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1.
Eur Heart J ; 2024 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-39185705

RESUMO

BACKGROUND AND AIMS: To explore male-female differences in aneurysm growth and clinical outcomes in a two-centre retrospective Dutch cohort study of adult patients with ascending aortic aneurysm (AscAA). METHODS: Adult patients in whom imaging of an AscAA (root and/or ascending: ≥40 mm) was performed between 2007 and 2022 were included. Aneurysm growth was analysed using repeated measurements at the sinuses of Valsalva (SoV) and tubular ascending aorta. Male-female differences were explored in presentation, aneurysm characteristics, treatment strategy, survival, and clinical outcomes. RESULTS: One thousand eight hundred and fifty-eight patients were included (31.6% female). Median age at diagnosis was 65.4 years (interquartile range: 53.4-71.7) for females and 59.0 years (interquartile range: 49.3-68.0) for males (P < .001). At diagnosis, females more often had tubular ascending aortic involvement (75.5% vs. 70.2%; P = .030) while males more often had SoV involvement (42.8% vs. 21.6%; P < .001). Maximum absolute aortic diameter, at any location, at diagnosis did not differ between females (45.0 mm) and males (46.5 mm; P = .388). In females, tubular ascending growth was faster (P < .001), whereas in males, SoV growth was faster (P = .005), corrected for covariates. Unadjusted 10-year survival was 72.5% [95% confidence interval (CI) 67.8%-77.6%] for females and 78.3% (95% CI 75.3%-81.3%) for males (P = .010). Twenty-three type A dissections occurred, with an incidence rate of 8.2/1000 patient-years (95% CI 4.4-14.1) in females and 2.4/1000 patient-years (95% CI 1.2-4.5) in males [incidence rate ratio females/males: 3.4 (95% CI 1.5-8.0; P = .004)]. CONCLUSIONS: In patients having entered a diagnostic programme, involvement of aortic segments and age- and segment-related growth patterns differ between women and men with AscAA, particularly at an older age. Unravelling of these intertwined observations will provide a deeper understanding of AscAA progression and outcome in women and men and can be used as an evidence base for patient-tailored clinical guideline development.

2.
Eur Heart J ; 45(32): 2954-2964, 2024 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-38733175

RESUMO

BACKGROUND AND AIMS: In patients with chronic heart failure (HF), the MONITOR-HF trial demonstrated the efficacy of pulmonary artery (PA)-guided HF therapy over standard of care in improving quality of life and reducing HF hospitalizations and mean PA pressure. This study aimed to evaluate the consistency of these benefits in relation to clinically relevant subgroups. METHODS: The effect of PA-guided HF therapy was evaluated in the MONITOR-HF trial among predefined subgroups based on age, sex, atrial fibrillation, diabetes mellitus, left ventricular ejection fraction, HF aetiology, cardiac resynchronization therapy, and implantable cardioverter defibrillator. Outcome measures were based upon significance in the main trial and included quality of life-, clinical-, and PA pressure endpoints, and were assessed for each subgroup. Differential effects in relation to the subgroups were assessed with interaction terms. Both unadjusted and multiple testing adjusted interaction terms were presented. RESULTS: The effects of PA monitoring on quality of life, clinical events, and PA pressure were consistent in the predefined subgroups, without any clinically relevant heterogeneity within or across all endpoint categories (all adjusted interaction P-values were non-significant). In the unadjusted analysis of the primary endpoint quality-of-life change, weak trends towards a less pronounced effect in older patients (Pinteraction = .03; adjusted Pinteraction = .33) and diabetics (Pinteraction = .01; adjusted Pinteraction = .06) were observed. However, these interaction effects did not persist after adjusting for multiple testing. CONCLUSIONS: This subgroup analysis confirmed the consistent benefits of PA-guided HF therapy observed in the MONITOR-HF trial across clinically relevant subgroups, highlighting its efficacy in improving quality of life, clinical, and PA pressure endpoints in chronic HF patients.


Assuntos
Insuficiência Cardíaca , Artéria Pulmonar , Qualidade de Vida , Humanos , Insuficiência Cardíaca/terapia , Insuficiência Cardíaca/fisiopatologia , Feminino , Masculino , Idoso , Pessoa de Meia-Idade , Artéria Pulmonar/fisiopatologia , Doença Crônica , Volume Sistólico/fisiologia , Terapia de Ressincronização Cardíaca/métodos , Desfibriladores Implantáveis
3.
Circ Res ; 130(2): 166-180, 2022 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-34886679

