Arterial stiffness assessment in coronary microvascular dysfunction and heart failure with preserved ejection fraction: An initial report from the WISE-CVD continuation study.

Background: Heart failure with preserved ejection fraction (HFpEF) is the most common cardiac complication in patients with coronary microvascular dysfunction (CMD), yet its underlying pathways remain unclear. Aortic pulse-wave velocity (aPWV) is an indicator of large artery stiffness and a predictor for cardiovascular disease. However, aPWV in CMD and HFpEF is not well characterized and may provide understanding of disease progression. Methods: Among participants without obstructive coronary artery disease, we evaluated 51 women with suspected CMD and 20 women and men with evidence of HFpEF. All participants underwent aPWV measurement (SphygmoCor, Atcor Medical) with higher aPWV indicating greater vascular stiffness. Cardiac magnetic resonance imaging (CMRI) assessed left ventricular (LV) ejection fraction, CMD via myocardial perfusion reserve index (MPRI), and ventricular remodeling via LV mass-volume ratio. . Statistical analysis was performed using Wilcoxon rank sum tests, Pearson correlations and linear regression analysis. Results: Compared to the suspected CMD group, the HFpEF participants were older (65 ± 12 vs 56 ± 11 yrs., p = 0.002) had higher BMI (31.0 ± 4.3 vs 27.8 ± 6.7 kg/m2, p = 0.013), higher aPWV (10.5 ± 2.0 vs 8.0 ± 1.6 m/s, p = 0.05) and lower MPRI (1.5 ± 0.3 vs1.8 ± 0.3, p = 0.02), but not remodeling. In a model adjusted for cardiovascular risk factors, the HFpEF group had a lower LVEF (estimate -4.78, p = 0.0437) than the suspected CMD group. Conclusions: HFpEF participants exhibit greater arterial stiffness and lower myocardial perfusion reserve, with lower LVEF albeit not remodeling, compared to suspected CMD participants. These findings suggest arterial stiffness may contribute to progression from CMD to HFpEF. Prospective work is needed and ongoing.

Cold Pressor Testing and Sympathetic Nervous System Contribution to Ischemia with No Obstructive Coronary Artery Disease: Results from the Women's Ischemia Syndrome Evaluation-Coronary Vascular Dysfunction Project.

Study Objective: Cold Pressor Testing (CPT) is a known stimulus of the sympathetic nervous system (SNS). To better understand sympathetic contribution to coronary blood flow regulation in women with suspected ischemia and no obstructive coronary arteries (INOCA), we compared myocardial perfusion reserve during CPT stress cardiac magnetic resonance (CMR) imaging between women with suspected INOCA and reference subjects. Design: Prospective cohort. Setting: Academic hospital. Participants: 107 women with suspected INOCA and 21-age-matched reference women. Interventions: CPT stress CMR was performed with measurement of myocardial perfusion reserve index (MPRI), adjusted for rate pressure product (MPRIRPP). Invasive coronary function testing in a subset of INOCA women (n=42) evaluated for endothelial dysfunction in response to acetylcholine, including impaired coronary diameter response ≤0% and coronary blood flow response (ΔCBF) <50%. Main Outcome Measure: MPRIRPP. Results: Compared to reference women, the INOCA group demonstrated higher resting RPP (p=0.005) and CPT MPRIRPP (1.09±0.36 vs 0.83±0.18, p=0.002). Furthermore, INOCA women with impaired ΔCBF (n=23) had higher CPT MPRIRPP (p=0.044) compared to reference women despite lower left ventricular ejection fraction (64±7 % vs 69±2 %, p=0.005) and mass-to-volume ratio (0.79±0.15 vs 0.62±0.09, p<0.0001). These differences in CPT MPRIRPP did not persist after adjusting for age, body mass index, and history of hypertension. CPT MPRIRPP among INOCA women did not differ based on defined acetylcholine responses. Conclusions: Myocardial perfusion reserve to CPT stress is greater among women with INOCA compared to reference subjects. CPT induced a higher MPRIRPP also in women with coronary endothelial dysfunction, suggesting a greater contribution of the SNS to coronary flow than endothelial dysfunction. Further investigation in a larger cohort is needed.

Coronary atheroma burden predicts flow reserve in women with ischemia and nonobstructive coronary artery disease.

