Impact of Complete Revascularization in the ISCHEMIA Trial.

BACKGROUND: Anatomic complete revascularization (ACR) and functional complete revascularization (FCR) have been associated with reduced death and myocardial infarction (MI) in some prior studies. The impact of complete revascularization (CR) in patients undergoing an invasive (INV) compared with a conservative (CON) management strategy has not been reported. OBJECTIVES: Among patients with chronic coronary disease without prior coronary artery bypass grafting randomized to INV vs CON management in the ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) trial, we examined the following: 1) the outcomes of ACR and FCR compared with incomplete revascularization; and 2) the potential impact of achieving CR in all INV patients compared with CON management. METHODS: ACR and FCR in the INV group were assessed at an independent core laboratory. Multivariable-adjusted outcomes of CR were examined in INV patients. Inverse probability weighted modeling was then performed to estimate the treatment effect had CR been achieved in all INV patients compared with CON management. RESULTS: ACR and FCR were achieved in 43.4% and 58.4% of 1,824 INV patients. ACR was associated with reduced 4-year rates of cardiovascular death or MI compared with incomplete revascularization. By inverse probability weighted modeling, ACR in all 2,296 INV patients compared with 2,498 CON patients was associated with a lower 4-year rate of cardiovascular death or MI (difference -3.5; 95% CI: -7.2% to 0.0%). In comparison, the event rate difference of cardiovascular death or MI for INV minus CON in the overall ISCHEMIA trial was -2.4%. Results were similar but less pronounced with FCR. CONCLUSIONS: The outcomes of an INV strategy may be improved if CR (especially ACR) is achieved. (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches [ISCHEMIA]; NCT01471522).

To study the usefulness and comparison of myocardial strain imaging by 2D and 3D echocardiography for early detection of cardiotoxicity in patients undergoing cardiotoxic chemotherapy.

BACKGROUND: Chemotherapy-induced cardiotoxicity constitutes subclinical myocardial dysfunction, arrhythmias, pericarditis, coronary vasospasm, and significant symptomatic heart failure. Anthracyclines pose higher risk for long-term cardiac dysfunction, with increased incidences of morbidity and mortality. Hence, early detection of chemotherapy-induced cardiac dysfunction may prompt an earlier treatment modification. AIM: To evaluate global, longitudinal, radial, and circumferential strain changes in adult patients undergoing anthracycline chemotherapy along with the usefulness of three-dimensional (3D) echocardiography as the new modality over two-dimensional (2D) echocardiography. METHODS: This was a single centre, prospective, observational study that included asymptomatic patients free from any cardiac signs and symptoms attributable to heart failure, who underwent potentially cardiotoxic chemotherapy for malignancy from December 2017 to November 2018 at a tertiary care centre in India. Baseline demographics were recorded, and 2D and 3D echocardiography was performed at baseline and after completion of four cycles of chemotherapy. RESULTS: All the 55 patients received a cumulative dose of doxorubicin of less than 550 mg/m2. Follow-up period from the beginning of doxorubicin therapy was 108 ± 14 days. 9 patients were excluded from the study due to poor 3D images, so data analysis was done only for 46 patients. In 2D echocardiography, only global longitudinal strain (GLS) was observed to be significantly reduced (Δ18.33%; P < 0.001). 2D ejection fraction (EF) did not show significant change (Δ0.67%; P = 0.176), while by 3D echo, EF reduced significantly (Δ3.55%; P < 0.001). 3D global longitudinal (Δ29.19%; P < 0.001), circumferential (Δ30.65%; P < 0.001), area (Δ21.61%; P < 0.001), and radial (Δ29.66%; P < 0.001) strains were observed to be significantly reduced at follow-up. CONCLUSION: Myocardial dysfunction induced by cardiotoxic chemotherapy can be detected earlier by using 2D GLS, 3D volumetric analysis, and 3D strain analysis by calculating global, longitudinal, radial, and circumferential strain changes. 3D echocardiographic assessment seems to be more accurate in picking out small changes in left ventricular functions, but at the cost of slightly poor image quality as compared to the 2D echocardiography. These newer techniques could potentially improve the ability for early detection of subclinical abnormalities of LV function in patients undergoing cardiotoxic chemotherapy and thus early initiation of treatment could be possible.

