Comparison of efficacy and safety of intracoronary nicardipine and adenosine for fractional flow reserve assessment of coronary stenosis.

BACKGROUND: Administration of intracoronary (IC) adenosine allows an easily feasible, inexpensive, and more rapid alternative method for fractional flow reserve (FFR). It is common practice in many centers worldwide. Nicardipine is a strong coronary vasodilator but its efficacy and safety for assessing FFR is not established. The purpose of present study was to compare the efficacy and safety of IC nicardipine and adenosine for assessing FFR. METHODS: One hundred and fifty-nine patients with a total of 193 vessels undergoing clinically indicated FFR assessment of intermediate coronary stenoses were included. For the initial assessment of FFR, hyperemia was induced by an IC adenosine. After a washout period of 3 min, FFR was reassessed using 200 µg of IC nicardipine. RESULTS: Hyperemic efficacy among two different stimuli was compared. The mean FFR with IC adenosine was 0.83 ± 0.09 and that with an IC nicardipine was 0.84 ± 0.09. The median FFR with an IC adenosine was 0.83 (0.78-0.91) and that with an IC nicardipine was 0.85 (0.79-0.91) (p-value 0.246). Both FFR values showed an excellent correlation (R2 = 0.982, p < 0.001). Nicardipine produced fewer changes in heart rate, less chest pain and less flushing than adenosine. Transient atrioventricular block occurred in 29 patients with IC adenosine and none with IC nicardipine. CONCLUSIONS: IC bolus injection of nicardipine could be introduced as a safe and practical alternative method of inducing hyperemia during FFR measurements. Compared to IC adenosine, IC nicardipine has a similar hyperemic efficacy and excellent side-effect profile.

Adoption of coronary artery disease - Reporting and Data System (CAD-RADS™) and observed impact on medical therapy and systolic blood pressure control.

BACKGROUND: CAD-RADS was developed to standardize communication of per-patient maximal stenosis on coronary CT angiography (CCTA) and provide treatment recommendations and may impact primary prevention care and resource utilization. The authors sought to evaluate CAD-RADS adoption on preventive medical therapy and risk factor control amongst a mixed provider population. METHODS: Statins, aspirin (ASA), systolic blood pressure and, when available, lipid panel changes were abstracted for 1796 total patients undergoing CCTA in the 12 months before (non-standard reporting, NSR, cohort) and after adoption of the CAD-RADS reporting template. Only initiation of a medication in a treatment naïve patient, escalation from baseline dose, or transition to a higher potency was considered an escalation/initiation in lipid therapy. RESULTS: The CAD-RADS reporting template was utilized in 83.7% (751/897) of CCTAs after the CAD-RADS adoption period. After adjusting for any coronary artery disease (CAD) on CCTA, statin initiation/escalation was more commonly observed in the CAD-RADS cohort (aOR 1.46; 95%CI 1.12-1.90, p = 0.005), driven by higher rates of new statin initiation (aOR 1.79; 95%CI 1.23-2.58, p = 0.002). This resulted in a higher observed rates of total cholesterol improvement in the CAD-RADS cohort (58% vs 49%, p = 0.016). New ASA initiation was similar between reporting templates after adjustment for CAD on CCTA (aOR 1.40; 95%CI 0.97-2.02, p = 0.069). The ordering provider's specialty (cardiology vs non-cardiology) did not significantly impact the observed differences in initiation/escalation of statins and ASA (pinteraction = NS). CONCLUSIONS: Adoption of CAD-RADS reporting was associated with increased utilization of preventive medications, regardless of ordering provider specialty.

Comparison of sodium nitroprusside and adenosine for fractional flow reserve assessment: a systematic review and meta-analysis.

BACKGROUND: Fractional flow reserve (FFR) has become a useful tool in the assessment of physiological significance of coronary artery stenosis (CAS), and Adenosine (ADE) is associated with a high incidence of transient side effects. Sodium nitroprusside (NPS) has been proposed as an alternative vasodilator agent. A meta-analysis of studies comparing ADE and NPS for FFR assessment in the same coronary lesions was performed. METHODS: Authors searched for articles comparing NPS and ADE for FFR assessment in intermediate coronary lesions published through January 2018. The following keywords were used: 'fractional flow reserve' AND 'nitroprusside'. Data were summarized using weighted mean differences for paired data. RESULTS: Seven studies were identified comprising 342 patients and 401 lesions. Four studies evaluated intravenous ADE and 3 studies intracoronary ADE administration. Weighted means FFR values obtained with ADE and NPS were 0.8411 and 0.8445, respectively (weighted mean difference: 0.00, 95% confidence interval (CI) -0.01 to 0.01, p = 0,548). Adverse events were significantly reduced with IC NPS (RR = 0.08, 95%CI 0.02-0.30, P < 0.0001). CONCLUSIONS: NPS produces similar FFR measurements compared to ADE with a significant reduction in adverse effects. These results may support its use as a suitable alternative to ADE for FFR assessment.

