Saline-induced coronary hyperemia with continuous intracoronary thermodilution is mediated by intravascular hemolysis.

BACKGROUND AND AIMS: Absolute coronary flow can be measured by intracoronary continuous thermodilution of saline through a dedicated infusion catheter (RayFlow®). A saline infusion rate at 15-20 mL/min induces an immediate, steady-state, maximal microvascular vasodilation. The mechanism of this hyperemic response remains unclear. We aimed to test whether local hemolysis is a potential mechanism of saline-induced coronary hyperemia. METHODS: Twelve patients undergoing left and right catheterization were included. The left coronary artery and the coronary sinus were selectively cannulated. Absolute resting and hyperemic coronary flow were measured by continuous intracoronary thermodilution. Arterial and venous samples were collected from the coronary artery and the coronary sinus in five phases: baseline (BL); resting flow measurement (Rest, saline infusion at 10 mL/min); hyperemia (Hyperemia, saline infusion at 20 mL/min); post-hyperemia (Post-Hyperemia, 2 min after the cessation of saline infusion); and control phase (Control, during infusion of saline through the guide catheter at 30 mL/min). RESULTS: Hemolysis was visually detected only in the centrifugated venous blood samples collected during the Hyperemia phase. As compared to Rest, during Hyperemia both LDH (131.50 ± 21.89 U/dL [Rest] and 258.33 ± 57.40 U/dL [Hyperemia], p < 0.001) and plasma free hemoglobin (PFHb, 4.92 ± 3.82 mg/dL [Rest] and 108.42 ± 46.58 mg/dL [Hyperemia], p < 0.001) significantly increased in the coronary sinus. The percentage of hemolysis was significantly higher during the Hyperemia phase (0.04 ± 0.02% [Rest] vs 0.89 ± 0.34% [Hyperemia], p < 0.001). CONCLUSIONS: Saline-induced hyperemia through a dedicated intracoronary infusion catheter is associated with hemolysis. Vasodilatory compounds released locally, like ATP, are likely ultimately responsible for localized microvascular vasodilation.

Effects of the Interactive Web-Based Video "Mon Coeur, Mon BASIC" on Drug Adherence of Patients With Myocardial Infarction: Randomized Controlled Trial.

BACKGROUND: Secondary prevention strategies after acute coronary syndrome (ACS) presentation with the use of drug combinations are essential to reduce the recurrence of cardiovascular events. However, lack of drug adherence is known to be common in this population and to be related to treatment failure. To improve drug adherence, we developed the "Mon Coeur, Mon BASIC" video. This online video has been specifically designed to inform patients about their disease and their current medications. Interactivity has been used to increase patient attention, and the video can also be viewed on smartphones and tablets. OBJECTIVE: The objective of this study was to assess the long-term impact of an informative web-based video on drug adherence in patients admitted for an ACS. METHODS: This randomized study was conducted with consecutive patients admitted to University Hospital of Lausanne for ACS. We randomized patients to an intervention group, which had access to the web-based video and a short interview with the pharmacist, and a control group receiving usual care. The primary outcome was the difference in drug adherence, assessed with the Adherence to Refills and Medication Scale (ARMS; 9 multiple-choice questions, scores ranging from 12 for perfect adherence to 48 for lack of adherence), between groups at 1, 3, and 6 months. We assessed the difference in ARMS score between both groups with the Wilcoxon rank sum test. Secondary outcomes were differences in knowledge, readmissions, and emergency room visits between groups and patients' satisfaction with the video. RESULTS: Sixty patients were included at baseline. The median age of the participants was 59 years (IQR 49-69), and 85% (51/60) were male. At 1 month, 51 patients participated in the follow-up, 50 patients participated at 3 months, and 47 patients participated at 6 months. The mean ARMS scores at 1 and 6 months did not differ between the intervention and control groups (13.24 vs 13.15, 13.52 vs 13.68, respectively). At 3 months, this score was significantly lower in the intervention group than in the control group (12.54 vs 13.75; P=.03). We observed significant increases in knowledge from baseline to 1 and 3 months, but not to 6 months, in the intervention group. Readmissions and emergency room visits have been very rare, and the proportion was not different among groups. Patients in the intervention group were highly satisfied with the video. CONCLUSIONS: Despite a lower sample size than we expected to reach, we observed that the "Mon Coeur, Mon BASIC" web-based interactive video improved patients' knowledge and seemed to have an impact on drug adherence. These results are encouraging, and the video will be offered to all patients admitted to our hospital with ACS. TRIAL REGISTRATION: ClinicalTrials.gov NCT03949608; https://clinicaltrials.gov/ct2/show/NCT03949608.

