bluuebunny/crossref_metadata_2025 huggingface dataset:
ECG in syncope, palpitations, dyspnoea, and chest pain
Authors: Moya Angel , Barrabés Jose
Published: March 2018

This chapter reviews the role of the electrocardiogram in the diagnosis of patients with syncope, palpitations, dyspnoea, and chest pain.
Contrast echocardiography
Authors: Vamvakidou Anastasia , Senior Roxy
Published: March 2018

The major requirement for optimal echocardiographic image interpretation, reproducibility, and diagnostic accuracy is image quality. Despite the use of harmonics, a significant proportion of patients have challenging images, which has an impact on diagnosis and management. The ultrasound contrast agents (UCAs), which are administered intravenously, have been a significant development in image quality optimization and have proved to be an important aid in the assessment of structural abnormalities, detection of regional wall motion abnormalities, and calculation of left ventricular ejection fraction. The use of UCAs is also of critical importance for the detection of ischaemia and the assessment of significant coronary artery disease through detection of inducible regional wall motion abnormalities during stress echocardiography. UCAs can also assess myocardial perfusion, which improves assessment of myocardial ischaemia during stress echocardiography. Similarly the simultaneous assessment of wall motion and perfusion improves assessment of viable myocardium in patients with left ventricular dysfunction. As the use of UCAs results in increased feasibility, reproducibility, and diagnostic and prognostic accuracy of echocardiography including cost-efficiency, both European and American guidelines endorse its use in clinical cardiology.
Three-dimensional echocardiography
Authors: Faletra Francesco F. , Leo Laura A. , Moccetti Tiziano , Monaghan Mark J.
Published: March 2018

Three-dimensional echocardiography (3DE) certainly represents one of the major innovations of the last decades. Nowadays, 3DE has achieved a well-established role in many fields of cardiovascular diseases. This chapter discusses the contribution of 3DE towards a more precise quantitative assessment of cardiac chambers, in refining the diagnosis of structural heart diseases, and in guiding catheter-based structural heart disease procedures. The last section discusses the evolving role of a novel imaging system that specifically fuses fluoroscopy and two/three-dimensional echocardiography on one screen and represents a new exciting approach to image guidance for structural heart disease interventions.
Computed tomography for cardiac interventions
Authors: Marwan Mohamed , Achenbach Stephan
Published: March 2018

Pre-procedural imaging is essential for successful planning and performance of several cardiac interventions. For this purpose, contrast-enhanced computed tomography (CT) imaging—owing to its high and isotropic spatial resolution as well as fast volume coverage—is gaining increasing importance. Cardiac CT offers high-resolution morphological and functional imaging of cardiac structures which is valuable for a variety of structural heart disease interventions, electrophysiology procedures, and coronary interventions. Over the last decade, the widened spectrum of transcatheter cardiac interventions has been associated with widespread acknowledgment that CT is particularly useful for pre-interventional imaging and increasing implementation in clinical routine. In this chapter, the role of cardiac CT for the guidance of coronary as well as non-coronary cardiac interventions is described.
Psychological factors and incident heart disease
Authors: Pedersen Susanne
Published: March 2018

This is a forthcoming chapter in ESC CardioMed. Please check back later for the full chapter.
Psychological impact of heart disease
Authors: Doyle Frank
Published: March 2018

This is a forthcoming chapter in ESC CardioMed. Please check back later for the full chapter.
Genetic counselling
Authors: Ingles Jodie , Burns Charlotte , Yeates Laura
Published: March 2018

Cardiac genetic counselling is an emerging but important subspecialty. The qualifications of cardiac genetic counsellors depend on the country of practice, but at a minimum they are Master’s-level trained health professionals with expertise in genetics, and are integral members of the multidisciplinary inherited cardiovascular disease clinic. Though the framework is diverse in different countries, key roles include investigation and confirmation of family history details, discussion of inheritance risks and facilitation of cardiac genetic testing, communication with at-risk relatives, and increasingly, curation of genetic test results. The use of next-generation sequencing technologies has seen a recent shift in the uptake of genetic testing, due to greater availability and lowered costs. As these gene tests become more comprehensive, including large panels of genes and even whole exome or whole genome sequencing, the need for cardiac genetic counsellors to provide informed consent, appropriate pre- and post-test genetic counselling, and ongoing curation of the variants identified is evident. Finally, given the improved understanding of the psychological implications of living with a cardiovascular genetic disease, cardiac genetic counsellors are integral in delivering psychosocial care and identifying patients requiring intervention with a clinical psychologist.
Genetics of cardiomyopathies: arrhythmogenic right ventricular cardiomyopathy
Authors: Pilichou Kalliopi , Basso Cristina , Celeghin Rudy , Thiene Gaetano
Published: March 2018