RESUMO

RATIONALE: Dextro-transposition of the great arteries (D-TGA) is a severe congenital heart defect which affects approximately 1 in 4,000 live births. While there are several reports of D-TGA patients with rare variants in individual genes, the majority of D-TGA cases remain genetically elusive. Familial recurrence patterns and the observation that most cases with D-TGA are sporadic suggest a polygenic inheritance for the disorder, yet this remains unexplored. OBJECTIVE: We sought to study the role of common single nucleotide polymorphisms (SNPs) in risk for D-TGA. METHODS AND RESULTS: We conducted a genome-wide association study in an international set of 1,237 patients with D-TGA and identified a genome-wide significant susceptibility locus on chromosome 3p14.3, which was subsequently replicated in an independent case-control set (rs56219800, meta-analysis P=8.6x10-10, OR=0.69 per C allele). SNP-based heritability analysis showed that 25% of variance in susceptibility to D-TGA may be explained by common variants. A genome-wide polygenic risk score derived from the discovery set was significantly associated to D-TGA in the replication set (P=4x10-5). The genome-wide significant locus (3p14.3) co-localizes with a putative regulatory element that interacts with the promoter of WNT5A, which encodes the Wnt Family Member 5A protein known for its role in cardiac development in mice. We show that this element drives reporter gene activity in the developing heart of mice and zebrafish and is bound by the developmental transcription factor TBX20. We further demonstrate that TBX20 attenuates Wnt5a expression levels in the developing mouse heart. CONCLUSIONS: This work provides support for a polygenic architecture in D-TGA and identifies a susceptibility locus on chromosome 3p14.3 near WNT5A. Genomic and functional data support a causal role of WNT5A at the locus.


Assuntos
Polimorfismo de Nucleotídeo Único , Transposição dos Grandes Vasos/genética , Animais , Células Cultivadas , Humanos , Camundongos , Herança Multifatorial , Miócitos Cardíacos/metabolismo , Proteínas com Domínio T/genética , Proteínas com Domínio T/metabolismo , Transposição dos Grandes Vasos/metabolismo , Proteína Wnt-5a/genética , Proteína Wnt-5a/metabolismo , Peixe-Zebra
4.
Br J Sports Med ; 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-39153748

RESUMO

OBJECTIVE: Concerns exist about the possible detrimental effects of exercise training on aortic size and valve function in individuals with bicuspid aortic valve (BAV). This multicentre international study aimed to determine the characteristics of aortic size and valve function in athletes versus non-athletes with BAV and athletes with tricuspid aortic valve (TAV). METHODS: We enrolled competitive athletes with BAV and age- and sex-matched athletes with TAV and non-athletes with BAV. We assessed valve function, aortic size and biventricular measures using echocardiography. Individuals with established moderate-severe AV stenosis, regurgitation or significant aortic dilation were excluded from the study. RESULTS: The study population comprised 504 participants: 186 competitive athletes with BAV (84% males; age 30±11 years), 193 competitive athletes with TAV and 125 non-athletes with BAV. The aortic annulus was greater in athletes with BAV than athletes with TAV and non-athletes with BAV (p<0.001). Both athletic and non-athletic individuals with BAV had greater sinuses of Valsalva, sino-tubular junction and ascending aorta diameters than athletes with TAV (p<0.001). However, no significant differences were found between athletes and non-athletes with BAV. Left ventricular index volumes and mass were greater in athletes with BAV than in the other two groups (p<0.001). Individuals with BAV (athletes and non-athletes) had greater mean gradients than TAV athletes. CONCLUSION: This multicentre international study demonstrates no differences between athletes with BAV and non-athletes with BAV regarding aortic valve function or aortic dimensions. However, athletes with BAV have larger aortic diameters and a relatively worse valvular function than athletes with TAV.

5.
Eur Heart J ; 44(19): 1705-1714, 2023 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-36755110

RESUMO

AIMS: Patients with suspected non-ST-segment elevation acute coronary syndrome (NSTE-ACS) are routinely transferred to the emergency department (ED). A clinical risk score with point-of-care (POC) troponin measurement might enable ambulance paramedics to identify low-risk patients in whom ED evaluation is unnecessary. The aim was to assess safety and healthcare costs of a pre-hospital rule-out strategy using a POC troponin measurement in low-risk suspected NSTE-ACS patients. METHODS AND RESULTS: This investigator-initiated, randomized clinical trial was conducted in five ambulance regions in the Netherlands. Suspected NSTE-ACS patients with HEAR (History, ECG, Age, Risk factors) score ≤3 were randomized to pre-hospital rule-out with POC troponin measurement or direct transfer to the ED. The sample size calculation was based on the primary outcome of 30-day healthcare costs. Secondary outcome was safety, defined as 30-day major adverse cardiac events (MACE), consisting of ACS, unplanned revascularization or all-cause death. : A total of 863 participants were randomized. Healthcare costs were significantly lower in the pre-hospital strategy (€1349 ± €2051 vs. €1960 ± €1808) with a mean difference of €611 [95% confidence interval (CI): 353-869; P < 0.001]. In the total population, MACE were comparable between groups [3.9% (17/434) in pre-hospital strategy vs. 3.7% (16/429) in ED strategy; P = 0.89]. In the ruled-out ACS population, MACE were very low [0.5% (2/419) vs. 1.0% (4/417)], with a risk difference of -0.5% (95% CI -1.6%-0.7%; P = 0.41) in favour of the pre-hospital strategy. CONCLUSION: Pre-hospital rule-out of ACS with a POC troponin measurement in low-risk patients significantly reduces healthcare costs while incidence of MACE was low in both strategies. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT05466591 and International Clinical Trials Registry Platform id NTR 7346.


