Mismatch Between Residual Mitral Regurgitation and Left Atrial Pressure Predicts Prognosis After Transcatheter Edge-to-Edge Repair.

BACKGROUND: The mechanism and impact of mismatch between residual mitral regurgitation (MR) and postprocedural left atrial pressure (LAP) after transcatheter edge-to-edge repair (TEER), which may adversely affect clinical outcome, is of great interest. OBJECTIVES: This study aimed to examine the effect of hemodynamic mismatch after TEER on clinical outcomes in patients with heart failure due to severe MR and investigate the predictive factors for the mismatch using a prospective multicenter registry. METHODS: We categorized 1,477 patients into optimal (residual MR grade ≤1 and postprocedural LAP ≤15 mm Hg), mismatched (residual MR grade >1 or postprocedural LAP >15 mm Hg), and poor (residual MR grade >1 and postprocedural LAP >15 mm Hg) groups and examined their prognosis. The primary endpoint was a composite of all-cause mortality and heart failure hospitalization. RESULTS: There were 927 (62.7%), 459 (31.1%), and 91 (6.2%) patients categorized into optimal, mismatched, and poor groups, respectively. Cox regression analysis, referenced to the optimal group, revealed that the mismatched and poor groups exhibited a higher risk for the primary endpoint (HR: 1.55; 95% CI: 1.28-1.88; and HR: 1.95; 95% CI: 1.38-2.74, respectively). Six risk factors were identified as predictors of hemodynamic mismatch after TEER: body mass index, baseline left atrial volume index, atrial fibrillation, tricuspid annular plane systolic excursion value, preprocedural mean left atrial pressure, and postprocedural mean mitral valve pressure gradient. CONCLUSIONS: Post-TEER hemodynamic mismatch between residual MR and postprocedural LAP was associated with a poor prognosis. Six readily accessible perioperative parameters predict the hemodynamic mismatch. (OCEAN-Mitral registry; UMIN000023653).

Addition of Ezetimibe to Intensive Lipid-Lowering Therapy Is Associated With a Lower Incidence of Heart Failure in Patients With Acute Coronary Syndrome.

BACKGROUND: This study investigated whether intensive lipid-lowering therapy with pitavastatin and ezetimibe lowers the incidence of heart failure (HF) events in patients with acute coronary syndrome (ACS). METHODS AND RESULTS: In the HIJ-PROPER study, 1,734 patients with ACS were randomly assigned to either pitavastatin plus ezetimibe therapy (n=864) or pitavastatin monotherapy (n=857). We examined the incidence of HF between these 2 groups over a 3.9-year period after ACS. The primary endpoint of the study was hospitalization for HF. The mean low-density lipoprotein cholesterol levels during the follow-up period were 65.1 mg/dL in the pitavastatin plus ezetimibe group and 84.6 mg/dL in the pitavastatin monotherapy group. The incidence of HF hospitalization was significantly lower in the pitavastatin plus ezetimibe group than in the pitavastatin monotherapy group (19 [2.2%] vs. 40 [4.7%] patients; hazard ratio 0.47, 95% confidence interval 0.27-0.81; P<0.005). This trend was consistent after multivariable analysis using multiple models. CONCLUSIONS: Intensive lipid-lowering therapy with pitavastatin and ezetimibe is associated with a lower incidence of hospitalization for HF in patients with ACS.

Imaging-guided PCI improves outcomes in patients with multivessel disease a meta-analysis of randomized and observational trials comparing treatment of ACS.

