Comparison of Quantitative Flow Ratio (QFR) with Fractional Flow Reserve (FFR) in the hemodynamic assessment of angiographic intermediate coronary artery stenoses

Einleitung: Die hämodynamische Beurteilung mittelgradiger Koronararterienstenosen kann die Risikostratifizierung verbessern, indem Ziele für Revaskularisationsverfahren identifiziert werden. Die fraktionelle Flussreserve (FFR) ist eine etablierte Methode in der invasiven Ischämiediagnostik und hat ihren prognostischen Nutzen in der Steuerung der Revaskularisationstherapie demonstriert. Die Angiographie-basierte Quantitative Flow Ratio (QFR) wurde als weniger invasive und adenosinfreie Methode eingeführt. Ziel dieser Dissertationsarbeit ist es, die diagnostische Leistung der Angiographie-basierten QFR mit der invasiv gemessenen FFR bei der funktionellen Beurteilung mittelgradiger Koronararterienstenosen in verschiedenen Patientensubgruppen zu vergleichen. Methoden: In den Projekten 1 und 2 wurden insgesamt 436 Patientinnen und Patienten mit chronischem Koronarsyndrom (CCS) und FFR-Messung während ihrer diagnostischen Koronarangiographie in der klinischen Routine retrospektiv eingeschlossen. Mittelgradige Koronararterienstenosen in 516 Gefäßen wurden zusätzlich hämodynamisch mittels QFR beurteilt. Die invasiv gemessene FFR diente als Referenzstandard für die QFR sowie Pd/Pa in Ruhe und anatomische Indizes. In Projekt 2 wurden die Patientinnen und Patienten entsprechend ihrem Referenzgefäßdurchmesser in zwei Gruppen eingeteilt (Gruppe 1: ≤2.8mm und Gruppe 2: >2.8mm). Auf diese Ergebnisse aufbauend, wurden in dem dritten Projekt 321 Patientinnen und Patienten mit akutem Koronarsyndrom (ACS) und geplanter zweiten Koronarintervention eingeschlossen und die diagnostische Leistung der QFR durch serielle Messungen untersucht. Ergebnisse: Das Projekt 1 zeigte eine signifikante Korrelation und gute Übereinstimmung der QFR mit der FFR. Die QFR demonstrierte eine ausgezeichnete und dem Ruheindex Pd/Pa überlegene diagnostische Leistung in der Identifizierung einer hämodynamischen Relevanz von Koronararterienstenosen. Diese sehr guten diagnostischen Ergebnisse konnten im Projekt 2 bestätigt und auf Stenosen in kleinen Koronararterien ausgeweitet werden. Darauf aufbauend zeigten Patientinnen und Patienten mit ACS und Mehrgefäßerkrankung in Projekt 3 eine exzellente diagnostische Leistung in der Identifizierung von funktionell signifikanten Non-Culprit Läsionen mit einer starken Korrelation und Übereinstimmung zwischen den QFR-Messungen zum Zeitpunkt des ACS und der geplanten zweiten Prozedur. Schlussfolgerung: Die QFR stellt ein auf Angiographie-basiertes Verfahren für die hämodynamische Beurteilung mittelgradiger Koronararterienstenosen dar, welches im Vergleich zu Ruheindizes und anatomischen Indizes eine überlegene diagnostische Leistung aufweist, unabhängig vom Referenzgefäßdurchmesser. Die Durchführbarkeit und diagnostische Genauigkeit der funktionellen Beurteilung von Koronarläsionen im Rahmen eines ACS konnten ebenfalls demonstriert werden und unterstützt die QFR als wertvolles Tool in verschiedenen Patientensubgruppen.Background: Hemodynamic assessment of intermediate coronary artery lesions can improve risk stratification by identifying targets for revascularization procedures. Fractional flow reserve (FFR) is an established modality in invasive ischemia diagnostics and has proven prognostic benefit in guiding revascularization therapy. Angiography-based Quantitative Flow Ratio (QFR) was introduced as less-invasive and adenosine-free method. The aim of this doctoral thesis is to compare the diagnostic performance of angiography based QFR with invasively assessed FFR in the functional evaluation of intermediate coronary artery lesions in different patient subsets. Methods: In projects 1 and 2, a total of 436 patients with chronic coronary syndrome (CCS) undergoing FFR measurement during diagnostic coronary angiography in clinical routine were retrospectively enrolled. Intermediate coronary artery stenoses in 516 vessels were additionally hemodynamically assessed by QFR. Invasively assessed FFR served as reference standard for QFR, resting Pd/Pa and anatomic indices. Patients were divided into two groups according to their reference vessel diameter (group 1: ≤2.8 mm and group 2: >2.8 mm) in project 2. Based on these results, 321 patients with acute coronary syndrome (ACS) and planned staged coronary intervention were included in project 3 and diagnostic performance of QFR was investigated by serial measurements. Results: In project 1, QFR demonstrated significant correlation and good agreement with FFR. QFR revealed excellent diagnostic performance superior to the resting index Pd/Pa for identifying functional significance of intermediate coronary artery stenoses. These very good diagnostic results could be strengthened in project 2 and extended to small-vessel disease. Based on these results, patients with ACS and multivessel disease in project 3 revealed excellent diagnostic performance in identifying functional significant non-culprit lesions with strong correlation and good agreement between QFR measurements at acute and staged setting. Conclusion: QFR provides an angiography-based diagnostic tool for hemodynamic assessment of intermediate coronary lesions with superior diagnostic performance as compared with resting and anatomic indices irrespective of the reference vessel diameter. The feasibility and diagnostic accuracy of functional lesion evaluation in setting of ACS could also be demonstrated and further support QFR as valuable tool in different patient subsets

