Microaxial Flow Pump or Standard Care in Infarct-Related Cardiogenic Shock.

BACKGROUND: The effects of temporary mechanical circulatory support with a microaxial flow pump on mortality among patients with ST-segment elevation myocardial infarction (STEMI) complicated by cardiogenic shock remains unclear. METHODS: In an international, multicenter, randomized trial, we assigned patients with STEMI and cardiogenic shock to receive a microaxial flow pump (Impella CP) plus standard care or standard care alone. The primary end point was death from any cause at 180 days. A composite safety end point was severe bleeding, limb ischemia, hemolysis, device failure, or worsening aortic regurgitation. RESULTS: A total of 360 patients underwent randomization, of whom 355 were included in the final analysis (179 in the microaxial-flow-pump group and 176 in the standard-care group). The median age of the patients was 67 years, and 79.2% were men. Death from any cause occurred in 82 of 179 patients (45.8%) in the microaxial-flow-pump group and in 103 of 176 patients (58.5%) in the standard-care group (hazard ratio, 0.74; 95% confidence interval [CI], 0.55 to 0.99; P = 0.04). A composite safety end-point event occurred in 43 patients (24.0%) in the microaxial-flow-pump group and in 11 (6.2%) in the standard-care group (relative risk, 4.74; 95% CI, 2.36 to 9.55). Renal-replacement therapy was administered to 75 patients (41.9%) in the microaxial-flow-pump group and to 47 patients (26.7%) in the standard-care group (relative risk, 1.98; 95% CI, 1.27 to 3.09). CONCLUSIONS: The routine use of a microaxial flow pump with standard care in the treatment of patients with STEMI-related cardiogenic shock led to a lower risk of death from any cause at 180 days than standard care alone. The incidence of a composite of adverse events was higher with the use of the microaxial flow pump. (Funded by the Danish Heart Foundation and Abiomed; DanGer Shock ClinicalTrials.gov number, NCT01633502.).

Percutaneous Coronary Intervention Versus Coronary Artery Bypass Grafting in Patients With Left Main Disease With and Without Diabetes: Findings From a Pooled Analysis of 4 Randomized Clinical Trials.

BACKGROUND: Diabetes may be associated with differential outcomes in patients undergoing left main coronary revascularization with percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). The aim of this study was to investigate outcomes in patients with left main disease with and without diabetes randomized to PCI versus CABG. METHODS: Individual patient data were pooled from 4 trials (SYNTAX [Synergy Between PCI With Taxus and Cardiac Surgery], PRECOMBAT [Premier of Randomized Comparison of Bypass Surgery Versus Angioplasty Using Sirolimus-Eluting Stent in Patients With Left Main Coronary Artery Disease], NOBLE [Nordic-Baltic-British Left Main Revascularisation Study], and EXCEL [Evaluation of XIENCE Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization]) that randomized patients with left main disease to PCI or CABG. Patients were considered suitable for either approach. Patients were categorized by diabetes status. Kaplan-Meier event rates, Cox model hazard ratios, and interactions were assessed. RESULTS: Among 4393 patients, 1104 (25.1%) had diabetes. Patients with diabetes experienced higher rates of 5-year death (158/1104 [Kaplan-Meier rate, 14.7%] versus 297/3289 [9.3%]; P<0.001), spontaneous myocardial infarction (MI; 67/1104 [6.7%] versus 114/3289 [3.7%]; P<0.001), and repeat revascularization (189/1104 [18.5%] versus 410/3289 [13.2%]; P<0.001). Rates of all-cause mortality did not differ after PCI versus CABG in those with (84/563 [15.3%] versus 74/541 [14.1%]; hazard ratio, 1.11 [95% CI, 0.82-1.52]) or without (155/1634 [9.7%] versus 142/1655 [8.9%]; hazard ratio, 1.08 [95% CI, 0.86-1.36; PintHR=0.87) diabetes. Rates of stroke within 1 year were lower with PCI versus CABG in the entire population, with no heterogeneity based on diabetes status (PintHR=0.51). The 5-year rates of spontaneous MI and repeat coronary revascularization were higher after PCI regardless of diabetes status (spontaneous MI: 45/563 [8.9%] versus 22/541 [4.4%] in diabetes and 82/1634 [5.3%] versus 32/1655 [2.1%] in no diabetes, PintHR=0.47; repeat revascularization: 127/563 [24.5%] versus 62/541 [12.4%] in diabetes and 254/1634 [16.3%] versus 156/1655 [10.1%] in no diabetes, PintHR=0.18). For spontaneous MI and repeat revascularization, there were greater absolute risk differences beyond 1 year in patients with diabetes (4.9% and 9.9%) compared with those without (2.1% and 4.3%; PintARD=0.047 and 0.016). CONCLUSIONS: In patients with left main disease considered equally suitable for PCI or CABG and with largely low to intermediate SYNTAX scores, diabetes was associated with higher rates of death and cardiovascular events through 5 years. Compared with CABG, PCI resulted in no difference in the risk of death and a lower risk of early stroke regardless of diabetes status, and a higher risk of spontaneous MI and repeat coronary revascularization, with larger late absolute excess risks in patients with diabetes. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT01205776, NCT0146651, NCT00422968, and NCT00114972.

