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Cardiovascular disease is the leading cause of death worldwide. The role of cardiac markers in the diagnosis, risk stratification, and treatment of patients with chest pain is vital. Patients with elevated cardiac troponin levels but negative CK-MB who were formerly diagnosed with unstable angina or minor myocardial injury are now reclassified as non–ST-segment elevation MI (NSTEMI) even in the absence of diagnostic ECG changes. CK-MB is both a sensitive and specific marker for myocardial infarction. Cardiac troponin T is a cardio-specific, highly sensitive marker for myocardial damage. Cardiac troponin I is a contractile protein exclusively present in the cardiac muscle. The absolute cardiospecificity of cTnI allows the diagnosis of myocardial infarction distinct from muscle lesions and non-cardiac surgery. In 2000, the European Society of Cardiology and the American College of Cardiology redefined AMI with a particular advocacy on troponin. The 2002/2007 American College of Cardiology (ACC) and the American Heart Association (AHA) Guideline Update for the management of these patients strongly recommend to include cTnI. Specifically, with rare exception, the diagnosis cannot be made in the absence of elevated biomarkers of cardiac injury.

Myocardial infarction (MI) is a clinical condition that develops associated with a sudden reduction or interruption of the blood flow of the vessels supplying the heart for various reasons. The electrocardiographic, echocardiographic and enzymatic diagnostic criteria of MI have been well defined in adults, in children there are some difficulties. Although seen more often in the presence of congenital heart disease (CHD), MI may also be seen in patients without CHD. Unlike atherosclerotic coronary artery disease in adult patients, ischaemia and infarct in children are often associated with coronary artery anomalies and CHD. In addition, congenital prothrombotic diseases, vasculitis, surgical or interventional procedures may also cause ischaemia and infarct. Subendocardial ischaemia, especially aortic stenosis characterised by hypertrophy in the left ventricle is often seen in hypertrophic cardiomyopathy or hypertensive patients. The most important risk factors in neonates and infants are the presence of CHD, coronary artery anomalies and perinatal asfixia. The most frequently seen causes of pediatric myocardial infarction (PMI) are abnormal left coronary artery originating from the pulmonary artery (ALCAPA) and Kawasaki disease. Another often seen cause of PMI is patients who underwent arterial switch operations.

Acute myocardial infarction and coronary artery disease (CAD) are the most common causes for the development of malignant arrhythmia often leading to cardiogenic shock and cardiac arrest. Structural heart disease represents the main pathology in older patients, whereas young adults mostly suffer from cardiomyopathies and channelopathies. This book chapter delineates modern interventional therapies for patients with cardiogenic shock or aborted cardiac arrest. Epidemiological data on the incidence of malignant arrhythmia depending causing cardiac arrest depending on the presence or absence of CAD and myocardial infarction are presented. Realistic difficulties within clinical decision-making are counterbalanced for and against an early, aggressive and invasive therapeutic approach including early coronary angiography with percutaneous coronary intervention (PCI), targeted temperature management and mechanical cardiac assist devices, depending on the individual clinical presentation and underlying cardiac arrhythmia.

Cardiovascular disease is expected to be the main cause of death globally due to the rapidly increasing prevalence of obesity, hypertension and diabetes mellitus. Atherosclerotic lesions and plaque rupture are the most common cause of myocardial infarction. Resting 12-lead ECG is the first diagnostic test for patients with chest pain and should be performed and interpreted within the first 10 min of the patient’s admission to the emergency department. Cardiac biomarkers preferably, high-sensitivity cardiac troponin, is mandatory in all patients with suspected NSTEMI for the diagnosis, risk stratification and treatment. Rapid, efficient diagnosis and risk stratification of patients with chest pain will help to administer the appropriate medication and plan for the timing of invasive strategy and the choice of revascularization. This chapter helps to simply but elaborately discuss the diagnosis, risk stratification and the management of patients with non-ST elevation of myocardial infarction.

Atrial flutter (AFL) is a regular, macro reentrant arrhythmia traditionally defined as a supraventricular tachycardia with an atrial rate of 240–320 beats per minute (bpm). Pathophysiology of atrial flutter and atrial fibrillation (AF) is closely related to the similar risk of stroke and they coexist clinically. Atrial flutter is classified to cavotricuspid isthmus (CTI) dependent (or typical) and non-isthmus dependent (atypical). Isthmus is a distinct structure in the right atrium (RA) through which atrial flutter passes and makes a good target for ablation therapy. Ablation is the primary therapy in atrial flutter, particularly in CTI dependent group, with regard to its safety profile and high success rate of approximately 90%. Three-dimensional electroanatomic mapping is progressively being used to ablate atypical forms of atrial flutter.

