bluuebunny/crossref_metadata_2025_split huggingface dataset:
Independent prognostic value of ejection fraction, resting coronary flow, coronary flow reserve, myocardial viability, and inducible ischemia in heart failure with a reduced ejection fraction
Authors: Ciampi Q , Cortigiani L , Rigo F , Gaibazzi N , Zagatina A , Wierzbowska-Drabik K , Kasprzak J , Djordjevic-Dikic A , Haberka M , Lorenzoni V , Barbieri A , Pepi M , Carerj S , Villari B , Picano E 
Published: November 2023

Abstract

Background and Aims
Patients with heart failure (HF) with reduced left ventricular (LV) ejection fraction (EF) have a heterogeneous prognosis, and assessment of coronary physiology with coronary flow velocity (CFV) and coronary flow velocity reserve (CFVR) may complement established predictors based on wall motion.

Methods and results
In a prospective multicenter study design, we enrolled 1,408 HF patients (age 66±12 years, 1,035 men), with EF &lt;50%, 743 (53%) with coronary artery disease, and 665 (47%) with normal coronary arteries. Recruitment (years 2004-2022) involved 8 accredited laboratories, with inter-observer variability &lt;10% for CFV measurement. Baseline CFV (abnormal value &gt;31 cm/s) was obtained by pulsed-wave Doppler in mid-distal LAD. Coronary flow velocity reserve (CFVR, abnormal value ≤2.0) was assessed with exercise (n=99), dobutamine (n=100), and vasodilator stress (dipyridamole in 1,149, adenosine in 60). Inducible myocardial ischemia was identified with wall motion score index (WMSI) stress&gt; rest (cut-off ∆≥0.12). LV contractile reserve (CR) was identified with WMSI stress&lt; rest (cutoff ∆≥0.25). Test response ranged from score 0 (EF&gt;30%, CFV ≤31 cm/s, CFVR &gt;2.0, LVCR present, ischemia absent) to score 5 (all steps abnormal). All-cause death was the only end-point.

Results
During a median follow-up of 990 days, 253 patients died. Independent predictors of death were EF (HR: 0.956, 95% CI: 0.943-0.968, p&lt;0.0001), CFV (HR: 2.407, 95% CI: 1.871-3.096, p&lt;0.001), CFVR (HR: 3.908, 95% CI: 2.903-5.260, p&lt;0.001), stress-induced ischemia (HR: 2.223, 95% CI: 1.642-3.009, p&lt;0.001), and LVCR (HR: 0.524, 95% CI: 0.324-.647, p=0.008). The annual mortality rate was lowest (1.2%) in patients with a score of 0 (n=61) and highest (31.9%) in patients with a score of 5 (n=15, p&lt;0.001).

Conclusion
High resting CFV predicts worse survival in ischemic and nonischemic HF with reduced EF. The value is independent and additive to resting EF, CFVR, LVCR, and inducible ischemia.
Effect of alirocumab on quantitative flow ratio and diameter stenosis in non-infarct related arteries from patients with acute myocardial infarction: a PACMAN-AMI randomized clinical trial substudy
Authors: Baer S , Kavaliauskaite R , Otsuka T , Ueki Y , Haener J , Siontis G C M , Van Geuns R , Daemen J , Spirk D , Engstrom T , Lang I , Windecker S , Koskinas K C , Losdat S , Raeber L 
Published: November 2023

Abstract

Introduction
Treating hypercholesterolemia with proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors on top of statins leads to plaque regression and stabilization. The effects of PCSK9 inhibitors on coronary physiology and angiographic diameter stenosis (DS%) are unknown. Quantitative Flow Ratio (QFR) is a novel method to assess coronary hemodynamics.

Purpose
We aimed to investigate the effects of the PCSK9 inhibitor alirocumab on QFR and 3D-Quantitative Coronary Angiography (3D-QCA) DS% in non-infarct-related arteries (non-IRA) among acute myocardial infarction (AMI) patients.

Methods
This was a pre-specified substudy of the PACMAN trial, a randomized, double-blind, placebo-controlled trial comparing alirocumab vs. placebo on top of high-intensity rosuvastatin among AMI patients. QFR and 3D-QCA were assessed at baseline and 1-year follow-up in any non-infarct related artery (non-IRA) with ≥2.0mm diameter and &gt;25% 3D-QCA DS%. The pre-specified primary endpoint was the number of patients with mean QFR increase from baseline to follow-up, and the secondary endpoint the change in 3D-QCA DS%.

