Pharmacogenetic Variation in Over 100 Genes in Patients Receiving Acenocumarol.

Coumarins are widely prescribed worldwide, and in Mexico acenocumarol is the preferred form. It is well known that despite its efficacy, coumarins show a high variability for dose requirements. We investigated the pharmacogenetic variation of 110 genes in patients receiving acenocumarol using a targeted NGS approach. We report relevant population differentiation for variants on CYP2C8, CYP2C19, CYP4F11, CYP4F2, PROS, and GGCX, VKORC1, CYP2C18, NQO1. A higher proportion of novel-to-known variants for 10 genes was identified on 41 core pharmacogenomics genes related to the PK (29), PD (3), of coumarins, and coagulation proteins (9) including, CYP1A1, CYP3A4, CYP3A5, and F8, and a low proportion of novel-to-known variants on CYP2E1, VKORC1, and SULT1A1/2. Using a Bayesian approach, we identified variants influencing acenocumarol dosing on, VKORC1 (2), SULT1A1 (1), and CYP2D8P (1) explaining 40-55% of dose variability. A collection of pharmacogenetic variation on 110 genes related to the PK/PD of coumarins is also presented. Our results offer an initial insight into the use of a targeted NGS approach in the pharmacogenomics of coumarins in Mexican Mestizos.

[When should patients with aortic valve stenosis be surgically treated?]. / Cuándo operar a los enfermos con estenosis de la válvula aórtica?

Optimal time for choosing Aortic Valve Replacement in Aortic Stenosis patients is based on understanding the natural history of the disease and prognostic variables, such as age, symptom status and co-morbid factors. In patients with advanced congestive heart failure, the valvular area and transvalvular gradients, determined by echocardiography and cardiac catheterization studies, have limitations for preoperative evaluation; before surgery the reversibility of this myocardial depression must be identified. At present, there is widespread agreement that valve replacement is indicated for symptomatic severe aortic stenosis regardless of age; however, cardiac surgery remains controversial in asymptomatic patients but with abnormal response to exercise, ventricular tachycardia, valve area lesser than 0.6 cm2, and marked or excessive left ventricular hypertrophy. The presence of moderate or severe valvular calcification, together with a rapid increase in aortic-jet velocity, identifies patients with a very poor prognosis and these patients should be considered for surgery. Finally, the decision to operate a patient must be considered on individual factors and whether quality of life is improved, and not just on operative mortality and morbidity.

[Late thrombolysis and electrical stability in acute myocardial infarction. Role of the collateral flow]. / Trombolisis tardía y estabilidad eléctrica en el infarto agudo del miocardio: importancia del flujo colateral.

We evaluated 249 patients (pts) with first acute myocardial infarction: 1. Pts without thrombolysis, n = 119, 2. Pts treated with thrombolysis within 6 hours following MI, n = 80 and 3. Pts treated with thrombolysis between 6-12 hours after MI. Arrhythmic events were evaluated during follow up. All underwent heart rate variability studies and coronary angiogram where anterograde flow (TIMI) and collateral flow (Rentrop scale 0-2 = poor collateral flow and 3 = good collateral flow) were determined. Pts in group 2 and 3 showed a better anterograde and collateral flow than group 1 (p < 0.001). A lower spectral power in the high frequency band and a higher ratio low/high frequency band were observed in group 1 (p < 0.05). Conjunctive consolidation analysis showed more malignant arrhythmias in TIMI 0-2 with poor collateral flow than TIMI 0-2 with good collateral flow (17/138-12.3% vs 0/14-0%). Kaplan Meier analysis was able to demonstrate more cardiac sudden death events in TIMI 0-2 with poor collateral flow than TIMI 0-2 with good collateral flow or TIMI 3 (x2 = 7.22, p = 0.028), independently of thrombolytic treatment.

[Myocardial bridging. The role of microcirculation, coronary reserve and systolic endothelial injury]. / Puentes miocárdicos. Papel de la microcirculación, reserva coronaria y daño endotelial sistólico.

BACKGROUND: The relationship between myocardial bridging (MB) and ischemic heart disease is still controversial. However, a recent new evidence suggests that this relation is not by chance. PURPOSE: The purpose of our study was to review in a critical manner, the evidence for the relationship between MB and myocardial ischemia and its possible consequences. METHODS: We present 2 cases of our series and review the medical literature from January 1966 to January 1998 published and included in Medline and Current Contents. RESULTS AND CONCLUSIONS: The principal findings after this review were: 1) MB is not a normal variant; 2) The clinical impact of MB depends on its anatomical extension and degree of compressive effect; 3) The MB muscle is not similar to myocytes from other cardiac areas; 4) The environment surrounding coronary artery may be a crucial factor in determining whether the MB influences the induction of heart disorders or not; 5) The overshoot due to compressive effect on coronary artery might determine endothelial injury in the microcirculation post-MB; 6) In some cases, the systolic endothelial injury may contribute to release factors that are able to reduce the coronary reserve, resulting in myocardial ischemia; 7) The possible role of PTCA in this disorder still has to be proven. Surgical treatment should be considered when important myocardial ischemia had been demonstrated, even in those asymptomatic cases.