Expanding opportunities to understand quality and outcomes of peripheral vascular interventions: The ACC NCDR PVI Registry.

Lower extremity peripheral artery disease (PAD) and cerebrovascular disease (CeVD) are prevalent conditions in the United States, and both are associated with significant morbidity (eg, stroke, myocardial infarction, and limb loss) and increased mortality. With a growth in invasive procedures for PAD and CeVD, this demands a more clear responsibility and introduces an opportunity to study how patients are treated and evaluate associated outcomes. The American College of Cardiology (ACC) National Cardiovascular Data Registry (NCDR) Peripheral Vascular Intervention (PVI) Registry is a prospective, independent collection of data elements from individual patients at participating centers, and it is a natural extension of the already robust NCDR infrastructure. As of September 20, 2018, data have been collected on 45,316 lower extremity PVIs, 12,417 carotid artery stenting procedures, and 11,027 carotid endarterectomy procedures at 208 centers in the United States. The purpose of the present report is to describe the patient and procedural characteristics of the overall cohort and the methods used to design and implement the registry. In collecting these data, ACC and ACC PVI Registry have the opportunity to play a pivotal role in scientific evidence generation, medical device surveillance, and creation of best practices for PVI and carotid artery revascularization.

Early Outcomes following Endovascular, Open Surgical, and Hybrid Revascularization for Lower Extremity Acute Limb Ischemia.

BACKGROUND: Acute limb ischemia (ALI) of the lower extremity is a potentially devastating condition that requires urgent and definitive management. This challenging scenario is often treated with endovascular, open surgical, or hybrid revascularization (HyR) in an urgent basis, but the comparative effects of such therapies remain poorly defined. The purpose of this study was to compare the outcomes of endovascular, open surgical, and HyR for ALI in the contemporary era. METHODS: A large statewide cardiovascular consortium of 45 hospitals was queried for patients between January 2012 and June 2015 who underwent an endovascular, open surgical, or HyR for ALI deemed at high risk of limb loss if not treated within 24 hr (Rutherford class IIA or IIB). A propensity score weighted analysis was performed controlling for demographics, medical history, and procedure type for patients. The primary outcomes were 30-day morbidity and mortality. RESULTS: A total of 1,480 patients underwent endovascular revascularization (ER; n = 818), open surgical revascularization (OSR; n = 195), or hybrid revascularization (HyR; n = 467) for ALI. The mean age was similar across revascularization technique with an increased predominance of male gender in open surgery cohort. Comorbidities for all groups were consistent with peripheral arterial disease. The most common endovascular procedures were angioplasty (93%) and thrombolysis (49.8%), whereas the most common surgical revascularization was femoral to popliteal bypass (32.8%), femoral to tibial bypass (28.2%), and thrombectomy (19.0%); ER as compared with OSR and HyR procedures was associated with less transfusion (OSR versus ER, odds ratio [OR] 2.7; HyR versus ER, OR 2.8; P < 0.001) and major amputation (OSR versus ER, OR 3.4; HyR versus ER, OR 4.0; P < 0.001) within 30 days of intervention. There was no difference in 30-day freedom from reintervention, myocardial infarction (MI), or mortality. CONCLUSIONS: Among patients requiring urgent revascularization for Rutherford grade IIA and IIB ischemia, ER has lower 30-day morbidity but similar mortality and rates of reintervention. Although long-term patency rates were not compared, ER may offer superior short-term outcomes compared with open surgery and hybrid revascularization.

Contrast-induced nephropathy in patients undergoing endovascular peripheral vascular intervention: Incidence, risk factors, and outcomes as observed in the Blue Cross Blue Shield of Michigan Cardiovascular Consortium.

BACKGROUND: The incidence, risk factors, and outcomes associated with Contrast-induced nephropathy (CIN) after Percutaneous Vascular Intervention (PVI) in contemporary medical practice are largely unknown. METHODS: A total of 13 126 patients undergoing PVI were included in the analysis. CIN was defined as an increase in serum creatinine from pre-PVI baseline to post-PVI peak Cr of ≥0.5 mg/dL. RESULTS: CIN occurred in 3% (400 patients) of the cohort, and 26 patients (6.5%) required dialysis. Independent predictors of CIN were high and low body weight, diabetes, heart failure, anemia, baseline renal dysfunction, critical limb ischemia, and a higher acuity of the PVI procedure and a contrast dose that was greater than three times the calculated creatinine clearance (CCC) (adjusted OR 1.4, 95% CI: 1.1-1.8, P = 0.003). CIN was strongly associated with adverse outcome including in-hospital death (adjusted OR 18.1, CI 10.7-30.6, P < 0.001), myocardial infarction (adjusted OR 16.2, CI 8.9-29.5, P < 0.001), transient ischemic attack/stroke (adjusted OR 5.5, CI 3.2-14.9, P = 0.001), vascular access complications (adjusted OR 3.4, CI 2.3-5, P < 0.001), and transfusion (adjusted OR 7, CI 5.4-9, P < 0.001). Hospital stay was longer in patients who developed CIN versus those who did not. CONCLUSIONS: CIN is not an uncommon complication associated with PVI, can be reliably predicted from pre-procedural variables, including a contrast dose of greater than three times the CCC and is strongly associated with the risk of in-hospital death, MI, stroke, transfusion, and increased hospital length of stay.