Results
Of 300 enrolled patients, 265 had serial follow-up, of which 193 underwent serial QFR/3D-QCA analysis in 282 non-IRA. Baseline mean QFR was 0.96[IQR 0.91-0.98] and mean DS% 36.96±7.88% in the alirocumab group vs. 0.96[IQR 0.91-0.99] (p=0.593) and 36.63±8.46% (p=0.742) in the placebo group. At 1-year, QFR increased in 50/94 (53.2%) patients with alirocumab vs. 40/99 (40.4%) with placebo (Δ12.8%; OR=1.7, 95%CI 0.9-3.0; p=0.076). When excluding non-IRA with QFR &gt;0.95, QFR increased in 37/57 (64.9%) patients with alirocumab vs. 22/50 (44.0%) with placebo (Δ20.9%; OR=2.4, 95%CI 1.1-5.2; p=0.031). DS% decreased by -1.03±7.28% with alirocumab and increased by +1.70±8.27% with placebo (Δ-2.54%, 95%CI -4.51 to -0.57; p=0.012).

Conclusions
Treatment of AMI patients with alirocumab vs. placebo for 1 year resulted in a significant regression in angiographic DS%. While no overall improvement of coronary hemodynamics was observed with alirocumab as compared to placebo, potential benefits were found in alirocumab treated patients with baseline QFR ≤0.95.Figure 1.Flowchart and primary endpointFigure 2.Secondary endpoint
Anonymous comparative assessment by an academic core laboratory of four angiography-derived fractional flow ratio software in patients with pressure derived iFR and FFR
Authors: Ninomiya K , Serruys P , Kotoku N , Kageyama S , Masuda S , Patel M , Escaned J , Akasaka T , Onuma Y 
Published: November 2023

Abstract

Background/Introduction
Functional assessment of coronary artery stenoses plays an important role in guiding the clinical management of patients with ischemic heart disease. Software to compute angiography-derived fractional flow ratio (angio-FFR) have been validated against pressure-wire-derived FFR (PW-FFR) with an area under the receiver operator characteristic curve (AUC) of 0.93-0.97. However, it is unknown whether commercially available angio-FFR software are equally reliable, and to what extent each might over- or under-estimate the true functional severity of a coronary artery lesion.

Purpose
The aim of this study was to investigate the diagnostic accuracies of five angio-FFR software/methods by an independent core-lab in a prospective cohort of 390 vessels with carefully documented sites of PW instantaneous-wave-free ratio (PW-iFR) and PW-FFR.

Methods
One "matcher investigator (MI)" colocalized on angiography the sites of PW measurement with angio-FFR measurements and provided the same two optimal angiographic views and frame selection to independent analysts, who were blinded to invasive physiological results and results from other software. Results are anonymized and randomly presented. The AUC of each angio-FFR was compared with 2D-quantative coronary angiography percent diameter stenosis (2D-QCA%DS) using a 2-tailed paired comparison of ROC (DeLong’s method).

Results
All 5 software/methods yielded a high proportion of analysable vessels (A:100%, B:100%, C:92.1%, D:99.5%, E:92.1%). The AUC’s for predicting an FFR≤0.8 for software A, B, C, D, E, and 2D-QCA%DS were 0.75, 0.74, 0.74, 0.73, 0.73, and 0.65, respectively (Figure A). The AUC for each angio-FFR was significantly greater than that for 2D-QCA%DS.
Furthermore, binary logistic regression analyses showed the predictors of false positives and false negative: severity of lesion stenosis, lesion location, microvascular resistance, and intermediate zone of angiography-derived FFR potentially reduce the diagnostic accuracy (Figure B).

Conclusions
This head-to-head comparison by an independent core-lab demonstrated that the diagnostic accuracy of various angio-FFR software for predicting a PW-FFR≤0.80 was useful, with a higher discrimination compared to 2D-QCA%DS, however it didn’t reach the diagnostic accuracy (AUC≥0.90) previously reported in validation studies of various vendors. The intrinsic clinical value of "angiography-derived FFR" therefore requires confirmation in large clinical trials.Figure AFigure B
Core laboratory comparative assessment of angiography-derived index of microvascular resistance (IMR) in patients with wire-based IMR
Authors: Tsai T , Gomez J , Wang B , He X C , Ninomia K , Kageyama S , Chenniganahosahalli Revaiah P , Kotoku N , Onuma Y , Serruys P 
Published: November 2023

Abstract

Background
Coronary microvascular disease (CMD) is responsible for nearly half of angina in the general population. The index of microvascular resistance (IMR) is the gold standard for the diagnosis of CMD. Abnormal IMR is independently associated with adverse outcomes and persistent angina after percutaneous coronary intervention (PCI) regardless of the achieved fractional flow reserve (FFR). However, the implementation of IMR in clinical practice is low due to cost and the need for hyperemia. Thus, multiple software and formulas have been developed to calculate wireless IMR via angiography analysis. However, these angiography-derived IMRs have never been compared head-to-head by an independent core laboratory.

