The Utility of Contrast Medium Fractional Flow Reserve in Functional Assessment Of Coronary Disease in Daily Practice.

BACKGROUND: Adenosine induced hyperaemic fractional flow reserve (aFFR) is a validated predictor of clinical outcome and part of routine interventional practice. Protocol issues associated with the adenosine infusion limit the use of aFFR in clinical practice. Contrast medium induced hyperaemic FFR (cFFR) is a simpler procedure from a practical standpoint. We compared the two in a real world setting. METHODS: We analysed 76 patients that had both cFFR and aFFR assessment of 100 angiographically indeterminate coronary stenosis. cFFR was performed with intracoronary contrast medium injections (10ml for left coronary lesions and 8ml for right coronary lesions). The diagnostic performance of cFFR was analysed and compared to the gold standard aFFR. RESULTS: Mean cFFR was 0.87 (±0.07) and mean aFFR was 0.84 (±0.08). Bland-Altman analysis revealed a close agreement between cFFR and aFFR (0.035±0.032; 95% CI: -0.028 to 0.098) and good linear correlation (r=0.92, r2=0.86; p<0.0001). Using cFFR cut-off values of ≤0.83 in predicting an aFFR value of ≤0.80 or a cFFR value ≥0.88, predicting an aFFR value of >0.80 yielded a sensitivity of 100%, specificity of 96.1%, positive predictive value of 92.3%, negative predictive value of 100% and diagnostic accuracy of 96%. Only 24% of cFFR values were in the 0.84 to 0.87 range. CONCLUSION: Contrast medium induced hyperaemic FFR as an initial assessment may limit the need for adenosine to when cFFR falls in the 0.84 to 0.87 range. The use of adenosine infusion potentially could have been avoided in the majority of patients in this study.

Comparative assessment of platelet GpIIb/IIIa receptor occupancy ratio with Eptifibatide/Tirofiban in patients presenting with ACS and undergoing PCI.

BACKGROUND: The level of platelet inhibition by a Glycoprotein IIb/IIIa (GpIIb/IIIa) antagonist therapy necessary to minimize thrombotic complications in patients undergoing percutaneous coronary intervention (PCI) is a subject of debate. The degree of platelet inhibition obtained 10 min after start of GpIIb/IIIa antagonist therapy predicts adverse events after PCI. The aim of this study was to look at platelet inhibition and to compare platelet GpIIb/IIIa receptors occupancy ratio (GpRO) with Eptifibatide and Tirofiban using various dose regimens and correlate with 30-day clinical outcomes in patients presenting with high-risk acute coronary syndromes (ACS) and undergoing PCI. METHODS: The patients were divided into four sub groups: (1) Eptifibatide two intracoronary bolus (180 µg/kg) alone (E(B)); or (2) two intravenous bolus (180 µg/kg) followed by infusion at 2 µg/kg/min for 24 h (E(B + Inf)); and (3) Tirofiban standard bolus dose (0.4 µg/kg) over 30 min followed by infusion at 0.1 µg/kg/min (T(Std)); or (4) at ADVANCE dose bolus (25 µg/kg) over 3 min, followed by infusion at 0.1 µg/kg/min (T(Adv)). Number of GpIIb/IIIa receptors was assessed by flow cytometry at baseline and 10 min after the bolus and percentage of free receptors was determined to calculate the GpRO. Patients were followed for 30 days for any major adverse cardiac events (MACE). RESULTS: 200 consecutive patients (including 74% with ST-elevation ACS) were enrolled. GpRO in groups E(B) (n = 48) and E(B + Inf) (n = 44) were 62.7% ± 27.2% and 61.4% ± 6.1% respectively while in the groups T(Std) (n = 96) and T(Adv) (n = 12) groups were 35.1% ± 17.74% and 68.8% ± 27.3% respectively. The GpRO was similar in E(B), E(B + Inf) and T(Adv) groups and was significantly higher than T(Std) group (p < 0.0001). The 30-day MACE rates in E(B) (4.2%), E(B + Inf) (4.5%) and T(Adv) (4.2%) were significantly lower than T(Std) group (12.5%) (p < 0.01). CONCLUSIONS: Standard dose Tirofiban results in significantly lower rates of GpIIb/IIIa receptor occupancy ratio and this correlated with higher incidence of 30-day MACE in high-risk ACS patients undergoing PCI.

Clinical correlation of multiple biomarkers for risk assessment in patients with acute coronary syndrome.

