Cross-Validation of Risk Scores for Patients Undergoing Transcatheter Edge-to-Edge Repair for Mitral Regurgitation.

Background: Risk scores may identify patients with mitral regurgitation (MR) who are at risk for adverse events, but who may still benefit from transcatheter edge-to-edge repair (TEER). We sought to cross-validate the MitraScore and COAPT risk score to predict adverse events in patients undergoing TEER. Methods: MitraScore validation was carried out in the COAPT population which included 614 patients with FMR who were randomized 1:1 to guideline-directed medical therapy (GDMT) with or without TEER and were followed for 2 years. Validation of the COAPT risk score was carried out in 1007 patients from the MIVNUT registry of TEER-treated patients with both FMR and degenerative MR who were followed for a mean of 2.1 years. The predictive value was assessed using the area under the receiver operating characteristic curve (AUC) plots. The primary outcome was all-cause mortality. Results: The MitraScore had fair to good predictive accuracy for mortality in the overall COAPT trial population (AUC, 0.67); its accuracy was higher in patients treated with TEER (AUC, 0.74) than GDMT alone (AUC, 0.65). The COAPT risk score had fair predictive accuracy for death in the overall MitraScore cohort (AUC, 0.64), which was similar in patients with FMR and degenerative MR (AUC, 0.64 and 0.66, respectively). There was a consistent benefit of treatment with TEER plus GDMT compared with GDMT alone in the COAPT trial population across all MitraScore risk strata. Conclusions: The COAPT risk score and MitraScore are simple tools that are useful for the prediction of 2-year mortality in patients eligible for or undergoing treatment with TEER.

Microvascular Obstruction in Patients With Anterior STEMI Treated With Supersaturated Oxygen.

Background: Supersaturated oxygen (SSO2) delivered into the left anterior descending coronary artery after percutaneous coronary intervention (PCI) for anterior ST-segment elevation myocardial infarction (STEMI) has been shown to reduce infarct size, but its effects on microvascular obstruction (MVO) are unknown. The aim of this study was to compare MVO in patients with anterior STEMI treated with SSO2 after successful primary PCI from 2 studies (the optimized SSO2 pilot and IC-HOT) with similar patients from 7 randomized trials who underwent primary PCI without SSO2 treatment. Methods: A total of 874 patients with anterior STEMI who underwent MVO assessment using cardiac magnetic resonance imaging within 10 days after primary PCI were included, of whom 90 patients (10.3%) were treated with SSO2. The primary end point was the extent of MVO as a continuous measure in a weighted multivariable model. The secondary end point was the presence of MVO. Results: SSO2 therapy was independently associated with a lower extent of MVO compared with no SSO2 therapy (coefficient, -1.35; 95% CI, -2.58 to -0.11; P = .03). SSO2 therapy was also associated with a borderline lower risk of any MVO (adjusted odds ratio, 0.56; 95% CI, 0.31-1.00; P = .051). Conclusions: In the present individual patient data pooled analysis from 9 studies, SSO2 therapy was associated with less MVO after successful primary PCI for anterior STEMI.

Implications of anemia in patients undergoing PCI with Impella-support: insights from the PROTECT III study.

