Coronary plaque composition may play an important role in the induction of myocardial ischemia. Our objective was to further clarify the relation between coronary plaque composition and myocardial ...Show moreCoronary plaque composition may play an important role in the induction of myocardial ischemia. Our objective was to further clarify the relation between coronary plaque composition and myocardial ischemiain patients with chest pain symptoms. The study population consisted of 103 patients who presented to the outpatient clinic or emergency department with chest pain symptoms and were referred for diagnostic invasivecoronary angiography. Intravascular ultrasound virtual histology was used for the assessment of coronary plaque composition. A noncalcified plaque was defined as a combination of necrotic core and fibrofatty tissue. Quantitative flow ratio (QFR), which is a coronary angiography-based technique used to calculate fractional flow reserve without the need for hyperemia induction or for a pressure wire, was used as the reference standard for the evaluation of myocardial ischemia. Coronary artery plaques with QFR of ≤0.80 were considered abnormal—that is, ischemia-generating. In total, 149 coronary plaques were analyzed, 21 of which (14%) were considered abnormal according to QFR. The percentage of noncalcified tissue was significantly higher in plaques with abnormal QFR (38.2 ± 6.5% vs 33.1 ± 9.0%, p = 0.014). After univariable analysis, both plaque load (odds ratio [OR] per 1% increase 1.081, p <0.001) and the percentage of noncalcified tissue (OR per 1% increase 1.070, p = 0.020) were significantly associated with reduced QFR. However, after multivariable analysis, only plaque load remained significantly associated with abnormal QFR (OR per 1% increase 1.072, p <0.001). In conclusion, the noncalcified plaque area was significantly higher in hemodynamically significant coronary lesions than in nonsignificant lesions. Although an increase in the noncalcified plaque area was significantly associated with a reduced QFR, this association lost significance after adjustment for localized plaque load. Show less
Background: Aims of this study were to investigate the prevalence and incidence of catheter-related infection, identify risk factors, and determine the relation of catheter-related infection with... Show moreBackground: Aims of this study were to investigate the prevalence and incidence of catheter-related infection, identify risk factors, and determine the relation of catheter-related infection with mortality in critically ill COVID-19 patients. Methods: This was a retrospective cohort study of central venous catheters (CVCs) in critically ill COVID-19 patients. Eligible CVC insertions required an indwelling time of at least 48 hours and were identified using a full-admission electronic health record database. Risk factors were identified using logistic regression. Differences in survival rates at day 28 of follow-up were assessed using a log-rank test and proportional hazard model. Results: In 538 patients, a total of 914 CVCs were included. Prevalence and incidence of suspected catheter-related infection were 7.9% and 9.4 infections per 1,000 catheter indwelling days, respectively. Prone ventilation for more than 5 days was associated with increased risk of suspected catheter-related infection; odds ratio, 5.05 (95% confidence interval 2.12-11.0). Risk of death was significantly higher in patients with suspected catheter-related infection (hazard ratio, 1.78; 95% confidence interval, 1.25-2.53). Conclusions: This study shows that in critically ill patients with COVID-19, prevalence and incidence of suspected catheter-related infection are high, prone ventilation is a risk factor, and mortality is higher in case of catheter-related infection. Show less
Background: Timely identification of deteriorating COVID-19 patients is needed to guide changes in clinical management and admission to intensive care units (ICUs). There is significant concern... Show moreBackground: Timely identification of deteriorating COVID-19 patients is needed to guide changes in clinical management and admission to intensive care units (ICUs). There is significant concern that widely used Early warning scores (EWSs) underestimate illness severity in COVID-19 patients and therefore, we developed an early warning model specifically for COVID-19 patients. Methods: We retrospectively collected electronic medical record data to extract predictors and used these to fit a random forest model. To simulate the situation in which the model would have been developed after the first and implemented during