Simplified hybrid algorithms for pressure wire interrogation exploiting advantages of a baseline and contrast Pd/Pa ratio indexes to predict stenosis significance: Insight from the SPARE multicenter prospective study.

BACKGROUND: Simplification of functional stenosis assessment with pressure guidewires may facilitate adoption of physiology-guided revascularization. An important step in this regard is the avoidance of hyperemic agents, required for fractional flow reserve (FFR) calculation. We evaluate the merits of a hybrid algorithms that combines the translesional pressure ratio (Pd/Pa) obtained at rest, after contrast medium injection (cFFR) and after adenosine administration (FFR). METHODS AND RESULTS: Eighty-six patients with 108 de novo intermediate coronary stenoses were included in this prospective, multicenter study. Using prespecified cut-off values that correctly identified stenosis with a 95% of agreement (<0.89 and >0.96 for Pd/Pa; <0.84 and > 0.87 for cFFR) we tested the efficiency of three different multi-step strategies combining the three indices to classify stenosis severity, using FFR-only measurement as reference. All three different hybrid algorithms (Pd/Pa-FFR; cFFR-FFR; Pd/Pa-cFFR-FFR) have more than 95% of agreement with FFR. Yet, the novel Pd/Pa-cFFR-FFR hybrid strategy demonstrated the best performance, avoiding the need of adenosine and medium contrast in 90% and 48% of cases, respectively. CONCLUSIONS: A hybrid Pd/Pa-cFFR-FFR decision-making algorithm could be an alternative and valuable strategy to increase the adoption of a physiology-guided PCI using conventional pressure guidewires and consoles.

Wave intensity analysis and its application to the coronary circulation.

Wave intensity analysis (WIA) is a technique developed from the field of gas dynamics that is now being applied to assess cardiovascular physiology. It allows quantification of the forces acting to alter flow and pressure within a fluid system, and as such it is highly insightful in ascribing cause to dynamic blood pressure or velocity changes. When co-incident waves arrive at the same spatial location they exert either counteracting or summative effects on flow and pressure. WIA however allows waves of different origins to be measured uninfluenced by other simultaneously arriving waves. It therefore has found particular applicability within the coronary circulation where both proximal (aortic) and distal (myocardial) ends of the coronary artery can markedly influence blood flow. Using these concepts, a repeating pattern of 6 waves has been consistently identified within the coronary arteries, 3 originating proximally and 3 distally. Each has been associated with a particular part of the cardiac cycle. The most clinically relevant wave to date is the backward decompression wave, which causes the marked increase in coronary flow velocity observed at the start of the diastole. It has been proposed that this wave is generated by the elastic re-expansion of the intra-myocardial blood vessels that are compressed during systolic contraction. Particularly by quantifying this wave, WIA has been used to provide mechanistic and prognostic insight into a number of conditions including aortic stenosis, left ventricular hypertrophy, coronary artery disease and heart failure. It has proven itself to be highly sensitive and as such a number of novel research directions are encouraged where further insights would be beneficial.

Optimizing vessel healing following drug eluting stent implantation with biodegradable polymer DES.

The introduction of coronary drug eluting stents (DES) more than 10 years ago drastically decreased the occurrence of restenosis, compared with first generation bare metal stents (BMS). However, the optimism created by the first studies was soon shadowed by the demonstration of higher rates of late and very late stent thrombosis (ST). The research performed in this phenomenon highlighted the causative role played by incomplete stent strut coverage, hypersensitivity reactions caused by the drug eluting polymer, and neoatherosclerosis, all markers of an inadequate vascular response to DES implantation. Over the following years, new development in stent and eluting polymer technologies have been incorporated in second generation DES to optimize the process of vessel healing and, thus, to avoid these complications. Furthermore, it is envisaged that adequate vessel healing would be followed by less dependence on double antiplatelet, a limiting aspect for DES use in different clinical scenarios. In this review, we focused on the use of biodegradable eluting polymers to increase DES safety, revisiting the rationale for its use and the synergic action with other changes in stent technology aimed to optimize vessel healing after DES implantation.