ST-segment elevation myocardial infarction: Management and association with prognosis during the COVID-19 pandemic in France.

BACKGROUND: Systems of care have been challenged to control progression of the COVID-19 pandemic. Whether this has been associated with delayed reperfusion and worse outcomes in French patients with ST-segment elevation myocardial infarction (STEMI) is unknown. AIM: To compare the rate of STEMI admissions, treatment delays, and outcomes between the first peak of the COVID-19 pandemic in France and the equivalent period in 2019. METHODS: In this nationwide French survey, data from consecutive STEMI patients from 65 centres referred for urgent revascularization between 1 March and 31 May 2020, and between 1 March and 31 May 2019, were analysed. The primary outcome was a composite of in-hospital death or non-fatal mechanical complications of acute myocardial infarction. RESULTS: A total of 6306 patients were included. During the pandemic peak, a 13.9±6.6% (P=0.003) decrease in STEMI admissions per week was observed. Delays between symptom onset and percutaneous coronary intervention were longer in 2020 versus 2019 (270 [interquartile range 150-705] vs 245 [140-646]min; P=0.013), driven by the increase in time from symptom onset to first medical contact (121 [60-360] vs 150 [62-420]min; P=0.002). During 2020, a greater number of mechanical complications was observed (0.9% vs 1.7%; P=0.029) leading to a significant difference in the primary outcome (112 patients [5.6%] in 2019 vs 129 [7.6%] in 2020; P=0.018). No significant difference was observed in rates of orotracheal intubation, in-hospital cardiac arrest, ventricular arrhythmias and cardiogenic shock. CONCLUSIONS: During the first peak of the COVID-19 pandemic in France, there was a decrease in STEMI admissions, associated with longer ischaemic time, exclusively driven by an increase in patient-related delays and an increase in mechanical complications. These findings suggest the need to encourage the population to seek medical help in case of symptoms.

Feasibility of Quantitative Flow Ratio in Adult Patients With Anomalous Aortic Origin of the Coronary Artery With 5 Years of Clinical Follow-up.

OBJECTIVES: Anomalous origin of the right coronary artery (ARCA) represents the most common form of abnormal coronary origin and may potentially increase the risk for sudden cardiac death. Morphological and functional evaluation of ARCA in adult patients referred for invasive coronary angiogram (ICA) is challenging. Quantitative flow ratio (QFR) is an available method able to virtually calculate fractional flow reserve using 3-dimensional quantitative coronary angiography (3D-QCA) based on ICA. We aimed to evaluate the feasibility of QFR analysis in patients with ARCA and its clinical impact. METHODS: Using the registry of proximal anomalous connections of coronary arteries (ANOCOR registry), a multicenter observational registry including 472 adult patients with ANOCOR between 2010 and 2013, we retrospectively performed QFR analysis from ICA and evaluated the rate of death, myocardial infarction, and unplanned revascularization at 5 years. RESULTS: Among 128 patients with ARCA, 41 (32%) could have QFR analysis with median clinical follow-up of 8.3 years. The mean QFR value was 0.90 ± 0.10, and 3D-QCA analysis showed preserved lumen area despite the elliptical shape of the proximal part of the ARCA, which in the worst cases appeared on ICA as a significant narrowing. The event rate was 12.2% (n = 5), including 3 deaths (1 due to cancer, 1 due to stroke, and 1 cause unknown) and 2 unplanned revascularizations at 5 years. No myocardial infarctions were reported. CONCLUSIONS: When QFR analysis of ARCA is feasible, non-significant QFR values are associated with good clinical outcome at 5 years.

Intracoronary Saline-Induced Hyperemia During Coronary Thermodilution Measurements of Absolute Coronary Blood Flow: An Animal Mechanistic Study.