OBJECTIVE: This meta-analysis sought to investigate if IVUS-guided PCI (IVUS-PCI) can improve outcomes compared to standard PCI and CABG in patients with multivessel CAD. BACKGROUND: Coronary artery disease (CAD) is traditionally revascularized by either percutaneous coronary intervention (PCI) or coronary artery bypass (CABG) with a historical benefit of CABG over PCI in multivessel CAD. Intravascular ultrasound-guided PCI (IVUS-PCI) may improve outcomes compared to angiography alone. METHODS: We undertook a systematic search using PubMed, MEDLINE, EMBASE, Web of Science, and Ovid from 2017 through 2022. We included randomized controlled trials and observational trials comparing PCI vs CABG for multivessel CAD evaluated by two independent reviewers. We extracted baseline data and major adverse cardiovascular events (MACE; death from any cause, MI, stroke, or repeat revascularization) at one year. Three trials were selected based on study arm criteria: FAME 3, BEST, and Syntax II. RESULTS: IVUS-PCI significantly reduced death from any cause (OR 0.45, CI 0.272-0.733, p = 0.001), repeat revascularization (OR 0.62, CI 0.41-0.95, p = 0.03), and showed a non-significant reduction in MACE (OR 0.74, CI 0.54-1.01, p = 0.054) when compared to CABG. IVUS-PCI significantly reduced MACE (OR 0.52, CI 0.38-0.72, p < 0.001) and showed a non-significant reduction in death (OR 0.66, CI 0.36-1.18, p = 0.16) and numerically reduced repeat revascularization (OR 0.66, CI95 0.431-1.02, p = 0.06) when compared to PCI without IVUS. CONCLUSION: IVUS-PCI reduces cardiovascular outcomes in patients with multivessel disease compared to CABG and angiographically-guided PCI at one year. These results reinforce the importance of IVUS-PCI in complex CAD and provide evidence for improved PCI outcomes compared to CABG for multivessel CAD.

Adverse clinical events after percutaneous coronary intervention in very elderly patients with acute coronary syndrome.

The number of very elderly patients with acute coronary syndrome (ACS) is increasing. Therefore, owing to the need for evidence-based treatment decisions in this population, this study aimed to examine the clinical outcomes during 1 year after percutaneous coronary intervention (PCI) in very elderly patients with ACS. This prospective multicenter observational study comprised 1337 patients with ACS treated with PCI, classified into the following four groups according to age: under 60, <60 years; sexagenarian, ≥60 and <69 years; septuagenarian, ≥70 and <80 years; and very elderly, ≥80 years. The primary endpoint was a composite of the first occurrence of all-cause death, nonfatal myocardial infarction, nonfatal stroke, and bleeding within 1 year after PCI. We used the sexagenarian group as a reference and compared outcomes with those of the other groups. The incidence of the primary endpoint was significantly higher in the very elderly group than in the sexagenarian group (36 [12.7%] vs. 24 [6.9%], respectively; hazard ratio, 1.94; 95% confidence interval: 1.16-3.26; p = 0.012). The higher incidence of the primary endpoint was primarily driven by a higher incidence of all-cause death. When the multivariable analysis was used to adjust for patient characteristics and comorbidities, no difference was observed in the primary endpoint between the very elderly and sexagenarian groups (p = 0.96). The incidence of adverse events after PCI, particularly all-cause death, in very elderly patients with ACS was high. However, if several confounders are adjusted, comparable outcomes may be expected within 1 year after PCI among this population.

Differential Effect of Aortic Valve Replacement for Severe Aortic Stenosis on Hyperemic and Resting Epicardial Coronary Pressure Indices.

BACKGROUND: Coronary pressure indices to assess coronary artery disease are currently underused in patients with aortic stenosis due to many potential physiological effects that might hinder their interpretation. Studies with varying sample sizes have provided us with conflicting results on the effect of transcatheter aortic valve replacement (TAVR) on these indices. The aim of this meta-analysis was to study immediate and long-term effects of TAVR on fractional flow reserve (FFR) and nonhyperemic pressure ratios (NHPRs). METHODS AND RESULTS: Lesion-specific coronary pressure data were extracted from 6 studies, resulting in 147 lesions for immediate change in FFR analysis and 105 for NHPR analysis. To investigate the long-term changes, 93 lesions for FFR analysis and 68 for NHPR analysis were found. Lesion data were pooled and compared with paired t tests. Immediately after TAVR, FFR decreased significantly (-0.0130±0.0406 SD, P: 0.0002) while NHPR remained stable (0.0003±0.0675, P: 0.9675). Long-term after TAVR, FFR decreased significantly (-0.0230±0.0747, P: 0.0038) while NHPR increased nonsignificantly (0.0166±0.0699, P: 0.0543). When only borderline NHPR lesions were considered, this increase became significant (0.0249±0.0441, P: 0.0015). Sensitivity analysis confirmed our results in borderline lesions. CONCLUSIONS: TAVR resulted in small significant, but opposite, changes in FFR and NHPR. Using the standard cut-offs in patients with severe aortic stenosis, FFR might underestimate the physiological significance of a coronary lesion while NHPRs might overestimate its significance. The described changes only play a clinically relevant role in borderline lesions. Therefore, even in patients with aortic stenosis, an overtly positive or negative physiological assessment can be trusted.

