Successful closure of transcatheter aortic valve replacement-induced Gerbode defect with valve-in-valve technique: A case report.

We present the first documented case of a successful closure of a transcatheter aortic valve replacement (TAVR)-induced Gerbode defect using a valve-in-valve approach. A 90-year-old female with severe aortic stenosis underwent TAVR. Following post-dilatation, the patient experienced hemodynamic deterioration and collapse due to tamponade and sub-annular rupture leading to hemodynamic deterioration and the development of a Gerbode defect with communication between the left ventricle and right atrium. Hemodynamic stabilization was achieved through pericardiocentesis, followed by the low implantation of a second valve, effectively sealing the rupture. This case showcases a valuable alternative for managing rare challenging complications during TAVR procedures.

Assessment of myocardial salvage in patients with STEMI undergoing thrombolysis: ticagrelor versus clopidogrel.

BACKGROUND: In the setting of ST-segment elevation myocardial infarction (STEMI), the faster and stronger antiplatelet action of ticagrelor compared to clopidogrel, as well as its pleiotropic effects, could result in a greater degree of cardioprotection and final infarct size (FIS) limitation. The aim of our study was to comparatively evaluate the effect of ticagrelor and clopidogrel on myocardial salvage index (MSI) in STEMI patients undergoing thrombolysis. METHODS: Forty-two STEMI patients treated with thrombolysis were randomized to receive clopidogrel (n = 21) or ticagrelor (n = 21), along with aspirin. Myocardial area at risk (AAR) was calculated according to the BARI and the APPROACH jeopardy scores. FIS was quantified by cardiac magnetic resonance imaging (CMR) performed 5-6 months post-randomization. MSI was calculated as (AAR-FIS)/AAR × 100%. Primary endpoint of our study was MSI. Secondary endpoints were FIS and CMR-derived left ventricular ejection fraction (LVEF) at 5 -6 months post-randomization. RESULTS: By using the BARI score for AAR calculation, mean MSI was 52.25 ± 30.5 for the clopidogrel group and 54.29 ± 31.08 for the ticagrelor group (p = 0.83), while mean MSI using the APPROACH score was calculated at 51.94 ± 30 and 53.09 ± 32.39 (p = 0.9), respectively. Median CMR-derived FIS-as a percentage of LV-was 10.7% ± 8.25 in the clopidogrel group and 12.09% ± 8.72 in the ticagrelor group (p = 0.6). Mean LVEF at 5-6 months post-randomization did not differ significantly between randomization groups. CONCLUSIONS: Our results suggest that the administration of ticagrelor in STEMI patients undergoing thrombolysis offer a similar degree of myocardial salvage, compared to clopidogrel.

The management of atrial fibrillation in heart failure: an expert panel consensus.

Heart failure (HF) and atrial fibrillation (AF) often coexist, being closely interrelated as the one increases the prevalence and incidence and worsens the prognosis of the other. Their frequent coexistence raises several challenges, including under-diagnosis of HF with preserved ejection fraction in AF and of AF in HF, characterization and diagnosis of atrial cardiomyopathy, target and impact of rate control therapy on outcomes, optimal rhythm control strategy in the era of catheter ablation, HF-related thromboembolic risk and management of anticoagulation in patients with comorbidities, such as chronic kidney disease or transient renal function worsening, coronary artery disease or acute coronary syndromes, valvular or structural heart disease interventions and cancer. In the present document, derived by an expert panel meeting, we sought to focus on the above challenging issues, outlining the existing evidence and identifying gaps in knowledge that need to be addressed.

Contemporary Antiplatelet Treatment in Acute Coronary Syndrome Patients with Impaired Renal Function Undergoing Percutaneous Coronary Intervention.