Heart transplant remains the gold standard treatment for end-stage heart failure, in spite of the recent advances in pharmacological treatment and device therapy. As expected, since the first heart transplant was performed 50 years ago, outcomes in heart transplant have continued to improve over the last decades focusing on perioperative management, the availability of newer and better mechanical circulatory support before and after heart transplant and immunosuppressive drug development. Nonetheless, in the last years we have witnessed a significant drop in the heart donor’s pool as the greatest limiting factor, coupled with a rising number of advanced heart failure patients. Moreover, the difficulty in handling these patients, with multiple and more complex comorbidities, is continuously increasing. More importantly and despite these difficulties, conditional half-life in transplanted patients has nowadays reached 12 years of life expectancy. Thus, besides trying to increase donor numbers, candidate selection emerges as one of the most challenging issues for heart transplant programs. In this chapter we review the latest knowledge on indications for heart transplant, as well as the available screening and optimization tools in candidate selection in order to continue improving outcomes.

Peripheral neuropathic pain presents one of the greatest on going challenges to both acute and chronic pain management yet our understanding of the origins and pathogenesis of this complex disease state are severely lacking. The purpose of this chapter is to review the current literature regarding neuropathic pain as impacted by hemodynamic alterations. Because of the varied origins of neuropathy, this cannot be discussed as a single entity but we can seek to identify a final common pathway. We will for this reason examine each known pathogenetic category of neuropathy separately then discuss the effect of hemodynamic alterations through changes in blood pressure to determine any correlations between these alterations and specific effects upon neural structure and function. We have divided this chapter into sections which describe the more commonly known and encountered neuropathies. These are diabetes mellitus, neurotoxic medications, alcohol-related neuropathy, Vitamin B12 deficiency, end-stage renal disease, inflammatory bowel disease, and rheumatoid arthritis.

Drug-induced cardiotoxicity is a major adverse effect that has been encountered for some clinically important drugs especially antineoplastic agents. This toxicity has previously led to the post-marketing withdrawal of numerous pharmacologically active drugs and limits the efficacy of other clinically useful ones. Currently, assessing the cardiotoxicity potential is a crucial parameter in drug development, and many models have been established to facilitate its prediction to avoid such toxicity. In this chapter, we will briefly discuss the mechanism of drug-induced cardiotoxicity, risk factors, how to prevent, early detection and/or management from a pharmacological and toxicological point of view.

Arrhythmogenic right ventricular dysplasia (ARVD), first recognized in 1977, is an inherited cardiomyopathy mostly due to mutations in both desmosomal and non-desmosomal genes. ARVD is considered as a leading cause of sudden cardiac death in the young and the athlete. It is characterized by an abnormality in the development of the right ventricular (RV) musculature. The final diagnosis of ARVD was pathologically based on the findings characterized by fibro-fatty infiltration and cardiomyocyte loss predominantly affecting the RV. Epsilon waves are a feature of ARVD reflecting postexcitation of the myocytes in the RV that are interspersed between fibrous and fatty tissue. Epsilon waves are considered to be one of the major diagnostic criteria of ARVD and appear to correlate with the extent of ARVD and arrhythmic risk. In this review, we will briefly review the discovery of ARVD and Epsilon waves, discuss the electrogenesis and various methods for recording Epsilon waves, provide evidence to assist in understanding the pathological and functional changes of the heart in ARVD, thus promoting the management of this disease in patients and family members.

Because oxidative stress after administration of doxorubicin was identified as playing a central role in cardiac dysfunction, we hypothesized that the expression (or overexpression) of TLR2 and TLR4 contributes to the pathogenesis of doxorubicin-induced cardiac dysfunction. Toll-like receptors (TLRs) are members of the interleukin-1 receptor family (IL1) and are involved in the ability to react to the molecular trigger associated with pathogenic microorganisms. Recent studies have shown that TLR receptors are activated by endogenous signals, such as heat shock proteins and oxidative stress, which can contribute to congestive heart failure. Until recently, the best detection method for cardiotoxicity induced by anthracyclines was myocardial biopsy. Other early screening and early diagnosis methods (biomarkers—cardiac troponins and natriuretic peptide) have not yet proven their efficacy. Our proposed method is a new, revolutionary one that does not imply any kind of physical (and psychic) aggression on the patient: the targeted genetic (TLR2/TLR4) analysis of the human peripheral blood (which is a minimally invasive procedure).

Fueled by the uncertainty and the time required to obtain a donor heart, mechanical circulatory support (MCS) forms an essential part of end-stage heart failure. Extracorporeal membrane oxygenation (ECMO) use is limited to a few days before serious complications like bleeding occur. Prolonged support in terms of ventricular assist device (VAD) as a bridge to transplantation (BTT) became mandatory to overcome death on the waiting list. Within the last decade, VADs in adults have evolved drastically with the introduction of continuous flow (cf) devices. Increased miniaturization of VADs and new support strategies have increased its use in the pediatric population even in small children and patients with congenital heart disease (CHD). Nevertheless, patient and device selection in this patient population remain challenging to achieve optimal outcome and decrease complication rates. This comes with the need for care providers specialized in this field. Size issues and anatomical diversity make decision making complex and unique when compared to general adult practice. Neonates with single ventricle physiology are the highest risk candidates for VADs. This chapter reviews the most relevant durable VADs used in children including the rapid evolution of using adult designed cf-VADs to support children with anatomical normal hearts and CHD.

