Evidence of a causal and modifiable relationship between kidney function and circulating trimethylamine N-oxide.

The host-microbiota co-metabolite trimethylamine N-oxide (TMAO) is linked to increased cardiovascular risk but how its circulating levels are regulated remains unclear. We applied "explainable" machine learning, univariate, multivariate and mediation analyses of fasting plasma TMAO concentration and a multitude of phenotypes in 1,741 adult Europeans of the MetaCardis study. Here we show that next to age, kidney function is the primary variable predicting circulating TMAO, with microbiota composition and diet playing minor, albeit significant, roles. Mediation analysis suggests a causal relationship between TMAO and kidney function that we corroborate in preclinical models where TMAO exposure increases kidney scarring. Consistent with our findings, patients receiving glucose-lowering drugs with reno-protective properties have significantly lower circulating TMAO when compared to propensity-score matched control individuals. Our analyses uncover a bidirectional relationship between kidney function and TMAO that can potentially be modified by reno-protective anti-diabetic drugs and suggest a clinically actionable intervention for decreasing TMAO-associated excess cardiovascular risk.

Comparison of Outcomes Between 1- and 2-Stent Techniques for Medina Classification 0.0.1 Coronary Bifurcation Lesions.

BACKGROUND: Although Medina 0.0.1 bifurcation lesions are often treated by percutaneous coronary intervention (PCI) in real-world practice, the optimal revascularization strategy for this lesion is uncertain. OBJECTIVES: The current study aimed to compare the clinical outcomes between 1- and 2-stent strategies in patients treated with PCI for Medina 0.0.1 bifurcation lesions. METHODS: The extended BIFURCAT (Combined Insights From the Unified RAIN [Very Thin Stents for Patients with Left Main or Bifurcation in Real Life] and COBIS [Coronary Bifurcation Stenting] Bifurcation Registries) registry was obtained by patient-level merging the dedicated bifurcation COBIS II, III, and RAIN registries. Among 8,434 patients with bifurcation lesions undergoing PCI, 345 (4.1%) with Medina 0.0.1 lesions were selected for the current analysis. The primary endpoint was major adverse cardiac event (MACE, a composite of all-cause death, myocardial infarction, target vessel revascularization, and stent thrombosis) at 800 days. RESULTS: In the total population, 209 patients (60.6%) received PCI with a 1-stent strategy and the remaining 136 patients (39.4%) with a 2-stent strategy. There was a tendency for higher use of a 1-stent strategy over time (36.0%, 47.4%, and 90.4% in 2003-2009, 2010-2014, and 2015-2017, respectively; P for trend < 0.001). For the treatment of Medina 0.0.1 lesions, there was no significant difference in the risk of MACE between 1- and 2-stent strategies (1 stent vs 2 stent, 14.3% vs 13.9%; HR: 1.034; 95% CI: 0.541-1.977; P = 0.92). The risk of MACE was also not significantly different when stratifying into 3 groups (1-stent crossover only, 1-stent with strut opening, and 2-stent strategy). CONCLUSIONS: In patients with a Medina 0.0.1 type bifurcation lesion, PCI with a 1-stent strategy showed comparable outcomes to that of a 2-stent strategy. (Coronary Bifurcation Stenting II [COBIS II]; NCT01642992; Coronary Bifurcation Stenting III [COBIS III]; NCT03068494; Very Thin Stents for Patients with Left Main or Bifurcation in Real Life [RAIN]; NCT03544294).

Implication of the new definition of pulmonary hypertension in patients evaluated for heart transplantation.

BACKGROUND: The 2018 World Symposium on Pulmonary Hypertension (WSPH) changed the definition of pulmonary hypertension (PH) with a new threshold of mean pulmonary artery pressure (mPAP) above 20 mmHg. OBJECTIVE: To evaluate the profile and prognosis of patients with chronic heart failure (HF) considered for heart transplantation with the new definition of PH. METHODS: Patients with chronic HF considered for heart transplantation were classified as mPAP≤20mmHg, mPAP 20-25 mmHg, and mPAP≥25mmHg. Using a multivariate Cox model, we compared the mortality of patients with mPAP20-25mmHg, and mPAP≥25mmHg versus those with mPAP≤20mmHg. RESULTS: Of 693 patients with chronic HF considered for heart transplantation, 12.7%, 77.5% and 9.8% were classified as mPAP20-25mmHg, mPAP≥ 25mmHg and mPAP≤20mmHg. Patients of mPAP ≥ 25mmHg and mPAP 20-25 mmHg categories were older than mPAP ≤ 20 mmHg (56 versus 55 and 52 year-old, p = 0.02) with more frequent co-morbidities. Within 2.8 years, the mPAP20-25mmHg category displayed a higher risk of mortality compared with those of the mPAP≤20mmHg category (aHR 2.75, 95% CI 1.27-5.97, p = 0.01). Overall, the new PH definition using a threshold of mPAP >20 mmHg was associated with a higher risk of death (adj HR 2.71, 95% CI 1.26-5.80) than the previous definition (mPAP >25 mmHg, aHR: 1.35 95% CI 1.00-1.83, p = 0.05). CONCLUSIONS: One out of 8 patients with severe HF are reclassified as having PH following the 2018 WSPH. Patients with mPAP20-25 evaluated for heart transplantation displayed significant co-morbidities and high mortality rates.

