Novel Imaging Approaches for the Detection of Hemodynamically Significant Coronary Artery Disease: Quantitative Flow Ratio and Artificial Intelligence-Based Ischemia Algorithm

ABSTRACT In coronary artery disease (CAD), the decision on revascularization is based on the hemodynamic significance of stenoses. However, this cannot directly be determined from the first-line anatomical imaging methods coronary computed tomography angiography (CCTA) in chronic coronary syndrome (CCS) or invasive coronary angiography (ICA) in acute coronary syndrome (ACS). The aim of this thesis was to investigate the prognostic value of two novel approaches to determine functionally significant CAD according to impaired invasive fractional flow reserve (FFR) directly from CCTA in CCS and ICA in ACS. Quantitative flow ratio (QFR) is a novel computational fluid dynamic-based technique to estimate the presence of impaired FFR from biplane ICA. In this study, QFR from untreated non-culprit lesions showed incremental 5-year prognostic value for major adverse cardiac events among ST-elevation myocardial infarction patients undergoing angiography-guided complete revascularization. However, non-culprit QFR did not independently predict non-target-vessel related events prior to planned staged percutaneous coronary intervention (PCI) in ACS patients, and the study does not provide conceptual evidence that QFR could be useful to refine the timing of staged PCI on top of clinical judgement. AI-QCTischemia is an artificial intelligence-based method to predict the probability of an impaired invasive FFR using 37 morphological features from CCTA. Among symptomatic patients with suspected CAD undergoing CCTA, AI-QCTischemia showed incremental prognostic value for the composite of death, myocardial infarction, or unstable angina pectoris throughout a median of 7 years follow-up. This risk stratification pertained especially to patients with no/non-obstructive disease. Patients with obstructive disease on CCTA were referred for downstream myocardial perfusion imaging with positron emission tomography (PET), and among those, AI-QCTischemia showed incremental risk stratification among patients with normal PET perfusion, but not among those with abnormal PET perfusion. KEYWORDS: coronary artery disease, quantitative flow ratio, coronary computed tomography angiography, artificial intelligence, prognosisTIIVISTELMÄ Sepelvaltimotaudissa revaskularisaatiopäätös perustuu hemodynaamisesti merkittävän ahtauman osoitukseen. Tätä ei voida kuitenkaan suoraan määrittää kaikilla kuvantamismenetelmillä, kuten sepelvaltimoiden tietokonetomografialla (TT) kroonisessa sepelvaltimo-oireyhtymässä tai kajoavalla angiografialla akuutissa sepelvaltimotautikohtauksessa. Tämän väitöskirjan tavoitteena oli tutkia kahden uuden sepelvaltimoahtauman hemodynaamisen merkityksen arvioimiseen käytettävän menetelmän ennusteellista arvoa: kajoavaan angiografiaan pohjautuva menetelmä akuutissa sepelvaltimotautikohtauksessa ja TT:aan pohjautuva menetelmä kroonisessa sepelvaltimo-oireyhtymässä. Kvantitatiivinen virtaussuhde (KVS) on uusi laskennalliseen virtausdynamiikkaan perustuva menetelmä, jolla kajoavaan painevaijerimittaukseen perustuvaa sydänlihas-iskemiaa pyritään arvioimaan suoraan tavanomaisista angiografiakuvista. Ei-revaskularisoidun non-culprit-ahtauman KVS:n määrityksellä osoitettiin ennusteellista lisäarvoa 5 vuoden sydän- ja verisuonitautitapahtumien suhteen ST-nousuinfarkti-potilailla, joille oli tehty angiografiaohjattu täydellinen revaskularisaatio. Non-culprit-ahtauman KVS ei kuitenkaan ennustanut kyseiseen suoneen liittyviä tapahtumia ennen suunniteltua viivästettyä non-culprit-ahtauman perkutaanista sepelvaltimotoimenpidettä, joten tämän tutkimuksen perusteella KVS ei vaikuta hyödylliseltä menetelmältä viivästetyn sepelvaltimotoimenpiteen ajoituksen optimoimiseksi. AI-QCTischemia on tekoälyyn perustuva menetelmä, jolla arvioidaan kajoavaan painevaijerimittaukseen perustuvan sydänlihasiskemian todennäköisyyttä käyttäen 37 morfologista sepelvaltimoiden TT:aan pohjautuvaa muuttujaa. Oireisilla potilailla, joille tehtiin TT-tutkimus sepelvaltimotaudin epäilyn vuoksi, AI-QCTischemia tarjosi ennusteellista lisäarvoa yhdistelmätapahtumalle (kuolema, sydäninfarkti tai epävakaa angina pectoris) 7 vuoden seurannan aikana. Tämä riskiluokittelu koski erityisesti potilaita, joilla ei todettu ahtauttavaa sepelvaltimotautia TT:ssa. Potilaat, joilla todettiin TT:n perusteella ahtauttava sepelvaltimotauti, ohjattiin sydänlihasperfuusion kuvantamiseen positroniemissiotomografialla (PET). Tässä joukossa AI-QCTischemia antoi ennusteellista lisätietoa potilailla, joilla oli normaali sydänlihasperfuusio, mutta ei niillä, joilla perfuusio oli alentunut. AVAINSANAT: sepelvaltimotauti, kvantitatiivinen virtaussuhde, tietokonetomografia, tekoäly, ennust

The neural network of saccadic foreknowledge.

