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Arrhythmogenic cardiomyopathy (AC) is a hereditary cardiac disorder characterized by the gradual replacement of cardiomyocytes with fibrous and adipose tissue, leading to ventricular wall thinning, chamber dilation, arrhythmias, and sudden cardiac death. Despite advances in treatment, disease management remains challenging. Animal models, particularly mice and zebrafish, have become invaluable tools for understanding AC's pathophysiology and testing potential therapies. Mice models, although useful for scientific research, cannot fully replicate the complexity of the human AC. However, they have provided valuable insights into gene involvement, signalling pathways, and disease progression. Zebrafish offer a promising alternative to mammalian models, despite the phylogenetic distance, due to their economic and genetic advantages. By combining animal models with in vitro studies, researchers can comprehensively understand AC, paving the way for more effective treatments and interventions for patients and improving their quality of life and prognosis.
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Modelos Animais de Doenças , Animais , Humanos , Peixe-Zebra , Arritmias Cardíacas/patologia , Arritmias Cardíacas/fisiopatologia , Arritmias Cardíacas/genética , Displasia Arritmogênica Ventricular Direita/genética , Displasia Arritmogênica Ventricular Direita/patologia , Camundongos , Cardiomiopatias/patologia , Cardiomiopatias/genéticaRESUMO
AIMS: Transvenous lead extraction (TLE) is potentially complicated by significant tricuspid valve regurgitation increase (TRI). However, there are limited data on the effect of the bidirectional rotational mechanical sheaths on significant TRI. The aim of the present study was to investigate the rate of significant changes in tricuspid regurgitation (TR) severity following mechanical rotational TLE and their outcomes. METHODS AND RESULTS: In 158 patients (mean age 66 ± 16.9 years) undergoing mechanical rotational TLE, acute changes in TR severity were assessed by echocardiography evaluation. A significant acute TRI was defined as an increase of at least one grade with a post-extraction severity at least moderate. A total of 290 leads were extracted (mean implant duration, 93 ± 65 months). Significant TRI was noted in 5.7% of patients, and it was linked to tricuspid valve damage, TLE infection indication, and longer lead implant duration. Univariate predictors of significant TRI included implant duration of all leads [odds ratio (OR) 1.01; 95% confidence interval (CI) 1.003-1.018; P = 0.001] and right ventricular leads (OR 1.01; 95% CI 1.004-1.017; P = 0.002). Severe increase of TR following TLE was an independent predictor of mortality [hazard ratio (HR) 5.20; 95% CI 1.44-18.73; P = 0.012 ] along with severe systolic dysfunction (HR 2.37; 95% CI 1.01-5.20; P = 0.032), and systemic infection (HR 2.28; 95% CI 1.06-4.89; P = 0.035). CONCLUSION: Significant TRI was detected in 5.7% of patients following transvenous rotational mechanical lead extraction. The duration of lead implantation emerged as the sole predictor of significant TRI. Physicians engaged in TLE should exercise greater vigilance for this potential complication.
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Desfibriladores Implantáveis , Remoção de Dispositivo , Insuficiência da Valva Tricúspide , Humanos , Insuficiência da Valva Tricúspide/etiologia , Masculino , Feminino , Remoção de Dispositivo/efeitos adversos , Idoso , Pessoa de Meia-Idade , Desfibriladores Implantáveis/efeitos adversos , Idoso de 80 Anos ou mais , Índice de Gravidade de Doença , Fatores de Risco , Resultado do Tratamento , Marca-Passo Artificial/efeitos adversos , Estudos Retrospectivos , Valva Tricúspide/diagnóstico por imagem , Valva Tricúspide/cirurgia , Valva Tricúspide/fisiopatologia , Fatores de TempoRESUMO
The role of the immune system in myocarditis onset and progression involves a range of complex cellular and molecular pathways. Both innate and adaptive immunity contribute to myocarditis pathogenesis, regardless of its infectious or non-infectious nature and across different histological and clinical subtypes. The heterogeneity of myocarditis etiologies and molecular effectors is one of the determinants of its clinical variability, manifesting as a spectrum of disease phenotype and progression. This spectrum ranges from a fulminant presentation with spontaneous recovery to a slowly progressing, refractory heart failure with ventricular dysfunction, to arrhythmic storm and sudden cardiac death. In this review, we first examine the updated definition and classification of myocarditis at clinical, biomolecular and histopathological levels. We then discuss recent insights on the role of specific immune cell populations in myocarditis pathogenesis, with particular emphasis on established or potential therapeutic applications. Besides the well-known immunosuppressive agents, whose efficacy has been already demonstrated in human clinical trials, we discuss the immunomodulatory effects of other drugs commonly used in clinical practice for myocarditis management. The immunological complexity of myocarditis, while presenting a challenge to simplistic understanding, also represents an opportunity for the development of different therapeutic approaches with promising results.
