Pavel Goykhman

Ranolazine Improves Angina in Women With Evidence of Myocardial Ischemia But No Obstructive Coronary Artery Disease

OBJECTIVES We conducted a pilot study for a large definitive clinical trial evaluating the impact of ranolazine in women with angina, evidence of myocardial ischemia, and no obstructive coronary artery disease (CAD). BACKGROUND Women with angina, evidence of myocardial ischemia, but no obstructive CAD frequently have microvascular coronary dysfunction. The impact of ranolazine in this patient group is unknown. METHODS A pilot randomized, double-blind, placebo-controlled, crossover trial was conducted in 20 women with angina, no obstructive CAD, and ≥ 10% ischemic myocardium on adenosine stress cardiac magnetic resonance (CMR) imaging. Participants were assigned to ranolazine or placebo for 4 weeks separated by a 2-week washout. The Seattle Angina Questionnaire and CMR were evaluated after each treatment. Invasive coronary flow reserve (CFR) was available in patients who underwent clinically indicated coronary reactivity testing. CMR data analysis included the percentage of ischemic myocardium and quantitative myocardial perfusion reserve index (MPRI). RESULTS The mean age of subjects was 57 ± 11 years. Compared with placebo, patients on ranolazine had significantly higher (better) Seattle Angina Questionnaire scores, including physical functioning (p = 0.046), angina stability (p = 0.008), and quality of life (p = 0.021). There was a trend toward a higher (better) CMR mid-ventricular MPRI (2.4 [2.0 minimum, 2.8 maximum] vs. 2.1 [1.7 minimum, 2.5 maximum], p = 0.074) on ranolazine. Among women with coronary reactivity testing (n = 13), those with CFR ≤ 3.0 had a significantly improved MPRI on ranolazine versus placebo compared to women with CFR > 3.0 (Δ in MPRI 0.48 vs. -0.82, p = 0.04). CONCLUSIONS In women with angina, evidence of ischemia, and no obstructive CAD, this pilot randomized, controlled trial revealed that ranolazine improves angina. Myocardial ischemia may also improve, particularly among women with low CFR. These data document approach feasibility and provide outcome variability estimates for planning a definitive large clinical trial to evaluate the role of ranolazine in women with microvascular coronary dysfunction. (Microvascular Coronary Disease In Women: Impact Of Ranolazine; NCT00570089).

Myocardial ischemia in the absence of obstructive coronary artery disease in systemic lupus erythematosus.

OBJECTIVES the purpose of this study was to evaluate the presence of myocardial ischemia measured by adenosine stress cardiac magnetic resonance (CMR) using visual myocardial perfusion and a quantitative myocardial perfusion reserve index (MPRI) in the absence of obstructive coronary artery disease (CAD) in women with systemic lupus erythematosus (SLE) with anginal chest pain (CP). BACKGROUND ischemic heart disease is a leading cause of morbidity and mortality in SLE. Previous studies demonstrated the presence of perfusion defects using adenosine stress CMR in patients with CP and no obstructive CAD, consistent with microvascular coronary dysfunction in patients without SLE. METHOD Twenty female SLE patients with typical and atypical anginal CP were prospectively enrolled. Patients with established cardiovascular disease were excluded. CMR was performed with 0.05 mmol/kg gadolinium adenosine stress first-pass perfusion in SLE patients and in 10 asymptomatic reference control women. SLE patients also underwent 64-slice coronary computed tomography angiography. CMR was scored visually and quantitatively (MPRI). RESULTS among 18 patients with complete data, no patient had obstructive CAD; however, 8 of 18 (44%) displayed visual perfusion defects on stress CMR compared with 0 in 10 control subjects (p = 0.014). The mean MPRI in patients versus controls was 2.0 ± 0.4 versus 2.4 ± 0.4 (p = 0.031) in the subepicardium and 1.8 ± 0.3 versus 2.1 ± 0.4 (p = 0.24) in the subendocardium. Multivariate linear regression revealed that SLE was the only predictor of subepicardial (p < 0.0025; β = -1.059) and subendocardial (p < 0.05; β = -0.529) MPRIs. CONCLUSIONS we observed a 44% prevalence of abnormal stress myocardial perfusion by CMR in the absence of obstructive CAD in SLE patients with anginal CP. Compared with controls, reduced MPRI was observed in SLE patients, and SLE presence was a significant predictor of an abnormal MPRI. These findings are consistent with the hypothesis that anginal CP in SLE patients without obstructive CAD is due to myocardial ischemia potentially caused by microvascular coronary dysfunction. Further research in a larger SLE population is warranted.

