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.

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.

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.

Impact of Incomplete Revascularization After PCI in Left Main Disease: The EXCEL Trial.

BACKGROUND: The importance of complete revascularization after percutaneous coronary intervention (PCI) in patients with left main coronary artery disease is uncertain. We investigated the clinical impact of complete revascularization in patients with left main coronary artery disease undergoing PCI in the EXCEL trial (Evaluation of XIENCE Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization). METHODS: Composite rates of death or myocardial infarction (MI) following PCI during 5-year follow-up were examined in 903 patients based on core laboratory definitions of anatomic and functional complete revascularization, residual SYNTAX score (The Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery), and residual Jeopardy Score (rJS). RESULTS: The risk of death or MI did not vary based on anatomic, functional, or residual SYNTAX score complete revascularization but did differ according to the rJS (5-year rates 17.6%, 19.5%, and 38.9% with rJS 0, 2, and ≥4, respectively; P=0.006). The higher rate of death or MI with rJS≥4 versus rJS≤2 was driven conjointly by increased mortality (adjusted hazard ratio, 2.29 [95% CI, 1.11-4.71]; P=0.02) and spontaneous MI (adjusted hazard ratio, 2.89 [95% CI, 1.17-7.17]; P=0.02). The most common location for untreated severe stenoses in the rJS≥4 group was the left circumflex artery (LCX), and the post-PCI absence, compared with the presence, of any untreated lesion with diameter stenosis ≥70% in the LCX was associated with reduced 5-year rates of death or MI (18.9% versus 35.2%; hazard ratio, 0.48 [95% CI, 0.32-0.74]; P<0.001). The risk was the highest for residual ostial/proximal LCX lesions. CONCLUSIONS: Among patients undergoing PCI in EXCEL trial, incomplete revascularization according to the rJS was associated with increased rates of death and spontaneous MI. Post-PCI untreated high-grade lesions in the LCX (especially the ostial/proximal LCX) drove these outcomes. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01205776.

Incidence, Predictors, and Impact of Hospital Readmission After Revascularization for Left Main Coronary Disease.

BACKGROUND: The frequency of and relationship between hospital readmissions and outcomes after revascularization for left main coronary artery disease (LMCAD) are unknown. OBJECTIVES: The purpose of this study was to study the incidence, predictors, and clinical impact of readmissions following percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) for LMCAD. METHODS: In the EXCEL (XIENCE Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) trial, 1,905 patients with LMCAD were randomized to PCI vs CABG. The cumulative incidence of readmissions was analyzed with multivariable Anderson-Gill and joint frailty models to account for recurrent events and the competing risk of death. The impact of readmission on subsequent mortality within 5-year follow-up was determined in a time-adjusted Cox proportional hazards model. RESULTS: Within 5 years, 1,868 readmissions occurred in 851 of 1,882 (45.2%) hospital survivors (2.2 ± 1.9 per patient with readmission[s], range 1-16), approximately one-half for cardiovascular causes and one-half for noncardiovascular causes (927 [49.6%] and 941 [50.4%], respectively). One or more readmissions occurred in 463 of 942 (48.6%) PCI patients vs 388 of 940 (41.8%) CABG patients (P = 0.003). After multivariable adjustment, PCI remained an independent predictor of readmission (adjusted HR: 1.22; 95% CI: 1.10-1.35; P < 0.0001), along with female sex, comorbidities, and the extent of CAD. Readmission was independently associated with subsequent all-cause death, with interaction testing indicating a higher risk after PCI than CABG (adjusted HR: 5.72; 95% CI: 3.42-9.55 vs adjusted HR: 2.72; 95% CI: 1.64-4.88, respectively; Pint = 0.03). CONCLUSIONS: In the EXCEL trial, readmissions during 5-year follow-up after revascularization for LMCAD were common and more frequent after PCI than CABG. Readmissions were associated with an increased risk of all-cause death, more so after PCI than with CABG.

One-month DAPT with ticagrelor and aspirin for patients undergoing coronary artery bypass grafting: rationale and design of the randomised, multicentre, double-blind, placebo-controlled ODIN trial.