Use of fractional flow reserve in contemporary scenarios of coronary revascularization.

Fractional flow reserve (FFR), an invasive pressure-derived index of stenosis severity, can be performed easily, rapidly, and safely in patients with coronary artery disease as a surrogate of non-invasive detection of ischemia. Over the last decades, profound clinical and scientific evaluation has demonstrated that FFR is one of the few diagnostic modalities that improve patient outcome and, at the same time, are cost-effective and cost-saving. The increasing use of PCI to treat multivessel disease and complex anatomical subsets has created new demands for accurate, "per stenosis" assessment, since revascularisation should be performed only in those stenosis that are ischaemia generating. Recent studies have demonstrated that this attitude results in better patient outcomes. Altogether, current evidence clearly supports the measurement of FFR in catheterization laboratories in order to provide objective and complementary data to coronary angiography. The purpose of this review is to discuss the value of FFR in the diagnosis and treatment of patients with different anatomical subsets, including intermediate stenosis, multivessel disease, left main disease, serial stenosis, ostial and bifurcation lesions, saphenous vein graft disease and in-stent restenosis, as well as in those presenting with acute coronary syndromes.

A national programme for patient and staff dose monitoring in interventional cardiology.

A national programme on patient and staff dose evaluation in interventional cardiology made in cooperation with the haemodynamic section of the Spanish Society of Cardiology has recently been launched. Its aim is to propose a set of national diagnostic reference levels (DRLs) for patients as recommended by the International Commission on Radiological Protection and to initiate several optimisation actions to improve radiological protection of both patients and staff. Six hospitals have joined the programme and accepted to submit their data to a central database. First to be acquired were the quality control data of the X-ray systems and radiation doses of patients and professionals. The results from 9 X-ray systems, 1467 procedures and staff doses from 43 professionals were gathered. Provisional DRLs resulted in 44 Gy cm(2) for coronary angiography and 78 Gy cm(2) for interventions. The X-ray systems varied up to a factor of 5 for dose rates in reference conditions. Staff doses showed that 50 % of interventional cardiologists do not use their personal dosemeters correctly.

Clinical variables related with in-stent restenosis late regression after bare metal coronary stenting

In-stent restenosis (ISR) has an incidence between 20% and 30% using bare metal stents. ISR late regression phenomenon (ISRLR) has been previously described, but clinical variables related with this phenomenon remain unclear. The aim of the study was to identify the variables related with ISRLR. METHODS: We identified from our data base 30 patients between November 1995 and September 2002 that fulfilled the following criteria: 1) Documented ISR at follow-up angiography (CA-1); 2) treated medically; and 3) Referred for a second follow-up angiography (CA-2). at least 3 months after CA-1. ISRLR was defined as a > 0.2 mm increase in MLD between CA-1 and CA-2, calculated as the 2-fold of our inter-observer variability. ISR late progression was defined as a > 0.2 mm decrease in minimum lumen diameter (MLD) between CA-1 and CA-2. RESULTS: At the time of CA-2 only 2 patients (6.7%) had symptoms related with the previously stented vessel. We found a mean MLD of 1.03+/-0.34 mm and 1.54+/-0.48 mm at CA-1 and CA-2 respectively (AMLD = 0.51 +/-0.34 mm; p < 0.001). Twenty four patients (80.0%) had ISRLR. Two variables were related to the presence or absence ISRLR: Current smoking at the time of coronary stenting (70.8% vs 20.0% respectively, p = 0.026) and acute coronary syndrome as clinical indication for coronary stenting (and 83.5% vs 40.0% respectively, p = 0.029). CONCLUSION: ISRLR is a frequent phenomenon in patients with ISR treated medically, probably contributing to the benign long-term clinical outcome that has been previously described in patients with asymptomatic or mildly symptomatic ISR. Current smoking at the time of coronary stenting and acute coronary syndrome as clinical indication for coronary stenting are associated with this phenomenon.

