Cholesteryl hemiazelate identified in CVD patients causes in vitro and in vivo inflammation.

Oxidation of PUFAs in LDLs trapped in the arterial intima plays a critical role in atherosclerosis. Though there have been many studies on the atherogenicity of oxidized derivatives of PUFA-esters of cholesterol, the effects of cholesteryl hemiesters (ChEs), the oxidation end products of these esters, have not been studied. Through lipidomics analyses, we identified and quantified two ChE types in the plasma of CVD patients and identified four ChE types in human endarterectomy specimens. Cholesteryl hemiazelate (ChA), the ChE of azelaic acid (n-nonane-1,9-dioic acid), was the most prevalent ChE identified in both cases. Importantly, human monocytes, monocyte-derived macrophages, and neutrophils exhibit inflammatory features when exposed to subtoxic concentrations of ChA in vitro. ChA increases the secretion of proinflammatory cytokines such as interleukin-1ß and interleukin-6 and modulates the surface-marker profile of monocytes and monocyte-derived macrophage. In vivo, when zebrafish larvae were fed with a ChA-enriched diet, they exhibited neutrophil and macrophage accumulation in the vasculature in a caspase 1- and cathepsin B-dependent manner. ChA also triggered lipid accumulation at the bifurcation sites of the vasculature of the zebrafish larvae and negatively impacted their life expectancy. We conclude that ChA behaves as an endogenous damage-associated molecular pattern with inflammatory and proatherogenic properties.

Adoption and patterns of use of invasive physiological assessment of coronary artery disease in a large cohort of 40821 real-world procedures over a 12-year period.

INTRODUCTION AND OBJECTIVES: Use of invasive physiological assessment in patients with coronary artery disease varies widely and is perceived to be low. We aimed to examine adoption rates as well as patterns and determinants of use in an unselected population undergoing invasive coronary angiography over a long time frame. METHODS: We retrospectively determined the per-procedure prevalence of physiological assessment in 40821 coronary cases performed between 2007 and 2018 in two large-volume centers. Adoption was examined according to procedure type and patient- and operator-related variables. Its association with relevant scientific landmarks, such as the release of clinical trial results and practice guidelines, was also assessed. RESULTS: Overall adoption was low, ranging from 0.6% in patients undergoing invasive coronary angiography due to underlying valve disease, to 6% in the setting of stable coronary artery disease (CAD); it was 3.1% in patients sustaining an acute coronary syndrome. Of scientific landmarks, FAME 1, the long-term results of FAME 2 and the 2014 European myocardial revascularization guidelines were associated with changes in practice. Publication of instantaneous wave-free ratio (iFR) trials had no influence on adoption rates, except for a higher proportion of iFR use. In 42.9% of stable CAD patients undergoing percutaneous coronary intervention there was no objective non-invasive evidence of ischemia, nor was physiological assessment performed. Younger operator age (4.5% vs. 4.0% vs. 0.9% for ages <40, 40-55 and >55 years, respectively; p<0.001) and later time of procedure during the day (2.9% between 6 and 8 p.m. vs. 4.4% at other times) were independent correlates of use of invasive physiology. CONCLUSIONS: Our study confirms the low use of invasive physiology in routine practice. The availability of resting indices did not increase adoption. Strategies are warranted to promote guideline implementation and to improve patient care and clinical outcomes.

Adoption and patterns of use of invasive physiological assessment of coronary artery disease in a large cohort of 40821 real-world procedures over a 12-year period.

