Soluble urokinase plasminogen activator receptor and functionally relevant coronary artery disease: a prospective cohort study.

BACKGROUND: Soluble urokinase plasminogen activator receptor (suPAR) is an emerging biomarker associated with anatomical CAD burden and cardiovascular outcomes including myocardial infarction (MI) and death. We aimed to validate previous findings of the prognostic value of suPAR and to evaluate its diagnostic potential for functional relevant CAD (fCAD). METHODS: Consecutive patients with suspected fCAD were enrolled. Adjudication of fCAD was performed blinded to suPAR concentrations by myocardial perfusion single-photon emission tomography (MPI-SPECT) and coronary angiography. Prognostic outcome measures included all-cause death, cardiovascular death, and incident MI during 2-year follow-up. RESULTS: Among consecutive 968 patients, suPAR concentrations were higher in patients with fCAD compared to those without (3.45 vs. 3.20 ng/mL, p = 0.007), but did not provide acceptable diagnostic accuracy (area under the curve [AUC]: 0.56, 95%CI 0.52-0.60). SuPAR correlated with high-sensitivity cardiac-troponin T (Spearman's rho (ρ) 0.393, p < 0.001), NT-proBNP (ρ = 0.327, p < 0.001), age (ρ = 0.364, p < 0.001) and very weakly with coronary atherosclerosis (ρ = 0.123, p < 0.001). Prognostic discrimination of suPAR was moderate for cardiovascular death (AUC = 0.72, 95%CI 0.62-0.81) and all-cause death (AUC = 0.72, 95%CI 0.65-0.79) at 2-years. SuPAR remained a significant predictor for all-cause death in multivariable Cox regression (HR = 1.96, p = 0.001). CONCLUSIONS: SuPAR was an independent predictor of all-cause death, without diagnostic utility for fCAD. CLINICAL TRIAL REGISTRATION: NCT01838148.

Effect of Alirocumab Added to High-Intensity Statin Therapy on Coronary Atherosclerosis in Patients With Acute Myocardial Infarction: The PACMAN-AMI Randomized Clinical Trial.

Importance: Coronary plaques that are prone to rupture and cause adverse cardiac events are characterized by large plaque burden, large lipid content, and thin fibrous caps. Statins can halt the progression of coronary atherosclerosis; however, the effect of the proprotein convertase subtilisin kexin type 9 inhibitor alirocumab added to statin therapy on plaque burden and composition remains largely unknown. Objective: To determine the effects of alirocumab on coronary atherosclerosis using serial multimodality intracoronary imaging in patients with acute myocardial infarction. Design, Setting, and Participants: The PACMAN-AMI double-blind, placebo-controlled, randomized clinical trial (enrollment: May 9, 2017, through October 7, 2020; final follow-up: October 13, 2021) enrolled 300 patients undergoing percutaneous coronary intervention for acute myocardial infarction at 9 academic European hospitals. Interventions: Patients were randomized to receive biweekly subcutaneous alirocumab (150 mg; n = 148) or placebo (n = 152), initiated less than 24 hours after urgent percutaneous coronary intervention of the culprit lesion, for 52 weeks in addition to high-intensity statin therapy (rosuvastatin, 20 mg). Main Outcomes and Measures: Intravascular ultrasonography (IVUS), near-infrared spectroscopy, and optical coherence tomography were serially performed in the 2 non-infarct-related coronary arteries at baseline and after 52 weeks. The primary efficacy end point was the change in IVUS-derived percent atheroma volume from baseline to week 52. Two powered secondary end points were changes in near-infrared spectroscopy-derived maximum lipid core burden index within 4 mm (higher values indicating greater lipid content) and optical coherence tomography-derived minimal fibrous cap thickness (smaller values indicating thin-capped, vulnerable plaques) from baseline to week 52. Results: Among 300 randomized patients (mean [SD] age, 58.5 [9.7] years; 56 [18.7%] women; mean [SD] low-density lipoprotein cholesterol level, 152.4 [33.8] mg/dL), 265 (88.3%) underwent serial IVUS imaging in 537 arteries. At 52 weeks, mean change in percent atheroma volume was -2.13% with alirocumab vs -0.92% with placebo (difference, -1.21% [95% CI, -1.78% to -0.65%], P < .001). Mean change in maximum lipid core burden index within 4 mm was -79.42 with alirocumab vs -37.60 with placebo (difference, -41.24 [95% CI, -70.71 to -11.77]; P = .006). Mean change in minimal fibrous cap thickness was 62.67 µm with alirocumab vs 33.19 µm with placebo (difference, 29.65 µm [95% CI, 11.75-47.55]; P = .001). Adverse events occurred in 70.7% of patients treated with alirocumab vs 72.8% of patients receiving placebo. Conclusions and Relevance: Among patients with acute myocardial infarction, the addition of subcutaneous biweekly alirocumab, compared with placebo, to high-intensity statin therapy resulted in significantly greater coronary plaque regression in non-infarct-related arteries after 52 weeks. Further research is needed to understand whether alirocumab improves clinical outcomes in this population. Trial Registration: ClinicalTrials.gov Identifier: NCT03067844.