OBJECTIVES: To assess the clinical impact of impaired renal function (IRF), in "real-world" acute coronary syndrome (ACS) patients, receiving clopidogrel, prasugrel, or ticagrelor. METHODS: This was a prospective, observational, multicenter, cohort study of ACS patients undergoing percutaneous coronary interventions (PCI) with IRF (creatinine clearance <60 mL/min by Cockroft-Gault equation), who were recruited into the Greek Antiplatelet Registry (GRAPE). Patients were followed-up until 1 year for major adverse cardiovascular events (MACE; a composite of death, nonfatal myocardial infarction, urgent revascularization, and stroke) and BARC (Bleeding Academic Research Consortium) bleeding. RESULTS: Out of 2,047 registered patients, there were 344 (16.8%) with IRF. At the 1-year follow-up, MACE occurred in 18.6 and 6.2% of those patients with and without IRF, respectively: adjusted hazard ratio (HR) = 2.13 (95% confidence interval, CI 1.16-3.91), p = 0.02. IRF patients were also at higher risk of death and BARC type ≥2 and ≥3 bleeding: adjusted HR = 3.55 (95% CI 1.73-7.27), p = 0.001; HR = 2.75 (95% CI 1.13-6.68), p = 0.03; and HR = 6.02 (95% CI 2.30-15.77), p < 0.001, respectively. Combined MACE and BARC type ≥2 bleeding occurred in 34.0 and 14.0% of those with and without IRF, respectively: adjusted HR = 2.65 (95% CI 1.36-5.16), p = 0.004. At discharge, clopidogrel was more frequently prescribed in IRF patients (61.0 vs. 33.1%, p < 0.001). CONCLUSIONS: Real-world ACS patients with IRF subjected to PCI demonstrate higher thrombotic and bleeding risks than patients with normal renal function.

Dyspnea in patients treated with P2Y12 receptor antagonists: insights from the GReek AntiPlatElet (GRAPE) registry.

In 'real life' acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI) and receiving contemporary antiplatelet treatment, data on dyspnea occurrence and impact on persistence with treatment are scarce. In a prospective, multicenter, cohort study, ACS patients undergoing PCI were recruited into the GReekAntiPlatElet (GRAPE) registry. During 1-year follow up, overall, 249/1989 (12.5%) patients reported dyspnea, more frequently at 1-month and decreasing thereafter. Multivariate analysis showed that ticagrelor administration (n = 738) at discharge was associated with the occurrence of dyspnea: Odds ratio 2.46 (95% confidence interval, CI, 1.87-3.25), p < 0.001. Older age, lower hematocrit, and prior bleeding event were also associated with dyspnea reports. Persistence, switching, and cessation rates were 68.3%, 20.9%, and 10.8% vs 76.7%, 12.5%, and 10.9% among patients reporting dyspnea compared with those who did not, p for trend = 0.002. In conclusion, in ACS patients undergoing PCI and treated with a P2Y12 receptor antagonist, dyspnea occurs commonly, particularly when ticagrelor is administered. Non-persistence with antiplatelet agents at discharge is more frequently observed among dyspnea-reporters.

Comparison of the antiplatelet effect of clopidogrel hydrogenosulfate and clopidogrel besylate in patients with stable coronary artery disease.

It is well known that patients with poor response to antiplatelet therapy are most likely to have more thrombotic events. Clopidogrel hydrogensulfate (CHS) is a thienopyridine acting as an important antiplatelet agent alone or in combination with acetylsalicylic acid to prevent cardiovascular complications. A different clopidogrel salt, clopidogrel besylate (CB), was recently approved as a generic drug for the same purpose while data about its antiplatelet effect are very scarce. Our study compared the antiplatelet effect of CHS and CB in patients with stable coronary artery disease. Patients with stable coronary artery disease (n = 101) (coronary lesions defined angiographically 30-70 %) were randomized to either CHS (n = 50) or CB (n = 51). After randomization a 600 mg loading dose of the drug was given and monitoring of antiplatelet effect was done 12-14 h later with VerifyNow assay. Antiplatelet response was measured with P2Y12 reaction units (PRU) and % inhibition P2Y12 from baseline (% inhibition P2Y12). Moreover CYP2C19*2, CYP2C19*3 and CYP3Α5 polymorphisms were studied in all patients. Clinical characteristics were similar between the two study groups. No significant difference was observed for baseline platelet reactivity between CHS and CB patients (258 ± 38 vs. 256 ± 38 respectively, p = 0.79). No difference was found for antiplatelet response between the CHS and the CB group, assessed by PRU (195 ± 74 vs. 204 ± 67 respectively, p = 0.51) and by % inhibition P2Y12 (24 ± 25 vs. 24 ± 22 % respectively, p = 0.95). Number of heterozygotes for CYP2C19*2 polymorphism was comparable and their platelet reactivity was similar between the two study groups. Our results indicate that both CB and CHS had an identical antiplatelet effect in patients with stable coronary artery disease. No difference on platelet reactivity of heterozygotes for CYP2C19*2 polymorphism was found between the two study groups.

