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BACKGROUND: The impact of incident sudden cardiac death (SCD) on the predictive accuracy of prognostic risk scores for patients with chronic heart failure (HF) has rarely been examined. We assessed the relationship between estimated probability of death and modes of death in this population, as well as the predictors of death and survival in prognostic outliers. METHODS AND RESULTS: The MAGGIC 3-year probability of death was estimated in 6,859 participants of the GISSI-HF trial (mean age 67±11 years, 78% men, 91% with ejection fraction <40%, mean follow-up 3.5±1.3 years, observed mortality 28.4%). The incidence of SCD progressively decreased with increased probability of death, and occurred in 52.5% of patients estimated at low-risk (N = 61 with probability <14%) vs. in 23.5% of the high-risk ones (N = 375 with probability >56%, P < .0001). On the contrary, death from worsening HF was significantly more frequent in the latter group (19.7% vs. 46.1%, P < .0001). The overall predictive accuracy of the MAGGIC model improved after excluding deaths from SCD (AUC from 0.731 to 0.760, P = .0034). Among patients estimated at low-risk (N = 61 dead, 743 alive), independent predictors of death were older age, longer history of HF, higher serum uric acid and chronic obstructive pulmonary disease. The only predictor of survival in patients estimated at high-risk (N = 210 alive, 375 dead) was higher systolic blood pressure. CONCLUSIONS: The MAGGIC risk score demonstrated its scarce ability to capture SCD, particularly in chronic HF patients estimated at low risk of death. Newer and better prognostic tools in the evolving horizon of HF are needed.
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Morte Súbita Cardíaca/epidemiologia , Insuficiência Cardíaca/mortalidade , Idoso , Área Sob a Curva , Causas de Morte , Feminino , Insuficiência Cardíaca/fisiopatologia , Humanos , Incidência , Masculino , Probabilidade , Prognóstico , Medição de Risco , Volume SistólicoRESUMO
INTRODUCTION: Hodgkin lymphoma (HL) is one of the most common types of cancers of the lymphatic system. The currently available therapies enable a cure in approximately 80-85% of treated patients. However, the cardiotoxicity of HL treatment has become a major cause of morbidity and mortality in survivors mainly related to the use of anthracycline. CASE REPORT: An HL, staged IIIB, was diagnosed in a 60-year-old man with no cardiovascular disease. During the first cycle of ABVD chemotherapy (Adriamycin; bleomycin; vinblastine; dacarbazine), near the end of the dacarbazine infusion, the patient presented a sudden cardiogenic shock characterized by a severe left ventricular systolic dysfunction. Laboratory and instrumental examinations performed did not suggest any specific etiology. After 15 days of medical support, the patient presented a complete cardiac function and clinical recovery. Subsequently bendamustine chemotherapy was started because of its limited extrahematological toxicity, but after 4 cycles the patient had progressive disease and died of septic shock. We concluded that a very rare hyperacute anthracycline cardiotoxicity was the most likely reason for this critical scenario. CONCLUSIONS: This rare event stresses our inability to correctly predict the risk of a patient developing cardiotoxicity and also highlights the need to improve the knowledge of underlying pathophysiological mechanisms; in fact, it suggests a possible genetic predisposition to develop cardiotoxicity due to a relatively limited dosage.