Effects of the PCSK9 antibody alirocumab on coronary atherosclerosis in patients with acute myocardial infarction: a serial, multivessel, intravascular ultrasound, near-infrared spectroscopy and optical coherence tomography imaging study-Rationale and design of the PACMAN-AMI trial.

BACKGROUND: The risk for cardiovascular adverse events after acute myocardial infarction (AMI) remains high despite potent medical treatment including low-density lipoprotein cholesterol (LDL-C) lowering with statins. Proprotein convertase subtilisin/kexin type 9 (PCSK9) antibodies substantially reduce LDL-C when added to statin. Alirocumab, a monoclonal antibody to PCSK9, reduces major adverse cardiovascular events after AMI. The effects of alirocumab on coronary atherosclerosis including plaque burden, plaque composition and fibrous cap thickness in patients presenting with AMI remains unknown. AIMS: To determine the effect of LDL-C lowering with alirocumab on top of high-intensity statin therapy on intravascular ultrasound (IVUS)-derived percent atheroma volume (PAV), near-infrared spectroscopy (NIRS)-derived maximum lipid core burden index within 4 mm (maxLCBI4 mm) and optical coherence tomography (OCT)-derived fibrous cap thickness (FCT) in patients with AMI. METHODS: In this multicenter, double-blind, placebo-controlled trial, 300 patients with AMI (ST-elevation or non-ST-elevation myocardial infarction) were randomly assigned to receive either biweekly subcutaneous alirocumab (150 mg) or placebo beginning <24 hours after the acute event as add-on therapy to rosuvastatin 20 mg. Patients undergo serial IVUS, NIRS and OCT in the two non-infarct related arteries at baseline (at the time of treatment of the culprit lesion) and at 52 weeks. The primary endpoint, change in IVUS-derived PAV, and the powered secondary endpoints, change in NIRS-derived maxLCBI4 mm, and OCT-derived minimal FCT, will be assessed 52 weeks post randomization. SUMMARY: The PACMAN-AMI trial will determine the effect of alirocumab on top of high-intensity statin therapy on high-risk coronary plaque characteristics as assessed by serial, multimodality intracoronary imaging in patients presenting with AMI. CLINICAL TRIAL REGISTRATION: NCT03067844.

Using High-Sensitivity Cardiac Troponin for the Exclusion of Inducible Myocardial Ischemia in Symptomatic Patients: A Cohort Study.