The optimal antiplatelet strategy after coronary artery bypass graft (CABG) surgery in patients with chronic coronary syndromes (CCS) is unclear. Adding the P2Y12 inhibitor, ticagrelor, to low-dose aspirin for 1 year is associated with a reduction in graft failure, particularly saphenous vein grafts, at the expense of an increased risk of clinically important bleeding. As the risk of thrombotic graft failure and ischaemic events is highest early after CABG surgery, a better risk-to-benefit profile may be attained with short-term dual antiplatelet therapy followed by single antiplatelet therapy. The One Month Dual Antiplatelet Therapy With Ticagrelor in Coronary Artery Bypass Graft Patients (ODIN) trial is a prospective, randomised, double-blind, placebo-controlled, international, multicentre study of 700 subjects that will evaluate the effect of short-term dual antiplatelet therapy with ticagrelor plus low-dose aspirin after CABG in patients with CCS. Patients will be randomised 1:1 to ticagrelor 90 mg twice daily or matching placebo, in addition to aspirin 75-150 mg once daily for 1 month; after the first month, antiplatelet therapy will be continued with aspirin alone. The primary endpoint is a hierarchical composite of all-cause death, stroke, myocardial infarction, revascularisation and graft failure at 1 year. The key secondary endpoint is a hierarchical composite of all-cause death, stroke, myocardial infarction, Bleeding Academic Research Consortium (BARC) type 3 bleeding, revascularisation and graft failure at 1 year (net clinical benefit). ODIN will report whether the addition of ticagrelor to low-dose aspirin for 1 month after CABG reduces ischaemic events and provides a net clinical benefit in patients with CCS. (ClinicalTrials.gov: NCT05997693).

Effects of pharmacological interventions on mortality in patients with Takotsubo syndrome: a report from the SWEDEHEART registry.

AIMS: Takotsubo syndrome (TS) is a heart condition mimicking acute myocardial infarction. TS is characterized by a sudden weakening of the heart muscle, usually triggered by physical or emotional stress. In this study, we aimed to investigate the effect of pharmacological interventions on short- and long-term mortality in patients with TS. METHODS AND RESULTS: We analysed data from the SWEDEHEART (the Swedish Web System for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies) registry, which included patients who underwent coronary angiography between 2009 and 2016. In total, we identified 1724 patients with TS among 228 263 individuals in the registry. The average age was 66 ± 14 years, and 77% were female. Nearly half of the TS patients (49.4%) presented with non-ST-elevation acute coronary syndrome, and a quarter (25.9%) presented with ST-elevation myocardial infarction. Most patients (79.1%) had non-obstructive coronary artery disease on angiography, while 11.7% had a single-vessel disease and 9.2% had a multivessel disease. All patients received at least one pharmacological intervention; most of them used beta-blockers (77.8% orally and 8.3% intravenously) or antiplatelet agents [aspirin (66.7%) and P2Y12 inhibitors (43.6%)]. According to the Kaplan-Meier estimator, the probability of all-cause mortality was 2.5% after 30 days and 16.6% after 6 years. The median follow-up time was 877 days. Intravenous use of inotropes and diuretics was associated with increased 30 day mortality in TS [hazard ratio (HR) = 9.92 (P < 0.001) and HR = 3.22 (P = 0.001), respectively], while angiotensin-converting enzyme inhibitors and statins were associated with decreased long-term mortality [HR = 0.60 (P = 0.025) and HR = 0.62 (P = 0.040), respectively]. Unfractionated and low-molecular-weight heparins were associated with reduced 30 day mortality [HR = 0.63 (P = 0.01)]. Angiotensin receptor blockers, oral anticoagulants, P2Y12 antagonists, aspirin, and beta-blockers did not statistically correlate with mortality. CONCLUSIONS: Our findings suggest that some medications commonly used to treat TS are associated with higher mortality, while others have lower mortality. These results could inform clinical decision-making and improve patient outcomes in TS. Further research is warranted to validate these findings and to identify optimal pharmacological interventions for patients with TS.

Outcomes by sex in the International Study of Comparative Health Effectiveness With Medical and Invasive Approaches (ISCHEMIA) trial.

