Predictors of vessel quantitative flow ratio loss in patients with severely calcified lesions after rotational atherectomy.

BACKGROUND: Previous studies have established that moderately to severely calcified lesions (MSCL) are associated with high rates of major adverse cardiovascular events, even when drug-eluting stents are implanted after rotational atherectomy (RA). Yet, the changes in coronary function indexes during follow-ups have never been investigated. The quantitative flow ratio (QFR), a novel coronary function index, has been increasingly adopted in daily practice in recent years. METHODS: A total of 111 MSCL patients were retrospectively enrolled in this study. The vessel QFR (QFRv) loss was defined as post-percutaneous coronary intervention QFRv minus follow-up QFRv. The study subjects were divided into high QFRv loss (n = 51) and low QFRv loss (n = 60) groups according to the binary method. The obtained predictors of QFRv loss were then analyzed. RESULTS: The results showed that the final burr-to-vessel ratio (B to V ratio) in the high QFRv loss group decreased significantly compared to the low QFRv loss group (p < 0.01). The univariate and multivariate regression analyses indicated that the final B to V ratio was an excellent predictor of QFRv loss. The cut-off value of the final B to V ratio for QFRv loss prediction was 0.50 (sensitivity: 50.98%, specificity: 68.33%, and area under the curve: 0.627 [95% confidence interval: 0.530-0.717], p < 0.05). Additionally, the target vessel failure incidence in the high QFRv loss group was higher than in the low QFRv loss group (p < 0.01). CONCLUSIONS: An increased burr-to-vessel ratio can prevent QFRv loss in patients with MSCLs after RA, an effect that might be closely associated with a low target vessel failure incidence.

Increased risk for developing major adverse cardiovascular events in stented Chinese patients treated with dual antiplatelet therapy after concomitant use of the proton pump inhibitor.

BACKGROUND: Some clinical studies have demonstrated that the proton pump inhibitor (PPI) could decrease clopidogrel platelet response and increase major adverse cardiovascular events (MACE) in white or black subjects. However, that remains to be determined in Chinese patients. In this study, we sought to determine whether there could be an increased risk for developing MACE after concomitant use of dual antiplatelet therapy (DAT) and a PPI in Chinese patients treated with percutaneous coronary intervention (PCI) and stenting. METHODS: This study was a 5-year, single-center, retrospective cohort analysis of eligible patients (n = 6188) who received DAT and a PPI concomitantly (defined as PPI users) before discharge and/or 12-month follow-up after discharge as compared with those who received DAT alone (also defined as non-PPI users, n = 1465). The incidence of recurrent MACE, such as myocardial infarction (MI), definite stent thromboses (ST), or cardiovascular death, was compared between the PPI users and non-users. RESULTS: PPI users had a significantly higher incidence of the MACE than non-users (13.9% vs. 10.6%; adjusted HR: 1.33; 95% CI: 1.12 - 1.57, P = 0.007). Stratified analysis revealed that concurrent use of DAT and a PPI was associated with a significantly increased risk for developing ST compared with DAT alone (1% vs. 0.4%; adjusted HR: 2.66, 95% CI: 1.16 - 5.87, P = 0.012). However, there were no significant differences in the risk of MI, cardiovascular death and other adverse events, regardless of combination of clopidogrel and a PPI. CONCLUSIONS: The study further suggests that concomitant use of DAT and a PPI may be associated with an increased risk for developing MACE, in particular definite ST, in Chinese PCI patients after discharge as compared with use of DAT alone.

Association of the use of amlodipine with clopidogrel response in Chinese patients undergoing percutaneous coronary intervention.

Until recently, the precise mechanism of clopidogrel resistance remains unclear. Some clinical studies have demonstrated that calcium channel blockers (CCBs) could reduce the antiplatelet effect of clopidogrel in white or black subjects, implicating in clopidogrel resistance. However, that remains to be determined in Chinese patients. In this study, we sought to determine whether there could be a decreased antiplatelet effect of clopidogrel and an increased risk for developing adverse cardiovascular events after concomitant use of different CCBs and clopidogrel in Chinese patients treated with percutaneous coronary intervention (PCI). A subcohort of 249 patients not carrying the CYP2C19 *2, *3 or *17 variant was identified from a total of 617 consecutive clopidogrel-treated patients undergoing PCI and then categorized into three groups according to various CCB treatments. Baseline data, clinical characteristics and blood samples were collected for all patients. The maximum platelet aggregation (MPA) was measured by light transmittance aggregometry (LTA) to assess the platelet function in blood samples obtained from patients on day 3 after starting daily clopidogrel maintenance doses. The primary clinical end-point was a definite stent thrombosis (ST) episode, whereas secondary end-points were other major adverse cardiovascular events within 12 months after stenting. Of the 249 patients not carrying CYP2C19 *2, *3 and *17 variants, the ADP-induced MPA differed significantly among the three groups (P < 0.001). The MPA values were 1.76 times in the amlodipine group (41.6 ± 23.0%) than in the No CCB group (23.7 ± 14.1%) (P < 0.001). Moreover, in a linear regression model, the use of amlodipine was independently associated with MPA values (R = 0.375, P < 0.001), suggesting that the use of amlodipine might link to the increased MPA. However, the incidence of 1-year ST was not significantly higher in the amlodipine group than the No CCB group (OR, 4.80; 95% CI, 0.87 to 26.52; P = 0.068), and none of the risks for other adverse cardiovascular events were significantly different across the three groups (P = 0.11).