Human immunodeficiency virus type 1 (HIV-1) promotes a generalized immune activation that alters the physiology of cells that are not sensitive to viral infection. Endothelial cells (ECs) display heavy dysfunctions in HIV-1-seropositive (HIV+) patients that persist even in patients under successful combined antiretroviral therapy (cART). In vivo studies failed to demonstrate the presence of replicating virus in ECs suggesting that a direct role of the virus in vascular dysfunction is unlikely. This finding paves the way to the hypothesis of a key role of molecules released in the microenvironment by HIV-1-infected cells in sustaining aberrant EC function. Here we review the current understanding regarding the contribution of HIV-1 infection to vascular dysfunction. In particular, we argue that different HIV-1 proteins may play a key role in driving and sustaining inflammation and EC dysregulation, thus underlining the need to target them for therapeutic benefit.

HOX genes belong to a family of transcription factors characterized by a 183 bp DNA sequence called homeobox, which code for a 61-amino-acid domain defined as the homeodomain. These genes play a central role during embryonic development by controlling body organization, organogenesis, and stem cell differentiation. They can also play a role in adult processes such as embryo implantation, hematopoiesis, and endothelial differentiation. Since endothelial cell differentiation is one of the main steps to initiate vasculogenesis and angiogenesis, we analyzed the role of several Hox genes in the regulation of these two processes. In this chapter, we summarized the evidence to support the function of Hox genes in adult tissues, specifically in endothelial cell differentiation, by studying their mechanism of action and how their target genes regulate vasculogenesis and angiogenesis. Understanding the cellular and molecular mechanisms triggered by Hox biological effects is pivotal for designing new drugs or therapies for high prevalent pathologies, such as cardiovascular diseases.

The treatment of patients with intravenous drug use (IVDU) has evolved to include a wide range of medications, psychiatric rehabilitation, and surgical interventions, especially for life-threatening complications such as infective endocarditis (IE). These interventions remain at the discretion of physicians, particularly surgeons, whose treatment decisions are influenced by several medical factors, unfortunately not without bias. The stigma associated with substance use disorder is prevalent, which leads to significant biases, even in the healthcare system. This bias is heightened when IVDU patients require repeat valve replacement surgeries for IE due to continued drug use. Patients who receive a valve replacement and continue to use illicit drugs intravenously often return to their medical providers, months to a few years later, with a reinfection of their bioprosthetic valve; such patients require additional surgeries which are at the center of many ethical discussions due to high mortality rates, for many complex medical and social reasons, associated with continuous chemical dependency after surgical interventions. This chapter examines the ethics of repeat heart valve replacement surgery for patients who are struggling with addiction. Considerations of justice, the fiduciary therapeutic relationship, and guiding ethical principles justify medically beneficial repeat heart valve replacement surgeries for IVDU patient populations.

The plasticity of adipose tissue (AT) is related to its angiogenic ability. Angiogenesis is a multistep process which involves endothelial cell (EC) proliferation, migration, invasion and finally tube formation. AT as a secretory organ produces adipokines, which contributes to the development of subclinical inflammation. The inflammation-related adipokines deteriorate EC function and in consequence change the production of endothelial mediators responsible for vascular homeostasis and angiogenesis, leading to cardiovascular diseases (CVD) in obese patients. Additionally, the recent observation suggests that AT is poorly oxygenated in obesity. Hypoxia limits the healthy expansion of AT and stimulates a molecular response, enhancing nuclear factor kappa-B (NF-kB) and hypoxia-inducible factor (HIF-1) expression. HIF-1α induction does not start a normal angiogenic process but rather induces inflammatory response and fibrosis that is strongly associated with insulin resistance (IR). It is believed that EC dysfunction in obesity can be reduced by caloric restriction (CR). Moderate CR reflects a real-life situation and could be optimal to achieve an EC improvement. It reduces adiposity leading to pro-angiogenic, anti-inflammatory and—to a lesser extent—anti-oxidative cellular effects, which not only preserves the healthy EC phenotype but also leads to an improvement of AT remodeling and prevent systemic IR.

Hypertrophic cardiomyopathy (HCM) is defined as left ventricular hypertrophy in the absence of abnormal loading conditions. In 50–60% of adolescents and adults with HCM, the disease is inherited as an autosomal dominant trait caused by mutations in cardiac sarcomere protein genes. The most cases are due to mutations in genes which determine the synthesis of myosin-binding protein C (MYBPC3) and beta-myosin heavy chain (MYH7). More rarely involved genes are those encoding myosin light chain 3 (MYL3), tropomyosin alpha-1 chain (TPM1), and cardiac troponins I and T (TNNI3, TNNT2). Mutations in genes encoding Z-disc or calcium-handling proteins account for less than 1% of cases. Multiple sarcomeric protein mutations are present in up to 5% of individuals. A further of 5% of patients have inherited metabolic or neuromuscular diseases, chromosome abnormalities, and genetic syndromes. HCM is characterized by a highly heterogeneous phenotype, highly variable intra- and interfamily expressivity and incomplete penetrance, therefore by a genotype-phenotype plasticity.

