Significance of Intermediate Values of Fractional Flow Reserve in Patients With Coronary Artery Disease.

BACKGROUND: The fractional flow reserve (FFR) value of 0.75 has been validated against ischemic testing, whereas the FFR value of 0.80 has been widely accepted to guide clinical decision making. However, revascularization when FFR is 0.76 to 0.80, within the so-called gray zone, is still debatable. METHODS AND RESULTS: From February 1997 to June 2013, all patients with single-segment disease and an FFR value within the gray zone or within the 2 neighboring FFR strata (0.70-0.75 and 0.81-0.85) were included. Study end points consisted of major adverse cardiovascular events (death, myocardial infarction, and any revascularization) up to 5 years. Of 17 380 FFR measurements, 1459 patients were included. Of them, 449 patients were treated with revascularization and 1010 patients were treated with medical therapy. In the gray zone, the major adverse cardiovascular events rate was similar (37 [13.9%] versus 21 [11.2%], respectively; P=0.3) between medical therapy and revascularization, whereas a strong trend toward a higher rate of death or myocardial infarction (25 [9.4] versus 9 [4.8], P=0.06) and overall death (20 [7.5] versus 6 [3.2], P=0.059) was observed in the medical therapy group. Among medical therapy patients, a significant step-up increase in major adverse cardiovascular events rate was observed across the 3 FFR strata, especially with proximal lesion location. In revascularization patients, the major adverse cardiovascular events rate was not different across the 3 FFR strata. CONCLUSIONS: FFR in and around the gray zone bears a major prognostic value, especially in proximal lesions. These data confirm that FFR≤0.80 is valid to guide clinical decision making.

First prospective multicenter experience with the 7 French Glidesheath slender for complex transradial coronary interventions.

PURPOSE: To assess the feasibility and safety of the 7 French (Fr) Glidesheath Slender for complex transradial (TR) percutaneous coronary interventions (PCI). BACKGROUND: The TR approach is increasingly used worldwide for coronary and peripheral vascular interventions. However, the small size of the radial artery remains an important limitation for the use of large-bore guiding catheters (>6 Fr), restricting thereby the treatment of highly complex lesions through the TR approach. The 7 Fr Glidesheath slender (Terumo, Tokyo, Japan) is a new dedicated radial sheath with a thinner wall and hydrophilic coating. It combines an inner diameter compatible with any 7 Fr guiding catheter and an outer diameter smaller than current 7 Fr sheaths. METHODS: Prospective multicenter registry of complex TR PCI cases using the 7 Fr Glidesheath Slender to determine the procedural success, rates of vascular complications, radial spasm, and radial artery occlusion (RAO). RESULTS: A total of 60 patients were included. Procedural success was 97% with only one access-site crossover. The use of a 7 Fr guiding catheter was indicated for the treatment of highly complex coronary lesions including distal left main (LM) disease (n = 20), complex non-LM bifurcation lesions (n = 16), chronic total occlusion (n = 15), and severely calcified vessels requiring rotational atherectomy (n = 10). There were three vascular access-site complications (4.7%) including two moderate (type II) local hematoma and one uncomplicated guiding catheter-induced brachial artery dissection. None of the patients experienced major bleeding. The occurrence of radial spasm was reported in seven patients (11%). Doppler ultrasound imaging of the radial artery at 1 month was available in 62 of 64 radial access with three cases of RAO (4.8%). CONCLUSIONS: Use of the 7 Fr Glidesheath slender for complex coronary interventions is feasible and associated with a high rate of procedural success and a low rate of vascular complications. These favorable results need be confirmed in larger multicenter studies. © 2016 Wiley Periodicals, Inc.

Clinical outcomes of secondary prevention strategies for young patients with cryptogenic stroke and patent foramen ovale.

Background The aim of this study was to compare the immediate and long-term clinical outcomes of medical therapy and percutaneous patent foramen ovale (PFO) closure as secondary prevention strategies in patients younger than 55 years of age presenting with cryptogenic stroke and PFO. Methods Between January 2006 and April 2015, all patients with the diagnosis of cryptogenic stroke and PFO were analysed and prospectively followed. Stroke was confirmed in 159 out of 309 patients (51%). In the remaining cases, other neurological conditions were found and therefore excluded from further analysis. Patients received PFO closure or medical therapy on the basis of a pre-specified algorithm. Primary outcome was the assessment of recurrent ischaemic events at follow-up. Results Percutaneous PFO closure was performed in 77 patients (48%) and 82 (52%) were treated medically. Mean follow-up was 51.6 ± 34.8 months. Two ischaemic strokes occurred in the medical group only (2.4% vs 0%; P = 0.16) and no complications related to the invasive procedure were observed. Conclusions The diagnosis of stroke in patients with PFO could be confirmed in 50% of cases only, underlining the importance of a multidisciplinary evaluation of these patients. A very low ischaemic recurrence rate was observed in the medical therapy group, suggesting that a personalized treatment based on a prespecified diagnostic algorithm yields good clinical results irrespective of the treatment modality. Given the low number of recurrences, larger cohorts may be needed to prove significant differences.

