Epidemiological and pathological aspects of cardiomyopathies in cats in Southern Brazil / Aspectos epidemiológicos e patológicos das cardiomiopatias em gatos no Sul do Brasil

Cardiomyopathies are considered one of the most important causes of heart failure in cats and are subdivided into three main morphological types: hypertrophic (HCM), dilated (DCM), and restrictive (RCM). This study aimed to determine the frequency and types of cardiomyopathies in cats diagnosed in southern Brazil, with an emphasis on their epidemiological and pathological aspects. Necropsy reports filed in a veterinary pathology laboratory were reviewed, and cats diagnosed with cardiomyopathy were selected for the study. Animal identification data, history and clinical signs, and gross lesions, were reviewed and compiled. During the study period, 1.594 cat necropsies were performed, of which 72 (4.5%) comprised a diagnosis of cardiomyopathy. HCM was the most frequent followed by CMR and CMD, representing 77.8%, 12.5% and 9.7%, respectively. Age ranged from three months to 18 years, with a median age of seven years. In relation to sex, 62.5% were males and 37.5% females. In 76.4% of the cases, it affected cats without a breed defined. Restrictive mixed dyspnea and hydrothorax were the main signs or findings of the clinical examination. Sudden death and acute paresis of the pelvic limbs due to aortic thromboembolism have also been described. In HCM, myocardial thickening was observed, with a reduction in the ventricular chamber. Hypertrophy, disarray, and fibrosis of the myofibers were the main histological findings. In RCM, whitish and thickened endocardium was seen in most cases. DCM was characterized by dilated cardiac chambers, and microscopic examination revealed no significant findings. The main extra cardiac lesions revealed pulmonary edema and congestion, hydrothorax and chronic passive congestion of the liver. Cardiomyopathies are important causes of death in cats and should be included in the differential diagnosis of patients with cardio respiratory clinical signs and in cases related to sudden death and acute paresis of the pelvic limbs.(AU)

As cardiomiopatias são consideradas umas das mais importantes causas de insuficiência cardíaca em gatos e são subdivididas morfologicamente em três principais tipos: cardiomiopatia hipertrófica (CMH), dilatada (CMD) e restritiva (CMR). Este trabalho teve como objetivo determinar a frequência e os tipos de cardiomiopatias em gatos diagnosticados no Sul do Brasil, abordando seus aspectos epidemiológicos e patológicos. Foram revisados os laudos de necropsias de gatos e selecionados para o estudo de diagnóstico de cardiomiopatia. Os dados referentes à identificação do animal, o histórico/sinais clínicos e lesões macroscópicas foram revisados e compilados. No período estudado, foram realizadas 1.594 necropsias de gatos, destas, 72 (4,5%) compreenderam diagnóstico de cardiomiopatia. A CMH foi a mais frequente seguida pela CMR e CMD, representando 77,8%, 12,5% e 9,7%, respectivamente. A idade variou de três meses a 18 anos, com a idade mediana de sete anos. Em relação ao sexo, 62,5% eram machos e 37,5% fêmeas. Em 76,4% dos casos, afetou gatos sem raça definida. Dispneia mista restritiva e hidrotórax foram os principais sinais ou achados do exame clínico. Morte súbita e paresia aguda de membros pélvicos em razão do tromboembolismo aórtico também foram descritos. Na CMH, observou-se espessamento do miocárdio, com redução da câmara ventricular. Hipertrofia, desarranjo e fibrose das miofibras foram os principais achados histológicos. Na CMR, visualizou-se endocárdio esbranquiçado e espessado na maioria dos casos. A CMD caracterizou-se pela dilatação das câmaras cardíacas, e sem lesão histológica significante. As principais lesões extracardíacas encontradas foram edema e congestão pulmonares, hidrotórax e congestão passiva crônica do fígado. As cardiomiopatias são causas importantes de morte em gatos, devem ser incluídas no diagnóstico diferencial de pacientes com sinais clínicos cardiorrespiratórios e também em casos relacionados a morte súbita e paresia aguda dos membros pélvicos.(AU)

Investigation of de novo variation in pediatric cardiomyopathy.