Arrhythmogenic cardiomyopathy (AC) is characterized by progressive non-ischaemic cardiomyocyte death and fibro-fatty repair, triggering ventricular arrhythmias and sudden death. A familial background consistent with an autosomal dominant trait of inheritance is described in nearly half of AC patients, even if recessive variants have also been reported, either associated or not with palmoplantar keratosis and woolly hair. Advances in DNA sequencing have led to the identification of more than 350 pathogenic mutations in 15 disease-causing genes associated with AC. Nearly half of patients with AC harbour mutations in genes encoding desmosomal proteins (plakoglobin, JUP; desmoplakin, DSP; plakophillin-2, PKP2; desmoglein-2, DSG2; and desmocollin-2, DSC2) and less than 1% carry mutations in non-desmosomal genes (transforming growth factor beta-3, TGFB3; desmin, DES; alpha-T catenin, CTNNA3; phospholamban, PLN; lamin A/C, LMNA; titin, and TTN; ryanodine receptor-2, RYR2). The inheritance pattern of AC is more complex than previously appreciated, with frequent requirement of more than one mutation for fully penetrant disease. Compound/digenic heterozygosity was identified in up to 25% of AC-causing desmosomal gene mutation carriers, explaining in part the phenotypic variability. In the era of next-generation sequencing, parallel analysis of thousands of genes is feasible and many rare variants can be detected (nearly 1000 nucleotide variants of unknown significance have been linked to AC), so the challenge is to distinguish causative mutations from the genetic noise since genetic testing may be a precious tool in distinguishing AC patients at risk of disease onset and of sudden death.
Genetics of vascular disease: Marfan syndrome and aortic disease
Authors: Schepers Dorien , Loeys Bart
Published: March 2018

Marfan syndrome is an autosomal dominant, multisystemic disorder, presenting with skeletal, ocular, and cardiovascular symptoms. This connective tissue disease is caused by mutations in FBN1, encoding fibrillin-1, which is an important extracellular matrix protein. Marfan syndrome shows significant clinical overlap with Loeys–Dietz syndrome, which is caused by genetic defects in components of the transforming growth factor-beta pathway: TGFBR1, TGFBR2, TGFB2, TGFB3, SMAD2, and SMAD3. Overlapping clinical features between Marfan syndrome and Loeys–Dietz syndrome include aortic root aneurysm, arachnodactyly, scoliosis, and pectus deformity.
Atrial septal defect
Authors: Yates Robert , Gewillig Marc
Published: March 2018

Secundum atrial septal defects are usually well tolerated in childhood but may cause significant symptoms in adults. Early closure is therefore recommended and can be achieved by catheter in the majority. Symptomatic benefit is noted at any age, but long-term follow-up is required as closure in adulthood does not prevent atrial arrhythmias.
Mechanisms: psychological factors and outcomes
Authors: von Kaenel Roland , Albus Christian
Published: March 2018

This is a forthcoming chapter in ESC CardioMed. Please check back later for the full chapter.
Introduction
Authors: Rogler Gerhard
Published: March 2018

Gastrointestinal disease and heart disease seem to be two groups of diseases that do not have much in common. However, recent insights have changed this assumption: the intestine’s basic functions, digestion and absorption, are obviously clinically relevant for almost all oral drug treatments of diseases. An impairment of intestinal barrier function is followed by increased bacterial translocation across the intestinal mucosa leading to increased levels of circulating bacteria and bacterial products. This is assumed to be associated with atherosclerosis and chronic heart failure. Vice versa, an impaired cardiac function in the setting of chronic heart failure may lead to a defect in the mucosal barrier and increased bacterial translocation via changes in intestinal microcirculation. In addition, recent evidence indicates that conditions such as metabolic syndrome or obesity—certainly risk factors for heart disease—are influenced by intestinal microbiota composition.
Pathogenesis: from acute rheumatic fever to rheumatic heart disease
Authors: Lawrenson John
Published: March 2018

Rheumatic heart disease is considered to be an autoimmune disease; the trigger of the process is a streptococcal throat infection which then initiates both a humeral and a cellular immune response in environmentally and genetically susceptible individuals.
Pathophysiology of acute coronary syndromes
Authors: Liuzzo Giovanna , Pedicino Daniela , Crea Filippo
Published: March 2018

Although the early outcome of acute coronary syndromes (ACS) has considerably improved in the last decade, cardiovascular diseases still represent the main cause of morbidity and mortality worldwide. The progression of coronary atherosclerosis can remain clinically silent even for life. In contrast, some patients at a certain point exhibit an ACS, followed by a period of stability, which can be short or last for years or decades. These clinical observations suggest that the mechanisms responsible for plaque growth and for plaque instability are different and that the causes of ACS are multiple and incompletely understood. Inflammation plays a key role in the pathogenesis of ACS. An outburst of the inflammatory process within the atherosclerotic plaque may lead to plaque fissure with thrombosis resulting in myocardial ischaemia and necrosis that is an additional source for a local and systemic inflammatory response. Furthermore, percutaneous coronary intervention may cause iatrogenic myocardial injury, a further source of inflammation. However, this notion is in contrast with the observation that about 40% of patients with an ACS have low or very low levels of high-sensitivity C-reactive protein, a very sensitive marker of inflammation. Moreover, coronary angiography fails to demonstrate obstructive atherosclerosis in up to one-third of patients with symptoms and signs suggestive of an ACS, suggesting that functional alterations of epicardial arteries and/or of coronary microcirculation play an important pathogenetic role. Thus, a better comprehension of the mechanisms responsible for coronary instability might lead to innovative preventive and therapeutic strategies.
Diagnosis and risk stratification of acute coronary syndromes
Authors: Mueller Christian
Published: March 2018

