RATIONALE:Increases in PA pressures and PVR are well-described at altitudes above 2400m. However, the potential hemodynamic implications of changes in altitude at lower elevations (<2000m) remains unexplored. OBJECTIVES:This study assessed hemodynamic changes associated with rising altitude under 2000m. METHODS:We analyzed the association of hemodynamics with altitude in a large cohort using the Veterans Affairs Clinical Assessment, Reporting, and Tracking (VA CART). Association between hemodynamic parameters and altitude was assessed using linear regression modeling, adjusting for age, sex, and body mass index. MEASUREMENTS AND RESULTS:The study included 91,128 patients undergoing RHC at 76 centers at altitudes between 0m-1640m. For every SD increase in altitude (364m), mean PA pressure (0.4 ±0.07 mmHg) and PVR (0.06 ± 0.01 WU) increased. The likelihood of meeting criteria for pulmonary hypertension (PH), specifically pre-capillary PH and combined pre- and post-capillary pulmonary hypertension, increased with altitude. For patients with reduced left ventricular systolic function (EF < 40%), we found that the likelihood of having a PVR >3WU increased with altitude. Patients with EF < 40% at ≥ 1000m elevation were 22% more likely to have a PVR >3 WU than those at < 500m (OR 1.22 95% CI 1.10-1.36; p < 0.001). Pulmonary vascular compliance did not change with altitude, and the pulmonary resistance-compliance relationship was shifted upward and to the right at higher altitude. CONCLUSIONS:Modest increases in altitude (between 0-1640m) are associated with clinically significant alterations in pulmonary artery hemodynamics. Such changes may impact PH diagnosis and classification and eligibility for advanced cardiovascular interventions.

BACKGROUND:Recent studies have questioned whether iodinated contrast is causally related to acute kidney injury (AKI). AIM:We pursed a contemporary analysis to determine the impact of contrast dose on AKI following coronary procedures in an era of lower contrast doses and less nephrotoxic agents. METHODS:This national cohort study examined patients who had percutaneous coronary intervention (PCI) or diagnostic angiography from October 2010 to May 2023. We used logistic regression to test associations between (1) baseline (pre-procedural) AKI risk and contrast dose, and (2) contrast dose and post-procedure AKI. Contrast exposure was quantified as a proportion of the maximal allowable contrast dose (MACD; 2.5 mL × body weight (kg)/serum creatinine). RESULTS:Median contrast volume decreased during our study period for PCI (200 to 150 mL, p < 0.01) and angiography (95 to 60 mL, p < 0.01). In the combined cohort of 175,963 procedures, the mean patient age was 68.5 years; 97.5% were male. Decile plots revealed that patients at higher baseline risk of AKI received lower contrast volumes. When the contrast dose exceeded MACD, there was a stepwise association between contrast dose and adjusted odds of AKI. The highest odds of AKI were observed for patients with eGFR < 30 who received > 200% of the MACD (OR, 2.89; 95% CI, 2.21 to 3.79). CONCLUSIONS:In this large national cohort of patients undergoing coronary procedures, there was a reduction in contrast dose over time and evidence that physicians are reducing contrast volume for high-risk patients. The MACD remains a reasonable target to reduce AKI.

BACKGROUND/AIMS:High-output heart failure (HOHF) is an under-recognised and understudied variant form of cardiac failure characterised by increased cardiac output (CO), low systemic vascular resistance, and higher filling pressures. This study aimed to compare mortality, morbidity, and haemodynamic profiles of patients with HOHF with those of patients with heart failure with preserved ejection fraction (HFpEF). METHOD:Patients diagnosed with HFpEF who underwent invasive haemodynamic assessment in the United States Veterans Affairs (VA) health system between 2007 and 2022 were divided into two groups based on the cardiac index (CI)/output-to-HOHF group and control group, respectively. We compared all-cause mortality, any hospitalisation, heart failure hospitalisations, and a composite outcome including mortality and rehospitalisations (within and outside the VA Health Care System) from the date of right heart catheterisation (RHC) to 1-year post-RHC or end of follow-up. Haemodynamics and clinical characteristics were also compared. RESULTS:A total of 116,229 patients with RHC were screened, and 13,422 were included for analysis. A total of 450 patients had CO ≥8 L/min and CI >4 L/min/m2 (study group); 12,972 had CO <8 L/min or CI ≤4 L/min/m2 (control group). There were no noticeable differences in the described outcomes between groups. Patients who died were older or had a higher prevalence of obstructive lung disease, alcohol abuse, tobacco abuse, atrial fibrillation, or liver disease. CONCLUSIONS:Despite distinct differences in pathophysiology and haemodynamics, our novel study findings suggest that HOHF is not associated with a noticeable difference in morbidity or mortality from that in patients with HFpEF.