Intravascular imaging-guided coronary drug-eluting stent implantation: an updated network meta-analysis.

BACKGROUND: Previous meta-analyses have shown reduced risks of composite adverse events with intravascular imaging-guided percutaneous coronary intervention (PCI) compared with angiography guidance alone. However, these studies have been insufficiently powered to show whether all-cause death or all myocardial infarction are reduced with intravascular imaging guidance, and most previous intravascular imaging studies were done with intravascular ultrasound rather than optical coherence tomography (OCT), a newer imaging modality. We aimed to assess the comparative performance of intravascular imaging-guided PCI and angiography-guided PCI with drug-eluting stents. METHODS: For this systematic review and updated meta-analysis, we searched the MEDLINE, Embase, and Cochrane databases from inception to Aug 30, 2023, for studies that randomly assigned patients undergoing PCI with drug-eluting stents either to intravascular ultrasound or OCT, or both, or to angiography alone to guide the intervention. The searches were done and study-level data were extracted independently by two investigators. The primary endpoint was target lesion failure, defined as the composite of cardiac death, target vessel-myocardial infarction (TV-MI), or target lesion revascularisation, assessed in patients randomly assigned to intravascular imaging guidance (intravascular ultrasound or OCT) versus angiography guidance. We did a standard frequentist meta-analysis to generate direct data, and a network meta-analysis to generate indirect data and overall treatment effects. Outcomes were expressed as relative risks (RRs) with 95% CIs at the longest reported follow-up duration. This study was registered with the international prospective register of systematic reviews (PROSPERO, number CRD42023455662). FINDINGS: 22 trials were identified in which 15 964 patients were randomised and followed for a weighted mean duration of 24·7 months (longest duration of follow-up in each study ranging from 6 to 60 months). Compared with angiography-guided PCI, intravascular imaging-guided PCI resulted in a decreased risk of target lesion failure (RR 0·71 [95% CI 0·63-0·80]; p<0·0001), driven by reductions in the risks of cardiac death (RR 0·55 [95% CI 0·41-0·75]; p=0·0001), TV-MI (RR 0·82 [95% CI 0·68-0·98]; p=0·030), and target lesion revascularisation (RR 0·72 [95% CI 0·60-0·86]; p=0·0002). Intravascular imaging guidance also reduced the risks of stent thrombosis (RR 0·52 [95% CI 0·34-0·81]; p=0·0036), all myocardial infarction (RR 0·83 [95% CI 0·71-0·99]; p=0·033), and all-cause death (RR 0·75 [95% CI 0·60-0·93]; p=0·0091). Outcomes were similar for OCT-guided and intravascular ultrasound-guided PCI. INTERPRETATION: Compared with angiography guidance, intravascular imaging guidance of coronary stent implantation with OCT or intravascular ultrasound enhances both the safety and effectiveness of PCI, reducing the risks of death, myocardial infarction, repeat revascularisation, and stent thrombosis. FUNDING: Abbott.

Transcatheter Aortic Valve Implantation in Low-Risk Tricuspid or Bicuspid Aortic Stenosis: The NOTION-2 Trial.