Detailed clinical assessment including vital signs; physical examination; a thorough patient history including chest pain characteristics, the electrocardiogram, and high-sensitivity cardiac troponin; and cardiac imaging are the four pillars in the early diagnosis and risk stratification of patients presenting with a suspected myocardial infarction. High-sensitivity cardiac troponin assays for the first time allowed the precise quantification of cardiomyocyte injury around the 99th percentile and thereby substantially increased the accuracy of myocardial infarction detection from blood obtained at presentation to the emergency department. Higher accuracy at emergency department presentation enabled the development and extensive validation of early high-sensitivity cardiac troponin-based diagnostic algorithms, which substantially reduced the time required for the safe rule-out or rule-in of myocardial infarction. More rapid rule-out and rule-in of myocardial infarction provides substantial medical value to patients, physicians, and institutions.
Clinical presentation of takotsubo syndrome
Authors: Wittstein Ilan
Published: March 2018

Takotsubo syndrome (TTS), also known as stress cardiomyopathy, left ventricular apical ballooning syndrome, and broken heart syndrome, is a syndrome of acute heart failure and transient ventricular dysfunction that is frequently precipitated by acute emotional or physical stress. A wide variety of emotional and physical stressors have been associated with this syndrome, and while acute stress is temporally related to syndrome onset in the majority of patients, a subset of patients have no identifiable antecedent trigger at the time of presentation. The syndrome has a striking predilection for older postmenopausal women, though it has been reported in men and in younger patients as well. The incidence of TTS is higher than initially thought and accounts for up to 5–10% of women presenting with a suspected acute coronary syndrome. Several groups have proposed variable criteria for the diagnosis of TTS, but universally accepted criteria are currently lacking. While patients with TTS typically present with chest pain, dynamic electrocardiographic changes, and elevated cardiac biomarkers, characteristic features of the syndrome that help to distinguish it from an acute myocardial infarction include the absence of plaque rupture and coronary thrombosis, unique patterns of ventricular dysfunction that typically involve more than one vascular territory, and rapid and complete recovery of ventricular systolic function. While the prognosis associated with TTS is generally favourable, the condition is not benign and has been associated with serious complications such as cardiogenic shock, thromboembolic events, and life-threatening arrhythmias. This chapter will highlight the clinical features that characterize TTS and that are central to its diagnosis.
Pathology of stable coronary artery disease
Authors: Joner Michael , Castellanos Maria Isabel , Bulin Anna , Steigerwald Kristin
Published: March 2018

Coronary artery disease remains the major cause of morbidity and mortality on a global scale. Intimal thickening and fatty streaks represent early adaptive vascular changes, which are often regressive. Pathological intimal thickening represents the earliest progressive atherosclerotic lesion characterized by a focal accumulation of smooth muscle cells and acellular areas, often associated with lipid pools. Fibroatheroma is characterized by a necrotic core and can be split into early and late fibroatheroma, where macrophage apoptosis and defective efferocytosis play important roles in lesion progression. Intraplaque hypoxia is believed to result in neovascularization with subsequent intraplaque haemorrhage because of immature and leaky microvessels. Due to excessive cholesterol in remnants of erythrocyte membranes, intraplaque haemorrhage may result in rapid progression of necrotic core and plaque destabilization. Healed plaque rupture has been well delineated as an important mechanism of gradual luminal narrowing, where changes in collagen deposition allow recognition of rupture and healing sites. Calcification results from apoptosis of smooth muscle cells and macrophages or may also be caused by active release of cellular vesicles involved in calcium haemostasis. Extracellular matrix changes are associated with progression of atherosclerosis, while integrin signalling has been recognized as an important outside-in transcellular target of the inflammatory response.
Myocardial ischaemia: definition and causes
Authors: Crea Filippo , Lanza Gaetano Antonio
Published: March 2018

Myocardial ischaemia is caused by a mismatch between myocardial oxygen demand and myocardial blood flow supply, which results in myocardial suffering and, when prolonged, injury. The main mechanisms of myocardial ischaemia include atherothrombotic lesions of epicardial coronary vessels, which may result in chronic and acute ischaemic syndromes; coronary artery spasm, which is mainly responsible for variant angina; and abnormalities in coronary microvascular function, which can cause or contribute to myocardial ischaemia in various clinical settings.
Refractory angina
Authors: Azzano Alessia , Verheye Stefan
Published: March 2018

A growing number of patients who are no longer candidates for surgical or percutaneous coronary revascularization, continue to experience persistent and invalidating angina despite optimal medical therapy. Despite the advances in medical and invasive therapies for the treatment of ischaemic heart disease, the management of patients with refractory angina remains a clinical challenge. Since mortality in this patient population has decreased, the treatment of refractory angina should therefore be focused on improving quality of life. Myocardial ischaemia is traditionally treated with risk factor modification and antianginal medications, as well as percutaneous or surgical revascularization, increasing coronary blood flow, blood oxygen-carrying capacity, and decreasing oxygen consumption. Based on new therapeutic principles, such as metabolic modulation, oxygen sparing, and coronary flow redistribution, emerging treatment options have emerged. They include novel medical agents (ivabradine, nicorandil, ranolazine, or trimetazidine) and novel interventional techniques (percutaneous coronary intervention for chronic total occlusions, and the narrowing of the coronary sinus), therapeutic angiogenesis through gene or cell therapy, shockwave therapy, and neuromodulation. The contemporary management of refractory angina might be individualized, patient-centred, and arise from an interdisciplinary approach (including psychological and self-management approaches).
Chronic ischaemic cardiomyopathy
Authors: Heggermont Ward A. , Vanderheyden Marc , Bartunek Jozef
Published: March 2018