Importance:The Department of Veterans Affairs (VA) Maintaining Internal Systems and Strengthening Integrated Outside Networks (MISSION) Act expanded opportunities for veterans to obtain care outside the VA. However, the impact on health care outcomes is uncertain. Objective:To measure the MISSION Act's impact on travel times and outcomes of percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG), and aortic valve replacement (AVR). Design, Setting, and Participants:This retrospective difference-in-differences cohort study included veterans receiving nonemergent/nonurgent PCI, CABG, or AVR between October 2016 and September 2022 in non-VA hospitals under MISSION Act coverage or in VA hospitals in the 48 contiguous US states or the District of Columbia. Analyses were conducted in 2023-2024. Exposures:Veterans eligible for non-VA care under the MISSION Act by living far from ( >60 minutes) the nearest VA medical center vs veterans living near (≤60 minutes) a VA medical center. Main Outcomes and Measures:Major adverse cardiovascular events (MACE), defined as rehospitalization for cardiovascular cause or mortality within 30 days of the procedure, and travel times for care were the primary outcomes. Results:The cohort comprised veterans receiving PCI (n = 43 000; 42 066 [98%] male; mean [SD] age, 69 [8.8] years), CABG (n = 23 301; 22 197 [98%] male; mean [SD] age, 69 [7.7] years), or AVR (n = 14 682; 14 336 [98%] male; mean [SD] age, 74 [9.6] years). After MISSION implementation, mean PCI travel times increased by 1.3 minutes for near patients and decreased by 29.2 minutes for far patients (difference in differences, -30.5 minutes; P < .001). Mean CABG travel times increased by 9.4 minutes for near patients and decreased by 18.1 minutes for far patients (difference in differences, -27.4 minutes; P < .001). Mean travel times for AVR increased by 10.0 minutes for near patients and decreased by 23.0 minutes for far patients (difference in differences, -33.1 minutes; P < .001). After MISSION implementation, mean PCI MACE rates decreased by 0.5 percentage points for near patients and increased by 2.3 percentage points for far patients (difference in differences, 2.8 percentage points; P <.001). Mean CABG MACE rates decreased by 6.5 percentage points for near patients and increased by 1.6 percentage points for far patients (difference in differences, 8.1 percentage points; P < .001). AVR MACE rates were not statistically different between the groups (P = .45). Conclusions and Relevance:MISSION Act implementation was associated with substantial decreases in travel times among veterans who became geographically eligible for non-VA care. For these patients undergoing PCI or CABG, MISSION Act implementation was also associated with worsened 30-day MACE rates.

BACKGROUND:Stroke is a recognized complication following transcatheter aortic valve replacement (TAVR). Although women have historically had a higher rate of bleeding and vascular complications after TAVR, contemporary data on sex differences in post-TAVR stroke and stroke severity are lacking. Disabling strokes significantly affect quality of life and outcomes, underscoring the need to explore sex-specific variations in post-TAVR stroke risk. METHODS:In this retrospective cohort study, we included all patients who underwent TAVR in the National Inpatient Sample from 2016 to 2021. Stroke and stroke severity were ascertained using validated claims-based algorithms. Disabling strokes were defined as those resulting in death or discharge to a nonhome location. We used multivariable logistic regression to evaluate the association between sex and stroke while adjusting for covariates, including cerebral embolic protection use, and accounting for survey weights. RESULTS:Among our weighted sample of 379 410 patients (43.9% female), women demonstrated higher overall in-hospital stroke incidence compared with men (2.31% versus 1.69%; adjusted odds ratio [aOR], 1.208 [95% CI, 1.082-1.350]). This difference was driven primarily by disabling strokes, which were more common in women (1.61% versus 1.01%; aOR, 1.327 [95% CI, 1.158-1.520]). Conversely, the incidence of nondisabling stroke was not statistically different between sexes (0.70% versus 0.67%;( aOR, 1.013 [95% CI, 0.844-1.215]). CONCLUSIONS:Among patients undergoing TAVR in contemporary practice, women had a higher rate of any stroke and disabling strokes compared with men. These findings emphasize the need for tailored strategies to mitigate stroke risk and improve outcomes for female TAVR patients.