Background: Women with signs and symptoms of ischemia and no obstructive coronary artery disease often have coronary microvascular dysfunction (CMD) with reduced coronary flow reserve (CFR), and compensatory coronary remodeling. Angiographic measurements of epicardial coronary anatomy (AMCA) may improve understanding of relations between CFR and atherosclerosis. We investigated AMCA and CFR in women evaluated for CMD. Methods: Women consecutively enrolled in the Women's Ischemia Syndrome Evaluation CVD Continuation (NCT00832702) were included. All underwent clinically indicated coronary function testing measuring CFR. AMCA included coronary angiographic atheroma burden (AB), percent diameter stenosis (PDS), and tapering reference diameter Z score (RDZ), derived for the left main and left anterior descending coronary epicardial segments. Results: The 51 women were aged 55.8 ±â€¯10.8 years, with 19(38%) hypertensive, 10(20.4%) hyperlipidemic, 4(7.8%) diabetic, 13(25.5%) prior smokers, and mean CFR 3.0 ±â€¯0.8. Both average and maximal AB negatively correlated with CFR (r = -0.30 and -0.31, with p = 0.04 for both), as did average and maximal PDS (r = -0.38 and -0.41 with p = 0.009 and p = 0.005) while average RDZ was directly related (r = 0.37, p = 0.01). Multiple linear regression analyses revealed that both average PDS (Units of CFR -0.03 95% CI: -0.06, -0.002, p = 0.023) and maximal PDS (-0.04 95% CI -0.07, -0.01, p = 0.007) were negatively related to CFR. Conclusions: Measures of epicardial coronary atheroma burden, size and tapering are related to CFR, suggesting that atherosclerotic anatomical findings may contribute to or be a consequence of CMD, with further work is needed to investigate these measures as treatment targets.

BMP-6 is more efficient in bone formation than BMP-2 when overexpressed in mesenchymal stem cells.

Bone regeneration achieved using mesenchymal stem cells (MSCs) and nonviral gene therapy holds great promise for patients with fractures seemingly unable to heal. Previously, MSCs overexpressing bone morphogenetic proteins (BMPs) were shown to differentiate into the osteogenic lineage and induce bone formation. In the present study, we evaluated the potential of osteogenic differentiation in porcine adipose tissue- and bone marrow-derived MSCs (ASCs and BMSCs, respectively) in vitro and in vivo when induced by nucleofection with rhBMP-2 or rhBMP-6. Our assessment of the in vivo efficiency of this procedure was made using quantitative micro-computed tomography (micro-CT). Nucleofection efficiency and cell viability were similar in both cell types; however, the micro-CT analyses demonstrated that in both ASCs and BMSCs, nucleofection with rhBMP-6 generated bone tissue faster and of higher volumes than nucleofection with rhBMP-2. RhBMP-6 induced more efficient osteogenic differentiation in vitro in BMSCs, and in fact, greater osteogenic potential was identified in BMSCs both in vitro and in vivo than in ASCs. On the basis of our findings, we conclude that BMSCs nucleofected with rhBMP-6 are superior at inducing bone formation in vivo than all other groups studied.

Comparing methods to identify hip fracture in a nursing home population using Medicare claims.

UNLABELLED: The inpatient principal diagnosis in Medicare claims identified 96% of hip fractures in hospitalized nursing home residents with high rates of confirmation by other claims files. INTRODUCTION: Hip fracture is typically identified in Medicare claims by examining only the principal diagnosis in the inpatient file, but this simple approach might be inadequate for nursing home residents. Our objective was to examine the impact of varied operational definitions for identifying hip fracture hospitalizations in administrative claims data. METHODS: We conducted a retrospective examination of Medicare inpatient and outpatient claims data for dually Medicaid- and Medicare-eligible nursing home residents in 1999 in California, Florida, Missouri, New Jersey, and Pennsylvania (n = 197,514). We determined the number of hip fractures identified in inpatient (Medicare A) diagnoses codes using differing definitions that varied according to whether or not hip fracture was required to be the principal diagnosis and whether or not confirmatory imaging and procedure codes were required to be found in other (Medicare B) claims files. RESULTS: Hip fractures were found in any inpatient diagnosis position in 4,680 subjects, with 4,479 of these found in the principal diagnosis position. With either approach to diagnosis position, confirmatory imaging and procedure codes were identified for 95% of persons hospitalized with hip fracture. CONCLUSION: The principal diagnosis alone will identify 96% of hip fracture diagnoses in hospitalized nursing home residents. Such diagnoses are confirmed at very high rates by other sources of claims data. Researchers may be confident using a simple approach to identifying hip fracture hospitalizations in this population, using inpatient claims alone and interrogating only the principal diagnosis position.