Background: Anemia is prevalent among patients with cardiovascular disease and is associated with adverse outcomes. However, data regarding the impact of anemia in high-risk percutaneous coronary intervention (HRPCI) are limited. Objectives: This study aimed to evaluate the impact of anemia in patients undergoing Impella-supported HRPCI in the PROTECT III study. Methods: Patients undergoing Impella-supported HRPCI in the multicenter PROTECT III study were assessed for anemia based on baseline hemoglobin levels according to World Health Organization criteria. Patients were stratified into three groups, namely, no anemia, mild anemia, and moderate or severe anemia. Major adverse cardiovascular and cerebrovascular events (MACCE: all-cause death, myocardial infarction, stroke/transient ischemic attack, and repeat revascularization) at 30 and 90 days, and major bleeding events were compared across groups. Results: Of 1,071 patients with baseline hemoglobin data, 37.9% had no anemia, 43.4% had mild anemia, and 18.7% had moderate or severe anemia. Anemic patients were older and more likely to have comorbidities. Anemia was associated with higher MACCE rates at 30 days (moderate to severe, 12.3%; mild, 9.8%; no anemia, 5.4%; p = 0.02) and at 90 days (moderate to severe, 18.7%; mild, 14.6%; none, 8.3%; p = 0.004). These differences persisted after adjustment for potential confounders at 30 and 90 days, and sensitivity analysis excluding dialysis showed similar results. Major bleeding at 30 days was also higher in anemic patients (5.5% vs. 1.2%, p = 0.002). Conclusion: Baseline anemia in Impella-supported HRPCI is common and independently associated with MACCE and major bleeding, emphasizing its significance as a prognostic factor. Specific management strategies to reduce anemia-associated MACCE risk after HRPCI should be examined. Clinical Trial Information Trial Name: The Global cVAD Study (cVAD)ClinicalTrial.gov Identifier: NCT04136392URL: https://clinicaltrials.gov/ct2/show/NCT04136392?term=cvad&draw=2&rank=2.

Cardiac biomarkers for screening and prognostication of cardiac dysfunction in critically ill patients.

AIMS: This study aimed to assess the use of high-sensitivity troponin T (hsTNT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) in screening for cardiac dysfunction [left ventricular (LV) systolic or diastolic dysfunction or right ventricular (RV) dysfunction] in mixed intensive care unit (ICU) patients and establish whether these biomarkers are independently associated with an increased risk of death. METHODS: We performed a secondary analysis of a single-centre prospective observational study in which consecutive ICU patients were examined with transthoracic echocardiography (TTE) and cardiac biomarkers. Patients with systolic or diastolic LV dysfunction, RV dysfunction or a combination of these were compared with patients with normal cardiac function. Sensitivity and specificity for different cut-off levels were calculated using receiver operating characteristic curves. Regression models were used to evaluate the associations between cardiac biomarkers, sepsis, renal failure and mortality. RESULTS: A total of 276 patients were included. Most of the patients had cardiac dysfunction on TTE (64%). Combined cardiac dysfunction was most prevalent (71 patients, 26%), followed by isolated diastolic LV dysfunction (40 patients, 15%). Levels of hsTNT and NT-proBNP were higher in all types of cardiac dysfunction versus patients with normal cardiac function. The area under the curve (AUC) for hsTNT to detect any cardiac dysfunction was 0.75. An optimal cut-off at 30.5 ng/L rendered a positive predictive value (PPV) of 80% and a negative predictive value (NPV) of 58%. The AUC for NT-proBNP to detect any cardiac dysfunction was 0.788. Using an optimal cut-off at 1145 ng/L rendered a PPV of 86% and an NPV of 58%. Using a clinically relevant 90% sensitivity for detecting cardiac dysfunction put the cut-offs at 14.1 ng/L for hsTNT and 247 ng/L for NT-proBNP, resulting in a specificity of 48% and 46%, respectively. Levels of NT-proBNP were associated with sepsis and renal failure (P < 0.001), while levels of hsTNT were associated with renal failure only (P < 0.001) after adjustment for cardiac dysfunction. Levels of biomarkers were associated with an increased risk of 90 day mortality after adjustments for age, Simplified Acute Physiology Score 3, cardiac dysfunction and factors independently associated with biomarker increase (sepsis and renal failure) (P = 0.048 for hsTNT and P < 0.006 for NT-proBNP). CONCLUSION: Cardiac biomarkers, hsTNT and NT-proBNP, are strongly correlated to cardiac dysfunction in ICU patients and have a robust association with increased mortality. However, the relatively low NPV and the low specificity at relevant sensitivity levels of the biomarkers make them unsuitable for use in screening for cardiac dysfunction.

Development of a small animal model replicating core characteristics of takotsubo syndrome in humans.