BACKGROUND: In the International Study of Comparative Health Effectiveness With Medical and Invasive Approaches (ISCHEMIA) trial, among participants with stable coronary artery disease, the risk of cardiac events was similar between an invasive (INV) strategy of angiography and coronary revascularisation and a conservative (CON) strategy of initial medical therapy alone. Outcomes according to participant sex were not reported. AIMS: We aimed to analyse the outcomes of ISCHEMIA by participant sex. METHODS: We evaluated 1) the association between participant sex and the likelihood of undergoing revascularisation for participants randomised to the INV arm; 2) the risk of the ISCHEMIA primary composite outcome (cardiovascular death, any myocardial infarction [MI] or rehospitalisation for unstable angina, heart failure or resuscitated cardiac arrest) by participant sex; and 3) the contribution of the individual primary outcome components to the composite outcome by participant sex. RESULTS: Of 5,179 randomised participants, 1,168 (22.6%) were women. Female sex was independently associated with a lower likelihood of revascularisation when assigned to the INV arm (adjusted odds ratio 0.75, 95% confidence interval [CI]: 0.57-0.99; p=0.04). The INV versus CON effect on the primary composite outcome was similar between sexes (women: hazard ratio [HR] 0.96, 95% CI: 0.70-1.33; men: HR 0.90, 95% CI: 0.76-1.07; pinteraction=0.71). The contribution of the individual components to the composite outcome was similar between sexes except for procedural MI, which was significantly lower in women (9/151 [5.9%]) than men (67/519 [12.9%]; p=0.01). CONCLUSIONS: In ISCHEMIA, women assigned to the INV arm were less likely to undergo revascularisation than men. The effect of an INV versus CON strategy was consistent by sex, but women had a significantly lower contribution of procedural MI to the primary outcome.

Hypertension, microvascular obstruction and infarct size in patients with STEMI undergoing PCI: Pooled analysis from 7 cardiac magnetic resonance imaging studies.

BACKGROUND: Mortality after ST-segment elevation myocardial infarction (STEMI) is increased in patients with hypertension. The mechanisms underlying this association are uncertain. We sought to investigate whether patients with STEMI and prior hypertension have greater microvascular obstruction (MVO) and infarct size (IS) compared with those without hypertension. METHODS: We pooled individual patient data from 7 randomized trials of patients with STEMI undergoing primary percutaneous coronary intervention (PCI) in whom cardiac magnetic resonance imaging was performed within 1 month after reperfusion. The associations between hypertension and MVO, IS, and mortality were assessed in multivariable adjusted models. RESULTS: Among 2174 patients (61.3 ± 12.6 years, 76% male), 1196 (55.0%) had hypertension. Patients with hypertension were older, more frequently diabetic and had more extensive coronary artery disease than those without hypertension. MVO and IS measured as percent LV mass were not significantly different in patients with and without hypertension (adjusted differences 0.1, 95% CI -0.3 to 0.6, P = .61 and -0.2, 95% CI -1.5 to 1.2, P = .80, respectively). Hypertension was associated with a higher unadjusted risk of 1-year death (hazard ratio [HR] 2.28, 95% CI 1.44-3.60, P < .001), but was not independently associated with higher mortality after multivariable adjustment (adjusted HR 1.04, 95% CI 0.60-1.79, P = .90). CONCLUSION: In this large-scale individual patient data pooled analysis, hypertension was not associated with larger IS or MVO after primary PCI for STEMI.

European Association of Cardio-Thoracic Surgery (EACTS) expert consensus statement on perioperative myocardial infarction after cardiac surgery.

Cardiac surgery may lead to myocardial damage and release of cardiac biomarkers through various mechanisms such as cardiac manipulation, systemic inflammation, myocardial hypoxia, cardioplegic arrest and ischaemia caused by coronary or graft occlusion. Defining perioperative myocardial infarction (PMI) after cardiac surgery presents challenges, and the association between the current PMI definitions and postoperative outcomes remains uncertain. To address these challenges, the European Association of Cardio-Thoracic Surgery (EACTS) facilitated collaboration among a multidisciplinary group to evaluate the existing evidence on the mechanisms, diagnosis and prognostic implications of PMI after cardiac surgery. The review found that the postoperative troponin value thresholds associated with an increased risk of mortality are markedly higher than those proposed by all the current definitions of PMI. Additionally, it was found that large postoperative increases in cardiac biomarkers are prognostically relevant even in absence of additional supportive signs of ischaemia. A new algorithm for PMI detection after cardiac surgery was also proposed, and a consensus was reached within the group that establishing a prognostically relevant definition of PMI is critically needed in the cardiovascular field and that PMI should be included in the primary composite outcome of coronary intervention trials.