Microbially Produced Imidazole Propionate Is Associated With Heart Failure and Mortality.

BACKGROUND: Over the past years, it has become clear that the microbial ecosystem in the gut has a profound capacity to interact with the host through the production of a wide range of bioactive metabolites. The microbially produced metabolite imidazole propionate (ImP) is clinically and mechanistically linked with insulin resistance and type 2 diabetes, but it is unclear how ImP is associated with heart failure. OBJECTIVES: The authors aimed to explore whether ImP is associated with heart failure and mortality. METHODS: ImP serum measurements in 2 large and independent clinical cohorts of patients (European [n = 1,985] and North American [n = 2,155]) with a range of severity of cardiovascular disease including heart failure. Univariate and multivariate Cox regression analyses were performed to delineate the impact of ImP on 5-year mortality in the North American cohort, independent of other covariates. RESULTS: ImP is independently associated with reduced ejection fraction and heart failure in both cohorts, even after adjusting for traditional risk factors. Elevated ImP was a significant independent predictor of 5-year mortality (for the highest quartile, adjusted HR: 1.85 [95% CI: 1.20-2.88]; P < 0.01). CONCLUSIONS: The gut microbial metabolite ImP is increased in individuals with heart failure and is a predictor of overall survival.

Bystander basic life support and survival after out-of-hospital cardiac arrest: A propensity score matching analysis.

INTRODUCTION AND OBJECTIVES: In out-of-hospital cardiac arrest, early recognition, calling for emergency medical assistance, and early cardiopulmonary resuscitation are acknowledged to be the three most important components in the chain of survival. However, bystander basic life support (BLS) initiation rates remain low. The objective of the present study was to evaluate the association between bystander BLS and survival after an out-of-hospital cardiac arrest (OHCA). METHODS: We conducted a retrospective cohort study of all patients with OHCA with a medical etiology treated by a mobile intensive care unit (MICU) in France from July 2011 to September 2021, as recorded in the French National OHCA Registry (RéAC). Cases in which the bystander was an on-duty fire fighter, paramedic, or emergency physician were excluded. We assessed the characteristics of patients who received bystander BLS vs. those who did not. The two classes of patient were then matched 1:1, using a propensity score. Conditional logistic regression was then used to probe the putative association between bystander BLS and survival. RESULTS: During the study, 52,303 patients were included; BLS was provided by a bystander in 29,412 of these cases (56.2%). The 30-day survival rates were 7.6% in the BLS group and 2.5% in the no-BLS group (p < 0.001). After matching, bystander BLS was associated with a greater 30-day survival rate (odds ratio (OR) [95% confidence interval (CI)] = 1.77 [1.58-1.98]). Bystander BLS was also associated with greater short-term survival (alive on hospital admission; OR [95%CI] = 1.29 [1.23-1.36]). CONCLUSIONS: The provision of bystander BLS was associated with a 77% greater likelihood of 30-day survival after OHCA. Given than only one in two OHCA bystanders provides BLS, a greater focus on life saving training for laypeople is essential.

Beta-blocker prescription and outcomes in uncomplicated acute myocardial infarction: Insight from the ePARIS registry.