Pediatric cardiomyopathies can be caused by variants in genes encoding the sarcomere and cytoskeleton in cardiomyocytes. Variants are typically inherited in an autosomal dominant manner with variable expressivity. De novo variants have been reported, however their overall frequency is largely unknown. We sought to determine the rate of de novo, pathogenic and likely pathogenic (P/LP) variants in children with a diagnosis of hypertrophic, dilated, or restrictive cardiomyopathy (HCM, DCM, or RCM), and to compare disease outcomes between individuals with and without a de novo variant. A retrospective record review identified 126 individuals with HCM (55%), DCM (37%), or RCM (8%) ≤18 years of age who had genetic testing. Overall, 50 (40%) had positive genetic testing and 18% of P/LP variants occurred de novo. The rate of de novo variation in those with RCM (80%) was higher than in those with HCM (9%) or DCM (20%). There was evidence of germline mosaicism in one family with RCM. Individuals with de novo variants were more likely than those without to have a history of arrhythmia (p = .049), sudden cardiac arrest (p = .024), hospitalization (p = .041), and cardiac transplantation (p = .030). The likelihood of de novo variation and impact on family risk and screening should be integrated into genetic counseling.

Clinical, epidemiological and echocardiographic features and prognostic factors in cats with restrictive cardiomyopathy: A retrospective study of 92 cases (2001-2015).

BACKGROUND: Restrictive cardiomyopathy (RCM) is a common primary cardiomyopathy of cats. However, little information is available regarding prognostic variables in large populations of cats with RCM. OBJECTIVES: To characterize the epidemiological, clinical, and echocardiographic features of cats with RCM and to document their survival times and risk factors for cardiac death (CD). ANIMALS: Ninety-two cats with RCM. METHODS: Retrospective study. Diagnosis of RCM was based on echocardiographic and Doppler criteria. Median survival time to CD and adjusted hazard ratios (HR) were estimated by the Kaplan-Meier method and multivariate Cox models, respectively. RESULTS: The feline population (median age [interquartile range], 8.6 years [4.1-12.4]; body weight, 4.0 kg [3.3-4.7]) included 83 cats (90%) with the myocardial RCM form and 9 (10%) with the endomyocardial fibrosis RCM form. Most RCM cats (64/92, 70%) were symptomatic at the time of diagnosis, with dyspnea related to congestive heart failure in 57 of 64 cats (89%). The median survival time of the 69 cats with the myocardial RCM form and available follow-up was 667 days (range, 2-3710 days) considering CD. Independent of age, biatrial enlargement, and arrhythmias, increase of the left atrium (LA)-to-aorta (Ao) ratio (hazard ration [HR], 2.5 per 0.5-unit increase; 95% confidence interval [CI], 1.5-4.2; P < .001) and presence of severe LA enlargement (end-diastolic LA : Ao ≥2; HR, 3.4; 95% CI, 1.3-8.7; P = .01) were significantly associated with shorter time to CD. CONCLUSIONS AND CLINICAL IMPORTANCE: Cardiac death is common in RCM cats, and LA enlargement seems independently associated with decreased survival time in these cats.

Spirometric impairments, cardiovascular outcomes, and noncardiovascular death in older persons.