Assuntos
Síndrome Coronariana Aguda , Troponina , Humanos , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/epidemiologia , Medição de Risco/métodos , Valor Preditivo dos Testes , Estudos Prospectivos , Hospitais , Biomarcadores , Eletrocardiografia/métodos
6.
Int J Mol Sci ; 25(9)2024 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-38732244

RESUMO

Cardiovascular outcome in Marfan syndrome (MFS) patients most prominently depends on aortic aneurysm progression with subsequent aortic dissection. Angiotensin II receptor blockers (ARBs) prevent aneurysm formation in MFS mouse models. In patients, ARBs only slow down aortic dilation. Downstream signalling from the angiotensin II type 1 receptor (AT1R) is mediated by G proteins and ß-arrestin recruitment. AT1R also interacts with the monocyte chemoattractant protein-1 (MCP-1) receptor, resulting in inflammation. In this study, we explore the targeting of ß-arrestin signalling in MFS mice by administering TRV027. Furthermore, because high doses of the ARB losartan, which has been proven beneficial in MFS, cannot be achieved in humans, we investigate a potential additive effect by combining lower concentrations of losartan (25 mg/kg/day and 5 mg/kg/day) with barbadin, a ß-arrestin blocker, and DMX20, a C-C chemokine receptor type 2 (CCR2) blocker. A high dose of losartan (50 mg/kg/day) slowed down aneurysm progression compared to untreated MFS mice (1.73 ± 0.12 vs. 1.96 ± 0.08 mm, p = 0.0033). TRV027, the combination of barbadin with losartan (25 mg/kg/day), and DMX-200 (90 mg/kg/day) with a low dose of losartan (5 mg/kg/day) did not show a significant beneficial effect. Our results confirm that while losartan effectively halts aneurysm formation in Fbn1C1041G/+ MFS mice, neither TRV027 alone nor any of the other compounds combined with lower doses of losartan demonstrate a notable impact on aneurysm advancement. It appears that complete blockade of AT1R function, achieved by administrating a high dosage of losartan, may be necessary for inhibiting aneurysm progression in MFS.


Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II , Aneurisma Aórtico , Losartan , Síndrome de Marfan , Transdução de Sinais , Camundongos , Síndrome de Marfan/tratamento farmacológico , Síndrome de Marfan/patologia , Modelos Animais de Doenças , Aneurisma Aórtico/tratamento farmacológico , Aneurisma Aórtico/prevenção & controle , Oligopeptídeos/administração & dosagem , Aorta Torácica/efeitos dos fármacos , Aorta Torácica/patologia , Pirimidinas/administração & dosagem , Combinação de Medicamentos , Losartan/administração & dosagem , Antagonistas de Receptores de Angiotensina/administração & dosagem , Transdução de Sinais/efeitos dos fármacos , Humanos , Bloqueadores do Receptor Tipo 1 de Angiotensina II/administração & dosagem
7.
Eur J Vasc Endovasc Surg ; 65(1): 120-130, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36220622

RESUMO

OBJECTIVE: Midaortic syndrome (MAS) is narrowing of the distal thoracic and or abdominal aorta with congenital, inflammatory, or idiopathic aetiology. If left untreated, the prognosis is poor due to hypertensive complications. Follow up data after treatment are sparse, contrary to aortic coarctation. This study aimed to investigate hypertension during follow up after medical, endovascular, and surgical therapy in juveniles and adults. DATA SOURCES: A meta-analysis of case series and reports was performed, focusing on the incidence of hypertension during the follow up of juvenile (i.e., age 0-17 years) and adult MAS patients after medical, endovascular, or surgical therapy. REVIEW METHODS: Search queries were performed in PubMed, Embase, and Web of Science, and eligible articles underwent quality control. Descriptive statistics were reported based on available data, and individual patient data meta-analyses were performed using a one stage approach, accounting for clustering by case series or decades of reporting for case reports. For the meta-analysis, missing outcome and aetiology data were multiply imputed. RESULTS: The number of juveniles and adults who underwent endovascular therapy (33.7% vs. 27.3%; p = .42) and surgery (52.2% vs. 58.0%; p = .46) was similar. At baseline, 92.4% of juveniles and 87.5% of adults were hypertensive, decreasing to 23.2% and 24.1% during a follow up of 23 months (juveniles) and 18 months (adults), respectively. More hypertension was found compared with surgery in juveniles after endovascular therapy (38.1% vs. 10.8%; p = .020). Meta-analysis also demonstrated a trend for hypertension after endovascular therapy in juveniles, whereas hypertension was more prevalent following surgery in adults compared with endovascular therapy or medication. CONCLUSION: This review and meta-analysis investigated therapeutic options for MAS in juveniles and adults. It found that complications and hypertension during follow up were more common in juveniles after endovascular treatment, whereas surgery in adults was associated with more hypertension.

