Reproducibility of bolus versus continuous thermodilution for assessment of coronary microvascular function in patients with ANOCA.

BACKGROUND: A bolus thermodilution-derived index of microcirculatory resistance (IMR) has emerged as the standard for assessing coronary microvascular dysfunction (CMD). Continuous thermodilution has recently been introduced as a tool to quantify absolute coronary flow and microvascular resistance directly. Microvascular resistance reserve (MRR) derived from continuous thermodilution has been proposed as a novel metric of microvascular function, which is independent of epicardial stenoses and myocardial mass. AIMS: We aimed to assess the reproducibility of bolus and continuous thermodilution in assessing coronary microvascular function. METHODS: Patients with angina and non-obstructive coronary artery disease (ANOCA) at angiography were prospectively enrolled. Bolus and continuous intracoronary thermodilution measurements were obtained in duplicate in the left anterior descending artery (LAD). Patients were randomly assigned in a 1:1 ratio to undergo either bolus thermodilution first or continuous thermodilution first. RESULTS: A total of 102 patients were enrolled. The mean fractional flow reserve (FFR) was 0.86±0.06. Coronary flow reserve (CFR) calculated with continuous thermodilution (CFRcont) was significantly lower than bolus thermodilution-derived CFR (CFRbolus; 2.63±0.65 vs 3.29±1.17; p<0.001). CFRcont showed a higher reproducibility than CFRbolus (variability: 12.7±10.4% continuous vs 31.26±24.85% bolus; p<0.001). MRR showed a higher reproducibility than IMR (variability 12.4±10.1% continuous vs 24.2±19.3% bolus; p<0.001). No correlation was found between MRR and IMR (r=0.1, 95% confidence interval: -0.09 to 0.29; p=0.305). CONCLUSIONS: In the assessment of coronary microvascular function, continuous thermodilution demonstrated significantly less variability on repeated measurements than bolus thermodilution.

Deferral of Coronary Revascularization in Patients With Reduced Ejection Fraction Based on Physiological Assessment: Impact on Long-Term Survival.

Background Deferring revascularization in patients with nonsignificant stenoses based on fractional flow reserve (FFR) is associated with favorable clinical outcomes up to 15 years. Whether this holds true in patients with reduced left ventricular ejection fraction is unclear. We aimed to investigate whether FFR provides adjunctive clinical benefit compared with coronary angiography in deferring revascularization of patients with intermediate coronary stenoses and reduced left ventricular ejection fraction. Methods and Results Consecutive patients with reduced left ventricular ejection fraction (≤50%) undergoing coronary angiography between 2002 and 2010 were screened. We included patients with at least 1 intermediate coronary stenosis (diameter stenosis ≥40%) in whom revascularization was deferred based either on angiography plus FFR (FFR guided) or angiography alone (angiography guided). The primary end point was the cumulative incidence of all-cause death at 10 years. The secondary end point (incidence of major adverse cardiovascular and cerebrovascular events) was a composite of all-cause death, myocardial infarction, any revascularization, and stroke. A total of 840 patients were included (206 in the FFR-guided group and 634 in the angiography-guided group). Median follow-up was 7 years (interquartile range, 3.22-11.08 years). After 1:1 propensity-score matching, baseline characteristics between the 2 groups were similar. All-cause death was significantly lower in the FFR-guided group compared with the angiography-guided group (94 [45.6%] versus 119 [57.8%]; hazard ratio [HR], 0.65 [95% CI, 0.49-0.85]; P<0.01). The rate of major adverse cardiovascular and cerebrovascular events was lower in the FFR-guided group (123 [59.7%] versus 139 [67.5%]; HR, 0.75 [95% CI, 0.59-0.95]; P=0.02). Conclusions In patients with reduced left ventricular ejection fraction, deferring revascularization of intermediate coronary stenoses based on FFR is associated with a lower incidence of death and major adverse cardiovascular and cerebrovascular events at 10 years.

Microvascular Dysfunction in Patients With Type II Diabetes Mellitus: Invasive Assessment of Absolute Coronary Blood Flow and Microvascular Resistance Reserve.