Aims: Adequate animal models are necessary to understand human conditions, such as takotsubo syndrome (TS) characterized by the heart's transient regional wall motion abnormalities. This study aims to develop a reproducible, low-mortality TS model that closely mimics the human condition and addresses the limitations of existing models. Methods and results: We conducted six experiments using 309 Sprague Dawley rats, each approximately 300 g and aged 7-8 weeks. Initially, we replicated an established model using intraperitoneal isoprenaline injections. Subsequent experiments varied the doses and infusion durations of intravenous isoprenaline and assessed the effects of sex, strain, and breeder on the development of reversible akinetic segments. High-resolution echocardiography monitored the regional wall motion over 30 days to correlate with histological changes. Increasing the isoprenaline dose and the infusion time significantly enhanced akinesia (P < 0.01), resulting in pronounced apical ballooning observed in three-dimensional imaging. Akinesia peaked at 6 h post-infusion, with recovery observed at 24 h; most rats recovered from akinetic segments within 48-72 h. Optimizing the mode of administration, dose, and duration achieved a TS-like phenotype in 90% of cases, with a 16.7% mortality rate. Histological examinations confirmed that myocardial injury occurred, independent of apical ballooning. Conclusion: This study presents a refined TS model that reliably replicates the syndrome's key features, including morphological and electrocardiographic changes, demonstrating its transient nature with high fidelity and reduced mortality. The model's reproducibility, evidenced by consistent results across trials, suggests its potential for broader application pending further validation.

Coronary Artery Bypass Graft Failure in Women: Incidence and Clinical Implications.

BACKGROUND: Women have worse outcomes after coronary artery bypass surgery (CABG) than men. OBJECTIVES: This study aimed to determine the incidence of CABG graft failure in women, its association with cardiac events, and whether it contributes to sex-related differences in outcomes. METHODS: A pooled analysis of individual patient data from randomized clinical trials with systematic imaging follow-up was performed. Multivariable logistic regression models were used to assess the association of graft failure with myocardial infarction and repeat revascularization between CABG and imaging (primary outcome) and death after imaging (secondary outcome). Mediation analysis was performed to evaluate the effect of graft failure on the association between female sex and risk of death. RESULTS: Seven randomized clinical trials (N = 4,413, 777 women) were included. At a median imaging follow-up of 1.03 years, graft failure was significantly more frequent among women than men (37.3% vs 32.9% at the patient-level and 20.5% vs 15.8% at the graft level; P = 0.02 and P < 0.001, respectively). In women, graft failure was associated with an increased risk of myocardial infarction and repeat revascularization (OR: 3.94; 95% CI: 1.79-8.67) and death (OR: 3.18; 95% CI: 1.73-5.85). Female sex was independently associated with the risk of death (direct effect, HR: 1.84; 95% CI: 1.35-2.50) but the association was not mediated by graft failure (indirect effect, HR: 1.04; 95% CI: 0.86-1.26). CONCLUSIONS: Graft failure is more frequent in women and is associated with adverse cardiac events. The excess mortality risk associated with female sex among CABG patients is not mediated by graft failure.

Importance of hospital and clinical factors for early mortality in Takotsubo syndrome: Insights from the Swedish Coronary Angiography and Angioplasty Registry.

BACKGROUND: Takotsubo syndrome (TTS) is an acute heart failure syndrome with symptoms similar to acute myocardial infarction. TTS is often triggered by acute emotional or physical stress and is a significant cause of morbidity and mortality. Predictors of mortality in patients with TS are not well understood, and there is a need to identify high-risk patients and tailor treatment accordingly. This study aimed to assess the importance of various clinical factors in predicting 30-day mortality in TTS patients using a machine learning algorithm. METHODS: We analyzed data from the nationwide Swedish Coronary Angiography and Angioplasty Registry (SCAAR) for all patients with TTS in Sweden between 2015 and 2022. Gradient boosting was used to assess the relative importance of variables in predicting 30-day mortality in TTS patients. RESULTS: Of 3,180 patients hospitalized with TTS, 76.0% were women. The median age was 71.0 years (interquartile range 62-77). The crude all-cause mortality rate was 3.2% at 30 days. Machine learning algorithms by gradient boosting identified treating hospitals as the most important predictor of 30-day mortality. This factor was followed in significance by the clinical indication for angiography, creatinine level, Killip class, and age. Other less important factors included weight, height, and certain medical conditions such as hyperlipidemia and smoking status. CONCLUSIONS: Using machine learning with gradient boosting, we analyzed all Swedish patients diagnosed with TTS over seven years and found that the treating hospital was the most significant predictor of 30-day mortality.