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Arrhythmogenic cardiomyopathy (ACM) is an inherited myocardial disease at risk of sudden death. Genetic testing impacts greatly in ACM diagnosis, but gene-disease associations have yet to be determined for the increasing number of genes included in clinical panels. Genetic variants evaluation was undertaken for the most relevant non-desmosomal disease genes. We retrospectively studied 320 unrelated Italian ACM patients, including 243 cases with predominant right-ventricular (ARVC) and 77 cases with predominant left-ventricular (ALVC) involvement, who did not carry pathogenic/likely pathogenic (P/LP) variants in desmosome-coding genes. The aim was to assess rare genetic variants in transmembrane protein 43 (TMEM43), desmin (DES), phospholamban (PLN), filamin c (FLNC), cadherin 2 (CDH2), and tight junction protein 1 (TJP1), based on current adjudication guidelines and reappraisal on reported literature data. Thirty-five rare genetic variants, including 23 (64%) P/LP, were identified in 39 patients (16/243 ARVC; 23/77 ALVC): 22 FLNC, 9 DES, 2 TMEM43, and 2 CDH2. No P/LP variants were found in PLN and TJP1 genes. Gene-based burden analysis, including P/LP variants reported in literature, showed significant enrichment for TMEM43 (3.79-fold), DES (10.31-fold), PLN (117.8-fold) and FLNC (107-fold). A non-desmosomal rare genetic variant is found in a minority of ARVC patients but in about one third of ALVC patients; as such, clinical decision-making should be driven by genes with robust evidence. More than two thirds of non-desmosomal P/LP variants occur in FLNC.
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Displasia Arritmogênica Ventricular Direita , Humanos , Displasia Arritmogênica Ventricular Direita/genética , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Proteínas de Membrana/genética , Caderinas/genética , Desmossomos/genética , Desmossomos/metabolismo , Predisposição Genética para Doença , Variação Genética , Filaminas/genética , Estudos Retrospectivos , Itália , Proteínas de Ligação ao Cálcio/genética , Antígenos CD/genéticaRESUMO
Mitral annular disjunction (MAD), a separation between the left atrium/mitral valve annulus and the left ventricular myocardium, is frequently seen in patients with arrhythmic mitral valve prolapse. Although an association exists between MAD and ventricular arrhythmias, little is known regarding the identification of individuals at high risk. Multimodality imaging including echocardiography, computed tomography, cardiac magnetic resonance, and positron emission tomography can play an important role in both the diagnosis and risk stratification of MAD. Due to a paucity of data, clinical decision making in a patient with MAD is challenging and remains largely empirical. Although MAD itself can be corrected surgically, the prevention and treatment of associated arrhythmias may require medical therapy, catheter ablation, and an implantable cardioverter-defibrillator. Prospective data are required to define the role of implantable cardioverter-defibrillators, targeted catheter ablation, and surgical correction in selected, at-risk patients.
