Economic Considerations in Access to Transcatheter Aortic Valve Replacement

Transcatheter aortic valve replacement (TAVR) has revolutionized the treatment of aortic stenosis, with the number of procedures and sites offering the procedure steadily rising over the past decade in the United States. Despite this, growth into certain markets has been limited as hospitals have to balance high TAVR costs with the ability to offer a complete array of state-of-the-art therapies for aortic stenosis. This trade-off often results in decreased access to TAVR services by patients cared for in hospitals that cannot afford these services or have difficulty meeting procedural requirements, recruiting skilled physicians, and initiating and then maintaining a functioning TAVR program. The lack of access is more common among patients of color or those who are socioeconomically disadvantaged. The purpose of this review is to describe the hospital-level economic considerations of TAVR in the United States and the resulting effects on geographic, racial, ethnic, and socioeconomic access for Americans.

Safety and Efficacy of Drug-Coated Balloons Versus Drug-Eluting Stents in Acute Coronary Syndromes: A Prespecified Analysis of BASKET-SMALL 2

Background: Drug-coated balloons (DCBs) are an established treatment strategy for coronary artery disease. Randomized data on the application of DCBs in patients with an acute coronary syndrome (ACS) are limited. We evaluated the impact of clinical presentation (ACS versus chronic coronary syndrome) on clinical outcomes in patients undergoing DCB or drug-eluting stent (DES) treatment in a prespecified analysis of the BASKET-SMALL 2 trial (Basel Kosten Effektivitäts Trial–Drug-Coated Balloons Versus Drug-Eluting Stents in Small Vessel Interventions). Methods: BASKET-SMALL 2 randomized 758 patients with small vessel coronary artery disease to DCB or DES treatment and followed them for 3 years regarding major adverse cardiac events (cardiac death, nonfatal myocardial infarction, and target vessel revascularization). Results: Among 758 patients, 214 patients (28.2%) presented with an ACS (15 patients [7%], ST-segment–elevation myocardial infarction; 109 patients [50.9%], non–ST-segment–elevation myocardial infarction; 90 patients [42.1%], unstable angina pectoris). At 1-year follow-up, there was no significant difference in the incidence of the primary end point by randomized treatment in patients with ACS (hazard ratio, 0.50 [95% CI, 0.19–1.26] for DCB versus DES) or chronic coronary syndrome (hazard ratio, 1.29 [95% CI, 0.67–2.47] for DCB versus DES). There was no significant interaction between clinical presentation and treatment effect ( P for interaction, 0.088). For cardiac death ( P for interaction, 0.049) and nonfatal myocardial infarction ( P for interaction, 0.010), a significant interaction between clinical presentation and treatment was seen at 1 year with lower rates of these secondary end points in patients with ACS treated by DCB. At 3 years, there were similar major adverse cardiac event rates throughout groups without significant interaction between clinical presentation and treatment ( P for interaction, 0.301). All-cause mortality was higher in ACS compared with chronic coronary syndrome; however, there was no difference between DCB and DES irrespective of clinical presentation. Conclusions: In this subgroup analysis of the BASKET-SMALL 2 trial, there was no interaction between indication for percutaneous coronary intervention (acute versus chronic coronary syndrome) and treatment effect of DCB versus DES in patients with small vessel coronary artery disease. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01574534.

Comparison of Intracoronary Epinephrine and Adenosine for No-Reflow in Normotensive Patients With Acute Coronary Syndrome (COAR Trial)

Background: Intracoronary epinephrine has been effectively used in treating refractory no-reflow, but there is a dearth of data on its use as a first-line drug in normotensive patients in comparison to the widely used adenosine. Methods: In this open-labeled randomized clinical trial, 201 patients with no-reflow were randomized 1:1 into intracoronary epinephrine as the treatment group and intracoronary adenosine as the control group and followed for 1 month. The primary end points were improvement in coronary flow, as assessed by TIMI (Thrombolysis in Myocardial Infarction) flow, frame counts, and myocardial blush. Secondary end points were in-hospital and short-term mortality and major adverse cardiac events. Results: In all, 101 patients received intracoronary epinephrine and 100 patients received adenosine. Epinephrine was generally well tolerated with no immediate table death or ventricular fibrillation. No-reflow was more effectively improved with epinephrine with final TIMI III flow (90.1% versus 78%, P =0.019) and final corrected TIMI frame count (24±8.43 versus 26.63±9.22, P =0.036). However, no significant difference was observed in final grade III myocardial blush (55.4% versus 45%, P =0.139), mean reduction of corrected TIMI frame count (−25.71±11.79 versus −26.08±11.71, P =0.825), in-hospital and short-term mortality, and major adverse cardiac events. Conclusions: Epinephrine is relatively safe to use in no-reflow in normotensive patients. A significantly higher frequency of post-treatment TIMI III flow grade and lower final corrected TIMI frame count with relatively better achievement of myocardial blush grade III translate into it displaying relatively better efficacy than adenosine. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04699110.

