RESUMO
BACKGROUND: Rheumatic heart disease affects more than 40.5 million people worldwide and results in 306,000 deaths annually. Echocardiographic screening detects rheumatic heart disease at an early, latent stage. Whether secondary antibiotic prophylaxis is effective in preventing progression of latent rheumatic heart disease is unknown. METHODS: We conducted a randomized, controlled trial of secondary antibiotic prophylaxis in Ugandan children and adolescents 5 to 17 years of age with latent rheumatic heart disease. Participants were randomly assigned to receive either injections of penicillin G benzathine (also known as benzathine benzylpenicillin) every 4 weeks for 2 years or no prophylaxis. All the participants underwent echocardiography at baseline and at 2 years after randomization. Changes from baseline were adjudicated by a panel whose members were unaware of the trial-group assignments. The primary outcome was echocardiographic progression of latent rheumatic heart disease at 2 years. RESULTS: Among 102,200 children and adolescents who had screening echocardiograms, 3327 were initially assessed as having latent rheumatic heart disease, and 926 of the 3327 subsequently received a definitive diagnosis on the basis of confirmatory echocardiography and were determined to be eligible for the trial. Consent or assent for participation was provided for 916 persons, and all underwent randomization; 818 participants were included in the modified intention-to-treat analysis, and 799 (97.7%) completed the trial. A total of 3 participants (0.8%) in the prophylaxis group had echocardiographic progression at 2 years, as compared with 33 (8.2%) in the control group (risk difference, -7.5 percentage points; 95% confidence interval, -10.2 to -4.7; P<0.001). Two participants in the prophylaxis group had serious adverse events that were attributable to receipt of prophylaxis, including one episode of a mild anaphylactic reaction (representing <0.1% of all administered doses of prophylaxis). CONCLUSIONS: Among children and adolescents 5 to 17 years of age with latent rheumatic heart disease, secondary antibiotic prophylaxis reduced the risk of disease progression at 2 years. Further research is needed before the implementation of population-level screening can be recommended. (Funded by the Thrasher Research Fund and others; GOAL ClinicalTrials.gov number, NCT03346525.).
Assuntos
Antibacterianos/uso terapêutico , Antibioticoprofilaxia , Penicilina G Benzatina/uso terapêutico , Cardiopatia Reumática/tratamento farmacológico , Adolescente , Antibacterianos/administração & dosagem , Criança , Pré-Escolar , Progressão da Doença , Ecocardiografia , Feminino , Humanos , Injeções Intramusculares , Análise de Intenção de Tratamento , Infecção Latente/tratamento farmacológico , Masculino , Programas de Rastreamento , Penicilina G Benzatina/administração & dosagem , Cardiopatia Reumática/diagnóstico por imagem , UgandaRESUMO
The global burden of rheumatic heart disease continues to be significant although it is largely limited to poor and marginalized populations. In most endemic regions, affected patients present with heart failure. This statement will seek to examine the current state-of-the-art recommendations and to identify gaps in diagnosis and treatment globally that can inform strategies for reducing disease burden. Echocardiography screening based on World Heart Federation echocardiographic criteria holds promise to identify patients earlier, when prophylaxis is more likely to be effective; however, several important questions need to be answered before this can translate into public policy. Population-based registries effectively enable optimal care and secondary penicillin prophylaxis within available resources. Benzathine penicillin injections remain the cornerstone of secondary prevention. Challenges with penicillin procurement and concern with adverse reactions in patients with advanced disease remain important issues. Heart failure management, prevention, early diagnosis and treatment of endocarditis, oral anticoagulation for atrial fibrillation, and prosthetic valves are vital therapeutic adjuncts. Management of health of women with unoperated and operated rheumatic heart disease before, during, and after pregnancy is a significant challenge that requires a multidisciplinary team effort. Patients with isolated mitral stenosis often benefit from percutaneous balloon mitral valvuloplasty. Timely heart valve surgery can mitigate the progression to heart failure, disability, and death. Valve repair is preferable over replacement for rheumatic mitral regurgitation but is not available to the vast majority of patients in endemic regions. This body of work forms a foundation on which a companion document on advocacy for rheumatic heart disease has been developed. Ultimately, the combination of expanded treatment options, research, and advocacy built on existing knowledge and science provides the best opportunity to address the burden of rheumatic heart disease.
