Abnormal conduction-induced cardiomyopathy: a poorly explored entity.

A dyssynchronous biventricular activation, which can be determined by left bundle branch block, chronic right ventricular pacing, frequent premature ventricular complexes, or pre-excitation, can cause a global abnormal contractility, thus leading to systolic dysfunction and left ventricular remodelling in a unique nosological entities: abnormal conduction-induced cardiomyopathies. In this clinical scenario, the mainstay therapy is eliminating or improving LV dyssynchrony, removing the trigger. This usually ensures the improvement and even recovery of cardiac geometry and left ventricular function, especially in the absence of genetic background. A multidisciplinary approach, integrating advanced multimodal imaging, is essential for the systematic aetiological definition and the subsequent evaluation and aetiology-guided therapies of patients and their families. This review aims to describe mechanisms, prevalence, risk factors, and diagnostic and therapeutic approach to the various abnormal conduction-induced cardiomyopathies, starting from reasonable certainties and then analysing the grey areas requiring further studies.

COVID-19-Related Myocarditis: Are We There Yet? A Case Report of COVID-19-Related Fulminant Myocarditis.

There is increasing evidence of cardiac involvement in COVID-19 cases, with a broad range of clinical manifestations spanning from acute life-threatening conditions such as ventricular dysrhythmias, myocarditis, acute myocardial ischemia and pulmonary thromboembolism to long-term cardiovascular sequelae. In particular, acute myocarditis represents an uncommon but frightening complication of SARS-CoV-2 infection. Even if many reports of SARS CoV-2 myocarditis are present in the literature, the majority of them lacks histological confirmation of cardiac injury. Here, we report a case of a young lady, who died suddenly a few days after testing positive for SARS-CoV-2, whose microscopic and genetics features suggested a direct cardiac involvement compatible with fulminant myocarditis.

How Coronary Perforation Looks at Optical Coherence Tomography Imaging.

In this case, review of OCT images after successful closure of a coronary perforation (CP) showed that the initial CP was visible as an abrupt interruption of the intimal tissue and the presence of a crater with blood reaching the external layers of vessel wall. CP was probably caused by overstretch of the vessel wall in an intramural segment of the left anterior descending coronary artery. CP is a possible complication of PTCA that is rarely documented with intracoronary imaging due to its rapid and dramatic evolution. We report the unique images of how an initial CP appears at OCT.

Clinical application of CMR in cardiomyopathies: evolving concepts and techniques : A position paper of myocardial and pericardial diseases and cardiac magnetic resonance working groups of Italian society of cardiology.

Cardiac magnetic resonance (CMR) has become an essential tool for the evaluation of patients affected or at risk of developing cardiomyopathies (CMPs). In fact, CMR not only provides precise data on cardiac volumes, wall thickness, mass and systolic function but it also a non-invasive characterization of myocardial tissue, thus helping the early diagnosis and the precise phenotyping of the different CMPs, which is essential for early and individualized treatment of patients. Furthermore, several CMR characteristics, such as the presence of extensive LGE or abnormal mapping values, are emerging as prognostic markers, therefore helping to define patients' risk. Lastly new experimental CMR techniques are under investigation and might contribute to widen our knowledge in the field of CMPs. In this perspective, CMR appears an essential tool to be systematically applied in the diagnostic and prognostic work-up of CMPs in clinical practice. This review provides a deep overview of clinical applicability of standard and emerging CMR techniques in the management of CMPs.

Infolding of Self-Expandable Transcatheter Valve: A Complication that Needs Prompt Diagnosis During TAVR Procedure.

Infolding of self-expandable prosthetic valve is a possible complication of transcatheter aortic valve replacement (TAVR). A prompt diagnosis during the procedure before full deployment of the valve is extremely important to avoid potentially lethal consequences.

Cardiology of the future: xenotransplantation with porcine heart.

The reduced availability of human donor hearts compared with the needs of patients with advanced heart failure refractory to medical therapy has promoted the search for therapeutic alternatives to cardiac allografts. Porcine heart xenotransplantation represents one of the most promising frontiers in this field today. From the first researches in the 1960s to today, the numerous advances achieved in the field of surgical techniques, genetic engineering and immunosuppression have made it possible at the beginning of 2022 to carry out the first swine-to-human heart transplant, attaining a survival of 2 months after surgery. The main intellectual and experimental stages that have marked the history of xenotransplantation, the latest acquisitions in terms of genetic editing, as well as the improvement of immunosuppressive therapy are discussed analytically in this article in order to illustrate the underlying complexity of this therapeutic model.