Coronary angiography following transcatheter aortic valve replacement: Insights from the SWEDEHEART registry.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is the most common treatment in patients with symptomatic severe aortic stenosis (AS). As concomitant coronary artery disease is common in AS patients, access to the coronary arteries following TAVR is of increasing importance. OBJECTIVES: This study evaluated the incidence and risk factors for unplanned coronary angiography following TAVR and, using fluoroscopic time as a surrogate, analyzed the complexity of coronary artery cannulation. METHODS: All patients who underwent TAVR in Sweden between 2008 and 2022 were identified using the SWEDEHEART registry. The cumulative incidence of coronary angiography after TAVR was analyzed with mortality as a competing risk. Angiography and PCI complexity were analyzed using fluoroscopic time and compared across different transcatheter heart valve designs. RESULTS: Out of 9806 patients, 566 subsequently required coronary angiography. The incidence was highest for three-vessel and/or left main disease. Younger age, the extent of prior coronary artery disease, and peripheral vascular disease were associated with an increased risk of coronary angiography. Fluoroscopy time was increased in TAVR patients compared to the control group with the longest fluoroscopy times observed in cases involving supra-annular and self-expanding valves. CONCLUSIONS: The incidence of coronary angiography following TAVR is still low. Younger patients and patients with concomitant coronary artery disease have a higher risk. Procedural time is longer in patients with a previous THV replacement. As TAVR is emerging as the first-line treatment in patients with longer life expectancy, facilitating coronary access is an important factor when considering which THV device to implant.

Revascularisation in Left Ventricular Systolic Dysfunction: A Meta-analysis of Kaplan-Meier Reconstructed Individual Patient Data.

BACKGROUND: Coronary artery disease is a common cause of ischemic left ventricular systolic dysfunction (LVSD), for which the optimal revascularisation strategy remains unclear. We aimed to determine whether percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) results in greater survival advantage in patients with LVSD. METHODS: Study-level (SLMA) and reconstructed individual patient data (rIPDMA) meta-analyses from Kaplan-Meier (KM) survival curves were performed. A systematic search of Medline, Embase, and Cochrane Library was conducted for observational and randomised studies published after 2010 that compared PCI and CABG in patients with left ventricular ejection fraction ≤ 40%. The primary outcome was all-cause mortality at longest follow-up. The secondary outcomes were myocardial infarction (MI), stroke, repeated revascularisation, cardiovascular mortality, and major adverse cardiovascular and cerebrovascular events (MACCE) at longest follow-up. RESULTS: Fourteen studies (11 observational, 3 randomised, 13,063 patients) were eligible for the SLMA. Seven contained digitisable KM curves from which individual patient data could be reconstructed. Study-level analysis found PCI to be associated with increased all-cause mortality (hazard ratio [HR] 1.41, 95% confidence interval [CI] 1.18-1.69), MI (HR 2.10, 95% CI 1.62-2.72), repeated revascularisation (HR 2.39, 95% CI 1.37-4.17), and MACCE (HR 1.58, 95% CI 1.23-2.03), without significant differences in stroke (HR 0.86, 95% CI 0.39-1.92) or cardiovascular mortality (HR 1.42, 95% CI 0.78-2.59). In the rIPDMA, PCI resulted in increased all-cause mortality (HR 1.57, 95% CI 1.34-1.87) and repeated revascularisation (HR 3.63, 95% CI 3.12-4.21) but overall lower risk of stroke (HR 0.62, 95% CI 0.39-0.99) owing to fewer events during initial follow-up. CONCLUSIONS: In patients with ischemic LVSD, PCI was associated with higher risk of all-cause mortality and repeated revascularisation than CABG, but lower risk of short-term stroke. (PROSPERO: CRD42021291408).

Association between overweight and obesity with coronary artery bypass graft failure: an individual patient data analysis of clinical trials.