Background Absolute hyperemic coronary blood flow and microvascular resistances can be measured by continuous thermodilution with a dedicated infusion catheter. We aimed to determine the mechanisms of this hyperemic response in animal. Methods and Results Twenty open chest pigs were instrumented with flow probes on coronary arteries. The following possible mechanisms of saline-induced hyperemia were explored compared with maximal hyperemia achieve with adenosine by testing: (1) various infusion rates; (2) various infusion content and temperature; (3) NO production inhibition with L-arginine methyl ester and endothelial denudation; (4) effects of vibrations generated by rotational atherectomy and of infusion through one end-hole versus side-holes. Saline infusion rates of 5, 10 and 15 mL/min did not reach maximal hyperemia as compared with adenosine. Percentage of coronary blood flow expressed in percent of the coronary blood flow after adenosine were 48±17% at baseline, 57±18% at 5 mL/min, 65±17% at 10 mL/min, 82±26% at 15 mL/min and 107±18% at 20 mL/min. Maximal hyperemia was observed during infusion of both saline at body temperature and glucose 5%, after endothelial denudation, l-arginine methyl ester administration, and after stent implantation. The activation of a Rota burr in the first millimeters of the epicardial artery also induced maximal hyperemia. Maximal hyperemia was achieved by infusion through lateral side-holes but not through an end-hole catheter. Conclusions Infusion of saline at 20 mL/min through a catheter with side holes in the first millimeters of the epicardial artery induces maximal hyperemia. The data indicate that this vasodilation is related neither to the composition/temperature of the indicator nor is it endothelial mediated. It is suggested that it could be elicited by epicardial wall vibrations.

Comparison of Side-Branch Dilation Techniques After Resorbable Magnesium Scaffold Implantation: A Bench Study.

BACKGROUND: The resorbable magnesium scaffold (RMS) has demonstrated a good safety profile to treat de novo lesions. Nevertheless, bifurcation lesions involving a side branch (SB) >2.0 mm in diameter were excluded from these studies, and such lesions remain technically challenging due to concerns of scaffold deformation or fracture. We sought to evaluate different SB dilation strategies after provisional T-stenting strategy with RMS using silicon bifurcation phantoms. METHODS AND RESULTS: Three different strategies were compared: proximal optimization technique (POT)-side-rePOT (rePOT), kissing-balloon inflation (KBI), and mini kissing-balloon inflation (MKBI) strategies. Strut and connector fractures were evaluated by micro computed tomography and apposition by optical coherence tomography (OCT). Twelve Magmaris scaffolds (Biotronik) were successfully implanted (4 in each group). There was no difference in strut and connector fractures among the three techniques, as no fracture was visualized. OCT demonstrated that MKBI significantly decreased global malapposition following SB inflation as compared with rePOT or KBI strategies (95.3% vs 88.3% of perfectly apposed struts [P<.001] and 93.6% [P<.01], respectively, for MKBI vs rePOT and KBI). After step-by-step over-expansion of 6 RMS devices with 3.75 mm, 4.0 mm, and 4.5 mm NC balloons at 16 atm (ie, +1.5 mm from the initial 3.0 mm RMS), no strut or connector fracture could be visualized. CONCLUSION: Provisional single-stent technique with the Magmaris RMS on a bifurcation lesion is technically feasible with these three different strategies without scaffold fracture. MKBI strategy resulted in better apposition rates as compared with KBI or rePOT strategies. Nevertheless, Magmaris use in bifurcation lesions should not be advised before similar results are confirmed by in vivo studies.

Pressure wire versus microcatheter for FFR measurement: a head-to-head comparison.

AIMS: Recently developed microcatheters can be used instead of a pressure wire for fractional flow reserve (FFR) measurement. We sought to assess the haemodynamic and clinical impact of using a larger profile device to measure FFR. METHODS AND RESULTS: Our prospective registry included 77 consecutive patients who underwent invasive FFR measurement of intermediate coronary stenoses between June 2015 and July 2016. FFR values were obtained first using a pressure wire only (FFRw), second using a Navvus microcatheter (FFRMC), and finally using the wire with the microcatheter still in the stenosis (FFRw-MC) during intravenous adenosine infusion. Eighty-eight stenoses were suitable for a thorough head-to-head comparison. Mean FFRw (0.83±0.08) was significantly higher than mean FFRMC (0.80±0.10) and FFRw-MC (0.80±0.10). Mean FFRMC and FFRw-MC did not differ significantly. Bland-Altman analysis showed a bias of -0.03±0.05 for lower FFRMC values compared to FFRw values. Using a threshold of 0.80 for FFR, the indication for revascularisation would have differed when based on FFRMC versus FFRw in 20/88 (23%) of the lesions and 18/77 (23%) of the patients. CONCLUSIONS: FFR measured using a microcatheter overestimates stenosis severity, leading to erroneous indication for revascularisation in a sizeable proportion of cases.