Intraoperative Anemia Mediates Sex Disparity in Operative Mortality After Coronary Artery Bypass Grafting.

BACKGROUND: Women undergoing coronary artery bypass grafting (CABG) have higher operative mortality than men. OBJECTIVES: The purpose of this study was to evaluate the relationship between intraoperative anemia (nadir intraoperative hematocrit), CABG operative mortality, and sex. METHODS: This was a cohort study of 1,434,225 isolated primary CABG patients (344,357 women) from the Society of Thoracic Surgeons Adult Cardiac Surgery Database (2011-2022). The primary outcome was operative mortality. The attributable risk (AR) (the risk-adjusted strength of the association of female sex with CABG outcomes) for the primary outcome was calculated. Causal mediation analysis derived the total effect of female sex on operative mortality risk and the proportion of that effect mediated by intraoperative anemia. RESULTS: Women had lower median nadir intraoperative hematocrit (22.0% [Q1-Q3: 20.0%-25.0%] vs 27.0% [Q1-Q3: 24.0%-30.0%], standardized mean difference 97.0%) than men. Women had higher operative mortality than men (2.8% vs 1.7%; P < 0.001; adjusted OR: 1.36; 95% CI: 1.30-1.41). The AR of female sex for operative mortality was 1.21 (95% CI: 1.17-1.24). After adjusting for nadir intraoperative hematocrit, AR was reduced by 43% (1.12; 95% CI: 1.09-1.16). Intraoperative anemia mediated 38.5% of the increased mortality risk associated with female sex (95% CI: 32.3%-44.7%). Spline regression showed a stronger association between operative mortality and nadir intraoperative hematocrit at hematocrit values <22.0% (P < 0.001). CONCLUSIONS: The association of female sex with increased CABG operative mortality is mediated to a large extent by intraoperative anemia. Avoiding nadir intraoperative hematocrit values below 22.0% may reduce sex differences in CABG operative mortality.

Pragmatic randomized controlled trials: strengthening the concept through a robust international collaborative network: PRIME-9-Pragmatic Research and Innovation through Multinational Experimentation.

In an era focused on value-based healthcare, the quality of healthcare and resource allocation should be underpinned by empirical evidence. Pragmatic clinical trials (pRCTs) are essential in this endeavor, providing randomized controlled trial (RCT) insights that encapsulate real-world effects of interventions. The rising popularity of pRCTs can be attributed to their ability to mirror real-world practices, accommodate larger sample sizes, and provide cost advantages over traditional RCTs. By harmonizing efficacy with effectiveness, pRCTs assist decision-makers in prioritizing interventions that have a substantial public health impact and align with the tenets of value-based health care. An international network for pRCT provides several advantages, including larger and diverse patient populations, access to a broader range of healthcare settings, sharing knowledge and expertise, and overcoming ethical and regulatory barriers. The hypothesis and study design of pRCT answers the decision-maker's questions. pRCT compares clinically relevant alternative interventions, recruits participants from diverse practice settings, and collects data on various health outcomes. They are scarce because the medical products industry typically does not fund pRCT. Prioritizing these studies by expanding the infrastructure to conduct clinical research within the healthcare delivery system and increasing public and private funding for these studies will be necessary to facilitate pRCTs. These changes require more clinical and health policy decision-makers in clinical research priority setting, infrastructure development, and funding. This paper presents a comprehensive overview of pRCTs, emphasizing their importance in evidence-based medicine and the advantages of an international collaborative network for their execution. It details the development of PRIME-9, an international initiative across nine countries to advance pRCTs, and explores various statistical approaches for these trials. The paper underscores the need to overcome current challenges, such as funding limitations and infrastructural constraints, to leverage the full potential of pRCTs in optimizing healthcare quality and resource utilization.

