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BACKGROUND: We aimed to evaluate the effect of dapagliflozin on short-term changes in hemoglobin in patients with stable heart failure with reduced ejection fraction (HFrEF) and whether these changes mediated the effect of dapagliflozin on functional capacity, quality of life and NT-proBNP levels. METHODS: This is an exploratory analysis of a randomized, double-blinded clinical trial in which 90 stable patients with HFrEF were randomly allocated to dapagliflozin or placebo to evaluate short-term changes in peak oxygen consumption (peak VO2) (NCT04197635). This substudy evaluated 1- and 3-month changes in hemoglobin levels and whether these changes mediated the effects of dapagliflozin on peak VO2, Minnesota Living-With-Heart-Failure test (MLHFQ) and NT-proBNP levels. RESULTS: At baseline, mean hemoglobin levels were 14.3 ± 1.7 g/dL. Hemoglobin levels significantly increased in those taking dapagliflozin (1 month:â¯+â¯0.45 g/dL (Pâ¯=â¯0.037) and 3 months:+ 0.55 g/dL (Pâ¯=â¯0.012)]. Changes in hemoglobin levels positively mediated the changes in peak VO2 at 3 months (59.5%; P < 0.001). Changes in hemoglobin levels significantly mediated the effect of dapagliflozin in the MLHFQ at 3 months (-53.2% and -48.7%; Pâ¯=â¯0.017) and NT-proBNP levels at 1 and 3 months (-68.0%; Pâ¯=â¯0.048 and -62.7%; Pâ¯=â¯0.029, respectively). CONCLUSIONS: In patients with stable HFrEF, dapagliflozin caused a short-term increase in hemoglobin levels, identifying patients with greater improvements in maximal functional capacity, quality of life and reduction of NT-proBNP levels.
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Insuficiência Cardíaca , Disfunção Ventricular Esquerda , Humanos , Insuficiência Cardíaca/tratamento farmacológico , Volume Sistólico , Qualidade de Vida , Estado Funcional , Peptídeos Natriuréticos , Peptídeo Natriurético Encefálico/uso terapêutico , Disfunção Ventricular Esquerda/tratamento farmacológico , Hemoglobinas , Fragmentos de PeptídeosRESUMO
PURPOSE OF THE WORK: Although sex-specific differences in heart failure (HF) or kidney disease (KD) have been analyzed separately, the predominant cardiorenal phenotype by sex has not been described. This study aims to explore the sex-related differences in cardiorenal syndrome (CRS) in a contemporary cohort of outpatients with HF. FINDINGS: An analysis of the Cardiorenal Spanish registry (CARDIOREN) was performed. CARDIOREN Registry is a prospective multicenter observational registry including 1107 chronic ambulatory HF patients (37% females) from 13 Spanish HF clinics. Estimated Glomerular Filtration Rate (eGFR) < 60 ml/min/1.73 m2 was present in 59.1% of the overall HF population, being this prevalence higher in the female population (63.2% vs. 56.6%, p = 0.032, median age: 81 years old, IQR:74-86). Among those with kidney dysfunction, women displayed higher odds of showing HF with preserved ejection fraction (HFpEF) (odds ratio [OR] = 4.07; confidence interval [CI] 95%: 2.65-6.25, p < 0.001), prior valvular heart disease (OR = 1.76; CI 95%:1.13-2.75, p = 0.014), anemia (OR: 2.02; CI 95%:1.30-3.14, p = 0.002), more advanced kidney disease (OR for CKD stage 3: 1.81; CI 95%:1.04-3.13, p = 0.034; OR for CKD stage 4: 2.49, CI 95%:1.31-4.70, p = 0.004) and clinical features of congestion (OR:1.51; CI 95%: 1.02-2.25, p = 0.039). On the contrary, males with cardiorenal disease showed higher odds of presenting HF with reduced ejection fraction (HFrEF) (OR:3.13; CI 95%: 1.90-5.16, p < 0.005), ischemic cardiomyopathy (OR:2.17; CI 95%: 1.31-3.61, p = 0.003), hypertension (OR = 2.11; CI 95%:1.18-3.78, p = 0.009), atrial fibrillation (OR:1.71; CI 95%: 1.06-2.75, p = 0.025), and hyperkalemia (OR:2.43, CI 95%: 1.31-4.50, p = 0.005). In this contemporary registry of chronic ambulatory HF patients, we observed sex-related differences in patients with combined heart and kidney disease. The emerging cardiorenal phenotype characterized by advanced CKD, congestion, and HFpEF was predominantly observed in women, whereas HFrEF, ischemic etiology, hypertension, hyperkalemia, and atrial fibrillation were more frequently observed in men.
