Normal values of myocardial blood flow measured with dynamic myocardial computed tomography perfusion.

AIMS: Dynamic myocardial computed tomography (CT) perfusion (DM-CTP) can, in combination with coronary CT angiography (CCTA), provide anatomical and functional evaluation of coronary artery disease (CAD). However, normal values of myocardial blood flow (MBF) are needed to identify impaired myocardial blood supply in patients with suspected CAD. We aimed to establish normal values for MBF measured using DM-CTP, to assess the effects of age and sex, and to assess regional distribution of MBF. METHODS AND RESULTS: A total of 82 healthy individuals (46 women) aged 45-78 years with normal coronary arteries by CCTA underwent either rest and adenosine stress DM-CTP (n = 30) or adenosine-induced stress DM-CTP only (n = 52). Global and segmental MBF were assessed. Global MBF at rest and during stress were 0.93 ± 0.42 and 3.58 ± 1.14 mL/min/g, respectively. MBF was not different between the sexes (P = 0.88 at rest and P = 0.61 during stress), and no correlation was observed between MBF and age (P = 0.08 at rest and P = 0.82 during stress). Among the 16 myocardial segments, significant intersegmental differences were found (P < 0.01), which was not related to age, sex, or coronary dominance. CONCLUSION: MBF assessed by DM-CTP in healthy individuals with normal coronary arteries displays significant intersegmental heterogeneity which does not seem to be affected by age, sex, or coronary dominance. Normal values of MBF may be helpful in the clinical evaluation of suspected myocardial ischaemia using DM-CTP.

Quantification of myocardial blood flow using dynamic myocardial CT perfusion compared with 82Rb PET.

PURPOSE: Absolute measures of myocardial blood flow (MBF) obtained with dynamic myocardial CT perfusion (DM-CTP) are underestimated when compared with reference standards. This is to some extent explained by incomplete extraction of iodinated contrast agent (iCA) to the myocardial tissue. We aimed to establish an extraction function for iCA, use the function to calculate MBFCT and to compare this with MBF measured with 82Rb positron emission tomography (PET). MATERIALS AND METHODS: Healthy individuals without coronary artery disease (CAD) were examined with 82Rb PET and DM-CTP. The factors a and ß of the generalized Renkin-Crone model were estimated using a non-linear least squares model. The factors providing the best fit for the data were subsequently used to calculate MBFCT. RESULTS: Of consecutive 91 individuals examined, 79 were eligible for analysis. The factors a and ß providing the best fit of the nonlinear least-squares model to the data were a â€‹= â€‹0.614 and ߠ​= â€‹0.218 (R-squared â€‹= â€‹0.81). Conversion of the CT inflow parameter (K1) values using the derived extraction function resulted in a significant correlation between MBF measured during stress using CT and PET (P â€‹= â€‹0.039). CONCLUSION: In healthy individuals, flow estimates obtained with dynamic myocardial CT perfusion during stress were, after conversion to MBF using the extraction of iodinated CT contrast agent, correlated with absolute MBF quantified with 82Rb PET.

Technical Considerations for Dynamic Myocardial Computed Tomography Perfusion as Part of a Comprehensive Evaluation of Coronary Artery Disease Using Computed Tomography.

Dynamic myocardial computed tomography perfusion (DM-CTP) has good diagnostic accuracy for identifying myocardial ischemia as compared with both invasive and noninvasive reference standards. However, DM-CTP has not yet been implemented in the routine clinical examination of patients with suspected or known coronary artery disease. An important hurdle in the clinical dissemination of the method is the development of the DM-CTP acquisition protocol and image analysis. Therefore, the aim of this article is to provide a review of critical parameters in the design and execution of DM-CTP to optimize each step of the examination and avoid common mistakes. We aim to support potential users in the successful implementation and performance of DM-CTP in daily practice. When performed appropriately, DM-CTP may support clinical decision making. In addition, when combined with coronary computed tomography angiography, it has the potential to shorten the time to diagnosis by providing immediate visualization of both coronary atherosclerosis and its functional relevance using one single modality.

Hemodynamic Effects of Cyclic Guanosine Monophosphate-Dependent Signaling Through ß3 Adrenoceptor Stimulation in Patients With Advanced Heart Failure: A Randomized Invasive Clinical Trial.

