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Background: Papillary muscle-delayed hyperenhancement (papHE) at cardiac magnetic resonance indicates fibrotic or infiltrative processes. Contrary to myocardial HE, the prevalence and prognostic implications of papHE in patients with nonischemic dilated cardiomyopathy are unclear. Objectives: The purpose of this study was to determine the prevalence of papHE and describe its association with adverse clinical outcomes. Methods: This prospective cohort study included 528 patients who underwent late gadolinium enhancement cardiac magnetic resonance. The primary outcomes were all-cause mortality, sudden cardiac death, life-threatening arrhythmia, and hospitalization for heart failure. Patients were allocated into 4 categories: the first without papHE and without myocardial HE, the second with papHE, the third with myocardial HE, and the fourth with papHE and myocardial HE. The hazards of the primary outcomes for each category were compared using multivariable Cox regression. Results: papHE was present in 131 patients (25%). The median follow-up duration was 6.1 years (IQR: 3.7-9.7 years). Isolated papHE and isolated myocardial HE were not significantly associated with any of the prespecified outcomes. Patients who had both myocardial HE and papHE were at an increased risk of all-cause mortality (HR: 2.33, 95% CI: 1.26-4.30), sudden cardiac death (HR: 3.77, 95% CI: 1.59-8.94), life-threatening arrhythmia (HR: 3.94, 95% CI: 1.34-11.58), and hospitalization for heart failure (HR: 2.97, 95% CI: 1.30-6.80). Conclusions: The combined presence of myocardial and papHE was independently associated with adverse outcomes. Future studies should investigate if the incorporation of papHE and myocardial HE may improve clinical decision-making strategies to select dilated cardiomyopathy patients who would benefit the most from ICD implantation.
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Recent landmark trials showed that colchicine provides a substantial benefit in reducing major cardiovascular events in patients with coronary artery disease. Yet, its exact mechanism of action is still poorly understood. This study aimed to unravel the effect of colchicine on monocyte and neutrophil phenotype and function. A randomized double-blind placebo-controlled cross-over intervention study was executed in patients with a history of myocardial infarction. In neutrophils, colchicine treatment decreased CD62L expression and NGAL release upon ex vivo stimulation and increased PMA-induced ROS production. The effects of colchicine on monocytes were limited to a decrease in HLA-DR expression in the intermediate and nonclassical monocytes. Also, on the level of RNA expression, colchicine did not affect monocyte phenotype, while affecting various immunomodulating genes in neutrophils. Overall, our study suggests that treatment with colchicine affects neutrophil function, particularly by reducing neutrophil recruitment, lowering concentrations of NGAL, and changing the expression of various genes with immunomodulatory potential, whereas the effect on monocytes is limited.
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Aims: Recently, novel post-processing tools have become available that measure intraventricular pressure gradients (IVPGs) on routinely obtained long-axis cine cardiac magnetic resonance (CMR) images. IVPGs provide a comprehensive overview of both systolic and diastolic left ventricular (LV) functions. Whether IVPGs are associated with clinical outcome after ST-elevation myocardial infarction (STEMI) is currently unknown. Here, we investigated the association between CMR-derived LV-IVPGs and major adverse cardiovascular events (MACE) in a large reperfused STEMI cohort with long-term outcome. Methods and results: In this prospectively enrolled multi-centre cohort study, 307 patients underwent CMR within 14 days after the first STEMI. LV-IVPGs (from apex-to-base) were estimated on the long-axis cine images. During a median follow-up of 9.7 (5.9-12.5) years, MACE (i.e. composite of cardiovascular death and de novo heart failure hospitalisation) occurred in 49 patients (16.0%). These patients had larger infarcts, more often microvascular injury, and impaired LV-IVPGs. In univariable Cox regression, overall LV-IVPG was significantly associated with MACE and remained significantly associated after adjustment for common clinical risk factors (hazard ratio (HR) 0.873, 95% confidence interval (CI) 0.794-0.961, P = 0.005) and myocardial injury parameters (HR 0.906, 95% CI 0.825-0.995, P = 0.038). However, adjusted for LV ejection fraction and LV global longitudinal strain (GLS), overall LV-IVPG does not provide additional prognostic information (HR 0.959, 95% CI 0.866-1.063, P = 0.426). Conclusion: Early after STEMI, CMR-derived LV-IVPGs are univariably associated with MACE and this association remains significant after adjustment for common clinical risk factors and measures of infarct severity. However, LV-IVPGs do not add prognostic value to LV ejection fraction and LV GLS.