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Fibrilação Atrial , Síndrome Cardiorrenal , Insuficiência Cardíaca , Hiperpotassemia , Hipertensão , Insuficiência Renal Crônica , Humanos , Masculino , Feminino , Síndrome Cardiorrenal/epidemiologia , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/epidemiologia , Volume Sistólico , Prognóstico , Fibrilação Atrial/complicações , Estudos Prospectivos , Caracteres Sexuais , Hipertensão/complicações , Insuficiência Renal Crônica/epidemiologia , Sistema de Registros , Estudos Multicêntricos como AssuntoRESUMO
AIMS: To study the impact of genotype on the performance of the 2019 risk model for arrhythmogenic right ventricular cardiomyopathy (ARVC). METHODS AND RESULTS: The study cohort comprised 554 patients with a definite diagnosis of ARVC and no history of sustained ventricular arrhythmia (VA). During a median follow-up of 6.0 (3.1,12.5) years, 100 patients (18%) experienced the primary VA outcome (sustained ventricular tachycardia, appropriate implantable cardioverter defibrillator intervention, aborted sudden cardiac arrest, or sudden cardiac death) corresponding to an annual event rate of 2.6% [95% confidence interval (CI) 1.9-3.3]. Risk estimates for VA using the 2019 ARVC risk model showed reasonable discriminative ability but with overestimation of risk. The ARVC risk model was compared in four gene groups: PKP2 (n = 118, 21%); desmoplakin (DSP) (n = 79, 14%); other desmosomal (n = 59, 11%); and gene elusive (n = 160, 29%). Discrimination and calibration were highest for PKP2 and lowest for the gene-elusive group. Univariable analyses revealed the variable performance of individual clinical risk markers in the different gene groups, e.g. right ventricular dimensions and systolic function are significant risk markers in PKP2 but not in DSP patients and the opposite is true for left ventricular systolic function. CONCLUSION: The 2019 ARVC risk model performs reasonably well in gene-positive ARVC (particularly for PKP2) but is more limited in gene-elusive patients. Genotype should be included in future risk models for ARVC.
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Displasia Arritmogênica Ventricular Direita , Arritmias Cardíacas , Displasia Arritmogênica Ventricular Direita/genética , Morte Súbita Cardíaca/epidemiologia , Morte Súbita Cardíaca/etiologia , Morte Súbita Cardíaca/prevenção & controle , Genótipo , Humanos , Medição de Risco , Fatores de RiscoRESUMO
BACKGROUND: Cancer therapy-induced cardiomyopathy (CCM) is associated with cumulative drug exposures and preexisting cardiovascular disorders. These parameters incompletely account for substantial interindividual susceptibility to CCM. We hypothesized that rare variants in cardiomyopathy genes contribute to CCM. METHODS: We studied 213 patients with CCM from 3 cohorts: retrospectively recruited adults with diverse cancers (n=99), prospectively phenotyped adults with breast cancer (n=73), and prospectively phenotyped children with acute myeloid leukemia (n=41). Cardiomyopathy genes, including 9 prespecified genes, were sequenced. The prevalence of rare variants was compared between CCM cohorts and The Cancer Genome Atlas participants (n=2053), healthy volunteers (n=445), and an ancestry-matched reference population. Clinical characteristics and outcomes were assessed and stratified by genotypes. A prevalent CCM genotype was modeled in anthracycline-treated mice. RESULTS: CCM was diagnosed 0.4 to 9 years after chemotherapy; 90% of these patients received anthracyclines. Adult patients with CCM had cardiovascular risk factors similar to the US population. Among 9 prioritized genes, patients with CCM had more rare protein-altering variants than comparative cohorts ( P≤1.98e-04). Titin-truncating variants (TTNtvs) predominated, occurring in 7.5% of patients with CCM versus 1.1% of The Cancer Genome Atlas participants ( P=7.36e-08), 0.7% of healthy volunteers ( P=3.42e-06), and 0.6% of the reference population ( P=5.87e-14). Adult patients who had CCM with TTNtvs experienced more heart failure and atrial fibrillation ( P=0.003) and impaired myocardial recovery ( P=0.03) than those without. Consistent with human data, anthracycline-treated TTNtv mice and isolated TTNtv cardiomyocytes showed sustained contractile dysfunction unlike wild-type ( P=0.0004 and P<0.002, respectively). CONCLUSIONS: Unrecognized rare variants in cardiomyopathy-associated genes, particularly TTNtvs, increased the risk for CCM in children and adults, and adverse cardiac events in adults. Genotype, along with cumulative chemotherapy dosage and traditional cardiovascular risk factors, improves the identification of patients who have cancer at highest risk for CCM. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifiers: NCT01173341; AAML1031; NCT01371981.
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Antineoplásicos/efeitos adversos , Cardiomiopatias/induzido quimicamente , Cardiomiopatias/genética , Variação Genética/genética , Neoplasias/tratamento farmacológico , Neoplasias/genética , Adulto , Idoso , Animais , Cardiomiopatias/epidemiologia , Estudos de Coortes , Feminino , Variação Genética/efeitos dos fármacos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Pessoa de Meia-Idade , Neoplasias/epidemiologia , Estudos Prospectivos , Estudos RetrospectivosRESUMO
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.