Assessment of the role and investigation particularities (comparative and complementary aspects, hierarchies, preferential indication) adapted to the context of a global cardiovascular (CV) evaluation, including clinical elements, non-invasive and invasive imagistic examination in order to estimate the cardiovascular risk (CVR) and to define the revascularization therapeutic strategy in patients with critical leg ischemia (CLI). Complete and accessible evaluation involves accessible means of investigation like clinical exam, electrocardiogram, cardiac biomarkers, arterial, cardiac, and carotid ultrasonography which could be affordable in all cardiovascular departments. Non-invasive stress tests, coronary and arterial cervical angiography imaging leads in selected cases and where is possible to the identification of significant coronary and/or carotid lesions potential responsible for cardiac and cerebrovascular events after vascular surgery. The evaluation algorithm allows better risk stratification of patients with CLI in high and intermediate CVR. The “poly-arterial” status in patients with CLI changes the intervention management with a more intensive pre-operative medical treatment, while the coronary and the carotid arteries revascularization might precedes the peripheral arterial revascularization procedures, in order to reduce the CV risk status.

Aortic root pathology is diverse, and it is the most common cause of aortic valve incompetence in the United States. Aortic root surgery is undergoing continuous development and refinements. From the original description of Bentall on aortic root replacement, many advances have been made in the field of aortic root surgery. The surgical armamentarium available today provides advanced repair options as well as replacement options for the aortic root. The aim of this chapter is to provide an insight into the basics of aortic root surgery as well as to further describes the current up-to-date solutions for aortic valve and aortic root pathologies.

Atherosclerosis is a vascular disorder consisting of thickening of arteries and lack of elasticity. Result of atherosclerosis is that arteries become narrowed and hardened due to an excessive buildup of plaque around the artery wall. The disease disrupts the flow of blood around the body, posing serious cardiovascular complications. Arteries contain what is called an endothelium, a thin layer of cells that keeps the artery smooth and allows blood to flow easily. Endothelial damage starts the first step of atherosclerosis. After this, low-density lipoprotein (LDL) cholesterol accumulates in the artery wall. Inflammatory process starts after this accumulation, and macrophages reach the endothelium to clean up cholesterol. But some macrophages are stuck in the affected part of the artery wall in this process. Over time, this results in plaque being built up, consisting of cholesterol and macrophage white blood cells. The plaque clogs up the artery, disrupting the flow of blood. This potentially causes blood clots that can result in life-threatening conditions such as heart attack and other cardiovascular diseases. Atherosclerosis can be seen in all arteries in the body. Atherosclerosis is the most common cause of death in the western countries. Some risk factors are as follows: age, sex, familial predisposition, hyperlipidemia, hypertension, diabetes mellitus, smoking, obesity, insufficient physical activity, etc. Whatever the main reason or the risk factor is, once atherosclerosis is formed, several life-threatening cardiovascular disorders can be seen. So, it has to be revealed.

Anthracyclines have a severe adverse effect in cardiac function. Same here, trastuzumab has cardiotoxicity even in single use and also should lead to exacerbation of anthracycline-induced cardiotoxicity. Concurrent administration of anthracycline and trastuzumab is dangerous, but sequential administration is also dangerous. We should carefully design trastuzumab-containing regimens based on anthracycline dosing, regardless of whether it is concurrent or sequential. Contraindication of concurrent use of anthracyclines and trastuzumab has distracted us from its potential efficacy as well as from the inherent danger of anthracyclines together with trastuzumab. Avoidance of concurrent dosing is insufficient. As anthracyclines and trastuzumab are essential agents for HER2-positive breast cancer, and so, we must continue to address this issue from both safety and efficacy aspects.

The main function of von Willebrand factor (vWF) is to initiate platelet adhesion upon vascular injury. The hallmark of acute and chronical inflammation is the widespread activation of endothelial cells which provokes excessive vWF secretion from the endothelial cell storage pool. The level of vWF in blood not only reflects the state of endothelial activation early on in the pathogenesis, but also predicts disease outcome. Elevation in the blood level of vWF occurs either by pathologic increase in the rate of basal vWF secretion or by increased evoked vWF release from dysfunctional/activated endothelial cells (ECs). The increase in plasma vWF is predictive of prothrombotic complications and multi-organ system failure associated with reduced survival in the context of severe inflammatory response syndrome, type II diabetes mellitus, stroke and other inflammatory cardiovascular disease states. This chapter focuses on the role of high circulating vWF levels in thrombotic and inflammatory disease while paying attention to the emerging vWF-related drug development strategies.

Patient management in heart transplant is quite complex and includes multiple steps from preoperative recipient evaluation to postoperative ICU treatment. Monitoring, anesthesia induction, and cardiopulmonary bypass weaning strategies are discussed. The success of the operation also depends on right heart support especially in case of pulmonary hypertension. Many details like fluid management, well-timed respiratory weaning, and primary graft dysfunction management can make the difference in terms of outcome. Pediatric heart transplants represent a small group of total cardiac transplant, but the differences in anatomy and physiology make the surgical and anesthesiological management more complex in unique scenario that requires a specific knowledge at different stages of growth, from newborn through childhood up to adulthood.