the second COVID-19 `wave' in the Netherlands, we performed a temporal validation by splitting all included patients into groups admitted before and after August 1, 2020. Furthermore, we propose a method for dynamic model updating to retain model performance over time. We evaluated model discrimination and calibration, performed a decision curve analysis, and quantified the importance of predictors using SHapley Additive exPlanations values. Results: We included 3514 COVID-19 patient admissions from six Dutch hospitals between February 2020 and May 2021, and included a total of 18 predictors for model fitting. The model showed a higher discriminative performance in terms of partial area under the receiver operating characteristic curve (0.82 [0.80-0.84]) compared to the National early warning score (0.72 [0.69-0.74]) and the Modified early warning score (0.67 [0.65-0.69]), a greater net benefit over a range of clinically relevant model thresholds, and relatively good calibration (intercept = 0.03 [- 0.09 to 0.14], slope = 0.79 [0.73-0.86]). Conclusions: This study shows the potential benefit of moving from early warning models for the general inpatient population to models for specific patient groups. Further (independent) validation of the model is needed. Show less
Rosendael, A.R. van; Smit, J.M.; El'Mahdiui, M.; Rosendael, P.J. van; Leung, M.; Delgado, V.; Bax, J.J. 2022
Aims: Left atrial (LA) volume and LA epicardial fat are both substrates for atrial fibrillation (AF), but may relate with AF at different (early vs. late) stages in the AF disease process. We... Show moreAims: Left atrial (LA) volume and LA epicardial fat are both substrates for atrial fibrillation (AF), but may relate with AF at different (early vs. late) stages in the AF disease process. We evaluated associations between LA epicardial fat and LA volume in patients with sinus rhythm (SR), paroxysmal AF (PAF), and persistent/permanent AF. Methods and results: In total, 300 patients (100 with SR, 100 with PAF, and 100 with persistent/permanent AF) who underwent cardiac computed tomography angiography (CTA) were included. The epicardial fat mass posterior to the LA and the LA volume were quantified from CTA and compared between patients with SR, PAF, and persistent/permanent AF. Furthermore, four groups were created by classifying LA epicardial fat and LA volume into large or small according to their median. The mean age of the population was 58.9 +/- 10.5 years and 69.7% was male. Left atrial epicardial fat mass was larger in patients with PAF compared with SR, but did not further increase from PAF to persistent/permanent AF. Left atrial volume increased significantly from SR to PAF and to persistent/permanent AF. Left atrial epicardial fat and LA volume were both concordantly large or small in 184 (61%) patients, and discordant in 116 (39%). When both were small, 65.2% of the patients had SR, 23.9% PAF, and 10.9% persistent/permanent AF. When the LA epicardial fat mass was large and the LA volume small (compared with both being small), patients were significantly more often in PAF (55.2 vs. 23.9, P < 0.05), less frequently in SR (32.8% vs. 65.2%, P < 0.05) but showed comparable rates of persistent/permanent AF (12.0% vs. 10.9%, P < 0.05). When the LA volume was large, most patients had persistent/permanent AF. Conclusion: Left atrial epicardial fat mass was larger in PAF vs. SR, possibly indicating a marker of early disease, while large LA volumes were associated with a high prevalence of persistent/permanent AF. Elevated LA epicardial fat mass without large LA volume may reflect the early AF disease process. Show less
Introduction: The role of the spatial relationship between the left superior pulmonary vein (LSPV) and left atrial appendage (LAA) is unknown. We sought to evaluate whether an abutting LAA and LSPV... Show moreIntroduction: The role of the spatial relationship between the left superior pulmonary vein (LSPV) and left atrial appendage (LAA) is unknown. We sought to evaluate whether an abutting LAA and LSPV play a role in AF recurrence after catheter ablation for paroxysmal AF. Methods: Consecutive patients, who underwent initial point-by-point radiofrequency catheter ablation for paroxysmal AF at the Heart and Vascular Center of Semmelweis University, Budapest, Hungary, between January of 2014 and December of 2017, were enrolled in the study. All patients underwent pre-procedural cardiac CT to assess left atrial (LA) and pulmonary vein (PV) anatomy. Abutting LAA-LSPV was defined as cases when the minimum distance between the LSPV and LAA was less than 2 mm. Results: We included 428 patients (60.7 +/- 10.8 years, 35.5% female) in the analysis. AF recurrence rate was 33.4%, with a median recurrence-free time of 21.2 (8.8-43.0) months. In the univariable analysis, female sex (HR = 1.45; 95%CI = 1.04-2.01; p = 0.028), LAA flow velocity (HR = 1.01; 95%CI = 1.00-1.02; p = 0.022), LAA orifice area (HR = 1.00; 95%CI = 1.00-1.00; p = 0.028) and abutting LAA-LSPV (HR = 1.53; 95%CI = 1.09-2.14; p = 0.013) were associated with AF recurrence. In the multivariable analysis, abutting LAA-LSPV (adjusted HR = 1.55; 95%CI = 1.04-2.31; p = 0.030) was the only independent predictor of AF recurrence. Conclusion: Abutting LAA-LSPV predisposes patients to have a higher chance for arrhythmia recurrence after catheter ablation for paroxysmal AF. Show less
Aims: The relationship between dyspnoea, coronary artery disease (CAD), and major cardiovascular events (MACE) is poorly understood. This study evaluated (i) the association of dyspnoea with the... Show moreAims: The relationship between dyspnoea, coronary artery disease (CAD), and major cardiovascular events (MACE) is poorly understood. This study evaluated (i) the association of dyspnoea with the severity of anatomical CAD by coronary computed tomography angiography (CCTA) and (ii) to which extent CAD explains MACE in patients with dyspnoea.Methods and results: From the international COronary CT Angiography EvaluatioN for Clinical Outcomes: An InteRnational Multicenter (CONFIRM) registry, 4425 patients (750 with dyspnoea) with suspected but without known CAD were included and prospectively followed for ≥5 years. First, the association of dyspnoea with CAD severity was assessed using logistic regression analysis. Second, the prognostic value of dyspnoea for MACE (myocardial infarction and death), and specifically, the interaction between dyspnoea and CAD severity was investigated using Cox proportional-hazard analysis. Mean patient age was 60.3 ± 11.9 years, 63% of patients were male and 592 MACE events occurred during a median follow-up duration of 5.4 (IQR 5.1-6.0) years. On uni- and multivariable analysis (adjusting for age, sex, body mass index, chest pain typicality, and risk factors), dyspnoea was associated with two- and three-vessel/left main (LM) obstructive CAD. The presence of dyspnoea increased the risk for MACE [hazard ratio (HR) 1.57, 95% confidence interval (CI): 1.29-1.90], which was modified after adjusting for clinical predictors and CAD severity (HR 1.26, 95% CI: 1.02-1.55). Conversely, when stratified by CAD severity, dyspnoea did not provide incremental prognostic value in one-, two-, or three-vessel/LM obstructive CAD, but dyspnoea did provide incremental prognostic value in non-obstructive CAD.Conclusion: In patients with suspected CAD, dyspnoea was independently associated with severe obstructive CAD on CCTA. The severity of obstructive CAD explained the elevated MACE rates in patients presenting with dyspnoea, but in patients with non-obstructive CAD, dyspnoea portended additional risk. Show less
Aims The relationship between dyspnoea, coronary artery disease (CAD), and major cardiovascular events (MACE) is poorly understood. This study evaluated (i) the association of dyspnoea with the... Show moreAims The relationship between dyspnoea, coronary artery disease (CAD), and major cardiovascular events (MACE) is poorly understood. This study evaluated (i) the association of dyspnoea with the severity of anatomical CAD by coronary computed tomography angiography (CCTA) and (ii) to which extent CAD explains MACE in patients with dyspnoea. Methods and results: From the international COronary CT Angiography EvaluatioN for Clinical Outcomes: An InteRnational Multicenter (CONFIRM) registry, 4425 patients (750 with dyspnoea) with suspected but without known CAD were included and prospectively followed for >= 5 years. First, the association of dyspnoea with CAD severity was assessed using logistic regression analysis. Second, the prognostic value of dyspnoea for MACE (myocardial infarction and death), and specifically, the interaction between dyspnoea and CAD severity was investigated using Cox proportional-hazard analysis. Mean patient age was 60.3 +/- 11.9 years, 63% of patients were male and 592 MACE events occurred during a median follow-up duration of 5.4 (IQR 5.1-6.0) years. On uni- and multivariable analysis (adjusting for age, sex, body mass index, chest pain typicality, and risk factors), dyspnoea was associated with two- and three-vessel/left main (LM) obstructive CAD. The presence of dyspnoea increased the risk for MACE [hazard ratio (HR) 1.57, 95% confidence interval (CI): 1.29-1.90], which was modified after adjusting for clinical predictors and CAD severity (HR 1.26, 95% CI: 1.02-1.55). Conversely, when stratified by CAD severity, dyspnoea did not provide incremental prognostic value in one-, two-, or three-vessel/LM obstructive CAD, but dyspnoea did provide incremental prognostic value in non-obstructive CAD. Conclusion: In patients with suspected CAD, dyspnoea was independently associated with severe obstructive CAD on CCTA. The severity of obstructive CAD explained the elevated MACE rates in patients presenting with dyspnoea, but in patients with non-obstructive CAD, dyspnoea portended additional risk. Show less