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Antraciclinas/efeitos adversos , Antineoplásicos/efeitos adversos , Doença de Hodgkin/tratamento farmacológico , Choque Cardiogênico/induzido quimicamente , Antraciclinas/administração & dosagem , Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Evolução Fatal , Doença de Hodgkin/complicações , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Medição de RiscoRESUMO
OBJECTIVES: More than 3.5 million invasive coronary angiographies (ICA) are performed in Europe annually. Approximately 2 million of these invasive procedures might be reduced by noninvasive tests because no coronary intervention is performed. Computed tomography (CT) is the most accurate noninvasive test for detection and exclusion of coronary artery disease (CAD). To investigate the comparative effectiveness of CT and ICA, we designed the European pragmatic multicentre DISCHARGE trial funded by the 7th Framework Programme of the European Union (EC-GA 603266). METHODS: In this trial, patients with a low-to-intermediate pretest probability (10-60 %) of suspected CAD and a clinical indication for ICA because of stable chest pain will be randomised in a 1-to-1 ratio to CT or ICA. CT and ICA findings guide subsequent management decisions by the local heart teams according to current evidence and European guidelines. RESULTS: Major adverse cardiovascular events (MACE) defined as cardiovascular death, myocardial infarction and stroke as a composite endpoint will be the primary outcome measure. Secondary and other outcomes include cost-effectiveness, radiation exposure, health-related quality of life (HRQoL), socioeconomic status, lifestyle, adverse events related to CT/ICA, and gender differences. CONCLUSIONS: The DISCHARGE trial will assess the comparative effectiveness of CT and ICA. KEY POINTS: ⢠Coronary artery disease (CAD) is a major cause of morbidity and mortality. ⢠Invasive coronary angiography (ICA) is the reference standard for detection of CAD. ⢠Noninvasive computed tomography angiography excludes CAD with high sensitivity. ⢠CT may effectively reduce the approximately 2 million negative ICAs in Europe. ⢠DISCHARGE addresses this hypothesis in patients with low-to-intermediate pretest probability for CAD.
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Angiografia Coronária/métodos , Doença da Artéria Coronariana/diagnóstico , Avaliação de Resultados em Cuidados de Saúde , Tomografia Computadorizada por Raios X/métodos , Idoso , Doença da Artéria Coronariana/economia , Análise Custo-Benefício , Europa (Continente) , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Qualidade de Vida , Estudos RetrospectivosRESUMO
BACKGROUND: The heart is commonly involved in maternally inherited mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome caused by the MT-TL1 m.3243A>G mutation of the mitochondrial DNA. Heart transplantation (HTx) is controversial and has rarely been performed with conflicting results. OBJECTIVES: We analyzed factors preventing HTx in consecutive adult patients with MELASMT-TL1:m.3243A>G cardiomyopathy diagnosed and followed during the last 23 years in our HTx referral center. METHODS: The series consists of 14 unrelated adult probands who were referred for evaluation of cardiomyopathy from 1998 to 2021. None had a suspected diagnosis of MELAS before referral. All patients underwent clinical and genetic visit and counseling, mitochondrial DNA sequencing, cardiovascular investigation (including right heart catheterization and endomyocardial biopsy in 10), multidisciplinary assessment, and biochemical tests. Family screening identified 2 affected relatives. RESULTS: The cardiac phenotype was characterized by hypertrophic, concentric, nonobstructive cardiomyopathy that often evolved into a dilated cardiomyopathy-like phenotype. Of the 14 probands, 7 were potential candidates for HTx, 2 for heart and kidney Tx, and 1 was on the active HTx list for 3 years. None of the 10 probands underwent HTx. One is currently being evaluated for HTx. All had diabetes, hearing loss, and myopathy, and 10 had chronic kidney disease and progressive encephalomyopathy. During follow-up, 10 died from heart failure associated with multiorgan failure within 5 years of the genetic diagnosis. CONCLUSIONS: High risk of stroke-like episodes, chronic kidney disease, and wasting myopathy in MELASMT-TL1:m.3243A>G patients prevents activation of plans for HTx. As a result, the management of their cardiomyopathy in this syndromic context remains an unmet clinical need.
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Cardiomiopatias , Transplante de Coração , Síndrome MELAS , Doenças Musculares , Insuficiência Renal Crônica , Cardiomiopatias/complicações , Cardiomiopatias/genética , Cardiomiopatias/cirurgia , DNA Mitocondrial/genética , Humanos , Síndrome MELAS/diagnóstico , Síndrome MELAS/genética , Síndrome MELAS/patologia , Mutação , Insuficiência Renal Crônica/complicaçõesRESUMO
Heart failure is a complex clinical syndrome with a severe prognosis, despite therapeutic progress. The management of the advanced stages of the syndrome is particularly complex in patients who are referred to palliative care as well as in those who are candidates for cardiac replacement therapy. For the latter group, a prompt recognition of the transition to the advanced stage as well as an early referral to the centers for cardiac replacement therapy are essential elements to ensure that patients follow the most appropriate diagnostic-therapeutic pathway. The aim of this document is to focus on the main diagnostic and therapeutic aspects related to the advanced stages of heart failure and, in particular, on the management of patients who are candidates for cardiac replacement therapy.