Aim
In this study, we aim to investigate the diagnostic accuracies of five angiography-derived IMR software/formulas by an independent core lab in a retrospective cohort undergoing follow-up angiograms after successful PCI.

Methods
We analyzed 43 patients from the FUNCOMBO trial and 34 patients from the RETROFI II trial. All patients have received successful PCI for STEMI, and wire-based IMR was measured at six months (for FUNCOMBO) and three years follow-up (for RETROFI II). Angiography-derived IMR was calculated with the QFR®2.1 software, the Flashangio CaIMR® software, and the AngioPlus software. In addition, using QFR-derived data, we calculated the angio-IMR using the formula of Escaned et al. [angio-IMR = (Pa–[0.1*Pa])*QFR*e-Tmn (where e-Tmn is an estimation of hyperaemic mean transit time)] and Scarsini et al. [NH-IMRangio=Pa(resting)x QFR x N frame(resting)/frame per second]. The threshold of CMD diagnosis is 25 for all five angiography-derived IMR methods. The correlation and agreement of the five methods were evaluated against wire-based IMR measurement.

Results
The wire-based IMR was significantly correlated with Medis IMR (r= 0.396, p=0.001) and NH-IMRangio (r=0.378, p=0.001). The agreements between IMR and the angiography-derived IMRs are demonstrated in figure 1. The sensitivity, specificity, positive predicted value, negative predicted value, and accuracy were demonstrated in figure 2, which showed that using the published criteria, the accuracy of diagnosis was 52%, 68%, 67%, 68%, and 49% for Medis IMR, CaIMR, AngioPlus IMR, angio-IMR, and NH-IMRangio, respectively. Comparison of all angiography-derived IMR with wire-based IMR yielded the AUC’s of 0.648, 0.561, 0.606, 0.674, 0.688 for Medis IMR, CaIMR, AngioPlus IMR, angio-IMR, and NH-IMRangio respectively. (Figure 2.)

Conclusion
In this small validation cohort, we found that all five angiography-derived IMR calculation methods had either poor or very poor diagnostic accuracy. Among the five methods, the Medis IMR, Angio-IMR, and NH-IMRangio may be viable options for wireless CMD diagnosis.Figure 1Figure 2
Non-hyperaemic coronary flow velocity acceleration indices correlate with hyperaemic microvascular resistance in patients with INOCA
Authors: Tas A , Broyd C J , Alan Y , Atay Z , Kara I , Umman S , Sezer M 
Published: November 2023

Abstract

Background
Coronary microvascular dysfunction (CMD) is associated with an overall worse prognosis. While the diagnosis and endo-typing of CMD currently rely on hyperaemic physiological indices, the search for accurate non-hyperaemic techniques continues. Flow velocity acceleration pattern is mechanistically associated with changes in shear stress, endothelial function, arterial stiffness and pressure in pulsatile flow systems (1-3).

Purpose
We aim to interrogate whether resting flow velocity acceleration indices correlate with hyperaemic microvascular resistance (HMR) in patients with Ischemia and no obstructive coronary artery disease (INOCA).

Methods
In 21 Patients with INOCA (all of whom had presented with typical angina pectoris, had no significant epicardial stenoses but positive myocardial perfusion scan test for ischemia) invasive physiological assessment was performed by means of intracoronary Doppler. Hyperaemia was induced with intracoronary adenosine administration. Coronary flow reserve (CFR) and HMR were calculated per their definitions. Flow velocity acceleration indices were derived from the first derivative of the averaged resting flow velocity waveforms with respect to time. We have defined 6 wave peaks of interest in all patients (peak diastolic acceleration (initial prominent peak with ventricular relaxation, referred as A), early diastolic deceleration (B), early re-acceleration wave (C), peak presystolic deceleration (seen just before initial systolic acceleration peak, J), initial systolic acceleration peak (X) and pre-diastolic deceleration nadir (Z)) and calculated the ratios between them as well as adjusted them with respect to resting mean flow velocity (Figure 1).