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This review explores the historical development of cardiology knowledge, from ancient Egyptian psychostasis to the modern comprehension of cardiac neuromodulation. In ancient Egyptian religion, psychostasis was the ceremony in which the deceased was judged before gaining access to the afterlife. This ritual was also known as the "weighing of the heart" or "weighing of the soul". The Egyptians believed that the heart, not the brain, was the seat of human wisdom, emotions, and memory. They were the first to recognize the cardiocentric nature of the body, identifying the heart as the center of the circulatory system. Aristotle (fourth century BC) considered the importance of the heart in human physiology in his philosophical analyses. For Galen (third century AD), the heart muscle was the site of the vital spirit, which regulated body temperature. Cardiology knowledge advanced significantly in the 15th century, coinciding with Leonardo da Vinci and Vesalius's pioneering anatomical and physiological studies. It was William Harvey, in the 17th century, who introduced the concept of cardiac circulation. Servet's research and Marcello Malpighi's discovery of arterioles and capillaries provided a more detailed understanding of circulation. Richard Lower emerged as the foremost pioneer of experimental cardiology in the late 17th century. He demonstrated the heart's neural control by tying off the vagus nerve. In 1753, Albrecht von Haller, a professor at Göttingen, was the first to discover the heart's automaticity and the excitation of muscle fibers. Towards the end of the 18th century, Antonio Scarpa challenged the theories of Albrecht von Haller and Johann Bernhard Jacob Behrends, who maintained that the myocardium possessed its own "irritability", on which the heartbeat depended, and was independent of neuronal sensitivity. Instead, Scarpa argued that the heart required innervation to maintain life, refuting Galenic notions. In contemporary times, the study of cardiac innervation has regained prominence, particularly in understanding the post-acute sequelae of SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) infection (PASC), which frequently involves cardiorespiratory symptoms and dysregulation of the intrinsic cardiac innervation. Recently, it has been recognized that post-acute sequelae of acute respiratory infections (ARIs) due to other pathogens can also be a cause of long-term vegetative and somatic symptoms. Understanding cardiac innervation and modulation can help to recognize and treat long COVID and long non-COVID-19 (coronavirus disease 2019) ARIs. This analysis explores the historical foundations of cardiac neuromodulation and its contemporary relevance. By focusing on this concept, we aim to bridge the gap between historical understanding and modern applications. This will illuminate the complex interplay between cardiac function, neural modulation, cardiovascular health, and disease management in the context of long-term cardiorespiratory symptoms and dysregulation of intrinsic cardiac innervations.
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For many years, cardiac pacing has been based on the stimulation of right ventricular common myocardium to correct diseases of the conduction system. The birth and the development of cardiac resynchronization have led to growing interest in the correction and prevention of pacing-induced dyssynchrony. Many observational studies and some randomized clinical trials have shown that conduction system pacing (CSP) can not only prevent pacing-induced dyssynchrony but can also correct proximal conduction system blocks, with reduction of QRS duration and with equal or greater effectiveness than biventricular pacing. Based on these results, many Italian electrophysiologists have changed the stimulation target from the right ventricular common myocardium to CSP. The two techniques with greater clinical impact are the His bundle stimulation and the left bundle branch pacing. The latter, in particular, because of its easier implantation technique and better electric parameters, is spreading like wildfire and is representing a real revolution in the cardiac pacing field. However, despite the growing amount of data, until now, the European Society of Cardiology guidelines give a very limited role to CSP.