Phase I study of multi-gene cell therapy in patients with peripheral artery disease.

UNLABELLED: Alternative treatment strategies for claudication are needed and cell-based therapies designed to induce angiogenesis are promising. The purpose of this report was to conduct a Phase I safety, dose-escalating, non-randomized, open-label study of autologous, fully differentiated venous endothelial and smooth muscle cells called MultiGeneAngio (MGA) for claudication due to peripheral artery disease. Twelve subjects, at two centers, received a single intra-arterial infusion of a suspension of equal amounts of transduced autologous venous smooth muscle cells expressing vascular endothelial growth factor (VEGF165) and endothelial cells expressing angiopoietin-1 (Ang-1) (Cohort 1: 1 × 10(7), Cohort 2: 2 × 10(7), Cohort 3: 5 × 10(7), Cohort 4: 7 × 10(7)). The treatment was given unblinded and in the more symptomatic lower extremity. Transduced cells were tested for in vitro doubling time, telomerase activity, and gene expression. The main outcomes were clinical safety and tolerability. Other safety measures included ankle-brachial index (ABI) and walking time on a treadmill. All subjects were male (mean age 60 ± 5 years) including 25% with diabetes mellitus. At 1-year follow-up, there was one serious adverse event possibly related to MGA. Safety endpoints including VEGF and Ang-1 plasma protein levels were within normal ranges in all subjects. The mean maximal walking time increased from baseline to 1 year and the index limb ABI was unchanged, indicating no safety concerns. MGA, an autologous, transduced, cell-based therapy was well tolerated and safe in this Phase I study. Further evaluation is warranted in randomized human studies. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00390767.

The association of perioperative transfusion with 30-day morbidity and mortality in patients undergoing major vascular surgery.

OBJECTIVE: Blood transfusions are common among patients undergoing major vascular surgery. Prior studies suggest an association between blood transfusion and increased morbidity and mortality among patients undergoing cardiac surgery. The predictors of perioperative transfusion and its impact on patients undergoing vascular surgery have been poorly defined. METHODS: We examined data from a large multicenter quality improvement vascular surgical registry of all patients undergoing elective or urgent open peripheral arterial disease procedures, endovascular aneurysm repair, or open abdominal aortic aneurysm (AAA) repair between January 2012 and December 2013. Emergency cases, carotid endarterectomy, and carotid artery stenting were excluded. Univariate and multivariate logistic regression modeling was used to identify predictors of transfusion and association of transfusion with outcomes. All regression models had Hosmer-Lemeshow P > .05 and area under the receiver operating characteristic curve of >0.8, confirming excellent goodness of fit and discrimination. RESULTS: Our study population comprised 2946 patients who underwent open peripheral arterial disease procedures (n = 1744), open AAA repair (n = 175), or endovascular aneurysm repair (n = 1027) at 22 hospitals. The overall transfusion rate was 25%, at a median nadir hemoglobin level of 7.7 g/dL. Independent factors predicting transfusion included female gender (odds ratio [OR], 2.6; 95% confidence interval [CI], 2.1-3.2), nonwhite race (OR, 2.7; 95% CI, 1.4-5.2), preoperative admission status (ie, acute care hospital) (OR, 2.6; 95% CI, 1.3-5.3), preoperative anemia (OR, 4.2; 95% CI, 3.3-5.1), congestive heart failure (OR, 1.4; 95% CI, 1.1-1.9), prior myocardial infarction (OR, 1.3; 95% CI, 1.01-1.6), clopidogrel (OR, 1.4; 95% CI, 1.2-1.8), open AAA repair (OR, 25; 95% CI, 17-39), open bypass (OR, 3.5; 95% CI, 2.7-4.6), and urgent procedures (OR, 1.4; 95% CI, 1.1-1.8). With adjustment for major covariates, perioperative transfusion was independently associated with death (OR, 6.9; 95% CI, 3.2-15), myocardial infarction (OR, 8; 95% CI, 3.7-17), and pneumonia (OR, 7.4; 95% CI, 3.3-17). CONCLUSIONS: Perioperative transfusion in vascular surgical patients is independently associated with increased 30-day morbidity and mortality. Given indeterminate causation, these data suggest the need for a prospective transfusion threshold study in vascular surgical patients.

If not now, when? Prescription of evidence-based medical therapy prior to hospital discharge increases utilization at 6 months in patients with symptomatic peripheral artery disease.