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BACKGROUND: It has been suggested that coronary microvascular function decreases with age, irrespective of the presence of epicardial atherosclerosis. AIMS: Our aim is to quantitatively investigate the effects of age on microvascular function in patients with normal coronary arteries. METHODS: In 314 patients with angina with no obstructive coronary artery disease (ANOCA), microcirculatory function was tested using the continuous thermodilution method. In 305 patients, the association between age and both resting and hyperaemic myocardial blood flow (Q), microvascular resistance (Rµ), absolute coronary flow reserve (CFR) and microvascular resistance reserve (MRR) was assessed. In addition, patients were divided into 3 groups to test for differences based on age quartiles (≤52 years [24.9%], 53-64 years [49.2%], ≥65 years [25.9%]). RESULTS: The mean age was 59±9 years with a range from 22 to 79 years. The mean resting Q (Qrest) was not different in the 3 age groups (88±34 mL/min, 82±29 mL/min, and 86±38 mL/min, R2=0.001; p=0.62). A trend towards a decreasing mean hyperaemic Q (Qmax) was observed with increasing age (223±79 mL/min, 209±84 mL/min, 200±80 mL/min, R2=0.010; p=0.083). The mean resting Rµ (Rµ,rest) were 1,204±460 Wood units (WU), 1,260±411 WU, and 1,289±455 WU (p=0.23). The mean hyperaemic Rµ (Rµ,hyp) increased significantly with advancing age (429±149 WU, 464±164 WU, 503±162 WU, R2=0.026; p=0.005). Consequently, MRR decreased with age (3.2±1.2, 3.1±1.0, 2.9±0.9; p=0.038). This trend was present in both the patients with (n=121) and without (n=184) coronary microvascular dysfunction (CMD). CONCLUSIONS: There is an age-dependent physiological increase in minimal microvascular resistance and decrease in microvascular function, which is represented by a decreased MRR and is independent of atherosclerosis. The age-dependent decrease in MRR was present in both patients with and without CMD and was most evident in patients with smooth coronary arteries.
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Circulación Coronaria , Vasos Coronarios , Microcirculación , Resistencia Vascular , Humanos , Persona de Mediana Edad , Masculino , Femenino , Anciano , Vasos Coronarios/fisiopatología , Vasos Coronarios/diagnóstico por imagen , Adulto , Circulación Coronaria/fisiología , Factores de Edad , Resistencia Vascular/fisiología , Adulto Joven , Enfermedad de la Arteria Coronaria/fisiopatología , Angina de Pecho/fisiopatologíaRESUMEN
BACKGROUND: During transcatheter aortic valve implantation (TAVI), secondary access is required for angiographic guidance and temporary pacing. The most commonly used secondary access sites are the femoral artery (angiographic guidance) and the femoral vein (temporary pacing). An upper extremity approach using the radial artery and an upper arm vein instead of the lower extremity approach using the femoral artery and femoral vein may reduce clinically relevant secondary access site-related bleeding complications, but robust evidence is lacking. TRIAL DESIGN: The TAVI XS trial is a multicentre, randomised, open-label clinical trial with blinded evaluation of endpoints. A total of 238 patients undergoing transfemoral TAVI will be included. The primary endpoint is the incidence of clinically relevant bleeding (i.e. Bleeding Academic Research Consortium (BARC) type 2, 3 or 5 bleeding) of the randomised secondary access site (either diagnostic or pacemaker access, or both) within 30 days after TAVI. Secondary endpoints include time to mobilisation after TAVI, duration of hospitalisation, any BARC type 2, 3 or 5 bleeding, and early safety at 30 days according to Valve Academic Research Consortium3 criteria. CONCLUSION: The TAVI XS trial is the first randomised trial comparing an upper extremity approach to a lower extremity approach with regard to clinically relevant secondary access site-related bleeding complications. The results of this trial will provide important insights into the safety and efficacy of an upper extremity approach in patients undergoing transfemoral TAVI.