Profile and prevalence of clopidogrel resistance in patients of acute coronary syndrome.

UNLABELLED: Recently reports of a variable platelet response to aspirin and potential resistance to therapy have emerged with thienopyridines group of drugs. However the data available on clopidogrel resistance is scarce. The present study was initiated to prospectively evaluate the prevalence of clopidogrel resistance in patients of acute coronary syndrome(ACS) presently on dual anti platelet therapy by using an established method of optical platelet aggregation. We studied 39 patients of ACS, who were on clopidogrel 300 mg bolus followed by 75 mg per day for 3 days along with aspirin 325 mg per day. Fasting blood samples were assessed using optical platelet aggregation (Chronolog Corp, USA). Clopidogrel resistance was defined as <10% decrease from baseline in platelet aggregation. Clopidogrel semi-responders were defined as 10-29% ( <30%) decrease from baseline in platelet aggregation. Clopidogrel non-responders were defined as a composite of resistant and semi-responders. A baseline mean platelet aggregation obtained from 18 healthy subjects was 63.8 +/- 14.75% with 5 mu and 68.8 +/-13.91% with 10 mu of Adenosine Diphosphate. Hence, the definition of clopidogrel resistance was set as aggregation of >57% with 5 mu ADP and >61.9% with 10 mu ADP (< 10% decrease from baseline). The definition of clopidogrel semi-responder was set as aggregation of >or=45% with 5 mu ADP and >or=48% with 10 mu ADP (10-29% decrease from baseline). The mean platelet aggregation with 5 mu and 10 mu of Adenosine Diphosphate in the patient group was 30.77 +/- 17.19% and 35.71 +/- 17.0% respectively. Based on these criteria, 2.54% patients were found to be clopidogrel resistant, 12.7% were clopidogrel semi-responders and 84.7% were clopidogrel responders. On comparison of clopidogrel responders with non-responders, females ( p=0.07) and patients with higher serum triglyceride levels (p=0.08), had a trend to be more inclined towards clopidogrel non-responders. All other parameters tested namely age, smoking, diabetes, hypertension, obesity, cholesterol, hemoglobin, platelet count, ejection fraction and concurrent drug intake did not show any statistically significant difference among the groups. CONCLUSIONS: This study shows that clopidogrel resistant and clopidogrel semi-responders do occur in Indian patients with ACS and there are no reliable clinical predictors for this condition. The diagnosis therefore relies primarily on laboratory tests.

Profile and prevalence of aspirin resistance in Indian patients with coronary artery disease.

BACKGROUND: Aspirin resistance is considered to be an enigma and the data available on aspirin resistance is scarce. This study was initiated to prospectively evaluate the prevalence of aspirin resistance in patients with stable coronary artery disease by using an established method of optical platelet aggregation. METHODS AND RESULTS: We studied 50 patients who were on 150 mg of aspirin for the previous 7 days. Fasting blood samples were assessed using optical platelet aggregation (Chronolog Corp, USA). The mean platelet aggregation with 10 microm of adenosine diphosphate in our patient group was 49.42 +/- 23.29% and with 0.5 mg/ ml of arachidonic acid it was 13.58 +/- 21.40%. Aspirin resistance was defined as a mean aggregation of > or =70% with 10 microm of adenosine diphosphate and a mean aggregation of > or =20% with 0.5 mg/ml of arachidonic acid. Aspirin semi responders were defined as those meeting only one of the criteria. Based on these criteria, 2.08% patients were found to be aspirin-resistant, 39.58% were aspirin semi responders and 58.33% were aspirin responders. Females tended to be more aspirin semi responsive (p = 0.08). All other parameters tested, namely, age, smoking, diabetes mellitus, hypertension, obesity, lipids, hemoglobin, platelet count, ejection fraction and drug intake did not show any statistically significant difference among the groups. Thus, in our group 41.66% patients showed inadequate response to aspirin. CONCLUSIONS: This study shows that aspirin resistance and aspirin semi responsiveness do occur in the Indian patients and there are no reliable clinical predictors for this condition. The diagnosis therefore relies primarily on laboratory tests.