Safety and Feasibility Using a Fluid-Filled Wire to Avoid Hydrostatic Errors in Physiological Intracoronary Measurements.

Background: Using a fluid-filled wire with a pressure sensor outside the patient compared to a conventional pressure wire may avoid the systematic error introduced by the hydrostatic pressure within the coronary circulation. Aims: To assess the safety and effectiveness of the novel fluid-filled wire, Wirecath (Cavis Technologies, Uppsala, Sweden), as well as its ability to avoid the hydrostatic pressure error. Methods and Results: The Wirecath pressure wire was used in 45 eligible patients who underwent invasive coronary angiography and had a clinical indication for invasive coronary pressure measurement at Sahlgrenska University Hospital, Gothenburg, Sweden. In 29 patients, a simultaneous measurement was performed with a conventional coronary pressure wire (PressureWire X, Abbott Medical, Plymouth, MN, USA), and in 19 patients, the vertical height difference between the tip of the guide catheter and the wire measure point was measured in a 90-degree lateral angiographic projection. No adverse events caused by the pressure wires were reported. The mean Pd/Pa and mean FFR using the fluid-filled wire and the sensor-tipped wire differed significantly; however, after correcting for the hydrostatic effect, the sensor-tipped wire pressure correlated well with the fluid-filled wire pressure (R = 0.74 vs. R = 0.89 at rest and R = 0.89 vs. R = 0.98 at hyperemia). Conclusion: Hydrostatic errors in physiologic measurements can be avoided by using the fluid-filled Wirecath wire, which was safe to use in the present study. This trial is registered with NCT04776577 and NCT04802681.

Clinical characteristics and outcomes of patients requiring prolonged mechanical circulatory support after high-risk percutaneous coronary intervention.

BACKGROUND: There are limited data on the clinical characteristics and outcomes of patients who require prolonged mechanical circulatory support (MCS) after Impella-supported high-risk percutaneous coronary intervention (HR-PCI). AIMS: The aim of this study is to describe the contemporary clinical characteristics, outcomes, and predictors associated with prolonged MCS support after assisted HR-PCI. METHODS: Patients enrolled in the prospective, multicentre, clinical endpoint-adjudicated PROTECT III study who had undergone HR-PCI using Impella were evaluated. Patient and procedural characteristics and outcomes for those who received prolonged MCS beyond the duration of their index procedure were compared to those in whom MCS was successfully weaned and explanted at the conclusion of the index PCI. RESULTS: Among 1,155 patients who underwent HR-PCI with Impella between 2017 and 2020 and had sufficient data to confirm the duration of Impella support, 16.5% received prolonged MCS (mean duration 25.2±31.1 hours compared with 1.8±5.8 hours for those who only received intraprocedural MCS). Patients receiving prolonged support presented with more urgent indications (e.g., acute coronary syndromes [ACS], lower ejection fraction [EF], elevated baseline heart rate and lower systolic blood pressure). Use of the Impella CP, intraprocedural complications, periprocedural complications and in-hospital mortality were all more common amongst the prolonged MCS group. Prolonged MCS was associated with increased rates of major adverse cardiovascular and cerebrovascular events, cardiovascular death, and all-cause mortality at 90-day follow-up. CONCLUSIONS: Patients receiving prolonged MCS after Impella-supported HR-PCI presented with more ACS, reduced EF and less favourable haemodynamics. Additionally, they were more likely to experience intraprocedural and periprocedural complications as well as increased in-hospital and post-discharge mortality.

Outcomes According to Coronary Revascularization Modality in the ISCHEMIA Trial.