Findings of intravascular ultrasound during acute stent thrombosis.

OBJECTIVE: To evaluate the potential role of intravascular ultrasound (IVUS) in evaluating patients experiencing an episode of acute stent thrombosis. DESIGN AND SETTING: Prospective observational study in a cardiac catheterisation laboratory in a university teaching hospital. PATIENTS AND INTERVENTIONS: IVUS was used to examine 12 patients undergoing coronary interventions for stent thrombosis to gain further mechanistic insights and to guide treatment. IVUS studies were obtained before and after intervention with a motorised pullback device. MAIN OUTCOME MEASURES: Qualitative and volumetric IVUS analyses. RESULTS: Angiographically, 10 patients had occluded vessels and two patients had intraluminal filling defects within the stent. IVUS showed an occlusive thrombus in all patients. Thrombus volume was 90 (77) mm3, which was 51 (21)% of total stent volume. There was evidence of severe stent underexpansion in most patients and no patient fulfilled standard criteria for optimal stent implantation. Stent malapposition was detected in four patients, edge dissections were seen in two patients, and significant inflow-outflow disease was present in 11 patients. During interventions IVUS findings led to the use of higher pressures or larger balloons than those used during initial stenting in 10 patients. In addition, four patients required additional stenting, whereas a thrombectomy device alone was selected for one patient. After the procedure final minimum stent area (7.1 (2.1) v 5.3 (2) mm2, p < 0.005) and stent expansion (83.2 (17) v 62.1 (15)%, p < 0.005) improved compared with pre-interventional values. However, residual lining thrombus was still visualised in eight patients (25 (19) mm3, accounting for a 17% of final stent volume). CONCLUSIONS: IVUS provides an attractive technique to characterise fully the pattern of stent thrombosis, to identify readily the underlying mechanical predisposing factors, and to guide repeated coronary interventions.

Predictors of failure in direct stenting in the real world.

INTRODUCTION: Stent implantation without predilation simplifies a large proportion of coronary intervention procedures, with a significant reduction in costs and procedure time. OBJECTIVES: To determine the variables associated with a higher probability of failure in direct stent implantation in daily practice in a wide range of clinical contexts and types of lesions. POPULATION AND METHODS: Over a period of 28 months, direct implantation of 931 stents was attempted in our Center (811 patients, 83% male, mean age 62 +/- 12 years; 1.1 stent per patient). In 59 patients (7.3%), balloon predilation was necessary, and the factors associated with direct implant failure were determined. RESULTS: The vessels treated were: anterior descending (373 lesions: 40.1%), right coronary artery (306 lesions: 32.9%, circumflex (210 lesions: 22.6%), saphenous vein (35 lesions: 3.8%), left main (5 lesions: 0.4%) and internal mammary artery (2 lesions: 0.2%). 54% of the lesions were of type B2/C (ACC/AHA classification). The characteristics significantly associated with, or with statistical tendency towards, a lower success rate in direct stent implantation were: Lesion in the circumflex (11% vs. 5.5%, p = 0.012); reference vessel diameter less than 3.0 mm (9.8% vs. 6.2%, p = 0.097); age over 65 years (8.5% vs. 4.5%, p = 0.017); left main disease, irrespective of the vessel treated (23.5%% vs. 6.5%, p = 0.023); B2/C lesion (7.8%, vs. 4.8%, p = 0.086); calcification (9.9% vs. 4.9%, p = 0.012); vessel angulation greater than 45 degrees (9.9% vs. 4.9%, p = 0.009); and Express stent implant (19.6% vs. 6.0%, p < 0.001). On multivariate analysis, independent predictors of failure in direct stent implantation were: left main lesion (RR 6.6; 95% CI 1.73-24.93; p = 0.013), presence of calcium (RR 1.9; 95% CI 1.02-3.37; p = 0.049), vessel curvature (RR 2.0; 95% CI 1.13-3.64; p = 0.018), reference vessel diameter less than 3 mm (RR 2.2; 95% CI 1.15-4.32; p = 0.023), lesion type B2/C (RR 1.9; 95% CI 1.0-3.52; p = 0.044) and Express stent (RR 2.7; 95% CI 1.07-6.79; p = 0.05). CONCLUSION: In a large and heterogeneous series of patients, direct stenting was not possible in 7.3% of cases, which required balloon predilation. Certain clinical and angiographic features can predict when this is more like to occur.