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Cardiomiopatias/epidemiologia , Cardiomiopatias/terapia , Sistema de Registros , Adulto , Fatores Etários , Displasia Arritmogênica Ventricular Direita/diagnóstico , Displasia Arritmogênica Ventricular Direita/epidemiologia , Displasia Arritmogênica Ventricular Direita/genética , Displasia Arritmogênica Ventricular Direita/terapia , Cardiomiopatias/diagnóstico , Cardiomiopatias/genética , Cardiomiopatia Dilatada/diagnóstico , Cardiomiopatia Dilatada/epidemiologia , Cardiomiopatia Dilatada/genética , Cardiomiopatia Dilatada/terapia , Cardiomiopatia Hipertrófica/diagnóstico , Cardiomiopatia Hipertrófica/epidemiologia , Cardiomiopatia Hipertrófica/genética , Cardiomiopatia Hipertrófica/terapia , Cardiomiopatia Restritiva/diagnóstico , Cardiomiopatia Restritiva/epidemiologia , Cardiomiopatia Restritiva/genética , Cardiomiopatia Restritiva/terapia , Desfibriladores , Gerenciamento Clínico , Europa (Continente)/epidemiologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
INTRODUCTION: Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is an inherited cardiomyopathy characterized by ventricular arrhythmias and heart failure. The variable phenotype suggesting that determined environmental factors may have an influence. The aim of our study was to discover the impact of the dynamic physical activity on patients with high-risk definite ARVC/D. METHODS AND RESULTS: Collection of data on physical activity at the time of diagnosis was conducted at an in-person clinical interview. The intensity of the activity was classified in accordance with the mean frequency of weekly physical exercise sessions in the 10 years before diagnosis and into the following three groups of dynamic activity: high/competitive (>3 h/wk), moderate (1 to 3 h) and minimal/inactive (<1 h). Seventeen patients practiced high dynamic physical activities. The intensity of dynamic activity was classified into three groups: 8 of high intensity, 9 moderate, and 19 inactive. The first major arrhythmic event and occurrence of severe right ventricular dysfunction were earlier in the high-intensity exercise group, followed by the moderate intensity group and at a later age in the low-intensity/inactive group. CONCLUSIONS: Dynamic exercise could be directly associated with the severity of the phenotype in relation to the precocity of major ventricular arrhythmic events and right ventricular systolic dysfunction in patients with high-risk definite ARVC/D.
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Displasia Arritmogênica Ventricular Direita/diagnóstico , Displasia Arritmogênica Ventricular Direita/fisiopatologia , Exercício Físico/fisiologia , Esforço Físico/fisiologia , Adulto , Estudos de Coortes , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Adulto JovemRESUMO
AIMS: Our aim was to describe the electrocardiographic findings of a large sample of Spanish workers from several different employment sectors. METHODS AND RESULTS: Between May 2008 and November 2010, 13 495 consecutive 12-lead resting electrocardiograms (ECGs) were obtained during health examinations of working adults aged 16-74 years in 5 cities in different regions of Spain. Of those, 13 179 ECGs suitable for interpretation were included in this study. All tracings were classified by the same cardiologist, according to the Minnesota Code criteria. The mean age of the sample was 40 years, and 73.4% were male. Frequencies of complete right bundle branch block, complete left bundle branch block, and left ventricular hypertrophy were 1.1, 0.2, and 3.6%, respectively. Major Q wave abnormalities were observed in 1.7% of the subjects, T wave abnormalities in 0.7%, early repolarization in 2.4%, and other ST segment abnormalities in 0.2%. Atrial fibrillation was present in 0.08% of the workers and atrial flutter in 0.02%. Frequencies of the Wolff-Parkinson-White pattern, Brugada pattern, long QT pattern, and short QT pattern were 0.2, 0.068, 0.038, and 0.015%, respectively. CONCLUSION: This study shows the electrocardiographic findings of a large sample of Spanish workers from several different employment sectors. The frequencies of many ECG patterns related to an adverse prognosis (left ventricular hypertrophy, complete left bundle branch block, T wave abnormalities, ST segment abnormalities, and atrial fibrillation) were low.