Prognostic Prediction of Genotype vs Phenotype in Genetic Cardiomyopathies.

BACKGROUND: Diverse genetic backgrounds often lead to phenotypic heterogeneity in cardiomyopathies (CMPs). Previous genotype-phenotype studies have primarily focused on the analysis of a single phenotype, and the diagnostic and prognostic features of the CMP genotype across different phenotypic expressions remain poorly understood. OBJECTIVES: We sought to define differences in outcome prediction when stratifying patients based on phenotype at presentation compared with genotype in a large cohort of patients with CMPs and positive genetic testing. METHODS: Dilated cardiomyopathy (DCM), arrhythmogenic right ventricular cardiomyopathy, left-dominant arrhythmogenic cardiomyopathy, and biventricular arrhythmogenic cardiomyopathy were examined in this study. A total of 281 patients (80% DCM) with pathogenic or likely pathogenic variants were included. The primary and secondary outcomes were: 1) all-cause mortality (D)/heart transplant (HT); 2) sudden cardiac death/major ventricular arrhythmias (SCD/MVA); and 3) heart failure-related death (DHF)/HT/left ventricular assist device implantation (LVAD). RESULTS: Survival analysis revealed that SCD/MVA events occurred more frequently in patients without a DCM phenotype and in carriers of DSP, PKP2, LMNA, and FLNC variants. However, after adjustment for age and sex, genotype-based classification, but not phenotype-based classification, was predictive of SCD/MVA. LMNA showed the worst trends in terms of D/HT and DHF/HT/LVAD. CONCLUSIONS: Genotypes were associated with significant phenotypic heterogeneity in genetic cardiomyopathies. Nevertheless, in our study, genotypic-based classification showed higher precision in predicting the outcome of patients with CMP than phenotype-based classification. These findings add to our current understanding of inherited CMPs and contribute to the risk stratification of patients with positive genetic testing.

Long-term effect of SARS-CoV-2 infection on cardiovascular outcomes and all-cause mortality.

Since the very beginning of the coronavirus disease 2019 (COVID-19) pandemic in early 2020, it was evident that patients with cardiovascular disease (CVD) were at an increased risk of developing severe illness, and complications spanning cerebrovascular disorders, dysrhythmias, acute coronary syndrome, ischemic and non-ischemic heart disease, pericarditis, myocarditis, heart failure, thromboembolic disease, stroke, and death. Underlying these was excessive systemic inflammation and coagulopathy due to SARS-COV-2 infection, the effects of which also continued long-term as evidenced by post-COVID-19 cardiovascular complications. The acute and chronic cardiovascular effects of COVID-19 occurred even among those who were not hospitalized and had no previous CVD or those with mild symptoms. This comprehensive review summarizes the current understanding of molecular mechanisms triggered by the SARS-CoV-2 virus on various cells that express the angiotensin-converting enzyme 2, leading to endothelial dysfunction, inflammation, myocarditis, impaired coagulation, myocardial infarction, arrhythmia and a multisystem inflammatory syndrome in children or Kawasaki-like disease.

Pulmonary Embolism Presenting with Pulmonary Infarction: Update and Practical Review of Literature Data.

Pulmonary infarction (PI) is a possible consequence of pulmonary embolism (PE). The real incidence of PI could be underestimated considering only non-fatal PE presentation. However, following postmortem examination, the prevalence of PI is considerably higher. This evidence suggests the necessity of proper diagnostic protocol for identifying PI. Unfortunately, PI diagnosis can sometimes be challenging, due to the overlapping of symptoms with other diseases. Nowadays, the diagnosis is mainly based on radiological evaluation, although the combination with emerging imaging techniques such as ultrasound and nuclear scanning might improve the diagnostic algorithm for PI. This review aims to summarize the available data on the prevalence of PI, the main predisposing factors for the development of PI among patients with PE, to resume the possible diagnostic tools, and finally the clinical and prognostic implications.

Sex differences in natural history of cardiovascular magnetic resonance- and biopsy-proven lymphocytic myocarditis.