BACKGROUND: In prior work involving older persons, the reported associations of spirometric impairments with cardiovascular outcomes may have been confounded by age-related changes in lung function. Hence, using more age-appropriate spirometric criteria from the Global Lung Function Initiative (GLI), we have evaluated the associations of spirometric impairments, specifically restrictive-pattern and airflow-obstruction, with cardiovascular death (CV-death) and hospitalization (CV-hospitalization). In these analyses, we also evaluated the competing outcome of noncardiovascular death (nonCV-death) and calculated measures of relative and absolute risk. METHODS: Our study sample was drawn from the Cardiovascular Health Study (CHS), including 4232 community-dwelling white persons aged ≥65 years. Multivariable regression models included the following baseline predictors: GLI-defined restrictive-pattern and airflow-obstruction, age, male gender, obesity, waist circumference, current smoker status, ≥10 pack-years of smoking, hypertension, dyslipidemia, diabetes, and cardiovascular and cerebrovascular disease. Outcomes included adjudicated CV-death, CV-hospitalization, and nonCV-death, ascertained over 10 years of follow-up. Measures of association included hazard ratios (HRs), rate ratios (RRs), and average attributable fraction (AAF), each with 95% confidence intervals. RESULTS: Restrictive-pattern and airflow-obstruction were associated with CV-death (adjusted HRs: 1.57 [1.18, 2.09] and 1.29 [1.04, 1.60]) and with nonCV-death (adjusted HRs: 2.10 [1.63, 2.69] and 1.79 [1.51, 2.12]), respectively. Airflow-obstruction, but not restrictive-pattern, was also associated with CV-hospitalization (adjusted RRs: 1.18 [1.02, 1.36] and 1.20 [0.96, 1.50], respectively). The adjusted AAFs of restrictive-pattern and airflow-obstruction were 1.68% (0.46, 3.06) and 2.35% (0.22, 4.72) for CV-death, and 3.44% (1.97, 5.08) and 7.77% (5.15, 10.60) for nonCV-death, respectively. CONCLUSION: Assessment of GLI-defined spirometric impairments contributes to broad geriatric risk stratifications for both cardiovascular and non-cardiovascular outcomes.

The Cardiomyopathy Registry of the EURObservational Research Programme of the European Society of Cardiology: baseline data and contemporary management of adult patients with cardiomyopathies.

Aims: The Cardiomyopathy Registry of the EURObservational Research Programme is a prospective, observational, and multinational registry of consecutive patients with four cardiomyopathy subtypes: hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), arrhythmogenic right ventricular cardiomyopathy (ARVC), and restrictive cardiomyopathy (RCM). We report the baseline characteristics and management of adults enrolled in the registry. Methods and results: A total of 3208 patients were enrolled by 69 centres in 18 countries [HCM (n = 1739); DCM (n = 1260); ARVC (n = 143); and RCM (n = 66)]. Differences between cardiomyopathy subtypes (P < 0.001) were observed for age at diagnosis, history of familial disease, history of sustained ventricular arrhythmia, use of magnetic resonance imaging or genetic testing, and implantation of defibrillators. When compared with probands, relatives had a lower age at diagnosis (P < 0.001), but a similar rate of symptoms and defibrillators. When compared with the Long-Term phase, patients of the Pilot phase (enrolled in more expert centres) had a more frequent rate of familial disease (P < 0.001), were more frequently diagnosed with a rare underlying disease (P < 0.001), and more frequently implanted with a defibrillator (P = 0.023). Comparing four geographical areas, patients from Southern Europe had a familial disease more frequently (P < 0.001), were more frequently diagnosed in the context of a family screening (P < 0.001), and more frequently diagnosed with a rare underlying disease (P < 0.001). Conclusion: By providing contemporary observational data on characteristics and management of patients with cardiomyopathies, the registry provides a platform for the evaluation of guideline implementation. Potential gaps with existing recommendations are discussed as well as some suggestions for improvement of health care provision in Europe.

Hip and knee arthroplasty are common among patients with transthyretin cardiac amyloidosis, occurring years before cardiac amyloid diagnosis: can we identify affected patients earlier?

Transthyretin cardiac amyloidosis (ATTR-CA) causes a restrictive cardiomyopathy in older adults, often diagnosed at advanced stages when emerging therapies in late phase clinical trials may not have clinical benefit. This investigation aimed to detect clinical entities that may provide more advanced warning of ATTR-CA. Since ATTR preferentially deposits in ligaments, tendons, and articular cartilage, we hypothesized that ATTR-CA patients have a greater prevalence of total hip (THA) and knee (TKA) arthroplasties compared with the general population, and that arthroplasty occurs significantly before ATTR-CA diagnosis. Three-hundred and thirteen patients with cardiac amyloidosis (172 with ATTR-CA, 141 with light-chain) from our institutional database were analyzed and compared to published data in over 300 million patients. Overall, 23.3% of patients with ATTR-CA and 9.2% of patients with light-chain cardiac amyloidosis (AL-CA) underwent lower extremity arthroplasty. Compared to the general population, both THA and TKA were significantly more common among patients with ATTR-CA (THA: RR 5.61, 95% CI 2.25-4.64; TKA: RR 3.32, 95% CI 2.25-4.64) but not those with AL-CA (THA: RR 1.87, 95% CI 0.85-4.08; TKA: RR 1.42, 95% CI 0.73-2.84). On an average, arthroplasty occurred 7.2 years before ATTR-CA diagnosis.