[Comparison of short- and long-term outcome after percutaneous transluminal interventional therapy in octogenarians with coronary artery disease from radial or femoral approach].

OBJECTIVE: To compare the short-term and long-term outcome after percutaneous coronary intervention (PCI) between transradial intervention (TRI) and transfemoral intervention (TFI) in elderly patients. METHODS: From January 2005 to December 2010, 488 consecutive elderly patients ( ≥ 80 years old) were enrolled in this retrospective study. Patients were divided into TRI group (n = 235, PCIs were performed trans-radial approach) and TFI group (n = 253, PCIs were performed trans-femoral approach). Efficacy and safety data were compared between the two groups. RESULTS: There were no differences in success rate of stenting, procedure time, contrast amount, rates of contrast-induced nephropathy, major adverse cardiovascular events during hospitalization, at one year follow up and at two years follow up. Lower vascular complications were associated with TRI approach[ 17.9% (42/253) vs. 26.9% (68/253) , P < 0.05], especially in TIMI major bleeding ratio [1.3% (3/235) vs. 4.7% (12/253) , P < 0.05], TIMI minor bleeding [5.1% (12/235) vs. 15.8% (40/253) , P < 0.01], and time lying in bed [3.6 (2.8-4.2)h vs. 24.4 (24.0-25.1)h, P < 0.01] and hospitalization [3.0 (3.0-4.0)d vs. 5.0 (5.0-6.0)d, P < 0.01], and higher rates of crossover approach were associated with TRI [11.5% (27/235) vs. 2.0(5/253) , P < 0.01]. CONCLUSION: TRI is as feasible, safe and effective as TFI in elderly patients during short-term and long-term follow up, and TRI is associated with higher rates of crossover approach.

Quantitative assessment of late lumen loss after biodegradable polymer and permanent polymer sirolimus-eluting stents implantation.

BACKGROUND: Sirolimus-eluting stents (SES) are reported to be associated with reduced late lumen loss (LLL), resulting in less frequent restenosis when compared to bare-metal stent. The current study aimed to assess the difference in LLL between SES with biodegradable and with permanent polymer. METHODS: From March 2010 to June 2011, 300 consecutive patients having only biodegradable polymers or permanent polymer SES for all diseased vessels were included. Serial quantitative coronary analysis was performed on both the "in-stent" and "segment" area, including the stented segment, as well as both five mm margins proximal and distal to the stent. The primary endpoint was the LLL defined as the minimal lumen diameter (MLD) post-stenting minus the MLD at nine-month after the indexed procedure. RESULTS: LLL was comparable between the two stents. Importantly, LLL for the distal segment (median 0.05 mm, interquartile 0 to 0.09 mm) was less severe compared with in-stent (median 0.13 mm, interquartile 0.08 to 0.18 mm) and proximal segment LLL (median 0.12 mm, interquartile 0.06 to 0.14 mm, all P < 0.001). In general, the LLL was associated with the post-procedure MLD (b = 0.28, P = 0.002), hyperlipidemia (b = 0.14, P = 0.021), and calcified lesions (b = 0.58, P = 0.001). The R(2) and Radj of the multiple regression model were 0.651 and 0.625, respectively. CONCLUSIONS: SES with either biodegradable or permanent polymer had lower value of LLL. The small amount of LLL at the distal segment possibly contributed to the less distal edge stenosis.

Influence of CYP2C19 loss-of-function variants on the antiplatelet effects and cardiovascular events in clopidogrel-treated Chinese patients undergoing percutaneous coronary intervention.