Assuntos
American Heart Association , Cardiopatia Reumática/diagnóstico , Cardiopatia Reumática/metabolismo , Cardiopatia Reumática/prevenção & controle , Cardiopatia Reumática/fisiopatologia , Efeitos Psicossociais da Doença , Feminino , Humanos , Masculino , Guias de Prática Clínica como Assunto , Estados UnidosRESUMO
BACKGROUND: Rheumatic heart disease (RHD) remains the leading cause of cardiac-related deaths and disability in children and young adults worldwide. In The Gambia, the RHD burden is thought to be high although no data are available and no control programme is yet implemented. We conducted a pilot study to generate baseline data on the clinical and valvular characteristics of RHD patients at first presentation, adherence to penicillin prophylaxis and the evolution of lesions over time. METHODS: All patients registered with acute rheumatic fever (ARF) or RHD at two Gambian referral hospitals were invited for a clinical review that included echocardiography. In addition, patients were interviewed about potential risk factors, disease history, and treatment adherence. All clinical and echocardiography information at first presentation and during follow-up was retrieved from medical records. RESULTS: Among 255 registered RHD patients, 35 had died, 127 were examined, and 111 confirmed RHD patients were enrolled, 64% of them females. The case fatality rate in 2017 was estimated at 19.6%. At first presentation, median age was 13 years (IQR [9; 18]), 57% patients had late stage heart failure, and 84.1% a pathological heart murmur. Although 53.2% of them reported history of recurrent sore throat, only 32.2% of them had sought medical treatment. A history suggestive of ARF was reported by 48.7% patients out of whom only 15.8% were adequately treated. Two third of the patients (65.5%) to whom it was prescribed were fully adherent to penicillin prophylaxis. Progressive worsening and repeated hospitalisation was experienced by 46.8% of the patients. 17 patients had cardiac surgery, but they represented only 18.1% of the 94 patients estimated eligible for cardiac surgery. CONCLUSION: This study highlights for the first time in The Gambia the devastating consequences of RHD on the health of adolescents and young adults. Our findings suggest a high burden of disease that remains largely undetected and without appropriate secondary prophylaxis. There is a need for the urgent implementation of an effective national RHD control programto decrease the unacceptably high mortality rate, improve case detection and management, and increase community awareness of this disease.
Assuntos
Antibacterianos/administração & dosagem , Penicilinas/administração & dosagem , Cardiopatia Reumática/prevenção & controle , Prevenção Secundária , Adolescente , Antibacterianos/efeitos adversos , Criança , Pré-Escolar , Progressão da Doença , Ecocardiografia Doppler , Feminino , Gâmbia/epidemiologia , Humanos , Masculino , Adesão à Medicação , Penicilinas/efeitos adversos , Projetos Piloto , Cardiopatia Reumática/diagnóstico por imagem , Cardiopatia Reumática/mortalidade , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
The diagnosis of cardiac tumors has been dramatically improved by modern cardiac imaging. In cases presenting with right intracavitary mass the diagnosis can rely on right endomyocardial biopsy. We report here a case of right ventricle tumor whose diagnosis was established as a colonic metastasis by using right endomyocardial biopsy.
Assuntos
Neoplasias do Colo , Neoplasias Cardíacas , Biópsia , Neoplasias do Colo/diagnóstico , Neoplasias Cardíacas/diagnóstico , Ventrículos do Coração , Humanos , MiocárdioRESUMO
AIMS: To identify independent electrocardiogram (ECG) predictors of long-term clinical outcome based on standardized analysis of the surface ECG in a large multicentre cohort of patients with sarcomeric hypertrophic cardiomyopathy (HCM). METHODS AND RESULTS: Retrospective observational study from the REMY French HCM clinical research observatory. Primary endpoint was a composite of all-cause mortality, major non-fatal arrhythmic events, hospitalization for heart failure (HF), and stroke. Secondary endpoints were components of the primary endpoint. Uni- and multivariable Cox proportional hazard regression analysis was performed to identify independent predictors. Among 994 patients with HCM, only 1.8% had a strictly normal baseline ECG. The most prevalent abnormalities were inverted T waves (63.7%), P-wave abnormalities (30.4%), and abnormal Q waves (25.5%). During a mean follow-up of 4.0 ± 2.0 years, a total of 272 major cardiovascular events occurred in 217 patients (21.8%): death or heart transplant in 98 (9.8%), major arrhythmic events in 40 (4.0%), HF hospitalization in 115 (11.6%), and stroke in 23 (2.3%). At multivariable analysis using ECG covariates, prolonged QTc interval, low QRS voltage, and PVCs of right bundle branch block pattern predicted worse outcome, but none remained independently associated with the primary endpoint after adjustment on main demographic and clinical variables. For secondary endpoints, abnormal Q waves independently predicted all-cause death [hazard ratio (HR) 2.35, 95% confidence interval (CI) 1.23-4.47; P = 0.009] and prolonged QTc the risk of HF hospitalization (HR 1.006, 95% CI 1.001-1.011; P = 0.024). CONCLUSION: The 12-lead surface ECG has no independent value to predict the primary outcome measure in patients with HCM. The 12-lead surface ECG has been widely used as a screening tool in HCM but its prognostic value remains poorly known. The value of baseline surface ECG to predict long-term clinical outcomes was studied in a cohort of 994 patients with sarcomeric HCM. The surface ECG has no significant additional value to predict outcome in this patient population.