Feasibility and diagnostic reliability of quantitative flow ratio in the assessment of non-culprit lesions in acute coronary syndrome

Several studies have demonstrated the feasibility and safety of hemodynamic assessment of non-culprit coronary arteries in setting of acute coronary syndromes (ACS) using fractional flow reserve (FFR) measurements. Quantitative flow ratio (QFR), recently introduced as angiography-based fast FFR computation, has been validated with good agreement and diagnostic performance with FFR in chronic coronary syndromes. The aim of this study was to assess the feasibility and diagnostic reliability of QFR assessment during primary PCI. A total of 321 patients with ACS and multivessel disease, who underwent primary PCI and were planned for staged PCI of at least one non-culprit lesion were enrolled in the analysis. Within this patient cohort, serial post-hoc QFR analyses of 513 non-culprit vessels were performed. The median time interval between primary and staged PCI was 49 [42-58] days. QFR in non-culprit coronary arteries did not change between acute and staged measurements (0.86 vs 0.87, p = 0.114), with strong correlation (r = 0.94, p ≤ 0.001) and good agreement (mean difference -0.008, 95%CI -0.013-0.003) between measurements. Importantly, QFR as assessed at index procedure had sensitivity of 95.02%, specificity of 93.59% and diagnostic accuracy of 94.15% in prediction of QFR ≤ 0.80 at the time of staged PCI. The present study for the first time confirmed the feasibility and diagnostic accuracy of non-culprit coronary artery QFR during index procedure for ACS. These results support QFR as valuable tool in patients with ACS to detect further hemodynamic relevant lesions with excellent diagnostic performance and therefore to guide further revascularisation therapy

Assessment of intermediate coronary lesions by fractional flow reserve and quantitative flow ratio in patients with small-vessel disease

BACKGROUND Quantitative flow ratio (QFR) has recently been introduced as a novel, less-invasive, adenosine-free measure for functional coronary lesion assessment. Whether reference vessel dimensions affect functional lesion assessment is uncertain. METHODS A total of 436 patients with 516 interrogated coronary vessels by means of FFR were included in the study. Patients were dichotomized according to the median reference vessel diameter (group 1: ≤2.8 mm and group 2: >2.8 mm). QFR analyses were performed offline at the institution's core laboratories. RESULTS Reference vessel diameter was 2.5 [2.3-2.7] mm in group 1 and 3.3 [3.0-3.6] mm in group 2. Diameter stenosis (41.4 [36.4-47.6] % vs. 41.4 [36.4-45.7] %, p = .20) did not differ among groups. Median FFR values were lower in group 1 (0.87 [0.81-0.92]) as compared with group 2 (0.89 [0.84-0.93], p = .001). Consistently, QFR values were lower in group 1 (0.88 [0.82-0.92]) than in group 2 (0.91 [0.85-0.94], p = .001). The proportions of functionally significant coronary lesions as defined by FFR ≤0.80 were 24.1% and 14.2% in groups 1 and 2 (p = .005), and as defined by cQFR ≤0.80 20.4% and 11.8% (p = 0.009), respectively. In ROC analysis for an FFR ≤.80, the AUC was 0.89 (95% CI 0.85-0.93, p < .001) in group 1 and 0.81 (95% CI 0.76-0.86, p < .001) in group 2. CONCLUSIONS These results suggest that QFR measurements are accurate irrespective of the reference vessel diameter. Future studies are needed to elucidate the higher percentage of functionally significant lesions observed in small vessels despite a similar angiographic lesion severity