Ischaemic cardiomyopathy is the most common cause of chronic heart failure. It is associated with several diagnostic and therapeutic challenges. They include mainly the detection of viable and ischaemic tissue amenable to improvement after revascularization. Revascularization is useful in patients with a critical mass of viable ischaemic myocardium. Provided that full revascularization is possible, percutaneous coronary intervention might be a valid alternative to surgical revascularization. Contrast-enhanced cardiac magnetic resonance is an important emerging tool to adequately detect viable myocardium. Right ventricular function and functional mitral regurgitations are important prognostic factors in ischaemic cardiomyopathy. Next to reshaping surgery, dedicated devices to restore left ventricular geometry, and stem cell therapy, are under clinical investigation.
Microvascular angina
Authors: Camici Paolo G. , Rimoldi Ornella
Published: March 2018

Atherosclerotic disease of the epicardial coronary arteries has been accepted as the cause of angina pectoris for more than two hundred years while sudden, thrombotic occlusion of an epicardial coronary artery has been well established as the cause of myocardial infarction for more than one hundred years. However, the epicardial arteries, also known as conductance vessels, are only one segment of the arterial coronary circulation. These vessels give rise to smaller arteries and arterioles which in turn feed the capillaries and constitute the coronary microcirculation, the main site of regulation of myocardial blood flow. In the past two decades, a number of studies have demonstrated that abnormalities in the function and structure of the coronary microcirculation occur in many clinical conditions. In some instances these abnormalities represent epiphenomena, whereas in others they represent important markers of risk or may even contribute to the pathogenesis of myocardial ischaemia, thus becoming therapeutic targets.
Arrhythmogenic right ventricular cardiomyopathy: diagnosis
Authors: Bass Cristina , Bauce Barbara , Thiene Gaetano
Published: March 2018

Arrhythmogenic cardiomyopathy is a heart muscle disease clinically characterized by life-threatening ventricular arrhythmias and pathologically by an acquired and progressive dystrophy of the ventricular myocardium with fibrofatty replacement. The clinical manifestations of arrhythmogenic cardiomyopathy vary according to the ‘phenotypic’ stage of the underlying disease process. Since there is no ‘gold standard’ to reach the diagnosis of arrhythmogenic cardiomyopathy, multiple categories of diagnostic information have been combined. Different diagnostic categories include right ventricular morphofunctional abnormalities (by echocardiography and/or angiography and/or cardiovascular magnetic resonance imaging), histopathological features on endomyocardial biopsy, electrocardiogram, arrhythmias, and family history, including genetics. The diagnostic criteria were revised in 2010 to improve diagnostic sensitivity, but with the important prerequisite of maintaining diagnostic specificity. Quantitative parameters have been put forward and abnormalities are defined based on the comparison with normal subject data. A definite diagnosis of arrhythmogenic cardiomyopathy is achieved when two major, or one major and two minor, or four minor criteria from different categories are met. The main differential diagnoses are idiopathic right ventricular outflow tract tachycardia, myocarditis, sarcoidosis, dilated cardiomyopathy, right ventricular infarction, congenital heart diseases with right ventricular overload, and athlete’s heart. Among diagnostic tools, contrast-enhanced cardiovascular magnetic resonance is playing a major role in detecting subepicardial-midmural left ventricular free wall involvement, even preceding morphofunctional abnormalities. Moreover, electroanatomical mapping is an invasive tool able to detect early right ventricular free wall involvement in terms of low-voltage areas. Both techniques are increasingly used in the diagnostic work-up although are not yet part of diagnostic criteria.
Arrhythmogenic right ventricular cardiomyopathy: management of symptoms and prevention of sudden cardiac death
Authors: Elliott Perry , Protonotarios Alexandros
Published: March 2018

Patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) have arrhythmia-related symptoms or are identified during screening of an affected family. Heart failure symptoms occur late in the disease’s natural history. As strenuous exercise has been associated with disease acceleration and worsening of ventricular arrhythmias, lifestyle modification with restricted athletic activities is recommended upon disease diagnosis or even identification of mutation carrier status. An episode of an haemodynamically unstable, sustained ventricular tachycardia or ventricular fibrillation as well as severe systolic ventricular dysfunction constitute definitive indications for implantable cardioverter defibrillator (ICD) implantation, which should also be considered following tolerated sustained or non-sustained ventricular tachycardia episodes, syncope, or in the presence of moderate ventricular dysfunction. Antiarrhythmic medications are used as an adjunct to device therapy. Catheter ablation is recommended for incessant ventricular tachycardia or frequent appropriate ICD interventions despite maximal pharmacological therapy. Amiodarone alone or in combination with beta blockers is most effective for symptomatic ventricular arrhythmias. Beta blockers are considered for use in all patients with a definite diagnosis but evidence for their prognostic benefit is sparse. Heart failure symptoms are managed using standard protocols and heart transplantation is considered for severe ventricular dysfunction or much less commonly uncontrollable ventricular arrhythmias.
Left ventricular non-compaction: genetics and embryology
Authors: Garcia-Pavia Pablo , Dominguez Fernando
Published: March 2018

