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Quantitative flow ratio (QFR) is a computation of fractional flow reserve (FFR) based on invasive coronary angiographic images. Calculating QFR is less invasive than measuring FFR and may be associated with lower costs. Current evidence supports the call for an adequately powered randomised comparison of QFR and FFR for the evaluation of intermediate coronary stenosis. The aim of the FAVOR III Europe Japan trial is to investigate if a QFR-based diagnostic strategy yields a non-inferior 12-month clinical outcome compared with a standard FFR-guided strategy in the evaluation of patients with intermediary coronary stenosis. FAVOR III Europe Japan is an investigator-initiated, randomised, clinical outcome, non-inferiority trial scheduled to randomise 2,000 patients with either 1) stable angina pectoris and intermediate coronary stenosis, or 2) indications for functional assessment of at least 1 non-culprit lesion after acute myocardial infarction. Up to 40 international centres will randomise patients to either a QFR-based or a standard FFR-based diagnostic strategy. The primary endpoint of major adverse cardiovascular events is a composite of all-cause mortality, any myocardial infarction, and any unplanned coronary revascularisation at 12 months. QFR could emerge as an adenosine- and wire-free alternative to FFR, making the functional evaluation of intermediary coronary stenosis less invasive and more cost-effective.

Zusammenfassung. Die koronare Mikrozirkulationsstörung weist insbesondere bei Frauen ab dem fünfzigsten Lebensjahr eine hohe Prävalenz auf und führt sowohl zu pektanginösen Symptomen wie auch zu einer erhöhten Rate kardiovaskulärer Ereignisse. Durch die auch heutzutage noch bestehende Unterdiagnostizierung haben viele Patientinnen und Patienten einen langen Leidensweg hinter sich. Mit einer invasiven Koronarangiografie, die sowohl eine Messung der koronaren Flussreserve wie auch eine Acetylcholin-Provokationstestung beinhaltet, kann die Diagnose einer koronaren Mikrozirkulationsstörung gestellt werden. Dies ist einerseits für das Wohl der Patientinnen und Patienten wichtig, ermöglicht andererseits aber auch eine gezielte Therapie. Diese besteht aus Lebensstilveränderungen, einer optimalen Kontrolle kardiovaskulärer Risikofaktoren sowie spezifischen anti-anginösen Medikamenten. Die aktuelle Forschung versucht, pathophysiologische Mechanismen besser zu verstehen und verbesserte oder alternative diagnostische Verfahren und neue Therapiekonzepte zu entwickeln.

The aim of this study was to determine the role of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in the prognostication of patients ≥80 years of age undergoing percutaneous coronary intervention (PCI).Elderly patients with coronary artery disease in need of PCI represent a growing patient population. Advanced risk prediction in this frail and comorbid patient population is important.A total of 460 consecutive patients ≥80 years of age undergoing PCI for acute (ACS) or chronic coronary syndromes (CCS) at the University Hospital Zurich, Switzerland, between January 2016 and December 2018 and with available baseline NT-proBNP levels were included in the analysis. Patients were stratified according to baseline NT-proBNP levels. The primary endpoint was all-cause mortality at a median follow-up of 33 (interquartile range: 3-392) days.Median baseline NT-proBNP levels were 1411 (457-3984) ng/L. All-cause mortality was 7.8% in the lowest and 27.8% in the highest NT-proBNP quartile group (p 0.001). In patients with ACS, all-cause mortality was 4.8% and 30.4% in the lowest and the highest NT-proBNP quartile (p 0.001), and corresponding rates in patients with CCS were 11.1% and 22.2% (p = 0.38). In multivariable Cox regression analysis, baseline NT-proBNP levels were independently associated with an increased risk of all-cause mortality (adjusted hazard ratio: 1.00, 95% confidence interval: 1.00-1.00, p = 0.04).Baseline NT-proBNP levels were identified as independent predictor of mortality in elderly (≥80 years) patients undergoing PCI. Hence, baseline NT-proBNP allows for the identification of a high-risk elderly patient subset.

