Özlem Demir

Effect of Mechanical Dyssynchrony and Cardiac Resynchronization Therapy on Left Ventricular Rotational Mechanics

Alterations in rotational mechanics can bring new aspects to the understanding of left ventricular (LV) dyssynchrony. The aims of this study were to investigate LV rotational mechanics in candidates for cardiac resynchronization therapy (CRT) and to assess the effect of CRT by speckle-tracking echocardiography. Fifty-four patients with heart failure and 33 healthy controls were studied. Thirty-three underwent CRT. Speckle tracking was applied to short- and long-axis views. Radial and longitudinal dyssynchrony were assessed as previously defined. Apical and basal rotations were measured as the average angular displacement about the LV central axis. LV twist and torsion were then calculated. Peak apical and basal rotation, peak LV twist and torsion, apical and basal rotation at aortic valve closure (AVC), and LV twist and torsion at AVC were significantly lower in patients than controls. Apical-basal rotation delay and AVC-to-peak LV twist interval were longer in patients and associated with decreased peak LV twist and LV twist at AVC, respectively. In patients, rotational indexes, particularly LV twist and torsion, were correlated strongly with radial dyssynchrony. LV torsion (cutoff 0.1 degrees /cm) and twist (cutoff 1 degrees ) at AVC had the highest sensitivity (90%) and specificity (77%) to predict CRT responders among all other parameters, including radial and longitudinal dyssynchrony. In conclusion, LV dyssynchrony is associated with discoordinate rotation of the apical and basal regions, which in turn significantly decreases peak LV twist and torsion and LV twist and torsion at AVC. CRT significantly restored the altered rotational mechanics in responders. These parameters have potential for predicting responders to CRT.

Right Ventricular Function Is a Determinant of Long-Term Survival after Cardiac Resynchronization Therapy

BACKGROUND Right ventricular (RV) dysfunction is a marker of poor prognosis in patients with heart failure. The aim of this study was to investigate the impact of RV function on the long-term outcomes of patients undergoing cardiac resynchronization therapy (CRT). METHODS A total of 120 consecutive patients treated with CRT according to guideline criteria were followed over 5 years. Comprehensive echocardiographic analyses of RV function and radial and longitudinal mechanical left ventricular dyssynchrony were performed at baseline and 6 months after implantation. RV function was evaluated by two-dimensional longitudinal strain of the free wall, fractional area change, tricuspid annular plane systolic excursion, and tricuspid annular systolic velocity. Long-term follow-up events were defined as all-cause mortality, heart transplantation, or assist device implantation. RESULTS Long-term events occurred in 38 patients. Among the studied variables for RV function, RV strain < 18% had the highest sensitivity (79%) and specificity (84%) to predict a poor outcome after CRT (area under curve, 0.821; P < .0001). When adjusted for confounding baseline variables of ischemic etiology, mechanical dyssynchrony, left ventricular end-systolic volume, mitral regurgitation, and medical therapy, RV dysfunction remained independently associated with outcomes, indicating a 5.7-fold increased risk for hard events (P < .0001). CONCLUSIONS Preserved RV function as assessed by speckle-tracking strain imaging appears to be an independent predictor of long-term event-free survival after CRT.

Association of serum adiponectin levels and coronary flow reserve in women with normal coronary angiography

Background Women may have atypical clinical presentations and atypical risk factors of coronary artery disease. Adiponectin has anti-insulin-resistant properties and antiatherogenic effects. We investigated the association between serum adiponectin levels and coronary flow reserve (CFR) in women with normal coronary arteries. Methods CFR was assessed in 45 consecutive women (mean age 54.2 ± 9.2 years) with normal epicardial coronary arteries by coronary angiography. Serum adiponectin, C-reactive protein, insulin, and glucose levels were examined and Homeostasis Model Assessment for Insulin Resistance index was calculated. Peak diastolic coronary flow velocities were measured in distal left anterior descending artery at baseline and after dipyridamole infusion by transthoracic pulsed wave Doppler echocardiography. CFR was calculated as the ratio of hyperemic to baseline peak diastolic velocities. A CFR value ≥ 2 was accepted as normal. Results Adiponectin levels were lower in patients with impaired CFR than those with normal CFR (7.1 ± 2.3 vs. 13.8 ±6.7 μg/ml P < 0.001). Adiponectin levels were correlated with CFR (r =0.531, P < 0.001) and inversely correlated with C-reactive protein (r = −0.308, P = 0.047), insulin (r = −0.426, P = 0.008), and Homeostasis Model Assessment for Insulin Resistance index (r = −0.442, P = 0.004). Adiponectin levels of ≤ 8.5 μU/ml had 83% sensitivity and 93% specificity [receiver operating characteristic area 0.084, P < 0.001, 95% confidence interval (0.56-1.08)] for predicting impaired CFR. Conclusion Decreased adiponectin levels are associated with impaired CFR in women with normal epicardial coronary arteries and hypoadiponectinemia may be a risk factor for impaired CFR in women.