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Terapia de Ressincronização Cardíaca , Insuficiência Cardíaca , Humanos , Bloqueio de Ramo , Resultado do Tratamento , Eletrocardiografia/métodos , Sistema de Condução Cardíaco , Terapia de Ressincronização Cardíaca/métodos , Miocárdio , Insuficiência Cardíaca/terapiaRESUMO
In 1900, Fiedler first reported autopsy cases with peculiar inflammation of the myocardium, which he named interstitial myocarditis. He postulated an isolated cardiac inflammation of the myocardium in the absence of multiorgan involvement and with a poor prognosis due to invisible microorganisms, which years later would have been identified as viruses. The revision of original histologic sections by Schmorl showed cases with lymphocytes and others with giant-cell inflammatory histotypes. The in vivo diagnosis of myocarditis became possible thanks to right cardiac catheterization with endomyocardial biopsy (EMB). The gold standard for diagnosis was achieved with the employment of immunohistochemistry and molecular investigation by Polymerase Chain Reaction (PCR), which allows for the detection of viruses as causal agents. Both RNA and DNA were revealed to be cardiotropic, with a common receptor (CAR). A protease, coded by coxsackie virus, disrupts the cytoskeleton and accounts for cell death. Unfortunately, vaccination, despite having been revealed to be effective in animal experiments, has not yet entered the clinical field for prevention. Cardiac Magnetic Resonance turned out to be a revolutionary tool for in vivo diagnosis through the detection of edema (inflammatory exudate). Myocarditis may be fulminant in terms of clinical presentation but not necessarily fatal. The application of ExtraCorporeal Membrane Oxygenation (ECMO) allows for relieving the overloaded native heart.
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OBJECTIVE: Evidence on the increased risk of sports-related sudden cardiac arrest and death (SCA/D) and the potential benefit of cardiovascular preparticipation screening (PPS) in children is limited. We assessed the burden and circumstances of SCA/D and the diagnostic yield of cardiovascular PPS in children aged 8-15 years. METHODS: Data on the incidence and causes of SCA/D from 2011 to 2020 were obtained from the Veneto region (Italy) sudden death registry, hospital records and local press. During the same period, we assessed the results of annual PPS in 25 251 young competitive athletes aged 8-15 years who underwent 58 185 evaluations (mean 2.3/athlete) in Padua, Italy. RESULTS: Over 10 years, 26 SCA/D occurred in children aged 8-15 years in the Veneto region: 6 in athletes (incidence 0.7/100 000/year, all ≥12 years) versus 20 in non-athletes (0.7/100 000/year, 17/20 ≥12 years). In total, 4/6 athletes versus 1/20 non-athletes survived. The cause of SCA/D remained unexplained in four athletes and in nine non-athletes. No athlete suffered SCA/D from structural diseases potentially identifiable by PPS. The incidence of SCA/D in athletes and non-athletes was 0.2/100 000/year in the 8-11 years group versus 1.3/100 000/year in the 12-15 years group. PPS identified 26 new diagnoses of cardiovascular diseases (CVDs) at risk of SCA/D, more often in children ≥12 years old (0.06%/evaluation) than <12 years old (0.02%/evaluation, p=0.02). Among athletes with a negative PPS, two suffered unexplained SCA/D during follow-up, one during exercise. CONCLUSIONS: In children aged 8-15 years, the incidence of SCA/D and the yield of PPS for identifying at-risk CVD were both substantially higher in those ≥12 years, suggesting that systematic PPS may be more useful beyond this age.
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Sistema Cardiovascular , Esportes , Criança , Humanos , Morte Súbita Cardíaca/epidemiologia , Morte Súbita Cardíaca/prevenção & controle , Morte Súbita Cardíaca/etiologia , Atletas , Programas de RastreamentoRESUMO
Bicuspid aortic valve (BAV) is the most frequent congenital heart disease, with an incidence of approximately 1%. It can be silent and associated with normal valve function. However, a series of complications, even catastrophic, may occur with time: valve incompetence, valve stenosis by dystrophic calcification, infective endocarditis, progressive dilatation of the ascending aorta, aortic dissection, sudden death. The problem of BAV is not just about the number of semilunar cusps, but also the aortic wall. Severe noninflammatory degenerative changes (elastic fiber fragmentation, smooth muscle cells death, mucoid extracellular matrix accumulation=MEMA) are observed in the aortic wall of BAV patients, with intrinsic weakness accounting for progressive aneurysmal dilatation of the ascending aorta, valve incompetence, and wall dissection. The link between valve and aortic wall pathology finds most probably an explanation in the embryology of the arterial pole since neurocrestal cells play a role in the development of both the ascending aorta, aortic arch, and semilunar valves. The frequent association of adult aortic coarctation and BAV provides evidence for this hypothesis. BAV has a significant genetic component as to require screening of first-degree relatives, as outlined by AHA/ACC 2022 guidelines.
