Current Issue 1 February 2012 | Vol. 109, No. 3

Coronary Artery Disease

• Association of Frontal QRS-T Angle – Age Risk Score on Admission Electrocardiogram with Mortality in Patients Admitted with an Acute Coronary Syndrome

Risk assessment is central to the management of acute coronary syndromes (ACS). Often, however, assessment is not complete until the troponin concentration is available. Using 2 multi-centre prospective observational studies (EMMACE-2, test cohort, 1,843 patients and EMMACE-1, validation cohort, 550 patients) of unselected ACS patients, we evaluated a point-of-admission risk stratification tool using frontal QRS-T angle derived from automated measurements and age for the prediction of 30-day and 2-year mortality. 2-year mortality was lowest in patients with a frontal QRS-T angle <38° and highest in patients with a frontal QRS-T angle >104° (44.7% versus 14.8%, P<0.001). Increasing Frontal QRS-T Angle – Age Risk (FAAR) scores were associated with increasing 30-day and 2-year mortality (2-year mortality: score 0 = 3.7%; score 4 = 57%, P<0.001). The FAAR score was a good discriminator of mortality; C statistic (95% CI) at 30-days 0.74 (0.71 to 0.78) and 2-years 0.77 (0.75 to 0.79), maintained its performance in the EMMACE-1 cohort at 30-days, C statistic (95% CI) at 30-days 0.76 (0.71 to 0.8) and 2-years 0.79 (0.75 to 0.83), in males and females, in STEMI and NSTEMI, and compared favourably with the GRACE score. The integrated discrimination improvement ('age' to 'FAAR score' at 30-days and at 2-years in EMMACE-1 and EMMACE-2) was P<0.001. The FAAR score is a point-of-admission risk tool that predicts 30-day and 2-year mortality from two variables across a spectrum of ACS patients. It does not require the results of biomarker assays nor relies upon the subjective interpretation of ECGs.

Preventive Cardiology

• Efficacy and Safety of Co-administration of Rosuvastatin, Ezetimibe and Colestimide in Heterozygous Familial Hypercholesterolemia

Aggressive low density lipoprotein (LDL)-cholesterol lowering therapy is important for high risk patients. However, little data exists regarding the impact of combined aggressive LDL-cholesterol lowering therapy in FH particularly in terms of side effects to changes in plasma coenzyme Q10 (CoQ10) and proproteinconvertasesutilisin/kexin type 9 (PCSK9) levels.We enrolled 17 Japanese patients with heterozygous FH (12 males, 63.9±7.4 years) with single LDL receptor gene mutations in a prospective open randomized study. Permitted maximum doses of rosuvastatin (20mg/day), ezetimibe (10mg/day) and granulated colestimide (3.62g/day) were introduced sequentially. Serum levels of LDL-cholesterol significantly decreased by -66.4%(p<0.001) and 44% of participants reached LDL-cholesterol levels of < 100mg/dL. There were no serious side effects or abnormal laboratory data that would have required the protocol to have been terminated except for a single patient suffering from myalgia. Coadministration of ezetimibe and granulated colestimide further reduced serum LDL-cholesterol more thanrosuvastatin alone without changing plasma CoQ10 and PCSK9 levels. In conclusion, adequate introduction of this aggressive cholesterol-lowering regimen can improve the lipid profile of FH.

Heart Failure

• Analysis of Circumferential and Longitudinal Left Ventricular Systolic Function in Patients with Non-ischemic Chronic Heart Failure and Preserved Ejection Fraction (From the CARRY-IN-HFpEF study)

Heart failure with preserved left ventricular (LV) ejection fraction (HFpEF) is implicitly attributed to diastolic dysfunction, often recognized in elderly patients with hypertension, diabetes, renal dysfunction. In these patients, LV circumferential and longitudinal shortening is often impaired in spite of normal ejection fraction. In this prospective study we analyzed circumferential and longitudinal shortening and their relationships in patients with non-ischemic HFpEF. Stress-corrected midwall shortening (sc-MS) and mitral annular peak systolic velocity (S') were measured in 60 patients (age 73 ± 13 years) with chronic non-ischemic HFpEF in stable NYHA functional class II-III, and compared with 120 healthy controls and 120 hypertensives without HFpEF. Sc-MS was classified low if < 89%, S' if < 8.5 cm/sec (10th percentiles of healthy controls). Isolated low sc-MS was detected in 46% of HFpEF, 27% of hypertensives and 2% of controls; isolated low S' in 11% of HFpEF, 7% of hypertensives and 5% of controls; combined low sc-MS and low S' in 26% of HFpEF, 9% of hypertensives and 5% of controls (HFpEF vs others, all p < 0.001). Thus, any alteration of systolic function was found in 83% of patients with HFpEF. The relation between sc-MS and S' was nonlinear (cubic). Changes in S' within normal values corresponded to negligible variations in sc-MS, whereas the progressive decrease below 8.5 cm/sec was associated with substantial decrease in sc-MS. In conclusion, circumferential and/or longitudinal systolic dysfunction is present in a large majority of patients with HFpEF. Circumferential shortening normalized by wall stress identifies more patients with concealed LV systolic dysfunction than longitudinal shortening.