Impact of CYP2D6*2A, CYP2D6*4 and CYP3A5*3 genetic polymorphisms on Bisoprolol peak concentration and clinical response in acute coronary syndrome patients.

AIMS: Acute coronary syndrome (ACS) represents a major cause of death. Bisoprolol is commonly used in the management of ACS. This study aims to investigate the impact of CYP2D6*2A, CYP2D6*4 and CYP3A5*3 genetic polymorphisms on pharmacokinetics and clinical response of bisoprolol in ACS patients. METHODS: This is an open-label cohort study that included 127 ACS patients and studied the effect of CYP3A5*3, CYP2D6*2A and CYP2D6*4 genotyping using real-time polymerase chain reaction on steady state bisoprolol plasma peak concentration analysed by high performance liquid chromatography-fluorescence detector. RESULTS: Regarding CYP3A5*3, the mean peak bisoprolol concentration for CC, CT and TT genotypes were 4.25 ± 1.20, 3.93 ± 1.10 and 1.79 ± 0.69 ng/mL, respectively (P < .001). Higher systolic (126 ± 5.47 mmHg), diastolic blood pressure (82 ± 2.73 mmHg) and heart rate (97.80 ± 3.03 beats/min) were also observed in CYP3A5*3 TT carriers (P < .05). In CYP2D6*2A, the peak concentration of bisoprolol was lower in CC carriers (3.54 ± 1 ng/mL) compared to GG (4.38 ± 1.25 ng/mL) and GC carriers (4.07 ± 1.29 ng/mL, P = .019). In CYP2D6*4, the mean bisoprolol peak concentration in CC carriers was 3.98 ± 1.31 ng/mL, which was lower than T allele carriers (4.5 ± 0.8, P = .02). No differences in heart rate, systolic, diastolic blood pressure or bisoprolol dose were observed among CYP2D6*2A or CYP2D6*4 variants. Smokers exhibited lower bisoprolol peak concentration (3.96 ± 1.2 ng/mL) compared to nonsmokers (4.55 ± 1.34 ng/mL, P = .037). CONCLUSION: There is an association between CYP3A5*3, CYP2D6*4, CYP2D6*2A variants and bisoprolol peak concentration, which may serve as a guide in the future in choosing the optimum dose of bisoprolol in ACS patients.

Very long versus overlapping drug eluting stents for the management of long coronary artery lesions.

BACKGROUND: The prevalence of long diffuse coronary artery disease (CAD) is increasing nowadays due to increase prevalence of multiple risk factors and population ageing. We aimed in our study to show the differences clinically or angiographically (guided by IVUS) between the use of single long stent versus overlapping stents in very long coronary lesions (≥40 mm) in patients presented with chronic coronary syndromes. METHODS: 550 patients presenting with chronic coronary syndromes were included: 320 treated with a single long stent (≥40 mm) and 230 patients with two or more overlapping stents. Angiographic follow-up (guided by IVUS) 6 months after PCI was performed only in 50 patients. We assessed the procedural characteristics and the occurrence of major adverse cardiovascular events (MACE) after a median follow-up of 24 months. RESULTS: Total stent length was 56.16 ± 14.85 mm and mean diameter was 3.05 ± 0.36 mm. At the end of follow-up, MACE rate in the single long stent group was 4.1% vs. 7.8% in the overlapping stents group, with higher incidence in overlapping stents group but non-statistically significant (p value = 0.059). PCI using overlapping stents consumed more contrast volume (248 ± 85.36 vs 164.5 ± 70.43 ml, p < 0.001), and higher fluoroscopy time (23.65 ± 9.19 vs 19.72 ± 9.19 min, p < 0.001). Regarding IVUS subgroup follow-up, there was no significant difference between both groups regarding in-stent restenosis and MACE. CONCLUSIONS: We can conclude that long or overlapping stents are both acceptable therapeutic choices for patients with long CAD. There was no difference between both strategies regarding angiographic follow-up guided by IVUS after 6 months.

The prognostic impact of HDL-C level in patients presenting with ST-elevation myocardial infarction.

Low high-density lipoprotein-cholesterol (HDL-C) concentration is among the strongest independent risk factors for cardiovascular disease, however, studies to assess the cardioprotective effect of normal or high HDL-C level are lacking. To determine the prognostic impact of initial serum HDL-C level on in-hospital major adverse cardiovascular and cerebrovascular events (MACCE) and the one-year all-cause mortality in patients presenting with ST-elevation myocardial infarction (STEMI) we performed a retrospective analysis of the data from 1,415 patients presenting with STEMI in a tertiary-care centre equipped with a 24-hour-ready catheterisation laboratory. The period from June 2014 to June 2017 was reviewed with a follow-up as regards one-year all-cause mortality. Patients were divided into two groups according to HDL-C level. HDL-C <40 mg/dL (2.22 mmol/L) was considered low, while HDL-C ≥40 mg/dL was considered normal. There were 1,109 patients with low HDL-C, while 306 had normal HDL-C levels, which was statistically significant (p<0.001). Total MACCE and all-cause mortality were significantly lower in patients with normal HDL-C (p=0.03 and p=0.01, respectively). In conclusion, this retrospective study to assess the prognostic effect of HDL-C in patients presenting with STEMI, found normal HDL-C level was associated with lower in-hospital MACCE and all-cause mortality at one-year follow-up.

Prognostic value of right ventricular diastolic dysfunction in patients with inferior ST-elevated myocardial infarction.