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Valva Aórtica , Doença da Válvula Aórtica Bicúspide , Doenças das Valvas Cardíacas , Humanos , Doença da Válvula Aórtica Bicúspide/patologia , Valva Aórtica/anormalidades , Valva Aórtica/patologia , Doenças das Valvas Cardíacas/patologia , Fatores de Risco , PrognósticoRESUMO
Sudden death by commotio cordis is rare. It is the consequence of a blunt trauma of the chest overlying the heart. The mechanism is a cardiac arrest by ventricular fibrillation in the absence of grossly or microscopically apparent myocardial injury. It has been reproduced in animals. The first historical case was reported by Giovanni Maria Lancisi in his book "De Subitaneis Mortibus'' published in 1707. Sudden death occurred in a man receiving a powerful blow under the xiphoid cartilage. Lancisi advanced the hypothesis of acute heart failure by a diastolic stand still ("death in diastole'').
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Commotio Cordis , Humanos , Commotio Cordis/história , Commotio Cordis/etiologia , Commotio Cordis/patologia , História do Século XVIII , Morte Súbita Cardíaca/etiologia , Morte Súbita Cardíaca/patologia , Masculino , Parada Cardíaca/história , Parada Cardíaca/etiologia , Ferimentos não Penetrantes/história , Ferimentos não Penetrantes/complicações , Ferimentos não Penetrantes/patologia , Fibrilação Ventricular/história , Fibrilação Ventricular/fisiopatologia , Fibrilação Ventricular/etiologiaRESUMO
Arrhythmogenic cardiomyopathy (ACM) is a heart muscle disease characterized by prominent "non-ischemic" myocardial scarring predisposing to ventricular electrical instability. Diagnostic criteria for the original phenotype, arrhythmogenic right ventricular cardiomyopathy (ARVC), were first proposed in 1994 and revised in 2010 by an international Task Force (TF). A 2019 International Expert report appraised these previous criteria, finding good accuracy for diagnosis of ARVC but a lack of sensitivity for identification of the expanding phenotypic disease spectrum, which includes left-sided variants, i.e., biventricular (ABVC) and arrhythmogenic left ventricular cardiomyopathy (ALVC). The ARVC phenotype together with these left-sided variants are now more appropriately named ACM. The lack of diagnostic criteria for the left ventricular (LV) phenotype has resulted in clinical under-recognition of ACM patients over the 4 decades since the disease discovery. In 2020, the "Padua criteria" were proposed for both right- and left-sided ACM phenotypes. The presently proposed criteria represent a refinement of the 2020 Padua criteria and have been developed by an expert European TF to improve the diagnosis of ACM with upgraded and internationally recognized criteria. The growing recognition of the diagnostic role of CMR has led to the incorporation of myocardial tissue characterization findings for detection of myocardial scar using the lategadolinium enhancement (LGE) technique to more fully characterize right, biventricular and left disease variants, whether genetic or acquired (phenocopies), and to exclude other "non-scarring" myocardial disease. The "ring-like' pattern of myocardial LGE/scar is now a recognized diagnostic hallmark of ALVC. Additional diagnostic criteria regarding LV depolarization and repolarization ECG abnormalities and ventricular arrhythmias of LV origin are also provided. These proposed upgrading of diagnostic criteria represents a working framework to improve management of ACM patients.