8.
Eur J Vasc Endovasc Surg ; 66(3): 332-341, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37245796

RESUMO

OBJECTIVE: Acute type B aortic dissection (ATBD) is a rare yet serious cardiovascular event that potentially has an impact on health related quality of life (HRQoL). However, long term follow up data on this topic are scarce. This study aimed to review the long term HRQoL among patients treated for ATBD. METHODS: In this multicentre, cross sectional survey study, consecutive treated patients with ATBD between 2007 and 2017 in four referral centres in the Netherlands were retrospectively included and baseline data were collected. Between 2019 and 2021 the 36 Item Short Form Survey (SF-36) was sent to all surviving patients (n = 263) and was compared with validated SF-36 scores in the Dutch general population stratified by age and sex. RESULTS: In total, 144 of 263 surviving patients completed the SF-36 (response rate 55%). Median (IQR) age was 68 (61, 76) years at completion of the questionnaire, and 40% (n = 58) were female. Initial treatment was medical in 55% (n = 79), endovascular in 41% (n = 59), and surgical in 4% (n = 6) of ATBD patients. Median follow up time was 6.1 (range 1.7-13.9; IQR 4.0, 9.0) years. Compared with the general population, patients scored significantly worse on six of eight SF-36 subdomains, particularly physical domains. Apart from bodily pain, there were no substantial differences in HRQoL between male and female ATBD patients. Compared with sex matched normative data, females scored significantly worse on five of eight subdomains, whereas males scored significantly lower on six subdomains. Younger patients aged 41-60 years seemed more severely impaired in HRQoL compared with the age matched general population. Treatment strategy did not influence HRQoL outcomes. Follow up time was associated with better Physical and Mental Component Summary scores. CONCLUSION: Long term HRQoL was impaired in ATBD patients compared with the Dutch general population, especially regarding physical status. This warrants more attention for HRQoL during clinical follow up. Rehabilitation programmes including exercise and physical support might improve HRQoL and increase patients' health understanding.


Assuntos
Dissecção Aórtica , Qualidade de Vida , Humanos , Masculino , Feminino , Estudos Transversais , Estudos Retrospectivos , Inquéritos e Questionários , Dissecção Aórtica/cirurgia
9.
Eur Heart J ; 43(29): 2801-2811, 2022 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-35560020

RESUMO

AIMS: To investigate the association between the timing of cardiac surgery during pregnancy and both maternal and foetal outcomes. METHODS AND RESULTS: Studies published up to 6 February 2021 on maternal and/or foetal mortality after cardiac surgery during pregnancy that included individual patient data were identified. Maternal and foetal mortality was analysed per trimester for the total population and stratified for patients who underwent caesarean section (CS) prior to cardiac surgery (Caesarean section (CaeSe) group) vs. patients who did not (Cardiac surgery (CarSu) group). Multivariable logistic regression analysis was performed to evaluate predictors of both maternal and foetal mortality. In total, 179 studies were identified including 386 patients of which 120 underwent CS prior to cardiac surgery. Maternal mortality was 7.3% and did not differ significantly among trimesters of pregnancy (P = 0.292) nor between subgroup CaeSe and CarSu (P = 0.671). Overall foetal mortality was 26.5% and was lowest when cardiac surgery was performed during the third trimester (10.3%, P < 0.01). CS prior to surgery was significantly associated with a reduced risk of foetal mortality in a multivariable model [odds ratio 0.19, 95% confidence interval [0.06-0.56)]. Trimester was not identified as an independent predictor for foetal nor maternal mortality. CONCLUSION: Maternal mortality after cardiac surgery during pregnancy is not associated with the trimester of pregnancy. Cardiac surgery is associated with high foetal mortality but is significantly lower in women where CS is performed prior to cardiac surgery. When the foetus is viable, CS prior to cardiac surgery might be safe. When CS is not feasible, trimester stage does not seem to influence foetal mortality.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Complicações Cardiovasculares na Gravidez , Trimestres da Gravidez , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Procedimentos Cirúrgicos Cardíacos/métodos , Cesárea , Feminino , Mortalidade Fetal , Humanos , Mortalidade Materna , Gravidez , Complicações Cardiovasculares na Gravidez/cirurgia , Resultado da Gravidez , Fatores de Tempo
10.
Am Heart J ; 252: 51-59, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35753356

RESUMO

BACKGROUND: Inflammation, measured by traditional biomarkers such as C-reactive protein, has been linked to cardiovascular (CV) events. Recent technological advancement has allowed for measuring larger numbers of inflammatory biomarkers. A contemporary evaluation with established and novel biomarkers of inflammation is needed. METHODS: 1,090 individuals who underwent coronary angiography were enrolled. Twenty-four inflammatory biomarkers were collected prior to angiography. Unsupervised machine learning cluster analyses determined unique patterns of inflammatory biomarkers. Cox proportional hazard regression assessed both association of inflammatory biomarker clusters and individual biomarker associations with major adverse cardiovascular events (MACE; non-fatal myocardial infarction or stroke, and CV death) during a median follow-up of 3.67 years. RESULTS: Four distinct clusters were recognized. Incremental increases in inflammatory biomarkers were observed from cluster 1 to cluster 4. During follow-up, 263 MACE were ascertained. Considering cluster 1 as a reference, study participants with inflammatory cluster 2 (Hazard ratio [HR] 1.55, 95% confidence interval [CI]: 1.01-2.37), cluster 3 (HR 1.89, CI: 1.25-2.85), and cluster 4 (HR 2.93, CI: 1.95-4.42) were at increased risk of MACE. Interleukin (IL)-1α IL-6, IL-8, IL-10, IL-12, Adhesion molecule-1 high-sensitivity C-reactive protein, ferritin, myeloperoxidase, macrophage inflammatory protein (MIP)-1a, MIP 3, and macrophage colony-stimulating factor-1 were independently associated with MACE. CONCLUSIONS: Among persons undergoing coronary angiography procedures, distinct clusters of inflammatory biomarker distributions with significant prognostic meaning may be identified. These results may identify unique targets for anti-inflammatory treatments aimed at CV disease.