Results
The mean age was 59 ± 8 years and the majority of the study group was female (%81). Cardiovascular risk factors were common amongst the study group.All patients had CFR &lt; 2.5. Mean CFR and HMR were 2.05 ± 0.32 and 2.20 ± 0.60 mmHg.cm.sec-1 respectively. Raw C peak magnitude was significantly correlated with APVh (rho:-0.457 p:0.037) and HMR (rho:0.612 p:0.004). Adjusting the C magnitudes with APVb at patient level yielded better correlations (APVh rho:-0.496 p:0.022 ; HMR:0.642 p:0.002). The ratio between diastolic reacceleration peak (C) and presystolic peak deceleration (J), C/J , adjusted with the APVb ((C/J)/APVb) showed the most pronounced correlation with HMR (rho: 0.758 p &lt; 0.001) (unadjusted C/J – HMR rho: 0.718 p&lt;0.001)(Figure 2).

Conclusion(s)
Acceleration characteristics of resting coronary flow velocity correlate with hyperaemic microvascular resistance indicating structurally impaired coronary microcirculation, hence their utilisation may aid developing non-hyperaemic physiological markers for coronary microvascular dysfunction in patients with INOCA.Derived Acceleration WaveformsCorrelations between HMR and C/J Ratio
Diabetes mellitus and response to IL-1 blockade with Anakinra after ST-elevation myocardial infarction: a pooled analysis of the VCU-ART studies
Authors: Moroni F , Del Buono M G , Wohlford G , Markley R , Turlington J , Kadaryia D , Trankle C , Biondi-Zoccai G , Lipinski M J , Roberts C , Kontos M C , Carbone S , Arena R , Van Tassell B , Abbate A 
Published: November 2023

Abstract

Background
ST segment elevation myocardial infarction (STEMI) elicits an intense inflammatory response which is thought to contribute to subsequent maladaptive myocardial healing and remodeling, ultimately leading to heart failure (HF). The interleukin-1 (IL-1) blocker anakinra administered during the first 14 days after STEMI patients has been shown to effectively dampen the inflammatory response and reduce the incidence of HF events in pilot randomized controlled trials. Diabetes mellitus is a condition of enhanced systemic inflammation.

Purpose
To assess the role of diabetes mellitus as a modulating factor in respect to the efficacy of anakinra treatment during the first 14 days after STEMI.

Methods
We conducted a pooled analysis of three previous proof of principle trials on anakinra in STEMI. Diabetes mellitus was defined based on clinical history, use of glucose-lowering medications, or elevated hemoglobin A1c &gt;6.5% at time of enrollment and further characterized as type I or type II based on the available clinical assessment. The area-under-the-curve for C reactive protein (AUC-CRP) at 14 days was used as a measure of the systemic inflammatory response during STEMI. The clinical endpoint was composite of death, hospitalizations for HF and urgent HF visits.

Results
The study population included 139 patients, of whom 39 (28%) had a diagnosis of diabetes mellitus at time of enrolment, all with type II. Median age was 56 [49-63] and 56 [49-63] years in patients with and without diabetes, respectively (p=0.652). There were 29 (21%) female and 52 (37%) Black-African American patients among those with diabetes compared to 29 (21%) female and 52 (37%) Black-African American patients in those without diabetes (p=0.69 and p=0.16, respectively). Treatment with anakinra (N=84) significantly dampened acute inflammation associated with STEMI in patients with diabetes (AUC-CRP 223 [117-399] vs 76 [42-148] mg•day/L, p&lt;0.001) and in those without diabetes (AUC-CRP 223 [117-399] vs 76 [42-148] mg•day/L, p&lt;0.001 – Figure 1). No statistically significant interaction between diabetes status and treatment with anakinra on outcomes was detected (pint=0.92): treatment with anakinra was associated with a hazard ratio [HR] 0.28 [0.09-0.84](p=0.02) in non-diabetic patients and HR 0.26 [0.11-1.32](p=0.10) in diabetic patients – Figure 2.

Conclusion
In this pooled analysis of the VCU-ART trials, the presence of type II diabetes mellitus showed no interaction with the efficacy of the treatment with anakinra early after STEMI in reducing the systemic inflammatory response or preventing new onset heart failure, hospitalization for HF or death.Figure 1.Figure 2
In-hospital and 1-year mortality associated with percutaneous coronary intervention use in patients with acute myocardial infarction older than 90 years
Authors: Trombara F , Cosentino N , Bonomi A , Milazzo V , Rubino M , De Metrio M , Resta M , Agostoni P G , Marenzi G 
Published: November 2023

Abstract

Background
Patients older than 90 years are less likely to receive percutaneous coronary intervention (PCI) for treatment of acute myocardial infarction (AMI). This is due to the lack of evidence derived from randomized trials, multimorbidity, and possible futility. We investigated the prognostic impact of PCI in a large population of patients hospitalized with AMI in the period 2003-2018, by using the Lombardy Health Database (Italy).