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Insuficiência Cardíaca , Transplante de Coração , Coração Auxiliar , Cardiotônicos/uso terapêutico , Procedimentos Clínicos , Humanos , Cuidados PaliativosRESUMO
BACKGROUND: The antiarrhythmic effects of n-3 polyunsaturated fatty acids (n-3PUFA) in ischemic heart disease have been demonstrated; however, studies in patients surviving malignant ventricular arrhythmias of different etiologies treated with an implantable cardioverter-defibrillator (ICD) have given conflicting results. The purpose of this study was to assess the antiarrhythmic effect of n-3PUFA versus placebo in 566 patients with heart failure enrolled in the GISSI-HF trial who received an ICD for secondary or primary prevention of ventricular fibrillation (VF) or tachycardia (VT). METHODS: Clinical data and arrhythmic event recordings extracted from the device memory were obtained. We tested the treatment effect by a multivariate Cox model adjusting for all clinical parameters associated with the primary end point defined as time to first appropriate ICD discharge for VT/VF. RESULTS: In the 566 patients with at least one recorded follow-up visit, 1363 VT and 316 VF episodes were terminated by ICD pacing or shock over a median follow-up of 928 days. The incidence of the primary end point event was 27.3% in the n-3PUFA group and 34.0% in the placebo group (adjusted hazard rate = 0.80, 95% CI 0.59-1.09, P = .152). Patients who received 1, 2 to 3, or >3 ICD discharges were 8.9%, 7.1%, and 11.1% in the n-3PUFA group, compared with slightly higher rates of 11.1%, 10.7%, and 12.1% in the placebo group (overall P = .30). Patients with the highest 3-month increase in plasma n-3PUFA had a somewhat lower incidence of arrhythmic events. CONCLUSIONS: The results of this study, though not statistically significant, support prior evidences of an antiarrhythmic effect of n-3PUFA in patients with ICD, although they leave open the issue of whether this effect leads to a survival benefit.
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Desfibriladores Implantáveis , Ácidos Graxos Ômega-3/uso terapêutico , Insuficiência Cardíaca/complicações , Taquicardia Ventricular/etiologia , Taquicardia Ventricular/terapia , Fibrilação Ventricular/etiologia , Fibrilação Ventricular/terapia , Idoso , Idoso de 80 Anos ou mais , Doença Crônica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Taquicardia Ventricular/tratamento farmacológico , Fibrilação Ventricular/tratamento farmacológicoRESUMO
Patients with a partial reduction of merosin due to mutations in the laminin-α2 chain gene usually present with a mild form of congenital muscular dystrophy or a limb-girdle-like muscular dystrophy. To our knowledge, cardiac impairment has never been reported in such patients. A longitudinal study of a patient with partial laminin-α2 deficiency secondary to mutations in the LAMA2 gene revealed dilated cardiomyopathy with ventricular arrhythmias. Is this a chance association or a novel phenotype?
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Arritmias Cardíacas/genética , Cardiomiopatia Dilatada/genética , Laminina/deficiência , Mutação/genética , Fenótipo , Adulto , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/metabolismo , Cardiomiopatia Dilatada/diagnóstico , Cardiomiopatia Dilatada/metabolismo , Sistema de Condução Cardíaco/metabolismo , Sistema de Condução Cardíaco/fisiopatologia , Humanos , Laminina/genética , Estudos Longitudinais , MasculinoRESUMO
INTRODUCTION: Familial dilated cardiomyopathy with conduction system defects variably associated with skeletal muscle abnormalities is frequently caused by LMNA gene mutations. METHODS: A family affected by cardiac abnormalities, either isolated or variably associated with skeletal muscle compromise, was identified. LMNA gene analysis was applied to all family members. RESULTS: A novel intron 5 (c.937-11 C > G) mutation was identified. mRNA transcription analysis was subsequently performed, and cDNA was obtained from mutated patients. It displayed an aberrant splice product featuring the insertion of 40 nucleotides from intron 5, leading to a frameshift. Computational predictions identified a cryptic splice site 40 bp upstream from the canonical site; this alternative splicing event was elicited by intronic mutation, which seems to interfere with the polypyrimidine tract of the canonical site. CONCLUSIONS: We have described the first mutation on the LMNA gene interfering with the polypyrimidine tract. Our findings underline the importance of including introns in the search for mutations.