Assuntos
Doença da Artéria Coronariana , Infarto do Miocárdio , Biomarcadores , Proteína C-Reativa/metabolismo , Angiografia Coronária , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/diagnóstico por imagem , Humanos , Inflamação , Interleucina-6 , Infarto do Miocárdio/complicações , Prognóstico , Fatores de Risco
11.
Clin Genet ; 102(5): 404-413, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36059006

RESUMO

Marfan syndrome (MFS) is a connective tissue disorder affecting the cardiovascular, ocular, and skeletal system, which may be accompanied by psychological features. This study aimed to determine the prevalence of fatigue, anxiety, and symptoms of depression in MFS patients, and to assess the degree to which sociodemographic and clinical variables are associated with fatigue and psychological aspects. The prevalence of fatigue, anxiety, and symptoms of depression were assessed in two cohorts of MFS patients and compared with healthy controls. The checklist individual strength (CIS), and hospital anxiety and depression scale (HADS) questionnaires were utilized. Medical status was assessed (family history of MFS, aortic root dilatation >40 mm, previous aortic surgery, aortic dissection, chronic pain, skeletal involvement, and scoliosis). Severe fatigue was experienced by 37% of the total MFS cohort (n = 155). MFS patients scored significantly higher on the CIS questionnaire, concerning severe fatigue, as compared with the general Dutch population (p < 0.0001). There were no differences in HADS anxiety or depression scores. In older MFS patients, with a more severe cardiovascular phenotype, chronic pain, and a higher unemployment rate, significantly more symptoms of depression were observed, when compared with the general population (p = 0.027) or compared with younger MFS patients (p = 0.026). Multivariate analysis, showed that anxiety was associated with chronic pain (p = 0.022) and symptoms of depression with unemployment (p = 0.024). MFS patients report significantly more severe fatigue as compared with the general population. Since the cause of fatigue is unclear, more research may be needed. Psychological intervention, for example, cognitive behavioral therapy, may contribute to a reduction in psychological symptoms.


Assuntos
Dor Crônica , Síndrome de Marfan , Ansiedade/epidemiologia , Ansiedade/etiologia , Ansiedade/psicologia , Estudos Transversais , Depressão/epidemiologia , Depressão/etiologia , Depressão/psicologia , Fadiga/complicações , Fadiga/etiologia , Humanos , Síndrome de Marfan/complicações , Síndrome de Marfan/diagnóstico , Síndrome de Marfan/epidemiologia
12.
J Card Fail ; 28(10): 1522-1530, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35705150

RESUMO

AIMS: It is common practice for clinicians to advise fluid restriction in patients with heart failure (HF), but data from clinical trials are lacking. Moreover, fluid restriction is associated with thirst distress and may adversely impact quality of life (QoL). To address this gap in evidence, the Fluid REStriction in Heart failure vs liberal fluid UPtake (FRESH-UP) study was initiated. METHODS: The FRESH-UP study is a randomized, controlled, open-label, multicenter trial to investigate the effects of a 3-month period of liberal fluid intake vs fluid restriction (1500 mL/day) on QoL in outpatients with chronic HF (New York Heart Association Classes II--III). The primary aim is to assess the effect on QoL after 3 months using the Overall Summary Score of the Kansas City Cardiomyopathy Questionnaire (KCCQ). Thirst distress, as assessed by the Thirst Distress Scale for patients with HF, KCCQ Clinical Summary Score, each of the KCCQ domains and clinically meaningful changes in these scores, the EQ-5D-5L, patient-reported fluid intake and safety (ie, death, HF hospitalizations) are secondary outcomes. The FRESH-UP study is registered at ClinicalTrials.gov (NCT04551729). CONCLUSION: The results of the FRESH-UP study will add substantially to the level of evidence concerning fluid management in chronic HF and may impact the QoL of these patients.


Assuntos
Ingestão de Líquidos , Insuficiência Cardíaca , Humanos , Doença Crônica , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como Assunto
13.
Am Heart J ; 226: 60-68, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32512291

RESUMO

There is much debate on the use of angiotensin receptor blockers (ARBs) in severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2)-infected patients. Although it has been suggested that ARBs might lead to a higher susceptibility and severity of SARS-CoV-2 infection, experimental data suggest that ARBs may reduce acute lung injury via blocking angiotensin-II-mediated pulmonary permeability, inflammation, and fibrosis. However, despite these hypotheses, specific studies on ARBs in SARS-CoV-2 patients are lacking. METHODS: The PRAETORIAN-COVID trial is a multicenter, double-blind, placebo-controlled 1:1 randomized clinical trial in adult hospitalized SARS-CoV-2-infected patients (n = 651). The primary aim is to investigate the effect of the ARB valsartan compared to placebo on the composite end point of admission to an intensive care unit, mechanical ventilation, or death within 14 days of randomization. The active-treatment arm will receive valsartan in a dosage titrated to blood pressure up to a maximum of 160 mg bid, and the placebo arm will receive matching placebo. Treatment duration will be 14 days, or until the occurrence of the primary end point or until hospital discharge, if either of these occurs within 14 days. The trial is registered at clinicaltrials.gov (NCT04335786, 2020). SUMMARY: The PRAETORIAN-COVID trial is a double-blind, placebo-controlled 1:1 randomized trial to assess the effect of valsartan compared to placebo on the occurrence of ICU admission, mechanical ventilation, and death in hospitalized SARS-CoV-2-infected patients. The results of this study might impact the treatment of SARS-CoV-2 patients globally.


Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Betacoronavirus , Unidades de Cuidados Coronarianos , Infecções por Coronavirus/complicações , Pneumonia Viral/complicações , Ensaios Clínicos Controlados Aleatórios como Assunto , Síndrome do Desconforto Respiratório/prevenção & controle , Valsartana/uso terapêutico , Adulto , Bloqueadores do Receptor Tipo 1 de Angiotensina II/administração & dosagem , COVID-19 , Infecções por Coronavirus/mortalidade , Método Duplo-Cego , Esquema de Medicação , Humanos , Pacientes Internados , Estudos Multicêntricos como Assunto , Países Baixos , Pandemias , Placebos/uso terapêutico , Pneumonia Viral/mortalidade , Respiração Artificial , Síndrome do Desconforto Respiratório/mortalidade , SARS-CoV-2 , Fatores de Tempo , Valsartana/administração & dosagem
14.
J Genet Couns ; 29(6): 1259-1269, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32519797

RESUMO

Hereditary thoracic aortic diseases (HTAD) such as Marfan syndrome (MFS) affect multiple organ systems and provide a risk of acute aortic dissection, which causes lifelong uncertainties. Although health-related quality of life (HRQOL) was found to be reduced in HTAD patients, no studies have evaluated male-female-specific aspects of HRQOL and coping in this population. This study aims to evaluate HRQOL in HTAD patients compared to the general population; assess male-female differences in HRQOL and factors associated with HRQOL; evaluate coping styles in male and female HTAD patients and identify factors associated with acceptance. All consecutive adult patients who visited the specialized HTAD outpatient clinic between 2013 and 2018 were asked to complete three HRQOL questionnaires: the Short Form 36 (SF-36), the Hospital Anxiety and Depression Scale (HADS), and the Nijmegen Clinical Screening Instrument (NCSI). In total, 142 patients were included (mean age 42.1 years, 65 females, 123 MFS). Compared to the general population, HTAD patients scored significantly lower on multiple SF-36 sub-domains (males: General Health 54.5 ± 18.8 vs. 71.6 ± 20.6, p < .001; Vitality 58.3 ± 20.4 vs. 71.9 ± 18.3, p < .001; females: Physical Functioning 67.5 ± 23.8 vs. 80.4 ± 24.2, p = .003; Role Physical 58.3 ± 45.1 vs. 73.8 ± 38.5, p = .047; General Health 49.4 ± 24.3 vs. 69.9 ± 20.6, p < .001; Social Functioning 73.5 ± 22.0 vs. 82.0 ± 23.5, p = .027). Females scored significantly lower than males on the SF-36 physical component score (41.6 [IQR 35.5-53.1] vs. 49.3 [IQR 42.3-54.6], p = .035). Males scored significantly higher on the coping style denial than females (2.75 [IQR 2.00-3.25] vs. 2.25 [IQR 1.75-3.25], p = .018). High scores on acceptance were found in 38 (26.8%) of HTAD patients, and these patients showed significantly better scores on the NCSI, SF-36, and HADS, except on NCSI Satisfaction Relationships and SF-36 Physical Functioning and Mental Health. Acceptance was associated with more medication use (beta blocker use, p = .008; angiotensin receptor blocker use, p = .003) and less hypertension (p = .001). In patients with MFS, employment was strongly associated with better scores on the NCSI. In conclusion, HTAD patients showed subnormal HRQOL, especially females. Interestingly, in both males and females factors such as employment, coping style, and disease acceptance seem more important for HRQOL than disease-related factors. This highlights the importance of genetic counseling and guidance for HTAD patients, and offers valuable leads for HRQOL improvement.


Assuntos
Adaptação Psicológica , Doenças da Aorta/psicologia , Síndrome de Marfan/psicologia , Qualidade de Vida/psicologia , Fatores Sexuais , Adulto , Doenças da Aorta/genética , Feminino , Humanos , Masculino , Saúde Mental , Pessoa de Meia-Idade , Inquéritos e Questionários
16.
Circulation ; 135(2): 116-127, 2017 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-27881568