Evolving concepts of angiogram: fractional flow reserve discordances in 4000 coronary stenoses.

AIMS: The present analysis addresses the potential clinical and physiologic significance of discordance in severity of coronary artery disease between the angiogram and fractional flow reserve (FFR) in a large and unselected patient population. METHODS AND RESULTS: Between September 1999 and December 2011, FFR and percent diameter stenosis (DS) as assessed by quantitative coronary angiography were obtained in 2986 patients (n = 4086 coronary stenoses), in whom at least one stenosis was of intermediate angiographic severity. Fractional flow reserve correlated slightly but significantly with DS [-0.38 (95% CI: -0.41; -0.36); P < 0.001]. The sensitivity, specificity, and diagnostic accuracy of a ≥ 50% DS for predicting FFR ≤ 0.80 were 61% (95% CI: 59; 63), 67% (95% CI: 65; 69), and 0.64 (95% CI: 0.56; 0.72), respectively. In different anatomical settings, sensitivity and specificity showed marked variations between 35 to 74% and 58 to 76%, respectively, resulting in a discordance in 35% of all cases for these thresholds. For an angiographic threshold of 70% DS, the diagnostic performance by the Youden's index decreased from 0.28 to 0.11 for the overall population. CONCLUSION: The data confirm that one-third of a large patient population shows discordance between angiogram ≥ 50%DS and FFR ≤ 0.8 thresholds of stenosis severity. Left main stenoses are often underestimated by the classical 50% DS cut-off compared with FFR. This discordance offers physiologic insights for future trials. It is hypothesized that the discordance between angiography and FFR is related to technical limitations, such as imprecise luminal border detection by angiography, as well as to physiologic factors, such as variable minimal microvascular resistance.

In-hospital switching of oral P2Y12 inhibitor treatment in patients with acute coronary syndrome undergoing percutaneous coronary intervention: prevalence, predictors and short-term outcome.

BACKGROUND: P2Y12 inhibitor switching has appeared in clinical practice as a consequence of prasugrel and ticagrelor availability, apart from clopidogrel, for use in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). METHODS: In the context of the GReek AntiPlatelet REgistry (GRAPE) we assessed the prevalence, predictive factors and short-term outcome of in-hospital P2Y12 inhibitor switching in 1794 ACS patients undergoing PCI. RESULTS: Switching occurred in 636 (35.5%) patients of which in the form of clopidogrel to a novel agent, novel agent to clopidogrel and between prasugrel and ticagrelor in 574 (90.4%), 34 (5.3%) and 27 (4.3%) patients, respectively. Presentation to non PCI-capable hospital, bivalirudin use, age ≥75 years (inverse predictor), and regional trends emerged as predictive factors of switching to a novel agent. At combined in-hospital and one-month follow-up, propensity matched pairs analysis showed no differences in major adverse cardiovascular (MACE) or bleeding events between switching from clopidogrel to a novel agent vs novel agent constant administration. More Bleeding Academic Research Consortium type 1, type 2 and any type events and fewer MACE were seen when switching from clopidogrel to a novel agent vs only clopidogrel administration (23.7%, 3.8%, 30.6%, 1.2% vs 8.9%, 1.2%, 12.0%, 3.8% with P < .001, P = .03, P < .001 and P = .03 respectively). CONCLUSIONS: In a real-life experience with contemporary antiplatelet treatment in ACS patients undergoing PCI, in-hospital switching represents common clinical practice. Clinical factors and regional practice differences seem to affect this strategy's choice, while switching to a novel agent may be associated with higher risk of bleeding.

Contraindications/special warnings and precautions for use of contemporary oral antiplatelet treatment in patients with acute coronary syndrome undergoing percutaneous coronary intervention.