Optimization of Absolute Coronary Blood Flow Measurements to Assess Microvascular Function: In Vivo Validation of Hyperemia and Higher Infusion Speeds.

BACKGROUND: Reliable assessment of coronary microvascular function is essential. Techniques to measure absolute coronary blood flow are promising but need validation. The objectives of this study were: first, to validate the potential of saline infusion to generate maximum hyperemia in vivo. Second, to validate absolute coronary blood flow measured with continuous coronary thermodilution at high (40-50 mL/min) infusion speeds and asses its safety. METHODS: Fourteen closed-chest sheep underwent absolute coronary blood flow measurements with increasing saline infusion speeds at different dosages under general anesthesia. An additional 7 open-chest sheep underwent these measurements with epicardial Doppler flow probes. Coronary flows were compared with reactive hyperemia after 45 s of coronary occlusion. RESULTS: Twenty milliliters per minute of saline infusion induced a significantly lower hyperemic coronary flow (140 versus 191 mL/min; P=0.0165), lower coronary flow reserve (1.82 versus 3.21; P≤0.0001), and higher coronary resistance (655 versus 422 woods units; P=0.0053) than coronary occlusion. On the other hand, 30 mL/min of saline infusion resulted in hyperemic coronary flow (196 versus 192 mL/min; P=0.8292), coronary flow reserve (2.77 versus 3.21; P=0.1107), and coronary resistance (415 versus 422 woods units; P=0.9181) that were not different from coronary occlusion. Hyperemic coronary flow was 40.7% with 5 mL/min, 40.8% with 10 mL/min, 73.1% with 20 mL/min, 102.3% with 30 mL/min, 99.0% with 40 mL/min, and 98.0% with 50 mL/min of saline infusion when compared with postocclusive hyperemic flow. There was a significant bias toward flow overestimation (Bland-Altman: bias±SD, -73.09±30.52; 95% limits of agreement, -132.9 to -13.27) with 40 to 50 mL/min of saline. Occasionally, ischemic changes resulted in ventricular fibrillation (9.5% with 50 mL/min) at higher infusion rates. CONCLUSIONS: Continuous saline infusion of 30 mL/min but not 20 mL/min induced maximal hyperemia. Absolute coronary blood flow measured with saline infusion speeds of 40 to 50 mL/min was not accurate and not safe.

Outcomes Based on Angiographic vs Functional Significance of Complex 3-Vessel Coronary Disease: FAME 3 Trial.

BACKGROUND: The functional SYNTAX score (FSS), which incorporates functional information as assessed by fractional flow reserve (FFR), is a better predictor of outcome after percutaneous coronary intervention (PCI) in patients with less complex coronary artery disease (CAD). OBJECTIVES: This study sought to test the prognostic value of the FSS in patients with complex CAD eligible for coronary artery bypass grafting (CABG). METHODS: The FAME 3 (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation 3) trial compared FFR-guided PCI with CABG in patients with angiographic 3-vessel CAD. In this prespecified substudy, the angiographic core laboratory calculated the SYNTAX score (SS) and then the FSS by eliminating lesions that were not significant based on FFR. Outcomes in the PCI patients based on the FSS and the SS were compared to each other and to the patients treated with CABG. RESULTS: The FSS reclassified more than one-quarter of patients from an SS >22 to an FSS ≤22. In the 50% of PCI patients who had an FSS ≤22, the primary endpoint occurred at a similar rate to patients treated with CABG (P = 0.77). The primary endpoint in patients without functionally significant 3-vessel CAD was similar to the CABG group (P = 0.97). The rate of myocardial infarction and revascularization among all deferred lesions was 0.5% and 3.2%, respectively. CONCLUSIONS: By measuring the FSS, one can identify 50% of patients who have a similar outcome at 1 year with PCI compared with CABG. Lesions deferred from PCI based on FFR have a low event rate.