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BACKGROUND: Accurate risk stratification identifying patients with hypertension at risk of future cardiovascular disease in primary care would be desirable. AIM: To investigate the association between elevated brain natriuretic peptide (BNP), left ventricular hypertrophy (LVH) on an electrocardiogram (ECG), and LVH on an echocardiogram and the development of cardiovascular events (CVEs), especially heart failure and all-cause mortality (ACM), in a primary care population with hypertension without symptoms of heart failure. DESIGN AND SETTING: A prospective cohort study in five Dutch general practices between 2010-2012 and 2020. METHOD: In total, 530 patients (aged 60-85 years) underwent laboratory testing, ECGs, and echocardiograms at baseline. The incidence of new CVEs and ACM at up to 9 years' follow-up was recorded by data extraction from the digital information systems. RESULTS: Among the 530 participants, 31 (5.8%) developed a coronary event, 44 (8.3%) a cerebrovascular accident, 53 (10.0%) atrial fibrillation, 23 (4.3%) heart failure, and 66 (12.5%) died. Cox regression analyses, adjusting for relevant Framingham covariates, showed that elevated BNP increased the risk of ACM, CVEs, and specifically heart failure independently by 44% (hazard ratio [HR] 1.44, 95% confidence interval [CI] = 1.07 to 1.94, P = -0.017), 45% (HR 1.45, 95% CI = 1.15 to 1.82, P = 0.002), and 288% (HR 3.88, 95% CI = 2.13 to 7.10, P<0.001), respectively. LVH on ECG increased the risk of ACM independently by 108% (HR 2.08, 95% CI = 1.14 to 3.81, P = 0.017). LVH either on an ECG and/or echocardiogram increased the risk of heart failure independently by 309% (HR 4.09, 95% CI = 1.34 to 12.49, P = 0.014). CONCLUSION: In primary care patients with hypertension, BNP seems to be an important marker predicting future CVEs, especially heart failure, as well as all-cause mortality.
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Fibrilación Atrial , Insuficiencia Cardíaca , Hipertensión , Humanos , Anciano , Estudios de Cohortes , Estudios Prospectivos , Factores de Riesgo , Hipertensión/complicaciones , Hipertensión/epidemiología , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/epidemiología , Hipertrofia Ventricular Izquierda/diagnóstico , Hipertrofia Ventricular Izquierda/epidemiología , Electrocardiografía , Atención Primaria de SaludRESUMEN
Background The femoral vein is commonly used as a pacemaker access site during transcatheter aortic valve replacement (TAVR). Using an upper arm vein as an alternative access site potentially causes fewer bleeding complications and shorter time to mobilization. We aimed to assess the safety and efficacy of an upper arm vein as a temporary pacemaker access site during TAVR. Methods We evaluated all patients undergoing TAVR in our center between January 2020 and January 2023. Upper arm, femoral, and jugular vein pacemaker access was used in 255 (45.8%), 191 (34.3%), and 111 (19.9%) patients, respectively. Clinical outcomes were analyzed according to pacemaker access in the overall population and in a propensity-matched population involving 165 upper arm and 165 femoral vein patients. Primary endpoint was Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 pacemaker access site-related bleeding. Results In the overall population, primary endpoint was lowest for upper arm, followed by femoral and jugular vein access (2.4% vs. 5.8% vs. 10.8%, p = 0.003). Time to mobilization was significantly longer (p < 0.001) in the jugular cohort compared with the other cohorts. In the propensity-matched cohort, primary endpoint showed a trend toward lower occurrence in the upper arm compared with the femoral cohort (2.4% vs. 6.1%, p = 0.10). Time to mobilization was significantly shorter (480 vs. 1140 min, p < 0.001) in the upper arm cohort, with a comparable skin-to-skin time (83 vs. 85 min, p = 0.75). Cross-over from upper arm pacemaker access was required in 17 patients (6.3% of attempted cases via an upper arm vein). Conclusions Using an upper arm vein as a temporary pacemaker access site is safe and feasible. Its use might be associated with fewer bleeding complications and shorter time to mobilization compared with the femoral vein.