(1) Background: High-level evidence on antithrombotic therapy after infrainguinal arterial bypass surgery in specific clinical scenarios is lacking. (2) Methods: A modified Delphi procedure was used to develop consensus statements. Experts voted on antithrombotic treatment regimens for three types of infrainguinal arterial bypass procedures: above-the-knee popliteal artery; below-the-knee popliteal artery; and distal, using vein, prosthetic, or biological grafts. The treatment regimens for these nine procedures were then voted on in three clinical scenarios: isolated PAOD, atrial fibrillation, and recent coronary intervention. (3) Results: The survey was conducted with 28 experts from 15 European countries, resulting in consensus statements on 25/27 scenarios. Experts recommended single antiplatelet therapy after above-the-knee popliteal artery bypasses regardless of the graft material used. For below-the-knee popliteal artery bypasses, experts suggested combining single antiplatelet therapy with low-dose rivaroxaban if the graft material used was autologous or biological. They did not recommend switching to triple therapy for patients on oral anticoagulants for atrial fibrillation or dual antiplatelet therapy in any scenario. (4) Conclusions: Great inconsistency in the antithrombotic therapy administered was found in this study. This consensus offers guidance for scenarios that are not covered in the current ESVS guidelines but must be interpreted within its limitations.

Randomized trials suggest benefits for fractional flow reserve (FFR)-guided vs. angiography-guided treatment strategies in well-defined and selected patient cohorts with acute coronary syndromes (ACS). The long-term prognostic value of FFR measurement in unselected all-comer ACS patients, however, remains unknown. This subanalysis of the Fractional FLOw Reserve In cardiovascular DiseAses (FLORIDA) study sought to investigate the long-term effects of FFR in the management of lesions in patients with acute coronary syndrome (ACS). FLORIDA was an observational all-comer cohort study performed in Germany, that was population-based and unselected. Patients enrolled into the anonymized InGef Research Database presenting with ACS and undergoing coronary angiography between January 2014 and December 2015 were included in the analysis. Patients were stratified into either the FFR-guided or the angiography-guided treatment arm, based on the treatment received. A matched cohort study design was used. The primary endpoint was all-cause mortality. The secondary endpoint was major adverse cardiovascular events (MACE), a composite of death, non-fatal myocardial infarction (MI), and repeat revascularization. Follow-up time was 3 years. Rates of 3-year mortality were 10.2 and 14.0% in the FFR-guided and the angiography-guided treatment arms (p = 0.04), corresponding to a 27% relative risk reduction for FFR in ACS patients. Rates of MACE were similar in both arms (47.7 vs. 51.5%, p = 0.14), including similar rates of non-fatal MI (27.7 vs. 25.4%, p = 0.47) and revascularization (9.9 vs. 12.1%, p = 0.17). In this large, all-comer observational study of ACS patients, FFR-guided revascularization was associated with a lower mortality at 3 years. This finding encourages the routine use of FFR to guide lesion revascularization in patients presenting with ACS.

Angina Pectoris and the Importance of Coronary Microcirculation in Practice

Cardiovascular diseases (CVD) remain the leading cause of mortality worldwide. Although major diagnostic and therapeutic advances have significantly improved the prognosis of patients with CVD in the past decades, these advances have less benefited women than age-matched men. Noninvasive cardiac imaging plays a key role in the diagnosis of CVD. Despite shared imaging features and strategies between both sexes, there are critical sex disparities that warrant careful consideration, related to the selection of the most suited imaging techniques, to technical limitations, and to specific diseases that are overrepresented in the female population. Taking these sex disparities into consideration holds promise to improve management and alleviate the burden of CVD in women. In this review, we summarize the specific features of cardiac imaging in four of the most common presentations of CVD in the female population including coronary artery disease, heart failure, pregnancy complications, and heart disease in oncology, thereby highlighting contemporary strengths and limitations. We further propose diagnostic algorithms tailored to women that might help in selecting the most appropriate imaging modality.

Background Current risk models show limited performances for predicting all-cause mortality after transcatheter aortic valve replacement (TAVR). Purpose To determine the prognostic value of coronary artery calcium (CAC) scoring for predicting 30-day and 1-year mortality in patients undergoing TAVR. Materials and Methods In this single-center institutional review board-approved secondary analysis of prospectively collected data (SwissTAVI Registry), the authors evaluated participants who, before TAVR, underwent CT that included a nonenhanced electrocardiography-gated cardiac scan between May 2008 and September 2019 and who had not undergone previous coronary revascularization. Clinical data, including the European System for Cardiac Operative Risk Evaluation (EuroSCORE II), were recorded. The CAC score was determined, and 30-day and 1-year all-cause mortality were assessed by using Cox regression analyses. Results In total, 309 participants (mean age ± standard deviation, 81 years ± 7; 175 women) were included, with a median CAC score of 334 (interquartile range, 104-987). Seventy-seven of the 309 participants (25%) had a CAC score greater than or equal to 1000. A CAC score of 1000 or greater served as an independent predictor of 30-day (hazard ratio [HR], 4.5 [95% CI: 1.5, 13.6] compared with a CAC score