BACKGROUND: Intravascular imaging (IVI) is widely recognized to improve outcomes after percutaneous coronary intervention (PCI). However, IVI is underutilized and is not yet established as a performance measure for quality PCI. METHODS: We examined temporal trends of IVI use for all PCIs performed at Veterans Affairs hospitals in the United States from 2010 to 2022 using retrospective observational cohorts. IVI was defined as intravascular ultrasound or optical coherence tomography. A contemporary subset of PCIs from 2020 to 2022 was used to examine clinical characteristics associated with IVI use and test the reliability of IVI as a pass/fail performance measure. We then used a generalized linear mixed model to estimate the proportion of IVI use variability attributable to the hospital, physician, and patient level. Cox proportional hazard models were used to assess the association of IVI with clinical outcomes at 1 year. RESULTS: IVI use increased from 12.3% in 2010 to 43.1% in 2022 in 136 071 PCIs included in the study. Among 22 918 PCIs in the contemporary cohort, IVI was more frequent with nonemergent presentations, chronic total occlusions, and left main lesions but usage variability was primarily attributable to hospital (54%) and physician (33%) levels. As a pass/fail performance measure, reliability was high (>0.96) at hospital and physician levels. However, IVI use was not associated with statistically significant differences in mortality or major adverse cardiovascular events in this cohort. CONCLUSIONS: IVI use for PCI is increasing rapidly at Veterans Affairs hospitals in the United States but with marked variation at the hospital and physician levels. IVI meets established criteria for an effective performance measure and should be measured and reported by local and national organizations to encourage further uptake. Ongoing training and quality improvement may be required to maximize the benefit of IVI as it is more widely utilized.

Importance:Adoption of novel therapeutics often lags for Black versus non-Hispanic White patients. Seminal clinical trials established the cardiovascular efficacy of sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) in patients with type 2 diabetes (T2D) and established atherosclerotic cardiovascular disease. However, it is uncertain whether race influences the evidence-based prescription of these agents. Objective:To determine whether evidence-based prescription of SGLT2i or GLP-1RA differs by Black versus White race in the Veterans Affairs (VA) healthcare system. Design Setting and Participants:Retrospective cohort study of US Veterans with T2D and angiographically confirmed coronary artery disease (CAD) at 84 VA medical centers over the period 2015-2023. Data from the VA Clinical Assessment, Reporting, and Tracking Program were used to construct cohorts eligible for SGLT2i or GLP-1RA treatment based on eligibility criteria for the seminal Empagliflozin, Cardiovascular Outcomes, and Mortality in T2D (EMPA-REG OUTCOME) or the Liraglutide Effect and Action in Diabetes (LEADER) trial, respectively. Multivariable logistic regression estimated adjusted odds of trial-concordant SGLT2i or GLP-1RA prescription by race. Exposures:Self-identified race. Main Outcomes and Measures:SGLT2i or GLP-1RA prescription among those with an evidence-based (trial-concordant) indication. Results:Of 63,561 Veterans with T2D and CAD, 3527 Black and 18,668 White patients met criteria for trial-concordant SGLT2i treatment and 2020 Black and 10,103 White patients for GLP1-RA treatment. Trial-concordant prescription of both classes increased over time for both races but reached only 42 % for SGLT2i and 15 % for GLP1-RA in 2023. Black versus White race was not associated with evidence-based SGLT2i prescription (adjusted odds ratio [OR] 0.96, 95 % CI 0.89-1.04, P = 0.32). However, Black Veterans were less likely than White to be provided with a trial-concordant GLP1-RA prescription (adjusted OR 0.85, 95 % CI 0.74-0.98, P = 0.025). Conclusions and Relevance:Among patients with T2D and CAD in the VA healthcare system, evidence-based SGLT2i and GLP1-RA prescription increased over time, but many eligible patients remained untreated. Although SGLT2i prescription did not differ by race, Black versus White Veterans were less likely to receive evidence-based GLP1-RA prescription. Racial disparities in evidence-based cardiovascular drug prescription exist even in a healthcare system with few economic barriers and may be drug class-specific.