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Displasia Arritmogênica Ventricular Direita , Cardiomiopatias , Humanos , Cicatriz , Consenso , Meios de Contraste , Gadolínio , Cardiomiopatias/diagnóstico por imagem , Arritmias Cardíacas/diagnósticoRESUMO
Arrhythmogenic cardiomyopathy (AC) is an inherited disorder characterized by progressive loss of the ventricular myocardium causing life-threatening ventricular arrhythmias, syncope and sudden cardiac death in young and athletes. About 40% of AC cases carry one or more mutations in genes encoding for desmosomal proteins, including Desmoplakin (Dsp). We present here the first stable Dsp knock-out (KO) zebrafish line able to model cardiac alterations and cell signalling dysregulation, characteristic of the AC disease, on which environmental factors and candidate drugs can be tested. Our stable Dsp knock-out (KO) zebrafish line was characterized by cardiac alterations, oedema and bradycardia at larval stages. Histological analysis of mutated adult hearts showed reduced contractile structures and abnormal shape of the ventricle, with thinning of the myocardial layer, vessels dilation and presence of adipocytes within the myocardium. Moreover, TEM analysis revealed "pale", disorganized and delocalized desmosomes. Intensive physical training protocol caused a global worsening of the cardiac phenotype, accelerating the progression of the disease. Of note, we detected a decrease of Wnt/ß-catenin signalling, recently associated with AC pathogenesis, as well as Hippo/YAP-TAZ and TGF-ß pathway dysregulation. Pharmacological treatment of mutated larvae with SB216763, a Wnt/ß-catenin agonist, rescued pathway expression and cardiac abnormalities, stabilizing the heart rhythm. Overall, our Dsp KO zebrafish line recapitulates many AC features observed in human patients, pointing at zebrafish as a suitable system for in vivo analysis of environmental modulators, such as the physical exercise, and the screening of pathway-targeted drugs, especially related to the Wnt/ß-catenin signalling cascade.
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History of cardiology starts scientifically in 1628, when William Harvey (1578-1657) published his revolutionary book Extercitatio anatomica de motu cordis et sanguinis in animalibus, where he described "general" circulation, movements and functions of heart, heart valves, veins and arteries [1]. Consequently, all theories and practices of ancient medicines were reduced to superstitions. Historians relegated pre-Harveian cardiology to roughs notes, preventing a proper historical evaluation of many centuries of conceptions and practices. All the ancient civilizations shared the conviction that the heart was the biological and spiritual center of the body, the seat of emotions, mind, will, a vital energy produced by breathing and healing, and the soul. This cardiocentric view maintained a special role both in religion and in medicine across millennia from east to west, passing over cultural and scientific revolutions. Here, we will try to give a schematic account of medical beliefs on the heart from the most important pre-classic medicines. Some of them today show to have a kernel of truth. This demonstrates, at least, that history is a non-linear process and that intuitions or even truths, potentially useful for the present and scientific development, can re-emerge from the past.
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The history of arrhythmogenic cardiomyopathy (AC) as a genetically determined desmosomal disease started since the original discovery by Lancisi in a four-generation family, published in 1728. Contemporary history at the University of Padua started with Dalla Volta, who haemodynamically investigated patients with "auricularization" of the right ventricle, and with Nava, who confirmed familiarity. The contemporary knowledge advances consisted of (a) AC as a heart muscle disease with peculiar electrical instability of the right ventricle; (b) the finding of pathological substrates, in keeping with a myocardial dystrophy; (c) the inclusion of AC in the cardiomyopathies classification; (d) AC as the main cause of sudden death in athletes; (e) the discovery of the culprit genes coding proteins of the intercalated disc (desmosome); (f) progression in clinical diagnosis with specific ECG abnormalities, angiocardiography, endomyocardial biopsy, 2D echocardiography, electron anatomic mapping and cardiac magnetic resonance; (g) the discovery of left ventricular AC; (h) prevention of SCD with the invention and application of the lifesaving implantable cardioverter defibrillator and external defibrillator scattered in public places and playgrounds as well as the ineligibility for competitive sport activity for AC patients; (i) genetic screening of the proband family to unmask asymptomatic carriers. Nondesmosomal ACs, with a phenotype overlapping desmosomal AC, are also treated, including genetics: Transmembrane protein 43, SCN5A, Desmin, Phospholamban, Lamin A/C, Filamin C, Cadherin 2, Tight junction protein 1.