INTRODUCTION AND OBJECTIVES: Use of invasive physiological assessment in patients with coronary artery disease varies widely and is perceived to be low. We aimed to examine adoption rates as well as patterns and determinants of use in an unselected population undergoing invasive coronary angiography over a long time frame. METHODS: We retrospectively determined the per-procedure prevalence of physiological assessment in 40821 coronary cases performed between 2007 and 2018 in two large-volume centers. Adoption was examined according to procedure type and patient- and operator-related variables. Its association with relevant scientific landmarks, such as the release of clinical trial results and practice guidelines, was also assessed. RESULTS: Overall adoption was low, ranging from 0.6% in patients undergoing invasive coronary angiography due to underlying valve disease, to 6% in the setting of stable coronary artery disease (CAD); it was 3.1% in patients sustaining an acute coronary syndrome. Of scientific landmarks, FAME 1, the long-term results of FAME 2 and the 2014 European myocardial revascularization guidelines were associated with changes in practice. Publication of instantaneous wave-free ratio (iFR) trials had no influence on adoption rates, except for a higher proportion of iFR use. In 42.9% of stable CAD patients undergoing percutaneous coronary intervention there was no objective non-invasive evidence of ischemia, nor was physiological assessment performed. Younger operator age (4.5% vs. 4.0% vs. 0.9% for ages <40, 40-55 and >55 years, respectively; p<0.001) and later time of procedure during the day (2.9% between 6 and 8 p.m. vs. 4.4% at other times) were independent correlates of use of invasive physiology. CONCLUSIONS: Our study confirms the low use of invasive physiology in routine practice. The availability of resting indices did not increase adoption. Strategies are warranted to promote guideline implementation and to improve patient care and clinical outcomes.

Electrocardiographic imaging (ECGI): What is the minimal number of leads needed to obtain a good spatial resolution?

AIMS: Assess the minimal number of ECGI leads needed to obtain a good spatial resolution. METHODS: We enrolled 20 patients that underwent ablation of premature ventricular or atrial contractions using Carto and ECGI with AMYCARD. We evaluated the agreement regarding the site of origin of the arrhythmia between the ECGI and Carto, the area and diameter of the earliest activation site obtained with the ECGI (EASa and EASd). Based on previous studies with pacemapping, we considered a good spatial resolution of the ECGI when the EASd measured on the isopotential map was less than 18 mm. In presence of agreement the ECGI was reprocessed: a) with half the number of electrode bands (8 leads per electrode band) and b) with 6 electrode bands. RESULTS: The initial map was obtained with 23 (22-23) electrode bands per patient, corresponding to 143 (130-170) leads. Agreement rate was 85%, the median EASa and EASd were: 0.7 (0.5-1.3) cm2 and 9 (8-13) mm. With half the number of electrode bands including 73 (60-79) leads, agreement rate was 80%, the EASa and EASd were: 2.1 (1.5-6.2) cm2 and 16 (14 -28) mm. With only six electrode bands using 38 (30-42) leads, agreement rate was 55%, EASa and EASd were: 4.0 (3.3-5.0) cm2 and 23 (21-25) mm. The number of leads was a predictor of agreement with a good spatial resolution, OR (95% CI) of 1.138 (1.050-1.234), p = .002. According to the ROC curve, the minimal number of leads was 74 (AUC 0.981; 95% CI: 0.949-1.00, p < .0001). CONCLUSION: Reducing the number of leads was associated with a lower agreement rate and a significant reduction of spatial resolution. However, the number of leads needed to achieve a good spatial resolution was less than the maximal available.

Safety and Long-Term Outcomes of Catheter Ablation of Atrial Fibrillation Using Magnetic Navigation versus Manual Conventional Ablation: A Propensity-Score Analysis.

INTRODUCTION: Whether or not the potential advantages of using a magnetic navigation system (MNS) translate into improved outcomes in patients undergoing atrial fibrillation (AF) ablation is a question that remains unanswered. METHODS AND RESULTS: In this observational registry study, we used propensity-score matching to compare the outcomes of patients with symptomatic drug-refractory AF who underwent catheter ablation using MNS with the outcomes of those who underwent catheter ablation using conventional manual navigation. Among 1,035 eligible patients, 287 patients in each group had similar propensity scores and were included in the analysis. The primary efficacy outcome was the rate of AF relapse after a 3-month blanking period. At a mean follow-up of 2.6 ± 1.5 years, AF ablation with MNS was associated with a similar risk of AF relapse as compared with manual navigation (18.4% per year and 22.3% per year, respectively; hazard ratio 0.81, 95% CI 0.63-1.05; P = 0.108). Major complications occurred in two patients (0.7%) using MNS, and in six patients (2.1%) undergoing manually navigated ablation (P = 0.286). Fluoroscopy times were 21 ± 10 minutes in the manual navigation group, and 12 ± 9 minutes in the MNS group (P < 0.001), whereas total procedure times were 152 ± 52 minutes and 213 ± 58 minutes, respectively (P < 0.001). CONCLUSIONS: In this propensity-score matched comparison, magnetic navigation and conventional manual AF ablations seem to have similar relapse rates and a similar risk of complications. AF ablations with magnetic navigation take longer to perform but expose patients to significantly shorter fluoroscopy times.