Left ventricular assist device (LVAD) infections are important causes of morbidity and mortality in patients who receive these mechanical circulatory supports as a bridge to transplantation (BTT) or as destination therapy (DT) (for individuals who are not candidates for cardiac transplant). Infections are more common among persons who received pulsatile flow LVADs as opposed to newer continuous flow (CF) devices. Other risk factors for infection include obesity, renal failure, depression and immunosuppression. An LVAD infection increases the risk of infections in persons who undergo cardiac transplantation. Infections include percutaneous site, driveline, pump pocket and pump/cannula infections; sepsis, bacteremia, mediastinitis and endocarditis. Diagnosis is achieved by monitoring LVAD flow parameters and observing typical clinical and laboratory manifestations of infection. Imaging such as PET-CT or SPECT-CT imaging can be helpful to establish a diagnosis of pump pocket infection. Echocardiography may aid in detecting native valve endocarditis and thrombus associated with the LVAD. The most common pathogens include Staphylococcus, Corynebacterium, Enterococcus, Pseudomonas and Candida spp. Treatment requires targeted antimicrobials plus surgical debridement of infected tissue and device components. In cases of pump/cannula/LVAD endocarditis, especially if fungal pathogens or Mycobacterium chimaera are involved, LVAD removal/reimplantation vs. transplant is necessary, combined with extended antimicrobial therapy.

Introductory Chapter: Superficial Femoral Arterial Disease

Introductory Chapter: Dedicated Initial Giants Breaking the Barriers to Successful Cardiac Transplantation Therapy

The manuscript will discuss the epidemiology and etiology of the adult with coarctation of the aorta (CoA) as well as describe the embryology, anatomy, pathophysiology, and clinical presentation in order to recognize and appropriately diagnose an adult patient with CoA. This chapter will also review diagnostic testing, management, therapeutic interventions including percutaneous and surgical procedures, and long-term complications that can arise in an adult with repaired CoA. It contains images with examples from echocardiography, cardiac computed tomography (CT), magnetic resonance imaging (MRI), and angiograms as part of the description.

Bicuspid aortic valve (BAV) is one of the most common congenital diseases, affecting 1–2% of the general population. Although most of them are sporadic, some familial cases have also been detected. BAV is a complex developmental and progressive pathology, which may present with various clinical findings from newborn to adulthood. It may be suspected during cardiac auscultation or may be diagnosed by echocardiography incidentally. Some BAV cases may remain symptomless for years, with findings like valvular stenosis, insufficiency, or dilatation in the ascending aorta, whereas some others may present with early severe aortic valve dysfunction, premature congestive heart failure, and aortic aneurysms even in the newborn period. Such heterogeneous presentations of BAV phenotypes may be associated with congenital, genetic, and/or connective tissue abnormalities. The natural course of BAV is nonpredictable, it may lead to severe morbidity and mortality.

Cardiac re-transplantation (ReTx) accounts for a small proportion of the patients undergoing heart transplantation every year. However, due to improved patient management following transplant, the number of patients potentially requiring re-transplant is growing. We will review the current epidemiology of ReTx and describe the potential increase in candidates for ReTx. We will also highlight important characteristics of patients undergoing ReTx including co-morbidities and allosensitization. We will summarize single-center and registry data on patient outcomes following ReTx, and discuss patient selection. Finally, we will outline the management of patients following cardiac ReTx as well as alternate therapies and ethical considerations in cardiac ReTx.

Exposed to the blood milieu and variable hemodynamic forces, endothelial cells of different vessels exhibit significant heterogeneity, directing also the variety of endothelial functions. Endothelial cells are actively involved in many physiological processes, including vascular tone regulation, fluid filtration and reabsorption processes, maintenance of blood fluidity and proper hemostasis, leucocyte trafficking, tissue repair, and angiogenesis; accordingly, healthy endothelium is crucial for vascular homeostasis. On the other hand, many exo- and endogenous harmful factors can cause endothelial dysfunction, associated with inflammation, thrombosis, pathological vascular wall remodeling, and predisposing to the development of cardiovascular and other diseases. In order to design accurate clinical and pharmacological strategies to postpone or ameliorate endothelial dysfunction, endothelial dysfunction should firstly be recognized. Therefore, understanding endothelial physiology is crucial for clinical measures to be timely taken. The review briefly outlines some basic concepts of endothelial structure and function, focusing on endothelial barrier function and endothelium-dependent vasodilation, and addressing some potential therapeutic targets. Additional specific concepts of endothelial (dys)function, with particular emphasis on its involvement in inflammation, hemostasis, and its (mal)adaptation to environmental challenges are extensively described in the following book chapters.