We evaluated the impact of the prescription of evidence-based medical therapy (EBMT) including aspirin (ASA), beta-blockers (BB), ACE-inhibitors or angiotensin receptor blockade (ACE/ARB), and statins prior to discharge after peripheral vascular intervention (PVI) on long-term medication utilization in a large multi-specialty, multicenter quality improvement collaborative. Among patients undergoing coronary revascularization, use of the component medications of EBMT at hospital discharge is a major predictor of long-term utilization. Predictors of EBMT use after PVI are largely unknown. A total of 10,169 patients undergoing PVI between 1 January 2008 and 31 December 2011 were included. Post-PVI discharge and 6-month medication utilization in patients without contra-indications to ASA, BB, ACE/ARB, and statins were compared. ASA was prescribed at discharge to 9345 (92%) patients, BB to 7012 (69%), ACE/ARB to 6424 (63%), and statins to 8342 (82%), and all four component drugs of EBMT in 3953 (39%). Compared with patients not discharged on the appropriate medications, post-procedural use was associated (all p<0.001) with reported 6-month use: ASA (84.5% vs 39.2%), BB (82.5% vs 11.1%), ACE/ARB (78.2% vs 11.8%), statins (84.6% vs 21.8%). Multivariable analysis revealed that prescription of EBMT at the time of discharge remained strongly associated with use at 6 months for each of the individual component drugs as well as for the combination of all four EBMT medications. In conclusion, prescription of the component medications of EBMT at the time of PVI is associated with excellent utilization at 6 months, while failure to prescribe EBMT at discharge is associated with low use of these medications 6 months later. These data suggest that the time of a PVI is a therapeutic window in which to prescribe EBMT in this high-risk cohort and represents an opportunity for quality improvement.

Current medical management of stable coronary artery disease before and after elective percutaneous coronary intervention.

BACKGROUND: Percutaneous coronary intervention (PCI) for stable coronary artery disease (CAD) is not superior to optimal medical therapy. It remains unclear if patients who receive PCI for stable CAD are receiving appropriate medical therapy. METHODS: We evaluated the medical management of 60,386 patients who underwent PCI for stable CAD between 2004 and 2009. We excluded patients with contraindications to aspirin, clopidogrel, statins, or ß-blockers (BBs). We defined essential medical therapy of stable CAD as treatment with aspirin, statin, and BB before PCI and treatment with aspirin, clopidogrel, and statin after PCI. RESULTS: Essential medical therapy was used in 53.0% of patients before PCI and 82.1% at discharge. Aspirin was used in 94.8% patients before PCI and 98.3% of after PCI. Statins were used in 69.5% of patients before PCI and 84.5% after PCI. ß-Blockers were used in 72.8% of patients before PCI. Clopidogrel was used in 97.3% of patients after PCI. Patients with a history of myocardial infarction or revascularization before PCI had better medical therapy compared with patients without such a history (62.8% vs 34.3% [P < .001] before PCI and 83.6% vs 79.1% [P < .001] after PCI). After adjusting for confounders and clustering, women (odds ratio 0.74, 95% CI 0.71-0.78) and patients on dialysis (odds ratio 0.68, 95% CI 0.57-0.80) were less likely to receive a statin at discharge. CONCLUSIONS: Medical therapy remains underused before and after PCI for stable CAD. Women are less likely to receive statin therapy. There are significant opportunities to optimize medical therapy in patients with stable CAD.

The Relationship Between Hospital Stroke Center Designation and TVT Reported Stroke: The Michigan TAVR Experience.

BACKGROUND: The 30-day rate of stroke after transcatheter aortic valve replacement (TAVR) has been suggested as a hospital quality metric. Thirty-day stroke rates for nonsurgical, high, and moderate-risk TAVR trials were 3.4% to 6.1%, whereas those in the national Transcatheter Valve Therapy (TVT) Registry for the same patient population were much lower. Hospital comprehensive stroke center (CSC) is the highest designation for integrated acute stroke recognition, management, and care. OBJECTIVES: Using Michigan TVT data, we assessed whether in-hospital post-TAVR stroke rates varied between CSC and non-CSC institutions. METHODS: TVT data submitted from the 22 Michigan Transcatheter Aortic Valve Replacement Collaborative participating institutions between January 1, 2016, and June 30, 2019, were included (N = 6,231). Bayesian hierarchical regression models accounting for patient clinical characteristics and hospital clustering were fitted to assess the association between hospital CSC accreditation and in-hospital post-TAVR stroke. Adjusted ORs and 95% credible intervals were estimated. The University of Michigan Institutional Review Board has waived the need for the approval of studies based on the data collected by the Blue Cross Blue Shield of Michigan Cardiovascular Consortium registry. RESULTS: There were 3,882 (62.3%) patients at 9 CSC sites and 2,349 (37.7%) patients at 13 non-CSC sites. CSC sites had significantly higher rates of in-hospital post-TAVR stroke (CSC: 2.65% vs non-CSC: 1.15%; P < 0.001). After adjustment, patients who underwent TAVR at a CSC hospital had a significantly higher risk of in-hospital stroke (adjusted OR: 2.21; 95% CI: 1.03-4.62). However, CSC designation was not significantly associated with other important post-TAVR clinical outcomes including 30-day mortality. CONCLUSIONS: Reported Michigan Transcatheter Aortic Valve Replacement Collaborative TVT stroke rates were significantly higher at sites with Joint Hospital Commission stroke designation status; however, other reported important clinical outcomes did not differ significantly based on this designation. CSC designation is a possible factor in stroke rate detection differences between TAVR institutions and might be a factor in the observed differences in stroke rates between TAVR trials and those reported in TVT. In addition, these data suggest that comparison between hospitals based on post-TAVR stroke rates is potentially problematic.