Clinical implications of guiding catheter extubation during fractional flow reserve measurements.

BACKGROUND: Fractional flow reserve (FFR) is defined by the maximal coronary flow ratio with and without stenosis. AIMS: We hypothesized that guiding catheter intubation in coronary ostia during FFR measurements may underestimate FFR value by limiting the increase of coronary flow during maximal hyperaemia. METHODS: Between June 2013 and January 2014, we prospectively included all patients with i.v. adenosine FFR measurements. FFR was measured with the guiding catheter intubated in the coronary ostia (FFRint) and extubated in the aorta (FFRext). We calculated the ratio between coronary ostium assessed by quantitative coronary angiography and guiding catheter surfaces, defined as the free ostial lumen ratio. RESULTS: In total, 151 lesions in 104 patients were included; 121 lesions and 88 patients were eligible for analysis. Mean±SD FFRext was significantly lower compared with FFRint; 0.82±0.08 and 0.84±0.08, respectively (P<0.001). Revascularization indication changed in 14 patients (16%). The difference induced by guiding extubation correlated significantly with the free ostial lumen ratio (R2=0.06, P=0.008). CONCLUSION: FFR value is significantly lower when the guiding catheter is extubated. The smaller the coronary ostium, the greater the difference observed between FFRext and FFRint. Guiding extubation during FFR measurements changed the revascularization indication in 16% of cases.

Saline-Induced Coronary Hyperemia: Mechanisms and Effects on Left Ventricular Function.

BACKGROUND: During thermodilution-based assessment of volumetric coronary blood flow, we observed that intracoronary infusion of saline increased coronary flow. This study aims to quantify the extent and unravel the mechanisms of saline-induced hyperemia. METHODS AND RESULTS: Thirty-three patients were studied; in 24 patients, intracoronary Doppler flow velocity measurements were performed at rest, after intracoronary adenosine, and during increasing infusion rates of saline at room temperature through a dedicated catheter with 4 lateral side holes. In 9 patients, global longitudinal strain and flow propagation velocity were assessed by transthoracic echocardiography during a prolonged intracoronary saline infusion. Taking adenosine-induced maximal hyperemia as reference, intracoronary infusion of saline at rates of 5, 10, 15, and 20 mL/min induced 6%, 46%, 111%, and 112% of maximal hyperemia, respectively. There was a close agreement of maximal saline- and adenosine-induced coronary flow reserve (intraclass correlation coefficient, 0.922; P<0.001). The same infusion rates given through 1 end hole (n=6) or in the contralateral artery (n=6) did not induce a significant increase in flow velocity. Intracoronary saline given on top of an intravenous infusion of adenosine did not further increase flow. Intracoronary saline infusion did not affect blood pressure, systolic, or diastolic left ventricular function. Heart rate decreased by 15% during saline infusion (P=0.021). CONCLUSIONS: Intracoronary infusion of saline at room temperature through a dedicated catheter for coronary thermodilution induces steady-state maximal hyperemia at a flow rate ≥15 mL/min. These findings open new possibilities to measure maximal absolute coronary blood flow and minimal microcirculatory resistance.

Diabetes does not impact the diagnostic performance of contrast-based fractional flow reserve: insights from the CONTRAST study.