Left ventricular non-compaction (LVNC) is a rare disorder that is considered an ‘unclassified cardiomyopathy’ by the European Society of Cardiology. Several different gene mutations related to LVNC have been identified, involving sarcomeric, cytoskeletal, Z-line, ion channel, mitochondrial, and signalling proteins. However, there is broad genetic overlap between LVNC and other inherited cardiac diseases such as dilated cardiomyopathy and hypertrophic cardiomyopathy. LVNC could also be part of multisystemic genetic entities such as Barth syndrome, or accompany congenital heart defects.
Left ventricular non-compaction: diagnosis and clinical management
Authors: Mogensen Jens , Rasmussen Torsten B
Published: March 2018

Left ventricular non-compaction (LVNC) is characterized by a specific morphological appearance of the myocardium with an inner non-compacted hypertrabeculated layer and deep recesses communicating with the left ventricular cavity, and an outer compacted myocardium. LVNC is a specific morphological finding and may be present in healthy individuals with apparently normal hearts and in patients with various cardiac and systemic conditions including X-linked Barth syndrome, cardiomyopathies, congenital heart diseases, and non-cardiac systemic diseases. Recent investigations have revealed that LVNC may appear as the sole manifestation of disease in carriers of genetic mutations associated with dilated and hypertrophic cardiomyopathies. Therefore, it is important to consider the possibility of familial disease when diagnosing LVNC and explore the family history of the patient. Clinical screening of relatives should be offered when familial disease is suspected or when LVNC remains unexplained. Anticoagulation should be considered when LVNC appears in patients with impaired systolic function of the left ventricle to avoid formation of thrombi and cardiac embolization following an assessment of the entire risk profile of the individual patient.
Overview of pericardial syndromes
Authors: Arad Michael , Adler Yehuda
Published: March 2018

Pericardial diseases manifest as a part of a systemic condition or in isolation. The clinical presentation is driven by inflammation (i.e. pericarditis), excess fluid accumulation (pericardial effusion), or pericardial stiffening (constriction). Corresponding symptoms and signs may include pain, stigmata of systemic inflammation, atrial arrhythmia, haemodynamic compromise, or chronic heart failure. Pericardial tumours and space-occupying lesions are uncommon and may be incidentally detected or present as one of the above-mentioned forms of pericardial disease. Aetiological work-up is usually unnecessary in acute pericarditis but is indicated in the incessant/chronic form and to exclude bacterial infection. Pericardial effusions need to be investigated when large and promptly evacuated when associated with haemodynamic compromise. The hallmark of constrictive physiology is ventricular interdependence. It is important to distinguish transient constriction and to treat inflammation according to aetiology prior to making a decision on surgical relief by pericardiectomy.
Pericardial effusion
Authors: Brucato Antonio , Maggiolini Stefano
Published: March 2018

Pericardial effusion is classified according to its onset—acute, subacute, or chronic (>3 months)—distribution (circumferential or loculated), and haemodynamic impact. Concerning the size, we propose a simple semiquantitative echocardiographic assessment: mild (<10 mm), moderate (10–20 mm), and large (>20 mm), evaluated as the largest telediastolic echo-free space in two-dimensional mode. Symptoms vary according to the speed of accumulation; slow accumulation may induce no or minor symptoms. In the presence of chronic, large pericardial effusions, appropriate tests for neoplasms, tuberculosis, and hypothyroidism should be considered. Chest computed tomography scanning is helpful in reaching an aetiological diagnosis (neoplasms, lymphomas, pneumonia, tuberculosis). High values of proteins, albumin, and lactate dehydrogenase are usually considered indicative of an exudate, as in pleural fluid, but this may not be true for pericardial fluid, and cytology has a sensitivity of only 50% for neoplasm. Mycobacterium cultures and a genome search for tuberculosis with the polymerase chain reaction in pericardial fluid are mandatory if pericardiocentesis is performed. If inflammatory signs are present, the clinical management should be that of pericarditis and a trial of non-steroidal anti-inflammatory drugs, colchicine, or low-dose corticosteroids, or a combination of these, may be tried. In about 60% of cases, the effusion is associated with a known disease, and the therapy should be targeted. When pericardiocentesis is performed in large effusions, prolonged pericardial drainage of up to 30 mL/24 h has been suggested to prevent recurrences, although evidence to support this is scarce. Prognosis is related to the aetiology, and idiopathic effusions may have a good prognosis especially if the effusion is mild to moderate.
Non-bacterial thrombotic endocarditis
Authors: Lancellotti Patrizio , Marchetta Stella
Published: March 2018