Fractional Flow Reserve-Guided PCI or Coronary Bypass Surgery for 3-Vessel Coronary Artery Disease: 3-Year Follow-Up of the FAME 3 Trial.

BACKGROUND: Previous studies comparing percutaneous coronary intervention (PCI) with coronary artery bypass grafting (CABG) in patients with multivessel coronary disease not involving the left main have shown significantly lower rates of death, myocardial infarction (MI), or stroke after CABG. These studies did not routinely use current-generation drug-eluting stents or fractional flow reserve (FFR) to guide PCI. METHODS: FAME 3 (Fractional Flow Reserve versus Angiography for Multivessel Evaluation) is an investigator-initiated, multicenter, international, randomized trial involving patients with 3-vessel coronary artery disease (not involving the left main coronary artery) in 48 centers worldwide. Patients were randomly assigned to receive FFR-guided PCI using zotarolimus drug-eluting stents or CABG. The prespecified key secondary end point of the trial reported here is the 3-year incidence of the composite of death, MI, or stroke. RESULTS: A total of 1500 patients were randomized to FFR-guided PCI or CABG. Follow-up was achieved in >96% of patients in both groups. There was no difference in the incidence of the composite of death, MI, or stroke after FFR-guided PCI compared with CABG (12.0% versus 9.2%; hazard ratio [HR], 1.3 [95% CI, 0.98-1.83]; P=0.07). The rates of death (4.1% versus 3.9%; HR, 1.0 [95% CI, 0.6-1.7]; P=0.88) and stroke (1.6% versus 2.0%; HR, 0.8 [95% CI, 0.4-1.7]; P=0.56) were not different. MI occurred more frequently after PCI (7.0% versus 4.2%; HR, 1.7 [95% CI, 1.1-2.7]; P=0.02). CONCLUSIONS: At 3-year follow-up, there was no difference in the incidence of the composite of death, MI, or stroke after FFR-guided PCI with current-generation drug-eluting stents compared with CABG. There was a higher incidence of MI after PCI compared with CABG, with no difference in death or stroke. These results provide contemporary data to allow improved shared decision-making between physicians and patients with 3-vessel coronary artery disease. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02100722.

Cardiovascular events in patients with deferred lesions and chronic kidney disease.

No study has reported the association between the worsening of chronic kidney disease (CKD) and cardiovascular events in patients with deferred coronary artery lesions. We included patients with deferred lesions, defined as a fractional flow reserve (FFR) value > 0.80 treated with conservative medical therapy. Patients were divided into three groups: group 1, CKD stages 1-2; group 2, CKD stages 3-5; and group 3, CKD stage 5D (hemodialysis), with the clinical outcomes compared. The primary endpoint was the first occurrence of target vessel myocardial infarction, ischemia-driven target-vessel revascularization, or all-cause death. The primary endpoint was noted in 17, 25, and 36 patients in groups 1, 2, and 3, respectively. Within the three groups, the incidence rate of deferred lesions was 7.0%, 10.4%, and 32.4%, respectively. No difference was observed in the incidence of the primary endpoint between groups 1 and 2 (log-rank p = 0.16). However, the patients in group 3 had a significantly higher risk for the primary endpoint than those in groups 1 and 2 (log-rank p < 0.0001). In the multivariate Cox proportional hazards model, the patients in group 3 exhibited a higher incidence of the primary endpoint than those in group 1 (HR: 2.14; 95% CI 1.02-4.49; p < 0.01). Careful management is needed in patients undergoing hemodialysis, even if coronary artery stenosis is considered a deferred lesion.