Cardiac magnetic resonance imaging myocardial perfusion reserve index assessment in women with microvascular coronary dysfunction and reference controls

OBJECTIVE We sought to comparatively assess cardiac magnetic resonance imaging (CMRI) myocardial perfusion reserve index (MPRI) in women with confirmed microvascular coronary dysfunction (MCD) cases and reference control women. BACKGROUND Women with signs or symptoms of myocardial ischemia in the absence of obstructive coronary artery disease (CAD) frequently have MCD which carries an adverse prognosis. Diagnosis involves invasive coronary reactivity testing (CRT). Adenosine CMRI is a non-invasive test that may be useful for the detection of MCD. METHODS Fifty-three women with MCD confirmed by CRT and 12 age- and estrogen-use matched reference controls underwent adenosine CMRI. CMRI was assessed for MPRI, calculated using the ratio of myocardial blood flow at hyperemia/rest for the whole myocardium and separately for the 16 segments as defined by the American Heart Association. Statistical analysis was performed using repeated measures ANOVA models. RESULTS Compared to reference controls, MCD cases had lower MPRI values globally and in subendocardial and subepicardial regions (1.63±0.39 vs. 1.98±0.38, P=0.007, 1.51±0.35 vs. 1.84±0.34, P=0.0045, 1.68±0.38 vs. 2.04±0.41, P=0.005, respectively). A perfusion gradient across the myocardium with lower MPRI in the subendocardium compared to the subepicardium was observed for both groups. CONCLUSIONS Women with MCD have lower MPRI measured by perfusion CMRI compared to reference controls. CMRI may be a useful diagnostic modality for MCD. Prospective validation of a diagnostic threshold for MPRI in patients with MCD is needed.

Reproducibility of myocardial perfusion reserve - variations in measurements from post processing using commercially available software

PURPOSE Adenosine stress first pass cardiac magnetic resonance imaging (CMRI) is a rapidly evolving tool in the diagnosis of ischemic heart disease (IHD). The rest and stress first pass myocardial perfusion data may be interpreted using commercially available software for calculation of time intensity curves in order to generate a numeric value of the segmental or whole heart myocardial perfusion reserve index (MPRI). The objective of this study was to determine the inter- and intra-observer reliability of the data generated by standard commercially available software. METHODS Data from 20 adenosine stress CMRI (1.5 T) studies were analyzed using commercially available CAAS MRV 3.3 software (Pie Medical Imaging B.V., Netherlands) for calculation of the MPRI. The stress CMRI was performed using a standardized protocol in 20 women including 10 women with angina and the absence of obstructive CAD and 10 healthy volunteers. MPRI calculation was made in a standardized manner on separate occasions by two independent observers. A single observer repeated the calculation of MPRI three months later, without reference to the prior data. Basal, mid, and apical segments, for the whole myocardium, sub-endocardium, and sub-epicardium were analyzed. Intra-class correlation coefficients (ICC), repeatability coefficients (RC), and coefficients of variation (CoV) were determined. RESULTS The MPRI results by repeated software measurements were highly correlated, with potentially important variations in measurement observed. The myocardial inter-observer ICC was 0.80 (95% CI, 0.57, 0.92) with a CoV of 7.5%, and intra-observer ICC was 0.89 (95% CI, 0.77, 0.95) with a CoV of 3.6%. The mid-ventricular level MPRI was most reproducible, with intra-observer ICC at 0.91 (95% CI, 0.77, 0.97); intra-observer measurement was more reproducible than inter-observer measurement. CONCLUSIONS There is variation in measurement of MPRI observed in post processing of perfusion data when using a standardized approach and commercially available software. This has implications in the interpretation of data obtained for clinical and research purposes.

