Angiography-derived assessment of coronary microcirculatory resistance in patients with suspected myocardial ischaemia and non-obstructive coronary arteries.

BACKGROUND: Myocardial ischaemia with non-obstructive coronary arteries (INOCA) represents a challenging and frequent, but largely underdiagnosed, condition. AIMS: We aimed to investigate the feasibility and diagnostic value of angiography-derived coronary microcirculatory resistance in patients with INOCA syndrome. METHODS: This is an investigator-driven, prospective and blinded study. The diagnostic yield of angiography-derived index of coronary microcirculatory resistance (angio-IMR) was investigated against thermodilution-derived IMR (thermo-IMR) in patients with clinically indicated coronary angiography due to suspected myocardial ischaemia and angiographically normal or non-obstructive coronary arteries. The angio-IMR was derived from resting angiograms (contrast-flow angio-IMR [cAngio-IMR]) by an expert analyst blinded to the thermo-IMR. An independent, blinded, physiology core laboratory analysed the raw intracoronary physiology data and provided the final thermo-IMR values. RESULTS: A total of 104 patients (108 coronary vessels) were analysed after fulfilling predefined inclusion criteria. Most patients were female (67%). Obstructive epicardial disease was angiographically (percent diameter stenosis <50%) and physiologically (fractional flow reserve>0.80) ruled out in all cases. Median thermo-IMR and cAngio-IMR were 16.6 (12.7, 23.0) and 16.8 (12.8, 23.1) units, respectively (median difference -0.31, 95% confidence interval: -1.53 to 1.00; p=0.654). cAngio-IMR showed good correlation (Pearson coefficient 0.76; p<0.001), agreement (mean bias 0.4), discriminatory power (area under the curve from the receiver operator characteristics 0.865; p<0.001) and accuracy (85%), compared to thermo-IMR (≥25 U). CONCLUSIONS: Evaluating coronary microcirculatory resistance in patients with INOCA syndrome using cAngio-IMR is feasible and accurate. By circumventing the need of coronary instrumentation and hyperaemic drugs, this method may facilitate the assessment of coronary microcirculatory resistance in patients with suspected INOCA. CLINICALTRIALS: gov: NCT04827498.

Maternal Cardiac Assessment at 35 to 37 Weeks Improves Prediction of Development of Preeclampsia.

Preeclampsia at term accounts for half of maternal deaths from hypertensive disorders. We aimed to assess differences in maternal cardiac indices at 35+0 to 36+6 weeks' gestation between women who subsequently developed preeclampsia at term compared with those with uncomplicated pregnancy and to evaluate whether cardiac indices offer incremental prognostic value to the available screening algorithm for preeclampsia. We recruited 1602 women with singleton pregnancies who attended for a routine hospital visit at 35+0 to 36+6 weeks' gestation between April and November 2018. We recorded maternal characteristics and preeclampsia-risk-score derived from a competing risks model and measured cardiac indices. Preeclampsia developed in 3.12% (50/1602) of participants. Women with preeclampsia, compared with those without, had increased mean arterial pressure (97.6, SD, 5.53 versus 87.9, SD, 6.82 mm Hg), systemic vascular resistance (1500, interquartile range, 1393-1831 versus 1400, interquartile range, 1202-1630 PRU) and preeclampsia-risk-score (23.4, interquartile range, 9.13-40 versus 0.9, interquartile range, 0.32-3.25). Multivariable analysis demonstrated independent association between the incidence of preeclampsia and E/e' (hazard ratio, 1.19/unit [95% CI, 1.03-1.37]; P=0.018) as well as left ventricular mass indexed for body surface area (hazard ratio, 1.03/[g·m2] [95% CI, 1.003-1.051]; P=0.029). Women with E/e' ≥7.3 and left ventricular mass indexed for body surface area ≥63.2 g/m2 had an increased risk for developing preeclampsia, despite low preeclampsia-risk-score <5% (hazard ratio, 20.1 [95% CI, 10.5-38.7], P<0.001). Increased left ventricular mass and E/e' offer incremental information to available scoring systems and better stratify women at risk of developing preeclampsia at term.

Non-invasive assessment of endothelial function in patients with spontaneous coronary artery dissection: A case-control study.

BACKGROUND: The physiopathology underlying spontaneous coronary artery dissection remains largely unknown. Endothelial dysfunction is an early feature of many vascular disorders. We sought to determine the endothelial function assessed by reactive hyperemia peripheral arterial tonometry (RH-PAT) in patients with SCAD and compare it to that of non-SCAD patients with similar cardiovascular risk profile. METHODS: This is a case-control study with the participation of 2 centers. Patients (cases) were diagnosed with SCAD between 2008 and 2018. Control subjects were individually matched 2:1 to SCAD cases from a cohort recruited for assessment with RH-PAT between 2006 and 2013. The primary measure variable was the mean difference in the log-transformed reactive hyperemia index (LnRH-PAT Index) between groups. RESULTS: LnRH-PAT data from 23 patients with SCAD and 46 matched controls were analyzed. No significant differences were noted in the matching variables (overall, 95.7% female with mean age 52.7 years). In the SCAD group, more patients reported migraine (61 vs. 21%) and more patients were on betablockers (70 vs 28%), ACE inhibitors (65 vs. 13%) and statins (70 vs. 28%), all differences statistically significant. The mean LnRH-PAT value was 0.55 ± 0.22 in patients with SCAD and 0.77 ± 0.23 in controls (mean difference: 0.22, p < 0.001). CONCLUSIONS: In this observational study, patients with SCAD had a poorer endothelial function than similar subjects without prior SCAD. This finding opens a new venue in the research of the physio pathologic mechanisms underlying SCAD.