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Processamento Alternativo/genética , Íntrons/genética , Lamina Tipo A/genética , Mutação/genética , Proteína de Ligação a Regiões Ricas em Polipirimidinas/genética , Adulto , Idoso , Sequência de Bases , Cardiomiopatia Dilatada/diagnóstico , Cardiomiopatia Dilatada/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , LinhagemRESUMO
The purpose of this study was to assess whether metabolomics, associated with echocardiography, was able to highlight pathophysiological differences between obstructive (OHCM) or non-obstructive (NOHCM) hypertrophic cardiomyopathy. Thirty-one HCM patients underwent standard and advanced echocardiography; a plasma sample was collected for metabolomic analysis. Results. Patients with OHCM compared with subjects with NOHCM had higher values of 2DLVEF (66.5 ± 3.3% vs. 60.6 ± 1.8%, p < 0.01), S wave (7.6 ± 1.1 vs. 6.3 ± 0.7 cm/s, p < 0.01) and 3D global longitudinal strain (17.2 ± 4.2%, vs. 13.4 ± 1.3%, p < 0.05). A 2-group PLS-Discriminant Analysis was performed to verify whether the two HCM groups differed also based on the metabolic fingerprint. A clear clustering was shown (ANOVA p = 0.014). The most discriminating metabolites resulted as follows: in the NOHCM Group, there were higher levels of threitol, aminomalonic acid, and sucrose, while the OHCM Group presented higher levels of amino acids, in particular those branched chains, of intermediates of glycolysis (lactate) and the Krebs cycle (fumarate, succinate, citrate), of fatty acids (arachidonic acid, palmitoleic acid), of ketone bodies (2-OH-butyrate). Our data point out a different systolic function related to a specific metabolic activity in the two HCM phenotypic forms, with specific metabolites associated with better contractility in OHCM.
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AIMS: We aim to describe one of the longest longitudinal follow-ups reported so far (>22 years), concerning a whole family affected by a missense lamin A/C mutation (Arg60Gly), which manifested as an overlapping phenotype with cardiac and extracardiac involvement over time. METHODS: Starting from the family history, two generations of that family were prospectively observed, from 1997 until 2020. At baseline, four individuals with dilated cardiomyopathy and cardiac conduction defects showed the same mutation. This was also found in three young individuals, phenotypically unaffected at baseline assessment. RESULTS: The prolonged clinical and laboratory evaluation has shown the evolution of an overlapping phenotype in which cardiac alterations have been associated with lipodystrophy and neurological manifestations. In the first observed generation, the prognosis was negatively affected by the progression of heart failure and lipodystrophy, whereas in the second generation the first phenotypic manifestations became evident after the 2nd decade. Cardiac magnetic resonance played a relevant role in the early detection of cardiac alteration. Right bundle branch block was another sign of initial phenotypical expression. CONCLUSION: In lamin A/C gene mutation carriers, a strict, multidisciplinary follow-up allows the opportunity to monitor the progress of the disease and to intervene precociously with the best available treatments.