Aims Rupture of the fibrous cap (RFC) represents the main pathophysiological mechanism causing acute coronary syndromes (ACS). Destabilization due to plaque biomechanics is considered to be importantly involved, exact mechanisms triggering plaque ruptures are, however, unknown. This study aims at characterizing the relation between plaque components and rupture points at ACS-causing culprit lesions in a large cohort of ACS-patients assessed by high-resolution intracoronary imaging. Methods and results Within the prospective, multicentric OPTICO-ACS study program, the ACS-causing culprit plaques of 282 consecutive patients were investigated following a standardized optical coherence tomography (OCT) imaging protocol. Each pullback was assessed on a frame-by-frame basis for the presence of lipid components (LC), calcium components (CC), and coexistence of both LC and CC (LCC) by two independent OCT-core labs. Of the 282 ACS-patients, 204 patients (72.3%) presented with ACS caused by culprit lesions with rupture of the fibrous cap (RFC-ACS) and 27.7% patients had ACS caused by culprit lesions with intact fibrous cap (IFC-ACS). When comparing RFC-ACS to IFC-ACS, a preferential occurrence of all three plaque components (LC, CC, and LCC) in RFC-ACS became apparent (P Conclusions Calcified- and lipid-containing components characterize ruptured fibrous cap ACS-causing culprit lesions. Their coexistence is accelerated directly at the ruptured point, suggesting a pathophysiological contribution in the development of RFC-ACS.

Early inflammation following acute ST-segment elevation myocardial infarction (STEMI) treated by primary percutaneous coronary intervention (PCI) affects myocardial infarct (MI) size and left ventricular remodeling. The mammalian target of rapamycin (mTOR) is involved in the enhanced inflammatory response and its inhibition has exerted beneficial effects on MI size in preclinical models of acute MI.The CLEVER-ACS (Controlled Level Everolimus in Acute Coronary Syndromes) trial evaluated the effects of targeting inflammation by mTOR inhibition in patients with STEMI undergoing PCI.CLEVER-ACS was a randomized, multicenter, international, double-blind, placebo-controlled trial. A total of 150 patients with STEMI undergoing PCI were randomly assigned to oral everolimus (days 1-3: 7.5 mg daily; days 4-5: 5.0 mg daily) or placebo for 5 days. The primary endpoint was the change in MI size. The secondary endpoint was the change in microvascular obstruction (MVO) from baseline (12 hours to 5 days after PCI) to 30 days as assessed by cardiac magnetic resonance imaging.The changes in MI size from baseline to 30 days, the primary endpoint, were -14.2 g (95% CI: -17.4 to -11.1 g) and -12.3 g (95% CI: -16.0 to -8.7 g) in the everolimus and placebo groups (P = 0.99). Corresponding changes in MVO were -4.8 g (95% CI: -6.7 to -2.9 g) and -6.3 g (95% CI: -8.7 to -4.0 g) in the everolimus and placebo groups (P = 0.14). Adverse events did not differ between the study groups.Among STEMI patients undergoing PCI, early mTOR inhibition with everolimus did not reduce MI size or MVO at 30 days. (CLEVER-ACS [Controlled Level Everolimus in Acute Coronary Syndromes; NCT01529554).

Coronary artery disease and severe aortic stenosis (AS) often coexist. This study sought to investigate the impact of normal coronary arteries as negative risk marker in patients undergoing transcatheter aortic valve implantation (TAVI). Consecutive patients with severe AS undergoing TAVI were dichotomized according to the presence or absence of normal coronary arteries, defined as absence of coronary lesions with diameter stenosis ≥30% in vessels ≥1.5 mm in diameter on coronary angiogram in patients without prior coronary revascularization. The primary end point was 1-year mortality. Out of 987 patients with severe AS undergoing TAVI, 258 (26%) patients had normal coronary arteries. These patients were younger, more likely women, and had lower EuroSCORE II and STS risk scores. Although mortality at 30 days was similar in the normal coronary artery and the coronary atherosclerosis groups (3.1% vs 5.6%, p = 0.11), it was lower in those with normal coronary arteries at 1 year (8.9% vs 17%, p = 0.003). In multivariable analysis, the presence of normal coronary arteries on coronary angiogram independently predicted 1-year mortality (adjusted HR 0.57, 95% CI 0.37 to 0.90, p = 0.02). In conclusion, this study defined normal coronary arteries as negative risk marker in patients with severe AS undergoing TAVI.