OBJECTIVE: Biochemical markers are useful for the prediction of future cardiovascular events in patients with non-ST-segment elevation acute coronary syndrome (ACS). The independent as well as the combined prognostic value of elevated troponin-T, high-sensitivity C-reactive protein (hs-CRP), and N-terminal pro-brain natriuretic peptide (NT-pro-BNP) on the Thrombolysis In Myocardial Infarction (TIMI) risk score and on the short-term prognosis were evaluated in a cohort of ACS patients. METHODS AND RESULTS: In an unselected, heterogeneous group of 80 patients with ACS (i.e., unstable angina [USA] or non-ST-elevation myocardial infarction [NSTEMI]), the levels of troponin-T, hs-CRP, and NT-pro-BNP were analyzed. The correlation between elevation of different biomarkers with TIMI risk score and their impact on 30-day major adverse cardiac events was sought. The levels of hs-CRP were significantly higher in patients who had angina as their predominant complaint (3.67 mg/dl vs. 1.67 mg/dl: p < 0.01), while levels of NT-pro-BNP was higher in those patients who had any element of heart failure at presentation (2616.39 pg/ml vs. 1068.3 pg/ml; p < 0.01). Troponin-T was highest in patients who had an element of both heart failure and angina at presentation (p < 0.01). The TIMI risk score expectedly had a positive and strong correlation with elevated troponin-T, but had no correlation with elevation of hs-CRP and NT-pro-BNP in isolation. However, when any two biomarkers were elevated, the patients were in the intermediate risk group as per TIMI risk score irrespective of troponin-T-elevation. When all the three biomarkers were elevated, the risk equaled the high-risk category of TIMI risk score. Elevated hs-CRP (3.40 mg/dl vs. 1.38 mg/dl; p < 0.001) and troponin-T (2.37 ng/ml vs. 1.23 ng/ml; p < 0.001) at baseline correlated independently with the occurrence of re-ischemia, while elevated NT-pro-BNP alone correlated significantly with the development of heart failure within 30 days of follow-up (4247.76 pg/ml vs. 1210.86 pg/ml; p < 0.01). The highest risk of death from any cardiovascular cause within 30 days of follow-up was significantly higher when all the three biomarkers were elevated. CONCLUSION: The use of NT-pro-BNP, hs-CRP, and troponin-T in combination appears to add critical prognostic insight to the assessment of patients with ACS.

"Poor man's risk factor": correlation between high sensitivity C-reactive protein and socio-economic class in patients of acute coronary syndrome.

OBJECTIVE: Inflammation has been proposed as one of the factors responsible for the development of coronary artery disease (CAD) and high sensitivity C-reactive protein (hs CRP) at present is the strongest marker of inflammation. We did a study to assess the correlation of hs-CRP with socio-economic status (SES) in patients of CAD presenting as acute coronary syndrome (ACS). METHODS: Baseline hs-CRP of 490 patients of ACS was estimated by turbidimetric immunoassay. Patients were stratified by levels of hs-CRP into low (<1 mg/L); intermediate (1-3 mg/L) or high (>3 mg/L) groups and in tertiles of 0-0.39 mg/L, 0.4-1.1 mg/L and >1.1 mg/L, respectively. Classification of patient into upper (21.4%), middle (45.37 percent) and lower (33.3%) SES was based on Kuppuswami Index which includes education, income and profession. Presence or absence of traditional risk factors for CAD diabetes, hypertension, dyslipidemia and smoking was recorded in each patient. RESULTS: Mean levels of hs-CRP in lower, middle and upper SES were 2.3 +/- 2.1 mg/L, 0.8 +/- 1.7 mg/L and 1.2 +/- 1.5 mg/L, respectively. hs-CRP levels were significantly higher in low SES compared with both upper SES (p = 0.033) and middle SES (p = 0.001). Prevalence of more than one traditional CAD risk factors was seen in 13.5%, 37.5% and 67.67 percent; in patient of lower, middle and upper SES. It was observed that multiple risk factors had a linear correlation with increasing SES. Of the four traditional risk factors of CAD, smoking was the only factor which was significantly higher in lower SES (73%) as compared to middle (51.67 percent;) and upper (39.4%) SES. We found that 62.3%, 20.8% and 26.5% patients of low, middle and upper SES had hs-CRP values in the highest tertile. Median value of the Framingham risk score in low, middle and upper SES as 11, 14 and 18, respectively. We observed that at each category of Framingham risk, low SES had higher hs-CRP. CONCLUSION: We conclude from our study that patient of lower SES have significantly higher levels of hs-CRP despite the fact that they have lesser traditional risk factors and lower Framingham risk. These findings add credit to our belief that inflammation may be an important link in the pathophysiology of atherosclerosis and its complications especially in patients of low SES who do not have traditional risk factors.