OBJECTIVES: The association between obesity and graft failure after coronary artery bypass grafting has not been previously investigated. METHODS: We pooled individual patient data from randomized clinical trials with systematic postoperative coronary imaging to evaluate the association between obesity and graft failure at the individual graft and patient levels. Penalized cubic regression splines and mixed-effects multivariable logistic regression models were performed. RESULTS: Six trials comprising 3928 patients and 12 048 grafts were included. The median time to imaging was 1.03 (interquartile range 1.00-1.09) years. By body mass index (BMI) category, 800 (20.4%) patients were normal weight (BMI 18.5-24.9), 1668 (42.5%) were overweight (BMI 25-29.9), 983 (25.0%) were obesity class 1 (BMI 30-34.9), 344 (8.8%) were obesity class 2 (BMI 35-39.9) and 116 (2.9%) were obesity class 3 (BMI 40+). As a continuous variable, BMI was associated with reduced graft failure [adjusted odds ratio (aOR) 0.98 (95% confidence interval (CI) 0.97-0.99)] at the individual graft level. Compared to normal weight patients, graft failure at the individual graft level was reduced in overweight [aOR 0.79 (95% CI 0.64-0.96)], obesity class 1 [aOR 0.81 (95% CI 0.64-1.01)] and obesity class 2 [aOR 0.61 (95% CI 0.45-0.83)] patients, but not different compared to obesity class 3 [aOR 0.94 (95% CI 0.62-1.42)] patients. Findings were similar, but did not reach significance, at the patient level. CONCLUSIONS: In a pooled individual patient data analysis of randomized clinical trials, BMI and obesity appear to be associated with reduced graft failure at 1 year after coronary artery bypass grafting.

Animal models of Takotsubo syndrome: bridging the gap to the human condition.

Modelling human diseases serves as a crucial tool to unveil underlying mechanisms and pathophysiology. Takotsubo syndrome (TS), an acute form of heart failure resembling myocardial infarction, manifests with reversible regional wall motion abnormalities (RWMA) of the ventricles. Despite its mortality and clinical similarity to myocardial infarction, TS aetiology remains elusive, with stress and catecholamines playing central roles. This review delves into current animal models of TS, aiming to assess their ability to replicate key clinical traits and identifying limitations. An in-depth evaluation of published animal models reveals a variation in the definition of TS among studies. We notice a substantial prevalence of catecholamine-induced models, particularly in rodents. While these models shed light on TS, there remains potential for refinement. Translational success in TS research hinges on models that align with human TS features and exhibit the key features, including transient RWMA. Animal models should be comprehensively evaluated regarding the various systemic changes of the applied trigger(s) for a proper interpretation. This review acts as a guide for researchers, advocating for stringent TS model standards and enhancing translational validity.

Antiplatelet therapy after coronary artery bypass surgery: five year follow-up of randomised DACAB trial.

OBJECTIVE: To assess the effect of different antiplatelet strategies on clinical outcomes after coronary artery bypass grafting. DESIGN: Five year follow-up of randomised Different Antiplatelet Therapy Strategy After Coronary Artery Bypass Grafting (DACAB) trial. SETTING: Six tertiary hospitals in China; enrolment between July 2014 and November 2015; completion of five year follow-up from August 2019 to June 2021. PARTICIPANTS: 500 patients aged 18-80 years (including 91 (18.2%) women) who had elective coronary artery bypass grafting surgery and completed the DACAB trial. INTERVENTIONS: Patients were randomised 1:1:1 to ticagrelor 90 mg twice daily plus aspirin 100 mg once daily (dual antiplatelet therapy; n=168), ticagrelor monotherapy 90 mg twice daily (n=166), or aspirin monotherapy 100 mg once daily (n=166) for one year after surgery. After the first year, antiplatelet therapy was prescribed according to standard of care by treating physicians. MAIN OUTCOME MEASURES: The primary outcome was major adverse cardiovascular events (a composite of all cause death, myocardial infarction, stroke, and coronary revascularisation), analysed using the intention-to-treat principle. Time-to-event analysis was used to compare the risk between treatment groups. Multiple post hoc sensitivity analyses examined the robustness of the findings. RESULTS: Follow-up at five years for major adverse cardiovascular events was completed for 477 (95.4%) of 500 patients; 148 patients had major adverse cardiovascular events, including 39 in the dual antiplatelet therapy group, 54 in the ticagrelor monotherapy group, and 55 in the aspirin monotherapy group. Risk of major adverse cardiovascular events at five years was significantly lower with dual antiplatelet therapy versus aspirin monotherapy (22.6% v 29.9%; hazard ratio 0.65, 95% confidence interval 0.43 to 0.99; P=0.04) and versus ticagrelor monotherapy (22.6% v 32.9%; 0.66, 0.44 to 1.00; P=0.05). Results were consistent in all sensitivity analyses. CONCLUSIONS: Treatment with ticagrelor dual antiplatelet therapy for one year after surgery reduced the risk of major adverse cardiovascular events at five years after coronary artery bypass grafting compared with aspirin monotherapy or ticagrelor monotherapy. TRIAL REGISTRATION: NCT03987373ClinicalTrials.gov NCT03987373.