Cost-effectiveness of different diagnostic strategies in suspected stable coronary artery disease in Portugal.

BACKGROUND: Cost-effectiveness is an increasingly important factor in the choice of a test or therapy. OBJECTIVE: To assess the cost-effectiveness of various methods routinely used for the diagnosis of stable coronary disease in Portugal. METHODS: Seven diagnostic strategies were assessed. The cost-effectiveness of each strategy was defined as the cost per correct diagnosis (inclusion or exclusion of obstructive coronary artery disease) in a symptomatic patient. The cost and effectiveness of each method were assessed using Bayesian inference and decision-making tree analyses, with the pretest likelihood of disease ranging from 10% to 90%. RESULTS: The cost-effectiveness of diagnostic strategies was strongly dependent on the pretest likelihood of disease. In patients with a pretest likelihood of disease of ≤50%, the diagnostic algorithms, which include cardiac computed tomography angiography, were the most cost-effective. In these patients, depending on the pretest likelihood of disease and the willingness to pay for an additional correct diagnosis, computed tomography angiography may be used as a frontline test or reserved for patients with positive/inconclusive ergometric test results or a calcium score of >0. In patients with a pretest likelihood of disease of ≥ 60%, up-front invasive coronary angiography appears to be the most cost-effective strategy. CONCLUSIONS: Diagnostic algorithms that include cardiac computed tomography angiography are the most cost-effective in symptomatic patients with suspected stable coronary artery disease and a pretest likelihood of disease of ≤50%. In high-risk patients (pretest likelihood of disease ≥ 60%), up-front invasive coronary angiography appears to be the most cost-effective strategy. In all pretest likelihoods of disease, strategies based on ischemia appear to be more expensive and less effective compared with those based on anatomical tests.

Custo-Efetividade de Diferentes Estratégias Diagnósticas de Doença Coronária Estável em Portugal / Cost-Effectiveness of Different Diagnostic Strategies in Suspected Stable Coronary Artery Disease in Portugal

Fundamento: O custo-efetividade é um fator de crescente importância na escolha de um exame ou terapêutica. Objetivo: Avaliar o custo-efetividade de vários métodos habitualmente empregados no diagnóstico de doença coronária estável em Portugal. Métodos: Foram avaliadas sete estratégias diagnósticas. O custo-efetividade de cada estratégia foi definido como o custo por cada diagnóstico correto (inclusão ou exclusão de doença arterial coronária obstrutiva) num doente sintomático. Os custos e a eficácia de cada método foram avaliados por meio de inferência bayesiana e análise de árvores de decisão, fazendo variar a probabilidade pré-teste entre 10 e 90%. Resultados: O custo-efetividade das várias estratégias diagnósticas é fortemente dependente da probabilidade pré-teste. Em doentes com probabilidade pré-teste ≤ 50%, os algoritmos diagnósticos, que incluem a angiotomografia computadorizada cardíaca são os mais custo-efetivos. Nesses doentes, dependendo da probabilidade pré-teste e da disponibilidade para pagar por diagnóstico correto adicional, a angiotomografia computadorizada pode ser usada como teste de primeira linha ou ser reservada a doentes com teste ergométrico positivo/inconclusivo ou escore de cálcio > 0. Em doentes com probabilidade pré-teste ≥ 60%, o envio direto para angiografia coronária invasiva parece ser a estratégia mais custo-efetiva. Conclusão: Os algoritmos diagnósticos, que incluem a angiotomografia computadorizada cardíaca, são os mais custo-efetivos em doentes sintomáticos com suspeita de doença arterial coronária estável e probabilidade pré-teste ≤ 50%. Em doentes de risco mais elevado (probabilidade pré-teste ≥ 60%), o envio ...