Assuntos
Cardiomiopatia Dilatada/genética , Lamina Tipo A/genética , Mutação de Sentido Incorreto , Adulto , Cardiomiopatia Dilatada/diagnóstico , Cardiomiopatia Dilatada/fisiopatologia , Cardiomiopatia Dilatada/terapia , Progressão da Doença , Feminino , Predisposição Genética para Doença , Hereditariedade , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Linhagem , Fenótipo , Prognóstico , Estudos Prospectivos , Fatores de Tempo , Adulto JovemRESUMO
AIMS: Patients with permanently increased risk of sudden cardiac death (SCD) can be protected by implantable cardioverter defibrillators (ICD). If an ICD must be removed due to infection, for example, immediate reimplantation might not be possible or indicated. The wearable cardioverter defibrillator (WCD) is an established, safe and effective solution to protect patients from SCD during this high-risk bridging period. Very few economic evaluations on WCD use are currently available. METHODS: We conducted a systematic review to evaluate the available evidence of WCD in patients undergoing ICD explant/lead extraction. Additionally, a decision model was developed to compare use and costs of the WCD with standard therapy (in-hospital stay). For this purpose, a cost-minimization analysis was conducted, and complemented by a one-way sensitivity analysis. RESULTS: In the base case scenario, the WCD was less expensive compared to standard therapy. The cost-minimization analysis showed a cost reduction of 1782 per patient using the WCD. If costs of standard care were changed, cost savings associated with the WCD varied from 3500 to 0, assuming costs for standard care of 6800 to 3600. CONCLUSION: After ICD explantation, patients can be safely and effectively protected from SCD after hospital discharge through WCD utilization. Furthermore, the use of a WCD for this patient group is cost saving when compared to standard therapy.
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Desfibriladores Implantáveis , Dispositivos Eletrônicos Vestíveis , Adulto , Análise Custo-Benefício , Morte Súbita Cardíaca/etiologia , Morte Súbita Cardíaca/prevenção & controle , Desfibriladores , Cardioversão Elétrica , HumanosRESUMO
BACKGROUND: Titin (TTN)-related dilated cardiomyopathy (DCM) has a higher likelihood of left ventricular reverse remodelling compared with other genetic etiologies. No data regarding the evolution of right ventricular dysfunction (RVD) according to genetic background are available. METHODS: Consecutive 104 DCM patients with confirmed pathogenic genetic variants (51 TTN-related DCM; 53 other genetic DCM) and a control group of 139 patients with negative genetic testing and available follow-up data at 12-24 months were analysed. RVD was defined as a right ventricular fractional area change (RVFAC) < 35%. The main study end point was the comparison of the evolution of RVD and the change of RVFAC throughout the follow-up according to etiology. A composite of all-cause mortality and heart transplantation was included as outcome measure. RESULTS: At enrollment, RVD was present in 29.1% of genetically positive DCM without differences between genetic cohorts. At 14 months follow-up, 5.9% of TTN-related DCM patients vs 35.8% of other genetic DCM patients had residual RVD after treatment (P < 0.001). Accordingly, RVFAC significantly improved in the TTN-related DCM cohort and remained stably impaired in other genetic DCM patients. However, the evolution of RVD was similar between TTN-related DCM and patients without a genetic mutation. After adjusting for RVD at follow-up, no differences in the outcome measure were seen in the study cohorts. CONCLUSIONS: The evolution of RVD in DCM is heterogeneous in different genetic backgrounds. TTN-related DCM is associated with a higher chance of RVD recovery compared with other genetic etiologies.
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Cardiomiopatia Dilatada/genética , Disfunção Ventricular Direita/epidemiologia , Função Ventricular Direita/fisiologia , Remodelação Ventricular/fisiologia , Adulto , Cardiomiopatia Dilatada/complicações , Cardiomiopatia Dilatada/fisiopatologia , Conectina/genética , Conectina/metabolismo , Feminino , Seguimentos , Patrimônio Genético , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Fenótipo , Prevalência , Estudos Retrospectivos , Disfunção Ventricular Direita/etiologia , Disfunção Ventricular Direita/fisiopatologiaRESUMO
The aim of this study is to report the evolution of a phenotype in members of a single family carrying the heterozygous exon 1 c.178 C/G, p.Arg 60 Gly LMNA gene mutation. All mutated family members underwent neurological and cardiological assessments for a period ranging from 10 to 20 years. At onset, 4 affected adult members presented a phenotype that required pacemaker implantation. Three subjects underwent cardiac transplantation leading to long-term survival in 2 of them. One of the 3 longest surviving relatives manifested late lipodystrophy, and the other 2 had lipodystrophy, insulin-resistant diabetes, and distal peripheral neuropathy. The findings demonstrate that the exon 1 c.178 C/G, p.Arg 60 Gly LMNA gene mutation is associated with a novel phenotype featuring cardiac involvement followed by late lipodystrophy, diabetes, and peripheral axonal neuropathy.