BACKGROUND: The prevalence of contraindications/special warnings and precautions (CON/SWP) for clopidogrel, prasugrel and ticagrelor use is not adequately studied and might affect P2Y12 inhibitor choice in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI). METHODS AND RESULTS: In the context of the GReek AntiPlatelet rEgistry (GRAPE) a detailed recording of CON/SWP for use of clopidogrel, prasugrel and ticagrelor was done for 1,280 consecutive, moderate-high-risk ACS patients undergoing PCI. At least 1 CON for use of clopidogrel, prasugrel and ticagrelor was present in 5 (0.4%), 49 (3.8%) and 12 patients (0.9%), respectively. Prevalence of at least 1 CON/SWP to clopidogrel (45.8%) was less frequent compared to prasugrel (49.1%) or ticagrelor (49.1%; P=0.02 and P=0.04, respectively), while 34% of patients had at least 1 CON/SWP to all the 3 P2Y12 inhibitors. At discharge, 482 (38.6%), 301 (24.1%) and 464 patients (37.2%) received clopidogrel, prasugrel and ticagrelor, respectively. Age ≥75 years, co-medication related to increased bleeding risk, and history of asthma/chronic obstructive pulmonary disease favored clopidogrel vs. prasugrel or ticagrelor use as discharge medication, while geographic region also affected this choice (C-statistic, 0.81; 95% CI: 0.78-0.83). CONCLUSIONS: In patients with ACS undergoing PCI the prevalence of CON to antiplatelet agents is low, whereas that of SWP is high. Certain SWP, along with regional trends may affect the choice of newer P2Y12 inhibitors vs. clopidogrel.

The Role of Intracoronary Imaging for the Management of Calcified Lesions.

Interventional cardiologists in everyday practice are often confronted with calcified coronary lesions indicated for percutaneous transluminal coronary angioplasty (PTCA). PTCA of calcified lesions is associated with diverse technical challenges resulting in suboptimal coronary stenting and adverse long-term clinical outcomes. Angiography itself offers limited information regarding coronary calcification, and the adjuvant use of intracoronary imaging such as intravascular ultrasound (IVUS) and Optical Coherence Tomography (OCT) can guide the treatment of calcified coronary lesions, optimizing the different stages of the procedure. This review offers a description of why, when, and how to use intracoronary imaging for PTCA of calcified coronary lesions in order to obtain the most favorable results. We used the PubMed and Google Scholar databases to search for relevant articles. Keywords were calcified coronary lesions, intracoronary imaging, IVUS, OCT, coronary calcium modification techniques, PTCA, and artificial intelligence in intracoronary imaging. A total of 192 articles were identified. Ninety-one were excluded because of repetitive or non-important information.

Dual Antiplatelet Therapy and Cancer; Balancing between Ischemic and Bleeding Risk: A Narrative Review.

Cardiovascular (CV) events in patients with cancer can be caused by concomitant CV risk factors, cancer itself, and anticancer therapy. Since malignancy can dysregulate the hemostatic system, predisposing cancer patients to both thrombosis and hemorrhage, the administration of dual antiplatelet therapy (DAPT) to patients with cancer who suffer from acute coronary syndrome (ACS) or undergo percutaneous coronary intervention (PCI) is a clinical challenge to cardiologists. Apart from PCI and ACS, other structural interventions, such as TAVR, PFO-ASD closure, and LAA occlusion, and non-cardiac diseases, such as PAD and CVAs, may require DAPT. The aim of the present review is to review the current literature on the optimal antiplatelet therapy and duration of DAPT for oncologic patients, in order to reduce both the ischemic and bleeding risk in this high-risk population.

Cardiology in the digital era: from artificial intelligence to Metaverse, paving the way for future advancements.

Tweetable abstract Cardiology's digital revolution: AI diagnoses, ChatGPT consults, Metaverse educates. Challenges & promises explored. #CardiologyTech #DigitalHealth.

Post-PCI corrected TIMI Frame Count predicts left ventricular global longitudinal strain at 90 days post-STEMI in thrombolysis-treated patients: A pre-specified analysis of the MIRTOS study.