Background: Cost-effectiveness is an increasingly important factor in the choice of a test or therapy. Objective: To assess the cost-effectiveness of various methods routinely used for the diagnosis of stable coronary disease in Portugal. Methods: Seven diagnostic strategies were assessed. The cost-effectiveness of each strategy was defined as the cost per correct diagnosis (inclusion or exclusion of obstructive coronary artery disease) in a symptomatic patient. The cost and effectiveness of each method were assessed using Bayesian inference and decision-making tree analyses, with the pretest likelihood of disease ranging from 10% to 90%. Results: The cost-effectiveness of diagnostic strategies was strongly dependent on the pretest likelihood of disease. In patients with a pretest likelihood of disease of ≤50%, the diagnostic algorithms, which include cardiac computed tomography angiography, were the most cost-effective. In these patients, depending on the pretest likelihood of disease and the willingness to pay for an additional correct diagnosis, computed tomography angiography may be used as a frontline test or reserved for patients with positive/inconclusive ergometric test results or a calcium score of >0. In patients with a pretest likelihood of disease of ≥ 60%, up-front invasive coronary angiography appears to be the most cost-effective strategy. Conclusions: Diagnostic algorithms that include cardiac computed tomography angiography are the most cost-effective in symptomatic patients with suspected stable coronary artery disease and a pretest likelihood of disease of ≤50%. In high-risk patients (pretest likelihood of disease ≥ 60%), up-front invasive coronary angiography appears to be the most cost-effective strategy. In all pretest likelihoods of disease, strategies based on ischemia appear to be more expensive and less effective compared with those based on anatomical tests. .

Percutaneous coronary intervention of unprotected left main disease: five-year outcome of a single-center registry.

INTRODUCTION AND AIMS: Percutaneous coronary intervention (PCI) is increasingly used as a treatment option for unprotected left main coronary artery (ULMCA) lesions. We aimed to evaluate the long-term outcome of patients undergoing ULMCA PCI. METHODS AND RESULTS: We retrospectively analyzed 95 consecutive patients (median EuroSCORE I 2.9 [IQR 1.4;6.1]) who underwent ULMCA PCI between 1999 and 2006, included in a single-center prospective registry. The primary outcome was major adverse cardiovascular events (MACE) defined as all-cause death, myocardial infarction (MI) and target lesion revascularization (TLR) at five years. Forty patients (42.1%) were treated in the setting of acute coronary syndrome and 81 patients (85%) had at least one additional significant lesion (SYNTAX score 24.2±11.8). Single ULMCA PCI was performed in 33% (81.1% with drug-eluting stents) and complete functional revascularization was achieved in 79% of the patients. During the observation period, 20 patients died (21.1%), 6 (6.3%) had MI and 11 (11.6%) had TLR (total combined MACE 28.4%). Independent predictors of MACE were previous MI (HR 2.9 95% CI 1.23-6.92; p=0.015), hypertension (HR 5.7 95% CI 1.86-17.47; p=0.002) and the EuroSCORE I (HR 1.1 95% CI 1.03-1.12; p=0.001). Drug-eluting stent implantation was associated with a significantly lower MACE rate, even after propensity score adjustment (AUC=0.84; HR [corrected] 0.1; 95% CI 0.04-0.26; p<0.001). CONCLUSIONS: Unprotected left main percutaneous coronary intervention, particularly using drug-eluting stents, can be considered a valid alternative to coronary artery bypass grafting, especially in high-risk surgical patients and with favorable anatomic features.

Coronary-subclavian steal syndrome: percutaneous approach.

Coronary subclavian steal syndrome is a rare ischemic cause in patients after myocardial revascularization surgery. Subclavian artery stenosis or compression proximal to the internal mammary artery graft is the underlying cause. The authors present a clinical case of a patient with previous history of non-ST elevation myocardial infarction, triple coronary bypass, and effort angina since the surgery, with a positive ischemic test. Coronary angiography revealed a significant stenosis of the left subclavian artery, proximal to the internal mammary graft.

Myocardial revascularization reverses adverse outcome in non-ST-elevation acute coronary syndromes complicated by heart failure.