Radiofrequency ablation (RFA) in Brugada syndrome (BrS) has been performed by both endocardial and epicardial. The substrate in BrS is not completely understood. We investigate the functional endocardial substrate and its correlation with clinical, electrophysiological and ECG findings in order to guide an endocardial ablation. Two patients agreed to undergo an endocardial biopsy and the samples were examined with transmission electron microscopy (TEM) to investigate the correlation between functional and ultrastructural alterations. About 13 patients (38.7 ± 12.3 years old) with spontaneous type 1 ECG BrS pattern, inducible VF with programmed ventricular stimulation (PVS) and syncope without prodromes were enrolled. Before endocardial mapping, the patients underwent flecainide testing with the purpose of measuring the greatest ST-segment elevation for to be correlated with the size and location of substrate in the electro-anatomic map. Patients underwent endocardial bipolar and electro-anatomic mapping with the purpose of identify areas of abnormal electrograms (EGMs) as target for RFA and determine the location and size of the substrate. When the greatest ST-segment elevation was in the third intercostal space (ICS), the substrate was located upper in the longitudinal plane of the right ventricular outflow tract (RVOT) and a greatest ST-segment elevation in fourth ICS correspond with a location of substrate in lower region of longitudinal plane of RVOT. A QRS complex widening on its initial and final part, with prolonged transmural and regional depolarization time of RVOT corresponded to the substrate located in the anterior-lateral region of RVOT. A QRS complex widening rightwards and only prolonged transmural depolarization time corresponded with a substrate located in the anterior, anterior-septal or septal region of RVOT. RFA of endocardial substrate suppressed the inducibility and ECG BrS pattern during 34.7 ± 15.5 months. After RFA, flecainide testing confirmed elimination of the ECG BrS pattern. Endocardial biopsy showed a correlation between functional and ultrastructural alterations. Endocardial RFA can eliminate the BrS phenotype and inducibility during programmed ventricular stimulation (PVS).

Aging is the main risk factor for cardiovascular diseases (CVD), and senescence in endothelial cells seems to be an initial step in the cascade of events that will culminate with the development of these pathologies. In this chapter, we examine the pathophysiological mechanism(s) involved in endothelial senescence, leading to CVD as well as the biochemical and cellular pathways that may explain the activation and development of the process of endothelial senescence, and we discuss new hypotheses supported by experimental results which suggest that the senescent endothelial cell may induce a general process of vascular senescence. This process is probably induced either by soluble molecules secreted by these senescent cells and/or by intercellular signals transported in cellular vesicles that may be useful as biomarkers and as potential therapeutic targets in endothelial senescence.

Interventional pediatric cardiology is a specialty of pediatric cardiology that deals specifically with the catheter-based treatment of congenital heart diseases. Cardiac catheterization involves the evaluation and manipulation of the heart and surrounding vessels through catheters place in peripheral vessels. In this chapter we begin by discussing the significant difference between adult and pediatric interventional cardiology. We will discuss basic hemodynamic measurements performed in cardiac catheterization and its application to congenital heart disease. Stent and balloon catheters are briefly discussed. Finally, specific catheter based interventional techniques, indications, and complications for various pediatric congenital heart disease is described.

Toxicomania is a worldwide emerging problem threatening young population. Several reports highlighted its hazardous cardiovascular effects. Sudden cardiac death secondary to cardiac arrhythmias is the most occupying issue. Different forms of cardiac rhythm disorders may be induced by illicit drug abuse according to the type of drug and the mechanism involved. In this review, we exposed the main ventricular and supraventricular arrhythmia complicating the common recreational drugs, and we explained their different mechanisms as well as the particularities of management.

Endocarditis caused by Abiotrophia and Granulicatella species, formerly known as nutritionally variant streptococci (NVS) is rare. It is associated with increased complications such as heart failure, systemic emboli, valve replacement surgery, treatment failures and mortality. The diagnosis of these infections is challenging due to specific nutritional growth requirements although modern techniques such as 16S rRNA sequence analysis and Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) are particularly useful. Penicillin resistance among these organisms is a growing problem. Penicillin and gentamicin combination or alternatively Vancomycin alone are the recommended treatment options, however there is increasing data regarding susceptibilities to other antibiotics. Varying susceptibilities to antibiotics among different species of NVS needs to be studied further.

Cocaine is a potent stimulant which affects cardiovascular system severely. The mechanism of cardiac toxicity depends on multiple factors. Cocaine increases sympathetic stimulation and causes excess catecholamine secretion. Besides, its indirect sympathomimetic effect also directly exerts cardiotoxic effect by different cellular, molecular, and ionic mechanisms, resulting in acute or chronic cardiovascular impairment. Cardiac arrhythmia and acute myocardial ischemia or infarction is the most common cause of cocaine-induced sudden cardiac death. Chronic cocaine abuse can develop sustained hypertension or myocarditis or cardiomyopathy leading to depressed left ventricular function. Therapy for cocaine induced cardiac toxicity generally includes use of benzodiazepine agents, nitric oxide mediated vasodilators, alpha blockers and even calcium channel blockers. Beta blockers are relatively contraindicated in acute settings of cocaine cardiovascular toxicity. Hypersensitivity reaction to cocaine is often manifested by infiltration of eosinophilic or mononuclear cells without myocardial cell damage. Vascular dissection, endocarditis, and tricuspid valvular abnormalities are some less frequent manifestations in cocaine-induced cardiac toxicity.