Sex Differences in Long-Term Outcomes in Patients With Deferred Revascularization Following Fractional Flow Reserve Assessment: International Collaboration Registry of Comprehensive Physiologic Evaluation.

Background Sex-specific differences may influence prognosis after deferred revascularization following fractional flow reserve (FFR) measurement. This study sought to investigate the sex differences in long-term prognosis of patients with deferred revascularization following FFR assessment. Methods and Results A total of 879 patients (879 vessels) with deferred revascularization with FFR >0.75 who underwent FFR and coronary flow reserve measurements were enrolled from 3 countries (Korea, Japan, and Spain). Long-term outcomes were assessed in 649 men and 230 women by the patient-oriented composite outcome (POCO, a composite of any death, any myocardial infarction, and any revascularization). We applied inverse-probability weighting based on propensity scores to account for differences at baseline between women and men (age, hyperlipidemia, diabetes mellitus, diameter stenosis, lesion length, multivessel disease, FFR, coronary flow reserve. The median follow-up duration was 1855 days (745-1855 days). Median FFR values were 0.88 (0.83-0.93) in men and 0.89 (0.85-0.94) in women, respectively. The occurrences of POCO were significantly high in men compared with that in women (10.5% versus 4.2%, P=0.007). Kaplan-Meier analysis revealed that women had a significantly lower risk of POCO (χ2=7.2, P=0.007). Multivariate COX proportional hazards regression analysis revealed that age, male, diabetes mellitus, diameter stenosis, lesion length, and coronary flow reserve were independent predictors of POCO. After applying IPW, the hazard ratio of males for POCO was 2.07 (95% CI, 1.07-4.04, P=0.032). Conclusions This large multinational study reveals that long-term outcome differs between women and men in favor of women after FFR-guided revascularization deferral. Clinical Trial Registration URL: http://www.ClinicalTrials.gov. Unique identifier: NCT02186093.

Angiography-derived functional assessment of non-culprit coronary stenoses in primary percutaneous coronary intervention.

AIMS: Functional assessment of non-culprit lesions (NCL) in patients presenting with ST-elevation myocardial infarction (STEMI) and multivessel disease constitutes an unmet need. This study aimed to evaluate the diagnostic accuracy of quantitative flow ratio (QFR) in the functional assessment of NCL during the acute phase of STEMI. METHODS AND RESULTS: This was a retrospective, observational, multicentre study including patients with STEMI and staged fractional flow reserve (FFR) assessment of NCL. QFR in NCL was calculated from the coronary angiogram acquired during primary PCI in a blinded fashion with respect to FFR. The diagnostic value of QFR in the STEMI population was compared with a propensity score-matched population of stable angina patients. Eighty-two patients (91 NCL) were included. Target lesions were of both angiographic and functional (mean FFR 0.82±0.09) intermediate severity. The diagnostic performance of QFR was high (AUC 0.91 [95% CI: 0.85-0.97]) and similar to that observed in the matched control population (AUC 0.91 vs 0.94, p=0.5). The diagnostic accuracy of QFR was very high (>95%) in those vessels (61.5%) with QFR values out of a ROC-defined "grey zone" (0.75-0.85). A hybrid FFR/QFR approach (FFR only when QFR is in the grey zone) would adequately classify 96.7% of NCL, avoiding 58.5% of repeat diagnostic procedures. CONCLUSIONS: QFR has a good diagnostic accuracy in assessing the functional relevance of NCL during primary PCI, similar to the accuracy observed in stable patients.

Influence of Microcirculatory Dysfunction on Angiography-Based Functional Assessment of Coronary Stenoses.

OBJECTIVES: The authors sought to evaluate the influence of coronary microcirculatory dysfunction (CMD) on the diagnostic performance of the quantitative flow ratio (QFR). BACKGROUND: Functional angiographic assessment of coronary stenoses based on fluid dynamics, such as QFR, constitutes an attractive alternative to fractional flow reserve (FFR). However, it is unknown whether CMD affects the reliability of angiography-based functional indices. METHODS: FFR and the index of microcirculatory resistance (IMR) were measured in 300 vessels (248 patients) as part of a multicenter international registry. QFR was calculated at a blinded core laboratory. Vessels were classified into 2 groups according to microcirculatory status: low IMR (<23 U), and high IMR (≥23 U, CMD). The impact of CMD on the diagnostic performance of QFR, as well as on incremental value of QFR over quantitative angiography, was assessed using FFR as reference. RESULTS: Percent diameter stenosis (%DS) and FFR were similar in low- and high-IMR groups (%DS 51 ± 12% vs. 53 ± 11%; p = 0.16; FFR 0.80 ± 0.11 vs. 0.81 ± 0.11; p = 0.23, respectively). In the overall cohort, classification agreement (CA) between QFR and FFR and diagnostic efficiency of QFR (area under the receiver-operating characteristics curve [AUC]) were high (CA: 88%; AUC: 0.93 [95% confidence interval (CI): 0.90 to 0.96]). However, when assessed according to microcirculatory status, a significantly lower CA and AUC of QFR were found in the high-IMR group as compared with the low-IMR group (CA: 76% vs. 92%; p < 0.001; AUC: 0.88 [95% CI: 0.79 to 0.94] vs. 0.96 [95% CI: 0.92 to 0.98]; p < 0.05). Compared with angiographic assessment, QFR increased by 0.20 (p < 0.001) and by 0.16 (p < 0.001) the AUC of %DS in low- and high-IMR groups, respectively. Independent predictors of misclassification between QFR and FFR were high IMR and acute coronary syndrome. CONCLUSIONS: CMD decreases the diagnostic performance of QFR. However, even in the presence of CMD, QFR remains superior to angiography alone in ascertaining functional stenosis severity.