Effects of bosentan on neointimal response following coronary angioplasty.

BACKGROUND: Endothelins are important vasoconstrictors and cellular-growth promoters. ETA-specific antagonists have been shown to reduce neointimal response to injury in some experimental angioplasty models. However, there is little information on the effects of dual ETA/ETB receptor blockers, such as bosentan, on neointimal proliferation following experimental coronary angioplasty. MATERIALS AND METHODS: Coronary injury was achieved by directional atherectomy in the left anterior descending artery of 20 pigs. Animals were randomly assigned to receive a daily dose of oral bosentan (30 mg kg-1) (group I, n = 10) or no treatment (group II, n = 10). At 4 weeks, arteries were processed for histomorphometry and endothelin characterization. RESULTS: Vessel injury score was similar among the two groups. Overall, a linear correlation was found between injury and neointimal development (r = 0.57, P = 0.01). This correlation had a lower slope in group I compared with group II (P < 0.001), indicating a smaller amount of neointimal development for a similar degree of injury in bosentan-treated animals. Multivariate regression showed that neointimal response was reduced by oral treatment with bosentan (beta: -0.59 mm2, 95% CI: -1.11/-0.06 mm2). In addition, immunostaining revealed fewer positive endothelin areas in group I arteries. CONCLUSIONS: Oral treatment with bosentan reduces neointimal development following coronary angioplasty in this experimental model.

Morning cortisol production in coronary heart disease patients.

BACKGROUND: The circadian cycle of the endogenous anti-inflammatory system (EAIS) is characterized by a morning increase in cortisol production. Circulating interleukin-6 (IL-6) activates the EAIS. A circadian variation in the onset of myocardial infarction, sudden death, stable angina (SA) and unstable angina (UA) has been reported. The aim of this study was to determine morning cortisol production in coronary heart disease (CHD) patients. MATERIALS AND METHODS: Serum cortisol and IL-6 were measured in 129 patients with either SA (n = 65) or UA (n = 64) and 40 healthy volunteers. Blood samples were taken between 9 : 00 h and 12 : 00 h. The upper normal range of cortisol (25 microg dL-1) was used as a reference to classify patients. RESULTS: Forty-eight patients had elevated cortisol levels (ECL) (32.5 +/- 5.4 microg dL-1), while 81 patients had normal cortisol levels (NCL) (15.7 +/- 5.9 microg dL-1). In NCL patients, IL-6 levels (26.6 pg mL-1, ranged from 0.2 to 183.7) were significantly higher (P < 0.004) than in ECL patients (9.70 pg mL-1, range 0.07-56.5). Forty-eight patients with UA belonged to the NCL group of patients, while only 16 UA patients belonged to the ECL group (chi(2) = 0.000). Thirty-two patients with SA belonged to the ECL group, and 33 to the NCL group (chi(2) = 0.08). CONCLUSIONS: Patients with 'inappropriately' normal morning cortisol production had high IL-6 levels. 'Inappropriately' normal cortisol, detected in 75% of UA and 50% of SA patients, may be insufficient for limiting inflammation. These findings have novel clinical implications and suggest new therapeutic approaches in the treatment of these patients.

[Effect of cAMP on the function of endothelial cells and fibromuscular proliferation after the injury of the carotid and coronary arteries in a porcine model]. / Efecto del AMPc sobre la función de las células endoteliales y la proliferación fibromuscular tras la lesión de las arterias carótida y coronaria en un modelo porcino.