Background: The optimal noninvasive method for surveillance in symptomatic patients with stable coronary artery disease (CAD) is unknown. Objective: To apply a novel approach using very low concentrations of high-sensitivity cardiac troponin I (hs-cTnI) for exclusion of inducible myocardial ischemia in symptomatic patients with CAD. Design: Prospective diagnostic cohort study. (ClinicalTrials.gov: NCT01838148). Setting: University hospital. Patients: 1896 consecutive patients with CAD referred with symptoms possibly related to inducible myocardial ischemia. Measurements: Presence of inducible myocardial ischemia was adjudicated using myocardial perfusion imaging with single-photon emission computed tomography, as well as coronary angiography and fractional flow reserve measurements where available. Staff blinded to adjudication measured circulating hs-cTn concentrations. An hs-cTnI cutoff of 2.5 ng/L, derived previously in mostly asymptomatic patients with CAD, was assessed. Predefined target performance criteria were at least 90% negative predictive value (NPV) and at least 90% sensitivity for exclusion of inducible myocardial ischemia. Sensitivity analyses were based on measurements with an hs-cTnT assay and an alternative hs-cTnI assay with even higher analytic sensitivity (limit of detection, 0.1 ng/L). Results: Overall, 865 patients (46%) had inducible myocardial ischemia. The hs-cTnI cutoff of 2.5 ng/L provided an NPV of 70% (95% CI, 64% to 75%) and a sensitivity of 90% (CI, 88% to 92%) for exclusion of inducible myocardial ischemia. No hs-cTnI cutoff reached both performance characteristics predefined as targets. Similarly, using the alternative assays for hs-cTnI or hs-cTnT, no cutoff achieved the target performance: hs-cTnT concentrations less than 5 ng/L yielded an NPV of 66% (CI, 59% to 72%), and hs-cTnI concentrations less than 2 ng/L yielded an NPV of 68% (CI, 62% to 74%). Limitation: Data were generated in a large single-center diagnostic study using central adjudication. Conclusion: In symptomatic patients with CAD, very low hs-cTn concentrations, including hs-cTnI concentrations less than 2.5 ng/L, do not generally allow users to safely exclude inducible myocardial ischemia. Primary Funding Source: European Union, Swiss National Science Foundation, Kommission für Technologie und Innovation (Innosuisse), Swiss Heart Foundation, Cardiovascular Research Foundation Basel, University of Basel, University Hospital Basel, Roche, Abbott, and Singulex.

Hyper-acute cardiovascular magnetic resonance T1 mapping predicts infarct characteristics in patients with ST elevation myocardial infarction.

BACKGROUND: Myocardial recovery after primary percutaneous coronary intervention in acute myocardial infarction is variable and the extent and severity of injury are difficult to predict. We sought to investigate the role of cardiovascular magnetic resonance T1 mapping in the determination of myocardial injury very early after treatment of ST-segment elevation myocardial infarction (STEMI). METHODS: STEMI patients underwent 3 T cardiovascular magnetic resonance (CMR), within 3 h of primary percutaneous intervention (PPCI). T1 mapping determined the extent (area-at-risk as %left ventricle, AAR) and severity (average T1 values of AAR) of acute myocardial injury, and related these to late gadolinium enhancement (LGE), and microvascular obstruction (MVO). The characteristics of myocardial injury within 3 h was compared with changes at 24-h to predict final infarct size. RESULTS: Forty patients were included in this study. Patients with average T1 values of AAR ≥1400 ms within 3 h of PPCI had larger LGE at 24-h (33% ±14 vs. 18% ±10, P = 0.003) and at 6-months (27% ±9 vs. 12% ±9; P < 0.001), higher incidence and larger extent of MVO (85% vs. 40%, P = 0.016) & [4.0 (0.5-9.5)% vs. 0 (0-3.0)%, P = 0.025]. The average T1 value was an independent predictor of acute LGE (ß 0.61, 95%CI 0.13 to 1.09; P = 0.015), extent of MVO (ß 0.22, 95%CI 0.03 to 0.41, P = 0.028) and final infarct size (ß 0.63, 95%CI 0.21 to 1.05; P = 0.005). Receiver-operating-characteristic analysis showed that T1 value of AAR obtained within 3-h, but not at 24-h, predicted large infarct size (LGE > 9.5%) with 100% positive predictive value at the optimal cut-off of 1400 ms (area-under-the-curve, AUC 0.88, P = 0.006). CONCLUSION: Hyper-acute T1 values of the AAR (within 3 h post PPCI, but not 24 h) predict a larger extent of MVO and infarct size at both 24 h and 6 months follow-up. Delayed CMR scanning for 24 h could not substitute the significant value of hyper-acute average T1 in determining infarct characteristics.

Impact of impaired fractional flow reserve after coronary interventions on outcomes: a systematic review and meta-analysis.