BACKGROUND: Systematic prescription of beta-blockers after myocardial infarction remains an open question in the era of revascularization, especially for patients with uncomplicated myocardial infarction. OBJECTIVE: To evaluate in a real-life registry the proportion of patients with uncomplicated myocardial infarction (preserved left ventricular ejection fraction and no cardiovascular event within the first 6 months), and to report their characteristics, outcomes and beta-blocker use. METHODS: We included 1887 consecutive patients with ST-segment elevation myocardial infarction from the prospective ePARIS registry. Patients were divided into three groups: the "uncomplicated myocardial infarction" group (n=1060), defined by a left ventricular ejection fraction ≥ 40% and a 6-month period free from cardiovascular events; the "complicated myocardial infarction" group (n=366), defined by a left ventricular ejection fraction ≥ 40% and a recurrent cardiovascular event in the first 6 months; and the "left ventricular dysfunction" group (n=461), defined by a left ventricular ejection fraction<40%. RESULTS: During a median follow-up of 2.7 years (interquartile range 1.0-4.9 years), the "uncomplicated myocardial infarction" group was at low mortality risk compared with the "complicated myocardial infarction" group (hazard ratio 0.38, 95% confidence interval 0.25-0.58; P<0.01) and the "left ventricular dysfunction" group (hazard ratio 0.22, 95% confidence interval 0.15-0.32; P<0.01). Beta-blockers were prescribed at discharge predominantly in the "uncomplicated myocardial infarction" group (93%) compared with 87% in the "complicated myocardial infarction" group and 81% in the "left ventricular dysfunction" group. CONCLUSIONS: Beta-blockers are less prescribed in patients who may need them the most. The benefit of beta-blockers-largely prescribed in lower-risk patients-remains to be shown beyond the first 6 months for these patients with no left ventricular dysfunction and no recurrent events.

Impact of Clinical and Lesion Features on Outcomes After Percutaneous Coronary Intervention in Bifurcation Lesions.

Background: Bifurcation percutaneous coronary intervention (PCI) is associated with higher risk of clinical events. Objectives: This study aimed to determine clinical and lesion features that predict adverse outcomes, and to evaluate the differential prognostic impact of these features in patients undergoing PCI for bifurcation lesions. Methods: We analyzed 5,537 patients from the BIFURCAT (comBined Insights From the Unified RAIN and COBIS bifurcAtion regisTries) registry. The primary outcome was major adverse cardiac events (MACE) at 2-year follow-up; secondary outcomes included hard endpoints (all-cause death, myocardial infarction) and lesion-oriented clinical outcomes (LOCO) (target-vessel myocardial infarction, target lesion revascularization). The least absolute shrinkage and selection operator (LASSO) model was used for feature selection. Results: During the 2-year follow-up period, MACE occurred in 492 patients (8.9%). The LASSO model identified 5 clinical features (old age, chronic renal disease, diabetes mellitus, current smoking, and left ventricular dysfunction) and 4 lesion features (left main disease, proximal main branch disease, side branch disease, and a small main branch diameter) as significant features that predict MACE. A combination of all 9 features improved the predictive value for MACE compared with clinical and lesion features (area under the receiver-operating characteristics curve: 0.657 vs 0.636 vs 0.581; P < 0.001). For secondary endpoints, the clinical features had a higher impact than lesion features on hard endpoints, whereas lesion features had a higher impact than clinical features on LOCO. Conclusions: In bifurcation PCI, 9 features were associated with MACE. Clinical features were predominant predictors for hard endpoints, and lesion features were predominant for predicting LOCO. Clinical and lesion features have distinct values, and both should be considered in bifurcation PCI.

Prediction of All-Cause Mortality Following Percutaneous Coronary Intervention in Bifurcation Lesions Using Machine Learning Algorithms.

Stratifying prognosis following coronary bifurcation percutaneous coronary intervention (PCI) is an unmet clinical need that may be fulfilled through the adoption of machine learning (ML) algorithms to refine outcome predictions. We sought to develop an ML-based risk stratification model built on clinical, anatomical, and procedural features to predict all-cause mortality following contemporary bifurcation PCI. Multiple ML models to predict all-cause mortality were tested on a cohort of 2393 patients (training, n = 1795; internal validation, n = 598) undergoing bifurcation PCI with contemporary stents from the real-world RAIN registry. Twenty-five commonly available patient-/lesion-related features were selected to train ML models. The best model was validated in an external cohort of 1701 patients undergoing bifurcation PCI from the DUTCH PEERS and BIO-RESORT trial cohorts. At ROC curves, the AUC for the prediction of 2-year mortality was 0.79 (0.74-0.83) in the overall population, 0.74 (0.62-0.85) at internal validation and 0.71 (0.62-0.79) at external validation. Performance at risk ranking analysis, k-center cross-validation, and continual learning confirmed the generalizability of the models, also available as an online interface. The RAIN-ML prediction model represents the first tool combining clinical, anatomical, and procedural features to predict all-cause mortality among patients undergoing contemporary bifurcation PCI with reliable performance.