Redo Surgical Aortic Valve Replacement After Prior Transcatheter Versus Surgical Aortic Valve Replacement.

BACKGROUND: Aortic stenosis treatment should consider risks and benefits for lifetime management. Although the feasibility of redo transcatheter aortic valve replacement (TAVR) remains unclear, concerns are emerging regarding reoperation after TAVR. OBJECTIVES: The authors sought to define comparative risk of surgical aortic valve replacement (SAVR) after prior TAVR or SAVR. METHODS: Data on patients undergoing bioprosthetic SAVR after TAVR and/or SAVR were extracted from the Society of Thoracic Surgeons Database (2011-2021). Overall and isolated SAVR cohorts were analyzed. The primary outcome was operative mortality. Risk adjustment using hierarchical logistic regression as well as propensity score matching for isolated SAVR cases were performed. RESULTS: Of 31,106 SAVR patients, 1,126 had prior TAVR (TAVR-SAVR), 674 had prior SAVR and TAVR (SAVR-TAVR-SAVR), and 29,306 had prior SAVR (SAVR-SAVR). Yearly rates of TAVR-SAVR and SAVR-TAVR-SAVR increased over time, whereas SAVR-SAVR was stable. The TAVR-SAVR patients were older, with higher acuity, and with greater comorbidities than other cohorts. The unadjusted operative mortality was highest in the TAVR-SAVR group (17% vs 12% vs 9%, respectively; P < 0.001). Compared with SAVR-SAVR, risk-adjusted operative mortality was significantly higher for TAVR-SAVR (OR: 1.53; P = 0.004), but not SAVR-TAVR-SAVR (OR: 1.02; P = 0.927). After propensity score matching, operative mortality of isolated SAVR was 1.74 times higher for TAVR-SAVR than SAVR-SAVR patients (P = 0.020). CONCLUSIONS: The number of post-TAVR reoperations is increasing and represent a high-risk population. Yet even in isolated SAVR cases, SAVR after TAVR is independently associated with increased risk of mortality. Patients with life expectancy beyond a TAVR valve and unsuitable anatomy for redo-TAVR should consider a SAVR-first approach.

Quality of Life After Transcatheter Aortic Valve Replacement in Normal-Flow, Low-Gradient Aortic Stenosis.

Background: Prior studies of aortic valve replacement (AVR) in patients with normal-flow, low-gradient aortic stenosis (NF-LG AS) have demonstrated conflicting results regarding the survival benefit of AVR. Changes in quality of life (QoL) after transcatheter AVR (TAVR) have not been reported in this population. Objectives: The purpose of this study was to compare changes in QoL after TAVR for patients with NF-LG AS to patients with high-gradient aortic stenosis (HG-AS). Methods: Patients who underwent TAVR for severe aortic stenosis (AS) were divided into 4 hemodynamic profiles of AS, including NF-LG AS. Changes in Kansas City Cardiomyopathy Questionnaire-12 score from baseline to 1 year were compared between AS groups. The primary composite outcome indicating clinical improvement consisted of survival to 1 year and improved Kansas City Cardiomyopathy Questionnaire overall summary score of ≥5 points while adjusting for relevant baseline factors. Results: Out of 860 patients who underwent TAVR, high gradient AS was present in 368 (42.8%) patients and NF-LG AS in 245 (28.5%). HG-AS and NF-LG AS groups had a similar proportion of patients who met the primary unadjusted outcome of clinical improvement (70.4% vs 63.9%, respectively; P = 0.189). One-year Kaplan-Meier mortality estimates were higher for NF-LG AS patients than HG-AS patients (12.9% vs 5.8%, P < 0.001). In the primary adjusted analysis, there was no significant difference in the composite outcome between HG and NF-LG AS groups (adjusted OR: 0.72, 95% CI: 0.47-1.11). Conclusions: Selected patients with NF-LG AS experienced similar improvement in QoL after TAVR compared with HG-AS. Further investigation of patients with NF-LG AS will help to inform optimal selection for treatment with TAVR.

Aortic valve reintervention in patients with failing transcatheter aortic bioprostheses: A statewide experience.