BACKGROUND: Right ventricle infarction (RVI) is predominantly a complication of inferior wall myocardial infarction; it occurs in approximately one third of these patients. Right ventricular dysfunction in patients with inferior STEMI and RV infarction was under assessed. Nevertheless, studies which targeted RV assessment by echocardiography, did not routinely evaluate RV diastolic dysfunction. In this study, we aimed to evaluate RV diastolic dysfunction and its prognostic value in patients with inferior STEMI and RVI. RESULTS: Sixty patients with inferior STEMI and RV infarction, who underwent primary PCI were enrolled in the study. Patients with pre-existing clinical conditions that might affect RV function, were excluded. Echocardiography was performed within twenty-four hours following the PCI, to assess the RV systolic and diastolic functions with special focus on tricuspid inflow velocities (E velocity, A velocity and E/A ratio) by pulsed wave (PW) doppler and tricuspid annular velocities by tissue doppler index (TDI) (E', A' and E/E' ratio). Clinical features and MACE, including cardiogenic shock, arrhythmia, stroke, reinfarction and death were analyzed in all our patients within 3 months follow up period. The average age of the study population was 51.58 ± 10.11 years, 10% were females. Five patients developed MACE (death, cardiogenic shock and pulmonary edema, anterior STEMI and cardiogenic shock, recurrent inferior STEMI, and arrhythmia and stroke), of whom four occurred in hospital within the first 48 h. Patients who developed MACE had high filling pressures, as all of them had E/E' > 6. E' velocity ≤ 6 cm/sec was associated with increased MACE as 25% of patients with E' velocity ≤ 6 had MACE compared with 2.3% of patients with E' velocity > 6 with a p value of 0.015. CONCLUSIONS: Tricuspid annular velocities by TDI are essential when evaluating RV diastolic dysfunction. E/E' and E' velocity have a prognostic value in patients with inferior STEMI and RV infarction; E/E' > 6 and E' velocity ≤ 6 cm/sec were associated more MACE in patients with inferior STEMI and RVI.

Subclavian angioplasty during coronary interventions using radial approach.

BACKGROUND: In the past years, the percentage of percutaneous coronary angiography and coronary interventions using radial access had significantly increased due to its higher safety, lower risk of major bleeding, and hence lower cardiovascular mortality. Subclavian artery stenosis is one of the challenges that may be met during transradial coronary interventions, which may necessitate femoral access crossover or conversion. AIMS: To evaluate the feasibility and safety of performing subclavian angioplasty via radial access during complex coronary interventions using the forearm approach. METHODS: A series of patients with complex radial approach due to subclavian stenosis received subclavian angioplasty during the procedure. We included 48 patients out of 22 500 procedures performed from February 2009 to February 2020. All patients did not have alternative vascular access due to extensive peripheral arterial disease (previous history of iliac stenting or distal aortic occlusion, which makes femoral access crossover difficult; also the contralateral radial/ulnar artery was very faint or not detectable at all). RESULTS: Mean age was 72 (10) years and 67% of patients were males. Subclavian angioplasty was successfully done in all patients via ipsilateral radial access; 44 patients (91.7%) required subclavian stenting, and 4 patients were treated by subclavian angioplasty without stenting. Coronary angiography or intervention was perfectly achieved through the revascularized subclavian artery; coronary stenting was successfully done in 36 patients as indicated. CONCLUSIONS: It can be concluded that percutaneous subclavian artery angioplasty can be done safely and effectively to facilitate complex transradial coronary procedures with an acceptable immediate technical success, especially in patients without alternative vascular access. Also, we may conclude that subclavian angioplasty may be successfully performed in patients with symptomatic upper limb ischemia, via the radial approach.

Feasibility and Clinical Outcomes of 48 mm Drug-Eluting Stents in the Management of Patients With Coronary Artery Disease.

BACKGROUND: Long coronary lesions represent a formidable challenge during percutaneous coronary intervention (PCI). Implantation of multiple contiguous stents may result in sections of overlapping stents or gaps of unstented segments and is an independent predictor of restenosis and major adverse cardiovascular events (MACEs). OBJECTIVES: The study goal was to assess the feasibility and short-term clinical outcomes of implanting 48 mm drug-eluting stents (DESs) for the treatment of long lesions in patients with coronary artery disease (CAD). METHODS: This prospective study enrolled 300 patients, with a single CAD planned to undergo PCI with 48 mm DES. Clinical data, procedural outcomes, and follow-up to 6 months were obtained. MACEs were considered the combined study endpoint, defined as cardiac death, non-fatal myocardial infarction, unstable angina, and the need for target-lesion revascularization (TLR). RESULTS: Among the 300 subjects enrolled, 80% were men and mean age was 60.8 ± 8.6 years. Procedural success rate was 97.3%. Failure of crossing was encountered in 4 patients due to severe tortuosity. Six-month clinical outcome was compared between diabetic (DM) (n = 90) and non-DM patients; 6-month cumulative MACEs were significantly lower in the non-DM group than in DM group (2.9% vs 13.3%, respectively; P=.01). Clinically driven TLR was 4% and 2 cardiac deaths were reported. The independent predictors of repeat revascularization were insulin-treated type 2 DM and reference vessel diameter (RVD) ≤2.75 mm. CONCLUSION: The use of 48 mm DES is feasible, safe, and cost effective in the treatment of long coronary lesions. Independent predictors of repeat revascularization are type 2 DM and RVD ≤2.75 mm.