Impact of Left Ventricular Ejection Fraction on Procedural and Long-Term Outcomes of Bifurcation Percutaneous Coronary Intervention.

The association of left ventricular ejection fraction (LVEF) with procedural and long-term outcomes after state-of-the-art percutaneous coronary intervention (PCI) of bifurcation lesions remains unsettled. A total of 5,333 patients who underwent contemporary coronary bifurcation PCI were included in the intercontinental retrospective combined insights from the unified RAIN (veRy thin stents for patients with left mAIn or bifurcatioN in real life) and COBIS (COronary BIfurcation Stenting) III bifurcation registries. Of 5,003 patients (93.8%) with known baseline LVEF, 244 (4.9%) had LVEF <40% (bifurcation with reduced ejection fraction [BIFrEF] group), 430 (8.6%) had LVEF 40% to 49% (bifurcation with mildly reduced ejection fraction [BIFmEF] group) and 4,329 (86.5%) had ejection fraction (EF) ≥50% (bifurcation with preserved ejection fraction [BIFpEF] group). The primary end point was the Kaplan-Meier estimate of major adverse cardiac events (MACEs) (a composite of all-cause death, myocardial infarction, and target vessel revascularization). Patients with BIFrEF had a more complex clinical profile and coronary anatomy. No difference in procedural (30 days) MACE was observed across EF categories, also after adjustment for in-study outcome predictors (BIFrEF vs BIFmEF: adjusted hazard ratio [adj-HR] 1.39, 95% confidence interval [CI] 0.37 to 5.21, p = 0.626; BIFrEF vs BIFpEF: adj-HR 1.11, 95% CI 0.25 to 2.87, p = 0.883; BIFmEF vs BIFpEF: adj-HR 0.81, 95% CI 0.29 to 2.27, p = 0.683). BIFrEF was independently associated with long-term MACE (median follow-up 21 months, interquartile range 10 to 21 months) than both BIFmEF (adj-HR 2.20, 95% CI 1.41 to 3.41, p <0.001) and BIFpEF (adj-HR 1.91, 95% CI 1.41 to 2.60, p <0.001) groups, although no difference was observed between BIFmEF and BIFpEF groups (adj-HR 0.87, 95% CI 0.61 to 1.24, p = 0.449). In conclusion, in patients who underwent PCI of a coronary bifurcation lesion according to contemporary clinical practice, reduced LVEF (<40%), although a strong predictor of long-term MACEs, does not affect procedural outcomes.

Microbiome and metabolome features of the cardiometabolic disease spectrum.

Previous microbiome and metabolome analyses exploring non-communicable diseases have paid scant attention to major confounders of study outcomes, such as common, pre-morbid and co-morbid conditions, or polypharmacy. Here, in the context of ischemic heart disease (IHD), we used a study design that recapitulates disease initiation, escalation and response to treatment over time, mirroring a longitudinal study that would otherwise be difficult to perform given the protracted nature of IHD pathogenesis. We recruited 1,241 middle-aged Europeans, including healthy individuals, individuals with dysmetabolic morbidities (obesity and type 2 diabetes) but lacking overt IHD diagnosis and individuals with IHD at three distinct clinical stages-acute coronary syndrome, chronic IHD and IHD with heart failure-and characterized their phenome, gut metagenome and serum and urine metabolome. We found that about 75% of microbiome and metabolome features that distinguish individuals with IHD from healthy individuals after adjustment for effects of medication and lifestyle are present in individuals exhibiting dysmetabolism, suggesting that major alterations of the gut microbiome and metabolome might begin long before clinical onset of IHD. We further categorized microbiome and metabolome signatures related to prodromal dysmetabolism, specific to IHD in general or to each of its three subtypes or related to escalation or de-escalation of IHD. Discriminant analysis based on specific IHD microbiome and metabolome features could better differentiate individuals with IHD from healthy individuals or metabolically matched individuals as compared to the conventional risk markers, pointing to a pathophysiological relevance of these features.

Combinatorial, additive and dose-dependent drug-microbiome associations.