RESUMO

BACKGROUND: Despite growing recognition of type 2 myocardial infarction (T2MI; related to supply/demand mismatch), little is known about its risk factors or its association with outcome. METHODS: A single-center cohort of patients undergoing coronary or peripheral angiography with or without intervention was prospectively enrolled and followed for incident type 1 and T2MI, and major adverse cardiovascular events (MACE, a composite of all-cause death, nonfatal myocardial infarction [MI], heart failure, stroke, transient ischemic attack, peripheral arterial complication, and cardiac arrhythmia), as well. T2MI was adjudicated using criteria from the Third Universal Definition of MI. Baseline characteristics, blood samples, and angiography information were obtained. Major end points subsequent to first MI were assessed using landmark analyses to compare the rates of first events only where everyone with a prior history of any MACE before MI were censored and adjusted for follow-up times. Cox proportional hazard models were used for time-to-event analyses with age and sex forced into all models and additional covariates evaluated by using the stepwise option for the selection. RESULTS: One thousand two hundred fifty-one patients were enrolled and followed for a median of 3.4 years. Of these patients, 152 (12.2%) had T2MI during follow-up; T2MI was frequently recurrent. Multivariable predictors of T2MI were older age, lower systolic blood pressure, history of coronary artery disease, heart failure, chronic obstructive pulmonary disease, diabetes mellitus, nitrate use, and elevated concentrations of glucose, N-terminal pro-B type natriuretic peptide, and cystatin C. Patients with T2MI had higher rates of subsequent adverse events than those without T2MI (per 100 person-years: MACE, 53.7 versus 21.1, P<0.001; all-cause death, 23.3 versus 3.3, P<0.001; cardiovascular death, 17.5 versus 2.6, P<0.001; heart failure events, 22.4 versus 7.4, P<0.001); these rates are similar to those seen in patients with type 1 MI. Incident diagnosis of T2MI strongly predicted risk for subsequent MACE (adjusted hazard ratio, 1.90; 95% confidence interval, 1.46-2.48; P<0.001), all-cause death (adjusted hazard ratio, 2.96; 95% confidence interval, 2.01-4.36; P<0.001), and cardiovascular death (adjusted hazard ratio, 2.16; 95% confidence interval, 1.36-3.43; P=0.001). CONCLUSIONS: T2MI is common and associated with poor prognosis. Studies evaluating treatment strategies for management of T2MI are needed. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00842868.


Assuntos
Angiografia , Doença da Artéria Coronariana/complicações , Infarto do Miocárdio/complicações , Infarto do Miocárdio/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Angiografia/efeitos adversos , Estudos de Coortes , Feminino , Seguimentos , Coração/fisiopatologia , Insuficiência Cardíaca/complicações , Humanos , Ataque Isquêmico Transitório/complicações , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/tratamento farmacológico , Medição de Risco , Fatores de Risco
17.
Clin Chem ; 64(11): 1617-1625, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30213784

RESUMO

BACKGROUND: Endothelin-1 (ET-1) is a vasoconstrictor produced by vascular endothelial cells and may play a role in risk for development of coronary artery disease (CAD) and heart failure (HF). In a cohort of 1084 patients referred for coronary angiography, we investigated cross-sectional associations between ET-1 concentrations and prevalent CAD, as well as value of ET-1 for prognostication of future cardiovascular events. METHODS: Associations between ET-1 and presence/severity of CAD were assessed. Patients were followed for a median of 4 years for outcomes including incident HF, myocardial infarction (MI), cardiovascular mortality, and all-cause mortality. RESULTS: The median concentration of ET-1 was 2.57 ng/L. Patients with ET-1 concentrations above the median were more likely to have higher risk clinical features. Among those without prevalent MI at presentation, ET-1 concentrations were not associated with presence or severity of CAD. In adjusted Cox proportional hazards analyses, log-transformed ET-1 concentrations predicted incident HF [hazard ratio (HR) = 1.51 per increase in log-SD; 95% CI, 1.06-2.15; P = 0.02] and all-cause mortality (HR = 1.61 per increase in log-SD; 95% CI, 1.03-2.53; P = 0.04). Concentrations of ET-1 above the median were associated with shorter time to incident HF, MI, cardiovascular mortality, all-cause mortality, and the composite of incident HF/MI/cardiovascular mortality (all log-rank P < 0.001). CONCLUSIONS: Despite epidemiologic links to CAD, we found no cross-sectional association between biologically active ET-1 and prevalent coronary atherosclerosis in an at-risk population referred for coronary angiography. Increased ET-1 concentrations independently predict incident HF and death and are associated with more near-term cardiovascular events.


Assuntos
Doenças Cardiovasculares/sangue , Endotelina-1/sangue , Endotélio Vascular/metabolismo , Biomarcadores/sangue , Doenças Cardiovasculares/diagnóstico por imagem , Doenças Cardiovasculares/mortalidade , Cateterismo , Angiografia Coronária , Estudos Transversais , Feminino , Seguimentos , Humanos , Masculino , Valor Preditivo dos Testes , Prevalência , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Fatores Sexuais
18.
Ann Intern Med ; 166(10): 689-697, 2017 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-28437795