Stockmans, T.A.; Snik, F.; Smit, J.M.; Rietjens, J.H.H.; Esposito, M.; Van Dijk, C.; Keller, C.U. 2022
Background and aims: Elevated triglycerides (TG) and low high-density lipoprotein cholesterol (HDL-C) define a specific lipid profile associated with residual coronary artery disease (CAD) risk... Show moreBackground and aims: Elevated triglycerides (TG) and low high-density lipoprotein cholesterol (HDL-C) define a specific lipid profile associated with residual coronary artery disease (CAD) risk independently of total cholesterol and low-density lipoprotein cholesterol (LDL-C) levels. Aim of the present study was to assess whether TG/ HDL-C ratio, coronary atherosclerosis and their change over time are characterized by a specific lipidomic profiling in stable patients with chronic coronary syndrome (CCS). Methods: TG/HDL-C ratio was calculated in 193 patients (57.8 +/- 7.6 years, 115 males) with CCS characterized by clinical, bio-humoral profiles and cardiac imaging. Patient-specific plasma targeted lipidomics was defined through a high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) strategy. Patients underwent coronary computed tomography angiography (CTA) and an individual CTA risk score, combining extent, severity, composition, and location of plaques, was calculated. All patients entered a follow-up (6.39 +/- 1.17 years), including clinical, lipidomics and coronary CTA assessments. Results: Patients were divided in groups according to baseline TG/HDL-C quartiles: IQ (<1.391), IIQ (1.392-2.000), IIIQ (2.001-3.286), and IVQ (>= 3.287). A specific pattern of altered lipids, characterized by reduced plasma levels of cholesterol esters, phosphatidylcholines and sphingomyelins, was associated with higher TG/HDL-C both at baseline and follow-up (IVQ vs IQ). The CTA risk score increased over time and this lipid signature was also associated with higher CTA score at follow-up. Conclusions: In stable CCS, a specific lipidomic signature identifies those patients with higher TG/HDL- C ratio and higher CTA score over time, suggesting possible molecular pathways of residual CAD risk not tackled by current optimal medical treatments. Show less
Simon, J.; Mahdiui, M. el; Smit, J.M.; Szaraz, L.; Rosendael, A.R. van; Herczeg, S.; ... ; Merkely, B. 2021
Introduction There are no consistently confirmed predictors of atrial fibrillation (AF) recurrence after catheter ablation. Therefore, we aimed to study whether left atrial appendage volume (LAAV)... Show moreIntroduction There are no consistently confirmed predictors of atrial fibrillation (AF) recurrence after catheter ablation. Therefore, we aimed to study whether left atrial appendage volume (LAAV) and function influence the long-term recurrence of AF after catheter ablation, depending on AF type. Methods AF patients who underwent point-by-point radiofrequency catheter ablation after cardiac computed tomography (CT) were included in this analysis. LAAV and LAA orifice area were measured by CT. Uni- and multivariable Cox proportional hazard regression models were performed to determine the predictors of AF recurrence. Results In total, 561 AF patients (61.9 +/- 10.2 years, 34.9% females) were included in the study. Recurrence of AF was detected in 40.8% of the cases (34.6% in patients with paroxysmal and 53.5% in those with persistent AF) with a median recurrence-free time of 22.7 (9.3-43.1) months. Patients with persistent AF had significantly higher body surface area-indexed LAV, LAAV, and LAA orifice area and lower LAA flow velocity, than those with paroxysmal AF. After adjustment left ventricular ejection fraction (LVEF) <50% (HR = 2.17; 95% CI = 1.38-3.43; p < .001) and LAAV (HR = 1.06; 95% CI = 1.01-1.12; p = .029) were independently associated with AF recurrence in persistent AF, while no independent predictors could be identified in paroxysmal AF. Conclusion The current study demonstrates that beyond left ventricular systolic dysfunction, LAA enlargement is associated with higher rate of AF recurrence after catheter ablation in persistent AF, but not in patients with paroxysmal AF. Show less