During the transition from a healthy state to cardiometabolic disease, patients become heavily medicated, which leads to an increasingly aberrant gut microbiome and serum metabolome, and complicates biomarker discovery1-5. Here, through integrated multi-omics analyses of 2,173 European residents from the MetaCardis cohort, we show that the explanatory power of drugs for the variability in both host and gut microbiome features exceeds that of disease. We quantify inferred effects of single medications, their combinations as well as additive effects, and show that the latter shift the metabolome and microbiome towards a healthier state, exemplified in synergistic reduction in serum atherogenic lipoproteins by statins combined with aspirin, or enrichment of intestinal Roseburia by diuretic agents combined with beta-blockers. Several antibiotics exhibit a quantitative relationship between the number of courses prescribed and progression towards a microbiome state that is associated with the severity of cardiometabolic disease. We also report a relationship between cardiometabolic drug dosage, improvement in clinical markers and microbiome composition, supporting direct drug effects. Taken together, our computational framework and resulting resources enable the disentanglement of the effects of drugs and disease on host and microbiome features in multimedicated individuals. Furthermore, the robust signatures identified using our framework provide new hypotheses for drug-host-microbiome interactions in cardiometabolic disease.

Performance of Thin-Strut Stents in Non-Left Main Bifurcation Coronary Lesions: A RAIN Subanalysis.

OBJECTIVES: This study assesses the safety and efficacy of thin-strut stents in non-left main (non-LM) bifurcation coronary lesions. BACKGROUND: Thinner struts of recent drug-eluting stent (DES) devices are associated with improved outcomes, but data about their performance in challenging scenarios are scant. METHODS: RAIN was a retrospective multicenter registry enrolling patients with coronary bifurcation lesions or left main (LM) disease treated with thin-strut DESs. Target-lesion revascularization (TLR) was the primary endpoint, while major adverse clinical event (MACE) rate, a composite of all-cause death, myocardial infarction (MI), target-vessel revascularization (TVR), TLR, and stent thrombosis (ST), and its single components were the secondary endpoints. Multivariable analysis was performed to identify predictors of TLR. Outcome incidences according to stenting strategy (provisional vs 2-stent technique), use of final kissing balloon (FKB), and intravascular ultrasound/optical coherence tomography optimization were further investigated in prespecified subanalyses. RESULTS: A total of 1803 patients (59% acute coronary syndrome, 41% stable coronary artery disease) with non-LM bifurcations were enrolled. After a median follow-up of 12 months, TLR incidence was 2.5% (2.2% for provisional stenting and 3.5% for 2-stent technique). MACE rate was 9.4% (all-cause death, 4.1%; MI, 3.2%; TVR, 3.7%; definite ST, 1.1%). After multivariable adjustment, postdilation (hazard ratio [HR], 0.32; 95% confidence interval [CI], 0.15-0.71; P<.01) and provisional stenting (HR, 0.62; 95% CI, 0.55-0.89; P=.03) were associated with lower TLR rates. FKB was associated with a lower incidence of TLR in the 2-stent subgroup (P=.03). Intracoronary imaging had no significant impact on the primary endpoint. CONCLUSIONS: Thin-strut DES options represent an effective choice in bifurcation lesions. Postdilation and provisional stenting are associated with a reduced risk of TLR. FKB should be recommended in 2-stent techniques.

Benefit of Extended Dual Antiplatelet Therapy Duration in Acute Coronary Syndrome Patients Treated with Drug Eluting Stents for Coronary Bifurcation Lesions (from the BIFURCAT Registry).

Optimal dual antiplatelet therapy (DAPT) duration for patients undergoing percutaneous coronary intervention (PCI) for coronary bifurcations is an unmet issue. The BIFURCAT registry was obtained by merging two registries on coronary bifurcations. Three groups were compared in a two-by-two fashion: short-term DAPT (≤ 6 months), intermediate-term DAPT (6-12 months) and extended DAPT (>12 months). Major adverse cardiac events (MACE) (a composite of all-cause death, myocardial infarction (MI), target-lesion revascularization and stent thrombosis) were the primary endpoint. Single components of MACE were the secondary endpoints. Events were appraised according to the clinical presentation: chronic coronary syndrome (CCS) versus acute coronary syndrome (ACS). 5537 patients (3231 ACS, 2306 CCS) were included. After a median follow-up of 2.1 years (IQR 0.9-2.2), extended DAPT was associated with a lower incidence of MACE compared with intermediate-term DAPT (2.8% versus 3.4%, adjusted HR 0.23 [0.1-0.54], p <0.001), driven by a reduction of all-cause death in the ACS cohort. In the CCS cohort, an extended DAPT strategy was not associated with a reduced risk of MACE. In conclusion, among real-world patients receiving PCI for coronary bifurcation, an extended DAPT strategy was associated with a reduction of MACE in ACS but not in CCS patients.