AIMS: The role of sex in determining the profile and the outcomes of patients with myocarditis is largely unexplored. We evaluated the impact of sex as a modifier factor in the clinical characterization and natural history of patients with definite diagnosis of myocarditis. METHODS AND RESULTS: We retrospectively analysed a single-centre cohort of consecutive patients with definite diagnosis of myocarditis (i.e. endomyocardial biopsy or cardiac magnetic resonance proven). Specific sub-analyses were performed in cohorts of patients with chest pain, ventricular arrhythmias, and heart failure as different main symptoms at presentation. The primary outcome measure was a composite of all-cause mortality or heart transplantation (HTx). We included 312 patients, of which 211, 68% of the whole population, were males. Despite no clinically relevant differences found at baseline presentation, males had a higher indexed left ventricular end-diastolic volume (62 ± 23 mL/m2 vs. 52 ± 20 mL/m2, P = 0.011 in males vs. females, respectively) at follow-up evaluation. At a median follow-up of 72 months, 36 (17%) males vs. 8 (8%) females experienced death or HTx (P = 0.033). Male sex emerged as predictors of all-cause mortality or HTx in every combination of covariates (HR 2.600; 1.163-5.809; P = 0.020). Results were agreeable regardless of the main symptom of presentation. CONCLUSIONS: In a large cohort of patients with definite diagnosis of myocarditis, females experienced a more favourable long-term prognosis than males, despite a similar clinical profile at presentation.

Common Shared Pathogenic Aspects of Small Vessels in Heart and Brain Disease.

Small-vessel disease (SVD), also known as microvascular endothelial dysfunction, is a disorder with negative consequences for various organs such as the heart and brain. Impaired dilatation and constriction of small vessels in the heart lead to reduced blood flow and ischemia independently of coronary artery disease (CAD) and are associated with major cardiac events. SVD is usually a silent form of subcortical vascular burden in the brain with various clinical manifestations, such as silent-lacunar-ischemic events and confluent white-matter hyperintensities. Imaging techniques are the main help for clinicians to diagnose cardiac and brain SVD correctly. Markers of inflammation, such as C-reactive protein, tumor-necrosis-factor α, and interleukin 6, provide insight into the disease and markers that negatively influence nitric-oxide bioavailability and promote oxidative stress. Unfortunately, the therapeutic approach against SVD is still not well-defined. In the last decades, various antioxidants, oxidative stress inhibitors, and superoxide scavengers have been the target of extensive investigations due to their potential therapeutic effect, but with unsatisfactory results. In clinical practice, traditional anti-ischemic and risk-reduction therapies for CAD are currently in use for SVD treatment.

Global longitudinal strain by CMR improves prognostic stratification in acute myocarditis presenting with normal LVEF.

BACKGROUND: Prognostic stratification of acute myocarditis (AM) presenting with normal left ventricular ejection fraction (LVEF) relies mostly on late gadolinium enhancement (LGE) characterization. Left ventricular peak global longitudinal strain (LV-GLS) measured by feature tracking analysis might improve prognostication of AM presenting with normal LVEF. METHODS: Data of patients undergoing cardiac magnetic resonance (CMR) for clinically suspected AM in seven European Centres (2013-2020) were retrospectively analysed. Patients with AM confirmed by CMR and LVEF ≥50% were included. LGE was visually characterized: localized versus. non-localized, subepicardial versus midwall. LV-GLS was measured by dedicated software. The primary outcome was the first occurrence of an adverse cardiovascular event (ACE) including cardiac death, life-threatening arrhythmias, development of heart failure or of LVEF <50%. RESULTS: Of 389 screened patients, 256 (66%) fulfilled inclusion criteria: median age 36 years, 71% males, median LVEF 60%, median LV-GLS -17.3%. CMR was performed at 4 days from hospitalization. At 27 months, 24 (9%) patients experienced ≥1 ACE (71% developed LVEF <50%). Compared to the others, they had lower median LV-GLS values (-13.9% vs. -17.5%, p = .001). At Kaplan-Meier analysis, impaired LV-GLS (both considered as > -20% or quartiles), non-localized and midwall LGE were associated with ACEs. Patients with LV-GLS ≤-20% did not experience ACEs. LV-GLS remained associated with ACEs after adjustment for non-localized and midwall LGE. CONCLUSION: In AM presenting with LVEF ≥50%, LV-GLS provides independent prognostic value over LGE characterization, improving risk stratification and representing a rationale for further studies of therapy in this cohort.

Old and Novel Therapeutic Approaches in the Management of Hyperglycemia, an Important Risk Factor for Atherosclerosis.

