Role of sex hormones in modulating myocardial perfusion and coronary flow reserve

Background A growing body of evidence highlights sex differences in the diagnostic accuracy of cardiovascular imaging modalities. Nonetheless, the role of sex hormones in modulating myocardial perfusion and coronary flow reserve (CFR) is currently unclear. The aim of our study was to assess the impact of female and male sex hormones on myocardial perfusion and CFR. Methods Rest and stress myocardial perfusion imaging (MPI) was conducted by small animal positron emission tomography (PET) with [18F]flurpiridaz in a total of 56 mice (7–8 months old) including gonadectomized (Gx) and sham-operated males and females, respectively. Myocardial [18F]flurpiridaz uptake (% injected dose per mL, % ID/mL) was used as a surrogate for myocardial perfusion at rest and following intravenous regadenoson injection, as previously reported. Apparent coronary flow reserve (CFRApp) was calculated as the ratio of stress and rest myocardial perfusion. Left ventricular (LV) morphology and function were assessed by cardiac magnetic resonance (CMR) imaging. Results Orchiectomy resulted in a significant decrease of resting myocardial perfusion (Gx vs. sham, 19.4 ± 1.0 vs. 22.2 ± 0.7 % ID/mL, p = 0.034), while myocardial perfusion at stress remained unchanged (Gx vs. sham, 27.5 ± 1.2 vs. 27.3 ± 1.2 % ID/mL, p = 0.896). Accordingly, CFRApp was substantially higher in orchiectomized males (Gx vs. sham, 1.43 ± 0.04 vs. 1.23 ± 0.05, p = 0.004), and low serum testosterone levels were linked to a blunted resting myocardial perfusion (r = 0.438, p = 0.020) as well as an enhanced CFRApp (r = −0.500, p = 0.007). In contrast, oophorectomy did not affect myocardial perfusion in females. Of note, orchiectomized males showed a reduced LV mass, stroke volume, and left ventricular ejection fraction (LVEF) on CMR, while no such effects were observed in oophorectomized females. Conclusion Our experimental data in mice indicate that sex differences in myocardial perfusion are primarily driven by testosterone. Given the diagnostic importance of PET-MPI in clinical routine, further studies are warranted to determine whether testosterone levels affect the interpretation of myocardial perfusion findings in patients.

Impaired coronary flow reserve in patients with supra-normal left ventricular ejection fraction at rest

Purpose Recently, a “U” hazard ratio curve between resting left ventricular ejection fraction (LVEF) and prognosis has been observed in patients referred for routine clinical echocardiograms. The present study sought to explore whether a similar “U” curve existed between resting LVEF and coronary flow reserve (CFR) in patients without severe cardiovascular disease (CVD) and whether impaired CFR played a role in the adverse outcome of patients with supra-normal LVEF (snLVEF, LVEF ≥ 65%). Methods Two hundred ten consecutive patients (mean age 52.3 ± 9.3 years, 104 women) without severe CVD underwent clinically indicated rest/dipyridamole stress electrocardiography (ECG)-gated 13 N-ammonia positron emission tomography/computed tomography (PET/CT). Major adverse cardiac events (MACE) were followed up for 27.3 ± 9.5 months, including heart failure, late revascularization, re-hospitalization, and re-coronary angiography for any cardiac reason. Clinical characteristics, corrected CFR (cCFR), and MACE were compared among the three groups categorized by resting LVEF detected by PET/CT. Dose–response analyses using restricted cubic spline (RCS) functions, multivariate logistic regression, and Kaplan–Meier survival analysis were conducted to evaluate the relationship between resting LVEF and CFR/outcome. Results An inverted “U” curve existed between resting LVEF and cCFR (p = 0.06). Both patients with snLVEF (n = 38) and with reduced LVEF (rLVEF, LVEF < 55%) (n = 66) displayed a higher incidence of reduced cCFR than those with normal LVEF (nLVEF, 55% ≤ LVEF < 65%) (n = 106) (57.9% vs 54.5% vs 34.3%, p < 0.01, respectively). Both snLVEF (p < 0.01) and rLVEF (p < 0.05) remained independent predictors for reduced cCFR after multivariable adjustment. Patients with snLVEF encountered more MACE than those with nLVEF (10.5% vs 0.9%, log-rank p = 0.01). Conclusions Patients with snLVEF are prone to impaired cCFR, which may be related to the adverse prognosis. Further investigations are warranted to explore its underlying pathological mechanism and clinical significance.