INTRODUCTION AND OBJECTIVE: Reendothelization of damaged blood vessels protects against the vascular injury response. We evaluated in vivo whether a systemic increase in cAMP accelerates reendothelization and attenuates intimal hyperplasia in injured swine carotid and coronary arteries. METHODS: Both carotid arteries of 10 swines were subjected to balloon injury. Five animals had been treated with 2 ml (10 mg) of Forskolin, an activator of the adenylate cyclase, and another 5 with 2 ml of saline solution. These animals were sacrificed at day 8, and carotid artery reendothelization was evaluated. The descendent coronary (DC) artery of another 19 pigs was injured by atherotome. Nine animals had been treated with 2 ml of Forskolin, and another 10 with 2 ml of saline solution. These animals were sacrificed at day 28, with myointimal proliferation and arterial geometric remodelation being evaluated. Likewise, in these animals intracellular cAMP levels were measured at baseline and 28 and 60 minutes after saline solution or Forskolin administration and 90 min after arterial injury. RESULTS: Eight days after balloon injury, carotid artery reendothelization was greater in the Forskolin-treated group compared with the control group (p = 0.02), and the number of CD31 positive cells was statistically increased in the treated group (38 +/- 11 cells) versus controls (11 +/- 9 cells). Although the degree of vascular injury caused by atherotome was similar in all of the arteries in the control group, restenosis was only observed in 40% of these animals. Correlation analysis demonstrated that intracellular cAMP may condition arterial geometric remodeling and the diameter of the lumen after vascular injury. CONCLUSION: Our results suggest that cAMP may promote reendothelization and attenuate fibromuscular proliferation.

Acute stent thrombosis visualized by intravascular ultrasound.

Subacute stent thrombosis is currently a rare but feared complication in patients undergoing coronary intervention. Intravascular ultrasound is a useful technique to guide stent implantation. However, its value in patients suffering from acute stent thrombosis has not been described. Herein, we present the intravascular ultrasound findings of a patient experiencing ongoing stent thrombosis and impending vessel closure.

Fractional flow reserve to determine the appropriateness of angioplasty in moderate coronary stenosis: a randomized trial.

BACKGROUND: PTCA of a coronary stenosis without documented ischemia at noninvasive stress testing is often performed, but its benefit is unproven. Coronary pressure-derived fractional flow reserve (FFR) is an invasive index of stenosis severity that is a reliable substitute for noninvasive stress testing. A value of 0.75 identifies stenoses with hemodynamic significance. METHODS AND RESULTS: In 325 patients for whom PTCA was planned and who did not have documented ischemia, FFR of the stenosis was measured. If FFR was >0.75, patients were randomly assigned to deferral (deferral group; n=91) or performance (performance group; n=90) of PTCA. If FFR was <0.75, PTCA was performed as planned (reference group; n=144). Clinical follow-up was obtained at 1, 3, 6, 12, and 24 months. Event-free survival was similar between the deferral and performance groups (92% versus 89% at 12 months and 89% versus 83% at 24 months) but was significantly lower in the reference group (80% at 12 months and 78% at 24 months). In addition, the percentage of patients free from angina was similar between the deferral and performance groups (49% versus 50% at 12 months and 70% versus 51% at 24 months) but was significantly higher in the reference group (67% at 12 and 80% at 24 months). CONCLUSIONS: In patients with a coronary stenosis without evidence of ischemia, coronary pressure-derived FFR identifies those who will benefit from PTCA.

Endogenous anti-inflammatory response after coronary injury in a porcine model.