BACKGROUND Activation of inflammatory pathways during acute myocardial infarction contributes to infarct size and left ventricular (LV) remodeling. The present prospective randomized clinical trial was designed to test the efficacy and safety of broad-spectrum anti-inflammatory therapy with a mammalian target of rapamycin (mTOR) inhibitor to reduce infarct size. DESIGN Controlled-Level EVERolimus in Acute Coronary Syndrome (CLEVER-ACS, clinicaltrials.gov NCT01529554) is a phase II randomized, double-blind, multi-center, placebo-controlled trial on the effects of a 5-day course of oral everolimus on infarct size, LV remodeling, and inflammation in patients with acute ST-elevation myocardial infarction (STEMI). Within 5 days of successful primary percutaneous coronary intervention (pPCI), patients are randomly assigned to everolimus (first 3 days: 7.5 mg qd; days 4 and 5: 5.0 mg qd) or placebo, respectively. The primary efficacy outcome is the change from baseline (defined as 12 h to 5 days after pPCI) to 30-day follow-up in myocardial infarct size as measured by cardiac magnetic resonance imaging (CMRI). Secondary endpoints comprise corresponding changes in cardiac and inflammatory biomarkers as well as microvascular obstruction and LV volumes assessed by CMRI. Clinical events, laboratory parameters, and blood cell counts are reported as safety endpoints at 30 days. CONCLUSION The CLEVER-ACS trial tests the hypothesis whether mTOR inhibition using everolimus at the time of an acute STEMI affects LV infarct size following successful pPCI.

Personalized Therapeutic Concepts in Chronic Coronary Syndromes

Zusammenfassung. Das chronische Koronarsyndrom stellt eine der häufigsten Erkrankungen dar. Die durch das chronische Koronarsyndrom bedingte myokardiale Ischämie kann sowohl durch morphologische wie auch funktionelle Veränderungen der Herzkranzgefässe bedingt sein, wobei Veränderungen das epikardiale Koronarsystem oder die koronare Mikrozirkulation betreffen können. Zur Abklärung von Personen mit Verdacht auf ein chronisches Koronarsyndrom werden nicht-invasive und invasive diagnostische Verfahren eingesetzt. Lebensstilveränderungen, optimale medikamentöse Therapie und die koronare Revaskularisation stellen die Hauptpfeiler in der Behandlung von Patientinnen und Patienten mit chronischem Koronarsyndrom dar. Der vorliegende Übersichtsartikel fasst die unterschiedlichen Formen des chronischen Koronarsyndroms zusammen und diskutiert Diagnostik und Therapie von Menschen mit chronischem Koronarsyndrom. Insbesondere wird der Stellenwert der perkutanen koronaren Revaskularisation in der Behandlung des chronischen Koronarsyndroms erörtert.

AIMS Interventional cardiologists are exposed to substantial occupational ionising radiation. This study sought to investigate differences in radiation exposure in biplane versus monoplane coronary angiography and percutaneous coronary interventions (PCI). METHODS AND RESULTS RAMBO (RAdiation exposure in Monoplane versus Biplane cOronary angiography and interventions) was a prospective, randomised, two-arm, single-centre, open-label trial, enrolling a total of 430 patients undergoing coronary angiography. Patients were randomly assigned to biplane or monoplane imaging. The primary efficacy measure, the operator radiation dose at the level of the left arm as measured by a wearable electronic dosimeter, was significantly higher in the biplane as compared to the monoplane group (4 [1-13] µSv vs 2 [0-6.8] µSv, p

Aims Longitudinal geographic mismatch (LGM) as well as edge dissections are associated with an increased risk of adverse events after percutaneous coronary intervention (PCI). Recently, a novel system of real-time optical coherence tomography (OCT) with angiographic co-registration (ACR) became available and allows matched integration of cross-sectional OCT images to angiography. The OPTICO-integration II trial sought to assess the impact of ACR for PCI planning on the risk of LGM and edge dissections. Methods A total of 84 patients were prospectively randomized to ACR-guided PCI, OCT-guided PCI (without co-registration), and angiography-guided PCI. Primary endpoint was a composite of major edge dissection and/or LGM as assessed by post-PCI OCT. Results The primary endpoint was significantly reduced in ACR-guided PCI (4.2%) as compared to OCT-guided PCI (19.1%; p = 0.03) and angiography-guided PCI (25.5%; p p = 0.04; ACR vs. angiography p = 0.04). The number of major edge dissections was low and without significant differences among the study groups (0% vs. 2.1% vs. 4.3%). Conclusion This study for the first time demonstrates superiority of ACR-guided PCI over OCT- and angiography-guided PCI in reducing the composite endpoint of major edge dissection and LGM, which was meanly driven by a reduction of LGM. Graphical abstract