BACKGROUND AND OBJECTIVES: A large number of clinical studies have well demonstrated that the loss-of-function variant allele CYP2C19 2 is associated with attenuated response to clopidogrel and increased risk of developing stent thrombosis (ST) in white or black patients with stenting. However, similar association studies on the effect of the CYP2C19 2 and 3 variants on maximum platelet aggregation (MPA) and the risk of cardiovascular events are currently unavailable for the Chinese patients. This work was aimed at assessing the impact of the CYP2C19 2 and 3 variants on the antiplatelet effects and adverse cardiovascular events in clopidogrel-treated Chinese patients undergoing percutaneous coronary intervention (PCI). METHODS: The study population consisted of 617 patients undergoing PCI. Genotypes were determined using MALDI/TOF-MS. MPA was measured by light transmittance aggregometry. The clinical end-point was the 1-year incidence of adverse cardiovascular events, including ST. RESULTS: Carriers of CYP2C19 heterozygous (1/2, or 1/3; n = 278) and mutant homozygous (2/2, 2/3, or 3/3, n = 80) genotypes had significantly higher MPA values than noncarriers (1/1; n = 259; P = 0.036 and 0.007 respectively). Moreover, the presence of the CYP2C19 2 or 3 mutant allele was significantly associated with an increased risk of developing ST, with the higher risk of ST being seen in patients homozygous for the CYP2C19 2 or 3 variant allele than in noncarriers (OR, 13.58; 95% CI, 1.49-123.31; P = 0.012). Furthermore, multivariate analysis revealed an independent association of the presence of CYP2C19*2 and/or 3 variant alleles with greater MPA values (P = 0.001) and increased risk of ST (OR, 11.67; 95% CI, 1.21-78.83; P = 0.022). However, there was no significant influence of CYP2C19 2 and 3 on the risk of developing other adverse cardiovascular events. CONCLUSIONS: Carriage of the loss-of-function genetic variants CYP2C19 2 and 3 is significantly associated with attenuated platelet response to clopidogrel and an increased risk of ST in Chinese patients treated with stenting.

Intravenous injection of nicardipine changed the distribution of coronary artery endothelial shear stress and fluid dynamics in patients with unstable angina.

BACKGROUND: Coronary endothelial shear stress (ESS) triggered the development of atherosclerosis. However, the effect of calcium channel antagonist on the distribution of ESS remained unclear. METHODS: Twenty consecutive patients with acute coronary syndrome (ACS) 48 hours after maximal medication with single left anterior descending artery stenosis < 50% were studied. Nicardipine was intravenously injected at 1 µg/kg after a bolus of 10 mg in order to achieve mean blood pressure (MBP) reduced by 10% or more, or the heart rate increased by 10 - 15 beats/min. Hemodynamic variables and angiogram at baseline and during injection of nicardipine were recorded, respectively. Coronary artery 3-D reconstruction was used for the analysis of ESS. RESULTS: Distal reference-vessel-diameter and minimal lumen diameter decreased significantly from (2.42 ± 0.41) mm and (1.47 ± 0.49) mm at baseline to (2.22 ± 0.35) mm and (1.35 ± 0.49) mm at maximal drug-dosage (P = 0.018 and 0.020, respectively). Nicardipine did not change blood velocity. Lowest mean shear stress at segments 2-mm distal to plaque increased significantly from (0.034 ± 0.519) Pa at baseline to (0.603 ± 0.728) Pa (P = 0.013) at peak effect of drug. CONCLUSIONS: Nicardipine was associated with the constriction of diseased vessel segment that adapted to the reduction of blood pressure, without dynamic change of blood velocity at each stage of whole cardiac cycle. Increased ESS value at segments distal to plaque reflected the cardioprotection by nicardipine (ChiCTR-TRC-10000964).

Hemodynamic changes of fractional flow reserve after double kissing crush and provisional stenting technique for true bifurcation lesions.