Assuntos
Cardiomiopatia Hipertrófica , Insuficiência Cardíaca , Cardiomiopatia Hipertrófica/complicações , Cardiomiopatia Hipertrófica/diagnóstico , Eletrocardiografia , Humanos , Prognóstico , Estudos Retrospectivos , Fatores de Risco , SarcômerosRESUMO
BACKGROUND: The evaluation process of French medical students will evolve in the next few years in order to improve assessment validity. Script concordance testing (SCT) offers the possibility to assess medical knowledge alongside clinical reasoning under conditions of uncertainty. In this study, we aimed at comparing the SCT scores of a large cohort of undergraduate medical students, according to the experience level of the reference panel. METHODS: In 2019, the authors developed a 30-item SCT and sent it to experts with varying levels of experience. Data analysis included score comparisons with paired Wilcoxon rank sum tests and concordance analysis with Bland & Altman plots. RESULTS: A panel of 75 experts was divided into three groups: 31 residents, 21 non-experienced physicians (NEP) and 23 experienced physicians (EP). Among each group, random samples of N = 20, 15 and 10 were selected. A total of 985 students from nine different medical schools participated in the SCT examination. No matter the size of the panel (N = 20, 15 or 10), students' SCT scores were lower with the NEP group when compared to the resident panel (median score 67.1 vs 69.1, p < 0.0001 if N = 20; 67.2 vs 70.1, p < 0.0001 if N = 15 and 67.7 vs 68.4, p < 0.0001 if N = 10) and with EP compared to NEP (65.4 vs 67.1, p < 0.0001 if N = 20; 66.0 vs 67.2, p < 0.0001 if N = 15 and 62.5 vs 67.7, p < 0.0001 if N = 10). Bland & Altman plots showed good concordances between students' SCT scores, whatever the experience level of the expert panel. CONCLUSIONS: Even though student SCT scores differed statistically according to the expert panels, these differences were rather weak. These results open the possibility of including less-experienced experts in panels for the evaluation of medical students.
Assuntos
Estudantes de Medicina , Competência Clínica , Avaliação Educacional , Humanos , Estatísticas não Paramétricas , IncertezaRESUMO
BACKGROUND: Screening echocardiography has emerged as a potentially powerful tool for early diagnosis of rheumatic heart disease (RHD). The utility of screening echocardiography hinges on the rate of RHD progression and the ability of penicillin prophylaxis to improve outcome. We report the longitudinal outcomes of a cohort of children with latent RHD and identify risk factors for unfavorable outcomes. METHODS: This was a prospective natural history study conducted under the Ugandan RHD registry. Children with latent RHD and ≥1 year of follow-up were included. All echocardiograms were re-reviewed by experts (2012 World Heart Federation criteria) for inclusion and evidence of change. Bi- and multivariable logistic regression, Kaplan-Meier analysis, and Cox proportional hazards models, as well, were developed to search for risk factors for unfavorable outcome and compare progression-free survival between those treated and not treated with penicillin. Propensity and other matching methods with sensitivity analysis were implemented for the evaluation of the penicillin effect. RESULTS: Blinded review confirmed 227 cases of latent RHD: 164 borderline and 63 definite (42 mild, 21 moderate/severe). Median age at diagnosis was 12 years and median follow-up was 2.3 years (interquartile range, 2.0-2.9). Penicillin prophylaxis was prescribed in 49.3% with overall adherence of 84.7%. Of children with moderate-to-severe definite RHD, 47.6% had echocardiographic progression (including 2 deaths), and 9.5% had echocardiographic regression. Children with mild definite and borderline RHD showed 26% and 9.8% echocardiographic progression and 45.2% and 46.3% echocardiographic improvement, respectively. Of those with mild definite RHD or borderline RHD, more advanced disease category, younger age, and morphological mitral valve features were risk factors for an unfavorable outcome. CONCLUSIONS: Latent RHD is a heterogeneous diagnosis with variable disease outcomes. Children with moderate to severe latent RHD have poor outcomes. Children with both borderline and mild definite RHD are at substantial risk of progression. Although long-term outcome remains unclear, the initial change in latent RHD may be evident during the first 1 to 2 years following diagnosis. Natural history data are inherently limited, and a randomized clinical trial is needed to definitively determine the impact of penicillin prophylaxis on the trajectory of latent RHD.