Impact of stent thickness on clinical outcomes in small vessel and bifurcation lesions: a RAIN-CARDIOGROUP VII sub-study.

BACKGROUND: The clinical impact of stent strut thickness in coronary bifurcation lesions in small vessels has not been assessed in a real-world population. METHODS: All 506 patients enrolled in the RAIN study, undergoing PCI in a vessel with a diameter 2.5 mm or less were retrospectively evaluated and divided into two groups according to stent strut thickness: 74 µm (n = 206) versus 81 µm (n = 300); 87.1% of the lesions involved bifurcations. TLF [defined as a composite of myocardial infarction (MI) and target lesion revascularization (TLR)] was the primary endpoint, with MACE (a composite of death, MI and TLR), its components and stent thrombosis the secondary endpoint. RESULTS: After 16 (14-18) months, a lower incidence of TLF (4.3 vs. 9.8%, P = 0.026) and ST (1.0 vs. 3.0%, P = 0.042) was seen in the 74 µm group, whereas MACE occurred in 60 of 506 patients, with no statistical difference between the two groups (9.7 vs. 13.3%, P = 0.070). At multivariate analysis, chronic renal failure increased the risk of TLF while thinner strut was an independent protective factor (hazard ratio 0.51, CI 0.17-0.85, P = 0.005). CONCLUSION: In this real-world population, patients being treated for small vessels lesions with thinner strut stents had lower rates of TLF, MI and ST.

Two-year outcomes after percutaneous coronary intervention with drug-eluting stents or bare-metal stents in elderly patients with coronary artery disease.

OBJECTIVES: Report the results at 2 years of the patients included in the SENIOR trial. BACKGROUND: Patients above 75 years of age represent a fast-growing population in the cathlab. In the SENIOR trial, patients treated by percutaneous coronary intervention (PCI) with drug eluting stent (DES) and a short duration of P2Y12 inhibitor (1 and 6 months for stable and unstable coronary syndromes, respectively) compared with bare metal stents (BMS) was associated with a 29% reduction in the rate of all-cause mortality, myocardial infarction (MI), stroke, and ischaemia-driven target lesion revascularization (ID-TLR) at 1 year. The results at 2 years are reported here. METHODS AND RESULTS: We randomly assigned 1,200 patients (596[50%] to the DES group and 604[50%] to the BMS group). At 2 years, the composite endpoint of all-cause mortality, MI, stroke and ID-TLR had occurred in 116 (20%) patients in the DES group and 131 (22%) patients in the BMS group (RR 0.90 [95%CI 0.72-1.13], p = .37). IDTLR occurred in 14 (2%) patients in the DES group and 41 (7%) patients in the BMS group (RR 0.35 [95%CI 0.16-0.60], p = .0002). Major bleedings (BARC 3-5) occurred in 27(5%) patients in both groups (RR 1.00, [95%CI 0.58-1.75], p = .99). Stent thrombosis rates were low and similar between DES and BMS (0.8 vs 1.3%, (RR 0.52 [95%CI 0.01-1.95], p = .27). CONCLUSION: Among elderly PCI patients, a strategy combining a DES together with a short duration of DAPT is associated with a reduction in revascularization up to 2 years compared with BMS with very few late events and without any increased in bleeding complications or stent thrombosis.

Accuracy of the PARIS score and PCI complexity to predict ischemic events in patients treated with very thin stents in unprotected left main or coronary bifurcations.

BACKGROUND: The PARIS risk score (PARIS-rs) and percutaneous coronary intervention complexity (PCI-c) predict clinical and procedural residual ischemic risk following PCI. Their accuracy in patients undergoing unprotected left main (ULM) or bifurcation PCI has not been assessed. METHODS: The predictive performances of the PARIS-rs (categorized as low, intermediate, and high) and PCI-c (according to guideline-endorsed criteria) were evaluated in 3,002 patients undergoing ULM/bifurcation PCI with very thin strut stents. RESULTS: After 16 (12-22) months, increasing PARIS-rs (8.8% vs. 14.1% vs. 27.4%, p < .001) and PCI-c (15.2% vs. 11%, p = .025) were associated with higher rates of major adverse cardiac events ([MACE], a composite of death, myocardial infarction [MI], and target vessel revascularization), driven by MI/death for PARIS-rs and target lesion revascularization/stent thrombosis for PCI-c (area under the curves for MACE: PARIS-rs 0.60 vs. PCI-c 0.52, p-for-difference < .001). PCI-c accuracy for MACE was higher in low-clinical-risk patients; while PARIS-rs was more accurate in low-procedural-risk patients. ≥12-month dual antiplatelet therapy (DAPT) was associated with a lower MACE rate in high PARIS-rs patients, (adjusted-hazard ratio 0.42 [95% CI: 0.22-0.83], p = .012), with no benefit in low to intermediate PARIS-rs patients. No incremental benefit with longer DAPT was observed in complex PCI. CONCLUSIONS: In the setting of ULM/bifurcation PCI, the residual ischemic risk is better predicted by a clinical risk estimator than by PCI complexity, which rather appears to reflect stent/procedure-related events. Careful procedural risk estimation is warranted in patients at low clinical risk, where PCI complexity may substantially contribute to the overall residual ischemic risk.