BACKGROUND: FFR is routinely used to guide percutaneous coronary interventions (PCI). Visual assessment of the angiographic result after PCI has limited efficacy. Even when the angiographic result seems satisfactory FFR after a PCI might be useful for identifying patients with a suboptimal interventional result and higher risk for poor clinical outcome who might benefit from additional procedures. The aim of this meta-analysis was to investigate available data of studies that examined clinical outcomes of patients with impaired vs. satisfactory fractional flow reserve (FFR) after percutaneous coronary interventions (PCI). METHODS: This meta-analysis was carried out according to the Cochrane Handbook for Systematic Reviews. The Mantel-Haenszel method using the fixed-effect meta-analysis model was used for combining the results. Studies were identified by searching the literature through mid-January, 2016, using the following search terms: fractional flow reserve, coronary circulation, after, percutaneous coronary intervention, balloon angioplasty, stent implantation, and stenting. Primary endpoint was the rate of major adverse cardiac events (MACE). Secondary endpoints included rates of death, myocardial infarction (MI), repeated revascularisation. RESULTS: Eight relevant studies were found including a total of 1337 patients. Of those, 492 (36.8 %) had an impaired FFR after PCI, and 853 (63.2 %) had a satisfactory FFR after PCI. Odds ratios indicated that a low FFR following PCI was associated with an impaired outcome: major adverse cardiac events (MACE, OR: 4.95, 95 % confidence interval [CI]: 3.39-7.22, p <0.001); death (OR: 3.23, 95 % CI: 1.19-8.76, p = 0.022); myocardial infarction (OR: 13.83, 95 % CI: 4.75-40.24, p <0.0001) and repeated revascularisation (OR: 4.42, 95 % CI: 2.73-7.15, p <0.0001). CONCLUSIONS: Compared to a satisfactory FFR, a persistently low FFR following PCI is associated with a worse clinical outcome. Prospective studies are needed to identify underlying causes, determine an optimal threshold for post-PCI FFR, and clarify whether simple additional procedures can influence the post-PCI FFR and clinical outcome.

How does coronary stent implantation impact on the status of the microcirculation during primary percutaneous coronary intervention in patients with ST-elevation myocardial infarction?

AIMS: Primary percutaneous coronary intervention (PPCI) is the optimal treatment for patients presenting with ST-elevation myocardial infarction (STEMI). An elevated index of microcirculatory resistance (IMR) reflects microvascular function and when measured after PPCI, it can predict an adverse clinical outcome. We measured coronary microvascular function in STEMI patients and compared sequential changes before and after stent implantation. METHODS AND RESULTS: In 85 STEMI patients, fractional flow reserve, coronary flow reserve, and IMR were measured using a pressure wire (Certus, St Jude Medical, St Paul, MN, USA) immediately before and after stent implantation. Stenting significantly improved all of the measured parameters of coronary physiology including IMR from 67.7 [interquartile range (IQR): 56.2-95.8] to 36.7 (IQR: 22.7-59.5), P < 0.001. However, after stenting, IMR remained elevated (>40) in 28 (32.9%) patients. In 15 of these patients (17.6% of the cohort), only a partial reduction in IMR occurred and these patients were more likely to be late presenters (pain to wire time >6 h). The extent of jeopardized myocardium [standardized beta: -0.26 (IMR unit/Bypass Angioplasty Revascularization Investigation score unit), P: 0.009] and pre-stenting IMR [standardized beta: -0.34 (IMR unit), P: 0.001] predicted a reduction in IMR after stenting (ΔIMR = post-stenting IMR - pre-stenting IMR), whereas thrombotic burden [standardized beta: 0.24 (IMR unit/thrombus score unit), P: 0.01] and deployed stent volume [standardized beta: 0.26 (IMR unit/mm(3) of stent), P: 0.01] were associated with a potentially deleterious increase in IMR. CONCLUSION: Improved perfusion of the myocardium by stent deployment during PPCI is not universal. The causes of impaired microvascular function at the completion of PPCI treatment are heterogeneous, but can reflect a later clinical presentation and/or the location and extent of the thrombotic burden.

The temporal recovery of fractional flow reserve, coronary flow reserve and index of microcirculatory resistance following myocardial infarction.