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AIMS: To compare the novel 2D multi-velocity encoding (venc) and 4D flow acquisitions with the standard 2D flow acquisition for the assessment of paravalvular regurgitation (PVR) after transcatheter aortic valve replacement (TAVR) using cardiac magnetic resonance (CMR)-derived regurgitant fraction (RF). METHODS AND RESULTS: In this prospective study, patients underwent CMR 1 month after TAVR for the assessment of PVR, for which 2D multi-venc and 4D flow were used, in addition to standard 2D flow. Scatterplots and Bland-Altman plots were used to assess correlation and visualize agreement between techniques. Reproducibility of measurements was assessed with intraclass correlation coefficients. The study included 21 patients (mean age ± SD 80 ± 5 years, 9 men). The mean RF was 11.7 ± 10.0% when standard 2D flow was used, 10.6 ± 7.0% when 2D multi-venc flow was used, and 9.6 ± 7.3% when 4D flow was used. There was a very strong correlation between the RFs assessed with 2D multi-venc and standard 2D flow (r = 0.88, P < 0.001), and a strong correlation between the RFs assessed with 4D flow and standard 2D flow (r = 0.74, P < 0.001). Bland-Altman plots revealed no substantial bias between the RFs (2D multi-venc: 1.3%; 4D flow: 0.3%). Intra-observer and inter-observer reproducibility for 2D multi-venc flow were 0.98 and 0.97, respectively, and 0.92 and 0.90 for 4D flow, respectively. CONCLUSION: Two-dimensional multi-venc and 4D flow produce an accurate quantification of PVR after TAVR. The fast acquisition of the 2D multi-venc sequence and the free-breathing acquisition with retrospective plane selection of the 4D flow sequence provide useful advantages in clinical practice, especially in the frail TAVR population.
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Insuficiencia de la Válvula Aórtica , Imagen por Resonancia Cinemagnética , Reemplazo de la Válvula Aórtica Transcatéter , Humanos , Masculino , Reemplazo de la Válvula Aórtica Transcatéter/efectos adversos , Femenino , Insuficiencia de la Válvula Aórtica/diagnóstico por imagen , Insuficiencia de la Válvula Aórtica/etiología , Insuficiencia de la Válvula Aórtica/cirugía , Insuficiencia de la Válvula Aórtica/fisiopatología , Estudios Prospectivos , Anciano de 80 o más Años , Anciano , Imagen por Resonancia Cinemagnética/métodos , Estenosis de la Válvula Aórtica/cirugía , Estenosis de la Válvula Aórtica/diagnóstico por imagen , Estenosis de la Válvula Aórtica/fisiopatología , Reproducibilidad de los Resultados , Velocidad del Flujo Sanguíneo , Complicaciones Posoperatorias/diagnóstico por imagen , Índice de Severidad de la Enfermedad , Estudios de CohortesRESUMEN
AIMS: Systemic sclerosis (SSc) is characterized by vasculopathy, inflammation, and fibrosis, and carries one of the worst prognoses if patients also develop pulmonary arterial hypertension (PAH). Although PAH is a known prognosticator, patients with SSc-PAH demonstrate disproportionately high mortality, presumably due to cardiac involvement. In this cross-sectional study, the relationship between cardiac involvement revealed by cardiovascular magnetic resonance (CMR) and systemic microvascular disease severity measured with nailfold capillaromicroscopy (NCM) in patients with SSc-PAH is evaluated and compared with patients with idiopathic PAH (IPAH). METHODS AND RESULTS: Patients with SSc-PAH and IPAH underwent CMR, echocardiography, and NCM with post-occlusive reactivity hyperaemia (PORH) testing on the same day. CMR imaging included T2 (oedema), native, and post-contrast T1 mapping to measure the extracellular volume fraction (ECV, fibrosis) and adenosine-stress-perfusion imaging measuring the relative myocardial upslope (microvascular coronary perfusion). Measures of peripheral microvascular function were related to CMR indices of oedema, fibrosis, and myocardial perfusion. SSc-PAH patients (n = 20) had higher T2 values and a trend towards a higher ECV, compared with IPAH patients (n = 5), and a lower nailfold capillary density (NCD) and reduced capillary recruitment after PORH. NCD correlated with ECV and T2 (r = -0.443 and -0.464, respectively, P < 0.05 for both) and with markers of diastolic dysfunction on echocardiography. PORH testing, but not NCD, correlated with the relative myocardial upslope (r = 0.421, P < 0.05). CONCLUSION: SSc-PAH patients showed higher markers of cardiac fibrosis and inflammation, compared with IPAH patients. These markers correlated well with peripheral microvascular dysfunction, suggesting that SSc-driven inflammation and vasculopathy concurrently affect peripheral microcirculation and the heart. This may contribute to the disproportionate high mortality in SSc-PAH.