BACKGROUND AND AIMS: Transcatheter aortic valve implantation (TAVI) has become the first choice to treat older patients with severe symptomatic aortic stenosis (AS). This study aimed to compare TAVI with surgery in low-risk patients ≤ 75 years of age, including both tricuspid and bicuspid AS. METHODS: The NOTION-2 trial enrolled and 1:1 randomized low-risk patients aged ≤ 75 years with severe symptomatic AS to TAVI or surgery. The primary endpoint was a composite of all-cause mortality, stroke or rehospitalization (related to the procedure, valve or heart failure) at 12 months. RESULTS: A total of 370 patients were enrolled with a mean age of 71.1 years and a median Society of Thoracic Surgeons risk score of 1.1%. A total of 100 patients had bicuspid AS. The 1-year incidence of the primary endpoint was 10.2% in the TAVI group and 7.1% in the surgery group (absolute risk difference 3.1%; 95% confidence interval [CI], -2.7% to 8.8%; hazard ratio (HR) 1.4, 95% CI: 0.7 to 2.9; p=0.3). Patients with TAVI, when compared to surgery, had lower risk of major bleeding and new-onset atrial fibrillation and higher risk of non-disabling stroke, permanent pacemaker implantation and moderate-or-greater paravalvular regurgitation. The risk of the primary composite endpoint was 8.7% and 8.3% in patients with tricuspid AS (HR 1.0, 95% CI: 0.5 to 2.3) and 14.3% and 3.9% in patients with bicuspid AS (HR 3.8, 95% CI: 0.8 to 18.5) treated with TAVI or surgery, respectively (P for interaction=0.1). CONCLUSIONS: Among low-risk patients aged ≤ 75 years with severe symptomatic AS, the rate of the composite of death, stroke, or rehospitalization at one year was similar between TAVI and surgery. TAVI outcomes in young bicuspid AS patients warrant caution and should be further investigated. (NOTION-2, ClinicalTrials.gov, NCT02825134).

Impact of Absolute Myocardial Blood Flow Quantification on the Diagnostic Performance of PET-Based Perfusion Scans Using 82Rubidium.

BACKGROUND: Guidelines propose the inclusion of quantitative measurements from 82Rubidium positron emission tomography (RbPET) to discriminate obstructive coronary artery disease (CAD). However, the effect on diagnostic accuracy is unknown. The aim was to investigate the optimal RbPET reading algorithm for improved identification of obstructive CAD. METHODS: Prospectively enrolled patients (N=400) underwent RbPET and invasive coronary angiography with fractional flow reserve and quantitative coronary angiography. Quantitative measurements (myocardial blood flow (MBF), MBF reserve, transient ischemic dilatation) by RbPET were step-wisely added to a qualitative assessment by the summed stress score based on their diagnostic accuracy of obstructive CAD by invasive coronary angiography-fractional flow reserve. Prespecified cutoffs were summed stress score ≥4, hyperemic MBF 2.00 mL/g per min, and MBF reserve 1.80, respectively. Hemodynamically obstructive CAD was defined as >90% diameter stenosis or invasive coronary angiography-fractional flow reserve ≤0.80, and sensitivity analyses included a clinically relevant reference of anatomically severe CAD (>70% diameter stenosis by invasive coronary angiography-quantitative coronary angiography). RESULTS: Hemodynamically obstructive CAD was present in 170/400 (42.5%) patients. Stand-alone summed stress score showed a sensitivity and specificity of 57% and 93%, respectively, while hyperemic MBF showed similar sensitivity (61%, P=0.57) but lower specificity (85%, P=0.008). With increased discrimination by receiver-operating characteristic curves (0.78 versus 0.85; P<0.001), combining summed stress score, MBF and MBF reserve showed the highest sensitivity of 77% but lower specificity of 74% (P<0.001 for both comparisons). Against anatomically severe CAD, all measures independently yielded high discrimination ≥0.90 with increased sensitivity and lower specificity by additional quantification. CONCLUSIONS: The inclusion of quantitative measurements to a RbPET read increases in the identification of obstructive CAD. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03481712.

Unintended Deformation of Stents During Bifurcation PCI: An OCTOBER Trial Substudy.

BACKGROUND: Unintended deformation of implanted coronary stents can lead to loss of coronary access, stent thrombosis and coronary events during follow-up. The incidence, mechanisms and clinical outcomes of unintended stent deformations (USD) during complex bifurcation stenting are not well characterized. OBJECTIVES: In a prespecified analysis of the OCTOBER (European Trial on Optical Coherence Tomography Optimized Bifurcation Event Reduction) trial, we aimed to: 1) determine the incidence and characterize mechanisms of USD identified by optical coherence tomography (OCT); and 2) evaluate physician's detection and correction of accidental abluminal rewiring and USD. METHODS: OCT scans were analyzed for accidental abluminal rewiring and USD. When USD was identified, the plausible mechanism was determined by analysis of all procedural OCT scans and the corresponding angiograms. RESULTS: USD was identified by the core lab in 9.3% (55/589) of OCT-guided cases. Accidental abluminal rewiring was the cause in 44% (24/55), and guide catheter collision was the cause in 40% (22/55) of cases. USD was found in 18.5% of all cases with left main bifurcation percutaneous coronary intervention. The total incidence of abluminal rewiring was 33 in 32 OCT-guided cases (5.4%) and was corrected by physicians in 18 of 33 appearances (54.5%). The 2-year major adverse cardiac event rate for patients with untreated USD (n = 30) was 23.3%, whereas patients with confirmed or possibly corrected USD (n = 25) had no events during follow-up. CONCLUSIONS: USD was associated with adverse procedural complications and cardiac events during follow-up when not identified and corrected. The predominant mechanisms were undetected abluminal rewiring and guide catheter collision. Left main bifurcation percutaneous coronary intervention was a particular risk with USD detected in 18.5% of cases.