BACKGROUND: Congestive heart failure (CHF) has a strong negative prognostic impact in patients with non-ST-elevation acute coronary syndromes (NSTE-ACS). The purpose of this study was to establish the effect of myocardial revascularization on prognosis in this setting. METHODS: We retrospectively studied 648 patients admitted with NSTE-ACS and not presenting cardiogenic shock. The effect of coronary revascularization on the outcome of patients with and without CHF was assessed using a propensity score-adjusted regression model. RESULTS: Congestive heart failure was present in 89 patients (14.5%) on hospital admission. During the index hospitalization, 426 patients received myocardial revascularization, through percutaneous coronary intervention (PCI) in 321 cases, and coronary artery bypass grafting (CABG) in 105. In a 6-month follow-up, 38 patients (6.2%) died and 42 (6.8%) experienced non-fatal myocardial infarction (MI). CHF was an independent predictor of both 6-month mortality (adjusted HR 3.6; 95% CI 1.86-6.95; p < 0.001) and 6-month death/(re-)MI (adjusted HR 2.1; 95% CI 1.3-3.5; p = 0.003). Revascularization significantly influenced the prognosis of patients presenting CHF (adjusted HR 0.31; 95% CI 0.13-0.73; p = 0.008), but not of those without CHF (adjusted HR 1.37; 95% CI 0.65-2.89; p = 0.4). A significant interaction was found between revascularization and the prognostic impact of CHF at admission (p = 0.021 for the interaction). CONCLUSIONS: In patients with NSTE-ACS, clinical manifestations of CHF constitute a strong predictor of adverse medium-term outcome that may be significantly modified by myocardial revascularization.

Radiation in cardiac CT: predictors of higher dose and its reduction over time.

INTRODUCTION: Cardiac CT provides noninvasive information on cardiac anatomy, particularly in coronary artery disease. However, exposure to radiation has been identified as a limitation of this exam. The aim of this study was to evaluate variations in radiation dose over time and to identify variables associated with use of higher radiation doses. METHODS: A prospective registry of 643 patients who underwent 64-slice dual source cardiac CT scan (Dual source CT--Somaton Definition, Siemens-Medical) during 2007 and 2008 was analyzed. RESULTS: The sample was divided into quartiles according to the chronological order of the exams. There was a progressive reduction in median radiation dose in the quartiles analyzed (Q1: 8.9 [5.9-14.1], Q2: 6.6 [5.5-10.7], Q3: 6.4 [5.3-8.7], Q4: 6.1 [5.2-7.9] mSv), significant when the first quartile was compared with the others (p < 0.05). Along with this reduction, was a progressive increase in the use of a tube voltage of 100 kV (p < 0.001). Predictors of a higher radiation dose were higher body mass index, previous cardiac surgery, atrial fibrillation during acquisition, longer acquisition time and use of a tube voltage of 120 kV. When one or more of these variables were present (one third of the population), the radiation dose was significant higher (12.1 [9.5-14.8] vs. 5.7 [5.0-6.7] mSv, p < 0.001).

Hypertrophic cardiomyopathy--two atypical forms diagnosed by cardiac CT.

Hypertrophic cardiomyopathy is a relatively common genetic disease (prevalence of 0.2%), with a clinical spectrum that ranges from absence of symptoms to presentation as sudden cardiac death. Atypical forms are a diagnostic challenge and recent cardiac imaging techniques, such as cardiac CT and magnetic resonance imaging, can make an important contribution. We present a review of this disease based on two case reports.

Femoral stenosis due to a collagen closure device treated percutaneously by peripheral stenting.

Late complications from vascular closure devices, such as puncture site stenosis, are not well documented. They may be of clinical significance and probably share the same mechanism that underlies intra-coronary stent restenosis. Thus, treatment approaches based on balloon angioplasty alone may not be sufficient, and the use of stents (when possible) is safe and effective in this setting. We describe the case of a 60-year-old patient with a 90% stenosis of the femoral artery, which CT angiography strongly suggested to be secondary to previous implantation of a closure device.

Lymphoma with clinical presentation of a primary pericardial tumor.

Primary malignant cardiac tumors, particularly lymphoma, are rare entities. Cardiac involvement or metastization of the heart from neoplasia located elsewhere are more frequently found. We present the case of a 79-year-old patient admitted with heart failure symptoms with a 3-week evolution. Evaluation led to the identification of a cardiac tumor with unusual clinical presentation and with a rapid and fatal evolution. Pathologic analysis identified a B-cell non-Hodgkin lymphoma.