PURPOSE OF REVIEW: The purpose of this review was to summarize the healing processes after myocardial infarction (MI) and to relate these temporal changes to data from serial imaging obtained by cardiac magnetic resonance, and then to relate these findings to the invasive measures of the indices of coronary physiology (e.g., fractional flow reserve, coronary flow reserve and index of microcirculatory resistance). RECENT FINDINGS: Indices of coronary physiology measured with an intracoronary wire represent an easily and readily available diagnostic tool for the management of coronary artery disease. Additionally, they give insight into the functional status of the coronary microvasculature. Recent evidence has confirmed initial observations that microvascular recovery occurs after MI and that this is reflected by a progressive improvement of all the indices of coronary physiology over time. More importantly, it has been clarified that this process is variable, but probably predictable as it is affected by the degree of microvascular injury occurring in the acute phase of MI. SUMMARY: Microvascular recovery after acute MI affects the measurement of the indices of coronary physiology. Use of fractional flow reserve, coronary flow reserve and index of microcirculatory resistance requires an understanding of how microvasculature evolves after MI. This understanding allows appropriate application of intracoronary physiology both clinically and in research settings.

Value of Periprocedural Electrophysiology Testing During Transcatheter Aortic Valve Replacement for Risk Stratification of Patients With New-Onset Left Bundle-Branch Block.

Background Despite being the most frequent complication following transcatheter aortic valve replacement (TAVR), optimal management of left bundle-branch block (LBBB) remains unknown. Electrophysiology study has been proposed for risk stratification. However, the optimal timing of electrophysiology study remains unknown. We aimed to investigate the temporal dynamics of atrioventricular conduction in patients with new-onset LBBB after TAVR by performing serial electrophysiology study and to deduce a treatment strategy. Methods and Results We assessed consecutive patients undergoing TAVR via His-ventricular interval measurement prevalve and postvalve deployment and the day after TAVR. Infranodal conduction delay was defined as a His-ventricular interval >55 milliseconds. Among 107 patients undergoing TAVR, 53 patients (50%) experienced new-onset LBBB postvalve deployment and infranodal conduction delay was noted in 24 of 53 patients intraprocedurally (45%). LBBB resolved the day after TAVR in 35 patients (66%). In patients with new-onset LBBB postvalve deployment and no infrahisian conduction delay intraprocedurally, the His-ventricular interval did not prolong in any patient to >55 milliseconds the following day. Overall, 4 patients (7.5%) with new-onset LBBB after TAVR were found to have persistent infrahisian conduction delay 24 hours after TAVR. During 30-day follow-up, 1 patient (1.1%) with new LBBB and a normal His-ventricular interval after TAVR developed new high-grade atrioventricular block. Conclusions Among patients with new-onset LBBB postvalve deployment, infrahisian conduction delay can safely be excluded intraprocedurally, suggesting that early intracardiac intraprocedural conduction studies may be of value in these patients.

Cardiovascular imaging following perioperative myocardial infarction/injury.

Patients developing perioperative myocardial infarction/injury (PMI) have a high mortality. PMI work-up and therapy remain poorly defined. This prospective multicenter study included high-risk patients undergoing major non-cardiac surgery within a systematic PMI screening and clinical response program. The frequency of cardiovascular imaging during PMI work-up and its yield for possible type 1 myocardial infarction (T1MI) was assessed. Automated PMI detection triggered evaluation by the treating physician/cardiologist, who determined selection/timing of cardiovascular imaging. T1M1 was considered with the presence of a new wall motion abnormality within 30 days in transthoracic echocardiography (TTE), a new scar or ischemia within 90 days in myocardial perfusion imaging (MPI), and Ambrose-Type II or complex lesions within 7 days of PMI in coronary angiography (CA). In patients with PMI, 21% (268/1269) underwent at least one cardiac imaging modality. TTE was used in 13% (163/1269), MPI in 3% (37/1269), and CA in 5% (68/1269). Cardiology consultation was associated with higher use of cardiovascular imaging (27% versus 13%). Signs indicative of T1MI were found in 8% of TTE, 46% of MPI, and 63% of CA. Most patients with PMI did not undergo any cardiovascular imaging within their PMI work-up. If performed, MPI and CA showed high yield for signs indicative of T1MI.Trial registration: https://clinicaltrials.gov/ct2/show/NCT02573532 .

Non-invasive predictors for infranodal conduction delay in patients with left bundle branch block after TAVR.