BACKGROUND: ß3-AR (ß3-adrenergic receptor) stimulation improved systolic function in a sheep model of systolic heart failure (heart failure with reduced ejection fraction [HFrEF]). Exploratory findings in patients with New York Heart Association functional class II HFrEF treated with the ß3-AR-agonist mirabegron supported this observation. Here, we measured the hemodynamic response to mirabegron in patients with severe HFrEF. METHODS: In this randomized, double-blind, placebo-controlled trial we assigned patients with New York Heart Association functional class III-IV HFrEF, left ventricular ejection fraction <35% and increased NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels to receive mirabegron (300 mg daily) or placebo orally for a week, as add on to recommended HF therapy. Invasive hemodynamic measurements during rest and submaximal exercise at baseline, 3 hours after first study dose and repeated after 1 week's treatment were obtained. Predefined parameters for analyses were changes in cardiac- and stroke volume index, pulmonary and systemic vascular resistance, heart rate, and blood pressure. RESULTS: We randomized 22 patients (age 66±11 years, 18 men, 16, New York Heart Association functional class III), left ventricular ejection fraction 20±7%, median NT-proBNP 1953 ng/L. No significant changes were seen after 3 hours, but after 1 week, there was a significantly larger increase in cardiac index in the mirabegron group compared with the placebo group (mean difference, 0.41 [CI, 0.07-0.75] L/min/BSA; P=0.039). Pulmonary vascular resistance decreased significantly more in the mirabegron group compared with the placebo group (-1.6 [CI, -0.4 to -2.8] Wood units; P=0.02). No significant differences were seen during exercise. There were no differences in changes in heart rate, systemic vascular resistance, blood pressure, or renal function between groups. Mirabegron was well-tolerated. CONCLUSIONS: Oral treatment with the ß3-AR-agonist mirabegron for 1 week increased cardiac index and decreased pulmonary vascular resistance in patients with moderate to severe HFrEF. Mirabegron may be useful in patients with worsening or terminal HF. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: 2016-002367-34.

Early Coronary Atherosclerosis in Women With Previous Preeclampsia.

BACKGROUND: Women with previous preeclampsia have an increased risk of coronary artery disease later in life. OBJECTIVES: This study aimed to determine the prevalence of coronary atherosclerosis in younger women with previous preeclampsia in comparison with women from the general population. METHODS: Women aged 40-55 years with previous preeclampsia were matched 1:1 on age and parity with women from the general population. Participants completed an extensive questionnaire, a clinical examination, and a coronary computed tomography angiography (CTA). The main study outcome was the prevalence of any coronary atherosclerosis on coronary CTA or a calcium score >0 in case of a nondiagnostic coronary CTA. RESULTS: A total of 1,417 women, with a mean age of 47 years, were included (708 women with previous preeclampsia and 709 control subjects from the general population). Women with previous preeclampsia were more likely to have hypertension (284 [40.1%] vs 162 [22.8%]; P < 0.001), dyslipidemia (338 [47.7%] vs 296 [41.7%]; P = 0.023), diabetes mellitus (24 [3.4%] vs 8 [1.1%]; P = 0.004), and high body mass index (27.3 ± 5.7 kg/m2 vs 25.0 ± 4.2 kg/m2; P < 0.001). Cardiac computed tomography was performed in all women. The prevalence of any coronary atherosclerosis was higher in the preeclampsia group (193 [27.4%] vs 141 [20.0%]; P = 0.001) with an OR: 1.41 (95% CI: 1.08-1.85; P = 0.012) after adjustment for age, dyslipidemia, diabetes mellitus, smoking, body mass index, menopause, and parity. CONCLUSIONS: Younger women with previous preeclampsia had a slightly higher prevalence of coronary atherosclerosis compared with age- and parity-matched women from the general population. Preeclampsia remained an independent risk factor after adjustment for traditional cardiovascular risk factors. (The CoPenHagen PREeClampsia and cardIOvascUlar diSease study [CPH-PRECIOUS]; NCT03949829).

Optimization of image sampling rate to lower the radiation dose of dynamic myocardial CT perfusion.

BACKGROUND: Dynamic myocardial CT perfusion (CTP) has emerged as a potential strategy to combine anatomical and functional evaluation in a single modality. However, this method results in a high radiation dose. METHODS: Dynamic CTP was performed in 56 patients with suspected or known ischemic heart disease of whom 48 had complete CT-data. Datasets with reduced sampling rate of 2- and 3 RR-intervals (2RR and 3RR) were constructed post hoc. Myocardial blood flow (MBF) estimates from the 2RR and 3RR datasets were compared with estimates based on the full dataset (1RR) using the two one-sided test of equivalence for paired samples. RESULTS: Significant equivalence was found for rest MBFLV (p â€‹< â€‹0.001), stress MBFLV (p â€‹< â€‹0.001) and for the CFRLV (p â€‹= â€‹0.005) when comparing 2RR blood flow estimates with the results based on the 1RR dataset. The 2RR reconstruction protocol led to an estimated reduction in radiation dose of 35.4 â€‹± â€‹3.8%. CONCLUSION: MBF can be quantitated with dynamic CTP using a sampling strategy of one volume for every second heartbeat. This strategy could lead to a significant reduction in radiation dose.

Radiocarbon dating reveals minimal collagen turnover in both healthy and osteoarthritic human cartilage.

The poor regenerative capacity of articular cartilage presents a major clinical challenge and may relate to a limited turnover of the cartilage collagen matrix. However, the collagen turnover rate during life is not clear, and it is debated whether osteoarthritis (OA) can influence it. Using the carbon-14 ((14)C) bomb-pulse method, life-long replacement rates of collagen were measured in tibial plateau cartilage from 23 persons born between 1935 and1997 (15 and 8 persons with OA and healthy cartilage, respectively). The (14)C levels observed in cartilage collagen showed that, virtually, no replacement of the collagen matrix happened after skeletal maturity and that neither OA nor tissue damage, per se, influenced collagen turnover. Regional differences in (14)C content across the joint surface showed that cartilage collagen located centrally on the joint surface is formed several years earlier than collagen located peripherally. The collagen matrix of human articular cartilage is an essentially permanent structure that has no significant turnover in adults, even with the occurrence of disease.