Assuntos
Ecocardiografia , Cardiopatia Reumática/diagnóstico por imagem , Adolescente , Fatores Etários , Antibacterianos/uso terapêutico , Criança , Progressão da Doença , Intervalo Livre de Doença , Diagnóstico Precoce , Feminino , Humanos , Estimativa de Kaplan-Meier , Modelos Logísticos , Masculino , Análise Multivariada , Razão de Chances , Penicilinas/uso terapêutico , Valor Preditivo dos Testes , Pontuação de Propensão , Modelos de Riscos Proporcionais , Estudos Prospectivos , Sistema de Registros , Cardiopatia Reumática/tratamento farmacológico , Cardiopatia Reumática/mortalidade , Cardiopatia Reumática/fisiopatologia , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , UgandaRESUMO
Tropical endomyocardial fibrosis (EMF) is a neglected disease of poverty that afflicts rural populations in tropical low-income countries, with some certain high-prevalence areas. Tropical EMF is characterized by the deposition of fibrous tissue in the endomyocardium, leading to restrictive physiology. Since the first descriptions in Uganda in 1948, high-frequency areas for EMF have included Africa, Asia, and South America. Although there is no clear consensus on a unified hypothesis, it seems likely that dietary, environmental, and infectious factors may combine in a susceptible individual to give rise to an inflammatory process leading to endomyocardial damage and scar formation. The natural history of EMF includes an active phase with recurrent flare-ups of inflammation evolving to a chronic phase leading to restrictive heart failure. In the chronic phase, biventricular involvement is the most common presentation, followed by isolated right-sided heart disease. Marked ascites out of proportion to peripheral edema usually develops as a typical feature of EMF. EMF carries a very poor prognosis. In addition to medical management of heart failure, early open heart surgery (endocardectomy and valve repair/replacement) appears to improve outcomes to some extent; however, surgery is technically challenging and not available in most endemic areas. Increased awareness among health workers and policy makers is the need of the hour for the unhindered development of efficient preventive and therapeutic strategies.
Assuntos
Fibrose Endomiocárdica/patologia , Fibrose Endomiocárdica/epidemiologia , Humanos , Prevalência , PrognósticoRESUMO
BACKGROUND: Sarcomeric gene mutations cause hypertrophic cardiomyopathy (HCM). In gene mutation carriers without left ventricular (LV) hypertrophy (G + LVH-), subclinical imaging biomarkers are recognized as predictors of overt HCM, consisting of anterior mitral valve leaflet elongation, myocardial crypts, hyperdynamic LV ejection fraction, and abnormal apical trabeculation. Reverse curvature of the interventricular septum (into the LV) is characteristic of overt HCM. We aimed to assess LV septal convexity in subclinical HCM. METHODS: Cardiovascular magnetic resonance was performed on 36 G + LVH- individuals (31 ± 14 years, 33 % males) with a pathogenic sarcomere mutation, and 36 sex and age-matched healthy controls (33 ± 12 years, 33 % males). Septal convexity (SCx) was measured in the apical four chamber view perpendicular to a reference line connecting the mid-septal wall at tricuspid valve insertion level and the apical right ventricular insertion point. RESULTS: Septal convexity was increased in G + LVH- compared to controls (maximal distance of endocardium to reference line: 5.0 ± 2.5 mm vs. 1.6 ± 2.4 mm, p ≤ 0.0001). Expected findings occurred in G + LVH- individuals: longer anterior mitral valve leaflet (23.5 ± 3.0 mm vs. 19.9 ± 3.1 mm, p ≤ 0.0001), higher relative wall thickness (0.31 ± 0.05 vs. 0.29 ± 0.04, p ≤ 0.05), higher LV ejection fraction (70.8 ± 4.3 % vs. 68.3 ± 4.4 %, p ≤ 0.05), and smaller LV end-systolic volume index (21.4 ± 4.4 ml/m(2) vs. 23.7 ± 5.8 ml/m(2), p ≤ 0.05). Other morphologic measurements (LV angles, sphericity index, and eccentricity index) were not different between G + LVH- and controls. CONCLUSIONS: Septal convexity is an additional previously undescribed feature of subclinical HCM.
