Coronary microvascular dysfunction (CMD) can cause myocardial ischemia in patients presenting with angina without obstructive coronary artery disease (ANOCA). Evaluating for CMD by using the thermodilution technique offers a widely accessible means of assessing microvascular resistance. Through this technique, 2 validated indices, namely coronary flow reserve and the index of microcirculatory resistance, can be computed, facilitating investigation of the coronary microcirculation. The index of microcirculatory resistance specifically estimates minimum achievable microvascular resistance within the coronary microcirculation. We aim to review the bolus thermodilution method, outlining the fundamental steps for conducting measurements and introducing an algorithmic approach (CATH CMD) to systematically evaluate the coronary microcirculation. Embracing a standardized approach, exemplified by the CATH CMD algorithm, will facilitate adoption of this technique and streamline the diagnosis of CMD.

Cardiac allograft vasculopathy is a leading cause of allograft failure and death among heart transplant recipients. Routine coronary angiography and intravascular ultrasound in the early posttransplant period are widely accepted as the current standard-of-care diagnostic modalities. However, many studies have now demonstrated that invasive coronary physiological assessment provides complementary long-term prognostic data and helps identify patients who are at risk of accelerated cardiac allograft vasculopathy and acute rejection.

UNASSIGNED: In patients with angina and non-obstructive coronary artery disease (ANOCA), diagnosis of coronary microvascular dysfunction (CMD) remains an unmet need. Magnetocardiography (MCG), is a rest-based, non-invasive scan that can detect weak electrophysiological changes that occur at the early phase of ischemia.
UNASSIGNED: This study assessed the ability of MCG to detect CMD in ANOCA patients as compared to reference standard, invasive coronary flow reserve (CFR).
UNASSIGNED: Patients with ANOCA and invasive coronary physiologic assessment using intracoronary flow measurements with Doppler and thermodilution methods were enrolled. CMD was defined dichotomously as an invasive CFR < 2.0 by Doppler or thermodilution assessment. Noninvasive 36-channel 90-s MCG scan was performed and quantitative assessment of four distinct MCG features was completed. We evaluated the diagnostic performance of 2 or more abnormal MCG features to detect CMD in the overall cohort and performed a subgroup analysis in the subset of patients with Doppler CFR assessment.
UNASSIGNED: Among 79 ANOCA patients, 25 were CMD positive and 54 patients were CMD negative by CFR. Using invasive CFR as reference, MCG had an ROC AUC of 0.66 with a sensitivity of 68 % and specificity of 65 % for the detection of CMD. In the subgroup with Doppler CFR assessment, MCG had an ROC AUC of 0.76 with a sensitivity of 75 % and specificity of 77 %.
UNASSIGNED: In ANOCA patients, MCG demonstrates the ability to detect CMD using a 90-second non-invasive scan without the need for an intravenous stressor or ionizing radiation. Further investigations are needed to validate an MCG-based diagnostic pathway for CMD.

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BACKGROUND: Myocardial bridging (MB) is accompanied by the dynamic extravascular compression of epicardial coronary arteries, leading to intracoronary hemodynamic disturbance with abnormal coronary flow profiles. We aimed to evaluate the prognostic implications of resistive reserve ratio (RRR), a composite measure of flow and pressure parameters that represents the vasodilatory capacity of the coronary arteries, in patients with angina with nonobstructive coronary artery disease (ANOCA) and MB, in comparison with coronary flow reserve (CFR).
RESULTS: In this retrospective cohort study, we included patients with ANOCA who underwent coronary reactivity testing, where MB was identified by transient constriction in coronary artery segments between systole and diastole. Abnormal CFR and RRR were defined as <2.5 and <2.62, respectively. Major adverse cardiac events, including cardiovascular death, stroke, myocardial infarction, heart failure, and late revascularization, served as outcomes. Among 1251 patients with ANOCA, 191 (15.3%) had MB. The prevalence of abnormal CFR or RRR was not significantly different between patients with and without MB (P=0.144 and P=0.398, respectively). Over a median follow-up time of 6.9 years, abnormal RRR predicted major adverse cardiac events in patients with MB (hazard ratio [HR], 4.38 [95% CI, 1.71-11.21]; P=0.002) and without MB (HR, 1.91 [95% CI, 1.38-2.64]; P<0.001). Abnormal CFR predicted major adverse cardiac events in patients without MB (HR, 2.15 [95% CI, 1.54-3.00]; P<0.001), whereas it was not predictive of major adverse cardiac events in patients with MB (HR, 2.29 [95% CI, 0.93-5.65]; P=0.073).
CONCLUSIONS: In patients with ANOCA and MB, impaired RRR was superior to impaired CFR in distinguishing patients at a higher risk of future adverse events, suggesting that RRR may serve as a risk stratification tool in patients with MB and ANOCA.

Ischemia with non-obstructive coronary arteries (INOCA) is an increasingly recognized entity. It encompasses different pathophysiological subtypes (i.e., endotypes), including coronary microvascular dysfunction (CMD), vasospastic angina (VSA) and mixed entities resulting from the variable combination of both. Diagnosing INOCA and precisely characterizing the endotype allows for accurate medical treatment and has proven prognostic implications. A breadth of diagnostic technique is available, ranging from non-invasive approaches to invasive coronary angiography adjuvated by functional assessment and provocative tests. This review summarizes the strength and limitations of these methodologies and provides the rationale for the routine referral for invasive angiography and functional assessment in this subset of patients.