BACKGROUND: Despite the rapid adoption of transcatheter aortic valve replacement since its approval, the frequency and outcomes of aortic valve reintervention after transcatheter aortic valve replacement are poorly understood. METHODS: Valve reinterventions, either surgical transcatheter aortic valve explantation or repeat transcatheter aortic valve replacement, between 2012 and 2019 were queried using the Society of Thoracic Surgeons Database and the Transcatheter Valve Therapy Registry through the Michigan Statewide quality collaborative. The reintervention frequency and clinical outcomes including observed-to-expected mortality ratio using Society of Thoracic Surgeons Predicted Risk of Mortality were reviewed. RESULTS: Among 9694 transcatheter aortic valve replacement recipients, a total of 87 patients (0.90%) received a reintervention, consisting of 34 transcatheter aortic valve explants and 53 repeat transcatheter aortic valve replacement procedures. The transcatheter aortic valve explant group demonstrated a higher Society of Thoracic Surgeons Predicted Risk of Mortality. Reintervention cases increased from 0 in 2012 and 2013 to 26 in 2019. The proportion of transcatheter aortic valve explants among all reinterventions increased and was 65% in 2019. Self-expandable devices had a higher reintervention rate than balloon-expandable devices secondary to a higher transcatheter aortic valve explant frequency (0.58% [23/3957] vs 0.19% [11/5737]; P = .001), whereas repeat transcatheter aortic valve replacement rates were similar (0.61% [24/3957] vs 0.51% [29/5737]; P = .51). Among patients with transcatheter aortic valve explants, contraindications to repeat transcatheter aortic valve replacement included unfavorable anatomy (75%), need for other cardiac surgery (29%), other structural issues by transcatheter aortic valve device (18%), and endocarditis (12%). For transcatheter aortic valve explant and repeat transcatheter aortic valve replacement, the 30-day mortality was 15% and 2% (P = .032) and the observed-to-expected mortality ratio was 1.8 and 0.3 (P = .018), respectively. CONCLUSIONS: Aortic valve reintervention remains rare but is increasing. The clinical impact of surgical device explantation was substantial, and the proportion of transcatheter aortic valve explants was significantly higher in patients with a self-expandable device.

Predictors and Variation in Cardiac Rehabilitation Participation After Transcatheter Aortic Valve Replacement.

Background: Cardiac rehabilitation (CR) is strongly recommended for a spectrum of cardiovascular conditions and procedures including aortic valve replacement. Objectives: The purpose of this study was to characterize patient and hospital factors associated with CR participation after transcatheter aortic valve replacement (TAVR) and determine which factors explain hospital-level variation in CR participation. Methods: We linked clinical and administrative claims data from patients who underwent TAVR at 24 Michigan hospitals between January 1, 2016 and June 30, 2020 and obtained rates of CR enrollment within 90 days of discharge. Sequential mixed models were fit to evaluate hospital variation in 90-day post-TAVR CR participation. Results: Among 3,372 patients, 30.6% participated in CR within 90-days after discharge. Several patient factors were negatively associated with CR participation after TAVR including older age, Medicaid insurance, atrial fibrillation/flutter, dialysis use, and slower baseline 5-m walk times. There was substantial hospital variation in CR participation after TAVR ranging from 5% to 60% across 24 hospitals. Patient case mix did not explain hospital variation in CR across hospitals with median OR numerically increasing from 2.11 (95% CI: 1.62-2.67) to 2.13 (95% CI: 1.61-2.68) after accounting for patient-level factors. Conclusions: Less than 1 in 3 patients who underwent TAVR in Michigan participated in CR within 90-days of discharge. Although several patient factors are associated with CR participation, hospital-level variation in CR participation after TAVR is not explained by patient case mix. Identifying hospital processes of care that promote CR participation after TAVR will be critical to improving CR participation after TAVR.

First-in-Human Multicenter Experience of the Newest Generation Supra-Annular Self-Expanding Evolut FX TAVR System.

BACKGROUND: The latest-generation Evolut FX TAVR system (Medtronic) offers several potential design improvements over its predecessors, but early reported experience has been limited. OBJECTIVES: This study sought to report our multicenter, limited market release, first-in-human experience of transcatheter aortic valve replacement (TAVR) with the Evolut FX system and compare it with a single-center PRO+ (Medtronic) experience. METHODS: From June 27 to September 16, 2022, 226 consecutive patients from 9 US centers underwent transfemoral TAVR with the Evolut FX system for native aortic stenosis (89.4%) or prosthetic valve degeneration (10.6%). Commissural alignment was defined as 0° to 30° between native and FX commissures. Patient, anatomical, and procedural characteristics were retrospectively reviewed, and 30-day clinical and echocardiographic outcomes per Valve Academic Research Consortium-3 definitions were reported. RESULTS: Of 226 patients, 34.1% were low risk, 4% had a bicuspid valve, and 11.5% had a horizontal root (≥60°). Direct Inline sheath (Medtronic) was used in 67.6% and Lunderquist stiff wire (Cook Medical) in 35.4% of cases. Optimal hat marker orientation during deployment was achieved in 98.4%, with commissural alignment in 96.5%. At 30 days, 14.3% mild, 0.9% moderate, and no severe paravalvular leak were observed. Compared with the Evolut PRO+ experience from 1 center, FX had a more symmetrical implantation with shallower depth at the left coronary cusp (P < 0.001), fewer device recaptures (26.1% vs 39.5%; P = 0.004), and improved commissural alignment (96.5% vs 80.2%; P < 0.001). CONCLUSIONS: The Evolut FX system demonstrated favorable 30-day outcomes with a significant improvement over PRO+ in achieving commissural alignment, fewer device recaptures, and more symmetrical implantation. These features may benefit younger patients undergoing TAVR with the supra-annular, self-expanding valve, where lifetime management would be important.