Comparison of long-term outcomes of drug-eluting stents and bare metal stents for saphenous vein graft stenosis.

Objective: Our aim was to compare the long‐term outcomes between drug‐eluting stents and bare‐metal stents for saphenous vein graft stenosis. Background: The ideal type of stent to treat saphenous vein graft stenosis has not been clearly established. Short‐term randomized controlled trial results comparing drug‐eluting stents with bare‐metal stents for saphenous vein graft stenosis are conflicting, intermediate‐term retrospective studies and meta‐analyses at two years suggest no difference in outcomes, and there are no long term follow‐up studies. The need for long term follow‐up data has become emerged with concern over late stent thrombosis. Methods: 246 saphenous vein graft patients undergoing stenting from August 2002–December 2008 were studied. Overall survival and event‐free survival were compared by Kaplan‐Meier method. Hazard ratios (HR) were calculated by Cox‐proportional hazards models. Results: We treated 133 patients with DES (median follow‐up four years) and 113 patients with BMS (median follow‐up four years) for SVG stenosis. Overall survival (77.0% ± 3.9% vs. 70.6% ± 4.6%, log‐rank P = 0.60) and MACE‐free survival (57.5% ± 4.6% vs. 56.8% ± 4.9, log‐rank P = 0.70) were not significantly different between the DES and BMS groups. Although BMS was associated with increased risk of target lesion revascularization (TLR) (freedom from TLR 85.2% ± 3.5% vs. 90.0% ± 3.0%, HR 2.07, 95% CI 0.97–4.42, log‐rank P = 0.05), there was no significant difference in the freedom from myocardial infarction (86.7% ± 3.3% vs. 88.7% ± 3.2%, log‐rank P = 0.39) or target vessel revascularization (77.1% ± 4.2% vs. 76.1% ± 4.2%, log‐rank P = 0.33) between the two groups. Conclusions: Although mortality is not statistically different between DES and BMS for SVG stenosis, BMS is associated with increased risk of revascularization, thus suggesting the superiority of DES over BMS in the long term.

Subendocardial ischemia and myocarditis in systemic lupus erythematosus detected by cardiac magnetic resonance imaging.

To the Editor: A 47-year-old woman with systemic lupus erythematosus (SLE) was referred for evaluation of persistent chest pain, characterized as pressure-like substernal pain, associated with shortness of breath and palpitations, worse with exertion, but also occurring at rest, not related to food or body positioning. Medications included hydroxychloroquine, candesartan, and intermittent methylprednisolone for SLE flares, most recently treated 4 months prior to the current office visit. Vital signs, physical examination, and echocardiogram were normal. Computed tomography angiography demonstrated normal coronary arteries without evidence of plaque or calcification. However, an adenosine stress cardiac magnetic resonance imaging (CMRI) perfusion study demonstrated nearly circumferential subendocardial hypoperfusion (Figures 1A, 1B) without evidence of abnormality on T2 or delayed enhancement (DE; Figure 2, A1 and A2) and with a calculated left ventricular ejection fraction (LVEF) of 70%. Selective left coronary angiography, as part of the research protocol, demonstrated no obstructive coronary artery disease (CAD; Figure 3). Coronary reactivity testing showed an abnormal coronary flow reserve of 1.35 (normal > 2.5) in response to intracoronary adenosine, consistent with microvascular coronary dysfunction. Therapy with low-dose aspirin, statin, and carvedilol was initiated, with improvement in chest pain symptoms. Figure 1. First-pass perfusion images through the short axis, 2-chamber views. The images show normal myocardial enhancement at rest (B, D, F) and … Address correspondence to Dr. C.N. Bairey Merz, Cedars-Sinai Medical Center, 444 S. San Vicente Blvd., Suite 600, Los Angeles, CA 90048, USA. E-mail: noel.baireymerz{at}cshs.org.