Epidemiological and clinical features of the endomyocardial form of restrictive cardiomyopathy in cats: a review of 41 cases.

Examination of our necropsy records for the period 2005 to 2014 yielded 41 cases of the endomyocardial form of restrictive cardiomyopathy among 327 cats with evidence of heart disease, and here, we reviewed their epidemiological and clinical features. The medical data obtained retrospectively included signalment, presenting complaints, findings of physical examination, results of various diagnostic tests, methods of treatment and survival times. Except for one Chinchilla Persian cat, all were domestic short-haired cats. The mean age at death was 7.3 ± 4.5 years (median, 6 years; range, 4 months to 19 years), and males accounted for 61% (25/41) of the total. Dyspnea was the most common clinical sign, being evident in 83% (35/41) of the cats. Hind limb paresis or paralysis due to aortic thromboembolism was evident in 41% (17/41). Arrhythmias of atrial origin were common. Echocardiography commonly revealed left atrial or biatrial enlargement with severe endocardial thickening of the left ventricle. Most of the affected cats had a poor outcome; the disease duration ranged from 1 to 977 days, and the median survival period was 30 days.

Evaluation of the role of endomyocardial biopsy in 851 patients with unexplained heart failure from 2000-2009.

BACKGROUND: Endomyocardial biopsy (EMB) is often considered when the pathogenesis of heart failure cannot be determined by noninvasive testing. Uncertainty remains about the diagnostic and clinical use of EMB in various clinical scenarios. METHODS AND RESULTS: We examined the characteristics of a cohort of patients with unexplained heart failure who underwent EMB at a tertiary care medical center. We categorized each patient into a clinical scenario as outlined by the 2007 AHA/ACC/ESC guidelines and determined the number of times EMB provided a diagnosis or altered the clinical course. A total of 851 patients underwent EMB from 2000-2009. Overall, 25.5% of EMBs provided a diagnosis and 22.7% of EMBs changed clinical course. Heart failure associated with unexplained restrictive cardiomyopathy was the most common clinical scenario, comprising 33.6% (286/851) of EMBs, and 84 (29.4%) of these EMBs were diagnostic. EMB for unexplained heart failure of <2 weeks duration had a diagnostic yield at 35% (39/109). There were 4 uncommon scenarios where EMB had a high diagnostic and clinical yield. There were 16 complications for an overall rate of 1.9%. CONCLUSIONS: We confirm that EMB is useful in acute onset unexplained cardiomyopathy. We demonstrate a role for EMB in suspected infiltrative disease and in the management of rare clinical scenarios, such as suspected hypersensitivity myocarditis, anthracycline cardiomyopathy, cardiac tumors, and arrhythmogenic right ventricular dysplasia/cardiomyopathy. Our results suggest low use of EMB in chronic heart failure that responds to usual care.

Fibrosis endomiocárdica tropical en nuestro medio / Tropical endomyocardial fibrosis in Spain

La fibrosis endomiocárdica es una miocardiopatía restrictiva de etiología desconocida, prevalente en regiones tropicales. Se caracteriza por la obliteración fibrótica del ápex de uno o ambos ventrículos, que puede extenderse a la cámara de entrada ventricular. Afecta predominantemente a niños y adultos jóvenes. No existe un tratamiento específico y suele tener un pobre pronóstico. No es una entidad frecuente en nuestro medio pero debido a la inmigración estamos presenciando un auge de la misma. Presentamos 4 casos clínicos de fibrosis endomiocárdica en niños diagnosticados y tratados en nuestro medio, y realizamos una revisión de la misma (AU)

Endomyocardial fibrosis is a restrictive cardiomyopathy of unknown etiology prevalent in tropical regions. It is characterized by fibrotic obliteration of the apex of one or both ventricles, which can be extended to the ventricular inlet chamber. It predominantly affects children and young adults. There is no specific treatment and usually has a poor prognosis. It is uncommon in Spain, but due to immigration, it appears to be increasing. Four cases of endomyocardial fibrosis in children diagnosed and treated in Spain are presented, as a well as a review of this disease (AU)

Endomyocardial fibrosis: the first report from Malawi.