Hyperglycemia is considered one of the main risk factors for atherosclerosis, since high glucose levels trigger multiple pathological processes, such as oxidative stress and hyperproduction of pro-inflammatory mediators, leading to endothelial dysfunction. In this context, recently approved drugs, such as glucagon-like-peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2i), could be considered a powerful tool for to reduce glucose concentration and cardiovascular risk. Interestingly, many patients with type 2 diabetes mellitus (T2DM) and insulin resistance have been found to be deficient in vitamin D. Recent studies pointed out the unfavorable prognostic values of T2DM and vitamin D deficiency in patients with cardiac dysfunction, either when considered individually or together, which shed light on the role of vitamin D in general health status. New evidence suggests that SGLT2i could adversely affect the production of vitamin D, thereby increasing the risk of fractures, which are common in patients with T2DM. Therefore, given the biological effects of vitamin D as an anti-inflammatory mediator and a regulator of endothelial function and calcium equilibrium, these new findings should be taken into consideration as well. The aim of this review is to gather the latest advancements regarding the use of antidiabetic and antiplatelet drugs coupled with vitamin D supplementation to control glucose levels, therefore reducing the risk of coronary artery disease (CAD).

The peculiar role of vitamin D in the pathophysiology of cardiovascular and neurodegenerative diseases.

Vitamin D is a hormone with both genomic and non-genomic actions. It exerts its activity by binding vitamin D receptor (VDR), which belongs to the superfamily of nuclear receptors and ligand-activated transcription factors. Since VDR has been found in various tissues, it has been estimated that it regulates approximately 3% of the human genome. Several recent studies have shown pleiotropic effects of vitamin D in various processes such as cellular proliferation, differentiation, DNA repair and apoptosis and its involvement in different pathophysiological conditions as inflammation, diabetes mellitus, and anemia. It has been suggested that vitamin D could play an important role in neurodegenerative and cardiovascular disorders. Moderate to strong associations between lower serum vitamin D concentrations and stroke and cardiovascular events have been identified in different analytic approaches, even after controlling for traditional demographic and lifestyle covariates. The mechanisms behind the associations between vitamin D and cerebrovascular and cardiologic profiles have been widely examined both in animal and human studies. Optimization of vitamin D levels in human subjects may improve insulin sensitivity and beta-cell function and lower levels of inflammatory markers. Moreover, it has been demonstrated that altered gene expression of VDR and 1,25D3-membrane-associated rapid response steroid-binding (1,25D3-MARRS) receptor influences the role of vitamin D within neurons and allows them to be more prone to degeneration. This review summarizes the current understanding of the molecular mechanisms underlying vitamin D signaling and the consequences of vitamin D deficiency in neurodegenerative and cardiovascular disorders.

Biomarkers in the management of acute heart failure: state of the art and role in COVID-19 era.

Acute heart failure (AHF) affects millions of people worldwide, and it is a potentially life-threatening condition for which the cardiologist is more often brought into play. It is crucial to rapidly identify, among patients presenting with dyspnoea, those with AHF and to accurately stratify their risk, in order to define the appropriate setting of care, especially nowadays due to the coronavirus disease 2019 (COVID-19) outbreak. Furthermore, with physical examination being limited by personal protective equipment, the use of new alternative diagnostic and prognostic tools could be of extreme importance. In this regard, usage of biomarkers, especially when combined (a multimarker approach) is beneficial for establishment of an accurate diagnosis, risk stratification and post-discharge monitoring. This review highlights the use of both traditional biomarkers such as natriuretic peptides (NP) and troponin, and emerging biomarkers such as soluble suppression of tumourigenicity (sST2) and galectin-3 (Gal-3), from patients' emergency admission to discharge and follow-up, to improve risk stratification and outcomes in terms of mortality and rehospitalization.

What the Cardiologist Needs to Consider in the Management of Oncologic Patients with STEMI-Like Syndrome: A Case Report and Literature Review.

In pre-hospital care, an accurate and quick diagnosis of ST-segment elevation myocardial infarction (STEMI) is imperative to promptly kick-off the STEMI network with a direct transfer to the cardiac catheterization laboratory (cath lab) in order to reduce myocardial infarction size and mortality. Aa atherosclerotic plaque rupture is the main mechanism responsible for STEMI. However, in a small percentage of patients, emergency coronarography does not reveal any significant coronary stenosis. The fluoropyrimidine agents such as 5-Fluorouracil (5-FU) and capecitabine, widely used to treat gastrointestinal, breast, head and neck cancers, either as a single agent or in combination with other chemotherapies, can cause potentially lethal cardiac side effects. Here, we present the case of a patient with 5-FU cardiotoxicity resulting in an acute coronary syndrome (ACS) with recurrent episodes of chest pain and ST-segment elevation.. Our case report highlights the importance of widening the knowledge among cardiologists of the side effects of chemotherapeutic drugs, especially considering the rising number of cancer patients around the world and that fluoropyrimidines are the main treatment for many types of cancer, both in adjuvant and advanced settings.