Troost-Kind, B.; Hemert, M.J. van; Pol, D. van de; Ende-Metselaar, H. van der; Merits, A.; Borggrewe, M.; ... ; Smit, J.M. 2021
Author summaryChikungunya fever is a debilitating disease caused by the mosquito-borne Chikungunya virus. Over the past two decades the geographical spread of the virus and its mosquito vector has... Show moreAuthor summaryChikungunya fever is a debilitating disease caused by the mosquito-borne Chikungunya virus. Over the past two decades the geographical spread of the virus and its mosquito vector has drastically increased thereby causing millions of infections. To date there is no antiviral drug and no vaccine available to treat/prevent Chikungunya virus infection. We recently showed that the natural steroidal alkaloid tomatidine has potent antiviral activity towards Chikungunya virus at submicromolar concentrations. In this study we dissected how tomatidine reduces the production of Chikungunya virus particles. We show that tomatidine lowers viral protein expression and we hypothesize that the effect of tomatidine on viral protein translation hampers the production of progeny viral RNA copies / number of infected cells thereby leading to a reduced production of secreted virus particles. Also, we show that Chikungunya virus does not readily become resistant to tomatidine. Collectively, we deciphered the mechanism by which tomatidine exerts antiviral activity to Chikungunya virus and our results strengthen the potential of tomatidine as an antiviral treatment strategy towards Chikungunya virus.Tomatidine, a natural steroidal alkaloid from unripe green tomatoes has been shown to exhibit many health benefits. We recently provided in vitro evidence that tomatidine reduces the infectivity of Dengue virus (DENV) and Chikungunya virus (CHIKV), two medically important arthropod-borne human infections for which no treatment options are available. We observed a potent antiviral effect with EC50 values of 0.82 mu M for DENV-2 and 1.3 mu M for CHIKV-LR. In this study, we investigated how tomatidine controls CHIKV infectivity. Using mass spectrometry, we identified that tomatidine induces the expression of p62, CD98, metallothionein and thioredoxin-related transmembrane protein 2 in Huh7 cells. The hits p62 and CD98 were validated, yet subsequent analysis revealed that they are not responsible for the observed antiviral effect. In parallel, we sought to identify at which step of the virus replication cycle tomatidine controls virus infectivity. A strong antiviral effect was seen when in vitro transcribed CHIKV RNA was transfected into Huh7 cells treated with tomatidine, thereby excluding a role for tomatidine during CHIKV cell entry. Subsequent determination of the number of intracellular viral RNA copies and viral protein expression levels during natural infection revealed that tomatidine reduces the RNA copy number and viral protein expression levels in infected cells. Once cells are infected, tomatidine is not able to interfere with active RNA replication yet it can reduce viral protein expression. Collectively, the results delineate that tomatidine controls viral protein expression to exert its antiviral activity. Lastly, sequential passaging of CHIKV in presence of tomatidine did not lead to viral resistance. Collectively, these results further emphasize the potential of tomatidine as an antiviral treatment towards CHIKV infection. Show less
Caselli, C.; Caterina, R. de; Smit, J.M.; Campolo, J.; Mahdiui, M. el; Ragusa, R.; ... ; SMARTool 2021
We assessed whether high triglycerides (TG) and low high-density lipoprotein cholesterol (HDL-C) levels, expressed by an increased TG/HDL-C ratio, predict coronary atherosclerotic disease (CAD)... Show moreWe assessed whether high triglycerides (TG) and low high-density lipoprotein cholesterol (HDL-C) levels, expressed by an increased TG/HDL-C ratio, predict coronary atherosclerotic disease (CAD) outcomes in patients with stable angina. We studied 355 patients (60 +/- 9 years, 211 males) with stable angina who underwent coronary computed tomography angiography (CTA), were managed clinically and followed for 4.5 +/- 0.9 years. The primary composite outcome was all-cause mortality and non-fatal myocardial infarction. At baseline, the proportion of males, patients with metabolic syndrome, diabetes and obstructive CAD increased across TG/HDL-C ratio quartiles, together with markers of insulin resistance, hepatic and adipose tissue dysfunction and myocardial damage, with no difference in total cholesterol or LDL-C. At follow-up, the global CTA risk score (HR 1.06, 95% confidence interval (CI) 1.03-1.09, P = 0.001) and the IV quartile of the TG/HDL-C ratio (HR 2.85, 95% CI 1.30-6.26, P < 0.01) were the only independent predictors of the primary outcome. The TG/HDL-C ratio and the CTA risk score progressed over time despite increased use of lipid-lowering drugs and reduction in LDL-C. In patients with stable angina, high TG and low HDL-C levels are associated with CAD related outcomes independently of LDL-C and treatments. Show less