Non-invasive assessment of coronary artery geometry using coronary CTA.

AIM: To assess the association of coronary artery geometry with the severity of coronary artery disease (CAD). METHODS: 73 asymptomatic individuals at increased risk of CAD due to peripheral vascular disease (18 women, mean age 63.5 ±â€¯8.2 years) underwent coronary computed tomography angiography (coronary CTA) using first generation dual-source CT. Curvature and tortuosity of the coronary arteries were quantified using semi-automatically generated centerlines. Measurements were performed for individual segments and for the entire artery. Coronary segments were labeled according to the presence of significant stenosis, defined as >70% luminal narrowing, and the presence of plaque. Comparisons were made by segment and by artery, using linear mixed models. RESULTS: Overall, median curvature and tortuosity were, respectively, 0.094 [0.071; 0.120] and 1.080 [1.040; 1.120] on a per-segment level, and 0.096 [0.078; 0.118] and 1.175 [1.090; 1.420] on a per-artery level. Curvature was associated with significant stenosis at a per-segment (p < 0.001) and per-artery level (p = 0.002). Curvature was 16.7% higher for segments with stenosis, and 13.8% higher for arteries with stenosis. Tortuosity was associated with significant stenosis only at the per-segment level (p = 0.002). Curvature was related to the presence of plaque at the per-segment (p < 0.001) and per-artery level (p < 0.001), tortuosity was only related to plaque at the per-segment level (p < 0.001). CONCLUSION: Coronary artery geometry as derived from coronary CTA is related to the presence of plaque and significant stenosis.

Efficacy of intravenous nicorandil for fractional flow reserve assessment: study protocol for a crossover randomised trial.

INTRODUCTION: Nicorandil has vasodilatory effects on both the epicardial coronary arteries and the coronary microvasculature, thereby increasing coronary blood flow. Intravenous administration of nicorandil can be applicable for fractional flow reserve (FFR) measurement as a hyperaemic agent and a possible alternative to adenosine. However, the effectiveness of intravenous nicorandil infusion for FFR measurement is largely unclear. METHODS AND ANALYSIS: This crossover randomised study is being performed to investigate the efficacy of intravenous administration of nicorandil for FFR measurement. Patients with an intermediate coronary artery stenosis who satisfy the eligibility criteria undergo FFR measurement with a consecutive randomised order of patient-blind infusions of continuous intravenous administration of adenosine and a single bolus intravenous administration of nicorandil. The primary end point of the study is the agreement between the FFR values obtained by the intravenous nicorandil and those obtained by the intravenous adenosine. Recruitment of this trial started in November 2015 and will end in March 2017, or until a total of 50 participants have been recruited. ETHICS AND DISSEMINATION: The protocol was approved by the Institutional Review Board at Chiba University Hospital. Study findings will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: UMIN000019309; Pre-results.

Serial assessment of coronary artery response to paclitaxel-eluting stents using optical coherence tomography.

BACKGROUND: The paucity of longitudinal, serial high-resolution imaging studies has limited our understanding of in vivo arterial response to drug-eluting stents. We sought to investigate the human coronary response to paclitaxel-eluting stent implantation, using serial optical coherence tomography assessments. METHODS AND RESULTS: Thirty patients with at least 2 significant coronary lesions in different vessels were treated with a paclitaxel-eluting stent. The most severe stenosis (lesion A) was treated at the initial procedure, and the second target vessel (lesion B) was stented 3 months later. Optical coherence tomography was performed at baseline, 3-, and 9-month follow-up for lesions A and baseline and 6 months for lesions B. Prespecified end points were percent of uncovered and malapposed struts over time. In lesions A, uncovered struts were 3.77±4.94% and 3.02±4.35% at 3 versus 9 months (P=NS). Malapposed struts were 3.55±5.16% at post-procedure, 1.51±3.52% at 3 months, and 0.60±1.82% at 9 months (P<0.05, at 3 versus 9 months). Strut-level neointimal thickness was 0.19±0.09 mm and 0.20±0.11 mm (P=NS) over time. Newly acquired malapposition was detected in 10.4% and 3.3% of 2.5-mm segments at 3- and 9-month follow-up. In lesions B, uncovered struts were 2.91±5.47% at 6-months. Malapposed struts were 4.94±6.70% post-procedure and 1.01±3.11% at 6 months (P<0.01), with 0.19±0.09-mm neointimal thickness at follow-up. CONCLUSIONS: Optical coherence tomography imaging suggested the first 3 months to be the period with most biological activity after paclitaxel-eluting stent implantation, when the proliferative reaction mainly occurs and malapposition resolves. A less active, yet continuous, dynamic arterial response, with resolution and development of malapposition, occurs through 9 months post-treatment.