BACKGROUND: Corticotropin-releasing hormone (CRH)/adrenocorticotropic hormone (ACTH)/cortisol is the major anti-inflammatory system. After percutaneous translumenal angioplasty, an inflammatory process is triggered. We investigate whether CRH/ACTH/cortisol axis is activated after deep vessel wall injury (DVWI). MATERIALS AND METHODS: Plasma and leukocyte CRH and ACTH, serum cortisol and IL-1beta, and leukocyte cAMP were measured (ELISA) in 16 pigs after anaesthesia (baseline), 60 min into anaesthesia without causing vascular injury and 90 min after DVWI of the left anterior descending (LAD) coronary artery induced by percutaneous directional atherectomy (Atherocath GTO 7F; DVI, Inc., Temecula, USA). Biochemical variables were also measured at baseline, 60 and 180 min into anaesthesia in six additional pigs without coronary intervention. RESULTS: MANOVA showed that CRH/ACTH/Cortisol, cAMP and IL-1beta production was not modified during anaesthesia. Post-DVWI plasma CRH (0.077 +/- 0.046 ng mL-1), and cellular cAMP (0.14 +/- 0.067 pmol 10(-6) cells) increased significantly (P = 0.001) with respect to their baseline values (CRH = 0.036 +/- 0.013 ng mL-1; cAMP = 0.081 +/- 0.034 pmol 10-6). There was also a statistically significant increase (P = 0.02) in post-DVWI IL-1beta (from 46.6 +/- 12.8 to 64.05 +/- 13.5 pg mL-1), and in serum cortisol (P = 0.05) compared to its baseline values (8.98 +/- 3.2 microgr dL-1 vs. 6.57 +/- 2.3 microgr dL-1, respectively). CONCLUSION: In our experimental model, coronary vessel wall injury-activated CRH/ACTH/cortisol axis caused a significant increase in plasma CRH, cortisol and cellular cAMP levels, which may influence the response of coronary arteries to injury.

Initial results and long-term clinical and angiographic outcome of coronary stenting in women.

To assess whether gender influences the results of coronary stenting, 158 consecutive women undergoing coronary stenting were compared with 823 consecutive men. Women had more adverse baseline characteristics, a higher hospital mortality, and were independently associated with procedural failure/complications (relative risk 2.4, 95% confidence interval 1.2 to 4.8); however, the long-term event-free survival and the restenosis rate were not influenced by gender.

Fate of stent-related side branches after coronary intervention in patients with in-stent restenosis.

OBJECTIVES: We sought to assess the fate of stent (ST)-related side branches (SB) after coronary intervention in patients with in-ST restenosis. BACKGROUND: In-ST restenosis constitutes a therapeutic challenge. Although the fate of lesion-related SB after conventional angioplasty or initial coronary stenting is well established, the outcome of ST-related SB in patients with in-ST restenosis undergoing repeat intervention is unknown. METHODS: One hundred consecutive patients (age 61 +/- 11 years, 22 women) undergoing repeat intervention for in-ST restenosis (101 ST) were prospectively studied. Two hundred and twenty-six SB spanned by the ST were identified. The SB size, type, ostium involvement, location within the ST and take-off angle were evaluated. The SB TIMI (Thrombolysis in Myocardial Infarction trial) flow grade was studied in detail before, during, immediately after the procedure, and at late angiography. RESULTS: Occlusion (TIMI flow grade = 0) was produced in 24 (10%) SB, whereas some degree of flow deterioration (> or = 1 TIMI flow grade) was observed in 57 SB (25%). The SB occlusion was associated with non-Q wave myocardial infarction in two patients (both had large and diseased SB). Side-branch occlusion at the time of initial stenting (RR [relative risk] 11.1, 95% CI [confidence interval] 3.5-35.5, p < 0.001), diabetes (RR 3.5, 95% CI 1.1-10.5, p = 0.02), SB ostium involvement (RR 5.0, 95% CI 1.4-17.2, p = 0.004), baseline SB TIMI flow grade <3 (RR 5.5, 95% CI 1.7-18.1, p = 0.005), and restenosis length (RR 1.05 95% CI 1.01-1.11, p = 0.03) were identified as independent predictors of SB occlusion. Late angiography in 19 initially occluded SB revealed that 17 (89%) were patent again. The long-term clinical event-free survival (81% vs. 82% at two years) in patients with and without initial SB occlusion was similar. CONCLUSIONS: Occlusion or flow deterioration of SB spanned by the ST is relatively common during repeat intervention for in-ST restenosis. Several factors (mainly anatomic features) are useful predictors of this event. However, most SB occlusions are clinically silent and frequently reappear at follow-up.