Foreknowledge about upcoming events may be exploited to optimize behavioural responses. In a previous work, using an eye movement paradigm, we showed that different types of partial foreknowledge have different effects on saccadic efficiency. In the current study, we investigated the neural circuitry involved in processing of partial foreknowledge using functional magnetic resonance imaging. Fourteen subjects performed a mixed antisaccade, prosaccade paradigm with blocks of no foreknowledge, complete foreknowledge or partial foreknowledge about stimulus location, response direction or task. We found that saccadic foreknowledge is processed primarily within the well-known oculomotor network for saccades and antisaccades. Moreover, we found a consistent decrease in BOLD activity in the primary and secondary visual cortex in all foreknowledge conditions compared to the no-foreknowledge conditions. Furthermore we found that the different types of partial foreknowledge are processed in distinct brain areas: response foreknowledge is processed in the frontal eye field, while stimulus foreknowledge is processed in the frontal and parietal eye field. Task foreknowledge, however, revealed no positive BOLD correlate. Our results show different patterns of engagement in the saccade-related neural network depending upon precisely what type of information is known ahead

Transient injection site reaction to alirocumab during immune system activation: a case series.

Background Injection site reactions (ISRs) are known side effects of the proprotein convertase subtilisin kexin 9 (PCSK9) inhibitor alirocumab. Transient ISR to alirocumab after a long phase of good tolerability have not been reported previously. Case summary A 55-year-old woman (Patient 1) and a 77-year-old man (Patient 2) were treated with alirocumab for the management of dyslipidaemia. Both patients tolerated the treatment without side effects for 7 and 2 months, respectively. After an upper respiratory tract infection in Patient 1 and a first COVID-19 vaccination in Patient 2, both patients suddenly developed ISR with erythema, calor, and itching upon 2 (Patient 1) and 1 (Patient 2) subsequent injection(s), respectively. Symptoms resolved with local steroids, oral antihistamines, and cooling. After termination of the presumed immune system activated state, alirocumab was well tolerated again in both patients without recurrence of any ISR upon repeated applications. Discussion These are the first cases to report transient ISR to a PCSK9 inhibitor, possibly triggered by activation of the immune system, after prolonged good tolerability. Based on the transient and benign nature of the reaction, such patients should be encouraged to continue supervised treatment, as tolerability may return after resolution of the pro-inflammatory state

Impact of intracoronary optical coherence tomography in routine clinical practice: A contemporary cohort study.

BACKGROUND/PURPOSE Guidelines recommend intracoronary optical coherence tomography (OCT) to assess stent failure and guide percutaneous coronary intervention (PCI) but OCT may be useful for other indications in routine clinical practice. METHODS/MATERIALS We conducted an international registry of OCT cases at two large tertiary care centers to assess clinical indications and the potential impact on decision making of OCT in clinical routine. Clinical indications, OCT findings, and their impact on interventional or medical treatment strategy were retrospectively assessed. RESULTS OCT was performed in 810 coronary angiography cases (1928 OCT-pullbacks). OCT was used for diagnostic purposes in 67% (N = 542) and OCT-guided percutaneous coronary intervention in 50% (N = 404, 136 cases with prior diagnostic indication). Most frequent indications for diagnostic OCT were culprit lesion identification in suspected ACS (29%) and stent failure assessment (28%). OCT findings in the diagnostic setting influenced patient management in 74%. OCT-guided PCIs concerned ACS patients in 45%. Among the 55% with chronic coronary syndrome, long lesions >28 mm (19%), left main PCI (16%), and bifurcation PCI with side-branch-stenting (5%) were the leading indications for PCI-guidance. Post-procedural OCT findings led to corrective measures in 52% (26% malapposition, 14% underexpansion, 6% edge dissection, 3% intrastent mass, 3% geographic plaque miss). CONCLUSIONS OCT was most frequently performed to identify culprit lesions in suspected ACS, for stent failure assessment, and PCI-guidance. OCT may impact subsequent treatment strategies in two out of three patients

German translation of the Alberta context tool and two measures of research use: methods, challenges and lessons learned