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Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/epidemiologia , Eletrocardiografia , Cardiopatias/diagnóstico , Cardiopatias/epidemiologia , Descrição de Cargo , Saúde Ocupacional , Potenciais de Ação , Adolescente , Adulto , Idoso , Arritmias Cardíacas/fisiopatologia , Estudos Transversais , Feminino , Cardiopatias/fisiopatologia , Frequência Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Fatores de Risco , Espanha/epidemiologia , Adulto JovemRESUMO
AIMS: Hypertrophic cardiomyopathy is one of the main causes of sudden death in young people. Recent clinical practice guidelines include a risk prediction model for sudden death (HCM Risk-SCD), which facilitates the decision of whether to implant a defibrillator. The aim of our study was to ascertain the percentage of events in our series of primary prevention implantable cardioverter-defibrillator recipients with hypertrophic cardiomyopathy and whether HCM Risk-SCD predicts the onset of arrhythmic events. METHODS AND RESULTS: This was an observational, retrospective cohort study, which included 48 primary prevention defibrillator recipient patients with HCM. We compiled their demographic and clinical characteristics, estimated 5-year risk using HCM Risk-SCD, and collected the documentation on arrhythmias during follow-up. The majority was male (66.7%) and mean age at implantation was 44.44 ± 14.46 years. Non-sustained ventricular tachycardia was the most prevalent risk factor (66.67%), followed by a family history of sudden death (47.92%). Mean HCM Risk-SCD was 6.15 ± 5.01%. HCM Risk-SCD was the only factor independently associated with the onset of ventricular tachyarrhythmia, above any other classic risk factor or association [odds ratio = 1.46 (95% confidence interval 1.051-2.013); P = 0.02]. None of the 11 patients estimated as low risk using HCM Risk-SCD suffered any appropriate events (P < 0.05). CONCLUSIONS: During an average follow-up of 4 years, 16.67% presented appropriate events (4.16%/year). HCM Risk-SCD predicted the onset of events more suitably than classic risk factors.
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Arritmias Cardíacas/epidemiologia , Cardiomiopatia Hipertrófica/complicações , Cardiomiopatia Hipertrófica/terapia , Morte Súbita Cardíaca/epidemiologia , Prevenção Primária/métodos , Adulto , Arritmias Cardíacas/prevenção & controle , Morte Súbita Cardíaca/prevenção & controle , Desfibriladores Implantáveis , Feminino , Humanos , Estimativa de Kaplan-Meier , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Estudos Retrospectivos , Fatores de Risco , EspanhaRESUMO
INTRODUCTION AND OBJECTIVES: Transthyretin cardiac amyloidosis (ATTR-CA) is a frequent cause of heart failure with preserved ejection fraction (HFpEF). This study sought to determine the prevalence of ATTR-CA among HFpEF patients in a multicenter nationwide study. METHODS: Consecutive ambulatory or hospitalized patients aged ≥ 50 years with HFpEF and left ventricle hypertrophy ≥ 12mm were studied at 20 Spanish hospitals. Screening for cardiac amyloidosis was initiated according to the usual clinical practice of each center. Positive scintigraphs were centrally analyzed. RESULTS: 422 patients were included, of whom 387 underwent further screening for cardiac amyloidosis. A total of 65 patients (16.8%) were diagnosed with ATTR-CA, none below 75 years. There was an increase of prevalence with age. Of them, 60% were male, with a mean age of 85.3±5.2 years, mean left ventricle ejection fraction of 60.3±7.6% and a mean maximum left ventricle wall thickness of 17.2 [12-25] mm. Most of the patients were New York Heart Association class II (48.4%) or III (46.8%). Besides being older than non-ATTR-CA patients, ATTR-CA patients had higher median NT-proBNP levels (3801 [2266-7132] vs 2391 [1141-4796] pg/mL; P=.003). There was no statistical difference in the prevalence of ATTR-CA by sex (19.7% for men and 13.8% for women, P=.085). A â¼7% (4/56) of the patients exhibited a genetic variant (ATTRv). CONCLUSIONS: This multicenter nationwide study found a prevalence of 16.8%, confirming that ATTR-CA is a significant contributor to HFpEF in male and female patients with left ventricle hypertrophy and more than 75 years.
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AIMS: Combination of hypertonic saline solution (HSS) with intravenous loop diuretics has been suggested to improve diuretic response in patients hospitalized for heart failure (HF). The efficacy and safety of this approach in the ambulatory setting remain unexplored. METHODS AND RESULTS: In this multicentre, double-blind, randomized study, we allocated ambulatory patients with worsening heart failure (WHF) to a 1-h infusion of intravenous furosemide (ivFurosemide)-HSS versus ivFurosemide. The primary endpoint was the volume of diuresis at 3 h. Secondary endpoints included 3-h natriuresis and weight variation, 7-day congestion data, kidney function and electrolytes, and 30-day clinical events. Overall, 167 participants (median age: 81 years, 30.5% female) were randomized across 13 sites between December 2020 and March 2023. There were no differences in 3-h diuresis between treatments (ivFurosemide-HSS: 1099 ml vs. ivFurosemide: 1103 ml, p = 0.963), 3-h natriuresis (∆ +2.642 mEq/L, p = 0.559), or 3-h weight (∆ +0.012 kg, p = 0.920). Patients in the ivFurosemide-HSS arm experienced significant weight decrease at 7 days (Δ -0.586 kg, p = 0.048). There were no between-treatment differences in clinical congestion score, biomarkers, inferior vena cava diameter, or the presence of lung ultrasound B-lines. At 30 days, 26.5% of the patients in the ivFurosemide-HSS group versus 33.3% in the ivFurosemide group experienced WHF (hazard ratio 0.76, p = 0.330). The incidence of death from any cause or HF hospitalization was 6% of patients in the ivFurosemide-HSS group and 8.3% of patients in the ivFurosemide group (hazard ratio 0.69, p = 0.521). The incidence of worsening kidney function or metabolic derangements was not significantly different in the two arms. CONCLUSIONS: A single infusion of ivFurosemide-HSS did not improve 3-h diuresis or congestion parameters in patients with ambulatory WHF. This therapy showed an appropriate safety profile.