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Hypertrophic cardiomyopathy (HCM) is an inherited myocardial disease at risk of sudden cardiac death and heart failure, even requiring heart transplantation. A "muscular mitral-aortic discontinuity" has been reported during surgery in the obstructive form. We aimed to validate these findings through pathological analysis of HCM heart specimens from the cardiovascular pathology tissue registry. Hearts with septal asymmetric HCM from sudden cardiac death, other causes of death, or heart transplantation were included. Sex-matched and age-matched patients without HCM served as controls. Gross and histologic analysis of the mitral valve (MV) apparatus and the mitral-aortic continuity were performed. Thirty HCM hearts (median age, 29.5 years; 15 men) and 30 controls (median age, 30.5 years; 15 men) were studied. In HCM hearts, a septal bulging was present in 80%, an endocardial fibrous plaque in 63%, a thickening of the anterior MV leaflet in 56.7%, and an anomalous insertion of papillary muscle in 10%. All cases but 1 (97%) revealed a myocardial layer overlapping the mitral-aortic fibrous continuity on the posterior side, corresponding to the left atrial myocardium. A negative correlation between the length of this myocardial layer and the age and the anterior MV leaflet length was found. The length did not differ between HCM and controls. Pathologic study of obstructive HCM hearts does not confirm the existence of a "muscular mitral-aortic discontinuity". An extension of left atrial myocardium, overlapping posteriorly the intervalvular fibrosa, is rather visible, and its length decreases with age, possibly as a consequence of left atrial remodeling. Our study highlights the fundamental role of thorough gross examination and the value of organ retention for further analysis in order to validate new surgical and imaging findings.
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Fibrilação Atrial , Cardiomiopatia Hipertrófica , Masculino , Humanos , Adulto , Cardiomiopatia Hipertrófica/diagnóstico por imagem , Cardiomiopatia Hipertrófica/patologia , Miocárdio/patologia , Valva Mitral/diagnóstico por imagem , Valva Mitral/patologia , Fibrose , Morte Súbita Cardíaca/patologiaRESUMO
AIMS: Myocardial longitudinal strain (LS) by two-dimensional (2D) speckle-tracking echocardiography has a diagnostic and prognostic role in cardiac amyloidosis (CA). Typically, the apical segments of the left ventricle (LV) are less affected by LS abnormalities, a finding called relative apical sparing (RELAPS). Whether a variable burden of CA might explain the RELAPS remains unknown.We aimed to evaluate the extent, distribution, and deposition pattern of amyloid in autopsy hearts of CA patients and to correlate the histopathology findings with 2D echocardiography. METHODS AND RESULTS: This is a retrospective study of whole heart specimens of CA patients who died and underwent autopsy and 2D echocardiography. Amyloid burden quantification was assessed by histomorphometry in each segment at different LV levels. The LS analysis results were compared with the amyloid burden and the base-to-apex distribution.Histopathology investigation of 27 hearts with CA [immunoglobulin light chains (AL) 17 cases and transthyretin (ATTR) 10 cases] demonstrated an amyloid base-to-apex gradient. In 11 CA patients with 2D echocardiography, analysis of LS and histological amyloid burden allowed to identify different patterns: RELAPS (8 cases, 73%), with (2) or without (6) amyloid gradient, normal or mildly reduced LS with diffuse low amyloid (2, 18%), and severely reduced LS with diffuse high amyloid (1, 9%). CONCLUSION: The typical RELAPS pattern at echocardiography is not always explained by a base-to-apex gradient of amyloid burden at histopathology, suggesting that RELAPS might be an epiphenomenon of complex interactions among amyloid infiltration, myocardial structure, and adaptation.