Left Atrial Improvement in Patients With Secondary Mitral Regurgitation and Heart Failure: The COAPT Trial.

BACKGROUND: Functional mitral regurgitation induces adverse effects on the left ventricle and the left atrium. Left atrial (LA) dilatation and reduced LA strain are associated with poor outcomes in heart failure (HF). Transcatheter edge-to-edge repair (TEER) of the mitral valve reduces heart failure hospitalization (HFH) and all-cause death in selected HF patients. OBJECTIVES: The aim of this study was to evaluate the impact of LA strain improvement 6 months after TEER on the outcomes of patients enrolled in the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) trial. METHODS: The difference in LA strain between baseline and the 6-month follow-up was calculated. Patients with at least a 15% improvement in LA strain were labeled as "LA strain improvers." All-cause death and HFH were assessed between the 6 and 24-month follow-up. RESULTS: Among 347 patients (mean age 71 ± 12 years, 63% male), 106 (30.5%) showed improvement of LA strain at the 6-month follow-up (64 [60.4%] from the TEER + guideline-directed medical therapy [GDMT] group and 42 [39.6%] from the GDMT alone group). An improvement in LA strain was significantly associated with a reduction in the composite of death or HFH between the 6-month and 24-month follow-up, with a similar risk reduction in both treatment arms (Pinteraction = 0.27). In multivariable analyses, LA strain improvement remained independently associated with a lower risk of the primary composite endpoint both as a continuous variable (adjusted HR: 0.94 [95% CI: 0.89-1.00]; P = 0.03) and as a dichotomous variable (adjusted HR: 0.49 [95% CI: 0.27-0.89]; P = 0.02). The best outcomes were observed in patients treated with TEER in whom LA strain improved. CONCLUSIONS: In symptomatic HF patients with severe mitral regurgitation, improved LA strain at the 6-month follow-up is associated with subsequently lower rates of the composite endpoint of all-cause mortality or HFH, both after TEER and GDMT alone. (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation [COAPT]; NCT01626079).

Angiographic Characteristics and Clinical Outcomes in Patients With Chronic Kidney Disease Undergoing Impella-Supported High-Risk Percutaneous Coronary Intervention: Insights From the cVAD PROTECT III Study.