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BACKGROUND: Genetic disease has recently emerged as a cause of cardiac conduction disorders (CCDs), but the diagnostic yield of genetic testing and the contribution of the different genes to CCD is still unsettled. OBJECTIVES: This study sought to determine the diagnostic yield of genetic testing in young adults with CCD of unknown etiology requiring pacemaker implantation. We also studied the prevalence of rare protein-altering variants across individual genes and functional gene groups. METHODS: We performed whole exome sequencing in 150 patients with CCD of unknown etiology who had permanent pacemaker implanted at age ≤60 years at 14 Spanish hospitals. Prevalence of rare protein-altering variants in patients with CCD was compared with a reference population of 115,522 individuals from gnomAD database (control subjects). RESULTS: Among 39 prioritized genes, patients with CCD had more rare protein-altering variants than control subjects (OR: 2.39; 95% CI: 1.75-3.33). Significant enrichment of rare variants in patients with CCD was observed in all functional gene groups except in the desmosomal genes group. Rare variants in the nuclear envelope genes group exhibited the strongest association with CCD (OR: 6.77; 95% CI: 3.71-13.87). Of note, rare variants in sarcomeric genes were also enriched (OR: 1.73; 95% CI: 1.05-3.10). An actionable genetic variant was detected in 21 patients (14%), with LMNA being the most frequently involved gene (4.6%). CONCLUSIONS: Unrecognized rare genetic variants increase the risk of CCD in young adults with CCD of unknown etiology. Genetic testing should be performed in patients age ≤60 years with CCD of unknown etiology. The role of genetic variants in sarcomeric genes as a cause of CCD should be further investigated.
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INTRODUCTION AND OBJECTIVES: Repetitive ambulatory doses of levosimendan are an option as a bridge to heart transplantation (HT), but evidence regarding the safety and efficacy of this treatment is scarce. The objective of the LEVO-T Registry is to describe the profile of patients on the HT list receiving levosimendan, prescription patterns, and clinical outcomes compared with patients not on levosimendan. METHODS: We retrospectively reviewed all patients listed for elective HT from 2015 to 2020 from 14 centers in Spain. RESULTS: A total of 1015 consecutive patients were included, of whom 238 patients (23.4%) received levosimendan. Patients treated with levosimendan had more heart failure (HF) admissions in the previous year and a worse clinical profile. The most frequent prescription pattern were fixed doses triggered by the patients' clinical needs. Nonfatal ventricular arrhythmias occurred in 2 patients (0.8%). No differences in HF hospitalizations were found between patients who started levosimendan in the first 30 days after listing and those who did not (33.6% vs 34.5%; P=.848). Among those who did not, 102 patients (32.9%) crossed over to levosimendan after an HF admission. These patients had a rate of 0.57 HF admissions per month before starting levosimendan and 0.21 afterwards. Propensity score matching analysis showed no differences in survival at 1 year after listing between patients receiving levosimendan and those who did not (HR, 1.03; 95%CI, 0.36-2.97; P=.958) or in survival after HT (HR, 0.97; 95%CI, 0.60-1.56; P=.958). CONCLUSIONS: Repetitive levosimendan in an ambulatory setting as a bridge to heart transplantation is commonly used, is safe, and may reduce HF hospitalizations.
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Insuficiência Cardíaca , Transplante de Coração , Piridazinas , Humanos , Simendana/uso terapêutico , Cardiotônicos/uso terapêutico , Estudos Retrospectivos , Resultado do Tratamento , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/cirurgia , Hidrazonas/uso terapêutico , Piridazinas/uso terapêuticoRESUMO
BACKGROUND: Despite the high burden of diabetes and cardiovascular risk factors in American Indian communities in the United States, prospective studies of heart failure (HF) in this population group are scarce, and the generalizability of previous HF risk scales may be limited. We developed a parsimonious HF risk prediction equation that accounts for relevant risk factors affecting American Indian communities, focusing on diabetes and kidney damage. METHODS AND RESULTS: A total of 3059 participants from the SHS (Strong Heart Study) (56±8 years of age, 58% women) were included. Five hundred seven developed HF. Progressively adjusted Cox proportional hazards models were used to identify risk factors for HF and HF subtypes. Predictors of risk at 5 and 10 years included older age (hazard ratio [HR], 1.79 [95% CI, 1.43-2.25]; HR, 1.68 [95% CI, 1.44-1.95]), smoking (HR, 2.26 [95% CI, 1.23-4.13]; HR, 2.08 [95% CI, 1.41-3.06]), macroalbuminuria (HR, 8.38 [95% CI, 4.44-15.83]; HR, 5.20 [95% CI, 3.42-7.9]), microalbuminuria (HR, 2.72 [95% CI, 1.51-4.90]; HR, 1.92 [95% CI, 1.33, 2.78]), and previous myocardial infarction (HR, 6.58 [95% CI, 2.54-17.03]; HR, 3.87 [95% CI, 2.29-6.54]), respectively. These predictors, together with diabetes diagnosis and glycated hemoglobin were significant at 10 and 28 years. High discrimination performance was achieved (C index, 0.81 [95% CI, 0.76-0.84]; C index, 0.78 [95% CI, 0.75-0.81]; and C index, 0.77 [95% CI, 0.74-0.78] at 5, 10, and up to 28 years of follow up, respectively). Some associations varied across HF subtypes, although diabetes, albuminuria, and previous myocardial infarction were associated with all subtypes. CONCLUSIONS: This prospective study of HF risk factors in American Indian communities identifies that smoking, body mass index, and indicators of diabetes control and kidney damage (glycated hemoglobin and albuminuria) are major determinants of HF. Our findings can improve HF risk assessment in populations with a high burden of diabetes.
