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

Management and outcomes of patients with left atrial appendage thrombus prior to percutaneous closure.

Left atrial appendage (LAA) thrombus has heretofore been considered a contraindication to percutaneous LAA closure (LAAC). Data regarding its management are very limited. The aim of this study was to analyse the medical and invasive treatment of patients referred for LAAC in the presence of LAA thrombus. This multicentre observational registry included 126 consecutive patients referred for LAAC with LAA thrombus on preprocedural imaging. Treatment strategies included intensification of antithrombotic therapy (IAT) or direct LAAC. The primary and secondary endpoints were a composite of bleeding, stroke and death at 18 months, and procedural success, respectively. IAT was the preferred strategy in 57.9% of patients, with total thrombus resolution observed in 60.3% and 75.3% after initial and subsequent IAT, respectively. Bleeding complications and stroke during IAT occurred in 9.6% and 2.9%, respectively, compared with 3.8% bleeding and no embolic events in the direct LAAC group before the procedure. Procedural success was 90.5% (96.2% vs 86.3% in direct LAAC and IAT group, respectively, p=0.072), without cases of in-hospital thromboembolic complications. The primary endpoint occurred in 29.3% and device-related thrombosis was found in 12.8%, without significant difference according to treatment strategy. Bleeding complications at 18 months occurred in 22.5% vs 10.5% in the IAT and direct LAAC group, respectively (p=0.102). In the presence of LAA thrombus, IAT was the initial management strategy in half of our cohort, with initial thrombus resolution in 60% of these, but with a relatively high bleeding rate (~10%). Direct LAAC was feasible, with high procedural success and absence of periprocedural embolic complications. However, a high rate of device-related thrombosis was detected during follow-up

Automation of intracoronary continuous thermodilution for absolute coronary flow and microvascular resistance measurements

AIM: Microvascular resistance reserve (MRR) as derived from continuous intracoronary thermodilution specifically quantifies microvasculature function. As originally described, the technique necessitates reinstrumentation of the artery and manual reprogramming of the infusion pump when performing resting and hyperemic measurements. To simplify and to render this procedure operator-independent, we developed a fully automated method. The aim of the present study is to validate the automated procedure against the originally described one. METHODS AND RESULTS: For the automated procedure, an infusion pump was preprogrammed to allow paired resting-hyperemic thermodilution assessment without interruption. To validate the accuracy of this new approach, 20 automated measurements were compared to those obtained in the same vessels with conventional paired resting-hyperemic thermodilution measurements (i.e., with a sensor pullback at each infusion rate and manual reprogramming of the infusion pump). A close correlation between the conventional and the automated measuring technique was found for resting flow (Qrest : r = 0.89, mean bias = 2.52; SD = 15.47), hyperemic flow (Qhyper : r = 0.88, mean bias = -2.65; SD = 27.96), resting microvascular resistance (Rμ-rest : r = 0.90, mean bias = 52.14; SD = 228.29), hyperemic microvascular resistance Rμ-hyper : r = 0.92, mean bias = 12.95; SD = 57.80), and MRR (MRR: r = 0.89, mean bias = 0.04, SD = 0.59). Procedural time was significantly shorter with the automated method (5'25″ ± 1'23″ vs. 4'36″​​​​​​​ ± 0'33″​​​​​​​, p = 0.013). CONCLUSION: Continuous intracoronary thermodilution-derived measurements of absolute flow, absolute resistance, and MRR can be fully automated. This further shortens and simplifies the procedure when performing paired resting-hyperemic measurements

Automation of intracoronary continuous thermodilution for absolute coronary flow and microvascular resistance measurements

Aim: Microvascular resistance reserve (MRR) as derived from continuous intracoronary thermodilution specifically quantifies microvasculature function. As originally described, the technique necessitates reinstrumentation of the artery and manual reprogramming of the infusion pump when performing resting and hyperemic measurements. To simplify and to render this procedure operator-independent, we developed a fully automated method. The aim of the present study is to validate the automated procedure against the originally described one. Methods and results: For the automated procedure, an infusion pump was preprogrammed to allow paired resting-hyperemic thermodilution assessment without interruption. To validate the accuracy of this new approach, 20 automated measurements were compared to those obtained in the same vessels with conventional paired resting-hyperemic thermodilution measurements (i.e., with a sensor pullback at each infusion rate and manual reprogramming of the infusion pump). A close correlation between the conventional and the automated measuring technique was found for resting flow (Qrest : r = 0.89, mean bias = 2.52; SD = 15.47), hyperemic flow (Qhyper : r = 0.88, mean bias = -2.65; SD = 27.96), resting microvascular resistance (Rμ-rest : r = 0.90, mean bias = 52.14; SD = 228.29), hyperemic microvascular resistance Rμ-hyper : r = 0.92, mean bias = 12.95; SD = 57.80), and MRR (MRR: r = 0.89, mean bias = 0.04, SD = 0.59). Procedural time was significantly shorter with the automated method (5'25″ ± 1'23″ vs. 4'36″ ± 0'33″, p = 0.013). Conclusion: Continuous intracoronary thermodilution-derived measurements of absolute flow, absolute resistance, and MRR can be fully automated. This further shortens and simplifies the procedure when performing paired resting-hyperemic measurements. Keywords: continuous intracoronary thermodilution; coronary flow reserve; coronary physiology; microvascular function; microvascular resistance reserv