Mitochondrial diseases are multisystem disorders, resulting from mitochondrial electron transport chain dysfunction and oxidative phosphorylation due to pathogenic variants in mitochondrial or nuclear DNA. The clinical presentations are variable in the age of onset, symptoms, and range and severity of organ involvement. Diagnosis requires a multidisciplinary approach and is based on clinical symptoms, laboratory tests, histopathological findings, and genetic analysis. Due to the multi-organ involvement, the evaluation of mitochondrial diseases should include a systemic screening for all targeted organs, including neuroimaging, ophthalmology, and hearing examinations. Cardiac involvement should be evaluated at the time of diagnosis, as cardiac involvement is an independent predictor of morbidity and early mortality, even in asymptomatic cases. Hypertrophic cardiomyopathy is the most common cardiac manifestation; however, mitochondrial cardiomyopathy might also present as left ventricular non-compaction (LVNC) or as dilated, histiocytoid, or restrictive cardiomyopathy. The precise evaluation of cardiac involvement is of clinical use in predicting future cardiac events and prognosis. Despite advancements in molecular biology, no satisfactory treatments for mitochondrial diseases exist. Treatment remains largely symptomatic and does not significantly alter disease progression.

Cardiac transplantation (TxC) is considered the first therapeutic option in patients with congestive heart failure, refractory to clinical treatment and without the possibility of conventional surgical treatment. The pathophysiological status, as a consequence of severe cardiomyopathy, is represented by various degrees of systolic and diastolic dysfunction, reflecting low ejection volumes and high diastolic volumes and high filling diastolic pressures, respectively. Patients in this pathophysiological context also present, among other symptoms, neurohormonal alterations of the renin-angiotensin aldosterone system, decreased renal, visceral and splanchnic perfusion, and increased levels of catecholamines. Barnard et al., in 1967, performed the first orthotopic heart transplantation among humans with relative success, Zerbini (1969) being the first to perform it in Brazil. The presence of high rates of graft rejection and infection accounted for small survival and caused great disinterest and abandonment of the technique in the 70’s. However, the experience accumulated by the groups that maintained TxC as a treatment, mainly after the introduction of cyclosporin A, first in kidney transplantation in 1978, and in 1980 in TxC, reinvigorated this therapeutic option, allowing the true development and the application of this treatment worldwide.

Cigarette smoking is a known risk factor for arteriosclerosis. In atheromatous plaques, the accumulation of vascular smooth muscle cells (VSMCs) have a phenotype differing from that of their normal contractile type. Nicotine is a major pharmacological agent in cigarette smoke. However, any direct effect of nicotine on VSMCs remains uncertain. We investigated the changes in the expression levels of differentiation markers and activity of mitogen-activated protein kinases (MAPKs) after nicotine exposure for 48 h using human aorta primary smooth muscle cells (HVSMC) differentiated with transforming growth factor-β. The results indicated that HVSMC phenotype changed to a synthetic-like phenotype after nicotine exposure. Nicotine is a factor that can change the expression of differentiation marker proteins in VSMCs. Thus, we proposed that nicotine directly affects the migration of VSMCs from the tunica media to atheromatous plaques in the vascular intima by inducing the transformation from a contractile-type to a synthetic-like type, which occurs before the development of atheromatous plaques. Nicotine is contained in nicotine patches and gums for smoking cessation. There may also promote atheromatous plaque formation. We anticipate that determining this mechanism will lead to new means of preventing and treating plaque formation and development in arteriosclerosis.

Orthotopic heart transplant is recognized as the gold standard for the treatment of end-stage heart disease. However, there is a perennial shortage of donor organs. Left ventricular assist devices (LVAD) represent a revolutionary tool for temporizing heart failure that is refractory to medical management until a suitable organ becomes available. This review highlights the LVAD as a tool for bridging to transplant. The history of the LVAD and its use in heart transplantation is described, as well as the current indications for use in the general heart transplant candidate as well as for selected subpopulations. It also highlights the major complications of LVAD use, advancements in the field, and selected current controversies related to the LVAD as bridge-to-transplant therapy.

The role of advanced glycation end products (AGEs) in cardiovascular diseases is a matter of interest in the last years and the strong association between the action of AGEs on their receptor (RAGE) and atherosclerosis has attracted increased attention. The aim of this chapter is to review the results of our laboratory and others on the molecular mechanisms triggered by AGEs in the endothelium that could participate in the atherosclerotic process. These mechanisms and molecular pathways could be the source of new therapeutic targets against atherosclerosis or vascular disease. Oxidative stress in endothelium induced by AGEs triggers molecular signaling pathways that produce an inflammatory response or even endothelial dysfunction. Adhesion molecules expression at the membranes of endothelial cells as a consequence of this response or induced by other mechanisms involving AGEs mediates the adhesion of leukocytes to endothelium. This adhesion is a key step in the atherogenesis process and the possible involvement of AGE-RAGE axis in this process should be considered as a potential therapeutic target. Finally, potential pharmacological modulation of AGE-RAGE axis activity at the endothelium is suggested, but the specific pharmacological tools available nowadays are missing; respectively, drugs used for the treatment of cardiovascular and metabolic diseases could be helpful for AGE-RAGE axis modulation, thus also affecting endothelial (dys)function.