BACKGROUND: Fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) is associated with fewer unfavorable events. However, the hemodynamic change in FFR after different stenting approaches for bifurcation lesions is still not fully studied. The aim of this study was to analyze the hemodynamic changes in FFR after double kissing (DK) crush and provisional side branch (SB) stenting (PS) for true coronary bifurcation lesions. METHODS: Seventy-five patients with true bifurcated lesions were randomly divided into DK (n = 38) and PS (n = 37) groups. Additional SB stenting in the PS group was required if there was any pinched SB ostium > 70% stenosis, or ≥ type B dissection, or TIMI flow < grade 3. FFR at hyperemia in the main vessel (MV) and SB was measured prior- and post-stenting, and at 8 months follow-up. RESULTS: Baseline clinical, angiographic and lesion characteristics were matched well between the two groups, with the exception of the final kissing balloon inflation (FKBI, 100.0% in the DK vs. 83.8% in the PS group, P < 0.001). Baseline FFR was comparable between the DK and the PS groups, however, the acute gain and late loss of SB FFR at 8-month follow-up in the DK group were 0.18 ± 0.15 and -0.06 ± 0.11, compared to 0.12 ± 0.18 (P = 0.044) and -0.002 ± 0.07 (P = 0.037) in the PS group, respectively. MV FFR post-stenting > 0.94 was seen in about 40% of patients. There was no significant difference in the clinical events at 1-year follow-up between the two groups. CONCLUSIONS: DK crush was associated with improved acute gain and late loss of SB FFR. The lower rate of FFR > 0.94 after stenting underscored the further improvement of stenting quality.

Clinical outcomes after recanalization of a chronic total occluded vessel with bifurcation lesions: results from single-center, prospective, chronic total occlusion registry study.

BACKGROUND: Stenting strategies and clinical outcomes of bifurcation lesions in a chronic total occlusion (CTO) vessel after successful recanalization remain to be unknown. METHODS: Between January 2001 and December 2009, 195 (41.1%) patients with 254 (47.0%) bifurcation lesions in CTO vessels from a pool of 564 patients with 659 CTO lesions were included and divided into proximal (n = 134) and distal (n = 120) groups, according to the location of the bifurcation lesions. The primary endpoint was the occurrence of major adverse cardiac events (MACE) at the end of clinical follow-up, including cardiac death, myocardial infarction, or target vessel revascularization (TVR). RESULTS: Collaterals with Rentrop class 3 were seen more in distal group (100% and 68.3%), compared to proximal group (76.9% and 45.6%). Two-stent technique for proximal bifurcation lesions was used in 24.6%, significantly different from the distal group (6.7%, P < 0.001), without significant difference in composite MACE between proximal and distal groups, or between one- and two-stent subgroups in proximal group. The composite MACE after 1-year in complete revascularization subgroup was 17.9% relative to 29.6% in the incomplete revascularization group (P = 0.044). Stents in long false lumen in main vessel were mainly attributive to decreased TIMI grade flow, with resultant increased in-stent restenosis, total occlusion, TVR and coronary aneurysms. Imcomplete revasculzarization (HR 2.028, P = 0.049, 95%CI 1.002 - 4.105) and post-stenting TIMI flow (HR 6.122, P = 0.020, 95%CI 1.334 - 28.092) were two independent predictors of composite MACE at the 1-year follow-up. CONCLUSIONS: Two-stent was more used for proximal bifurcation lesions. No significant difference was observed in MACE between proximal and distal, or between one- and two-stent subgroups in the proximal group. Placement of a safety wire was critical for proximal bifurcation lesions. Complete revascularization was mandatory to improve clinical outcomes.

Contradictory shear stress distribution prevents restenosis after provisional stenting for bifurcation lesions.

BACKGROUND: Endothelial shear stress is one of the local hemodynamic factors suspected in the development of coronary atherosclerosis in bifurcation lesions. In patients with provisional stenting, the endothelial shear stress (SS) distribution is unknown. OBJECTIVE: The aim of this study was to investigate the magnitude and distribution of the SS of coronary bifurcation lesions stenting by the provisional approach. METHODS: Ten consecutive patients were included in this study. Quantitative coronary analysis, flow study, and three-dimensional computational analysis with the aid of the commercial software CD STAR-CCM+ were done before and after the provisional stenting procedure and also 8 months later. RESULTS: Clinical and angiographic follow-up were available in all patients. No patient had a side branch (SB) stent. At the 8-month follow-up, no major adverse cardiac event (MACE) occurred. There was also no clinical and angiographic restenosis. Before PCI, the distal main vessel (MV)-lateral, and the SB-lateral subsegments had relative nonsignificant lower SS value (4.08 +/- 2.78 Pa and 4.35 +/- 5.04 Pa, respectively) when compared to other segments. After 8-month follow-up, sustained decreased SS value was shown in the distal MV-lateral segment (4.08 +/- 2.78-1.68 +/- 1.65 Pa), when compared with significantly increased SS value in the SB-lateral subsegment 4.35 +/- 5.04-16.50 +/- 40.45 Pa). The explanation is that after stenting in the MV, the flow was redistributed immediately after percutaneous coronary intervention (PCI) and reversed back to its original 8 months later. However, the growth of the fibrous tissue causing in-stent restenosis (ISR) is prohibited by sirolimus on the stent struts. In contrast, in a branch opened up by plain old balloon angioplasty (POBA), the flow did not change much, the flow could even be worse because it is shifted to the MV after the cross-sectional area of the MV improved by stenting. However, thanks to POBA, there is increased fibrous tissue formation, enough to increase the SS and prevent further accumulation of cell and cholesterol needed for more restenosis. CONCLUSION: In the provisional approach, low endothelial SS correlated with no restenosis for patients who underwent stenting of the MV, while a contradictory combination of high SS and no restenosis was seen in the SB after only POBA. The mechanism of prevention of restenosis in the SB is by increasing the SS while in the MV, the mechanism of prevention of ISR is secondary to sirolimus on the stents struts.