Assuntos
Cardiomiopatia Dilatada/genética , DNA/genética , Família , Lamina Tipo A/genética , Mutação , Adolescente , Adulto , Cardiomiopatia Dilatada/diagnóstico , Cardiomiopatia Dilatada/metabolismo , Doença de Charcot-Marie-Tooth/diagnóstico , Doença de Charcot-Marie-Tooth/genética , Doença de Charcot-Marie-Tooth/metabolismo , Análise Mutacional de DNA , Eletromiografia , Éxons , Feminino , Seguimentos , Humanos , Lamina Tipo A/metabolismo , Lipodistrofia/diagnóstico , Lipodistrofia/genética , Lipodistrofia/metabolismo , Imageamento por Ressonância Magnética , Masculino , Linhagem , Fenótipo , Fatores de Tempo , Tomografia Computadorizada por Raios X , Adulto JovemRESUMO
Laminopathies are a heterogeneous group of LMNA-gene-mutation-related clinical disorders associated with alterations of cardiac and skeletal muscle and peripheral nerves, metabolic defects, and premature aging. Leg muscle imaging investigations were performed in a cohort of patients with LMNA gene alterations who were suffering from Emery-Dreifuss muscular dystrophy, limb-girdle muscular dystrophy type 1B, isolated cardiac disorders or a phenotype of cardiac disorders, and lipodystrophy, including one individual with peripheral neuropathy. Leg muscle imaging revealed varying degrees of alteration in the soleus and medial head of gastrocnemius in each subject. This study demonstrates that LMNA-gene-mutated patients devoid of any clinically detectable skeletal muscle involvement have the same pattern of leg muscle involvement as patients with overt skeletal muscle compromise. This finding suggests the presence of a continuum of skeletal muscle involvement among phenotypes of LMNA-gene-mutation-related skeletalmyopathy and cardiomyopathy.
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Lamina Tipo A/genética , Lipodistrofia/genética , Imageamento por Ressonância Magnética , Músculo Esquelético/patologia , Mutação/genética , Fenótipo , Adolescente , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Lipodistrofia/diagnóstico , Masculino , Pessoa de Meia-Idade , Distrofia Muscular do Cíngulo dos Membros/diagnóstico , Distrofia Muscular do Cíngulo dos Membros/genética , Distrofia Muscular de Emery-Dreifuss/diagnóstico , Distrofia Muscular de Emery-Dreifuss/genética , Adulto JovemRESUMO
AIMS: This ancillary analysis of the GISSI-HF database aims at assessing the effect of rosuvastatin on the occurrence of atrial fibrillation (AF) in patients with chronic heart failure (HF) who were not in AF at study entry. METHODS AND RESULTS: GISSI-HF was a double-blind, placebo-controlled trial testing n-3 PUFA and rosuvastatin vs. corresponding placebos in patients with chronic HF. Atrial fibrillation occurrence was defined as the presence of AF in the electrocardiogram (ECG) performed at each visit during the trial or AF as a cause of worsening HF or hospital admission or as an event during hospitalization. Among the 3690 patients (80.7%) without AF on their baseline ECG, 15.0% developed AF during a median follow-up period of 3.7 years, 258 randomized to rosuvastatin (13.9%) vs. 294 allocated to placebo (16.0%). Although the difference was not significant at unadjusted analysis (P = 0.097) and multivariable analysis adjusting for clinical variables (P = 0.067), it became significant after adjustment for clinical variables and laboratory examinations (P = 0.039), and for clinical variables, laboratory examinations, and background therapies (P = 0.038). CONCLUSION: This study shows that there is some evidence of a beneficial effect of rosuvastatin in terms of reduction of AF occurrence in patients with HF. Larger populations are needed to provide a definite answer to the question. ClinicalTrials.gov Identifier: NCT00336336.