BACKGROUND: In the ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) trial, the risk of ischemic events was similar in patients with stable coronary artery disease treated with an invasive (INV) strategy of angiography and percutaneous coronary intervention (PCI) or surgical (coronary artery bypass grafting [CABG]) coronary revascularization and a conservative (CON) strategy of initial medical therapy. OBJECTIVES: The authors analyzed separately the outcomes of INV patients treated with PCI or CABG. METHODS: Patients without preceding primary outcome events were categorized as INV-PCI or INV-CABG from the time of revascularization. The ISCHEMIA primary outcome (composite of cardiovascular death, protocol-defined myocardial infarction or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest) was used. RESULTS: Among INV-CABG patients, primary outcome events occurred in 84 of 512 (16.4%) at a median follow-up of 2.85 years; 48 events (57.1%) occurred within 30 days after CABG, including 40 procedural MIs. Among INV-PCI patients, primary outcome events occurred in 147 of 1,500 (9.8%) at median follow-up of 2.94 years; 31 of which (21.1%) occurred within 30 days after PCI, including 24 procedural MIs. In comparison, 352 of 2,591 CON patients (13.6%) had primary outcome events at a median follow-up of 3.2 years, 22 of which (6.3%) occurred within 30 days of randomization. The adjusted primary outcome risks were higher after both CABG and PCI within 30 days (HR: 16.25 [95% CI: 11.44-23.07] and HR: 2.99 [95% CI: 1.97-4.53]) and lower thereafter (0.63 [95% CI: 0.44-0.89] and 0.66 [95% CI: 0.53-0.82]). CONCLUSIONS: In ISCHEMIA, early revascularization by PCI and CABG was associated with higher early risks and lower long-term risks of cardiovascular events compared with CON. The early risk was greatest after CABG, owing to protocol-defined procedural MIs.

Design and rationale of the evaluation of transcatheter aortic valve replacement compared to surveillance for patients with asymptomatic severe aortic stenosis: The EARLY TAVR trial.

BACKGROUND: For patients with asymptomatic, severe aortic stenosis (AS) and preserved left ventricular ejection fraction, current guidelines recommend clinical surveillance every 6 to 12 months. To date, no randomized trials have examined whether an early intervention with transcatheter aortic valve replacement (TAVR) will improve outcomes among these patients. STUDY DESIGN AND OBJECTIVES: EARLY TAVR is a prospective, randomized, controlled, and multicenter trial, with an event-based design. Asymptomatic severe AS patients (n = 900) are randomized 1:1 to either clinical surveillance or TAVR with the Edwards SAPIEN 3/SAPIEN 3 Ultra transcatheter heart valve. Patients are stratified by whether they are able to perform a treadmill stress test. The primary end point is death, stroke, or unplanned cardiovascular hospitalization. Patients who are asymptomatic but have a positive stress test will be followed in a registry and undergo aortic valve replacement as per current guidelines. CONCLUSIONS: EARLY TAVR is the largest randomized trial to date assessing the role of early intervention among patients with asymptomatic severe AS compared to clinical surveillance and the first to study the role of TAVR. TRIAL REGISTRATION NUMBER: NCT03042104.

Influence of left ventricular ejection fraction in patients undergoing contemporary pLVAD-supported high-risk PCI.

BACKGROUND: Left ventricular (LV) systolic dysfunction worsens outcomes in patients undergoing percutaneous coronary intervention (PCI). The objective of this study, therefore, was to evaluate outcomes of pLVAD-supported high-risk PCI (HRPCI) patients according to LV ejection fraction (LVEF). METHODS: Patients from the PROTECT III study undergoing pLVAD-supported HRPCI were stratified according to baseline LVEF: severe LV dysfunction (LVEF <30%), mild and moderate LV dysfunction (LVEF ≥30% to <50%), or preserved LV function (LVEF ≥50%). Major adverse cardiovascular and cerebrovascular events (MACCE: composite of all-cause death, myocardial infarction, stroke/transient ischemic attack, and repeat revascularization), and PCI-related complications were assessed at 90 days and mortality was assessed at 1-year. RESULTS: From March 2017 to March 2020, 940 patients had evaluable baseline LVEF recorded in the study database. Patients with preserved LV function were older, more frequently presented with myocardial infarction, and underwent more left main PCI and atherectomy. Immediate PCI-related coronary complications were infrequent (2.7%, overall), similar between groups (P = 0.98), and not associated with LVEF. Unadjusted 90-day MACCE rates were similar among LVEF groups; however, as a continuous variable, LVEF was associated with both 90-day MACCE (adj.HR per 5% 0.89, 95% CI [0.80, 0.98], P = 0.018) and 1-year mortality (adj.HR per 5% 0.84 [0.78, 0.90], P <0.0001). CONCLUSIONS: Patients who underwent pLVAD-supported HRPCI exhibited low incidence of PCI-related complications, regardless of baseline LVEF. However, LVEF was associated with 90-day MACCE and 1-year mortality.