Background Quantitative flow ratio (QFR) is a novel, adenosine-free method for functional lesion interrogation based on 3-dimensional quantitative coronary angiography and computational algorithms. We sought to investigate the diagnostic performance of QFR versus myocardial perfusion imaging positron emission tomography (MPI-PET), which yields the highest accuracy for detection of myocardial ischemia. Methods Diagnostic performance of QFR versus MPI-PET was assessed in consecutive patients undergoing both clinically indicated coronary angiography and 13N-ammonia MPI-PET within a six-month period. Results Out of 176 patients (439 coronary arteries), 19.3% were women. Percent area stenosis was 45 [32–58] %. Myocardial ischemia on 13N-ammonia MPI-PET was detected in 106 (24.1%) vessel territories and hemodynamic significance defined as contrast-flow vessel QFR ≤ 0.80 was observed in 83 (18.9%) vessels. Diagnostic accuracy, sensitivity, and specificity of contrast-flow vessel QFR for the prediction of myocardial ischemia on 13N-ammonia MPI-PET were 92.5 (95% CI 89.6–94.7) %, 73.6 (95% CI 64.1–81.7) %, and 98.5 (95% CI 96.5–99.5) %, respectively. The AUCs for contrast-flow vessel QFR, percent diameter stenosis, and percent area stenosis were 0.85 (95% CI 0.81–0.88, p Conclusions QFR, a novel diagnostic tool for functional coronary lesion assessment, provides good diagnostic agreement with MPI-PET and superior diagnostic accuracy for the detection of myocardial ischemia as compared to anatomic indices. Future studies will have to determine the non-inferiority of QFR to fractional flow reserve with respect to clinical outcomes.

Aims To assess whether the combination of transthoracic echocardiography (TTE) and multidetector computed tomography (MDCT) data affects the grading of aortic stenosis (AS) severity under consideration of the energy loss index (ELI) in patients undergoing transcatheter aortic valve replacement (TAVR). Methods and results Multimodality imaging was performed in 197 patients with symptomatic severe AS undergoing TAVR at the University Hospital Zurich, Switzerland. Fusion aortic valve area index (fusion AVAi) assessed by integrating MDCT derived planimetric left ventricular outflow tract area into the continuity equation was significantly larger as compared to conventional AVAi (0.41 ± 0.1 vs. 0.51 ± 0.1 cm2/m2; P 0.6 cm2/m2. ELI was obtained for conventional AVAi and fusion AVAi based on sinotubular junction area determined by TTE (ELILTL 0.47 ± 0.1 cm2/m2; fusion ELILTL 0.60 ± 0.1 cm2/m2) and MDCT (ELIMDCT 0.48 ± 0.1 cm2/m2; fusion ELIMDCT 0.61 ± 0.05 cm2/m2). When ELI was calculated with fusion AVAi the effective orifice area was >0.6 cm2/m2 in 85 patients (43.1%). Survival rate 3 years after TAVR was higher in patients reclassified to moderate AS according to multimodality imaging derived ELI (78.8% vs. 67%; P = 0.01). Conclusion Multimodality imaging derived ELI reclassifies AS severity in 43% undergoing TAVR and predicts mid-term outcome.

ObjectiveLeft ventricular (LV) twist is a major component of ventricular mechanics reflecting the helical orientation of cardiac fibres and compensating for afterload mismatch. However, it is not known whether it determines outcome after transcatheter aortic valve implantation (TAVI). This study sought to investigate TAVI-induced short-term changes of LV twist and to define its role in outcome prediction.MethodsA total of 146 patients (median age 81.78 years, 50.7% male) undergoing TAVI for severe aortic stenosis were included. LV rotation and twist were determined by speckle tracking echocardiography within 3 months before and 2 weeks after TAVI. All-cause mortality at 2 years was defined as primary end point.ResultsPatients who survived exhibited a higher apical peak systolic rotation (APSR) (pConclusionAPSR, twist and torsion pre-TAVI as well as their change within 2 weeks after TAVI predict 2-year all-cause mortality after TAVI, adding incremental prognostic value to LVEF and GLS.