The changing definition of contrast-induced nephropathy and its clinical implications: insights from the Blue Cross Blue Shield of Michigan Cardiovascular Consortium (BMC2).

BACKGROUND: The traditional definition of contrast-induced nephropathy (CIN) has been an absolute rise of serum creatinine (Cr) of ≥0.5 mg/dL, although most recent clinical trials have included a ≥25% increase from baseline Cr. The clinical implication of this definition change remains unknown. METHODS AND RESULTS: We compared the association of the two definitions with risk of death or need for dialysis among 58,957 patients undergoing percutaneous coronary intervention in 2007 to 2008 in a large collaborative registry. Patients with a preexisting history of renal failure requiring dialysis were excluded. Contrast-induced nephropathy as defined by a rise in Cr ≥0.5 mg/dL (CIN(Traditional)) developed in 1,601, whereas CIN defined either as Cr ≥0.5 mg/dL or ≥25% increase in baseline Cr (CIN(New)) developed in 4,308 patients. Patients meeting the definition of CIN(New) but not CIN(Traditional) were classified as CIN(Incremental) (n = 2,707). Compared with CIN(New), CIN(Traditional) was more commonly seen in patients with abnormal renal function, which was more likely to develop in patients with normal renal function at baseline. Compared with CIN(Incremental), patients meeting the definition of CIN(Traditional) were more likely to die (16.7% vs 1.7%) and require in-hospital dialysis (9.8% vs 0%). CONCLUSIONS: Our data suggest that the traditional definition of CIN (a rise in Cr of ≥0.5 mg/dL) in patients undergoing PCI is superior to ≥25% increase in Cr at identifying patients at greater risk for adverse renal and cardiac events.

Multifaceted Intervention to Improve P2Y12 Inhibitor Adherence After Percutaneous Coronary Intervention: A Stepped Wedge Trial.

Background P2Y12 inhibitor medications are critical following percutaneous coronary intervention (PCI); however, adherence remains suboptimal. Our objective was to assess the effectiveness of a multifaceted intervention to improve P2Y12 inhibitor adherence following PCI. Methods and Results This was a modified stepped wedge trial of 52 eligible hospitals, of which 15 were randomly selected and agreed to participate (29 hospitals declined, and 8 eligible hospitals were not contacted). At each intervention hospital, patient recruitment occurred for 6 months and enrolled patients were followed up for 1 year after PCI. Three control groups were used: patients at intervention hospitals undergoing PCI (1) before the intervention period (preintervention); (2) after the intervention period (postintervention); or (3) at the 8 hospitals not contacted (concurrent controls). The intervention consisted of 4 components: (1) P2Y12 inhibitor delivered to patients' bedside after PCI; (2) education on importance of P2Y12 inhibitors; (3) automated reminder telephone calls to refill medication; and (4) outreach to patients if they delayed refilling P2Y12 inhibitor. The primary outcomes were as follows: (1) proportion of patients with delays filling P2Y12 inhibitor at hospital discharge and (2) proportion of patients who were adherent in the year after PCI using pharmacy refill data. Primary analysis compared intervention with preintervention control patients. There were 1377 (intent-to-treat) potentially eligible patients, of whom 803 (per protocol) were approached at intervention sites versus 5910 preintervention, 2807 postintervention, and 4736 concurrent control patients. In the intent-to-treat analysis, intervention patients were less likely to delay filling P2Y12 at hospital discharge (-3.4%; 98.3% CI, -1.2% to -5.6%) and more likely to be adherent to P2Y12 (4.1%; 98.3% CI, 1.0%-7.1%) at 1 year, but had more clinical events (3.2%; 98.3% CI, 2.3%-4.1%) driven by repeated PCI compared with preintervention patients. In post hoc analysis looking at myocardial infarction, stroke, and death, intervention patients had lower event rates compared with preintervention patients (-1.7%; 98.3% CI, -2.3% to -1.1%). Conclusions A 4-component intervention targeting P2Y12 inhibitor adherence was difficult to implement. The intervention produced mixed results. It improved P2Y12 adherence, but there was also an increase in repeat PCI. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01609842.

Surgical Explantation of Transcatheter Aortic Valve Bioprostheses: A Statewide Experience.