Regurgitant Volume to LA Volume Ratio in Patients with Secondary MR: The COAPT Trial.

AIMS: The conceptual framework of proportionate versus disproportionate mitral regurgitation (MR) translates poorly to individual patients with heart failure (HF) and secondary MR. A novel index, the ratio of MR severity to left atrial volume (LAV), may identify patients with "disproportionate" MR and a higher risk of events. The objectives, therefore, were to investigate the prognostic impact of MR severity to LAV ratio on outcomes among HF patients with severe secondary MR randomized to transcatheter edge-to-edge repair (TEER) with the MitraClipTM device plus guideline-directed medical therapy (GDMT) vs. GDMT alone in the COAPT trial. METHODS AND RESULTS: The ratio of preprocedural regurgitant volume (RVol) to LAV was calculated from baseline transthoracic echocardiograms. The primary endpoint was 2-year covariate-adjusted rate of HF hospitalization (HFH).Among 567 patients, the median RVol/LAV was 0.67 (IQR 0.48-0.91). In patients randomized to GDMT alone, lower RVol/LAV was independently associated with an increased 2-year risk of HFH (adjHR: 1.77; 95% CI: 1.20-2.63). RVol/LAV was a stronger predictor of adverse outcomes than RVol or LAV alone. Treatment with TEER plus GDMT compared with GDMT alone was associated with lower 2-year rates of HFH both in patients with low and high RVol/LAV (Pinteraction = 0.28). Baseline RVol/LAV ratio was unrelated to 2-year mortality, health status, or functional capacity in either treatment group. CONCLUSIONS: Low RVol/LAV ratio was an independent predictor of 2-year HFH in HF patients with severe MR treated with GDMT alone in the COAPT trial. TEER improved outcomes regardless of baseline RVol/LAV ratio. CLINICAL TRIAL REGISTRATION: Trial Name: Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation (The COAPT Trial) (COAPT) ClinicalTrial.gov Identifier: NCT01626079 URL: https://clinicaltrials.gov/ct2/show/NCT01626079.

Distal aortic biomechanics after transcatheter versus surgical aortic valve replacement: a hypothesis generating study.

BACKGROUND: Biomechanical effects of transcatheter (TAVR) versus surgical (SAVR) aortic valve interventions on the distal aorta have not been studied. This study utilized global circumferential strain (GCS) to assess post-procedural biomechanics changes in the descending aorta after TAVR versus SAVR. METHODS: Patients undergoing TAVR or SAVR for aortic stenosis were included. Transesophageal (TEE) and transthoracic (TTE) echocardiography short-axis images of the aorta were used to image the descending aorta immediately before and after interventions. Image analysis was performed with two-dimensional speckle tracking echocardiography and dedicated software. Delta GCS was calculated as: post-procedural GCS-pre-procedural GCS. Percentage delta GCS was calculated as: (delta GCS/pre-procedural GCS) × 100. RESULTS: Eighty patients, 40 TAVR (median age 81 y/o, 40% female) and 40 SAVR (median 72 y/o, 30% female) were included. The post-procedure GCS was significantly higher than the pre-procedural GCS in the TAVR (median 10.7 [interquartile range IQR 4.5, 14.6] vs. 17.0 [IQR 6.1, 20.9], p = 0.009) but not in the SAVR group (4.4 [IQR 3.3, 5.3] vs. 4.7 [IQR 3.9, 5.6], p = 0.3). The delta GCS and the percentage delta GCS were both significantly higher in the TAVR versus SAVR group (2.8% [IQR 1.4, 6] vs. 0.15% [IQR - 0.6, 1.5], p < 0.001; and 28.8% [IQR 14.6%, 64.6%] vs. 4.4% [IQR - 10.6%, 5.6%], p = 0.006). Results were consistent after multivariable adjustment for key clinical and hemodynamic characteristics. CONCLUSIONS: After TAVR, there was a significantly larger increase in GCS in the distal aorta compared to SAVR. This may impact descending aortic remodeling and long-term risk of aortic events.