Ischemic cardiomyopathy, disease of the heart muscle due to coronary artery disease, is the most common cardiomyopathy. It is often difficult to discern the etiology of heart failure, and often there are multiple underlying causes. Ischemic cardiomyopathy most often presents with a dilated morphology with wall motion defects and a history of previous myocardial infarction or confirmed coronary artery disease. Mechanisms of myocardial depression in ischemia are necrosis of myocardial cells resulting in irreversible loss of function or reversible damage, either short term through myocardial stunning or long term through hibernation. In ischemic cardiomyopathy, echocardiography may be extended with stress testing or other imaging modalities such as myocardial scintigraphy and cardiac magnetic resonance tomography. Coronary angiography is often considered a gold standard; however, other modalities such as positron emission tomography can be needed to detect small vessel disease. Cardiac revascularization, through percutaneous coronary intervention and coronary artery bypass grafting, both in acute coronary syndrome and in stable coronary artery disease, relieves symptoms and improves prognosis. Therapy should aspire to treat ischemia, arrhythmias in addition to heart failure management, which includes device therapy with cardiac resynchronization therapy, implantable cardioverter defibrillators, and mechanical support as bridging or destination therapy in end-stage disease.

Idiopathic ventricular arrhythmias (VAs) occur with a mechanism that is unrelated to myocardial scar. Idiopathic VAs most commonly occur in patients without structural heart disease, but can occur in those with structural heart disease. Idiopathic VAs present as a sustained or a non-sustained ventricular tachycardia or premature ventricular contractions. Imaging examinations such as echocardiography, nuclear tests, and cardiac magnetic resonance imaging are helpful for excluding any association of an idiopathic VA occurrence with myocardial scar. For the past two decades, the sites of idiopathic VA origins, commonly endocardial but sometimes epicardial, have been increasingly recognized. Idiopathic VAs usually originate from specific anatomical structures and exhibit characteristic electrocardiograms based on their anatomical background. Idiopathic VAs are basically benign, but they require medical treatment or catheter ablation when idiopathic VAs are symptomatic, frequent, or cause tachycardia-induced cardiomyopathy. This book chapter describes the up-to-date information on the prevalence of idiopathic VA origins relevant to the anatomy, diagnosis, and treatment of idiopathic VAs.

Atrial fibrillation (AF), which causes severe health problems, is a multi-factor disorder and is increasing day by day. AF is known to be one of the most common cardiac arrhythmias in clinical practice. AF can also be described as a cardiac dysrhythmia that causes severe cardiovascular morbidity and mortality. AF is known as an independent risk factor for death and it occurs a significant risk of morbidity due to stroke. There are many diseases that contribute to the development of AF. Diseases such as aging, heart failure, heart valve disorders, myocardial infarction, hypertension and diabetes mellitus are important factors in the development of structural AF. It is a known fact that AF prevalence increases with age. The mechanism underlying of AF is not fully understood, but genetic factors play an important role in the pathogenesis of this disease. There have been many studies aimed at investigating the genetic basis of AF, especially in recent years. In these studies, many mutations and variants have emerged which are identified as genetic risk factors in the development of AF. Identification of gene polymorphisms that play a role in the development of AF will be an important guide in the development of new therapies for the treatment of this condition.

Modified ultrafiltration is used in cardiac surgery with cardiopulmonary bypass in order to diminish systemic inflammatory response syndrome. We aimed to show its utility for removing pro-inflammatory agents in operated pediatric patients with congenital heart disease and its impact at operative care. A clinical case control trial was designed, including patients with simple congenital heart disease operated on with cardiopulmonary bypass in a 1-year period. We randomized them to a problematic group (with modified ultrafiltration, n = 15) and a control group (without it, n = 16), and blood samples to measure interleukins (6 and 10), 3d and 4d complement fraction concentrations were taken at the following times: baseline, before cardiopulmonary bypass, after it, after modified ultrafiltration, and from the ultrafiltration concentrate. Operative clinical end points of success were defined as hemodynamic stability, absence of morbidity, and lack of mortality. We observed a higher significant interleukin six concentration in the problematic group patients at baseline, as well as a higher removal of this pro-inflammatory agent at the ultrafiltration concentrate. Modified ultrafiltration has a positive impact over simple congenital heart disease surgery with cardiopulmonary bypass because of removing interleukin 6. We recommend its routinely use when hemodynamic conditions are favorable.

The prevalence of atrial fibrillation and the likelihood of undergoing concomitant surgical ablation at the time of open heart surgery are increasing. Currently, the conventional cut-and-sew Maze procedure has been predominantly replaced by Cox-Maze IV procedure, in which new energy sources such as radiofrequency energy and/or cryoablation are applied. Cox-Maze IV procedure has been associated with lower rate of complications than a cut-and-sew procedure. However, some previous studies reported the lower success rate of Cox-Maze IV procedure, possibly because radiofrequency ablation or cryoablation cannot always achieve transmurality. For the success of surgical ablation, achieving transmurality, defined as complete atrial wall thickness of fibrotic changes, is of paramount importance. A review of previous articles regarding histopathological changes of the atrial tissue following surgical ablation is performed. The effectiveness of new energy sources such as radiofrequency and cryoablation in terms of histological transmurality is discussed.