a 69-year-old male who was brought to the emergency department with a history of hypertension on medication. Later, the patient was transferred to the cardiology department. The patient was brought to the hospital after midnight and had bleeding gums, and experienced bleeding from the site of needle puncture. Earlier reports showed that the international normalised ratio was >6.0, and the 2D echocardiogram showed large LV blood clots, mild LV dysfunction, mild mitral regurgitation, and aortic valve stenosis. Finally, the patient was diagnosed with ischaemic cardiomyopathy associated with LV dysfunction. During discharge, the patient and patient’s representative were counselled in layman’s language about the conditions and prognosis of the disease, the use and adherence to medications, lifestyle modifications, and were advised to review back to the cardiologist.

AMI causing cardiogenic shock in patients with severely depressed left ventricular function

Introduction Left ventricular function is assumed to be the main predictor of cardiogenic shock (CS), however trials and registries show that in average left ventricular function is only moderately depressed in CS after acute myocardial infarction. Purpose Characterize population of patients (Pts) with CS after acute myocardial infarction (AMI) and with severe left ventricular dysfunction (defined as ejection fraction (EF) &lt;30%). Methods From a national multicenter registry, we evaluated 729ptswith CS after AMI.We considered 2 groups: Group 1 – pts with CS and EF &lt;30% and Group 2 – pts with CS and EF &gt;30%. We registered age, gender, cardiovascular and non-cardiovascular comorbidities, electrocardiographic presentation, vital signs at admission, reperfusion strategy and coronary anatomy. We also evaluated in-hospital complications, such as re-infarction, mechanical complications, high-grade atrial ventricular block, sustained ventricular tachycardia (VT), atrial fibrillation (AF) and stroke. We compared in-hospital mortality and multivariate analysis was performed to assess the impact of EF in in-hospital mortality and to identify predictors of severe left ventricular function. Results Severe dysfunction in Cardiogenic shock due to AMI was present in 28.9% (n=211) of pts (68% male, mean age of 72±12 years old). Group 1 had higher incidence of previous heart disease, such as AMI, previous PCI and congestive heart failure (27% vs 14%, p&lt;0.001; 17.7% vs 9.6% p=0.002 and 16% vs 10%, p=0.022, respectively). STEMI pts were 71% (n=149), and timing from symptoms until first contact was longer (185 min (90; 437) vs 123 (60; 300), p&lt;0.001). Undetermined location AMI was more often in group 1 (8% vs 2%, p&lt;0.001), particularly due to left or right bundle brunch block (13% vs 4.7%, p&lt;0.001, and 15% vs 10%, p=0.041 respectively). Anterior STEMI was also more prevalent in this groups (81% vs 46%, p&lt;0.001). No differences were observed on coronariography rate, rate or type of reperfusion nor multivessel disease. Group 1 pts presented more with left main (LM) (25% vs 12%, p&lt;0.001) and anterior descending (AD) (9.4% vs 2.4%, p&lt;0.001) arteries lesions (88% vs 72.4%, p&lt;0.001) or occlusion (65.5% vs 33.7%, p&lt;0.001). Group 1 presented more with in-hospital VT (16% vs 10.8%, p=0.048). In-hospital mortality was also higher (56.5% vs 29.5%, p&lt;0.001). After multivariate analysis we found that severe left ventricular dysfunction was a mortality predictor (OR 3.37; 95% CI 2.05–5.54, p&lt;0.001). LM (OR 3.41; 95% CI 1.86–6.26, p&lt;0.001) and AD (OR 2.74; 95% CI 1.51–4.96, p=0.001) arteries disease and previous AMI (OR 2.36; 95% CI 1.28–4.37, p=0.006) were predictors of severe LV dysfunction. Conclusions Severely depressed EF is a predictor of in-hospital mortality. Left main and anterior descending artery disease and previous AMI were identified as predictors of an EF &lt;30%. FUNDunding Acknowledgement Type of funding sources: None.