Background In the IMPROVE AKI (A Cluster‐Randomized Trial of Team‐Based Coaching Interventions to Improve Acute Kidney Injury) trial, a combination of team‐based coaching and data‐driven surveillance dashboards reduced the odds of AKI following cardiac catheterization by 46%. The objective of this study was to determine if improvements in AKI outcomes would be sustained after completion of the active intervention. Methods and Results A 2×2 factorial cluster‐randomized trial with an 18‐month active intervention phase (October 2019–March 2021) and an 18‐month sustainability phase (April 2021–September 2022) conducted among cardiac catheterization laboratories in 20 Veterans Affairs sites. Interventions included team‐based coaching in a virtual learning collaborative or technical assistance, with and without access to an automated surveillance reporting dashboard. Data were collected on procedures involving adult patients undergoing diagnostic coronary angiography or percutaneous coronary interventions and not receiving chronic dialysis. The main outcome was AKI within 7 days of cardiac catheterization among all participants and those with preexisting chronic kidney disease. In addition, survey and focused interview data were collected to understand barriers and facilitators to sustaining AKI improvements. In this phase, 440 of 4160 patients experienced AKI, including 216 of 1260 patients with chronic kidney disease. Compared with technical assistance alone, we observed a reduction in AKI among virtual learning collaborative + automated surveillance reporting sites (adjusted odds ratio, 0.60 [95% CI, 0.42–0.86]). Sites had implemented standardized orders (11), oral and intravenous hydration standing orders (13), and contrast limiting protocols (10). Conclusions Team‐based coaching coupled with data‐driven surveillance dashboards reduced AKI by 40% during the 18 months after active participation in the trial. Process improvement education, care process standardization, and automated outcome feedback may be effective and durable methods for reducing AKI. Registration URL: https://clinicaltrials.gov/; Unique Identifier: NCT03556293.

BACKGROUND:Afflicting up to 1% of population, pulmonary hypertension (PH) is commonly associated with cardiopulmonary and metabolic diseases, but the effect of COVID-19 in patients with pre-existing PH remains unclear. METHODS:We conducted a retrospective cohort study in patients who had undergone right-heart-catheterization within the VA Healthcare system and had a subsequent hospital admission with COVID-19 (inpatient cohort, n=1204) or had COVID-19 positivity but not admitted (outpatient cohort, n=6576). Inpatient findings were confirmed in a non-VA validation cohort (n=656) who had undergone echocardiography with subsequent admission. PH was defined invasively as mean pulmonary artery pressure (mPAP) >20 mmHg and non-invasively as estimated right ventricular systolic pressure (RVSP) >30 mmHg. In-hospital outcomes (inpatient cohort) and 1-year mortality (outpatient cohort) were assessed using multivariable logistic or Cox regression adjusting for confounders. RESULTS:Pre-existing PH was independently associated with greater in-hospital mortality (PH using mPAP: adjusted odds ratio [aOR] 1.60, 95%CI: 1.04-2.46; PH using RVSP: aOR 2.12, 95% CI 1.18-3.82). Among outpatients, those with COVID-19 had >8-fold higher 90-day and 2.8 fold higher 91-365 day adjusted hazard of mortality irrespective of PH status. Hazards of 90-day hospitalization were similarly driven by COVID-19. The findings were comparable for patient subgroup with normal pulmonary capillary wedge pressures. CONCLUSION:Pre-existing PH is independently associated with higher in-hospital COVID-19 mortality. In outpatients, COVID-19 positivity was associated with increased mortality over 1 year irrespective of PH status, with highest risk within the first 90 days.

BACKGROUND:Case-based peer review of percutaneous coronary intervention (PCI) is used by many hospitals for quality improvement and to make decisions regarding physician competency. However, there are no studies testing the reliability or validity of peer review for PCI performance evaluation. METHODS:We recruited interventional cardiologists from 12 Veterans Affairs Health System facilities throughout the United States to provide PCI cases for review. Ten reviewers performed blinded reviews such that each case was reviewed twice. Cases were rated on a scale of 1 to 5 (with 5 being the best) for 6 care domains (Appropriateness, Lesion Suitability, Strategy, Technical Performance, Outcome, and Documentation) with a summary performance score calculated as the average of all domains. Separately, reviewers determined whether the standard of care was met. Interobserver reliability of the summary performance score was calculated using interclass correlation coefficient. We examined procedural complications and 30-day mortality and major adverse cardiac events for all PCIs performed by these operators from 2019 to 2022 when stratified in tertiles by summary performance score. RESULTS:Of the 65 cases provided by 13 operators, the mean summary performance score was 3.90 (SD=0.78) out of 5. The interclass correlation coefficient was 0.53, indicating moderate interobserver reliability. For 19 cases (29.2%), 1 reviewer indicated that the performance did not meet the standard of care; however, the second reviewer disagreed in all these cases. Average performance scores ranged from 3.35 to 4.38. Among the 3390 PCIs performed by reviewed cardiologists from 2019 to 2022, the lowest-rated tertile had higher rates of complications (2.9% versus 1.8%, P<0.01) and major adverse cardiac events (10.6% versus 8.0%, P<0.01) compared with the highest-rated tertile. CONCLUSIONS:Case-based peer review identifies variation in physician performance that is correlated with PCI outcomes. However, reviewer disagreements about the standard of care raise concerns about the use of peer review for high-stakes assessments of physician competency.