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Antiarrítmicos/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Ácidos Graxos Ômega-3/uso terapêutico , Fluorbenzenos/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Pirimidinas/uso terapêutico , Sulfonamidas/uso terapêutico , Idoso , Doença Crônica , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Rosuvastatina Cálcica , Resultado do TratamentoRESUMO
BACKGROUND AND AIM: Cardiac resynchronization therapy (CRT) reduces mortality and morbidity in chronic heart failure symptomatic patients with broad QRS who are already undergoing optimal medical treatment. However, approximately one-third of implanted patients do not show any benefit from this treatment. Right ventricle (RV) dysfunction leads to a worse outcome in patients with heart failure, but its role in predicting the response to CRT has shown conflicting results. The purpose of our study was to investigate how the RV function, assessed by cardiac magnetic resonance (CMR), could influence the outcome of heart failure patients treated with CRT. METHODS AND RESULTS: We retrospectively enrolled 72 heart failure patients, 38 affected by dilated cardiomyopathy (DCM) and 34 by ischemic dysfunction, with left bundle branch block, QRS greater than 120âms and standard indications to CRT. We defined the response to CRT as an improvement of at least 10% of the left ventricular ejection fraction (LVEF) or at least one of the NYHA functional classes. We stratified the population into two groups based on the right ventricle ejection fraction (RVEF) at CMR: group 1 RVEF at least 55% (nâ=â32), group 2 RVEF less than 55% (nâ=â40). After a mean follow-up of 38â±â12 months, 44 patients (61%) were considered responders whereas 28 (39%) did not show any benefit. Patients in group 1 had a higher rate of response to CRT (75 vs. 50%, Pâ=â0.03). At the univariate analysis RVEF [54 vs. 43%; confidence interval (CI)â=â0.907-0.980; hazard ratioâ=â0.943; Pâ=â0.003], RV end-systolic volume (56 vs. 84âml; CIâ=â1.005-1.034; hazard ratioâ=â1.019; Pâ=â0.008) and tricuspid annular plane systolic excursion (TAPSE) (16.4 vs. 14âmm; CI 0.745-0.976; heart rateâ=â0.853; Pâ=â0.021) were the parameters most strongly associated with the response to CRT. Male sex, atrial fibrillation, and older age also negatively influenced the outcome. At a multivariate model, RVEF and older age remained significant. CONCLUSION: In our experience, patients with RV dysfunction less likely benefited from CRT. RV assessment, studied with CMR, appears to be a good predictor of the response to biventricular stimulation.
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Terapia de Ressincronização Cardíaca , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/terapia , Imageamento por Ressonância Magnética , Volume Sistólico , Disfunção Ventricular Direita/diagnóstico por imagem , Disfunção Ventricular Direita/terapia , Função Ventricular Direita , Fatores Etários , Idoso , Terapia de Ressincronização Cardíaca/efeitos adversos , Tomada de Decisão Clínica , Feminino , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Recuperação de Função Fisiológica , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Disfunção Ventricular Direita/fisiopatologiaRESUMO
Clinical guidelines, while representing an objective reference to perform appropriate treatment choices, contain grey zones, where recommendations are not supported by solid evidence. In a conference held in Bergamo in October 2018, an attempt was made to highlight some of the main grey zones in Cardiology and, through a comparison between experts, to draw shared conclusions that can illuminate our clinical practice. This manuscript contains the statements of the symposium concerning the controversies regarding new oral anticoagulants (NOACs) and atrial fibrillation (AF). The manuscript represents the organization of the meeting, with an initial review of current guidelines on this topic, followed by an expert presentation of pros (white) and cons (black) related to the identified "gaps of evidence". For every issue is then reported the response derived from the votes of the experts and the public, the discussion and, finally, the highlights, which are intended as practical "take home messages" to be used in everyday clinical practice. The first topic concerns the indication for anticoagulant therapy in patients with subclinical AF revealed by implanted devices. The second issue examines the opportunity to use NOACs in oncological patients with AF. The third gap evaluates the necessity of anticoagulating patients with AF and CHA2DS2-VASc 1 or CHA2DS2-VASc 2 if women. The last "gap in evidence" concerns the preference of triple or double therapy in patients with AF and acute coronary syndrome/coronary stenting. The work has also been implemented with evidences deriving from important randomized studies published after the date of the Conference.