Assessment of coronary flow parameters by transesophageal echocardiography in patients with isolated coronary artery ectasia: effect of intravenous nitroglycerin.

BACKGROUND: We sought to assess coronary flow parameters in patients with isolated coronary artery ectasia (CAE) as compared to subjects with normal coronaries. METHODS: Consecutively, we enrolled 30 patients with ectasia of the left anterior descending (LAD) coronary artery (study group), and 10 subjects with normal coronaries (control group). All patients underwent transesophageal echocardiography to visualize the LAD. Spectral recordings of proximal LAD flow velocities were made and velocity time integrals were calculated. The diameter of the proximal LAD was measured and LAD blood flow was calculated. Nitroglycerin (0.3 mg) was administered intravenously and measurements were repeated 5 minutes later. RESULTS: The mean age of the whole series was 48.6 ± 8 years, 39 (97.5%) being males. A significantly higher baseline systolic, diastolic, and total coronary blood flow was found in the study group as compared to the control group (46.1 ± 34.3 vs. 23.1 ± 8.2, 123.9 ± 73.3 vs. 68.1 ± 21.6, 170.1 ± 97.9 vs. 91.1 ± 26.8 cm(3) /min, respectively, P < 0.05 for all). Within the study group, nitroglycerin administration caused a significant decrease in peak diastolic velocity; systolic, diastolic, and total velocity time integrals; and both diastolic and total coronary blood flow (P < 0.05 for all). Meanwhile, within the control group, nitroglycerin administration caused a significant increase in the total coronary blood flow (P < 0.05). CONCLUSIONS: Patients with CAE have higher resting coronary blood flow in comparison with subjects with normal coronaries. Intravenous nitroglycerin administration causes significant reduction of coronary blood flow in ectatic coronary arteries.

Quality of life after late invasive therapy for occluded arteries.

BACKGROUND: The open-artery hypothesis postulates that late opening of an infarct-related artery after myocardial infarction will improve clinical outcomes. We evaluated the quality-of-life and economic outcomes associated with the use of this strategy. METHODS: We compared percutaneous coronary intervention (PCI) plus stenting with medical therapy alone in high-risk patients in stable condition who had a totally occluded infarct-related artery 3 to 28 days after myocardial infarction. In 951 patients (44% of those eligible), we assessed quality of life by means of a battery of tests that included two principal outcome measures, the Duke Activity Status Index (DASI) (which measures cardiac physical function on a scale from 0 to 58, with higher scores indicating better function) and the Medical Outcomes Study 36-Item Short-Form Mental Health Inventory 5 (which measures psychological well-being). Structured quality-of-life interviews were performed at baseline and at 4, 12, and 24 months. Costs of treatment were assessed for 458 of 469 patients in the United States (98%), and 2-year cost-effectiveness was estimated. RESULTS: At 4 months, the medical-therapy group, as compared with the PCI group, had a clinically marginal decrease of 3.4 points in the DASI score (P=0.007). At 1 and 2 years, the differences were smaller. No significant differences in psychological well-being were observed. For the 469 patients in the United States, cumulative 2-year costs were approximately $7,000 higher in the PCI group (P<0.001), and the quality-adjusted survival was marginally longer in the medical-therapy group. CONCLUSIONS: PCI was associated with a marginal advantage in cardiac physical function at 4 months but not thereafter. At 2 years, medical therapy remained significantly less expensive than routine PCI and was associated with marginally longer quality-adjusted survival. (ClinicalTrials.gov number, NCT00004562.)

Drug-eluting stents: new era and new concerns.

At present there is much excitement about drug-eluting stents, which hold promise for the treatment of coronary artery disease. This ingenious therapy involves coating the outside of a standard coronary stent with a thin polymer containing medication that can prevent scarring at the site of coronary intervention. Early trials with sirolimus coated stents showed that they might prevent coronary artery restenosis, but later studies, involving more complex coronary lesions, did not show a complete absence of restenosis. Recent studies have demonstrated the long term cost effectiveness of drug-eluting stents as they have reduced the need for revascularisation procedures. At present there are few data on the safety and effectiveness of stents over follow up periods exceeding two years, and data obtained from animal models of stenting might not be completely applicable to humans. There are concerns that drug-eluting stents might delay, rather than inhibit, restenosis. Also there is concern regarding the inflammation caused by the polymer substrate. This article reviews the present data on drug-eluting stents and their benefits, shortcomings, and concerns.