A Sex-Based Analysis From the RAIN-CARDIOGROUP VII Study (VeRy Thin Stents for Patients With Left MAIn or BifurcatioN in Real Life) on Left Main Stenting.

INTRODUCTION: There is a lack of data on clinical outcomes of percutaneous coronary intervention (PCI) with ultrathin stents on unprotected left main (ULM) coronary artery comparing women and men. METHODS: All patients treated with ULM-PCI with ultrathin stents (struts ≤81 µm) enrolled in the RAIN-CARDIOGROUP VII study were analyzed according to a sex-assessment evaluation. Major adverse cardiovascular event (MACE, a composite of all-cause death, myocardial infarction, target-lesion revascularization [TLR], and stent thrombosis) was the primary endpoint, whereas single components of MACE were the secondary endpoints. RESULTS: Out of a cohort of 793 patients, a total of 172 women (21.7%) and 621 men (78.3%) were included. Compared with men, women were older and less frequently smokers, had more frequently a history of previous PCI, and presented more frequently with an acute coronary syndrome. Among women, ostial lesions were more prevalent and mean stent diameter was lower compared with men. After 13.4 months (range, 8.4-21.6 months), 32 women (18.6%) and 106 men (17.1%) experienced MACE (P=.64). Censoring follow-up data at 3 years, no differences were observed in MACE (16.9 vs 14.7 per 100•patient-years; log-rank P=.61) and their single components between women and men. At multivariate analysis, chronic kidney disease (hazard ratio [HR], 1.91: 95% confidence interval [CI], 1.23 to -2.95; P<.01) and acute coronary syndrome presentation (HR, 1.84; 95% CI, 1.22-2.77; P=.01) were independent predictors of MACE overall. Larger stent size (HR, 0.65; 95% CI, 0.48-0.89; P<.01) and longer dual-antiplatelet therapy duration (HR, 0.95; 95% CI, 0.90-0.99; P=.03) were associated with a reduced risk of MACE during the subsequent follow-up. CONCLUSION: Ultrathin stents offer low rates of MACE and TLR in the overall population without significant differences between sexes.

Comparison of bioresorbable vs durable polymer drug-eluting stents in unprotected left main (from the RAIN-CARDIOGROUP VII Study).

BACKGROUND: There are limited data regarding the impact of bioresorbable polymer drug eluting stent (BP-DES) compared to durable polymer drug eluting stent (DP-DES) in patients treated with percutaneous coronary intervention using ultrathin stents in left main or bifurcations. METHODS: In the RAIN registry (ClinicalTrials NCT03544294, june 2018 retrospectively registered) patients with a ULM or bifurcation stenosis treated with PCI using ultrathin stents (struts thinner than 81 µm) were enrolled. The primary endpoint was the rate of target lesion revascularization (TLR); major adverse cardiovascular events (MACE, a composite of all-cause death, myocardial infarction, TLR and stent thrombosis) and its components, along with target vessel revascularization (TVR) were the secondary ones. A propensity score with matching analysis to compare patients treated with BP-DES versus DP-DES was also assessed. RESULTS: From 3001 enrolled patients, after propensity score analysis 1400 patients (700 for each group) were selected. Among them, 352 had ULM disease and 1048 had non-LM bifurcations. At 16 months (12-22), rates of TLR (3.7% vs 2.9%, p = 0.22) and MACE were similar (12.3% vs. 11.6%, p = 0.74) as well as for the other endpoints. Sensitivity analysis of outcomes after a two-stents strategy, showed better outcome in term of MACE (20.4% vs 10%, p = 0.03) and TVR (12% vs 4.6%, p = 0.05) and a trend towards lower TLR in patients treated with BP-DES. CONCLUSION: In patients with bifurcations or ULM treated with ultrathin stents BP-DES seems to perform similarly to DP-DES: the trends toward improved clinical outcomes in patients treated with the BP-DES might potentially be of value for speculating the stent choice in selected high-risk subgroups of patients at increased risk of ischemic events. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03544294. Retrospectively registered June 1, 2018.