Saline-induced coronary hyperemia with continuous intracoronary thermodilution is mediated by intravascular hemolysis

BACKGROUND AND AIMS: Absolute coronary flow can be measured by intracoronary continuous thermodilution of saline through a dedicated infusion catheter (RayFlow®). A saline infusion rate at 15-20 mL/min induces an immediate, steady-state, maximal microvascular vasodilation. The mechanism of this hyperemic response remains unclear. We aimed to test whether local hemolysis is a potential mechanism of saline-induced coronary hyperemia. METHODS: Twelve patients undergoing left and right catheterization were included. The left coronary artery and the coronary sinus were selectively cannulated. Absolute resting and hyperemic coronary flow were measured by continuous intracoronary thermodilution. Arterial and venous samples were collected from the coronary artery and the coronary sinus in five phases: baseline (BL); resting flow measurement (Rest, saline infusion at 10 mL/min); hyperemia (Hyperemia, saline infusion at 20 mL/min); post-hyperemia (Post-Hyperemia, 2 min after the cessation of saline infusion); and control phase (Control, during infusion of saline through the guide catheter at 30 mL/min). RESULTS: Hemolysis was visually detected only in the centrifugated venous blood samples collected during the Hyperemia phase. As compared to Rest, during Hyperemia both LDH (131.50 ± 21.89 U/dL [Rest] and 258.33 ± 57.40 U/dL [Hyperemia], p < 0.001) and plasma free hemoglobin (PFHb, 4.92 ± 3.82 mg/dL [Rest] and 108.42 ± 46.58 mg/dL [Hyperemia], p < 0.001) significantly increased in the coronary sinus. The percentage of hemolysis was significantly higher during the Hyperemia phase (0.04 ± 0.02% [Rest] vs 0.89 ± 0.34% [Hyperemia], p < 0.001). CONCLUSIONS: Saline-induced hyperemia through a dedicated intracoronary infusion catheter is associated with hemolysis. Vasodilatory compounds released locally, like ATP, are likely ultimately responsible for localized microvascular vasodilation

Saline-induced coronary hyperemia with continuous intracoronary thermodilution is mediated by intravascular hemolysis

BACKGROUND AND AIMS Absolute coronary flow can be measured by intracoronary continuous thermodilution of saline through a dedicated infusion catheter (RayFlow®). A saline infusion rate at 15-20 mL/min induces an immediate, steady-state, maximal microvascular vasodilation. The mechanism of this hyperemic response remains unclear. We aimed to test whether local hemolysis is a potential mechanism of saline-induced coronary hyperemia. METHODS Twelve patients undergoing left and right catheterization were included. The left coronary artery and the coronary sinus were selectively cannulated. Absolute resting and hyperemic coronary flow were measured by continuous intracoronary thermodilution. Arterial and venous samples were collected from the coronary artery and the coronary sinus in five phases: baseline (BL); resting flow measurement (Rest, saline infusion at 10 mL/min); hyperemia (Hyperemia, saline infusion at 20 mL/min); post-hyperemia (Post-Hyperemia, 2 min after the cessation of saline infusion); and control phase (Control, during infusion of saline through the guide catheter at 30 mL/min). RESULTS Hemolysis was visually detected only in the centrifugated venous blood samples collected during the Hyperemia phase. As compared to Rest, during Hyperemia both LDH (131.50 ± 21.89 U/dL [Rest] and 258.33 ± 57.40 U/dL [Hyperemia], p < 0.001) and plasma free hemoglobin (PFHb, 4.92 ± 3.82 mg/dL [Rest] and 108.42 ± 46.58 mg/dL [Hyperemia], p < 0.001) significantly increased in the coronary sinus. The percentage of hemolysis was significantly higher during the Hyperemia phase (0.04 ± 0.02% [Rest] vs 0.89 ± 0.34% [Hyperemia], p < 0.001). CONCLUSIONS Saline-induced hyperemia through a dedicated intracoronary infusion catheter is associated with hemolysis. Vasodilatory compounds released locally, like ATP, are likely ultimately responsible for localized microvascular vasodilation

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

Global Longitudinal Strain Predicts Outcomes in Patients with Reduced Left Ventricular Function Undergoing Transcatheter Edge-to-Edge Mitral Repair

Background: The timing and selection of optimal candidates for mitral transcatheter edge-to-edge valve repair remains to be fully determined, especially in cases with severely depressed left ventricular ejection fraction (LVEF). The objective of this study is to evaluate the prognostic value of myocardial strain (LVGLS) in this setting. Methods: Retrospectively, 172 consecutive patients with LVEF ≤40% and severe MR treated with MitraClip were included. Four groups were generated according to the LVEF (≥30%) and median LVGLS. The primary end-point was cardiovascular mortality. Results: Procedural success was high (96.5%) and complications were rare. At one-year follow-up, 82.5% of patients maintained MR grade ≤2, 79.2% were at a NYHA class ≤II and a reduction of 80% in heart failure admissions was observed in all groups. Interestingly, among patients with a more depressed LVEF, LVGLS was found to be an independent predictor for cardiovascular mortality (HR: 3.3; 95% CI: 1.1–10, p = 0.023). Conclusions: Mitral valve repair with MitraClip is safe and it improves the mid-term functional class of patients regardless of LVEF. LVGLS can help in the selection of optimal candidates and timing for this procedure, as well as in the recognition of those patients with worse prognoses