In the last decade, ultrasound has found its place in the intensive care unit (ICU). Initially, ultrasound was used primarily to increase the safety and efficacy of line insertion, but currently... Show moreIn the last decade, ultrasound has found its place in the intensive care unit (ICU). Initially, ultrasound was used primarily to increase the safety and efficacy of line insertion, but currently many intensivists use point-of-care ultrasound (POCUS) to aid in making the diagnosis, monitoring therapy, and supporting therapeutic interventions. In this series, we aim to highlight one specific POCUS technique at a time, which we believe will prove to be useful in your clinical practice. This specific article will focus on assessment of right ventricular (RV) size and function, and the application of tricuspid annular plane systolic excursion (TAPSE). RV assessment during focused cardiac ultrasound (FoCUS) depends, currently, on visual evaluation - 'eyeballing' - of the RV size and function and left and right ventricular interaction. However, 'eyeballing' is subjective, depends on experience and may be misleading if done by unexperienced sonographers. Objective measurements of RV size and function are necessary and provide an additional understanding of RV performance. There are different ways to assess the RV objectively. Many of these measurements, however, require a lot of training and are not yet available in portable devices. Evaluation of TAPSE is a validated and reproducible way of evaluating RV function and only requires the utilisation of M-mode or a 2D measurement. TAPSE, assessed in the apical four-chamber view, is sometimes difficult to measure, especially in mechanically ventilated patients. In recent years subcostal variants have been introduced: the subcostal echocardiographic assessment of tricuspid annular kick (SEATAK) and the subcostal-TAPSE (S-TAPSE). These measurements are alternatives when the 'classical' TAPSE cannot reliably be evaluated. Show less
Background Coronary artery calcium (CAC) score has shown to provide incremental prognostic information when added to the Framingham risk score. Although the relation between CAC and myocardial... Show moreBackground Coronary artery calcium (CAC) score has shown to provide incremental prognostic information when added to the Framingham risk score. Although the relation between CAC and myocardial ischemia has been evaluated, there has been little evaluation of the relationship between CAC score and inducible myocardial ischemia on computed tomography myocardial perfusion (CTP). Methods and Results Patients who were referred with stable chest pain from the outpatient clinic and who underwent non-contrast computed tomography scan, coronary computed tomography angiography, and adenosine stress CTP were included in this study. CAC score was subdivided in four groups (1 to 99; 100 to 399, 400 to 999, and >= 1000). Inducible myocardial ischemia was considered when reversible perfusion defects were observed in >= 1 segment. A total of 131 patients (age 62 +/- 9.4 years; 56% male) were included. The median CAC score was 241 (73 to 539). Forty-nine patients (37%) had evidence of inducible myocardial ischemia. The presence of inducible myocardial ischemia increased with increasing CAC score from 22% in the CAC score 1 to 99 subgroup to 35, 47, and 65% in the 100 to 399, 400 to 999, and >= 1000 CAC score subgroup, respectively. In multivariable analysis CAC score was the only determinant that significantly predicted the presence of inducible myocardial ischemia on CTP. Conclusions In a population of symptomatic patients, the majority of patients with extensive calcification had evidence of inducible myocardial ischemia on CTP. CAC score was the only independent predictor of inducible myocardial ischemia on CTP. Show less
Smit, J.M.; Simon, J.; Mahdiui, M. el; Szaraz, L.; Rosendael, P.J. van; Kolassvary, M.; ... ; Bax, J.J. 2021