Increased serum gamma-glutamyltransferase activity in patients with metabolic syndrome

OBJECTIVES Accumulating data indicate that serum gamma-glutamyltransferase (GGT) activity represents a true marker of atherosclerotic cardiovascular disease and has prognostic importance. In this study, we sought to evaluate serum GGT activity in patients with metabolic syndrome (MetS). STUDY DESIGN We enrolled 232 patients (mean age 60.4 years) from our outpatient cardiology clinic, 117 with and 115 without MetS (control group) as defined by the ATP-III criteria. The results of serum liver function tests including serum GGT and C-reactive protein (CRP) levels were compared between the two groups. RESULTS The two groups were similar with regard to age, sex, smoking, and family history of coronary artery disease (p>0.05). The prevalences of hypertension and dyslipidemia were significantly higher in patients with MetS. Compared with controls, patients with MetS had significantly higher serum GGT [(median 21, interquartile range (16-33) vs. 19 (14-26) U/l; p=0.008] and C-reactive protein levels [6.2 (3.6-9.4) vs. 5.0 (3.1-7.0) U/l; p=0.044]. A high GGT activity (>40 U/l) was determined in 14.5% of the patients with MetS and in 4.4% of the control subjects (p=0.012). Serum GGT level showed significant correlations with MetS (r=0.24, p=0.001), CRP (r=0.20, p=0.003), triglyceride (r=0.18, p=0.006), HDL cholesterol (r=-0.19, p=0.004), aspartate aminotransferase (r=0.15, p=0.02), alanine aminotransferase (r=0.32, p=0.001), and alkaline phosphatase (r=0.16, p=0.01). This significant association continued only for MetS (β=-0.25, p=0.03), HDL cholesterol (β=-0.18, p=0.03), and alkaline phosphatase (β=0.17, p=0.01) in multivariate regression analysis. CONCLUSION Our findings suggest that patients with MetS have higher serum GGT and CRP levels compared with controls. This increased GGT level might be a marker of increased oxidative stress and premature atherosclerosis.

Effect of right ventricular pacing lead on left ventricular dyssynchrony in patients receiving cardiac resynchronization therapy.

Right ventricular (RV) pacing-induced left ventricular (LV) dyssynchrony can be 1 reason of nonresponse to cardiac resynchronization therapy (CRT) by potentially interfering with spontaneous dyssynchrony. We investigated the effect of the RV pacing lead on LV dyssynchrony in patients receiving CRT. LV radial dyssynchrony was assessed in a 16-segment model by using the novel speckle-tracking imaging before CRT and after the procedure, when the device was randomized to biventricular and RV pacing with crossover after 48 hours. LV lead tip was localized under fluoroscopic guidance. Of 43 patients, 30 (70%) acutely responded to CRT by a decrease in end-systolic volume >10%. RV pacing did not significantly increase the magnitude but altered the pattern of intraventricular dyssynchrony in the overall study group. During RV pacing, major shifts in the latest activated region occurred in 20 patients. However, LV radial dyssynchrony during spontaneous rhythm, but not the 1 induced by RV pacing, predicted response to CRT. When lead localization was optimal according to spontaneous dyssynchrony, response rate was 89% compared with 50% when lead localization was not optimal (p = 0.01). In contrast, when lead localization was optimal according to RV pacing-induced dyssynchrony, response rate was 81% compared with 67% when lead localization was not optimal (p = NS). In conclusion, RV apical pacing can alter the pattern of spontaneous LV dyssynchrony in patients receiving CRT. However, this alteration does not detract from the value of assessing LV dyssynchrony during spontaneous rhythm to predict responders to CRT.

Assessment of biochemical aspirin resistance at rest and immediately after exercise testing

Some aspirin-treated patients experience thromboembolic events, a phenomenon termed ‘aspirin resistance’, which may be clinical or biochemical by definition. Physical exercise is known to enhance platelet secretion and aggregability. To evaluate the presence of biochemical aspirin resistance at rest and immediately after exercise in individuals with stable coronary artery disease or coronary artery disease risk factors. We prospectively enrolled 101 patients who had received 100 or 300 mg/day enteric-coated aspirin for at least 7 days. Biochemical aspirin resistance (defined as normal collagen-epinephrine closure time < 165 s) was studied using the standardized platelet function analyzer. Of the 101 patients, 63 were aspirin sensitive both at rest and immediately after exercise, 18 exhibited biochemical aspirin resistance both at rest and after exercise, and 20 were aspirin sensitive at rest but exhibited biochemical aspirin resistance immediately after exercise. The results of exercise testing were similar in all three groups (each P > 0.05). Our results indicate that in almost 20% of the patients, aspirin did not seem to protect against exercise-induced platelet activation, despite the presence of aspirin sensitivity at rest. We did not, however, determine the extent to which the biochemical aspirin resistance noted in our study applied to clinical events.

C-reactive protein levels increase after exercise testing in patients with increased platelet reactivity.

Aspirin has the potential to influence C-reactive protein (CRP) levels, an inflammatory marker, by its anti-inflammatory activity. Persistently increased platelet reactivity, however, can be detected with different laboratory methods despite aspirin therapy in some patients. The aim of this study was to investigate the effects of increased platelet reactivity on CRP levels at rest and after exercise in patients with documented or suspected coronary artery disease. Blood samples were collected from 100 patients (age, 58.1±8.5 years; 63.0% men) who were treated with 100 or 300 mg/day enteric-coated aspirin for at least 7 days, before and immediately after treadmill test for CRP analyses. Platelet reactivity was measured by the standardized platelet function analyzer-100, and increased platelet reactivity was defined as a normal collagen/epinephrine closure time (<165 s). Of the 100 patients, 82 had normal platelet reactivity (group A) and 18 had increased platelet reactivity (group B). The CRP levels increase was statistically significant after exercise in patients with increased platelet reactivity [group A: 2.3 (1.4–4.3) to 2.8 (1.6–4.9) mg/l, P=0.09; group B: 3.3 (2.0–4.5) to 4.7 (2.9–8.5) mg/l, P=0.02]. Detecting increased platelet reactivity is associated with an increase in CRP levels. The clinical significance of this finding needs to be further investigated.