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INTRODUCTION AND OBJECTIVES: Patients with combined heart failure (HF) and chronic kidney disease (CKD) have been underrepresented in clinical trials. The prevalence of CKD in these patients and their clinical profile require constant evaluation. This study aimed to analyze the prevalence of CKD, its clinical profile, and patterns of use of evidence-based medical therapies in HF across CKD stages in a contemporary cohort of ambulatory patients with HF. METHODS: From October 2021 to February 2022, the CARDIOREN registry included 1107 ambulatory HF patients from 13 HF clinics in Spain. RESULTS: The median age was 75 years, 63% were male, and 48% had heart failure with reduced left ventricular ejection fraction (HFrEF). A total of 654 (59.1%) had an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2, and 122 (11%) patients with eGFR ≥ 60 mL/min/1.73 m2 had a urine albumin-creatinin ratio ≥ 30 mg/g. The most important variables associated with lower eGFR were age (R2=61%) and furosemide dose (R2=21%). The proportion of patients receiving an angiotensin-converting enzyme inhibitor (ACEI)/ angiotensin II receptor blockers (ARB), an angiotensin receptor-neprilysin inhibitor (ARNi), a sodium-glucose cotransporter 2 inhibitor (SGLT2i), or a mineralocorticoid receptor antagonist (MRA) progressively decreased with lower eGFR categories. Notably, 32% of the patients with HFrEF and an eGFR <30 mL/min/1.73 m2 received the combination of ACEI/ARB/ARNi+beta-blockers+MRA+SGLT2i. CONCLUSIONS: In this contemporary HF registry, 70% of patients had kidney disease. Although this population is less likely to receive evidence-based therapies, structured and specialized follow-up approaches within HF clinics may facilitate the adoption of these life-saving drugs.
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Insuficiência Cardíaca , Insuficiência Renal Crônica , Humanos , Masculino , Idoso , Feminino , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/epidemiologia , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Volume Sistólico , Antagonistas de Receptores de Angiotensina/uso terapêutico , Prevalência , Função Ventricular Esquerda , Doença Crônica , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/epidemiologia , Sistema de RegistrosRESUMO
Background: Albuminuria could potentially emerge as a novel marker of congestion in acute heart failure. However, the current evidence linking albuminuria and congestion in patients with congestive heart failure (CHF) remains somewhat scarce. This study aimed to evaluate the prevalence of albuminuria in a cohort of patients with CHF, identify the independent factors associated with albuminuria and analyse the correlation with different congestion parameters. Methods: This is a subanalysis of the Spanish Cardiorenal Registry, in which we enrolled 864 outpatients with heart failure and a value of urinary albumin:creatinine ratio (UACR) at the first visit. Results: The median age was 74 years, 549 (63.5%) were male and 438 (50.7%) had a reduced left ventricular ejection fraction. A total of 350 patients (40.5%) had albuminuria. Among these patients, 386 (33.1%) had a UACR of 30-300 mg/g and 64 (7.4%) had a UACR >300 mg/g. In order of importance, the independent variables associated with higher UACR were estimated glomerular filtration rate determined by the Chronic Kidney Disease Epidemiology Collaboration equation (R2 = 57.6%), systolic blood pressure (R2 = 21.1%), previous furosemide equivalent dose (FED; R2 = 7.5%), antigen carbohydrate 125 (CA125; R2 = 6.1%), diabetes mellitus (R2 = 5.6%) and oedema (R2 = 1.9%). The combined influence of oedema, elevated CA125 levels and the FED accounted for 15.5% of the model's variability. Conclusions: In patients with chronic stable heart failure, the prevalence of albuminuria is high. The risk factors of albuminuria in this population are chronic kidney disease and hypertension. Congestion parameters are also associated with increased albuminuria.