The present sub-analysis from the randomized UDDC-Radial-Trial sought to compare one-catheter concepts (OCC) with two-catheter concepts (TCC) in different patient subgroups, particularly in those depending on gender and age.There is an ongoing debate regarding potential performance differences of OCC compared to TCC for transradial coronary angiography in specific patient subgroups.The randomized UDDC-Radial-Trial enrolled a total of 300 patients planed for coronary angiography in a 2:1 ratio to either OCC by Tiger II (n = 100) and BLK (n = 100) or TCC by Judkins (n = 100) catheters. Predefined patient subgroups stratified for age, gender and patient constitution were analyzed with regard to the primary outcome measure of time required for a complete coronary angiography.In male patients time for coronary angiography was significantly shorter in the TCC group compared to the OCC group (510 ± 37 s vs. 615 ± 35 s; p = 0.046). No difference between the catheter concepts was observed in the subset of female patients (525 ± 34 s vs. 583 ± 54 s; p = 0.43). TCC was associated with shorter coronary angiography time in patients aged71 years compared to OCC (462 ± 23 s vs. 570 ± 38 s; p = 0.018). In patients ≥72 years of age no difference was detected (573 ± 41 s vs. 636 ± 45 s; p = 0.31). Other subgroups showed no relevant differences in angiography time among OCC and TCC.The present subgroup analysis from the UDDC-radial trial demonstrates the use of OCC in transradial diagnostic angiography to be inferior compared to TCC in terms of angiography time in younger and male patients.

Background This study sought to investigate the role of postprocedural troponin elevations in mortality prediction after transcatheter aortic valve implantation and to define the threshold at which clinically relevant postprocedure myocardial injury determines mortality. Methods and Results A total of 1333 consecutive patients with transcatheter aortic valve implantation with available postprocedural high‐sensitivity cardiac troponin T measurements were included in the analysis. The threshold at which postprocedure myocardial injury determines long‐term mortality was identified using restricted cubic spline analysis. A >18.3‐fold increase of troponin above the upper reference limit was identified as threshold for relevant postprocedure myocardial injury. Associations remained significant in a landmark analysis between 30 days and 2 years (hazard ratio [HR], 1.61, [95% CI, 1.13–2.28]; P =0.01), after adjusting for known confounders (adjusted HR, 1.90 [95% CI, 1.40–2.57]; P P P P =0.003). Conclusions This study determined a troponin threshold for the identification of patients at increased mortality risk after transcatheter aortic valve implantation. The proposed definition of postprocedure myocardial injury advances risk stratification in patients with transcatheter aortic valve implantation and may assist in postprocedural patient management.

Background: Quantitative flow ratio (QFR) has been introduced as a novel angiography-based modality for fast hemodynamic assessment of coronary artery lesions and validated against fractional flow reserve. This study sought to define the prognostic role of pancoronary QFR assessment in patients with acute coronary syndrome (ACS) including postinterventional culprit and nonculprit vessels. Methods: In a total of 792 patients with ACS (48.6% ST-segment–elevation ACS and 51.4% non–ST-segment–elevation ACS), QFR analyses of postinterventional culprit (n=792 vessels) and nonculprit vessels (n=1231 vessels) were post hoc performed by investigators blinded to clinical outcomes. The follow-up comprised of major adverse cardiovascular events, including all-cause mortality, nonfatal myocardial infarction, and ischemia-driven coronary revascularization within 2 years after the index ACS event. Results: Major adverse cardiovascular events as composite end point occurred in 99 patients (12.5%). QFR with an optimal cutoff value of 0.89 for postinterventional culprit vessels and 0.85 for nonculprit vessels emerged as independent predictor of major adverse cardiovascular events after ACS (nonculprit arteries: adjusted odds ratio, 3.78 [95% CI, 2.21–6.45], P P Conclusions: The present study for the first time demonstrates the prognostic implications of a pancoronary angiography-based functional lesion assessment in patients with ACS. Hence, QFR offers a novel tool to advance risk stratification and guide therapeutic management after ACS.

Purpose 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 PC. Methods 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. Results 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. Conclusions The present study for the first time confirmed the feasibility and diagnostic accuracy of non-culprit coronary artery QFR during primary PCI. 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.

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

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/m2, middle BMI tertile: 24.1–27.2 kg/m2, and highest BMI tertile: ≫27.2 kg/m2). 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.