Oculomotor Nerve Palsy as a Presenting Symptom of Epstein-Barr Virus-Associated Infectious Mononucleosis: Case Report and Review of the Literature

Primary Epstein-Barr virus (EBV) infection is the main cause of infectious mononucleosis (IM), which typically presents with a triad of fever, lymphadenopathy, and tonsillar pharyngitis in young adults. In contrast, neurological manifestations of IM are rare. We report on a 23-year-old man with subacute oculomotor nerve palsy followed by symptoms of IM 6 days later. Primary EBV infection was confirmed by PCR detection of EBV DNA in blood as well as by subsequent serology. High-resolution magnetic resonance imaging revealed an edematous change at the root exit zone and gadolinium enhancement of the right oculomotor nerve as well as pial enhancement adjacent to the right ventral mesencephalon. A review of the literature identified 5 further patients with isolated oculomotor nerve palsy as the presenting symptom of unfolding primary EBV infection. MRIs performed in 3 of those 5 patients revealed a pattern of contrast enhancement similar to that of the present case. This case report and literature review highlight that, although rare, IM should be considered in the differential diagnosis of oculomotor nerve palsy in young adults

Impact of acute kidney injury in elderly (≥80 years) patients undergoing percutaneous coronary intervention

OBJECTIVES This study sought to investigate the prevalence and impact of acute kidney injury (AKI) in elderly patients undergoing percutaneous coronary intervention (PCI). BACKGROUND AKI may complicate PCI and has been associated with worse outcomes. Data on AKI following PCI in elderly patients are scarce. METHODS A total of 458 elderly (≥80 years) patients undergoing PCI at Charité-University Medicine Berlin between January 2009 and December 2014 were stratified according to the presence/absence of AKI. The primary endpoint was all-cause mortality. The secondary endpoint was rate of major adverse cardiovascular events (MACE), a composite of all-cause mortality, non-fatal myocardial infarction, non-fatal stroke, and rehospitalization for heart failure. Median follow-up was 280 (interquartile range 22-1190) days. RESULTS Of the 458 patients, 125 (27.3%) developed AKI following PCI. Age >90 years, congestive heart failure, and C-reactive protein at presentation emerged as independent predictors of AKI. All-cause mortality was 20.0% and 8.4% in patients with and without AKI (P = 0.001), and corresponding rates of MACE were 39.2% and 26.4% (P = 0.01), respectively. The occurrence of AKI was associated with an increased risk of all-cause mortality (adjusted HR 2.41, 95%CI 1.12-5.17, P = 0.02) and MACE (adjusted HR 1.75, 95%CI 1.15-2.67, P = 0.01). CONCLUSIONS AKI occurs in a third of elderly (≥80 years) patients undergoing PCI and is associated with increased mortality. These findings underline the unmet clinical need to identify novel strategies for the prevention of AKI in this high-risk patient subset

Comparison of resting distal to aortic coronary pressure with angiography-based quantitative flow ratio

BACKGROUND Quantitative flow ratio (QFR) is a novel, adenosine-free method for functional coronary lesion interrogation, which is based on 3-dimensional quantitative coronary angiography and computational algorithms. Data on QFR in all-comer patients with intermediate coronary lesions are scarce, and the diagnostic performance in comparison to resting distal to aortic coronary pressure (Pd/Pa) ratio unknown. METHODS A total of 436 patients with 516 vessels undergoing FFR measurements were included in the analysis. Diagnostic performance of QFR, distal to aortic coronary pressure (Pd/Pa) ratio, and anatomic indices versus FFR was assessed. RESULTS FFR ≤0.80 was measured in 19.4% of interrogated vessels. QFR significantly correlated with FFR (r = 0.82, p < 0.001) with good agreement between QFR and FFR (mean difference 0.011, 95% CI 0.008-0.015). The AUC for an FFR ≤0.80 was 0.86 (95% CI 0.83-0.89, p < 0.001) for QFR, 0.76 (0.72-0.80, p < 0.001) for resting Pd/Pa ratio, and 0.63 (0.59-0.67, p < 0.001) for diameter stenosis. The diagnostic accuracy for identifying an FFR ≤0.80 was 93.4% for QFR, 84.3% for resting Pd/Pa ratio, and 80.4% for diameter stenosis. CONCLUSIONS QFR provides a novel diagnostic tool for functional coronary lesion assessment with superior diagnostic accuracy as compared with resting Pd/Pa ratio and anatomic indices. Future studies are needed to determine the non-inferiority of QFR analysis to FFR assessment with respect to clinical outcomes

