Impact of myocardial viability assessed by myocardial perfusion imaging on ventricular tachyarrhythmias in cardiac resynchronization therapy.

BACKGROUND: The presence of myocardial fibrosis is associated with ventricular tachyarrhythmia (VT) occurrence irrespective of cardiomyopathy etiology. The aim of our study was to evaluate the impact of global and regional viability on VTs in patients undergoing cardiac resynchronization therapy (CRT). METHODS: Fifty-seven patients with advanced heart failure (age 62.3 ± 10.2; 38 men; 24 ischemic etiology) were evaluated using single-photon emission computed tomography myocardial perfusion imaging before CRT defibrillator device implantation. Global myocardial viability was determined by the number of viable segments in a 20-segment model. Regional viability was calculated as the mean tracer activity in the corresponding segments at left ventricular (LV) lead position. LV lead segments were determined at implant venography using 2 projections (left anterior oblique 30 and right anterior oblique 30) of coronary sinus tributaries. Patients were followed 30 (24-34) months for the occurrence of VTs. RESULTS: VTs were registered in 18 patients (31.6%). Patients without VTs had significantly more viable segments (17.6 ± 2.35 vs 14.2 ± 4.0; P = .002) and higher regional myocardial viability at LV lead position (66.1% ± 10.3% vs 54.8% ± 11.4% of tracer activity; P = .001) than those with VTs. In multivariate logistic regression models, the number of viable segments (OR = 0.66; 95% confidence interval (CI) 0.53-0.85; P = .001) and regional viability (OR = 0.90; 95% CI 0.85-0.97; P = .003) were the only independent predictors of VT occurrence. CONCLUSION: Global and regional myocardial viability are independently related to the occurrence of VTs in patients after CRT.

Procoagulant state in heart failure with preserved left ventricular ejection fraction.

The impact of heart failure with preserved left ventricular ejection fraction (LVEF) on activated hemostasis is still unclear. We sought to compare the activation of hemostasis in patients with heart failure with preserved LVEF, with impaired LVEF, and in healthy controls. Biomarkers of coagulation and fibrinolysis (D-dimer, tPA and PAI-1) were determined in outpatients with chronic stable (NYHA I-III), optimally managed heart failure with preserved LVEF (n = 46) and with impaired LVEF (n = 52), and in healthy age- and gender-matched controls (n = 14). In comparison to healthy controls, patients with heart failure and preserved LVEF had increased median D-dimer levels (606 [330-1222] microg/L versus 174 [86-249] microg/L; P < 0.001), and median PAI-1 (20 [15.3-33.1] microg versus 6.2[3.4-8.9] microg/L; P < 0.001) and tPA antigen concentrations (9.6 [8.1-13.3] versus 3.6 [2.2-5.0] microg/L; P < 0.001). However, unlike tPA and PAI antigens, D-dimer levels in preserved LVEF did not reach values as high as in impaired LVEF (917 [454-1185] microg/L; P = 0.013). Moreover, in patients with impaired LVEF, but not in those with preserved LVEF, age and NT-proBNP emerged as independent predictors of log-transformed D-dimer levels. Heart failure with preserved LVEF is associated with a procoagulant state as determined by increased levels of D-dimer, tPA and PAI-1 antigens. D-dimer levels are significantly higher in patients with impaired LVEF, while tPA and PAI-1 levels are increased regardless of LVEF.

Prognostic impact of haemostatic derangements in chronic heart failure.

Heart failure is characterised by activation of haemostasis. We sought to explore the prognostic impact of deranged haemostasis in chronic heart failure. In stable, optimally managed outpatients with chronic heart failure, baseline levels of prothrombin fragment F1+2, D-dimer, and tPA and PAI-1 antigens were determined. Clinical follow-up was obtained and the rate of events (heart failure related deaths or hospitalisations) was recorded. We included 195 patients [32.3% female, NYHA class II (66.2%) or III (33.8%), mean age 71 years]. During a median follow up of 693 (interquartile range [IQR] 574-788) days, 63 (30.9%) patients experienced an event; those with an event had higher levels of tPA antigen (median 11.8 [IQR 8.7-14.0] vs. 9.4 [7.9-12.1] microg/l; p = 0.033) and D-dimer (938 [485-1269] vs. 620 [37-1076] microg/l; p = 0.018). However, on Cox multivariate analysis, only tPA levels above optimal cut-off value of 10.2 microg/l (but not D-dimer) emerged as an independent predictor of prognosis (HR(adjusted) 2.695, 95% confidence interval 1.233-5.363; p = 0.017). Our findings suggest that elevated tPA antigen levels are an independent prognostic predictor in patients with chronic stable heart failure.

Interleukin-6 is a stronger prognostic predictor than high-sensitive C-reactive protein in patients with chronic stable heart failure.

Heart failure is characterized by activation of the immune system which is strongly associated with disease severity and outcome. We sought to compare the prognostic impact of two established inflammatory markers - interleukin-6 (IL-6) and high-sensitivity C-reactive protein (hsCRP) - in patients with chronic heart failure. In stable, optimally managed outpatients with chronic heart failure, baseline levels of hsCRP and IL-6 were determined. Clinical follow-up was obtained and the rate of events (heart failure related deaths or hospitalizations) were recorded. We included 201 patients (32.7% female, NYHA class II [66.2%] or III [33.8%], mean age 70 years). During a median follow up of 614 (367-761) days, 64 (30.9%) patients experienced an event; those with an event had higher levels of hsCRP (median 2.93 [interquartile range 2.36-8.92] vs 2.23 [1.32-5.77] mmol/l) and IL-6 (7.8 [4.7-10.3] vs 4.3 [2.6-7.9] pg/ml). However, on Cox multivariate analysis, IL-6 but not hsCRP emerged as an independent predictor of prognosis (hazard ratio HR(adjusted) 2.74, 95% confidence interval 1.17-6.43; P = 0.020). Our findings suggest that IL-6 is a better prognostic predictor than hsCRP in patients with chronic stable heart failure.

A randomized, placebo-controlled trial of the effects of continuous combined hormone replacement therapy on coagulation and fibrinolytic systems in healthy postmenopausal women.

OBJECTIVE: To investigate the effects of combined hormone replacement therapy (HRT) on various parameters of coagulation and fibrinolysis that may contribute to increased risk for venous thromboembolic events. DESIGN: Prospective, randomized, double-blind, placebo-controlled study. SETTING: Academic hospital. PATIENT(S): Sixty-one healthy postmenopausal women with intact uterus. INTERVENTION(S): Patients were randomized to receive continuous combined HRT (estradiol, 2 mg/d, and norethisterone acetate, 1 mg/d) or placebo for 6 months. MAIN OUTCOME MEASURE(S): Markers of coagulation and fibrinolysis were measured before therapy and after 3 and 6 months of therapy. RESULT(S): The groups did not differ significantly in levels of prothrombin fragments 1 and 2 and thrombin-antithrombin III complex after 3 and 6 months of therapy. After 6 months of HRT, significant decreases in activity of antithrombin III and protein C and levels of plasminogen activator inhibitor-1 antigen, tissue-type plasminogen activator antigen, and euglobulin clot lysis time and a significant increase in D-dimer level were found compared with placebo. CONCLUSION(S): Continuous combined HRT for several months produced no net activation of coagulation but improved fibrinolysis in healthy postmenopausal women with no risk factors for venous thromboembolic events.