Non-bacterial thrombotic endocarditis (NBTE) is characterized by the presence of sterile vegetations on cardiac valves that consist of fibrin and platelet aggregates. These vegetations are neither associated with bacteraemia nor with destructive changes of the underlying valve. The diagnosis of NBTE relies on strong clinical suspicion in the context of (a) a disease process known to be associated with NBTE, (b) the presence of a heart murmur, (c) a negative blood culture, (d) the presence of vegetations not responding to antibiotic treatment, and (e) evidence of multiple systemic emboli. The same initial diagnostic work-up as for infective endocarditis is recommended. Serial blood cultures, exhaustive haematological and coagulation studies, and a comprehensive echocardiography should be performed. The management of NBTE is challenging and a tailored approach should be advocated. It should first focus on the underlying pathology. In the absence of contraindications, an anticoagulation treatment should be given. Surgical intervention is not recommended unless the patient has clear indications (i.e. heart failure due to valve dysfunction).
Definition, epidemiology, and burden of disease: HFrEF
Authors: Maggioni Aldo Pietro , Chioncel Ovidiu
Published: March 2018

Heart failure is the final common stage of many diseases of the heart, caused by structural and/or functional cardiac abnormalities, resulting in a reduced cardiac output. The clinical profile of patients with heart failure with reduced ejection fraction (HFrEF) is generally more severe than that of patients with heart failure and preserved ejection fraction. HFrEF remains a relevant problem, despite the improvements in its management achieved in the last decades, leading to large economic costs, frequent hospitalization, and high levels of mortality.
HFrEF pharmacological treatment: ivabradine
Authors: Komajda Michel
Published: March 2018

Ivabradine slows down the heart rate through a blockade of the funny current channels in the sinoatrial node cells. The efficacy of the drug was tested in a large outcome clinical trial in stable chronic heart failure with reduced ejection fraction, in sinus rhythm, on a contemporary background therapy including beta blockers.
HFpEF treatment: pharmacological therapy
Authors: Cikes Maja , Solomon Scott D.
Published: March 2018

Heart failure with preserved ejection fraction (HFpEF) is a diverse syndrome characterized by signs and symptoms of heart failure with relatively preserved ejection fraction. Despite the established efficacy of numerous classes of drugs and devices in heart failure with reduced ejection fraction, no specific therapy has yet proven to reduce morbidity and mortality in HFpEF. Currently, treatment of HFpEF remains empiric, and includes diuretic therapy for decongestion, treatment of hypertension, diagnosis and treatment of ischaemia, rate control for atrial fibrillation, and treatment of co-morbidities. While outcomes trials in HFpEF have tested renin–angiotensin–aldosterone inhibitors, and none have met their primary endpoint, there is some evidence that in appropriate patients, the mineralocorticoid receptor antagonist spironolactone may be helpful to reduce heart failure hospitalizations. Several other medications have been tested in phase II trials. Sildenafil, isosorbide mononitrate, and the soluble guanylate cyclase stimulator vericiguat did not show benefit in phase II trials. In contrast, sacubitril/valsartan was associated with a significant decrease in N-terminal pro-B-type natriuretic peptide values and improvement in left atrial size in a phase II trial. A large phase III trial to confirm these findings is under way.
Anatomy and physiology of the sinus node
Authors: Zaza Antonio
Published: March 2018

The sinoatrial node (SAN) is the dominant pacemaker structure in the mammalian heart. It is endowed with robust intrinsic automaticity, providing periodic electrical excitation with a cycle widely modulated by autonomic influences. A number of membrane channels and transporters contribute to the net membrane current supporting SAN electrical activity, whose periodicity is determined by the interplay of two oscillators termed ‘membrane’ and ‘calcium’ clock respectively. This chapter describes the structure of the SAN, the peculiarities of its electrical cycle, the nature and modulation of the underlying clocks, and SAN interaction with atrial muscle. Moreover, the features and determinants of the temporal variability of the pacemaker cycle, clinically used to assess autonomic balance, are briefly discussed.
Atrioventricular conduction abnormalities and atrioventricular blocks: role of electrophysiology testing
Authors: Katritsis Demosthenes G. , Josephson Mark E.
Published: March 2018

In sinus bradycardia, the role of electrophysiology studies is not established. A marked prolongation of the corrected sinus node recovery time (>800 ms) is a highly predictive but insensitive sign for sick sinus syndrome. In atrioventricular conduction disturbances, an electrophysiology study may be necessary both for the establishment of atrioventricular block as the main cause of symptoms, and for identification of the anatomical site of block that may dictate the potential need of permanent pacing. Prediction of development of complete heart block may not be possible. An HV interval greater than 70 ms is a non-specific predictor of development of high-grade atrioventricular block, whereas an HV interval greater than 100 ms is highly predictive but insensitive. Drug testing with adenosine triphosphate/adenosine, and procainamide has a rather limited diagnostic yield in patients with atrioventricular conduction disturbances.
Congenital atrioventricular block: clinical presentation, clinical evaluation, and management
Authors: Fabrizio Drago , Irma Battipaglia
Published: March 2018