Introduction: Ticagrelor has been established as the P2Y12-inhibitor of choice in ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI); however, its use has not been adequately studied in the context of thrombolysis. In the present study, we sought to investigate whether the administration of ticagrelor together with thrombolysis could result in a greater degree of left ventricular systolic function recovery compared to clopidogrel, at 90 days post-STEMI, as well as to evaluate post-PCI corrected TIMI Frame Count (CTFC) as a predictive marker of myocardial recovery in thrombolysis-treated patients. Material and methods: In this pre-specified analysis of the MIRTOS trial, the degree of change in left ventricular ejection fraction (ΔLVEF) and left ventricular longitudinal strain (ΔLV-GLS) from baseline to 90 days post-randomization in all patients who underwent conventional and speckle-tracking echocardiography at both timepoints was compared between the ticagrelor and clopidogrel groups. In addition, speckle-tracking echocardiographic measurements were evaluated for any correlations to post-PCI CTFC. Results: No statistically significant differences were detected between the ticagrelor and clopidogrel groups for ΔLVEF (+3.61 ± 5.08 % versus +2.21 ± 4.78 %; P = 0.18) and ΔLV-GLS (-1.53 ± 2.7 % versus -1.21 ± 3.05 %; P = 0.73). A strong negative correlation was found between post-PCI CTFC and the absolute value of LV-GLS at 90 days post-randomization (r = -0.33, P = 0.014). Conclusions: Our work suggests that both P2Y12-inhibitors are accompanied with a similar degree of myocardial recovery in the context of lytic therapy. Importantly, post-PCI microvascular integrity is a predictor of 3-month left ventricular systolic function in STEMI patients initially treated with thrombolysis.

Relationship between peripheral arterial reactive hyperemia and residual platelet reactivity after 600 mg clopidogrel.

Clopidogrel reduces long-term ischemic events in patients with acute coronary syndrome or stable angina (SA) undergoing percutaneous coronary intervention (PCI). Endothelial function improvement has been proposed, among other factors, for this beneficial effect of clopidogrel, but whether this might be associated to its anti-platelet action remains unclear. We tested the hypothesis that clopidogrel improvement of peripheral vascular endothelial function might be associated with inhibition of platelet aggregation. Endothelial function was evaluated before and at least 12 h after 600 mg clopidogrel in 43 SA pts undergoing elective PCI by: (a) reactive hyperemia peripheral arterial tonometry (measuring the Endoscore); (b) circulating endothelial microparticles (EMPs). Response to clopidogrel was measured with point-of-care VerifyNow P2Y12 assay and expressed as platelet reaction unit (PRU) and percent platelet inhibition (%PI). High platelet reactivity after clopidogrel was defined as PRU ≥ 240. Endothelial function improved after clopidogrel in 20 pts. Changes in Endoscore (Δ Endoscore) were significantly correlated with both PRU (r = -0.61, P < 0.001) and %PI (r = 0.57, P < 0.001). Endoscore significantly increased after clopidogrel in pts with PRU < 240 (0.38 ± 0.26 to 0.57 ± 0.33, P < 0.001), but did not in pts with PRU ≥ 240 (0.53 ± 0.31 to 0.40 ± 0.37, P = 0.12). EMPs were also significantly reduced in pts with PRU < 240 (222 [140-593] to 142 [83-371]/µl, P = 0.001), while no changes were observed in pts with PRU ≥ 240 (256 [178-531] to 388 [238-499]/µl, P = 0.55). In patients with stable coronary artery disease, a single 600 mg clopidogrel loading dose improves vascular endothelial function. This improvement is associated with optimal platelet inhibition and it is not observed in patients with post-clopidogrel high platelet reactivity.

Ticagrelor versus clopidogrel in patients with STEMI treated with thrombolysis: the MIRTOS trial.

AIMS: We aimed to demonstrate whether coronary microvascular function is improved after ticagrelor administration compared to clopidogrel administration in STEMI subjects undergoing thrombolysis. METHODS AND RESULTS: MIRTOS is a multicentre study of ticagrelor versus clopidogrel in STEMI subjects treated with fibrinolysis. We enrolled 335 patients <75 years old with STEMI eligible for thrombolysis, of whom 167 were randomised to receive clopidogrel and 168 to receive ticagrelor together with thrombolysis. Primary outcome was the difference in post-PCI corrected TIMI frame count (CTFC). All clinical events were recorded in a three-month follow-up period. From the 335 patients who were randomised, 259 underwent PCI (129 clopidogrel and 130 ticagrelor) and 154 angiographies were analysable for the study primary endpoint. No significant difference was found between the clopidogrel (n=85) and ticagrelor (n=69) groups for CTFC (24.33±17.35 vs 28.33±17.59, p=0.10). No significant differences were observed in MACE and major bleeding events between randomisation groups (OR 2.0, 95% CI: 0.18-22.2, p=0.99). CONCLUSIONS: Thrombolysis with ticagrelor in patients <75 years old was not able to demonstrate superiority compared to clopidogrel in terms of microvascular injury, while there was no difference between the two groups in MACE and major bleeding events. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02429271. EudraCT Number 2014-004082-25.