Accumulating evidence indicates that coronary microvascular dysfunction (CMD) caused by hypercholesterolemia can lead to myocardial ischemia, with or without obstructive atherosclerotic coronary artery disease (CAD). However, the molecular pathways associated with compromised coronary microvascular function prior to the development of myocardial ischemic injury remain poorly defined. In this study, we investigated the effects of hypercholesterolemia on the function and integrity of the coronary microcirculation in mice and the underlying mechanisms. Mice were fed with a hypercholesterolemic Paigen\'s diet (PD) for 8 weeks. Echocardiography data showed that PD caused CMD, characterized by significant reductions in coronary blood flow and coronary flow reserve (CFR), but did not affect cardiac remodeling or dysfunction. Immunofluorescence studies revealed that PD-induced CMD was associated with activation of coronary arterioles inflammation and increased myocardial inflammatory cell infiltration. These pathological changes occurred in parallel with the upregulation of lysosomal signaling pathways in endothelial cells (ECs). Treating hypercholesterolemic mice with the cholesterol-lowering drug ezetimibe significantly ameliorated PD-induced adverse effects, including hypercholesterolemia, steatohepatitis, reduced CFR, coronary EC inflammation, and myocardial inflammatory cell infiltration. In cultured mouse cardiac endothelial cells (MCECs), 7-ketocholesterol (7K) increased mitochondrial reactive oxygen species (ROS) and inflammatory responses. Meanwhile, 7K induced the activation of TFEB and lysosomal signaling in MCECs, whereas the lysosome inhibitor bafilomycin A1 blocked 7K-induced TFEB activation and exacerbated 7K-induced inflammation and cell death. Interestingly, ezetimibe synergistically enhanced 7K-induced TFEB activation and attenuated 7K-induced mitochondrial ROS and inflammatory responses in MCECs. These results suggest that CMD can develop and precede detectable cardiac functional or structural changes in the setting of hypercholesterolemia, and that upregulation of TFEB-mediated lysosomal signaling in ECs plays a protective role against CMD.

In patients with diabetes mellitus, accelerated progression of atherosclerosis can lead to worse clinical outcomes. Determining the best diagnostic strategy to identify patients with increased cardiovascular risk is challenging. Current guidelines recommend using both functional imaging and CT angiography to detect myocardial ischemia and coronary artery disease based on pre-test probability. Functional imaging is suggested for patients with a higher clinical likelihood due to its higher rule-in diagnostic capacity. On the other hand, CT angiography is preferred for patients with lower pre-test probability because of its excellent negative predictive value. The optimal management strategy for asymptomatic diabetic patients remains unclear. In asymptomatic diabetic patients, previous randomized trials have not shown benefits from diagnostic testing over standard care. However, these trials were methodologically inconsistent and lacked clear stratification of cardiovascular risk. In terms of invasive evaluation, a combined invasive functional and anatomic imaging approach for angiographically intermediate coronary stenosis appears to be the best, most effective decision pathway for managing diabetic patients.

Background: This study investigated the prognostic value of cardiovascular magnetic resonance (CMR)-derived global coronary flow reserve (G-CFR) in addition to cardiopulmonary exercise testing (CPET) variables in patients with acute myocardial infarction (AMI). Methods and Results: We investigated 127 patients with AMI who underwent primary or urgent percutaneous coronary intervention (PCI) and post-intervention CMR and CPET. The incidence of major cardiac and cerebrovascular events (MACCE), defined as all-cause death, recurrent non-fatal myocardial infarction, re-hospitalization due to congestive heart failure, and stroke, was evaluated (median follow-up, 2.8 years). Patients with MACCE (n=14) had lower ejection fraction (EF) (50 [43-59] vs. 58 [51-63]%; P=0.014), lower G-CFR (1.74 [1.19-2.20] vs. 2.40 [1.61-3.66]; P=0.008), and lower peak oxygen consumption (V̇O2) (15.16±2.64 vs. 17.19±3.70 mL/kg/min; P=0.049) than patients without MACCE. G-CFR<2.33 and peak V̇O2 <15.65 mL/kg/min (cut-off values derived from receiver operating characteristic curve analyses) were significantly associated with the incidence of MACCE (log-rank test, P=0.01). The combination of low G-CFR and low peak V̇O2 improved risk discrimination for MACCE when added to the reference clinical model including age, male sex, post-PCI peak creatine kinase, EF, and left anterior descending artery culprit lesion. Conclusions: G-CFR and peak V̇O2 showed incremental prognostic information compared with the reference model using historically important clinical risk factors, indicating that this approach may help identify high-risk patients who suffer subsequent adverse events.

Ischemic heart disease (IHD) affects more than 20 million adults in the United States. Although classically attributed to atherosclerosis of the epicardial coronary arteries, nearly half of patients with stable angina and IHD who undergo invasive coronary angiography do not have obstructive epicardial coronary artery disease. Ischemia with nonobstructive coronary arteries is frequently caused by microvascular angina with underlying coronary microvascular dysfunction (CMD). Greater understanding the pathophysiology, diagnosis, and treatment of CMD holds promise to improve clinical outcomes of patients with ischemic heart disease.