Endomyocardial fibrosis (EMF) is a restrictive cardiomyopathy of unknown aetiology previously unreported in Malawi. Six Malawian children (three males) aged between 12 and 16 years who presented with EMF in 2009/10 are described. Five were from the Southern Highlands.

Restrictive cardiomyopathy in childhood.

Depending on the part of the world one lives in, restrictive cardiomyopathy is either one of the rarest forms of cardiomyopathy in childhood, with no cause usually identified, or it is secondary to a poorly understood disease, endomyocardial fibrosis, that is endemic in some populations. Regardless of the underlying cause, the outcome is poor once symptoms develop. This article reviews the definitions, epidemiology, etiologies, genetics, "overlap" phenotypes, clinical presentation, diagnostic evaluation, outcome, and management of pediatric patients with restrictive cardiomyopathy.

Amiloidosis cardiaca: la importancia del manejo multidisciplinario / Cardiac Amyloidosis: the importance of a multidisciplinary approach

La amiloidosis cardiaca causa una miocardiopatía restrictiva de mal pronóstico debida al depósito intersticial de proteína anómala en el miocardio. Esta proteína puede tener diversos orígenes y dar lugar a subtipos de amiloidosis con diferente pronóstico y manejo terapéutico. Los fármacos utilizados habitualmente en la insuficiencia cardiaca son poco eficaces en la amiloidosis, y la indicación de trasplante cardiaco es controvertida porque la enfermedad afecta a múltiples órganos y por la probabilidad de recidiva en el órgano trasplantado. La utilización de nuevas técnicas para la identificación del tipo de amiloidosis, la aparición de procedimientos capaces de impedir o disminuir la producción de amiloide, la posibilidad de monitorizar la respuesta al tratamiento y, sobre todo, la formación de equipos multidisciplinarios capaces de realizar tratamientos combinados, que incluyen el trasplante multiorgánico, han contribuido a mejorar sustancialmente el pronóstico de la enfermedad (AU)

Cardiac amyloidosis is associated with the interstitial deposition of abnormal protein in the myocardium, which can lead to a form of restrictive cardiomyopathy with a poor prognosis. This protein can have a number of different origins, which give rise to various subtypes of amyloidosis that have different prognoses and that require different therapeutic approaches. Drugs commonly used in heart failure have little effect in amyloidosis and the use of heart transplantation is controversial because amyloidosis is a multi-organ disease and because there is a possibility of disease recurrence in the graft. The use of new techniques to identify the specific amyloidosis subtype, the emergence of novel ways of preventing or decreasing amyloid production, the ability to monitor responses to therapy and, above all, the introduction of multidisciplinary teams that can implement a combination of therapies, including multiple organ transplantation, have contributed to a substantial improvement in the prognosis of this disease (AU)

Restrictive cardiomyopathy in India: the story of a vanishing mystery.

Endomyocardial fibrosis is the most common restrictive cardiomyopathy observed world wide. The disease occurs in its classical endemic form in the selected coastal belt in Kerala, India, affecting young people of lower socioeconomic families, and attracting worldwide attention. Geographical identification of high levels of cerium in the soil samples of this coastal belt generated a new "geochemical hypothesis" for endocardial injury. Endocardial calcification, a pathognomonic, but less common feature of the disease, may share the same pathobiology of vascular and valvar calcification occurring in other diseases. Over the past four decades, Kerala has witnessed a tremendous change in its socioeconomic and health status and a corresponding decline in new cases of endomyocardial fibrosis in the younger age group. This decline parallels the decline of rheumatic fever reported earlier in developed nations. Socioeconomic development is, therefore, a major factor in the control of this enigmatic disease.