Assuntos
Cardiomiopatia Hipertrófica/diagnóstico , Ventrículos do Coração/patologia , Imagem Cinética por Ressonância Magnética , Adolescente , Adulto , Doenças Assintomáticas , Cardiomiopatia Hipertrófica/genética , Cardiomiopatia Hipertrófica/patologia , Cardiomiopatia Hipertrófica/fisiopatologia , Estudos de Casos e Controles , Feminino , Marcadores Genéticos , Predisposição Genética para Doença , Ventrículos do Coração/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Fenótipo , Valor Preditivo dos Testes , Volume Sistólico , Função Ventricular Esquerda , Adulto JovemRESUMO
AIMS: To assess long-term outcomes and the management of critical left-sided infective endocarditis (IE) and evaluate the impact of surgery. METHODS AND RESULTS: Among the 198 patients included prospectively for IE across 33 adult intensive care units (ICU) in France from 1 April 2007 to 1 October 2008, 137 (69%) were dead at a median follow-up time of 59.5 months. Characteristics significantly associated with mortality were: Sepsis-related Organ-Failure Assessment (SOFA) score at ICU admission [Hazard ratio (HR), 95% Confidence Interval (CI) of 1.43 (0.79-2.59) for SOFA 5-9; 2.01 (1.05-3.85) for SOFA 10-14; 3.53 (1.75-7.11) for SOFA 15-20; reference category SOFA 0-4; P = 0.003]; prosthetic mechanical valve IE [HR 2.01; 95% CI 1.09-3.69, P = 0.025]; vegetation size ≥15 mm [HR 1.64; 95% CI 1.03-2.63, P = 0.038]; and cardiac surgery [HR (95%CI), 0.33 (0.16-0.67) for surgery ≤1 day after IE diagnosis; 0.61 (0.29-1.26) for surgery 2-7 days after IE diagnosis; 0.42 (0.21-0.83) for surgery >7 days after IE diagnosis; reference category no surgery; P = 0.005]. One hundred and three (52%) patients underwent cardiac surgery after a median time of 6 (16) days. Independent predictors of surgical intervention on multivariate analysis were: age ≤60 years [Odds ratio (OR) 5.30; 95% CI (2.46-11.41), P < 0.01], heart failure [OR 3.27; 95% CI (1.03-10.35), P = 0.04], cardiogenic shock [OR 3.31; 95% CI (1.47-7.46), P = 0.004], septic shock [OR 0.25; 95% CI (0.11-0.59), P = 0.002], immunosuppression [OR 0.15; 95% CI (0.04-0.55), P = 0.004], and diagnosis before or within 24 h of ICU admission [OR 2.81; 95% CI (1.14-6.95), P = 0.025]. SOFA score calculated the day of surgery was the only independently associated factor with long-term mortality [HR (95% CI) 1.59 (0.77-3.28) for SOFA 5-9; 3.56 (1.71-7.38) for SOFA 10-14; 11.58 (4.02-33.35) for SOFA 15-20; reference category SOFA 0-4; P < 0.0001]. Surgical timing was not associated with post-operative outcomes. Of the 158 patients with a theoretical indication for surgery, the 58 deemed not fit had a 95% mortality rate. CONCLUSION: Mortality in patients with critical IE remains unacceptably high. Factors associated with long-term outcomes are the severity of multiorgan failure, prosthetic mechanical valve IE, vegetation size ≥15 mm, and surgical treatment. Up to one-third of potential candidates do not undergo surgery and these patients experience extremely high mortality rates. The strongest independent predictor of post-operative mortality is the pre-operative multiorgan failure score while surgical timing does not seem to impact on outcomes.