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Imagen por Resonancia Cinemagnética , Esclerodermia Sistémica , Humanos , Esclerodermia Sistémica/complicaciones , Esclerodermia Sistémica/diagnóstico por imagen , Esclerodermia Sistémica/fisiopatología , Femenino , Masculino , Persona de Mediana Edad , Estudios Transversales , Imagen por Resonancia Cinemagnética/métodos , Adulto , Hipertensión Arterial Pulmonar/fisiopatología , Hipertensión Arterial Pulmonar/diagnóstico por imagen , Ecocardiografía/métodos , Microcirculación , Índice de Severidad de la Enfermedad , Hipertensión Pulmonar/diagnóstico por imagen , Hipertensión Pulmonar/fisiopatología , Hipertensión Pulmonar/etiología , Angioscopía Microscópica , Anciano , PronósticoRESUMEN
BACKGROUND AND AIMS: The healthcare burden of acute chest pain is enormous. In the randomized ARTICA trial, we showed that pre-hospital identification of low-risk patients and rule-out of non-ST-segment elevation acute coronary syndrome (NSTE-ACS) with point-of-care (POC) troponin measurement reduces 30-day healthcare costs with low major adverse cardiac events (MACE) incidence. Here we present the final 1-year results of the ARTICA trial. METHODS: Low-risk patients with suspected NSTE-ACS were randomized to pre-hospital rule-out with POC troponin measurement or emergency department (ED) transfer. Primary 1-year outcome was healthcare costs. Secondary outcomes were safety, quality of life (QoL), and cost-effectiveness. Safety was defined as a 1-year MACE consisting of ACS, unplanned revascularization, or all-cause death. QoL was measured with EuroQol-5D-5L questionnaires. Cost-effectiveness was defined as 1-year healthcare costs difference per QoL difference. RESULTS: Follow-up was completed for all 863 patients. Healthcare costs were significantly lower in the pre-hospital strategy (1932 ± 2784 vs. 2649 ± 2750), mean difference 717 [95% confidence interval (CI) 347 to 1087; P < 0.001]. In the total population, the 1-year MACE rate was comparable between groups [5.1% (22/434) in the pre-hospital strategy vs. 4.2% (18/429) in the ED strategy; P = 0.54]. In the ruled-out ACS population, 1-year MACE remained low [1.7% (7/419) vs. 1.4% (6/417)], risk difference 0.2% (95% CI -1.4% to 1.9%; P = 0.79). QoL showed no significant difference between strategies. CONCLUSIONS: Pre-hospital rule-out of NSTE-ACS with POC troponin testing in low-risk patients is cost-effective, as expressed by a sustainable healthcare cost reduction and no significant effect on QoL. One-year MACE remained low for both strategies.