Data on the prevalence of infections in patients who underwent percutaneous coronary intervention (PCI) and their impact on outcomes are scarce. In this study, a total of 644 patients ≥80 years of age who underwent PCI were stratified according to the presence/absence of infections requiring antibiotic therapy. The primary end point was major adverse cardiovascular events (MACE) after discharge, a composite of all-cause mortality, nonfatal myocardial infarction, and rehospitalization for heart failure. Median follow-up was 1.2 (interquartile range 0.1 to 3.4) years. Of the 644 patients, 186 (28.9%) had infections during index hospitalization, with 84 (13%) and 59 (9.2%) patients having pneumonia and urinary tract infections, respectively. Patients with infections were older, more often women, and had an increased prevalence of atrial fibrillation and congestive heart failure. Infections prolonged hospital stay (10 [7 to 16] vs 5 [3 to 7] days, p0.001), but were not related to rates of MACE (20% vs 19%, adjusted hazard ratio [HR] 1.41, 95% confidence intervals 0.84 to 2.38, p = 0.20). Pneumonia was significantly associated with increased rates of MACE (27% vs 18%, adjusted HR 2.19, 95% confidence intervals 1.23 to 3.91, p = 0.008) and rehospitalization for heart failure (17% vs 10%, adjusted HR 2.66 (1.25 to 5.63, p = 0.01), whereas urinary tract infections were not. In conclusion, concomitant infections are frequent in patients ≥80 years of age who underwent PCI, and associated with an increased risk of adverse events when affecting the respiratory system.

Objectives The authors investigated the development of pulmonary hypertension (PH), predictors of PH regression, and its prognostic impact on short, mid-, and long-term outcomes in patients undergoing transcatheter aortic valve replacement (TAVR) for severe aortic stenosis (AS). Background PH represents a common finding in patients with AS. Although TAVR is frequently associated with regression of PH, the predictors of reversible PH and its prognostic significance remain uncertain. Methods In this study, 617 consecutive patients undergoing TAVR between 2009 and 2015 were stratified per baseline tertiles of pulmonary artery systolic pressure (PASP) as follows: normal (PASP Results In patients with both mild-to-moderate and severe PH at baseline, PASP decreased significantly at discharge (ΔPASP 3.0 ± 9.3 mm Hg and 12.0 ± 10.0 mm Hg, respectively) and 1 year (ΔPASP 5.0 ± 9.7 mm Hg and 18.0 ± 14.0 mm Hg, respectively). At a median follow-up of 370 days (interquartile range [IQR]: 84 to 500 days), the risk of all-cause mortality was similar among baseline PASP groups at all time intervals evaluated. After TAVR, a significant regression of PH was observed in 46% of patients. Contrarily, patients with residual PH had a higher risk of all-cause mortality at 30 days (hazard ratio [HR]: 3.49, 95% confidence interval [CI]: 1.74 to 6.99; p 40% (odds ratio [OR]: 3.56, 95% CI: 2.24 to 5.65; p Conclusions In most patients with PH and AS, TAVR is associated with a significant early and late reduction of PASP. Patients with reversible PH after TAVR are at lower risk of all-cause mortality at early, mid-, and long-term follow-up. Therefore, the presence of PH should not preclude treatment with TAVR.

Patients suffering from cardiogenic shock (CS) have a high mortality and morbidity. The Impella percutaneous left-ventricular assist device (LVAD) decreases LV preload, increases cardiac output, and improves coronary blood flow. We aimed to review and meta-analyze available data comparing Impella versus intra-aortic pump (IABP) counterpulsation or medical treatment in CS due to acute myocardial infarction or post-cardiac arrest. Study-level data were analyzed. Heterogeneity was assessed using the I2 statistic. Risk rates were calculated and obtained using a random-effects model (DerSimonian and Laird). Four studies were found suitable for the final analysis, including 588 patients. Primary endpoint was short-term mortality (in-hospital or 30-day mortality). In a meta-analysis of four studies comparing Impella versus control, Impella was not associated with improved short-term mortality (in-hospital or 30-day mortality; RR 0.84; 95% CI 0.57–1.24; p = 0.38; I2 55%). Stroke risk was not increased (RR 1.00; 95% CI 0.36–2.81; p = 1.00; I22 0%), but risk for major bleeding (RR 3.11 95% CI 1.50–6.44; p = 0.002; I2 0%) and peripheral ischemia complications (RR 2.58; 95% CI 1.24–5.34; p = 0.01; I2 0%) were increased in the Impella group. In patients suffering from severe CS due to AMI, the use of Impella is not associated with improved short-time survival but with higher complications rates compared to IABP and medical treatment. Better patient selection avoiding Impella implantation in futile situations or in possible lower risk CS might be necessary to elucidate possible advantages of Impella in future studies.