Background: Coronary microvascular dysfunction (CMD) is an early feature of diabetic cardiomyopathy, which usually precedes the onset of diastolic and systolic dysfunction. Continuous intracoronary thermodilution allows an accurate and reproducible assessment of absolute coronary blood flow and microvascular resistance thus allowing the evaluation of coronary flow reserve (CFR) and Microvascular Resistance Reserve (MRR), a novel index specific for microvascular function, which is independent from the myocardial mass. In the present study we compared absolute coronary flow and resistance, CFR and MRR assessed by continuous intracoronary thermodilution in diabetic vs. non-diabetic patients. Left atrial reservoir strain (LASr), an early marker of diastolic dysfunction was compared between the two groups. Methods: In this observational retrospective study, 108 patients with suspected angina and non-obstructive coronary artery disease (NOCAD) consecutively undergoing elective coronary angiography (CAG) from September 2018 to June 2021 were enrolled. The invasive functional assessment of microvascular function was performed in the left anterior descending artery (LAD) with intracoronary continuous thermodilution. Patients were classified according to the presence of DM. Absolute resting and hyperemic coronary blood flow (in mL/min) and resistance (in WU) were compared between the two cohorts. FFR was measured to assess coronary epicardial lesions, while CFR and MRR were calculated to assess microvascular function. LAS, assessed by speckle tracking echocardiography, was used to detect early myocardial structural changes potentially associated with microvascular dysfunction. Results: The median FFR value was 0.83 [0.79-0.87] without any significant difference between the two groups. Absolute resting and hyperemic flow in the left anterior descending coronary were similar between diabetic and non-diabetic patients. Similarly, resting and hyperemic resistances did not change significantly between the two groups. In the DM cohort the CFR and MRR were significantly lower compared to the control group (CFR = 2.38 ± 0.61 and 2.88 ± 0.82; MRR = 2.79 ± 0.87 and 3.48 ± 1.02 for diabetic and non-diabetic patients respectively, [p < 0.05 for both]). Likewise, diabetic patients had a significantly lower reservoir, contractile and conductive LAS (all p < 0.05). Conclusions: Compared with non-diabetic patients, CFR and MRR were lower in patients with DM and non-obstructive epicardial coronary arteries, while both resting and hyperemic coronary flow and resistance were similar. LASr was lower in diabetic patients, confirming the presence of a subclinical diastolic dysfunction associated to the microcirculatory impairment. Continuous intracoronary thermodilution-derived indexes provide a reliable and operator-independent assessment of coronary macro- and microvasculature and might potentially facilitate widespread clinical adoption of invasive physiologic assessment of suspected microvascular disease.

Microvascular Resistance Reserve for Assessment of Coronary Microvascular Function: JACC Technology Corner.

The need for a quantitative and operator-independent assessment of coronary microvascular function is increasingly recognized. We propose the theoretical framework of microvascular resistance reserve (MRR) as an index specific for the microvasculature, independent of autoregulation and myocardial mass, and based on operator-independent measurements of absolute values of coronary flow and pressure. In its general form, MRR equals coronary flow reserve (CFR) divided by fractional flow reserve (FFR) corrected for driving pressures. In 30 arteries, pressure, temperature, and flow velocity measurements were obtained simultaneously at baseline (BL), during infusion of saline at 10 mL/min (rest) and 20 mL/min (hyperemia). A strong correlation was found between continuous thermodilution-derived MRR and Doppler MRR (r = 0.88; 95% confidence interval: 0.72-0.93; P < 0.001). MRR was independent from the epicardial resistance, the lower the FFR value, the greater the difference between MRR and CFR. Therefore, MRR is proposed as a specific, quantitative, and operator-independent metric to quantify coronary microvascular dysfunction.

Simplified Assessment of the Index of Microvascular Resistance.

BACKGROUND: To validate a simplified invasive method for the calculation of the index of microvascular resistance (IMR). METHODS: This is a prospective, single-center study of patients with chronic coronary syndromes presenting with nonobstructive coronary artery disease. IMR was obtained using both intravenous (IV) adenosine and intracoronary (IC) papaverine. Each IMR measurement was obtained in duplicate. The primary objective was the agreement between IMR acquired using adenosine and papaverine. Secondary objectives include reproducibility of IMR and time required for the IMR measurement. RESULTS: One hundred and sixteen IMR measurements were performed in 29 patients. The mean age was 68.8 ± 7.24 years, and 27.6% was diabetics. IMR values were similar between papaverine and adenosine (17.7 ± 7.26 and 20.1 ± 8.6, p=0.25; Passing-Bablok coefficient A 0.58, 95% CI -2.42 to 3.53; coefficient B 0.90, 95% CI -0.74 to 1.07). The reproducibility of IMR was excellent with both adenosine and papaverine (ICC 0.78, 95% CI 0.63 to 0.88 and ICC 0.93, 95% CI 0.87 to 0.97). The time needed for microvascular assessment was significantly shortened by the use of IC papaverine (3.23 (2.84, 3.78) mins vs. 5.48 (4.94, 7.09) mins, p < 0.0001). CONCLUSION: IMR can be reliably measured using IC papaverine with similar results compared to intravenous infusion of adenosine with increased reproducibility and reduced procedural time. This approach simplifies the invasive assessment of the coronary microcirculation in the catheterization laboratory.