Background: Understanding the relationship between organizational context and research utilization is key to reducing the research-practice gap in health care. This is particularly true in the residential long term care (LTC) setting where relatively little work has examined the influence of context on research implementation. Reliable, valid measures and tools are a prerequisite for studying organizational context and research utilization. Few such tools exist in German. We thus translated three such tools (the Alberta Context Tool and two measures of research use) into German for use in German residential LTC. We point out challenges and strategies for their solution unique to German residential LTC, and demonstrate how resolving specific challenges in the translation of the health care aide instrument version streamlined the translation process of versions for registered nurses, allied health providers, practice specialists, and managers. Methods: Our translation methods were based on best practices and included two independent forward translations, reconciliation of the forward translations, expert panel discussions, two independent back translations, reconciliation of the back translations, back translation review, and cognitive debriefing. Results: We categorized the challenges in this translation process into seven categories: (1) differing professional education of Canadian and German care providers, (2) risk that German translations would become grammatically complex, (3) wordings at risk of being misunderstood, (4) phrases/idioms non-existent in German, (5) lack of corresponding German words, (6) limited comprehensibility of corresponding German words, and (7) target persons’ unfamiliarity with activities detailed in survey items. Examples of each challenge are described with strategies that we used to manage the challenge. Conclusion: Translating an existing instrument is complex and time-consuming, but a rigorous approach is necessary to obtain instrument equivalence. Essential components were (1) involvement of and co-operation with the instrument developers and (2) expert panel discussions, including both target group and content experts. Equivalent translated instruments help researchers from different cultures to find a common language and undertake comparative research. As acceptable psychometric properties are a prerequisite for that, we are currently carrying out a study with that focus

Plaque erosion causing ST-elevation myocardial infarction after consumption of cannabis and N2O in a 27-year old man: a case report.

BACKGROUND The recreational drugs cannabis and nitrous oxide (N2O) are known for pro-atherogenic effects and are associated with an elevated risk of myocardial infarction. These cardiovascular effects might be underestimated by the public. Culprit-lesion composition of myocardial infarctions associated with cannabis and N2O has been unknown so far. This case report aims to raise the awareness of the adverse cardiovascular effects of cannabis and N2O and reports, for the first time, optical coherence tomography (OCT) findings of the culprit lesion. CASE PRESENTATION This is a case report of a 27-year old man with anterior ST-segment-elevation myocardial infarction (STEMI) after intoxication with cannabis and N2O. Coronary angiography and OCT revealed plaque erosion with subsequent subtotal thrombotic occlusion of the left anterior descending artery that was successfully treated with 1 drug-eluting stent. The patient was symptom free at 6 months follow-up and had been able to abstain from drug consumption. CONCLUSIONS This is the first case to demonstrate the association between cannabis and N2O abuse and plaque erosion on OCT in a young man with STEMI. In contrast to smoking, whose adverse effects are well-known, the cardiovascular effects of cannabis and N2O might be underestimated. These adverse effects should gain more awareness in the public to prevent early vascular events in young adults

Ominous triad triggered by high-dose glucocorticosteroid therapy.

Glucocorticosteroids (CS) play a key role in the treatment of numerous diseases. Nonetheless, they can be accompanied by several adverse effects. We present the case of a 51-year-old woman who was treated with high-dose CS for a relapse of her multiple sclerosis. After 5 days of treatment, the patient developed severe diabetic ketoacidosis, hypertriglyceridemia and acute pancreatitis-a potentially life-threatening triad which has previously been described, in our case, however, for the first time as a complication of CS therapy. Our patient's condition was further aggravated by a circulatory shock, haemodynamic relevant bleeding from a duodenal ulcer and psychotic symptoms. In the intensive care unit, intravenous insulin infusion, fluid resuscitation, catecholamine support, electrolyte supplementation, endoscopic haemoclipping and antibiotic and antipsychotic treatment were administered, leading to a continuous improvement of the patient's health state

[Intracoronary imaging - an essential tool on the way to an individualized therapy of coronary artery disease?]

Intracoronary imaging - an essential tool on the way to an individualized therapy of coronary artery disease? Abstract. Since decades, coronary angiography is the standard method to assess coronary anatomy and guide percutaneous coronary intervention. However, coronary angiography is limited to the lumen and a resolution of 200 - 300 micrometers. Thus, anything beyond is not detectable. Intracoronary imaging methods by means of intravascular ultrasound (IVUS) and particularly optical coherence tomography (OCT), provide incremental effects on coronary diagnostics and therapeutic decisions. Plaque burden and -composition (lipid, fibrous, calcific tissue, intramural hematoma), small intraluminal structures (thrombus), and implanted stents are uniquely detectable by intracoronary imaging. The use of these techniques inevitably leads to improved precision in coronary diagnostics and optimization of stent implantation