Long-term clinical outcome after fractional flow reserve-guided treatment in patients with angiographically equivocal left main coronary artery stenosis.

BACKGROUND: Significant left main coronary artery stenosis is an accepted indication for surgical revascularization. The potential of angiography to evaluate the hemodynamic severity of a stenosis is limited. The aims of the present study were to assess the long-term clinical outcome of patients with an angiographically equivocal left main coronary artery stenosis in whom the revascularization strategy was based on fractional flow reserve (FFR) and to determine the relationship between quantitative coronary angiography and FFR. METHODS AND RESULTS: In 213 patients with an angiographically equivocal left main coronary artery stenosis, FFR measurements and quantitative coronary angiography were performed. When FFR was > or =0.80, patients were treated medically or another stenosis was treated by coronary angioplasty (nonsurgical group; n=138). When FFR was <0.80, coronary artery bypass grafting was performed (surgical group; n=75). The 5-year survival estimates were 89.8% in the nonsurgical group and 85.4% in the surgical group (P=0.48). The 5-year event-free survival estimates were 74.2% and 82.8% in the nonsurgical and surgical groups, respectively (P=0.50). Percent diameter stenosis at quantitative coronary angiography correlated significantly with FFR (r=-0.38, P<0.001), but a very large scatter was observed. In 23% of patients with a diameter stenosis <50%, the left main coronary artery stenosis was hemodynamically significant by FFR. CONCLUSIONS: In patients with equivocal stenosis of the left main coronary artery, angiography alone does not allow appropriate individual decision making about the need for revascularization and often underestimates the functional significance of the stenosis. The favorable outcome of an FFR-guided strategy suggests that FFR should be assessed in such patients before a decision is made "blindly" about the need for revascularization.

Functional Recovery of a Failed Radial Artery Graft After Progression of Native Coronary Stenosis.

Competitive flow from the native vessel can lead to coronary graft failure. However, restoration of graft patency can occasionally occur. We present the case of subtotal occlusion of a radial artery graft bypassing a lesion with moderate stenosis, with subsequent late functional recovery once the native vessel disease had progressed. (Level of Difficulty: Intermediate.).

In vitro and in vivo studies on thermistor-based intracoronary temperature measurements: effect of pressure and flow.

BACKGROUND: Intracoronary thermography has been proposed to detect vulnerable plaques. We hypothesized that changes in coronary pressure and flow in the coronary tree may interfere with the temperature measurements obtained with thermistors. METHODS AND RESULTS: First, a very close correlation was found in vitro between the temperature measured by a thermocouple and by a thermistor-based temperature measuring guide wire (PressureWire, PW) over a large temperature range. Second, the PW was tested in a vitro low pressure model of "hot plaque". The sensor of the PW could detect changes in temperature of the wall of 0.5 degrees C as long as the distance from the wall was less than 0.5 mm and the flow less than 60 mL/min. Third, in 18 patients with an acute myocardial infarction, intracoronary pressure and temperature variations were assessed. Although crossing the occlusion, the temperature rose by 0.059 +/- 0.02 degrees C and this increase was correlated with the distal coronary pressure (r = 0.72, P < 0.001). Fourth, a balloon coronary occlusion (BCO) with the sensor distally in the distal part of the vessel (low flow/low pressure conditions) systematically induced an increase in temperature (0.14 +/- 0.07 degrees C) while with the sensor proximally to the balloon occlusion (low flow/normal pressure conditions), no change occurred. CONCLUSION: Taken together these observations suggest that thermistor-based sensors are not suited for assessing thermal heterogeneity in the vascular wall and that the data obtained so far in patients with acute coronary syndromes might have been flawed by pressure (and flow) artifacts.