Deferral vs. performance of percutaneous coronary intervention of functionally non-significant coronary stenosis: 15-year follow-up of the DEFER trial.

AIMS: Stenting an angiographically intermediate but functionally non-significant stenosis is controversial. Nevertheless, it has been questioned if deferral of a functionally non-significant lesion on the basis of fractional flow reserve (FFR) measurement, is safe, especially on the long term. Five-year follow-up of the DEFER trial showed that outcome after deferral of percutaneous coronary intervention (PCI) of an intermediate coronary stenosis based on FFR ≥ 0.75 is excellent and was not improved by stenting. The aim of this study was to investigate the validity of this position on the very long term. METHODS AND RESULTS: In 325 patients scheduled for PCI of an intermediate stenosis, FFR was measured just before the planned intervention. If FFR was ≥0.75, patients were randomly assigned to deferral (Defer group; n = 91) or performance (Perform group; n = 90) of PCI. If FFR was <0.75, PCI was performed as planned (Reference group; n = 144). Clinical follow-up was 15 years. There were no differences in baseline clinical characteristics between the randomized groups. Complete 15-year follow-up was obtained in 92% of patients. After 15 years of follow-up, the rate of death was not different between the three groups: 33.0% in the Defer group, 31.1% in the Perform group, and 36.1% in the Reference group (Defer vs. Perform, RR 1.06, 95% CI: 0.69-1.62, P = 0.79). The rate of myocardial infarction was significantly lower in the Defer group (2.2%) compared with the Perform group (10.0%), RR 0.22, 95% CI: 0.05-0.99, P = 0.03. CONCLUSION: Deferral of PCI of a functionally non-significant stenosis is associated with a favourable very long-term follow-up without signs of late 'catch-up' phenomenon.

Prevalence, timing, and haemodynamic correlates of prodromes in patients with vasovagal syncope induced by head-up tilt test.

AIMS: To evaluate the prevalence, timing, and haemodynamic characteristics of prodromal symptoms in patients experiencing vasovagal syncope (VVS) during a head-up tilt test (HUT) potentiated with nitroglycerin, and their relationships with those reported before spontaneous episodes. METHODS AND RESULTS: Symptoms preceding HUT-induced syncope were recorded, together with heart rate (HR) and arterial blood pressure (BP) values, in 149 otherwise healthy and drug-free subjects with recurrent unexplained syncope. Head-up tilt test significantly increase the number of patients capable of recognizing the premonitory symptoms of VVS than before spontaneous episodes (96 vs. 79%; P<0.001). The nine most frequent symptoms were stratified into three groups on the basis of their characteristics: headache, hot flashes, and palpitations occurred more than 3 min before syncope, with a very slight reduction in BP; nausea, asthenia, diaphoresis, vertigo, and epigastric discomfort preceded syncope by 1-3 min and were associated with a slight reduction in BP; and blurred vision appeared the last minute before syncope and was characterized by the lowest BP and HR values. CONCLUSION: In comparison with spontaneous syncopal episodes, HUT allows the more frequent recognition of prodromes also providing useful information in terms of timing and haemodynamic characteristics of symptoms that may allow more tailored patient counselling.

Visual and Quantitative Assessment of Coronary Stenoses at Angiography Versus Fractional Flow Reserve: The Impact of Risk Factors.