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Síndrome Coronario Agudo , Troponina , Humanos , Masculino , Femenino , Síndrome Coronario Agudo/sangre , Síndrome Coronario Agudo/epidemiología , Síndrome Coronario Agudo/complicaciones , Troponina/sangre , Persona de Mediana Edad , Anciano , Biomarcadores/sangre , Estudios de Seguimiento , Análisis Costo-Beneficio , Electrocardiografía , Servicios Médicos de Urgencia , Factores de Tiempo , Calidad de Vida , Infarto del Miocardio sin Elevación del ST/epidemiología , Infarto del Miocardio sin Elevación del ST/sangreRESUMEN
BACKGROUND: Traditional risk stratification modestly predicts adverse cardiovascular events in patients with coronary artery disease (CAD). Our aim was to investigate the association between monocyte subsets numbers and function, and the first major adverse cardiovascular event (MACE) in patients with symptomatic stable CAD and angiographically documented coronary atherosclerosis. METHODS: Patients with stable CAD were screened for inclusion. Using flow cytometry, we identified classical, intermediate, and non-classical monocyte subsets and we assessed cytokine production capacity after ex-vivo stimulation of peripheral blood mononuclear cells. Clinical follow-up was performed after four years. The endpoint was the composite of cardiovascular death, acute myocardial infarction, and ischemic stroke. RESULTS: A cohort of 229 patients was recruited. The percentage of intermediate monocytes was positively associated with adverse cardiovascular events at follow-up (HR 1.09; 95%CI 1.02-1.16; p = 0.006), while the percentage of classical monocytes was identified as a protective factor for adverse outcomes (HR 0.96; 95%CI 0.94-0.99; p = 0.02). The percentage of intermediate monocytes remained independently associated with outcomes after adjusting for age, systolic blood pressure, and left ventricular ejection fraction (HR 1.07; 95% CI 1.01-1.14; p = 0.04). Several correlations were identified between monocyte subsets and stimulated cytokine production, but cytokine production capacity was not associated with adverse outcomes. CONCLUSIONS: In patients with stable CAD, intermediate monocytes were associated with MACE at follow-up. The association was not due to an increased cytokine production capacity. Novel biomarkers could improve risk stratification in patients with stable CAD and could represent new pharmacological targets against atherosclerosis progression.
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Enfermedad de la Arteria Coronaria , Humanos , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Monocitos , Leucocitos Mononucleares , Volumen Sistólico , Función Ventricular Izquierda , Citocinas , Factores de RiesgoRESUMEN
AIMS/HYPOTHESIS: Hypomagnesaemia has been associated with insulin resistance and an increased risk of type 2 diabetes. Whether magnesium supplementation improves insulin sensitivity in people with type 2 diabetes and a low serum magnesium level is unknown. METHODS: Using a randomised, double-blind (both participants and investigators were blinded to the participants' treatment sequences), placebo-controlled, crossover study design, we compared the effect of oral magnesium supplementation (15 mmol/day) for 6 weeks with that of matched placebo in individuals with insulin-treated type 2 diabetes (age ≥18 years, BMI 18-40 kg/m2, HbA1c <100 mmol/mol [11.3%], serum magnesium ≤0.79 mmol/l). Participants were recruited from the outpatient clinic and through advertisements. Randomisation to a treatment sequence order was done using a randomisation list. We used block randomisation and the two possible treatment sequences were evenly distributed among the trial population. The primary outcome was the mean glucose infusion rate during the final 30 min of a hyperinsulinaemic-euglycaemic clamp (i.e. M value). Secondary outcomes included variables of glucose control, insulin need, BP, lipid profile and hypomagnesaemia-related symptoms during follow-up. RESULTS: We recruited 14 participants (50% women, 100% White, mean ± SD age 67±6 years, BMI 31±5 kg/m2, HbA1c 58±9 mmol/mol [7.4±0.9%]) with insulin-treated type 2 diabetes. Magnesium supplementation increased both mean ± SEM serum magnesium level (0.75±0.02 vs 0.70±0.02 mmol/l, p=0.016) and urinary magnesium excretion (magnesium/creatinine ratio, 0.23±0.02 vs 0.15±0.02, p=0.005), as compared with placebo. The M value of the glucose clamp did not differ between the magnesium and placebo study arms (4.6±0.5 vs 4.4±0.6 mg kg-1 min-1, p=0.108). During the 6 weeks of treatment, continuous glucose monitoring outcomes, HbA1c, insulin dose, lipid profile and BP also did not differ, except for a lower HDL-cholesterol concentration after magnesium compared with placebo (1.14±0.08 vs 1.20±0.09 mmol/l, p=0.026). Symptoms potentially related to hypomagnesaemia were similar for both treatment arms. CONCLUSIONS/INTERPRETATION: Despite an albeit modest increase in serum magnesium concentration, oral magnesium supplementation does not improve insulin sensitivity in people with insulin-treated type 2 diabetes and low magnesium levels. TRIAL REGISTRATION: EudraCT number 2021-001243-27. FUNDING: This study was supported by a grant from the Dutch Diabetes Research Foundation (2017-81-014).