Background: The left atrial appendage (LAA) has been regarded as an important source of cardiac thrombus formation and appears important in the contribution to thromboembolism in patients with... Show moreBackground: The left atrial appendage (LAA) has been regarded as an important source of cardiac thrombus formation and appears important in the contribution to thromboembolism in patients with atrial fibrillation (AF). Our aim was to evaluate the relationship between LAA morphology and previous stroke or transient ischemic attack in 2 large and distinct patient cohorts with and without known AF. Methods: The study population consisted of patients with and without drug-refractory AF who underwent computed tomography before transcatheter AF ablation or clinically indicated for suspected coronary artery disease. The computed tomography data were used for volumetric assessment of the left atrium and LAA and to determine LAA morphology. The LAA was classified by 3 readers in consensus as chicken wing, swan, cauliflower, or windsock, based on predefined morphology classification criteria. Results: In total, 1813 patients (mean age 59 +/- 11 years, 42% female) who underwent computed tomography were included in this analysis (908 patients with AF and 905 patients without known AF). Swan LAA morphology was independently associated with prior stroke/transient ischemic attack in the overall study population (odds ratio, 3.40, P<0.001), and in patients with (odds ratio, 2.88, P=0.012) and without known AF (odds ratio, 3.96, P=0.011). Conclusions: Swan morphology of the LAA is independently associated with prior stroke or transient ischemic attack in patients with known AF, as well as in patients not previously diagnosed with AF. Show less
Bodini, A.; Michelucci, E.; Giorgi, N. di; Caselli, C.; Signore, G.; Neglia, D.; ... ; Rocchiccioli, S. 2021
Background: Lipidomics is emerging for biomarker discovery in cardiovascular disease, and circulating lipids are increasingly incorporated in risk models to predict cardiovascular events. Moreover,... Show moreBackground: Lipidomics is emerging for biomarker discovery in cardiovascular disease, and circulating lipids are increasingly incorporated in risk models to predict cardiovascular events. Moreover, specific classes of lipids, such as sphingomyelins, ceramides, and triglycerides, have been related to coronary artery disease (CAD) severity and plaque characteristics. To avoid unnecessary testing, it is important to identify individuals at low CAD risk. The only pretest model available so far to rule out the presence of coronary atherosclerosis in patients with chest pain, but normal coronary arteries, is the minimal risk tool (MRT).Aim: Using state-of-the-art statistical methods, we aim to verify the additive predictive value of a set of lipids, derived from targeted plasma lipidomics of suspected CAD patients, to a re-estimated version of the MRT for ruling out the presence of coronary atherosclerosis assessed by coronary CT angiography (CCTA).Methods: Two hundred and fifty-six subjects with suspected stable CAD recruited from five European countries within H2020-SMARTool, undergoing CCTA and blood sampling for clinical biochemistry and lipidomics, were selected. The MRT was validated by regression methods and then re-estimated (reMRT). The reMRT was used as a baseline model in a likelihood ratio test approach to assess the added predictive value of each lipid from 13 among ceramides, triglycerides, and sphingomyelins. Except for one lipid, the analysis was carried out on more than 240 subjects for each lipid. A sensitivity analysis was carried out by considering two alternative models developed on the cohort as baseline models.Results: In 205 subjects, coronary atherosclerosis ranged from minimal lesions to overt obstructive CAD, while in 51 subjects (19.9%) the coronary arteries were intact. Four triglycerides and seven sphingomyelins were significantly (p < 0.05) and differentially expressed in the two groups and, at a lesser extent, one ceramide (p = 0.067). The probability of being at minimal risk was significantly better estimated by adding either Cer(d18:1/16:0) (p = 0.01), SM(40:2) (p = 0.04), or SM(41:1) at a lesser extent (p = 0.052) to reMRT than by applying the reMRT alone. The sensitivity analysis confirmed the relevance of these lipids. Furthermore, the addition of SM(34:1), SM(38:2), SM(41:2), and SM(42:4) improved the predictive performance of at least one of the other baseline models. None of the selected triglycerides was found to provide an added value.Conclusions: Plasma lipidomics can be a promising source of diagnostic and prognostic biomarkers in cardiovascular disease, exploitable not only to assess the risk of adverse events but also to identify subjects without coronary atherosclerosis, thus reducing unnecessary further testing in normal subjects. Show less