BACKGROUND: Adenosine-free coronary pressure wire metrics have been proposed to test the functional significance of coronary artery lesions, but it is unexplored whether their diagnostic performance might be altered in patients with diabetes. METHODS: We performed a post-hoc analysis of the CONTRAST study, which prospectively enrolled an international cohort of patients undergoing routine fractional flow reserve (FFR) assessment for standard indications. Paired, repeated measurements of all physiology metrics (Pd/Pa, iFR, contrast-based FFR, and FFR) were made. A central core laboratory analyzed blinded pressure tracings in a standardized fashion. RESULTS: Of 763 subjects enrolled at 12 international centers, 219 (29%) had diabetes. The two groups were well-balanced for age, clinical presentation (stable or unstable), coronary vessel studied, volume and type of intracoronary contrast, and volume of intracoronary adenosine. A binary threshold of cFFR ≤ 0.83 produced an accuracy superior to both Pd/Pa and iFR when compared with FFR ≤ 0.80 in the absence of significant interaction with diabetes status; indeed, accuracy in subgroups of patients with or without diabetes was similar for cFFR (86.7 vs 85.4% respectively; p = 0.76), iFR (84.2 vs 80.0%, p = 0.29) and Pd/Pa (81.3 vs 78.9%, p = 0.55). There was no significant heterogeneity between patients with or without diabetes in terms of sensitivity and specificity of all metrics. The area under the receiver operating characteristic (ROC) curve was largest for cFFR compared with Pd/Pa and iFR which were equivalent (cFFR 0.961 and 0.928; Pd/Pa 0.916 and 0.870; iFR 0.911 and 0.861 in diabetic and non-diabetic patients respectively). CONCLUSIONS: cFFR provides superior diagnostic performance compared with Pd/Pa or iFR for predicting FFR irrespective of diabetes (clinicaltrials.gov identifier NCT02184117).

Continuum of Vasodilator Stress From Rest to Contrast Medium to Adenosine Hyperemia for Fractional Flow Reserve Assessment.

OBJECTIVES: This study compared the diagnostic performance with adenosine-derived fractional flow reserve (FFR) ≤0.8 of contrast-based FFR (cFFR), resting distal pressure (Pd)/aortic pressure (Pa), and the instantaneous wave-free ratio (iFR). BACKGROUND: FFR objectively identifies lesions that benefit from medical therapy versus revascularization. However, FFR requires maximal vasodilation, usually achieved with adenosine. Radiographic contrast injection causes submaximal coronary hyperemia. Therefore, intracoronary contrast could provide an easy and inexpensive tool for predicting FFR. METHODS: We recruited patients undergoing routine FFR assessment and made paired, repeated measurements of all physiology metrics (Pd/Pa, iFR, cFFR, and FFR). Contrast medium and dose were per local practice, as was the dose of intracoronary adenosine. Operators were encouraged to perform both intracoronary and intravenous adenosine assessments and a final drift check to assess wire calibration. A central core lab analyzed blinded pressure tracings in a standardized fashion. RESULTS: A total of 763 subjects were enrolled from 12 international centers. Contrast volume was 8 ± 2 ml per measurement, and 8 different contrast media were used. Repeated measurements of each metric showed a bias <0.005, but a lower SD (less variability) for cFFR than resting indexes. Although Pd/Pa and iFR demonstrated equivalent performance against FFR ≤0.8 (78.5% vs. 79.9% accuracy; p = 0.78; area under the receiver-operating characteristic curve: 0.875 vs. 0.881; p = 0.35), cFFR improved both metrics (85.8% accuracy and 0.930 area; p < 0.001 for each) with an optimal binary threshold of 0.83. A hybrid decision-making strategy using cFFR required adenosine less often than when based on either Pd/Pa or iFR. CONCLUSIONS: cFFR provides diagnostic performance superior to that of Pd/Pa or iFR for predicting FFR. For clinical scenarios or health care systems in which adenosine is contraindicated or prohibitively expensive, cFFR offers a universal technique to simplify invasive coronary physiological assessments. Yet FFR remains the reference standard for diagnostic certainty as even cFFR reached only ∼85% agreement.

Fractional Flow Reserve-Guided Revascularization in Patients With Aortic Stenosis.