BACKGROUND:Ineligibility for surgical revascularization is increasingly prevalent and associated with increased mortality after percutaneous coronary intervention (PCI). High-quality, contemporary, multicenter data regarding clinical outcomes after PCI is scarce and poses a barrier to clinical decision-making for surgically ineligible patients. The aim of this study was to describe and compare the clinical characteristics, institutional variation, and longitudinal outcomes of PCI among surgically eligible and ineligible patients in the Veterans Affairs Healthcare System. METHODS:Patients with left main and/or multivessel coronary artery disease undergoing index PCI between October 1, 2017 and September 30, 2022 were identified and the prevalence of surgical ineligibility determined by review of the electronic medical record. The association between surgical ineligibility and mortality and major adverse cardiovascular events (MACE; death, myocardial infarction, repeat revascularization, and stroke) was assessed. RESULTS:A total of 6192 patients with left main and/or multivessel coronary artery disease (842 surgically ineligible and 5350 surgically eligible) underwent PCI during the study period. After adjustment, surgical ineligibility was associated with a significantly decreased time to mortality (time ratio, 0.801 [95% CI, 0.662-0.970]) over a median 1045-day (interquartile range, 583-1600) follow-up period, though not associated with composite MACE (time ratio, 0.859 [95% CI, 0.685-1.078]). After adjustment for target lesion characteristics and procedural complexity, the association between surgical ineligibility and mortality was attenuated (time ratio, 0.842 [95% CI, 0.688-1.030]). CONCLUSIONS:Ineligibility for surgical revascularization was associated with increased risk of long-term mortality after PCI. The risk of adverse outcomes after PCI, however, was similar among surgically eligible and ineligible patients after adjusting for measured comorbidities, coronary anatomic features, and procedural complexity.

Background Limited data exist on noncardiac surgery patients with prior percutaneous coronary intervention (PCI) in the contemporary era. The objective was to examine rate, characteristics, and outcomes of patients who underwent noncardiac surgery within 2 years of PCI and develop a risk model of factors that predict long‐term postoperative outcomes among patients with recent PCI. Methods and Results Patients in the Veterans Affairs Surgical Quality Improvement Program database who underwent noncardiac surgery between October 1, 2017 and September 30, 2021 were included. Patients with versus without PCI within 2 years were propensity matched to examine major adverse cardiovascular events (MACE), defined as a 1‐year composite of mortality, revascularization, and rehospitalization for myocardial infarction or stroke. Among patients with recent PCI, multivariable logistic regression was used to develop a risk model to predict 1‐year postoperative MACE. Among 334 828 patients undergoing surgery, 2297 (0.68%) had PCI within 2 years. Among 9160 propensity‐matched veterans, there was no difference in MACE between patients with and without preceding PCI (hazard ratio [HR], 1.04 [95% CI, 0.96–1.17]). Patients with versus without preceding PCI within 2 years had lower risk of all‐cause death (HR, 0.83 [95% CI, 0.72–0.96]) but higher risk of revascularization (HR, 1.88 [95% CI, 1.50–2.36]) at 1 year. A 13‐component MACE prediction model among patients with recent PCI had moderate discrimination (area under the receiver operating characteristic curve 0.73 derivation, 0.72 validation). Conclusions Among patients who underwent surgery, risk of MACE did not differ, but the risk of revascularization was higher and all‐cause death was lower in patients with versus without recent PCI. A risk model can be used to stratify risk of surgery among patients with preceding PCI.