Prevalence, clinical significance, and genetic basis of hypertrophic cardiomyopathy with restrictive phenotype.

OBJECTIVES: The purpose of this study was to determine the prevalence, clinical significance, and genetic basis of hypertrophic cardiomyopathy (HCM) with "restrictive phenotype" characterized by restrictive filling and minimal or no left ventricular hypertrophy. BACKGROUND: Hypertrophic cardiomyopathy is a heterogeneous myocardial disorder with a broad spectrum of clinical presentation and morphologic features. Recent reports indicated that some patients with restrictive cardiomyopathy, which is an uncommon condition defined by restrictive filling and reduced diastolic volumes with normal or near normal left ventricular wall thickness and contractile function, have features suggestive of HCM with mutations in cardiac troponin I, myocyte disarray at explant/autopsy, and relatives with HCM. Systematic evaluation of the restrictive phenotype in HCM patients has not been performed. METHODS: We evaluated 1,226 patients from 688 consecutive HCM families to identify individuals who fulfilled diagnostic criteria for "restrictive phenotype." RESULTS: Nineteen of 1,226 affected individuals (1.5%) from 16 families (2.3%) had the "restrictive phenotype." During follow up (53.7 +/- 49.2 months), 17 patients (89%) experienced dyspnea (New York Heart Association functional class > or =2). The 5-year survival rate from all-cause mortality, cardiac transplantation, or implantable cardioverter-defibrillator discharge was 56.4%. Mutation analysis for 5 sarcomere genes was feasible in 15 of 16 probands. Mutations were found in 8: 4 in beta-myosin heavy chain, and 4 in cardiac troponin I. CONCLUSIONS: The "restrictive phenotype" in isolation is an uncommon presentation of the clinical spectrum of HCM and is associated with severe limitation and poor prognosis. This phenotype may be associated with beta-myosin heavy chain and cardiac troponin I mutations.

Epidemiology of idiopathic cardiomyopathy in Japan: results from a nationwide survey.

OBJECTIVE: To estimate the total number of patients with idiopathic cardiomyopathy in Japan and the prevalence of the disorder. DESIGN: A nationwide epidemiological survey. SETTING: Hospitals selected randomly from among all hospitals in Japan. PATIENTS: Patients presenting with any of the three types of idiopathic cardiomyopathy: dilated cardiomyopathy, hypertrophic cardiomyopathy, and restrictive cardiomyopathy. MAIN OUTCOME MEASURES: The total number of patients in Japan was estimated using the sampling and response rates in each stratum with respect to hospital size. The second survey was conducted for patients reported in the first survey in order to obtain detailed information, including age, sex, and specific clinical data. RESULTS: Estimated patient totals and 95% confidence intervals (CI) were 17 700 (95% CI 16 500 to 18 800) for dilated cardiomyopathy, 21 900 (95% CI 20 600 to 23 200) for hypertrophic cardiomyopathy, and 300 (95% CI 250 to 350) for restrictive cardiomyopathy. Crude prevalence per 100 000 population was estimated as 14.0 for dilated cardiomyopathy, 17.3 for hypertrophic cardiomyopathy, and 0.2 for restrictive cardiomyopathy; crude incidence per 100 000 person-years was estimated as 3.58, 4.14, and 0.06, respectively. CONCLUSIONS: The total number and prevalence of patients with idiopathic cardiomyopathy in Japan are estimated for the first time in a nationwide survey. The prevalence of dilated cardiomyopathy in Japan appears to be about half that of Western populations, while that of hypertrophic cardiomyopathy is about the same.

Hypertrophic and restrictive cardiomyopathies in the elderly.

Congestive heart failure (CHF) increases with age, but most CHF in the elderly is due to diastolic dysfunction with preserved systolic function. The etiology, pathophysiology, diagnosis, natural history, and treatment of hypertrophic and restrictive cardiomyopathies in the elderly are discussed as a paradigm for CHF with normal systolic function. Hypertrophic obstructive and hypertensive hypertrophic cardiomyopathies are compared and contrasted. As an example of a restrictive cardiomyopathy, the various types of amyloidosis and their clinical import in older patients are covered.