Pressure- and 3D-derived coronary Flow Reserve with Hydrostatic Pressure Correction - A Validation by Intracoronary Doppler Measurements

Purpose: To develop a method of coronary flow reserve (CFR) calculation derived from threedimensional (3D) coronary angiographic parameters and intracoronary pressure data during fractional flow reserve (FFR) measurement. Methods: Altogether 19 coronary arteries of 16 native and 3 stented vessels were reconstructed in 3D. The measured distal intracoronary pressures were corrected to the hydrostatic pressure based on the height differences between the levels of the vessel orifice and the sensor position. Classical fluid dynamic equations were applied to calculate the flow during the resting state and vasodilatation on the basis of morphological data and intracoronary pressure values. 3D-derived coronary flow reserve (CFR p-3D ) was defined as the ratio between the calculated hyperemic and the resting flow and was compared to the CFR values simultaneously measured by the Doppler sensor (CFR Doppler ). Results: Haemodynamic calculations using the distal coronary pressures corrected for hydrostatic pressures showed a strong correlation between the individual CFR p-3D values and the CFR Doppler measurements (r=0.89, p<0.0001). Hydrostatic pressure correction increased the specificity of the method from 46.1% to 92.3% for predicting an abnormal CFR Doppler <2. Conclusions : CFR p-3D calculation with hydrostatic pressure correction during FFR measurement facilitates a comprehensive haemodynamic assessment, supporting the complex evaluation of macro- and microvascular coronary artery disease.

Comorbidities associated with anatomical and functional myocardial impairments assessed by 13 N-ammonia positron emission tomography

Background There has been an increase in the number of comorbidities in that predispose to ischemic heart disease in developing countries. Nevertheless, the identification of associated risk factors could unveil impairments within myocardial function Purpose We aimed to assess the prevalence and factors associated with reduced modifications of LVEF (&gt;5%), ischemia (SDS ≥6 pts), reduced coronary flow reserve (≤2.5 pts) and coronary artery obstruction (≥50%) using a positron emission tomography–computed tomography. Methods A cross-sectional study of patients with clinical suspicious of angina who attended the PET/CT unity in a faculty of medicine was designed. We designed a clinical questionnaire to capture information regarding clinical history of comorbidities, angina, medication use and lifestyle habits. A myocardial perfusion study (MPS) was performed to identify myocardial ischemia, infarction, dyssynchrony and reduced coronary flow reserve. Logistic regression analyses were performed to identify associated factors. Results 1273 patients underwent a PET/CT study; 66.1% (n=841) were male with a median age of 62.4 (±12.7) years. In our population, 36.4% (n=464) reported 1 or 2 comorbidities, 31.6% (n=402) 3 to 4 and 4.7% (n=60) more than 5; arterial hypertension (46.9%), dyslipidemia (43.9%), and diabetes (20.8%) were highly prevalent. Angina (34.4%) and palpitations (13%) were the most frequent symptoms at evaluation (Table 1). We found that that the presence of age ≥65 years, history of myocardial infarction, male sex, precordial chest pain, agrarians in chest pain, familiar history of myocardial infarction and comorbidities such as diabetes, arterial hypertension and obesity were associated with impairments in LVEF, ischemia, reduced coronary flow reserve and coronary artery obstruction (Figure 1). Conclusions The presence of comorbidities in our population is high. The identification of a cardiovascular profile using associated factors would allow early identification of those patients with alterations in myocardial function parameters. FUNDunding Acknowledgement Type of funding sources: None.

Physiological significance of pericoronary inflammation in epicardial functional stenosis and global coronary flow reserve

Both fractional flow reserve (FFR) and global coronary flow reserve (g-CFR) provide prognostic information in patients with stable coronary artery disease (CAD). Inflammation plays a vital role in impaired endothelial dysfunction and atherosclerotic progression, potentially predicting cardiovascular mortality. This study aimed to evaluate the physiological significance of pericoronary adipose tissue inflammation assessed by CT attenuation (PCATA) in epicardial functional stenosis severity and g-CFR in patients with CAD. A total of 131 CAD patients with a single de novo epicardial coronary stenosis who underwent coronary CT-angiography (CCTA), phase-contrast cine-magnetic resonance imaging (PC-CMR) and FFR measurement were studied. PCATA was assessed using the mean CT attenuation value. G-CFR was obtained by quantifying absolute coronary sinus flow (ml/min/g) by PC-CMR at rest and during maximum hyperemia. Median FFR, g-CFR, and PCATA values were 0.75, 2.59, and − 71.3, respectively. Serum creatinine, NT-proBNP, left ventricular end-diastolic volume, and PCATA were independently associated with g-CFR. PCATA showed a significant incremental predictive efficacy for impaired g-CFR (< 2.0) when added to the clinical risk model. PCATA was significantly associated with g-CFR, independent of FFR. Our results suggest the pathophysiological mechanisms linking perivascular inflammation with g-CFR in CAD patients.