BACKGROUND: Despite the rapid adoption of transcatheter aortic valve replacement (TAVR) since its initial approval in 2011, the frequency and outcomes of surgical explantation of TAVR devices (TAVR-explant) is poorly understood. METHODS: Patients undergoing TAVR-explant between January 2012 and June 2020 at 33 hospitals in Michigan were identified in the Society of Thoracic Surgeons Database and linked to index TAVR data from the Transcatheter Valve Therapy Registry through a statewide quality collaborative. The primary outcome was operative mortality. Indications for TAVR-explant, contraindications to redo TAVR, operative data, and outcomes were collected from Society of Thoracic Surgeons and Transcatheter Valve Therapy databases. Baseline Society of Thoracic Surgeons Predicted Risk of Mortality was compared between index TAVR and TAVR-explant. RESULTS: Twenty-four surgeons at 12 hospitals performed TAVR-explants in 46 patients (median age, 73). The frequency of TAVR-explant was 0.4%, and the number of explants increased annually. Median time to TAVR-explant was 139 days and among known device types explanted, most were self-expanding valves (29/41, 71%). Common indications for TAVR-explant were procedure-related failure (35%), paravalvular leak (28%), and need for other cardiac surgery (26%). Contraindications to redo TAVR included need for other cardiac surgery (28%), unsuitable noncoronary anatomy (13%), coronary obstruction (11%), and endocarditis (11%). Overall, 65% (30/46) of patients underwent concomitant procedures, including aortic repair/replacement in 33% (n=15), mitral surgery in 22% (n=10), and coronary artery bypass grafting in 16% (n=7). The median Society of Thoracic Surgeons Predicted Risk of Mortality was 4.2% at index TAVR and 9.3% at TAVR-explant (P=0.001). Operative mortality was 20% (9/46) and 76% (35/46) of patients had in-hospital complications. Of patients alive at discharge, 37% (17/37) were discharged home and overall 3-month survival was 73±14%. CONCLUSIONS: TAVR-explant is rare but increasing, and its clinical impact is substantial. As the utilization of TAVR expands into younger and lower-risk patients, providers should consider the potential for future TAVR-explant during selection of an initial valve strategy.

Safety and efficacy of thrombectomy in patients undergoing primary percutaneous coronary intervention for acute ST elevation MI: a meta-analysis of randomized controlled trials.

BACKGROUND: Clinical trials comparing thrombectomy devices with conventional percutaneous coronary interventions (PCI) in patients with acute ST elevation myocardial infarction (STEMI) have produced conflicting results. The objective of our study was to systematically evaluate currently available data comparing thrombectomy followed by PCI with conventional PCI alone in patients with acute STEMI. METHODS: Seventeen randomized trials (n = 3,909 patients) of thrombectomy versus PCI were included in this meta-analysis. We calculated the summary odds ratios for mortality, stroke, post procedural myocardial blush grade (MBG), thrombolysis in myocardial infarction (TIMI) grade flow, and post procedural ST segment resolution (STR) using random-effects and fixed-effects models. RESULTS: There was no difference in risk of 30-day mortality (44/1914 vs. 50/1907, OR 0.84, 95% CI 0.54-1.29, P = 0.42) among patients randomized to thrombectomy, compared with conventional PCI. Thrombectomy was associated with a significantly greater likelihood of TIMI 3 flow (1616/1826 vs. 1533/1806, OR 1.41, P = 0.007), MBG 3 (730/1526 vs. 486/1513, OR 2.42, P < 0.001), STR (923/1500 vs. 715/1494, OR 2.30, P < 0.001), and with a higher risk of stroke (14/1403 vs. 3/1413, OR 2.88, 95% CI 1.06-7.85, P = 0.04). Outcomes differed significantly between different device classes with a trend towards lower mortality with manual aspiration thrombectomy (MAT) (21/949 vs.36/953, OR 0.59, 95% CI 0.35-1.01, P = 0.05), whereas mechanical devices showed a trend towards higher mortality (20/416 vs.10/418, OR 2.07, 95% CI 0.95-4.48, P = 0.07). CONCLUSIONS: Thrombectomy devices appear to improve markers of myocardial perfusion in patients undergoing primary PCI, with no difference in overall 30-day mortality but an increased likelihood of stroke. The clinical benefits of thrombectomy appear to be influenced by the device type with a trend towards survival benefit with MAT and worsening outcome with mechanical devices.

Early Structural Valve Degeneration of Trifecta Bioprosthesis.

BACKGROUND: Structural valve degeneration (SVD) is a major flaw of bioprostheses. An apparent increase in the SVD rate has been observed among patients who received the Trifecta bioprosthesis (Abbott Vascular, Santa Clara, CA). METHODS: This study retrospectively reviewed 1058 consecutive patients who underwent aortic valve placement with a stented bioprosthesis between January 2011 and December 2015. Patients were grouped into a Trifecta group (508 [48.0%] patients with Trifecta bioprostheses) and a non-Trifecta group (550 [52.0%] patients with other bioprostheses). RESULTS: Patients in the Trifecta group were older (69.7 years vs 64.6 years; P = .001), were more likely female (40.4% vs 28.0%; P = .001), more often had aortic stenosis (85.1% vs 77.1%; P = .001), and received smaller valves (23.0 mm vs 25.0 mm; P < .001) than patients in the non-Trifecta group. SVD occurred in 28 patients (Trifecta, n = 22; non-Trifecta, n = 6) within 7 years. Aortic regurgitation or mixed stenosis/regurgitation was observed as the mode of failure in more than 50% of the Trifecta group, whereas none in non-Trifecta group. The cumulative incidence of SVD was higher in the Trifecta group both in the entire cohort (13.3% vs 4.6%; P = .010) and in the younger cohort (age ≤ 65 years; 27.9% vs 6.9%; P = .004), with a notable increase between 5 and 7 years. Multivariable competing risks regression in the Trifecta group revealed younger age (hazard ratio, 0.56 per 10-point decrease; 95% confidence interval, 0.44 to 0.72; P < .001) to be the sole contributor to SVD. CONCLUSIONS: The SVD rate of the Trifecta bioprosthesis has been greater than expected, compared with other bioprostheses, particularly in younger patients. In view of the large number of Trifecta bioprostheses implanted worldwide, further investigation involving other institutions is warranted.