This article is part of the point-of-care ultrasound (POCUS) series. During cardiopulmonary resuscitation, bedside ultrasound has important clinical value for confirming a diagnosis, establishing a... Show moreThis article is part of the point-of-care ultrasound (POCUS) series. During cardiopulmonary resuscitation, bedside ultrasound has important clinical value for confirming a diagnosis, establishing a prognosis and in therapeutic decision-making. In this article we provide a practical review on how to implement and apply POCUS during cardiopulmonary resuscitation and discuss its merits and pitfalls. Show less
Michelucci, E.; Giorgi, N. di; Finamore, F.; Smit, J.M.; Scholte, A.J.H.A.; Signore, G.; Rocchiccioli, S. 2021
Molecular markers are suggested to improve the diagnostic and prognostic accuracy in patients with coronary artery disease (CAD) beyond current clinical scores based on age, gender, symptoms and... Show moreMolecular markers are suggested to improve the diagnostic and prognostic accuracy in patients with coronary artery disease (CAD) beyond current clinical scores based on age, gender, symptoms and traditional risk factors. In this context, plasma lipids are emerging as predictors of both plaque composition and risk of future events. We aim to identify plasma lipid biomarkers associated to CAD indexes of stenosis severity, plaque lipid content and a comprensive score of CAD extent and its risk. We used a simple high performance liquid chromatography-tandem mass spectrometry method to identify 69 plasma lipids in 132 subjects referred to Coronary Computed Tomography Angiography (CCTA) for suspected CAD, all under statin treatment. Patients were stratified in groups using three different CCTA-based annotations: CTA-risk score, lipid plaque prevalence (LPP) ratio and the coronary artery disease-reporting and data system (CAD-RADS). We identified a common set of lipid biomarkers composed of 7 sphingomyelins and 3 phosphatidylethanolamines, which discriminates between high risk CAD patients and controls regardless of the CAD annotations used (CTA score, LPP ratio, or CAD-RADS). These results highlight the potential of circulating lipids as biomarkers of stenosis severity, non calcified plaque composition and overall plaque risk of events. Show less
Mahdiui, M. el; Simon, J.; Smit, J.M.; Kuneman, J.H.; Rosendael, A.R. van; Steyerberg, E.W.; ... ; Maurovich-Horvat, P. 2021
BACKGROUND: Atrial fibrillation (AF) recurrence following catheter ablation remains high. Recent studies have shown a relation between epicardial adipose tissue and AF. epicardial adipose tissue... Show moreBACKGROUND: Atrial fibrillation (AF) recurrence following catheter ablation remains high. Recent studies have shown a relation between epicardial adipose tissue and AF. epicardial adipose tissue secretes several proinflammatory and anti-inflammatory adipokines that directly interact with the adjacent myocardium. The aim of the current study was to evaluate whether posterior left atrial (LA) adipose tissue attenuation, as marker of inflammation, is related to AF recurrences after catheter ablation.METHODS: Consecutive patients with symptomatic AF referred for first AF catheter ablation who underwent computed tomography were included. The total epicardial adipose tissue and posterior LA adipose tissue were manually traced and adipose tissue was automatically recognized as tissue with Hounsfield units (HU) between -195 and -45. The attenuation value of the posterior LA adipose tissue was assessed, and the population was divided according to the mean HU value (-96.4 HU).RESULTS: In total, 460 patients (66% male, age 61 +/- 10 years) were included in the analysis. After a median follow-up of 18 months (interquartile range, 6-32), 168 (37%) patients had AF recurrence. Patients with higher attenuation (>=-96.4 HU) of the posterior LA adipose tissue showed higher AF recurrence rates compared with patients with lower attenuation (P=0.046). Univariate analysis showed an association between AF recurrence and higher posterior LA adipose tissue attenuation (>=-96.4 HU; P<0.05). On multivariable analysis, posterior LA adipose tissue attenuation (hazard ratio, 1.26 [95% CI, 0.90-1.76]; P=0.181) remained a promising predictor of AF recurrence following catheter ablation.CONCLUSIONS: Posterior LA adipose tissue attenuation is a promising predictor of AF recurrence in patients who undergo catheter ablation. Higher adipose tissue attenuation might signal increased local inflammation and serve as an imaging biomarker of increased risk of AF recurrence.GRAPHIC ABSTRACT: A is available for this article. Show less