Traditional and Emerging Biomarkers in Asymptomatic Left Ventricular Dysfunction-Promising Non-Coding RNAs and Exosomes as Biomarkers in Early Phases of Cardiac Damage.

Heart failure (HF) is one of the major causes of morbidity and mortality worldwide and represents an escalating problem for healthcare systems. The identification of asymptomatic patients with underlying cardiac subclinical disease would create an opportunity for early intervention and prevention of symptomatic HF. Traditional biomarkers are very useful as diagnostic and prognostic tools in the cardiovascular field; however, their application is usually limited to overt cardiac disease. On the other hand, a growing number of studies is investigating the diagnostic and prognostic potential of new biomarkers, such as micro-RNAs (miRNA), long non-coding RNAs, and exosome cargo, because of their involvement in the early phases of cardiac dysfunction. Unfortunately, their use in asymptomatic phases remains a distant goal. The aim of this review is to gather the current knowledge of old and novel biomarkers in the early diagnosis of cardiac dysfunction in asymptomatic individuals.

Electroanatomic voltage mapping for tissue characterization beyond arrhythmia definition: A systematic review.

Three-dimensional (3D) reconstruction by means of electroanatomic mapping (EAM) systems, allows for the understanding of the mechanism of focal or re-entrant arrhythmic circuits, which can be identified by means of dynamic (activation and propagation) and static (voltage) color-coded maps. However, besides this conventional use, EAM may offer helpful anatomical and functional information for tissue characterisation in several clinical settings. Today, data regarding electromechanical myocardial viability, scar detection in ischaemic and nonischaemic cardiomyopathy and arrhythmogenic right ventricle dysplasia (ARVC/D) definition are mostly consolidated, while emerging results are becoming available in contexts such as Brugada syndrome and cardiac resynchronisation therapy (CRT) implant procedures. As part of an invasive procedure, EAM has not yet been widely adopted as a stand-alone tool in the diagnostic path. We aim to review the data in the current literature regarding the use of 3D EAM systems beyond the definition of arrhythmia.

Myocarditis: Which Role for Genetics?

PURPOSE OF REVIEW: Myocarditis is a polymorphic disease, both in its presentation and clinical course. Recent data suggests that the genetic background, interacting with environmental factors, could be diriment both in the susceptibility and evolution of myocarditis in different clinical presentations. The aim of this paper is to expose the current available evidences and the evolving concepts on this topic, in order to provide insight for improving the clinical management of those patients. In this regard, the main goal is an optimal characterization of each patient's risk, with the purpose of individualizing the treatment and the follow-up. RECENT FINDINGS: The latest research highlights the possible prognostic role of some pathogenic mutations that could create a vulnerable myocardium prone to myocardial inflammation and also to the development of a long-lasting cardiomyopathy. The identification of these genetic defects and of myocarditis patients requiring genetic testing is emerging as a challenge for the future. In fact, identifying a possible genetic background responsible for a particularly high-risk profile could be of extreme importance in improving management of myocarditis. This and many other aspects in the genetics of myocarditis remain uncovered, and further studies are expected based to refine our daily clinical practice.

Left ventricle pacing challenges in cardiac resynchronization therapy systems.

Left ventricle (LV) pacing can be considered peculiar due to its different lead/tissue interface (epicardial pacing) and the small vein wedging lead locations with less reliable lead stability. The current technologies available for LV capture automatic confirmation adopt the evoked response (ER), as well as "LV pace to right ventricular (RV) sense" algorithms. The occurrence of anodal RV capture is today completely solved by the use of bipolar LV leads, while intriguing data are recently published regarding the unintentional LV anodal capture beside the cathodal one, which may enlarge the front wave of cardiac resynchronization therapy (CRT) delivery. The LV threshold behavior over time leading to ineffective CRT issues (subthreshold stimulation or concealed loss of capture), the extracardiac capture with phrenic nerve stimulation (PNS), the flexible electronic cathode reprogramming and the inadequate CRT delivery related to inadequate AV and VV pace timing (and its management by LV "dromotropic pace-conditioning") are discussed. Moreover, recently, His bundle pacing (HBP) and left bundle branch pacing (LBBP) have shown growing interest to prevent pacing-induced cardiomyopathy as well as for direct intentional CRT. The purpose of the present review is to explore these new challenges regarding LV pacing starting from old concepts.