Randomized Trial of Cholesterol Lowering With Evolocumab for Cardiac Allograft Vasculopathy in Heart Transplant Recipients.

BACKGROUND: Cardiac allograft vasculopathy is characterized by increased coronary intimal thickness and is a leading cause of death in heart transplant (HTx) recipients despite the routine use of statins. The experience with inhibitors of proprotein convertase subtilisin-kexin type 9 in HTx recipients is limited. Our hypothesis was that lowering cholesterol with the proprotein convertase subtilisin-kexin type 9inhibitor evolocumab would reduce coronary intimal thickness in these patients without compromising safety. OBJECTIVES: This double blind, randomized trial was conducted to test whether evolocumab reduces the burden of cardiac allograft vasculopathy. METHODS: Patients who had received a cardiac allograft at one of the Nordic transplant centers within the prior 4 to 8 weeks were randomized to monthly subcutaneous injections of evolocumab 420 mg or matching placebo. The primary endpoint was the baseline-adjusted maximal intimal thickness as measured by intracoronary ultrasound after 12 months' treatment. RESULTS: The trial enrolled 128 patients between June 2019 and May 2022. Matched pairs of coronary ultrasound images were available for 56 patients assigned to evolocumab and 54 patients assigned to placebo. At 12 months, the adjusted mean difference in the maximal intimal thickness between the 2 arms was 0.017 mm (95% CI: -0.006 to 0.040; P = 0.14). The mean reduction in low-density lipoprotein cholesterol with evolocumab compared with placebo was 1.11 mmol/L (95% CI: 0.86-1.37 mmol/L). The use of evolocumab was not associated with an increase in adverse events. CONCLUSIONS: Twelve months of treatment with evolocumab substantially reduced low-density lipoprotein cholesterol but did not reduce maximal coronary intimal thickness in HTx recipients. (Cholesterol Lowering With EVOLocumab to Prevent Cardiac Allograft Vasculopathy in De-novo Heart Transplant Recipients [EVOLVD]; NCT03734211).

Impact of sex on the assessment of the microvascular resistance reserve.

BACKGROUND: The microvascular resistance reserve (MRR) is an innovative index to assess the vasodilatory capacity of the coronary circulation while accounting for the presence of concomitant epicardial disease. The MRR has shown to be a valuable diagnostic and prognostic tool in the general coronary artery disease (CAD) population. However, considering the fundamental aspects of its assessment and the unique hemodynamic characteristics of women, it is crucial to provide additional considerations for evaluating the MRR specifically in women. AIM: The aim of this study was to assess the diagnostic and prognostic applicability of the MRR in women and assess the potential differences across different sexes. METHODS: From the ILIAS Registry, we enrolled all patients with a stable indication for invasive coronary angiography, ensuring complete physiological and follow-up data. We analyzed the diagnostic value by comparing differences between sexes and evaluated the prognostic value of the MRR specifically in women, comparing it to that in men. RESULTS: A total of 1494 patients were included of which 26% were women. The correlation between MRR and CFR was good and similar between women (r = 0.80, p < 0.005) and men (r = 0.81, p < 0.005). The MRR was an independent and important predictor of MACE in both women (HR 0.67, 0.47-0.96, p = 0.027) and men (HR 0.84, 0.74-0.95, p = 0.007). The optimal cut-off value for MRR in women was 2.8 and 3.2 in men. An abnormal MRR similarly predicted MACE at 5-year follow-up in both women and men. CONCLUSION: The MRR seems to be equally applicable in both women and men with stable coronary artery disease.

Impact of hyperaemic stenosis resistance on long-term outcomes of stable angina in the ILIAS Registry.