Self-Expanding Transcatheter Aortic Valve Replacement in Patients With Low-Gradient Aortic Stenosis.

OBJECTIVES: The authors sought to compare clinical and hemodynamic outcomes in patients receiving transcatheter aortic valve replacement (TAVR) for low-gradient (LG) aortic stenosis in the CoreValve EUS (Expanded Use Study) versus those with high-gradient (HG) aortic stenosis from the CoreValve U.S. Pivotal Extreme Risk Trial and CAS (Continued Access Study). BACKGROUND: The EUS examined the impact of TAVR in patients unsuitable for surgical aortic valve replacement who were excluded from the U.S. Pivotal Extreme Risk Trial due to LG aortic stenosis. METHODS: EUS patients were stratified by left ventricular ejection fraction: normal (≥50%, LG-normal ejection fraction), and low (<50%, did not respond to dobutamine by generating a mean gradient >40 mm Hg and/or velocity >4.0 m/s, "nonresponders"), and compared with extreme-risk patients from U.S. Pivotal and CAS that had either low resting gradient and responded to dobutamine ("responders"), or a high resting gradient (HG) or velocity. The primary endpoint was all-cause mortality or major stroke at 1 year. Hemodynamics and quality of life are reported at 30 days and 1 year. RESULTS: At 30 days, patients with LG/low left ventricular ejection fraction (nonresponders and responders) had significantly higher rates of all-cause mortality or major stroke, all-cause mortality, and cardiovascular mortality than both HG and LG-normal ejection fraction patients. At 1 year, only the responders had higher rates of these outcomes in comparison to the other 3 groups. Mean gradient and effective orifice area improved significantly in all patients and were maintained through 1 year. New York Heart Association functional classification and Kansas City Cardiomyopathy Questionnaire overall summary scores improved (p < 0.05) in all cohorts through 1 year. When all 4 subgroups were pooled, both decreasing mean gradient and stroke volume index were associated with increased mortality. Pre-procedural mean gradient was the only hemodynamic independent predictor of 1-year mortality by multivariate analysis. CONCLUSIONS: In this study, TAVR provided EUS patients significant hemodynamic relief with both 1-year survival and quality of life outcomes comparable to Pivotal and CAS patients (Safety & Efficacy Study of the Medtronic CoreValve System-Treatment of Symptomatic Severe Aortic Stenosis With Significant Comorbidities in Extreme Risk Subjects Who Need Aortic Valve Replacement, NCT01675440; Safety and Efficacy Study of the Medtronic CoreValve System in the Treatment of Symptomatic Severe Aortic Stenosis in High Risk and Very High Risk Subjects Who Need Aortic Valve Replacement, NCT01240902; Safety and Efficacy Continued Access Study of the Medtronic CoreValve System in the Treatment of Symptomatic Severe Aortic Stenosis in Very High Risk Subjects and High Risk Subjects Who Need Aortic Valve Replacement, NCT01531374).

Use of a constitutively active hypoxia-inducible factor-1alpha transgene as a therapeutic strategy in no-option critical limb ischemia patients: phase I dose-escalation experience.

BACKGROUND: Critical limb ischemia, a manifestation of severe peripheral atherosclerosis and compromised lower-extremity blood flow, results in a high rate of limb loss. We hypothesized that adenoviral delivery of a constitutively active form of the transcription factor hypoxia-inducible factor-1alpha (ie, Ad2/HIF-1alpha/VP16 or HIF-1alpha) into the lower extremity of patients with critical limb ischemia would be safe and might result in a durable clinical response. METHODS AND RESULTS: This phase I dose-escalation program included 2 studies: a randomized, double-blind, placebo-controlled study and an open-label extension study. In total, 34 no-option patients with critical limb ischemia received HIF-1alpha at doses of 1x10(8) to 2x10(11) viral particles. No serious adverse events were attributable to study treatment. Five deaths occurred: 3 in HIF-1alpha and 2 in placebo patients. In the first (randomized) study, 7 of 21 HIF-1alpha patients met treatment failure criteria and had major amputations. Three of the 7 placebo patients rolled over to receive HIF-1alpha in the extension study. No amputations occurred in the 2 highest-dose groups of Ad2/HIF-1alpha/VP16 (1x10(11) and 2x10(11) viral particles). The most common adverse events included peripheral edema, disease progression, and peripheral ischemia. At 1 year, limb status observations in HIF-1alpha patients included complete rest pain resolution in 14 of 32 patients and complete ulcer healing in 5 of 18 patients. CONCLUSIONS: HIF-1alpha therapy in patients with critical limb ischemia was well tolerated, supporting further, larger, randomized efficacy trials.