BACKGROUND: The correlation between angiographic assessment of coronary stenoses and fractional flow reserve (FFR) is weak. Whether and how risk factors impact the diagnostic accuracy of angiography is unknown. We sought to evaluate the diagnostic accuracy of angiography by visual estimate and by quantitative coronary angiography when compared with FFR and evaluate the influence of risk factors (RF) on this accuracy. METHODS AND RESULTS: In 1382 coronary stenoses (1104 patients), percent diameter stenosis by visual estimation (DSVE) and by quantitative coronary angiography (DSQCA) was compared with FFR. Patients were divided into 4 subgroups, according to the presence of RFs, and the relationship between DSVE, DSQCA, and FFR was analyzed. Overall, DSVE was significantly higher than DSQCA (P<0.0001); nonetheless, when examined by strata of DS, DSVE was significantly smaller than DSQCA in mild stenoses, although the reverse held true for severe stenoses. Compared with FFR, a large scatter was observed for both DSVE and DSQCA. When using a dichotomous FFR value of 0.80, C statistic was significantly higher for DSVE than for DSQCA (0.712 versus 0.640, respectively; P<0.001). C statistics for DSVE decreased progressively as RFs accumulated (0.776 for ≤1 RF, 0.750 for 2 RFs, 0.713 for 3 RFs and 0.627 for ≥4 RFs; P=0.0053). In addition, in diabetics, the relationship between FFR and angiographic indices was particularly weak (C statistics: 0.524 for DSVE and 0.511 for DSQCA). CONCLUSIONS: Overall, DSVE has a better diagnostic accuracy than DSQCA to predict the functional significance of coronary stenosis. The predictive accuracy of angiography is moderate in patients with ≤1 RFs, but weakens as RFs accumulate, especially in diabetics.

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.

Overview of the clinical trials on bioresorbable vascular scaffold.

Although several new scaffolds are progressively being investigated and entering the clinical scene, BRS has accumulated the largest experience by far including detailed evaluation of the first patients studied followed almost in parallel by clinical evaluation and worldwide randomized evaluation for non-inferiority against best contemporary metallic DES. Available evidence shows that careful procedural technique is required for proper and safe delivery of the current generation scaffolds. Future studies will indicate whether all or only selected patient or lesion subsets will ultimately benefit from treatment with fully bioresorbable devices.

The present day potential role of fractional flow reserve-guided coronary artery bypass graft surgery.

The favorable impact of fractional flow reserve measurements on the decision-making and overall outcomes of percutaneous coronary artery intervention is well established. However, the clinical application of fractional flow reserve in surgical revascularizations is still debated. The purpose of this article is to provide a comprehensive review on the current potential role of fractional flow reserve guidance in coronary artery bypass grafting.

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.

Diagnostic Accuracy of Fast Computational Approaches to Derive Fractional Flow Reserve From Diagnostic Coronary Angiography: The International Multicenter FAVOR Pilot Study.

OBJECTIVES: The aim of this prospective multicenter study was to identify the optimal approach for simple and fast fractional flow reserve (FFR) computation from radiographic coronary angiography, called quantitative flow ratio (QFR). BACKGROUND: A novel, rapid computation of QFR pullbacks from 3-dimensional quantitative coronary angiography was developed recently. METHODS: QFR was derived from 3 flow models with: 1) fixed empiric hyperemic flow velocity (fixed-flow QFR [fQFR]); 2) modeled hyperemic flow velocity derived from angiography without drug-induced hyperemia (contrast-flow QFR [cQFR]); and 3) measured hyperemic flow velocity derived from angiography during adenosine-induced hyperemia (adenosine-flow QFR [aQFR]). Pressure wire-derived FFR, measured during maximal hyperemia, served as the reference. Separate independent core laboratories analyzed angiographic images and pressure tracings from 8 centers in 7 countries. RESULTS: The QFR and FFR from 84 vessels in 73 patients with intermediate coronary lesions were compared. Mean angiographic percent diameter stenosis (DS%) was 46.1 ± 8.9%; 27 vessels (32%) had FFR ≤ 0.80. Good agreement with FFR was observed for fQFR, cQFR, and aQFR, with mean differences of 0.003 ± 0.068 (p = 0.66), 0.001 ± 0.059 (p = 0.90), and -0.001 ± 0.065 (p = 0.90), respectively. The overall diagnostic accuracy for identifying an FFR of ≤0.80 was 80% (95% confidence interval [CI]: 71% to 89%), 86% (95% CI: 78% to 93%), and 87% (95% CI: 80% to 94%). The area under the receiver-operating characteristic curve was higher for cQFR than fQFR (difference: 0.04; 95% CI: 0.01 to 0.08; p < 0.01), but did not differ significantly between cQFR and aQFR (difference: 0.01; 95% CI: -0.04 to 0.06; p = 0.65). Compared with DS%, both cQFR and aQFR increased the area under the receiver-operating characteristic curve by 0.20 (p < 0.01) and 0.19 (p < 0.01). The positive likelihood ratio was 4.8, 8.4, and 8.9 for fQFR, cQFR, and aQFR, with negative likelihood ratio of 0.4, 0.3, and 0.2, respectively. CONCLUSIONS: The QFR computation improved the diagnostic accuracy of 3-dimensional quantitative coronary angiography-based identification of stenosis significance. The favorable results of cQFR that does not require pharmacologic hyperemia induction bears the potential of a wider adoption of FFR-based lesion assessment through a reduction in procedure time, risk, and costs.