BACKGROUND:The Veterans Affairs (VA) Healthcare System maintains the largest integrated health system in the United States but also supports fee-for-service insurance for veterans receiving care in community facilities outside the VA. We sought to evaluate the management and outcomes of patients referred for consultation in either venue, using cardiovascular evaluation as a model. METHODS:We conducted a retrospective cohort study identifying patients enrolled in the VA Healthcare System referred for cardiovascular evaluation from October 2020 through September 2024 and stratified the population based on the venue in which evaluation was completed. The primary outcome was major adverse cardiovascular events (acute coronary syndromes/stroke/mortality) in a matched population. RESULTS:Among 235 197 consultations for cardiovascular evaluation, 201 453 were completed in the chosen venue within 6 months. The time between consultation and evaluation was similar across venues (community, 35 days [95% CI, 17-65] versus VA, 33 days [95% CI, 19-53]), with comparable delays to diagnostic testing or therapeutic interventions. Patients receiving care in the community were more likely to undergo stress testing (43.2% versus 36.4%, P=1.5×10-46) and coronary angiography (23.1% versus 17.4%, P=2.1×10-51) within 2 years compared with those treated in the VA Healthcare System. Despite this, patients treated in the community had a significantly higher rate of major adverse events at 2 years (17.6% versus 15.3%, P=5.9×10-10) compared with those treated in the VA Healthcare System. CONCLUSIONS:Patients undergoing cardiovascular evaluation in community practices were not evaluated more rapidly than those seen in the VA, though they were more likely to receive initial and repeat diagnostic testing. Adverse events were more common among community-treated patients than those in the VA, suggesting an opportunity to optimize access to care while improving clinical outcomes.

OBJECTIVE:Documentation of myocardial ischemia prior to invasive coronary angiography is recommended to minimize patient risk. However, obtaining this information for quality-of-care assessment often requires extracting clinical information from unstructured electronic medical records text. To this end, we sought to evaluate multiple natural language processing (NLP) systems in their ability to classify cardiac stress test reports as documenting ischemia or no ischemia, implementing the one with the best combination of accuracy and feasibility. RESULTS:Four BERT large language models (LLMs) were fine-tuned, and a rules-based system was designed by training, validating, and testing on an annotated sample of 654 stress test reports from a multisite and multiyear dataset from the Veterans Health Administration (VHA). The LLM with the highest performance was a ClinicalBERT with precision, recall, and F1 of 86.4%, 100%, and 92.7%, respectively. The rules-based NLP system achieved similar results of 88.1%, 97.4%, and 92.5%, respectively. Stress test reports totaling 1,692,171 and representing 1,096,341 unique patients were classified using the rules-based system after ascertaining current technological limitations, and the system is presently operational for care quality evaluations. Utilizing NLP allows for accurate, high-throughput analysis of cardiac stress test text reports.

he long-term impact of beta-blocker use after myocardial infarction (MI) is unknown. Although there are robust data supporting post-MI beta-blocker use in the prere perfusion era and in the setting of reduced left ventricular ejection fraction (LVEF), data on long-term beta-blocker use among contemporary populations or those with preserved LVEF are conflicting. The REDUCE-A MI (Randomized Evaluation of Decreased Usage of trial showed no benefit of long-term beta-blocker use among patients with MI with preserved LVEF.1 In contrast, interruption of beta-blocker use among patients with prior MI was not noninferior to continuation in the ABYSS (Assessment of Beta patients in the interruption group having greater

To efficiently distribute blood flow to cardiac muscle, the coronary artery tree must follow a specific branching pattern over the heart. How this pattern arises in humans is unknown due to the limitations of studying human heart development. Here, we leveraged a natural variation of coronary artery anatomy, known as coronary dominance, in genetic association studies to identify the first known driver of human coronary developmental patterning. Coronary dominance refers to whether the right, left, or both coronary arteries branch over the posterior left ventricle, but whether this variability is heritable and how it would be genetically regulated was completely unknown. By conducting the first large-scale, multi-ancestry genome-wide association study (GWAS) of coronary dominance in 61,043 participants of the VA Million Veteran Program, we observed moderate heritability (27.7%) with ten loci reaching genome wide significance. An exceptionally strong association mapped DNA variants to a non-coding region near the chemokine CXCL12 in both European and African ancestries, which overlapped with variants associated with coronary artery disease. Genomic analyses predicted these variants to impact CXCL12 levels, and imaging revealed dominance to develop during fetal life coincident with CXCL12 expression. Reducing Cxcl12 in mice to model the human genetics altered septal artery dominance patterns and caused coronary branches to develop away from Cxcl12 expression domains. Cxcl12 heterozygosity did not compromise overall artery coverage as seen with full deletion, but instead changed artery patterning, reminiscent of the human scenario. Together, our data support CXCL12 as a critical determinant of human coronary artery growth and patterning and lay a foundation for the utilization of developmental pathways to guide future precision 'medical revascularization' therapeutics.