Patient-Reported Outcome Measures in Symptomatic, Non–Limb-Threatening Peripheral Artery Disease: A State-of-the-Art Review

Patient-reported outcome measures (PROMs) are health outcomes directly reported by the patient that can be used to measure the effect of disease and treatments on patient perceived well-being. This review summarizes current evidence regarding the validation of PROMs in people with symptomatic, nonlimb-threatening peripheral artery disease. A literature search was conducted to identify studies of symptomatic peripheral artery disease without limb-threatening ischemia that included PROMs and had sample sizes ≥25. PROMs were summarized along a continuum of validation using classical test theory framework and according to whether they fulfilled defined criteria for (1) content validity; (2) psychometric validation; and (3) further validation evidence base expansion. Of 2198 articles identified, 157 (7.1%) met inclusion criteria. Twenty-four PROMs in patients with symptomatic peripheral artery disease were reviewed. Among disease-specific PROMs, 8 of 15 had excellent reliability as measured by a Cronbach alpha ≥0.80. Based on established criteria for PROM responsiveness, 6 of 15 disease-specific PROMs demonstrated excellent sensitivity to change. Of these, the disease-specific peripheral artery questionnaire, vascular quality of life questionnaire, and walking impairment questionnaire met criteria for validation at each stage of the continuum. For generic (nondisease specific) PROMs, the European Quality of Life 5-Dimension and SF-36 had the most extensive evidence of validation. Evidence from this review can inform selection of PROMs aligned with scientific and clinical goals, given the variable degree of validation and potential complementary nature of the measures.

Percutaneous Coronary Intervention Following Diagnostic Angiography by Noninterventional Versus Interventional Cardiologists: Insights From the CathPCI Registry

Background: There are limited contemporary, national data describing diagnostic cardiac catheterization with subsequent percutaneous coronary intervention (ad hoc percutaneous coronary intervention [PCI]) performed by an invasive-diagnostic and interventional (Dx/IC) operator team versus solo interventional operator (solo-IC). Using the CathPCI Registry, this study aimed at analyzing trends and outcomes in ad hoc PCI among Dx/IC versus solo-IC operators. Methods: Quarterly rates (January 2012 to March 2018) of ad hoc PCI cases by Dx/IC and solo-IC operators were obtained. Odds of inhospital major adverse cardiovascular events, net adverse cardiovascular events (ie, composite major adverse cardiovascular event+bleeding), and rarely appropriate PCI were estimated using multivariable regression. Results: From 1077 sites, 1 262 948 patients were included. The number of invasive-diagnostic operators and cases performed by Dx/IC teams decreased from nearly 9% to 5% during the study period. Patients treated by Dx/IC teams were more often White and had fewer comorbidities compared with patients treated by solo-IC operators. Considerable variation existed across sites, and over two-fifths of sites had 0% ad hoc PCI performed by Dx/IC. In adjusted analyses, ad hoc performed by Dx/IC had similar risks of major adverse cardiovascular event (OR, 1.04 [95% CI, 0.97–1.11]) and net adverse cardiovascular events (OR, 0.98 [95% CI, 0.94–1.03]) compared with solo-IC. Rarely appropriate PCI, although low overall (2.1% versus 1.9%) occurred more often by Dx/IC compared with solo-IC (OR, 1.20 [95% CI, 1.13–1.26]). Conclusions: Contemporary, nationwide data from the CathPCI Registry demonstrates the number of Dx/IC operator teams and cases has decreased but that case volume is stable among operators. Outcomes were independent of operator type, which supports current practice patterns. The finding of a higher risk of rarely appropriate PCI in Dx/IC teams should be further studied.

Long-Term Outcomes After Melody Transcatheter Pulmonary Valve Replacement in the US Investigational Device Exemption Trial

Background: The Melody valve was developed to extend the useful life of previously implanted right ventricular outflow tract (RVOT) conduits or bioprosthetic pulmonary valves, while preserving RV function and reducing the lifetime burden of surgery for patients with complex congenital heart disease. Methods: Enrollment for the US Investigational Device Exemption study of the Melody valve began in 2007. Extended follow-up was completed in 2020. The primary outcome was freedom from transcatheter pulmonary valve (TPV) dysfunction (freedom from reoperation, reintervention, moderate or severe pulmonary regurgitation, and/or mean RVOT gradient >40 mm Hg). Secondary end points included stent fracture, catheter reintervention, surgical conduit replacement, and death. Results: One hundred seventy-one subjects with RVOT conduit or bioprosthetic pulmonary valve dysfunction were enrolled. One hundred fifty underwent Melody TPV replacement. Median age was 19 years (Q1–Q3: 15–26). Median discharge mean RVOT Doppler gradient was 17 mm Hg (Q1–Q3: 12–22). The 149 patients implanted >24 hours were followed for a median of 8.4 years (Q1–Q3: 5.4–10.1). At 10 years, estimated freedom from mortality was 90%, from reoperation 79%, and from any reintervention 60%. Ten-year freedom from TPV dysfunction was 53% and was significantly shorter in children than in adults. Estimated freedom from TPV-related endocarditis was 81% at 10 years (95% CI, 69%–89%), with an annualized rate of 2.0% per patient-year. Conclusions: Ten-year outcomes from the Melody Investigational Device Exemption trial affirm the benefits of Melody TPV replacement in the lifetime management of patients with RVOT conduits and bioprosthetic pulmonary valves by providing sustained symptomatic and hemodynamic improvement in the majority of patients. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT00740870.