Congenital atrioventricular block (CAVB) is a cardiac conduction disorder that is diagnosed in utero, at birth, or within the first month of life. When it is diagnosed between the first month and the 18th year of life, it is defined as childhood atrioventricular (AV) block. CAVB may occur in association with concomitant congenital heart disease, or be isolated, in a structurally normal heart (e.g. immune-mediated, inherited, or idiopathic CAVB). The majority of isolated CAVB is an immune-mediated AV block, due to transplacental passage of maternal autoantibodies, damaging the fetal cardiac conduction system. Only in a third of infants with immune-mediated CAVB is a well-defined autoimmune disease known in the mother. During fetal life, fetal echocardiography still represents the gold standard for the diagnosis of CAVB. Two major negative prognostic markers are low ventricular rate and the appearance of fetal hydrops. As regards prognosis, a risk for heart failure, syncope, and sudden death is present both during fetal and postnatal life. Dilated cardiomyopathy represents another complication in CAVB history, with different possible aetiologies (right ventricular permanent pacing, reactivation of autoimmune myocarditis). The indications for pacemaker implantation in patients with CAVB are similar to those for acquired heart disease, with some special technical considerations due to young age (epicardial versus endocardial systems, pacing site, etc.). As a future perspective, leadless cardiac stimulation in children with CAVB may represent a definitive solution and an answer to many questions.
Introduction
Authors: Camm A. John
Published: March 2018

Although a condition associated with a fully irregular pulse has been known to physicians for centuries, it was only towards the end of the nineteenth century and the beginning of the twentieth century that some mechanistic understanding of the arrhythmia was gained from the jugular venous and arterial pulse recordings (polysomnography) made by Mackenzie and the electrocardiograms recorded by Einthoven and Lewis. It was apparent that atrial contraction was absent, that the normal atrial activation (P wave) was replaced by a higher-frequency atrial fibrillatory wave, and that the QRS complexes were usually narrow and consistent with a normal supraventricular origin.
Rate control: ablation and device therapy (ablate and pace)
Authors: Gasparini Maurizio , Galimberti Paola
Published: March 2018

The atrioventricular junction ablation (AVJA) and pacing method has been a well-known strategy since the 1980s. It is nowadays essentially performed in two groups of patients. First of all, it is indicated in atrial fibrillation (AF) patients who have failed rhythm control with pulmonary vein isolation ablation and different medical rate control strategies. The procedure dramatically reduces symptoms and it is associated with an increase in ejection fraction in patients with AF-induced cardiomyopathy. The second group of patients is represented by heart failure patients with a cardiac resynchronization system presenting with a low biventricular pacing percentage due to a high AF burden. Several studies have documented the necessity to achieve the highest biventricular pacing to maximize cardiac resynchronization therapy (CRT) benefits. In this context of AF patient with CRT, AVJA is the only tool that allows complete rhythm regularization and heart rate control, thus favouring a ‘pure’, constant delivery of CRT, while negative chronotropic drug use is limited and device algorithms only partially effective. An improvement of symptoms, of left ventricular function, as well as survival benefit has been clearly documented after AVJA in AF CRT patients. The procedure is usually safe and effective; nonetheless, it is often perceived as a potentially harmful therapy that should be avoided as much as possible because it causes pacemaker dependency. However, no studies on conventional ablate and pace therapy have reported significant complications during the follow-up. Furthermore, the aforementioned benefits of AVJA in the heart failure population seem to well overweigh possible risks associated with pacemaker dependency.
Polymorphic ventricular tachycardias including torsade de pointes
Authors: Mitchell L. Brent
Published: March 2018

Polymorphic ventricular tachycardia (PMVT) is a rapid ventricular tachycardia in which the QRS complexes vary in coupling interval, morphology, and axis on a beat-to-beat basis. PMVT occurs in two distinct forms: PMVT without QT interval prolongation and PMVT with QT interval prolongation. The two types differ in important ways with respect to their differential diagnosis and treatment. PMVT without QT interval prolongation usually emerges in the setting of an unstable structural heart disorder, such as acute ischaemia or decompensated heart failure. Treatment is directed at the underlying heart disorder, correction of acid–base disturbances, hypoxia, and electrolyte abnormalities along with beta-blocking therapy and amiodarone. Invasive antiarrhythmic interventions, such as sympathetic denervation and transcatheter ablation, are occasionally required. Long-term treatment often includes an implantable cardioverter defibrillator. PMVT with QT interval prolongation, known as torsade de pointes PMVT, occurs when repolarization reserve has been exhausted by either inherited or acquired factors that prolong the QT interval. Classical features of the ‘twisting-of-the-points’ polymorphism and the short–long–short initiation sequence are common but are not universal. Treatment is directed at removal of the cause of the QT interval prolongation, correction of electrolyte disturbances (hypokalaemia and hypomagnesaemia), supplemental magnesium therapy, and treatments to shorten the QT interval such as isoproterenol, pacing, or lidocaine. Long-term treatment is focused on avoidance of QT interval prolonging factors. If the likelihood of subsequent recurrence is not low, consideration is given to placement of a permanent pacemaker or implantable cardioverter defibrillator.
New techniques for risk assessment in sudden cardiac death
Authors: Fernandez-Armenta Juan , Berruezo Antonio , Acosta Juan , Penela Diego
Published: March 2018