Methods
We analyzed data of all patients &gt;90 years hospitalized with AMI (both STEMI and NSTEMI) in Lombardy. Patients were grouped according to whether they were treated or not with PCI during index hospitalization. The primary outcome was in-hospital mortality. One-year mortality and 1-year re-hospitalization for acute heart failure (AHF) or AMI were considered as secondary endpoints.

Results
During the study period, 15,954 patients (median age 92 [91-94] years); 50% STEMI) were hospitalized with a primary diagnosis of AMI. Twelve percent of them (n=1,954) were treated with PCI. The in-hospital mortality rate in the entire cohort was 22% (29% in STEMI and 15% in NSTEMI). It was significantly lower in patients treated with PCI than in those not treated with PCI (15% vs. 23%; P&lt;0.0001). In the overall population, 1-year mortality was 56% and 1-year re-hospitalization for AHF/AMI was 19%. Both these endpoints were less frequent in PCI-treated (37% vs. 58% and 16% vs. 21%, respectively; P&lt;0.0001). The adjusted risk of the study endpoints was significantly lower in patients treated with PCI: OR 0.61 (95% CI 0.54-0.69) for in-hospital mortality; HR 0.53 (95% CI 0.49-0.57) for 1-year mortality; HR 0.68 (95% CI 0.66-0.70) for 1-year re-hospitalization for AHF/AMI. The figure shows the 1-year survival curves of AMI patients treated or not treated with PCI. Similar results were found in STEMI and NSTEMI patients considered separately.

Conclusions
Our real-world data showed that in patients with AMI older than 90 years of age, PCI use is associated with a significant in-hospital and 1-year clinical benefit.
Exercise ECG and myocardial perfusion SPECT show high prognostic value up to four years after examination
Authors: Kraen M , Akil S , Heden B , Kjellstrom B , Berg J , Ostenfeld E , Arheden H , Carlsson M , Engblom H 
Published: November 2023

Abstract

Background
Abnormal results of myocardial perfusion SPECT (MPS) or exercise ECG (Ex-ECG) is known to be associated with increased risk of ischemic cardiac events. The predictive value of stress testing however, is influenced by underlying risk factors as well as follow up duration and may vary considerably over time. With traditional Cox proportional hazards analysis the time-varying effects are not sufficiently accounted for.

Purpose
To evaluate the prognostic longevity of MPS and Ex-ECG using statistical methods that allow hazard ratio changes over time.

Methods
908 patients (age 63 years, 49% male, 45% prior ischemic heart disease (IHD)) referred for MPS were prospectively included. Ex-ECG was performed in conjunction with MPS. Registry data were used for follow up. The outcome was a composite of acute myocardial infarction, unstable angina, unplanned revascularization, and cardiovascular death. Cox proportional hazard analysis and smoothed hazard functions with splines were used for risk assessment during follow up.

Results
Ex-ECG or MPS were abnormal in 198 (22%) or 148 (16%) of patients respectively. The mean follow up time was 8.2±2.6 years and the composite end point was reached in 189 patients (21%). The Kaplan-Meier curves suggest an interaction with time with the risk of event for subjects with abnormal test results being highest in the 2-3 of years after which the curves are approximately parallel (Figure 1). In multivariable models the best fit (lowest Akaike information criterion (AIC) value) was obtained with a logarithmic interaction term for time. With this approach and controlling for known risk factors the hazard ratio (HR) drops to 1 after approximately four years for both Ex-ECG and MPS (Figure 2). Age (HR=1.04, p&lt;0.001), sex (HR=2.0, p&lt;0.001), IHD (HR=1.7, p&lt;0.001) and reduced exercise capacity (HR=0.99, p&lt;0.001) were independent significant predictors of risk.

Conclusions
The high risk associated with abnormal MPS and Ex-ECG results decrease rapidly over time and after approximately 4 years the predictive value is lost. Thus, the long-term impact on prognosis of stress testing appear questionable. The time-varying effects on risk are substantial and warrant statistical considerations when designing clinical follow up studies of chronic coronary syndrome.