Racial Disparities in Invasive Management for Patients With Acute Myocardial Infarction With Chronic Kidney Disease

Background: Due to increased risks of contrast nephropathy, chronic kidney disease (CKD) can deter consideration of invasive management for patients with myocardial infarction (MI). Black patients have a higher prevalence of CKD. Whether racial disparities exist in the use of invasive MI management for patients with CKD presenting with MI is unknown. Methods: We examined 717 012 White and 99 882 Black patients with MI treated from 2008 to 2017 at 914 hospitals in the National Cardiovascular Data Registry Chest Pain—MI Registry. CKD status was defined as estimated glomerular filtration rate (eGFR) ≥90 mL/(min·1.73 m 2 ; no CKD), eGFR <90 but ≥60 (mild), eGFR <60 but ≥30 (moderate), and eGFR <30 or dialysis (severe). We used multivariable logistic regression models to examine the interaction of race and CKD severity in invasive MI management. Results: Among those with MI, Black patients were more likely than White patients to have CKD (eGFR <90; 61.4% versus 58.5%; P <0.001). Among those with MI and CKD, Black patients were more likely than White patients to have severe CKD (21.2% versus 12.4%; P <0.001). Patients with CKD were more likely than those without CKD to have diabetes or heart failure; Black patients with CKD were more likely to have these comorbidities when compared with White patients with CKD (all P <0.0001). Black race and CKD were associated with a lower likelihood of invasive management (adjusted odds ratio, 0.78 [95% CI, 0.75–0.81]; adjusted odds ratio, 0.72 [95% CI, 0.70–0.74]; P <0.001 for both). At eGFR levels ≥10, Black patients were significantly less likely than White patients to undergo invasive management. Conclusions: Black patients with MI and mild or moderate CKD were less likely to undergo invasive management compared with White patients with similar CKD severity. National efforts are needed to address racial disparities that may remain in the invasive management of MI.

Ischemic Events Occur Early in Patients Undergoing Percutaneous Coronary Intervention and Are Reduced With Cangrelor: Findings From CHAMPION PHOENIX

Background: Thrombotic events are reduced with cangrelor, an intravenous P2Y 12 inhibitor. We sought to characterize the timing, number, and type of early events (within 2 hours of randomization) in CHAMPION PHOENIX (A Clinical Trial Comparing Cangrelor to Clopidogrel Standard of Care Therapy in Subjects Who Require Percutaneous Coronary Intervention). Methods: CHAMPION PHOENIX was a double-blind, placebo-controlled trial that randomized patients undergoing percutaneous coronary intervention to cangrelor or clopidogrel. For this analysis, we evaluated the efficacy of cangrelor in the first 2 hours postrandomization with regards to the primary end point (death, myocardial infarction, ischemia-driven revascularization, or stent thrombosis). Sensitivity analyses were performed evaluating a secondary, post hoc end point (death, Society of Coronary Angiography and Intervention myocardial infarction, ischemia-driven revascularization, or Academic Research Consortium definite stent thrombosis). Results: The majority of events (63%) that occurred in the trial occurred within 2 hours of randomization. The most common early event was myocardial infarction; next were stent thrombosis, ischemia driven revascularization, and death. In the first 2 hours after randomization, cangrelor significantly decreased the primary composite end point compared with clopidogrel (4.1% versus 5.4%; hazard ratio, 0.76 [95% CI, 0.64–0.90], P =0.002). Similar findings were seen for the composite end point of death, Society of Coronary Angiography and Intervention myocardial infarction, ischemia-driven revascularization, or Academic Research Consortium stent thrombosis at 2 hours (0.9% versus 1.6%; hazard ratio, 0.57 [95% CI, 0.40–0.80], P =0.001). Between 2 and 48 hours, there was no difference in the primary composite end point (0.6% versus 0.5%; odds ratio, 1.17 [95% CI, 0.71–1.93]; P =0.53). Early (≤2 hours of randomization) GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) moderate or severe bleeding events were infrequent, and there was no significant difference with cangrelor compared with clopidogrel (0.2% [n=10] versus 0.1% [n=4]; adjusted odds ratio, 1.41 [95% CI, 0.37–5.40]; P =0.62). Conclusions: The reductions in ischemic events and overall efficacy seen with cangrelor in CHAMPION PHOENIX occurred early and during the period of time in which patients were being actively treated with cangrelor. These findings provide evidence that supports the importance of potent platelet inhibition during percutaneous coronary intervention. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01156571.