AIMS: Left bundle branch block (LBBB) is the most common conduction disorder after transcatheter aortic valve replacement (TAVR) with an increased risk of atrioventricular (AV) block. The aim of the current study was to identify non-invasive predictors for infranodal conduction delay in patients with LBBB. METHODS: We analyzed consecutive patients undergoing TAVR with pre-existing or new-onset LBBB between August 2014 and August 2020. His ventricular (HV) interval measurement was performed on day 1 after TAVR. Baseline, procedural, as well as surface and intracardiac electrocardiographic parameters were included. Infranodal conduction delay was defined as HV interval > 55 ms. RESULTS: Of 825 patients screened after TAVR, 151 patients (82 ± 6 years, 39% male) with LBBB were included. Among these, infranodal conduction delay was observed in 25%. ΔPR (difference in PR interval after and before TAVR), PR and QRS duration after TAVR were significantly longer in the group with HV prolongation. In a multivariate analysis in patients with sinus rhythm (n = 123), ΔPR (OR per 10 ms increase: 1.52; 95%CI: 1.19-2.01; p = 0.002) was the only independent factor associated with infranodal conduction delay. A change in PR interval by 20 ms yielded a specificity of 83% and a sensitivity of 46%, with a negative predictive value of 84% and a positive predictive value of 45% to predict HV prolongation. CONCLUSIONS: Simple analysis of surface ECG and a calculated ΔPR < 20 ms can be used as predictor for the absence of infranodal conduction delay in post-TAVR patients with LBBB.

Adverse Events of Percutaneous Microaxial Left Ventricular Assist Devices-A Retrospective, Single-Centre Cohort Study.

Worldwide, the left ventricular assist device Impella® (Abiomed, Danvers, MA, USA) is increasingly implanted in patients with acute cardiogenic shock or undergoing high-risk cardiac interventions. Despite its long history of use, few studies have assessed its safety and possible complications associated with its use. All patients treated with a left-sided Impella® device at the University Hospital of Basel from 1 January 2011 to 31 December 2019 were enrolled. The primary endpoint was the composite rate of mortality and adverse events (bleeding, acute kidney injury, and limb ischemia). Out of 281 included patients, at least one adverse event was present in 262 patients (93%). Rates of in-hospital, 90-day, and one-year mortality were 48%, 47%, and 50%, respectively. BARC type 3 bleeding (62%) and hemolysis (41.6%) were the most common complications. AKI was observed in 50% of all patients. Renal replacement therapy was required in 97 (35%) of all patients. Limb ischemia occurred in 13% of cases. Bleeding and hemolysis are common Impella®-associated complications. Additionally, we found a high rate of AKI. A careful selection of patients receiving microaxial LV support and defining the indication for its use are essential measures to be taken for the benefits to outweigh potential complications.

Effect of COVID-19 on acute treatment of ST-segment elevation and Non-ST-segment elevation acute coronary syndrome in northwestern Switzerland.

BACKGROUND: To investigate the effect of the corona virus disease 2019 (COVID-19) pandemic on the acute treatment of patients with ST-segment elevation (STEMI) and Non-ST-segment elevation acute coronary syndrome (NSTE-ACS). METHODS: We retrospectively identified patients presenting to the emergency department (ED) with suspected ACS. We evaluated the number of percutaneous coronary interventions (PCIs) for STEMI, NSTE-ACS, and elective PCI cases. In STEMI patients, we assessed the time from chest pain onset (cpo) to ED presentation, post-infarction left ventricular ejection fraction (LVEF), and time from ED presentation to PCI. We directly compared cases from two time intervals: January/February 2020 versus March/April 2020 (defined as 2 months before and after the COVID-19 outbreak). In a secondary analysis, we directly compared cases from March/April 2020 with patients from the same time interval in 2019. RESULTS: From January to April 2020, 765 patients presented with acute chest pain to the ED. A dramatic reduction of ED presentations after compared to before the COVID-19 outbreak (31% relative reduction) was observed. Overall, 398 PCIs were performed, 220/398 PCIs (55.3%) before versus 178/398 PCIs (44.7%) after the outbreak. While numbers for NSTE-ACS and elective interventions declined by 21% and 31%, respectively, the number of STEMI cases remained stable. Time from cpo to ED presentation, post-infarction LVEF, and median door-to-balloon time remained unchanged. CONCLUSIONS: In contrast to previous reports, our findings do not confirm the dramatic drop in STEMI cases and interventions in northwestern Switzerland as observed in other regions and hospitals around the world.