BACKGROUND: Prior studies have found that patients with chronic kidney disease (CKD) have worse outcomes following percutaneous coronary intervention (PCI). There are no data about patients with advanced CKD undergoing Impella-supported high-risk PCI. We, therefore, aimed to evaluate angiographic characteristics and clinical outcomes in patients with CKD who received Impella-supported high-risk PCI as part of the catheter-based ventricular assist device PROTECT III study (A Prospective, Multi-Center, Randomized Controlled Trial of the IMPELLA RECOVER LP 2.5 System Versus Intra Aortic Balloon Pump [IABP] in Patients Undergoing Non Emergent High Risk PCI). METHODS: Patients enrolled in the PROTECT III study were analyzed according to their baseline estimated glomerular filtration rate (eGFR). The primary outcome was 90-day major adverse cardiovascular and cerebrovascular events (the composite of all-cause death, myocardial infarction, stroke/transient ischemic attack, and repeat revascularization). RESULTS: Of 1237 enrolled patients, 1052 patients with complete eGFR baseline assessment were evaluated: 586 with eGFR ≥60 mL/min per 1.73 m2, 190 with eGFR ≥45 to <60, 105 with eGFR ≥30 to <45, and 171 with eGFR <30 or on dialysis. Patients with lower eGFR (all groups with eGFR <60) were more frequently females and had a higher prevalence of hypertension, diabetes, anemia, and peripheral artery disease. The baseline Synergy Between PCI With Taxus and Cardiac Surgery score was similar between groups (28.2±12.6 for all groups). Patients with lower eGFR were more likely to have severe coronary calcifications and higher usage of atherectomy. There were no differences in individual PCI-related coronary complications between groups, but the rates of overall PCI complications were less frequent among patients with lower eGFR. Major adverse cardiovascular and cerebrovascular events at 90 days and 1-year mortality were significantly higher among patients with eGFR <30 mL/min per 1.73 m2 or on dialysis. CONCLUSIONS: Patients with advanced CKD undergoing Impella-assisted high-risk PCI tend to have higher baseline comorbidities, severe coronary calcification, and higher atherectomy usage, yet CKD was not associated with a higher rate of immediate PCI-related complications. However, 90-day major adverse cardiovascular and cerebrovascular events and 1-year mortality were significantly higher among patients with eGFR<30 mL/min per 1.73 m2 or on dialysis. Future studies of strategies to improve intermediate and long-term outcomes of these high-risk patients are warranted. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04136392.

Ischemic preconditioning affects phosphosites and accentuates myocardial stunning while reducing infarction size in rats.

Background and aims: Ischemic preconditioning (IPC), i.e., brief periods of ischemia, protect the heart from subsequent prolonged ischemic injury, and reduces infarction size. Myocardial stunning refers to transient loss of contractility in the heart after myocardial ischemia that recovers without permanent damage. The relationship between IPC and myocardial stunning remains incompletely understood. This study aimed primarily to examine the effects of IPC on the relationship between ischemia duration, stunning, and infarct size in an ischemia-reperfusion injury model. Secondarily, this study aimed to examine to which extent the phosphoproteomic changes induced by IPC relate to myocardial contractile function. Methods and results: Rats were subjected to different durations of left anterior descending artery (LAD) occlusion, with or without preceding IPC. Echocardiograms were acquired to assess cardiac contraction in the affected myocardial segment. Infarction size was evaluated using triphenyl tetrazolium chloride staining. Phosphoproteomic analysis was performed in heart tissue from preconditioned and non-preconditioned animals. In contrast to rats without IPC, reversible akinesia was observed in a majority of the rats that were subjected to IPC and subsequently exposed to ischemia of 13.5 or 15 min of ischemia. Phosphoproteomic analysis revealed significant differential regulation of 786 phosphopeptides between IPC and non-IPC groups, with significant associations with the sarcomere, Z-disc, and actin binding. Conclusion: IPC induces changes in phosphosites of proteins involved in myocardial contraction; and both accentuates post-ischemic myocardial stunning and reduces infarct size.

Statistical primer: individual patient data meta-analysis and meta-analytic approaches in case of non-proportional hazards.

Individual patient data (IPD) meta-analyses build upon traditional (aggregate data) meta-analyses by collecting IPD from the individual studies rather than using aggregated summary data. Although both traditional and IPD meta-analyses produce a summary effect estimate, IPD meta-analyses allow for the analysis of data to be performed as a single dataset. This allows for standardization of exposure, outcomes, and analytic methods across individual studies. IPD meta-analyses also allow the utilization of statistical methods typically used in cohort studies, such as multivariable regression, survival analysis, propensity score matching, uniform subgroup and sensitivity analyses, better management of missing data, and incorporation of unpublished data. However, they are more time-intensive, costly, and subject to participation bias. A separate issue relates to the meta-analytic challenges when the proportional hazards assumption is violated. In these instances, alternative methods of reporting time-to-event estimates, such as restricted mean survival time should be used. This statistical primer summarizes key concepts in both scenarios and provides pertinent examples.