BACKGROUND: The hyperaemic stenosis resistance (HSR) index was introduced to provide a more comprehensive indicator of the haemodynamic severity of a coronary lesion. HSR combines both the pressure drop across a lesion and the flow through it. As such, HSR overcomes the limitations of the more traditional fractional flow reserve (FFR) or coronary flow reserve (CFR) indices. AIMS: We aimed to identify the diagnostic and prognostic value of HSR and evaluate the clinical implications. METHODS: Patients with chronic coronary syndromes (CCS) and obstructive coronary artery disease were selected from the multicentre ILIAS Registry. For this study, only patients with combined Doppler flow and pressure measurements were included. RESULTS: A total of 853 patients with 1,107 vessels were included. HSR more accurately identified the presence of inducible ischaemia compared to FFR and CFR (area under the curve 0.71 vs 0.66 and 0.62, respectively; p<0.005 for both). An abnormal HSR measurement was an independent and important predictor of target vessel failure at 5-year follow-up (hazard ratio 3.80, 95% confidence interval: 2.12-6.73; p<0.005). In vessels deferred from revascularisation, HSR seems to identify more accurately those vessels that may benefit from revascularisation rather than FFR and/or CFR. CONCLUSIONS: The present study affirms the theoretical advantages of the HSR index for the detection of ischaemia-Âinducing coronary lesions in a large CCS population. (Inclusive Invasive Physiological Assessment in Angina Syndromes Registry [ILIAS Registry], ClinicalTrials.gov: NCT04485234).

Prognostic Implications of Individual and Combinations of Resting and Hyperemic Coronary Pressure and Flow Parameters.

Background: Coronary pressure- and flow-derived parameters have prognostic value. Objectives: This study aims to investigate the individual and combined prognostic relevance of pressure and flow parameters reflecting resting and hyperemic conditions. Methods: A total of 1,971 vessels deferred from revascularization after invasive pressure and flow assessment were included from the international multicenter registry. Abnormal resting pressure and flow were defined as distal coronary pressure/aortic pressure ≤0.92 and high resting flow (1/resting mean transit time >2.4 or resting average peak flow >22.7 cm/s), and abnormal hyperemic pressure and flow as fractional flow reserve ≤0.80 and low hyperemic flow (1/hyperemic mean transit time <2.2 or hyperemic average peak flow <25.0 cm/s), respectively. The clinical endpoint was target vessel failure (TVF), myocardial infarction (MI), or cardiac death at 5 years. Results: The mean % diameter stenosis was 46.8% ± 16.5%. Abnormal pressure and flow were independent predictors of TVF and cardiac death/MI (all P < 0.05). The risk of 5-year TVF or MI/cardiac death increased proportionally with neither, either, and both abnormal resting pressure and flow, and abnormal hyperemic pressure and flow (all P for trend < 0.001). Abnormal resting pressure and flow were associated with a higher rate of TVF or MI/cardiac death in vessels with normal fractional flow reserve; this association was similar for abnormal hyperemic pressure and flow in vessels with normal resting distal coronary pressure/aortic pressure (all P < 0.05). Conclusions: Abnormal resting and hyperemic pressure and flow were independent prognostic predictors. The abnormal flow had an additive prognostic value for pressure in both resting and hyperemic conditions with complementary prognostic between resting and hyperemic parameters.

Sex-Specific Clinical Outcomes After Treatment of Left Main Coronary Artery Disease. A NOBLE Substudy.

Background: While female sex has been associated with worse outcomes following coronary revascularization, previous analyses in left main coronary artery (LMCA) disease have been conflicting. In addition, a signal that increased mortality may be specific to women treated with percutaneous coronary intervention (PCI) requires further investigation. Methods: Nordic-Baltic-British left main revascularization study (NOBLE) was a randomized trial comparing PCI to coronary artery bypass surgery (CABG) in patients with LMCA disease. The primary endpoint was a composite of all-cause mortality, nonprocedural myocardial infarction, repeat revascularization, and stroke (major adverse cardiovascular and cerebrovascular events [MACCE]). We report the 5-year sex-specific outcomes. Results: Of 1184 patients analyzed, 256 (22%) were female and 928 (78%) were male. There were no significant within-sex differences in baseline characteristics, disease location, or complexity between those treated with PCI and those with CABG. The 5-year MACCE rates were 29% and 15% in females and 28% and 20% in males treated with PCI and CABG, respectively. Within both sexes, there was an increased risk of MACCE with PCI compared with CABG, but no difference in all-cause mortality. On multivariate analysis, female sex was not an independent predictor of MACCE. Conclusions: Following the treatment of LMCA disease, long-term outcomes favored CABG over PCI in both sexes. Importantly, there was no difference in all-cause mortality in females or males at 5 â€‹years.