Coronary Microvascular Dysfunction Assessed by Pressure Wire and CMR After STEMI Predicts Long-Term Outcomes.

OBJECTIVES: This study sought to evaluate the long-term prognostic implications of coronary microvascular dysfunction (CMD) when assessed with both cardiovascular magnetic resonance (CMR) and index of microcirculatory resistance (IMR) in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). BACKGROUND: Post-ischemic CMD can be assessed using the pressure-wire based IMR and/or by the presence of microvascular obstruction (MVO) on CMR. METHODS: A total of 198 patients with STEMI underwent IMR and MVO assessment. Patients were classified as follows: Group 1, no significant CMD (low IMR [≤40 U] and no MVO); Group 2, CMD with either high IMR (>40 U) or MVO; Group 3, CMD with both IMR >40 U and MVO. The primary endpoint was the composite of all-cause mortality, diagnosis of new heart failure, cardiac arrest, sustained ventricular tachycardia/fibrillation, and cardioverter defibrillator implantation. RESULTS: CMD with both high IMR and MVO was present in 23.7% of the cases (Group 3) and CMD with either high IMR or MVO was observed in 40.9% of cases (Group 2). At a median follow-up of 40.1 months, the primary endpoint occurred in 34 (17%) cases. At 1 year of follow-up, Group 3 (hazard ratio [HR]: 12.6; 95% confidence interval [CI]: 1.6 to 100.6; p = 0.017) but not Group 2 (HR: 7.2; 95% CI: 0.9 to 57.9; p = 0.062) had worse clinical outcomes compared with those with no significant CMD in Group 1. However, in the long-term, patients in Group 2 (HR: 4.2; 95% CI: 1.4 to 12.5; p = 0.009) and those in Group 3 (HR: 5.2; 95% CI: 1.7 to 16.2; p = 0.004) showed similar adverse outcomes, mainly driven by the occurrence of heart failure. CONCLUSIONS: Post-ischemic CMD predicts a more than 4-fold increase in long-term risk of adverse outcomes, mainly driven by the occurrence of heart failure. Defining CMD by either invasive IMR >40 U or by CMR-assessed MVO showed similar risk of adverse outcomes.

In vivo relationship between near-infrared spectroscopy-detected lipid-rich plaques and morphological plaque characteristics by optical coherence tomography and intravascular ultrasound: a multimodality intravascular imaging study.

AIMS: We assessed morphological features of near-infrared spectroscopy (NIRS)-detected lipid-rich plaques (LRPs) by using optical coherence tomography (OCT) and intravascular ultrasound (IVUS). METHODS AND RESULTS: IVUS-NIRS and OCT were performed in the two non-infarct-related arteries (non-IRAs) in patients undergoing percutaneous coronary intervention for treatment of an acute coronary syndrome. A lesion was defined as the 4 mm segment with the maximum amount of lipid core burden index (maxLCBI4mm) of each LRP detected by NIRS. We divided the lesions into three groups based on the maxLCBI4mm value: <250, 250-399, and ≥400. OCT analysis and IVUS analysis were performed blinded for NIRS. We measured fibrous cap thickness (FCT) by using a semi-automated method. A total of 104 patients underwent multimodality imaging of 209 non-IRAs. NIRS detected 299 LRPs. Of those, 41% showed a maxLCBI4mm <250, 39% a maxLCBI4mm 251-399, and 19% a maxLCBI4mm ≥400. LRPs with a maxLCBI4mm ≥400, as compared with LRPs with a maxLCBI4mm 250-399 and <250, were more frequently thin-cap fibroatheroma (TCFA) (42.1% vs. 5.1% and 0.8%; P < 0.001) with a smaller minimum FCT (80 µm vs. 110 µm and 120 µm; P < 0.001); a higher IVUS-derived percent atheroma volume (53% vs. 53% and 44%; P < 0.001) and a higher remodelling index (1.08 vs. 1.02 and 1.01; P < 0.001). MaxLCBI4mm correlated with OCT-derived FCT (r = 0.404; P < 0.001) and was the best predictor for TCFA with an optimal cut-off value of 401 (area under the curve = 0.882; P < 0.001). CONCLUSION: LRPs with increasing maxLCBI4mm exhibit OCT and IVUS features of presumed plaque vulnerability including TCFA morphology, increased plaque burden, and positive remodelling.