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INTRODUCTION AND OBJECTIVES: Vaccines against SARS-CoV-2 have been a major scientific and medical achievement in the control of the COVID-19 pandemic. However, very infrequent cases of inflammatory heart disease have been described as adverse events, leading to uncertainty in the scientific community and in the general population. METHODS: The Vaccine-Carditis Registry has included all cases of myocarditis and pericarditis diagnosed within 30 days after COVID-19 vaccination since August 1, 2021 in 29 centers throughout the Spanish territory. The definitions of myocarditis (probable or confirmed) and pericarditis followed the consensus of the Centers for Disease Control and the Clinical Practice Guidelines of the European Society of Cardiology. A comprehensive analysis of clinical characteristics and 3-month evolution is presented. RESULTS: From August 1, 2021, to March 10, 2022, 139 cases of myocarditis or pericarditis were recorded (81.3% male, median age 28 years). Most cases were detected in the 1st week after administration of an mRNA vaccine, the majority after the second dose. The most common presentation was mixed inflammatory disease (myocarditis and pericarditis). 11% had left ventricular systolic dysfunction, 4% had right ventricular systolic dysfunction, and 21% had pericardial effusion. In cardiac magnetic resonance studies, left ventricular inferolateral involvement was the most frequent pattern (58%). More than 90% of cases had a benign clinical course. After a 3-month follow-up, the incidence of adverse events was 12.78% (1.44% mortality). CONCLUSIONS: In our setting, inflammatory heart disease after vaccination against SARS-CoV-2 predominantly affects young men in the 1st week after the second dose of RNA-m vaccine and presents a favorable clinical course in most cases.
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Vacinas contra COVID-19 , COVID-19 , Miocardite , Pericardite , Adulto , Feminino , Humanos , Masculino , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Progressão da Doença , Miocardite/induzido quimicamente , Miocardite/epidemiologia , Pericardite/induzido quimicamente , Pericardite/epidemiologia , Sistema de Registros , Vacinação/efeitos adversos , EspanhaRESUMO
OBJECTIVE: Analyzing the most frequent reasons for telephone demand in the heart failure nurse's consultation and to evaluate the response resolution capacity after the call. METHOD: Descriptive, retrospective study of all telephone calls recorded between June 2020 and April 2021 in a specific nursing consultation for heart failure care. The main sociodemographic and clinical variables, reason for calling and action carried out by the nurse were extracted from the electronic medical records. For its subsequent descriptive análisis. RESULTS: 643 calls were analyzed, 354 (55.1%) were made by the patients. The most frequent reason for calling was to consult symptoms 45.8% (nâ¯=â¯162). 71.6% (nâ¯=â¯116) of the consultations were resolved by adjusting the pharmacological treatment by telephone, 24.7% (nâ¯=â¯40) required a face-to-face visit in the nurse's consultation, 22 (13.6%) needed emergency care. 5 due to worsening heart failure. The patients who consulted for symptoms had a worse functional class (pâ¯=â¯0.007) and had been referred from hospitalization (pâ¯=â¯0.023). CONCLUSIONS: The telephone consultation was shown to be useful for patients with heart failure, being mainly demanded by users who present symptoms of worsening of their disease.
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Serviços Médicos de Emergência , Insuficiência Cardíaca , Humanos , Encaminhamento e Consulta , Estudos Retrospectivos , Telefone , Insuficiência Cardíaca/terapiaRESUMO
BACKGROUND: Fabry disease (FD) is an X-linked condition caused by variants in the GLA gene. Since females have two X chromosomes, they were historically thought to be carriers. Although increased knowledge has shown that females often develop the disease, data from Spain and other countries reported that females were undertreated. The aim of this study was to provide a wider and more recent description of the disease characteristics and associated management of females with a GLA variant in a Spanish cohort. RESULTS: Ninety-seven females from 12 hospitals were included in this retrospective study. Mean age was 50.1 ± 17.2 years. Median follow-up time from GLA variant identification was 36.1 months, and most (70.1%) were identified through family screening. Variants associated with classic/non-classic phenotypes were similarly distributed (40.2%/53.6%). Missense variants were the most prevalent (n = 84, 86.6%). In the overall group, 70.4% had major organ involvement (i.e., cardiac, renal, cerebrovascular, peripheral nervous system or gastrointestinal), and 47.3% also had typical Fabry signs (angiokeratoma, cornea verticillata or increased plasma lyso-Gb3). Cardiac involvement was the most prevalent (49.5%) and the main reason for treatment initiation. A total of 33 (34%) patients received disease-specific therapy, 55% of whom were diagnosed by family screening. Females carrying variants associated with a classic phenotype had higher frequencies of clinical manifestations (92.3%) and were predominant in the treated subgroup (69.7%). Despite this, there were 34 untreated females (56.7% of total untreated), with both phenotypes represented, who had major organ involvement, with 27 of cardiac, renal or cerebrovascular nature. Age or comorbidities in this subgroup were comparable to the treated subgroup (P = 0.8 and P = 0.8, respectively). CONCLUSIONS: Efforts have been made in recent years to diagnose and treat timely Fabry females in Spain. A high percentage of females with pathogenic variants, regardless of their associated phenotype, will likely develop disease. A proportion of females with severe disease in this cohort received specific treatment. Still a significant number of females, even with same profile as the treated ones, who may be eligible for treatment according to European recommendations, remained untreated. Reasons for this merit further investigation.