Assuntos
Endocardite/cirurgia , Adolescente , Adulto , Idoso , Estado Terminal , Estudos Transversais , Tratamento de Emergência/mortalidade , Tratamento de Emergência/estatística & dados numéricos , Endocardite/mortalidade , Feminino , França/epidemiologia , Doenças das Valvas Cardíacas/mortalidade , Doenças das Valvas Cardíacas/cirurgia , Implante de Prótese de Valva Cardíaca/mortalidade , Implante de Prótese de Valva Cardíaca/estatística & dados numéricos , Humanos , Terapia de Imunossupressão/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento , Adulto JovemAssuntos
Antineoplásicos Imunológicos/efeitos adversos , Carcinoma de Células Renais/tratamento farmacológico , Ipilimumab/efeitos adversos , Neoplasias Renais/tratamento farmacológico , Miocardite/induzido quimicamente , Nivolumabe/efeitos adversos , Carcinoma de Células Renais/cirurgia , Quimioterapia Adjuvante , Humanos , Ipilimumab/uso terapêutico , Neoplasias Renais/cirurgia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Miocardite/diagnóstico por imagem , Miocardite/imunologia , Nivolumabe/uso terapêuticoRESUMO
BACKGROUND: Data on the management of patients with cancer presenting with sudden cardiac arrest (SCA) are scarce. We aimed to assess the characteristics and outcomes of SCA according to cancer history. METHODS: Prospective, population-based registry including every out-of-hospital SCA in adults in Paris and its suburbs, between 2011 and 2019, with a specific focus on patients with cancer. RESULTS: Out of 4069 patients who had SCA admitted alive in hospital, 207 (5.1%) had current or past medical history of cancer. Patients with cancer were older (69.2 vs 59.3 years old, p<0.001), more often women (37.2% vs 28.0%, p=0.006) with more frequent underlying cardiovascular disease (41.1% vs 32.5%, p=0.01). SCA happened more often with a non-shockable rhythm (62.6% vs 43.1%, p<0.001) with no significant difference regarding witness presence and cardiopulmonary resuscitation (CPR) performed. Cardiac causes were less frequent among patients with cancer (mostly acute coronary syndromes, 25.5% vs 46.8%, p<0.001) and had more respiratory causes (pulmonary embolism and hypoxaemia in 34.2% vs 10.8%, p<0.001). Still, no difference regarding in-hospital survival was found after SCA in patients with cancer versus other patients (26.2% vs 29.8%, respectively, p=0.27). Public location, CPR by witness and shockable rhythm were independent predictors of in-hospital survival after SCA in the cancer group. CONCLUSIONS: One in 20 SCA occurs in patients with a history of cancer, yet with fewer cardiac causes than in patients who are cancer-free. Still, in-hospital outcomes remain similar even in patients with known cancer. Cancer history should therefore not compromise the initiation of resuscitation in the context of SCA.
Assuntos
Reanimação Cardiopulmonar , Neoplasias , Sistema de Registros , Humanos , Feminino , Neoplasias/complicações , Neoplasias/epidemiologia , Masculino , Pessoa de Meia-Idade , Paris/epidemiologia , Idoso , Estudos Prospectivos , Reanimação Cardiopulmonar/métodos , Parada Cardíaca Extra-Hospitalar/terapia , Parada Cardíaca Extra-Hospitalar/epidemiologia , Parada Cardíaca Extra-Hospitalar/mortalidade , Parada Cardíaca Extra-Hospitalar/etiologia , Fatores de Risco , Morte Súbita Cardíaca/epidemiologia , Morte Súbita Cardíaca/etiologia , Taxa de Sobrevida/tendênciasRESUMO
BACKGROUND: Immune checkpoint inhibitors (ICIs) can induce cardiovascular toxicities. OBJECTIVES: To prospectively assess the incidence of major cardiovascular events (MACE) on ICIs in solid cancer patients: myocarditis, pericarditis, acute coronary syndrome, heart failure, high-degree conduction abnormalities or sustained ventricular arrhythmias, or cardiovascular death at 6 weeks (early MACE), including asymptomatic clinical changes by an independent adjudication committee using current recommended diagnostic criteria. The secondary objective was the incidence of the above-mentioned events adding atrial fibrillation (AF) at 6 months (late MACE). RESULTS: Participants underwent pre-ICIs and repeated multimodality cardiac imaging (echocardiogram, cardiac magnetic resonance (CMR)), serum biomarkers (ultrasensitive troponin I), and rhythm surveillance (ambulatory ECG monitoring) at 6 weeks and 6 months. Forty-nine patients (38 (77.6%) male; mean age 64.3 (SD 11.0) years old) were included (June 2020-December 2021). Early MACE were observed in 9 (18.4%) patients at mean 40.1 (SD 5.9) days, with heart failure (HF) in 5 (10.2%), ventricular arrhythmias, or new conduction disorders in 4 (8.2%) patients. History of AF (HR 4.49 (CI 1.11-18.14), P = 0.035) predicted early MACE. At 6 months follow-up, 18 MACE were observed in 15/49 (31%) patients, with 6 (12.2%) HF events, 5 (10.2%) significant ventricular arrhythmias, or conduction disorders, and 4 (8.2%) AF. There was a significant decline in LVEF (P < 0.001) in patients with no MACE (P = 0.003) or HF (P = 0.0028). Higher creatinine at inclusion (HR 0.99 [0.98-1.00], P = 0.006) predicted HF on multivariate analysis. There were no significant T1 or T2 mapping changes in our study cohort on repeated CMR. CONCLUSIONS: Cardiotoxicity on ICIs is more frequent than previously described when using a thorough detection strategy, consisting mainly in HF and asymptomatic rhythm disorders.