3D-Printed Visualization of a Complex Coronary-Venous Fistula With Additional Feeders From the Descending Aorta.

In a 32-year-old patient with chest pain, a large, complex coronary-venous fistula with additional feeders from the descending aorta was detected with computed tomography. Multimodality imaging, including multicolor 3-dimensional printing, allowed precise anatomic visualization of the origin, course and drainage site of the fistula. The patient was treated conservatively. (Level of Difficulty: Advanced.).

A Randomized Trial of Recombinant Human C1-Esterase-Inhibitor in the Prevention of Contrast-Induced Kidney Injury.

OBJECTIVES: This study sought to determine the efficacy profile and safety of recombinant human C1 esterase inhibitor (rhC1INH) in the prevention of contrast-associated acute kidney injury after elective coronary angiography. BACKGROUND: Contrast-associated acute kidney injury is caused by tubular cytotoxicity and ischemia/reperfusion injury. rhC1INH is effective in reducing renal ischemia/reperfusion injury in experimental models. METHODS: In this placebo-controlled, double-blind, single-center trial 77 patients with chronic kidney disease were randomized to receive 50 IU/kg rhC1INH before and 4 h after elective coronary angiography or placebo. The primary outcome was the peak change of urinary neutrophil gelatinase-associated lipocalin within 48 h, a surrogate marker of kidney injury. RESULTS: Median peak change of urinary neutrophil gelatinase-associated lipocalin was lower in the rhC1INH group (4.7 ng/ml vs. 22.5 ng/ml; p = 0.038) in the per-protocol population but not in the modified intention-to-treat analysis, and in patients with percutaneous coronary interventions (median, 1.8 ng/ml vs. 26.2 ng/ml; p = 0.039 corresponding to a median proportion peak change of 11% vs. 205%; p = 0.002). The incidence of a cystatin C increase ≥10% within 24 h was lower in the rhC1INH group (16% vs. 33%; p = 0.045), whereas the frequency of contrast-associated acute kidney injury was comparable. Adverse events during a 3-month follow-up were similarly distributed. CONCLUSIONS: Administration of rhC1INH before coronary angiography may attenuate renal injury as reflected by urinary neutrophil gelatinase-associated lipocalin and cystatin C. The safety profile of rhC1INH was favorable in a patient population with multiple comorbidities. (Recombinant Human C1 Esterase Inhibitor in the Prevention of Contrast-induced Nephropathy in High-risk Subjects [PROTECT]; NCT02869347).

Electrophysiology Testing to Stratify Patients With Left Bundle Branch Block After Transcatheter Aortic Valve Implantation.

Background Left bundle branch block (LBBB) is common after transcatheter aortic valve implantation (TAVI) and is an indicator of subsequent high-grade atrioventricular block (HAVB). No standardized protocol is available to identify LBBB patients at risk for HAVB. The aim of the current study was to evaluate the safety and efficacy of an electrophysiology study tailored strategy in patients with LBBB after TAVI. Methods and Results We prospectively analyzed consecutive patients with LBBB after TAVI. An electrophysiology study was performed to measure the HV-interval the day following TAVI. In patients with normal His-ventricular (HV)-interval ≤55 ms, a loop recorder was implanted (ILR-group), whereas pacemaker implantation was performed in patients with prolonged HV-interval >55 ms (PM-group). The primary end point was occurrence of HAVB during a follow-up of 12 months. Secondary end points were symptoms, hospitalizations, adverse events because of device implantation or electrophysiology study, and death. Of 373 patients screened after TAVI, 56 patients (82±6 years, 41% male) with LBBB were included. HAVB occurred in 4 of 41 patients (10%) in the ILR-group and in 8 of 15 patients (53%) in the PM-group (P<0.001). We did not identify other predictors for HAVB than the HV interval. The negative predictive value for the cut-off of HV 55 ms to detect HAVB was 90%. No HAVB-related syncope occurred in the 2 groups. Conclusions An electrophysiology study tailored strategy to LBBB after TAVI with a cut-off of HV >55 ms is a feasible and safe approach to stratify patients with regard to developing HAVB during a follow-up of 12 months.