Assuntos
Anticoagulantes/administração & dosagem , Fibrilação Atrial/tratamento farmacológico , Guias de Prática Clínica como Assunto , Administração Oral , Humanos , Próteses e Implantes , Ensaios Clínicos Controlados Aleatórios como Assunto , StentsRESUMO
BACKGROUND: Several epidemiological and experimental studies suggest that n-3 polyunsaturated fatty acids (PUFA) can exert favourable effects on atherothrombotic cardiovascular disease, including arrhythmias. We investigated whether n-3 PUFA could improve morbidity and mortality in a large population of patients with symptomatic heart failure of any cause. METHODS: We undertook a randomised, double-blind, placebo-controlled trial in 326 cardiology and 31 internal medicine centres in Italy. We enrolled patients with chronic heart failure of New York Heart Association class II-IV, irrespective of cause and left ventricular ejection fraction, and randomly assigned them to n-3 PUFA 1 g daily (n=3494) or placebo (n=3481) by a concealed, computerised telephone randomisation system. Patients were followed up for a median of 3.9 years (IQR 3.0-4.5). Primary endpoints were time to death, and time to death or admission to hospital for cardiovascular reasons. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00336336. FINDINGS: We analysed all randomised patients. 955 (27%) patients died from any cause in the n-3 PUFA group and 1014 (29%) in the placebo group (adjusted hazard ratio [HR] 0.91 [95.5% CI 0.833-0.998], p=0.041). 1981 (57%) patients in the n-3 PUFA group and 2053 (59%) in the placebo group died or were admitted to hospital for cardiovascular reasons (adjusted HR 0.92 [99% CI 0.849-0.999], p=0.009). In absolute terms, 56 patients needed to be treated for a median duration of 3.9 years to avoid one death or 44 to avoid one event like death or admission to hospital for cardiovascular reasons. In both groups, gastrointestinal disorders were the most frequent adverse reaction (96 [3%] n-3 PUFA group vs 92 [3%] placebo group). INTERPRETATION: A simple and safe treatment with n-3 PUFA can provide a small beneficial advantage in terms of mortality and admission to hospital for cardiovascular reasons in patients with heart failure in a context of usual care.
Assuntos
Ácidos Graxos Ômega-3/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Idoso , Doença Crônica , Método Duplo-Cego , Determinação de Ponto Final , Ácidos Graxos Ômega-3/efeitos adversos , Ácidos Graxos Ômega-3/farmacologia , Feminino , Seguimentos , Insuficiência Cardíaca/classificação , Insuficiência Cardíaca/mortalidade , Hospitalização/estatística & dados numéricos , Humanos , Itália , Masculino , Função Ventricular Esquerda/efeitos dos fármacosRESUMO
BACKGROUND: Large observational studies, small prospective studies and post-hoc analyses of randomised clinical trials have suggested that statins could be beneficial in patients with chronic heart failure. However, previous studies have been methodologically weak. We investigated the efficacy and safety of the statin rosuvastatin in patients with heart failure. METHODS: We undertook a randomised, double-blind, placebo-controlled trial in 326 cardiology and 31 internal medicine centres in Italy. We enrolled patients aged 18 years or older with chronic heart failure of New York Heart Association class II-IV, irrespective of cause and left ventricular ejection fraction, and randomly assigned them to rosuvastatin 10 mg daily (n=2285) or placebo (n=2289) by a concealed, computerised telephone randomisation system. Patients were followed up for a median of 3.9 years (IQR 3.0-4.4). Primary endpoints were time to death, and time to death or admission to hospital for cardiovascular reasons. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00336336. FINDINGS: We analysed all randomised patients. 657 (29%) patients died from any cause in the rosuvastatin group and 644 (28%) in the placebo group (adjusted hazard ratio [HR] 1.00 [95.5% CI 0.898-1.122], p=0.943). 1305 (57%) patients in the rosuvastatin group and 1283 (56%) in the placebo group died or were admitted to hospital for cardiovascular reasons (adjusted HR 1.01 [99% CI 0.908-1.112], p=0.903). In both groups, gastrointestinal disorders were the most frequent adverse reaction (34 [1%] rosuvastatin group vs 44 [2%] placebo group). INTERPRETATION: Rosuvastatin 10 mg daily did not affect clinical outcomes in patients with chronic heart failure of any cause, in whom the drug was safe.