Assuntos
Inibidores de Checkpoint Imunológico , Neoplasias , Humanos , Masculino , Feminino , Inibidores de Checkpoint Imunológico/efeitos adversos , Pessoa de Meia-Idade , Estudos Prospectivos , Neoplasias/tratamento farmacológico , Incidência , Idoso , Cardiotoxicidade , Imagem Cinética por Ressonância Magnética/métodos , Imagem Multimodal/métodos , Ecocardiografia/métodos , Eletrocardiografia Ambulatorial , Fatores de Risco , Seguimentos , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologiaRESUMO
BACKGROUND: Secondary antibiotic prophylaxis reduces progression of latent rheumatic heart disease (RHD) but not all children benefit. Improved risk stratification could refine recommendations following positive screening. We aimed to evaluate the performance of a previously developed echocardiographic risk score to predict mid-term outcomes among children with latent RHD. METHODS: We included children who completed the GOAL, a randomized trial of secondary antibiotic prophylaxis among children with latent RHD in Uganda. Outcomes were determined by a 4-member adjudication panel. We applied the point-based score, consisting of 5 variables (mitral valve (MV) anterior leaflet thickening (3 points), MV excessive leaflet tip motion (3 points), MV regurgitation jet length ≥ 2 cm (6 points), aortic valve focal thickening (4 points) and any aortic regurgitation (5 points)), to panel results. Unfavorable outcome was defined as progression of diagnostic category (borderline to definite, mild definite to moderate/severe definite), worsening valve involvement or remaining with mild definite RHD. RESULTS: 799 patients (625 borderline and 174 definite RHD) were included, with median follow-up of 24 months. At total 116 patients (14.5%) had unfavorable outcome per study criteria, 57.8% not under prophylaxis. The score was strongly associated with unfavorable outcome (HR = 1.26, 95% CI 1.16-1.37, p < 0.001). Unfavorable outcome rates in low (≤6 points), intermediate (7-9 points) and high-risk (≥10 points) children at follow-up were 11.8%, 30.4%, and 42.2%, (p < 0.001) respectively (C-statistic = 0.64 (95% CI 0.59-0.69)). CONCLUSIONS: The simple risk score provided an accurate prediction of RHD status at 2-years, showing a good performance in a population with milder RHD phenotypes.
Assuntos
Doenças das Valvas Cardíacas , Insuficiência da Valva Mitral , Cardiopatia Reumática , Criança , Humanos , Antibacterianos/uso terapêutico , Ecocardiografia/métodos , Programas de Rastreamento/métodos , Prevalência , Cardiopatia Reumática/diagnóstico por imagem , Cardiopatia Reumática/epidemiologia , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Rheumatic heart disease (RHD) is an important and preventable cause of morbidity and mortality among children and young adults in low-income and middle-income countries, as well as among certain at-risk populations living in high-income countries. The 2012 World Heart Federation echocardiographic criteria provided a standardized approach for the identification of RHD and facilitated an improvement in early case detection. The 2012 criteria were used to define disease burden in numerous epidemiological studies, but researchers and clinicians have since highlighted limitations that have prompted a revision. In this updated version of the guidelines, we incorporate evidence from a scoping review, an expert panel and end-user feedback and present an approach for active case finding for RHD, including the use of screening and confirmatory criteria. These guidelines also introduce a new stage-based classification for RHD to identify the risk of disease progression. They describe the latest evidence and recommendations on population-based echocardiographic active case finding and risk stratification. Secondary antibiotic prophylaxis, echocardiography equipment and task sharing for RHD active case finding are also discussed. These World Heart Federation 2023 guidelines provide a concise and updated resource for clinical and research applications in RHD-endemic regions.