Fractional flow reserve (FFR) has never been investigated in patients with aortic stenosis (AS). From 2002 to 2010, we identified 106 patients with AS and coronary artery disease with at least one intermediate lesion treated according to FFR guidance. We matched 212 contemporary control patients with AS in which revascularization was decided on angiography only. More patients in the FFR-guided group underwent percutaneous coronary intervention (24% vs 13%; p = 0.019), whereas there was a trend toward less coronary artery bypass grafting (CABG) performed. After FFR, the number of diseased vessels was downgraded within the FFR-guided group (from 1.85 ± 0.97 to 1.48 ± 1; p <0.01) and compared with the angio-guided group (1.48 ± 1 vs 1.8 ± 0.97; p <0.01). Less aortic valve replacement was reported in the FFR-guided group (46% vs 57%; p = 0.056). In patients who underwent CABG, less venous conduits (0.5 ± 0.69 vs 0.73 ± 0.76; p = 0.05) and anastomoses (0.61 ± 0.85 vs 0.94 ± 1; p = 0.032) were necessary in the FFR-guided group. Up to 5 years, we found no difference in major adverse cardiac events (38% vs 39%; p = 0.98), overall death (32% vs 31%; p = 0.68), nonfatal myocardial infarction (2% vs 2%; p = 0.79), and revascularization (8% vs 7%; p = 0.76) between the 2 groups. In conclusion, FFR guidance impacts the management of selected patients with moderate or severe AS and coronary artery disease by resulting into deferral of aortic valve replacement, more patients treated with percutaneous coronary intervention, and in patients treated with CABG, into less venous grafts and anastomoses without increasing adverse event rates up to 5 years.

Clinical Outcome of Patients with Aortic Stenosis and Coronary Artery Disease Not Treated According to Current Recommendations.

We evaluated the clinical outcome of patients with moderate/severe aortic stenosis and significant coronary disease not treated according to guidelines, recommending combined aortic valve replacement (AVR) and coronary artery bypass grafting (CABG). From 2002 to 2010, we assessed death up to 5 years in 650 patients with moderate/severe aortic stenosis and at least one coronary lesion (>50 %): 23 % were treated conservatively (MT), 17 % with percutaneous coronary intervention (PCI), 11 % with AVR, and 49 % with combined CABG and AVR. At a median follow-up of 58 months, overall death decreased over the groups (MT, 68 % vs. PCI, 44 % vs. AVR, 34 % vs. CABG and AVR, 23 %, p < 0.01). Compared to the MT group, Cox regression analysis adjusted for potential confounders showed significantly reduced mortality in the PCI, AVR, and CABG and AVR groups. When combined CABG and AVR is not feasible, PCI or AVR alone still improves significantly long-term survival as compared with MT alone.

Intracoronary Adenosine: Dose-Response Relationship With Hyperemia.

OBJECTIVES: The present study sought to establish the dosage of intracoronary (IC) adenosine associated with minimal side effects and above which no further increase in flow can be expected. BACKGROUND: Despite the widespread adoption of IC adenosine in clinical practice, no wide-ranging, dose-response study has been conducted. A recurring debate still exists regarding its optimal dose. METHODS: In 30 patients, Doppler-derived flow velocity measurements were obtained in 10 right coronary arteries (RCAs) and 20 left coronary arteries (LCAs) free of stenoses >20% in diameter. Flow velocity was measured at baseline and after 8 ml bolus administrations of arterial blood, saline, contrast medium, and 9 escalating doses of adenosine (4 to 500 µg). The hyperemic value was expressed in percent of the maximum flow velocity reached in a given artery (Q/Qmax, %). RESULTS: Q/Qmax did not increase significantly beyond dosages of 60 µg for the RCA and 160 µg for LCA. Heart rate did not change, whereas mean arterial blood pressure decreased by a maximum of 7% (p < 0.05) after bolus injections of IC adenosine. The incidence of transient A-V blocks was 40% after injection of 100 µg in the RCA and was 15% after injection of 200 µg in the LCA. The duration of the plateau reached 12 ± 13 s after injection of 100 µg in the RCA and 21 ± 6 s after the injection of 200 µg in the LCA. A progressive prolongation of the time needed to return to baseline was observed. Hyperemic response after injection of 8 ml of contrast medium reached 65 ± 36% of that achieved after injection of 200 µg of adenosine. CONCLUSIONS: This wide-ranging, dose-response study indicates that an IC adenosine bolus injection of 100 µg in the RCA and 200 µg in the LCA induces maximum hyperemia while being associated with minimal side effects.