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Distrofias Hereditárias da Córnea , Doença de Fabry , Feminino , Humanos , Estudos Retrospectivos , Cognição , Doença de Fabry/epidemiologia , Doença de Fabry/genética , FenótipoRESUMO
INTRODUCTION AND OBJECTIVES: Arrhythmogenic cardiomyopathy (ACM) is a hereditary heart disease defined by the progressive replacement of the ventricular myocardium with fibroadipose tissue, which can act as a substrate for arrhythmias, sudden death, or even give rise to heart failure (HF). Sudden death is frequently the first manifestation of the disease, particularly among young patients. The aim of this study is to describe a new pathogenic variant in the PKP2 gene. METHODS: A descriptive observational study that included eight initially non-interrelated families with a diagnosis of ACM undergoing follow-up at our HF and Familial Cardiomyopathies Unit, who were carriers of the NM_004572.3:c.775_776insG; p.(Glu259Glyfs*77) variant in the PKP2 gene. The genetic testing employed next-generation sequencing for the index cases and the Sanger method for the targeted study with family members. We compiled personal and family histories, demographic and clinical characteristics, data from the additional tests at the time of diagnosis, and arrhythmic events at diagnosis and during follow-up. RESULTS: We included 47 subjects, of whom 8 were index cases (17%). Among the evaluated family members, 16 (34%) were carriers of the genetic variant, 3 of whom also had a diagnosis of ACM. The majority were women (26 patients; 55.3%), with a mean age on diagnosis of 48.9 ± 18.6 years and a median follow-up of 39 [24-59] months. Worthy of note are the high incidences of arrhythmic events as the form of presentation and in follow-up (21.5% and 20.9%, respectively), and the onset of HF in 25% of the sample. The most frequent ventricular involvements were right (four patients, 16.7%) and biventricular (four patients, 16.7%); we found no statistical differences in any of the variables analysed. CONCLUSIONS: This variant is a pathogenic variant of gene PKP2 that has not previously been described and is not present in the control groups associated with ACM. It has incomplete penetrance, a highly variable phenotypic expressivity, and was identified in eight families of our geographical area in Malaga (Andalusia, Spain), suggesting a founder effect in this area and describe the clinical and risk characteristics.
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Displasia Arritmogênica Ventricular Direita , Cardiomiopatias , Insuficiência Cardíaca , Humanos , Masculino , Feminino , Displasia Arritmogênica Ventricular Direita/diagnóstico , Espanha , Cardiomiopatias/genética , Heterozigoto , Testes Genéticos , Insuficiência Cardíaca/genética , Placofilinas/genéticaRESUMO
AIM: Patients with advanced heart failure (AHF) who are not candidates to advanced therapies have poor prognosis. Some trials have shown that intermittent levosimendan can reduce HF hospitalizations in AHF in the short term. In this real-life registry, we describe the patterns of use, safety and factors related to the response to intermittent levosimendan infusions in AHF patients not candidates to advanced therapies. METHODS AND RESULTS: Multicentre retrospective study of patients diagnosed with advanced heart failure, not HT or LVAD candidates. Patients needed to be on the optimal medical therapy according to their treating physician. Patients with de novo heart failure or who underwent any procedure that could improve prognosis were not included in the registry. Four hundred three patients were included; 77.9% needed at least one admission the year before levosimendan was first administered because of heart failure. Death rate at 1 year was 26.8% and median survival was 24.7 [95% CI: 20.4-26.9] months, and 43.7% of patients fulfilled the criteria for being considered a responder lo levosimendan (no death, heart failure admission or unplanned HF visit at 1 year after first levosimendan administration). Compared with the year before there was a significant reduction in HF admissions (38.7% vs. 77.9%; P < 0.0001), unplanned HF visits (22.7% vs. 43.7%; P < 0.0001) or the combined event including deaths (56.3% vs. 81.4%; P < 0.0001) during the year after. We created a score that helps predicting the responder status at 1 year after levosimendan, resulting in a score summatory of five variables: TEER (+2), treatment with beta-blockers (+1.5), Haemoglobin >12 g/dL (+1.5), amiodarone use (-1.5) HF visit 1 year before levosimendan (-1.5) and heart rate >70 b.p.m. (-2). Patients with a score less than -1 had a very low probability of response (21.5% free of death or HF event at 1 year) meanwhile those with a score over 1.5 had the better chance of response (68.4% free of death or HF event at 1 year). LEVO-D score performed well in the ROC analysis. CONCLUSION: In this large real-life series of AHF patients treated with levosimendan as destination therapy, we show a significant decrease of heart failure events during the year after the first administration. The simple LEVO-D Score could be of help when deciding about futile therapy in this population.