RESUMO

BACKGROUND: The HEART (History, Electrocardiogram, Age, Risk factors, and initial Troponin) score is an easy-to-apply instrument to stratify patients with chest pain according to their short-term risk for major adverse cardiac events (MACEs), but its effect on daily practice is unknown. OBJECTIVE: To measure the effect of use of the HEART score on patient outcomes and use of health care resources. DESIGN: Stepped-wedge, cluster randomized trial. (ClinicalTrials.gov: NCT01756846). SETTING: Emergency departments in 9 Dutch hospitals. PATIENTS: Unselected patients with chest pain presenting at emergency departments in 2013 and 2014. INTERVENTION: All hospitals started with usual care. Every 6 weeks, 1 hospital was randomly assigned to switch to "HEART care," during which physicians calculated the HEART score to guide patient management. MEASUREMENTS: For safety, a noninferiority margin of a 3.0% absolute increase in MACEs within 6 weeks was set. Other outcomes included use of health care resources, quality of life, and cost-effectiveness. RESULTS: A total of 3648 patients were included (1827 receiving usual care and 1821 receiving HEART care). Six-week incidence of MACEs during HEART care was 1.3% lower than during usual care (upper limit of the 1-sided 95% CI, 2.1% [within the noninferiority margin of 3.0%]). In low-risk patients, incidence of MACEs was 2.0% (95% CI, 1.2% to 3.3%). No statistically significant differences in early discharge, readmissions, recurrent emergency department visits, outpatient visits, or visits to general practitioners were observed. LIMITATION: Physicians were hesitant to refrain from admission and diagnostic tests in patients classified as low risk by the HEART score. CONCLUSION: Using the HEART score during initial assessment of patients with chest pain is safe, but the effect on health care resources is limited, possibly due to nonadherence to management recommendations. PRIMARY FUNDING SOURCE: Netherlands Organisation for Health Research and Development.


Assuntos
Dor no Peito/etiologia , Doença das Coronárias/diagnóstico , Eletrocardiografia , Serviço Hospitalar de Emergência , Anamnese , Troponina/sangue , Fatores Etários , Dor no Peito/sangue , Análise Custo-Benefício , Serviço Hospitalar de Emergência/economia , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Gastos em Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Medição de Risco/métodos , Fatores de Risco
19.
Pediatr Radiol ; 45(1): 5-19, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25552386

RESUMO

Due to advances in cardiac surgery, survival of patients with congenital heart disease has increased considerably during the past decades. Many of these patients require repeated cardiovascular magnetic resonance imaging to assess cardiac anatomy and function. In the past decade, technological advances have enabled faster and more robust cardiovascular magnetic resonance with improved image quality and spatial as well as temporal resolution. This review aims to provide an overview of advances in cardiovascular magnetic resonance hardware and acquisition techniques relevant to both pediatric and adult patients with congenital heart disease and discusses the techniques used to assess function, anatomy, flow and tissue characterization.


Assuntos
Técnicas de Imagem de Sincronização Cardíaca/métodos , Cardiopatias Congênitas/patologia , Aumento da Imagem/métodos , Imageamento Tridimensional/métodos , Imageamento por Ressonância Magnética/métodos , Criança , Humanos , Imageamento por Ressonância Magnética/instrumentação , Adulto Jovem
20.
J Am Heart Assoc ; 13(12): e034774, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38860394

RESUMO

BACKGROUND: Higher lipoprotein(a) and oxidized phospholipid concentrations are associated with increased risk for coronary artery disease and valvular heart disease. The role of lipoprotein(a) or oxidized phospholipid as a risk factor for incident heart failure (HF) or its complications remains uncertain. METHODS AND RESULTS: A total of 1251 individuals referred for coronary angiography in the Catheter Sampled Blood Archive in Cardiovascular Diseases (CASABLANCA) study were stratified on the basis of universal definition of HF stage; those in stage A/B (N=714) were followed up for an average 3.7 years for incident stage C/D HF or the composite of HF/cardiovascular death. During follow-up, 105 (14.7%) study participants in stage A/B progressed to symptomatic HF and 57 (8.0%) had cardiovascular death. In models adjusted for multiple HF risk factors, including severe coronary artery disease and aortic stenosis, individuals with lipoprotein(a) ≥150 nmol/L were at higher risk for progression to symptomatic HF (hazard ratio [HR], 1.90 [95% CI, 1.15-3.13]; P=0.01) or the composite of HF/cardiovascular death (HR, 1.71 [95% CI, 1.10-2.67]; P=0.02). These results remained significant after further adjustment of the model to include prior myocardial infarction (HF: HR, 1.89, P=0.01; HF/cardiovascular death: HR, 1.68, P=0.02). Elevated oxidized phospholipid concentrations were similarly associated with risk, particularly when added to higher lipoprotein(a). In Kaplan-Meier analyses, individuals with stage A/B HF and elevated lipoprotein(a) had shorter time to progression to stage C/D HF or HF/cardiovascular death (both log-rank P<0.001). CONCLUSIONS: Among individuals with stage A or B HF, higher lipoprotein(a) and oxidized phospholipid concentrations are independent risk factors for progression to symptomatic HF or cardiovascular death. REGISTRATION: URL: https://wwwclinicaltrials.gov; Unique identifier: NCT00842868.


Assuntos
Biomarcadores , Progressão da Doença , Insuficiência Cardíaca , Lipoproteína(a) , Oxirredução , Fosfolipídeos , Humanos , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/diagnóstico , Feminino , Masculino , Idoso , Lipoproteína(a)/sangue , Pessoa de Meia-Idade , Fosfolipídeos/sangue , Biomarcadores/sangue , Fatores de Risco , Fatores de Tempo , Estudos Prospectivos , Medição de Risco , Incidência , Angiografia Coronária , Prognóstico
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