Distribution and magnitude of shear stress after coronary bifurcation lesions stenting with the classical crush technique: a new predictor for in-stent restenosis.

BACKGROUND: Wall shear stress (SS) plays an important role in the initiation and proliferation of coronary atherosclerosis, especially for bifurcations. Stenting in the coronary artery will cause many different changes in velocity, flow, cross-sectional area, and especially the wall SS. However, it is still unknown how much wall SS distribution varies with stenting in coronary bifurcation. OBJECTIVE: The purpose of this study was to investigate the magnitude and distribution of wall SS after the classical crush stenting for bifurcation lesions. METHODS: Eleven patients with true coronary bifurcation stenting by the classical crush technique were included. We studied the difference of wall SS between restenosis and nonrestenosis groups in these patients. The differences in SS between preprocedure and postprocedure, as well as between immediately postprocedure and after an 8-month follow-up, were also analyzed. Diameter stenosis or minimal lumen diameter were measured by quantitative coronary analysis. The commercial CD STAR-CCM+ was used to calculate the SS. RESULTS: At baseline, the SS in all the segments of all patients was high. The baseline SS of the restenosis group was 50% lower than the nonrestenosis group. Immediately after percutaneous coronary intervention (PCI), the SS in both areas decreased; however, the SS of the nonrestenosis group decreased to its lowest level possible while the SS of the restenosis group decreased moderately. Eight months later, the SS of all the segments of the nonrestenosis group remained persistently low at the same level of right after PCI. In contrary, the SS in the restenosis group returned to near its baseline level. CONCLUSION: From our study, after a 2-stent crush technique using drug-eluting stents (DES), the degree of SS reduction appears to predict in-stent restenosis (ISR). A SS decrease to its lowest level and remaining homogenously low is a prime condition to prevent ISR. A baseline low SS, which decreases minimally after PCI and recovers to around its baseline level, appears to be the setting for restenosis. These conditions can be evaluated as predictors of lesions that may need surveillance angiography and proper IVUS evaluation to prevent future in-stent restenosis.

The acute changes of fractional flow reserve in DK (double kissing), crush, and 1-stent technique for true bifurcation lesions.

BACKGROUND: While many studies confirmed the importance of fractional flow reserve (FFR) in guiding complex percutaneous coronary interventions (PCI), data regarding the significance of FFR for bifurcation lesions are still lacking. METHODS: Between October 2008 and October 2009, 51 patients with true bifurcation lesions were consecutively enrolled and randomized into double kissing (DK) crush (n = 25), and provisional 1-stent (n = 26) groups. FFR measurements at baseline and hyperemia were measured at pre-PCI, post-PCI, and at 8-month follow-up. RESULTS: Clinical follow-ups were available in 100% of patients while only 33% of patients underwent angiographic follow-up. Baseline clinical and angiographic characteristics were matched between the 2 groups. Pre-PCI FFR of the main branch (MB) in the DK group was 0.76 +/- 0.15, which was significantly lower than in the provisional 1-stent group (0.83 +/- 0.10, P = 0.029). This difference disappeared after the PCI procedure (0.92 +/- 0.04 vs. 0.92 +/- 0.05, P = 0.58). There were no significant differences in terms of baseline, angiographic, procedural indexes, and FFR of side branch (SB) between the 2 treatment arms. However, immediately after PCI, the patient with DK crush had higher FFR in the SB as compared to the provisional 1-stent group (0.94 +/- 0.03 vs. 0.90 +/- 0.08, P = 0.028, respectively) and also they had lower diameter stenosis (8.59 +/- 6.41% vs. 15.62 +/- 11.69%, P = 0.015, respectively). CONCLUSION: In the acute phase, immediately after PCI for bifurcation lesion, DK crush stenting was associated with higher FFR and lower residual diameter stenosis in the SB, as compared with the provisional 1-stent group.