Role of incremental doses of intracoronary adenosine for fractional flow reserve assessment.

BACKGROUND: The achievement of maximal vasodilatation of the coronary microvessels is mandatory for the accurate determination of fractional flow reserve (FFR); the optimal dosing to achieve maximal vasodilation is unclear. This study was designed to address the hypothesis that incremental doses of intracoronary adenosine are necessary to ensure complete vasodilatation of the coronary microcirculation and accurate assessment of FFR. We also examined the relationship between FFR and coronary artery disease risk factors. METHODS: A total of 191 patients (215 vessels) with intermediate coronary lesions were examined. FFR was measured during cardiac catheterization with a pressure monitoring wire. Incremental doses of intracoronary adenosine (12-42 microg, left coronary artery; 12-48 microg, right coronary artery) were administered. RESULTS: Diabetes mellitus was present in 23% of patients, hypertension was present in 65% of patients, and prior myocardial infarction had occurred in 25% of patients. The average percent stenosis in vessels was 57% +/- 15%. Vessels were subdivided on the basis of initial FFR (group 1, <0.75; group II, 0.75-0.79; group III, 0.80-0.89; group IV, >or=0.9). Five of the 24 (21%) vessels with an initial FFR in the 0.75 to 0.80 range had a subsequent FFR of <0.75. There was no difference in FFR or doses of adenosine in the patients with coronary artery disease risk factors. The average adenosine dose given at the achievement of minimal FFR was 26 microg in the right coronary artery (RCA) and 34 microg in the left coronary artery (LCA). The average maximum dose of intracoronary adenosine administered was 29 microg for the RCA and 37 microg for the LCA. The maximum dose of adenosine ever required to achieve minimum FFR was 42 microg in both the LCA and RCA. CONCLUSION: This study suggests that a single high dose of 42 microg of intracoronary adenosine for both the RCA and LCA is sufficient to achieve maximum hyperemia and accurate FFR in most patients, independent of risk factors. Alternatively, when a lower initial dose is administered and FFR is in the 0.75 to 0.90 range, incremental doses of adenosine should be administered to ensure maximal hyperemia.

[Off-label use of clopidogrel after coronary stent implantation in Germany: optional or mandatory?]. / "Off-Label"-Verschreibung von Clopidogrel nach Stentimplantation: verzichtbar oder zwingend?

Although the combined use of acetylsalicylic acid (ASA) and clopidogrel represents the standard in the 4-week treatment after coronary stent implantation, a discussion persists in Germany regarding clopidogrel use and the actual measures for cost containment in the healthcare system. Indeed, clopidogrel has not been approved in Germany for use after stent im-plantation. The prescription of clopidogrel in this context is thus considered off-label use. Consequently, patients with social healthcare insurance should pay for clopidogrel out of their own pockets. This regimen, however, bears the inherent risk that patients will not purchase the drug and thus not take it. This overview article describes the risk to patients when social healthcare insurance companies would not pay for clopidogrel after coronary stent implantation. Five international, prospective, randomized and control-led studies in 3,230 patients have shown that "double" antiaggregation, i.e. a combination of ASA and the thienopyridin derivative ticlopidin, compared with ASA alone clearly reduced death, myocardial infarction and the need for another PCI or CABG to a manifold extent. Due to its lower rate of side effects, clopidogrel has replaced ticlopidin since mid-1998. The clinical results of three prospective, randomized studies and seven single-center registries in approximately 14,000 patients have shown that the combination of ASA and clopidogrel results not only in a lower rate of side effects, but also in a significant rate reduction of cardiovascular events of ca. 50% (from 4.0% to 2.1%). Therefore, the combined use of ASA and clopidogrel should be prescribed to avoid (sub)acute stent thrombosis --even if this is not according to the rules of the German healthcare system. The threat of fines to physicians prescribing clopdiogrel at the expense of the social health care insurance is counterproductive and jeopardizes the life of the patients.

ReoPro rules: results from the 'Do Tirofiban and ReoPro Give Similar Efficacy Trial' (TARGET).

In the treatment of atherosclerotic disease, stenting in the presence of a glycoprotein (GP) IIb/IIIa antagonist is becoming an increasingly common procedure. The 'Do Tirofiban and ReoPro Give Similar Efficacy Trial' (TARGET) was designed to determine whether the cheaper tirofiban was as effective and safe as abciximab in the prevention of ischaemic events with stenting. Unexpectedly, abciximab was shown to be superior to tirofiban. Tirofiban is a selective GP IIb/IIIa antagonist whereas abciximab has additional anti-inflammatory actions, which may contribute to its superiority.