Risk stratification for sudden cardiac death (SCD) is one of the main objectives of clinical arrhythmology. Despite increased knowledge of the fundamental basis and predictors of SCD, the estimation of individual risk remains challenging. To date, symptomatic heart failure and reduced left ventricular ejection fraction are the main variables used to identify patients at high risk of SCD who could potentially benefit from preventive therapies. Beyond left ventricular ejection fraction, new diagnostic tools have been proposed to better stratify patients at risk of SCD. Among them, cardiovascular magnetic resonance imaging, which allows direct visualization of the arrhythmogenic substrate, is considered particularly promising. Genetic testing and serum biomarkers may also have a role in SCD risk assessment.
Secondary prevention of sudden cardiac death in ischaemic cardiomyopathy
Authors: Nielsen Jens Cosedis , Kristensen Jens
Published: March 2018

The most common reason for sudden cardiac death is ischaemic heart disease. Patients who survive cardiac arrest are at particularly high risk of recurrent ventricular arrhythmia and sudden cardiac death, and are candidates for secondary prevention defined as ‘therapies to reduce the risk of sudden cardiac death in patients who have already experienced an aborted cardiac arrest or life-threatening arrhythmias’. The mainstay therapy for secondary prevention of sudden cardiac death is implantation of an implantable cardioverter defibrillator. Furthermore, revascularization and optimal medical therapy for heart failure and concurrent cardiovascular diseases should be ensured.
Device-based treatment for hypertension
Authors: Kulenthiran Saarraaken , Ewen Sebastian , Mahfoud Felix
Published: March 2018

Autonomic imbalance is thought to play an important role in the pathophysiology of hypertension. Despite the availability of diverse pharmacological options, non-adherence to medication or inability to tolerate current pharmacological therapies has led to the development of various device-based therapy options. Inhibiting components of the sympathetic nervous system offers a unique opportunity to target the ‘neural’ component of the neurohormonal axis. Combining novel drug-, device-, and procedure-based strategies with improved utilization of existing therapies (including appropriate attention to diet, exercise, and weight control) may result in improved outcomes. This chapter discusses the rationale and current experimental and clinical data of several novel device-based treatment options—renal nerve ablation, carotid body ablation, carotid baroreceptor stimulation, and central arteriovenous anastomosis.
Introduction
Authors: Humbert Marc
Published: March 2018

This chapter acts as an introduction to Section 45 on pulmonary hypertension.
Screening for pulmonary arterial hypertension
Authors: Coghlan John
Published: March 2018

Screening programmes for pulmonary hypertension are justifiable in some circumstances but not others. The inherent inaccuracies of the diagnostic tools and the low prevalence of pulmonary hypertension renders screening programmes ineffective unless the population evaluated with the primary screening tool (echocardiography) can be enriched. Nevertheless, significant progress has been made over the past 5 years and screening programmes are now strongly recommended (class 1 recommendation) in asymptomatic systemic sclerosis, BMPR2 mutation carriers, first-degree relatives of patients with hereditable pulmonary hypertension, and patients with portal hypertension referred for transplantation.
Pulmonary arterial hypertension associated with congenital heart diseases
Authors: Brida Margarita , Diller Gerhard-Paul , Gatzoulis Michael A.
Published: March 2018

Pulmonary arterial hypertension (PAH) is commonly associated with congenital heart disease (CHD) and relates to the type of the underlying defects and repair strategies. Large pulmonary shunts may develop PAH if untreated or repaired late. PAH, when present, markedly increases morbidity and mortality in CHD patients. Significant progress has been made for patients with Eisenmenger syndrome in pathophysiology, prognostication, and disease-targeting therapy. Patients with PAH-CHD and left-to-right shunting may benefit from late defect closure if pulmonary vascular resistance is normal or near normal. Patients with PAH-CHD and coincidental defects and also patients with previous repair of CHD should be managed as those with idiopathic PAH. All patients with PAH-CHD should be cared for at expert centres and those with Eisenmenger syndrome benefit from a proactive disease-targeting therapy approach. More research in this growing cardiovascular field is clearly warranted.
Genetic counselling in pre-capillary pulmonary hypertension
Authors: Girerd Barbara , Montani David , Humbert Marc
Published: March 2018

Pre-capillary pulmonary hypertension can be heritable in the context of pulmonary arterial hypertension (an autosomal dominant disease mainly due to mutations in BMPR2), and pulmonary veno-occlusive disease or pulmonary capillary haemangiomatosis (an autosomal recessive disease due to biallelic mutations in the EIF2AK4 gene). Genetic counselling can be implemented in referral centres for pulmonary hypertension as outlined in this chapter.
Genetic diseases of the aorta: aortic diseases associated with bicuspid aortic valves
Authors: Meijboom Folkert , Sieswerda Gert-Jan
Published: March 2018

There is a genetic cause of bicuspid aortic valve. Dilatation of the aortic root and ascending aorta has long been considered genetically determined too and treated accordingly. In recent years, basic research combined with advanced cardiac imaging has made a strong case for another cause of this dilatation: an altered flow profile in the ascending aorta due to the abnormal geometry of the bicuspid valve, leading to an area of altered wall shear stress, which in turn leads to remodelling of the aortic wall, with apoptosis of vascular smooth muscle cells and disruption of media layer as a result. These histological changes, previously referred to as cystic medial necrosis, form the basis of a loss of structural integrity of the aortic wall, which makes it prone to dilatation, dissection, and rupture.