The Role of Percutaneous Coronary Revascularization in Chronic Coronary Syndromes

BACKGROUND AND AIMS Residual inflammatory risk (RIR) after acute coronary syndromes (ACS) may identify patients likely to benefit from anti-inflammatory therapies. METHODS Patients from the Special Program University Medicine ACS cohort were divided into four groups according to level of hsCRP at baseline and after 12 months: persistently high RIR, increased RIR (first low, then high hsCRP), attenuated RIR (first high, then low hsCRP), or persistently low RIR. High RIR was defined as hsCRP ≥ 2 mg/L. An independently adjudicated incident of combined adverse events was defined as the composite of myocardial infarction, clinically indicated coronary revascularization or cerebrovascular events. RESULTS Among 1209 patients with available hsCRP, clinical and demographic data, 295 (24.4%) patients had persistently high RIR (delta hsCRP median (IQR): 2.3 (-9.9; 0.3) (mg/L) and 72 (5.96%) patients had increased RIR (delta hsCRP median (IQR): +2.45 (1.2; 8.35) (mg/L). A total of 390 (32.26%) patients had attenuated RIR (delta hsCRP median (IQR): 3.55 (-10; -2) (mg/L) and 452 (37.38%) patients had persistently low RIR (delta hsCRP median (IQR): 0.2 (-0.6; 0.1) (mg/L). Of 90 combined adverse events, 31 (10.5%) occurred in the persistently high (multivariable adjusted OR: 1.71, (95% CI 1.08-2.7), p = 0.022) compared with the three other groups combined (increased RIR: 3 (4.2%), attenuated RIR 30 (7.7%), persistently low RIR 26 (5.8%). CONCLUSIONS Persistently elevated hsCRP after ACS is found in a quarter of patients with the highest risk of combined adverse events. This underlines the need to perform anti-inflammatory intervention trials in RIR patients.

Background Patients with signs and symptoms suggestive of myocardial infarction and non-obstructive coronary arteries are at increased risk of adverse events. The aim of this study was to investigate the predictive role of renal function in troponin-positive patients with non-obstructive coronary arteries. Methods A total of 564 troponin-positive patients with non-obstructive coronary arteries at coronary angiography and available baseline creatinine levels were stratified according to baseline renal function (normal/stage 1: estimated glomerular filtration rate [eGFR] >90 ml/min/1.73m2, stage 2: 60 to 89 ml/min/1.73m2, stage 3: 30 to 59 ml/min/1.73m2, and stage 4: Results A total of 73 (12.9%), 195 (34.6%), 231 (41.0%), and 65 (11.5%) patients were in the normal/stage 1, stage 2, stage 3, and stage 4 renal dysfunction groups. With progressive renal impairment, patients were older, more frequently presented with established coronary or peripheral artery disease, and had an increased prevalence of cardiovascular risk factors. Cumulative mortality increased with progressive renal dysfunction (normal/stage 1: 0.0%, stage 2: 3.6%, stage 3: 12.1%, and stage 4: 32.3%, log rank p Conclusions Renal impairment was associated with mortality in patients presenting with elevated cardiac troponin and non-obstructive coronary arteries. Hence, renal function should be incorporated into the risk stratification of these patients.

Background: \ud About half of patients with acute ST-segment elevation myocardial infarction (STEMI) present with multivessel coronary artery disease (MVD). Recent evidence supports complete revascularization in these patients. However, optimal timing of non-culprit lesion revascularization in STEMI patients is unknown because dedicated randomized trials on this topic are lacking.\ud \ud Study design: \ud The MULTISTARS AMI trial is a prospective, international, multicenter, randomized, two-arm, open-label study planning to enroll at least 840 patients. It is designed to investigate whether immediate complete revascularization is non-inferior to staged (within 19-45 days) complete revascularization in patients in stable hemodynamic conditions presenting with STEMI and MVD and undergoing primary percutaneous coronary intervention (PCI). After successful primary PCI of the culprit artery, patients are randomized in a 1:1 ratio to immediate or staged complete revascularization. The primary endpoint is a composite of all-cause death, non-fatal myocardial infarction, ischemia-driven revascularization, hospitalization for heart failure, and stroke at 1 year.\ud \ud Conclusions: \ud The MULTISTARS AMI trial tests the hypothesis that immediate complete revascularization is non-inferior to staged complete revascularization in stable patients with STEMI and MVD.