Assuntos
Cardiopatia Reumática , Criança , Adulto Jovem , Humanos , Cardiopatia Reumática/diagnóstico por imagem , Cardiopatia Reumática/epidemiologia , Ecocardiografia , Programas de Rastreamento , Antibacterianos/uso terapêutico , Fatores de Risco , PrevalênciaRESUMO
The advent of immunological therapies has revolutionized the treatment of solid and haematological cancers over the last decade. Licensed therapies which activate the immune system to target cancer cells can be broadly divided into two classes. The first class are antibodies that inhibit immune checkpoint signalling, known as immune checkpoint inhibitors (ICIs). The second class are cell-based immune therapies including chimeric antigen receptor T lymphocyte (CAR-T) cell therapies, natural killer (NK) cell therapies, and tumour infiltrating lymphocyte (TIL) therapies. The clinical efficacy of all these treatments generally outweighs the risks, but there is a high rate of immune-related adverse events (irAEs), which are often unpredictable in timing with clinical sequalae ranging from mild (e.g. rash) to severe or even fatal (e.g. myocarditis, cytokine release syndrome) and reversible to permanent (e.g. endocrinopathies).The mechanisms underpinning irAE pathology vary across different irAE complications and syndromes, reflecting the broad clinical phenotypes observed and the variability of different individual immune responses, and are poorly understood overall. Immune-related cardiovascular toxicities have emerged, and our understanding has evolved from focussing initially on rare but fatal ICI-related myocarditis with cardiogenic shock to more common complications including less severe ICI-related myocarditis, pericarditis, arrhythmias, including conduction system disease and heart block, non-inflammatory heart failure, takotsubo syndrome and coronary artery disease. In this scientific statement on the cardiovascular toxicities of immune therapies for cancer, we summarize the pathophysiology, epidemiology, diagnosis, and management of ICI, CAR-T, NK, and TIL therapies. We also highlight gaps in the literature and where future research should focus.
RESUMO
Rheumatic heart disease, often neglected by media and policy makers, is a major burden in developing countries where it causes most of the cardiovascular morbidity and mortality in young people, leading to about 250,000 deaths per year worldwide. The disease results from an abnormal autoimmune response to a group A streptococcal infection in a genetically susceptible host. Acute rheumatic fever--the precursor to rheumatic heart disease--can affect different organs and lead to irreversible valve damage and heart failure. Although penicillin is effective in the prevention of the disease, treatment of advanced stages uses up a vast amount of resources, which makes disease management especially challenging in emerging nations. Guidelines have therefore emphasised antibiotic prophylaxis against recurrent episodes of acute rheumatic fever, which seems feasible and cost effective. Early detection and targeted treatment might be possible if populations at risk for rheumatic heart disease in endemic areas are screened. In this setting, active surveillance with echocardiography-based screening might become very important.
Assuntos
Cardiopatia Reumática , Criança , Ecocardiografia , Humanos , Febre Reumática/diagnóstico , Cardiopatia Reumática/diagnóstico , Cardiopatia Reumática/epidemiologia , Cardiopatia Reumática/fisiopatologia , Cardiopatia Reumática/prevenção & controleRESUMO
Cancer-associated venous thrombosis (CAT) is a common, multifactor event known to complicate the course of cancer and jeopardize a patient's prognosis. The current guidelines regarding the prevention of CAT are sometimes considered insufficiently precise about specific situations, or are poorly applied. The expected benefits of thromboprophylaxis are balanced by the risk of major bleeding induced by anticoagulation, which implies a need to accurately identify ambulatory patients at high risk of thrombosis or hemorrhage. The Khorana score is commonly used for this, but is limited by the non-reproducibility of predicted performance across cancer types, and by the fact that antitumor treatment and cardiovascular risks are not included. The COMPASS-CAT score, which includes those two aspects, was found to be a more accurate predictor of venous thromboembolism in patients with lung cancer, and to better distinguish between patients at low or high risk of thrombosis. The frailty of patients with cancer is also a major issue, and should be taken into account when thromboprophylaxis is considered. According to current guidelines, CAT prophylaxis should be considered for hospitalized patients, those for whom surgery is scheduled, or those with pancreatic cancers. In ambulatory patients, decisions should be made according to patient, cancer and antitumoral treatment characteristics. Low molecular weight heparin is the gold standard of CAT prophylaxis. Despite increased risks of bleeding or drug-drug interactions in cancer patients, direct oral anticoagulants could be alternate options for high-risk ambulatory patients that should be accompanied by a careful global analysis of benefits, harms, and patient preferences.