Association of the body mass index with outcomes in elderly patients (≥80 years) undergoing percutaneous coronary intervention

BACKGROUND The obesity paradox has been recognized in patients with cardiovascular disease. The association between obesity and outcomes in elderly patients undergoing percutaneous coronary intervention (PCI) has not been investigated, yet. METHODS A total of 990 elderly (≥80 years) patients undergoing PCI at our institution between January 2009 and December 2017 and with available data on body mass index (BMI) were divided according to BMI tertiles (lowest BMI tertile: ≪24.1 kg/m$^{2}$, middle BMI tertile: 24.1-27.2 kg/m$^{2}$, and highest BMI tertile: ≫27.2 kg/m$^{2}$). The primary endpoint was all-cause mortality at a median follow-up of 233 [34-862] days. RESULTS All-cause mortality was 11.2%, 7.6%, and 5.8% in the lowest, the middle, and the highest BMI tertiles (Log Rank p = 0.008). Belonging to the lowest BMI tertile was associated with an increased risk of all-cause mortality (HR 2.14, 95% CI 1.23-3.73, p = 0.007), and associations remained significant after multivariable adjustments (adjusted HR 1.92, 95% CI 1.05-3.52, p = 0.03). While belonging to the lowest BMI tertile was independently associated with an increased all-cause mortality in patients with acute coronary syndromes (HR 2.32, 95% CI 1.24-4.35, p = 0.009; adjusted HR 2.40, 95% CI 1.19-4.84, p = 0.01), relations were not significant in patients with stable coronary artery disease (HR 1.32, 95% CI 0.38-4.56, p = 0.67; adjusted HR 0.80, 95% CI 0.21-3.05, p = 0.75). CONCLUSIONS In elderly (≥80 years) patients undergoing PCI, belonging to the lowest BMI tertile was associated with an increased mortality, mainly in acute coronary syndromes. Hence, the BMI should be incorporated into the risk stratification of elderly patients with coronary artery disease

Association of left ventricular end-diastolic pressure with mortality in patients undergoing percutaneous coronary intervention for acute coronary syndromes

OBJECTIVES This study sought to investigate the relation between left ventricular end-diastolic pressure (LVEDP) and outcomes in patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndromes (ACS). BACKGROUND Risk stratification in ACS patients is important. Data on the role of LVEDP in the prognostication of ACS patients are scarce. METHODS A total of 1,410 patients undergoing PCI for ACS and with available data on LVEDP were divided according to LVEDP tertiles (lowest tertile: ≤13 mmHg, intermediate tertile: 14-20 mmHg, and highest tertile: >20 mmHg). The primary endpoint was all-cause mortality at a median follow-up of 246 [28-848] days. RESULTS Median LVEDP was 16 (11-22) mmHg. All-cause mortality was 2.8%, 4.5%, and 15.0% in the lowest, the intermediate, and the highest LVEDP tertile groups (p < .001), respectively. Belonging to the highest LVEDP tertile was associated with an increased risk of all-cause mortality (adjusted hazard ratio [HR] = 2.66, 95% confidence interval [CI] [1.30, 5.47], p = .008). By receiver operating characteristic curve analysis, the optimal cut-off value for predicting all-cause mortality was 20 mmHg (sensitivity 68.3%, specificity 72.5%). There was no differential effect of LVEDP on mortality in patients with and without LV dysfunction (interaction p = .23) or ST-elevation myocardial infarction as index ACS event (interaction p = .86). CONCLUSIONS In patients undergoing PCI for ACS, LVEDP was independently related with mortality. Hence, LVEDP should be incorporated into early risk stratification and clinical decision making of ACS patients