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.

iFR-FFR comparison in daily practice: a single-center, prospective, online assessment.

AIMS: To compare the performance of instantaneous wave-free ratio (iFR) with fractional flow reserve (FFR) in a real-life, prospective, single-center, and independent study. METHODS AND RESULTS: Fifty-four patients were included and 89 angiographic intermediate lesions underwent functional evaluation with both iFR and FFR. FFR was used as the gold standard, and the patients having FFR values 0.80 or less only underwent percutaneous coronary intervention. Linear regression demonstrated close agreement between the two techniques (R = 0.83, P < 0.0001). Receiver operator characteristic analysis confirmed the strong correlation, with an area under the curve approximately equal to unity. iFR detected ischemia with a sensitivity and specificity of 100 and 87%, respectively, thus revealing a positive predictive value of 78% and a negative predictive value of 100%. In addition, according to FFR assessment, percutaneous coronary intervention was performed on 39 lesions (43.8%) in 27 patients (50%), whereas positive iFR values were found in 52 lesions (+14.6% compared with FFR). At clinical follow-up (ranging from 6 to 16 months), all patients remained asymptomatic and none of them experienced major adverse cardiovascular events. CONCLUSIONS: In this independent, online, comparison of iFR-FFR values in patients with angiographic intermediate lesions, results are consistent with those derived from previous offline controlled trials, and support the correlation between iFR and FFR in daily clinical practice.

Single String Technique for Coronary Bifurcation Stenting: Detailed Technical Evaluation and Feasibility Analysis.

OBJECTIVES: The study aimed to evaluate the adequacy and feasibility of the single string bifurcation stenting technique. BACKGROUND: Double-stent techniques may be required for complex bifurcations. Currently applied methods all have their morphological or structural limitations with respect to wall coverage, multiple strut layers, and apposition rate. METHODS: Single string is a novel method in which, first, the side branch (SB) stent is deployed with a single stent cell protruding into the main branch (MB). Second, the MB stent is deployed across this protruding stent cell. The procedure is completed by final kissing balloon dilation. The single string technique was first tested in vitro (n = 20) and next applied in patients (n = 11) with complex bifurcation stenoses. RESULTS: All procedures were performed successfully, crossing a single stent cell in 100%. Procedure duration was 23.0 ± 7.9 min, and the fluoroscopy time was 9.4 ± 3.5 min. The results were evaluated by optical coherence tomography, showing fully apposed struts in 83.0 ± 9.2% in the bifurcation area. Residual area obstruction in the MB was 6.4 ± 5.6% and 25.0 ± 16.9% in the SB, as evaluated by micro computed tomography. All the human cases were performed successfully with excellent angiographic results: the residual area stenosis was 27 ± 8% and 29 ± 10% in the MB and in the SB, respectively, by 3-dimensional quantitative coronary angiography. No relevant periprocedural enzyme increase was observed. During follow-up (6 ± 4 months), no adverse clinical events (death, myocardial infarction, target vessel revascularization) were noted. CONCLUSIONS: The single string technique for complex bifurcation dilation was shown to be adequate in vitro and feasible in humans, with favorable results in terms of stent overlap, malapposition rate, and low residual obstruction in both the MB and SB.

Single-side renal sympathetic denervation to treat malignant refractory hypertension in a solitary kidney patient.

Renal sympathetic denervation (RSD) is emerging as a new therapeutic option for patients with severe hypertension refractory to medical therapy. Patients affected by renovascular or anatomical abnormalities have hitherto been systematically excluded from clinical trials with RSD because of concern about safety and the unknown efficacy of the procedure in this subgroup of patients. We describe the management of a case of RSD in a single-kidney patient with refractory hypertension; the patient had had a previous surgical right nephrectomy for renal cell carcinoma that subsequently required no other oncologic treatment. After multidisciplinary assessment, the patient underwent RSD. The procedure was performed through a 6F femoral access using the Symplicity™ RSD system (Medtronic, Mountain View, CA, USA). Radiofrequency was applied to the renal artery wall in 6 different points under general sedation with midazolam to control back pain caused by the procedure, that was performed without periprocedural complications. The patient was discharged 2 days later after a control of the vascular access site and routine biochemical examinations. The following 9-month follow up showed a significant reduction in blood pressure and stable renal function, without signs of renal damage. Our report confirms the feasibility of RSD in this delicate context, without evident negative effects on kidney function and with a significant reduction in blood pressure. Future studies are needed to fully clarify the value of RSD in single-kidney patients.