Impact of Kissing Balloon in Patients Treated With Ultrathin Stents for Left Main Lesions and Bifurcations: An Analysis From the RAIN-CARDIOGROUP VII Study.

BACKGROUND: There are limited data regarding the impact of final kissing balloon (FKI) in patients treated with percutaneous coronary intervention using ultrathin stents in left main or bifurcations. METHODS: All patients undergoing left main or bifurcations percutaneous coronary intervention enrolled in the RAIN registry (Very Thin Stents for Patients With MAIN or BiF in Real Life: The RAIN, a Multicenter Study) evaluating ultrathin stents were included. Major adverse cardiac event (a composite of all-cause death, myocardial infarction, target lesion revascularization, and stent thrombosis) was the primary end point, while its components, along with target vessel revascularization, were the secondary end points. The main analysis was performed comparing patients with and without FKI after adjustment with inverse probability of treatment weighting. Subgroup analyses were performed according to FKI (short [<3 mm] versus long overlap), strategy (provisional versus 2-stent), routine versus bail-out FKI, and the use of imaging and proximal optimization technique. RESULTS: Two thousand seven hundred forty-two patients were included. At 16 months (8-20) follow-up, inverse probability of treatment weighting adjusted rates of major adverse cardiac event were similar between FKI and no-FKI group (15.1% versus 15.5%; P=0.967), this result did not change with use of imaging, proximal optimization technique, or routine versus bail-out FKI. In the 2-stent subgroup, FKI was associated with lower rates of target vessel revascularization (7.8% versus 15.9%; P=0.030) and target lesion revascularization (7.3% versus 15.2%; P=0.032). Short overlap FKI was associated with a lower rate of target lesion revascularization compared with no FKI (2.6% versus 5.4%; P=0.034), while long overlap was not (6.8% versus 5.4%; P=0.567). CONCLUSIONS: In patients with bifurcations or unprotected left main treated with ultrathin stents, short overlap FKI is associated with less restenosis. In a 2-stent strategy, FKI was associated with less target vessel revascularization and restenosis. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03544294.

Incidence of Adverse Events at 3 Months Versus at 12 Months After Dual Antiplatelet Therapy Cessation in Patients Treated With Thin Stents With Unprotected Left Main or Coronary Bifurcations.

Incidence and predictors of adverse events after dual antiplatelet therapy (DAPT) cessation in patients treated with thin stents (<100 microns) in unprotected left main (ULM) or coronary bifurcation remain undefined. All consecutive patients presenting with a critical lesion of an ULM or involving a main coronary bifurcation who were treated with very thin strut stents were included. MACE (a composite end point of cardiovascular death, myocardial infarction [MI], target lesion revascularization [TLR], and stent thrombosis [ST]) was the primary endpoint, whereas target vessel revascularization (TVR) was the secondary endpoint, with particular attention to type and occurrence of ST and occurrence of ST, CV death, and MI during DAPT or after DAPT discontinuation. All analyses were performed according to length of DAPT dividing the patients in 3 groups: Short DAPT (3-months), intermediate DAPT (3 to 12 months), and long DAPT (12-months). A total of 117 patients were discharged with an indication for DAPT ≤3 months (median 1: 1 to 2.5), 200 for DAPT between 3 and 12 months (median 8: 7 to 10), and 1,958 with 12 months DAPT. After 12.8 months (8 to 20), MACE was significantly higher in the 3-month group compared with 3 to 12 and 12-month groups (9.4% vs 4.0% vs 7.2%, p ≤0.001), mainly driven by MI (4.4% vs 1.5% vs 3%, p ≤0.001) and overall ST (4.3% vs 1.5% vs 1.8%, p ≤0.001). Independent predictors of MACE were low GFR and a 2 stent strategy. Independent predictors of ST were DAPT duration <3 months and the use of a 2-stent strategy. In conclusion, even stents with very thin strut when implanted in real-life ULM or coronary bifurcation patients discharged with short DAPT have a relevant risk of ST, which remains high although not significant after DAPT cessation.