DACH1 stimulates shear stress-guided endothelial cell migration and coronary artery growth through the CXCL12-CXCR4 signaling axis.

Sufficient blood flow to tissues relies on arterial blood vessels, but the mechanisms regulating their development are poorly understood. Many arteries, including coronary arteries of the heart, form through remodeling of an immature vascular plexus in a process triggered and shaped by blood flow. However, little is known about how cues from fluid shear stress are translated into responses that pattern artery development. Here, we show that mice lacking endothelial Dach1 had small coronary arteries, decreased endothelial cell polarization, and reduced expression of the chemokine Cxcl12 Under shear stress in culture, Dach1 overexpression stimulated endothelial cell polarization and migration against flow, which was reversed upon CXCL12/CXCR4 inhibition. In vivo, DACH1 was expressed during early arteriogenesis but was down in mature arteries. Mature artery-type shear stress (high, uniform laminar) specifically down-regulated DACH1, while the remodeling artery-type flow (low, variable) maintained DACH1 expression. Together, our data support a model in which DACH1 stimulates coronary artery growth by activating Cxcl12 expression and endothelial cell migration against blood flow into developing arteries. This activity is suppressed once arteries reach a mature morphology and acquire high, laminar flow that down-regulates DACH1. Thus, we identified a mechanism by which blood flow quality balances artery growth and maturation.

Altered Cardiac Energetics and Mitochondrial Dysfunction in Hypertrophic Cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a complex disease partly explained by the effects of individual gene variants on sarcomeric protein biomechanics. At the cellular level, HCM mutations most commonly enhance force production, leading to higher energy demands. Despite significant advances in elucidating sarcomeric structure-function relationships, there is still much to be learned about the mechanisms that link altered cardiac energetics to HCM phenotypes. In this work, we test the hypothesis that changes in cardiac energetics represent a common pathophysiologic pathway in HCM. METHODS: We performed a comprehensive multiomics profile of the molecular (transcripts, metabolites, and complex lipids), ultrastructural, and functional components of HCM energetics using myocardial samples from 27 HCM patients and 13 normal controls (donor hearts). RESULTS: Integrated omics analysis revealed alterations in a wide array of biochemical pathways with major dysregulation in fatty acid metabolism, reduction of acylcarnitines, and accumulation of free fatty acids. HCM hearts showed evidence of global energetic decompensation manifested by a decrease in high energy phosphate metabolites (ATP, ADP, and phosphocreatine) and a reduction in mitochondrial genes involved in creatine kinase and ATP synthesis. Accompanying these metabolic derangements, electron microscopy showed an increased fraction of severely damaged mitochondria with reduced cristae density, coinciding with reduced citrate synthase activity and mitochondrial oxidative respiration. These mitochondrial abnormalities were associated with elevated reactive oxygen species and reduced antioxidant defenses. However, despite significant mitochondrial injury, HCM hearts failed to upregulate mitophagic clearance. CONCLUSIONS: Overall, our findings suggest that perturbed metabolic signaling and mitochondrial dysfunction are common pathogenic mechanisms in patients with HCM. These results highlight potential new drug targets for attenuation of the clinical disease through improving metabolic function and reducing mitochondrial injury.

miR-106a-363 cluster in extracellular vesicles promotes endogenous myocardial repair via Notch3 pathway in ischemic heart injury.

Endogenous capability of the post-mitotic human heart holds great promise to restore the injured myocardium. Recent evidence indicates that the extracellular vesicles (EVs) regulate cardiac homeostasis and regeneration. Here, we investigated the molecular mechanism of EVs for self-repair. We isolated EVs from human iPSC-derived cardiomyocytes (iCMs), which were exposed to hypoxic (hEVs) and normoxic conditions (nEVs), and examined their roles in in vitro and in vivo models of cardiac injury. hEV treatment significantly improved the viability of hypoxic iCMs in vitro and cardiac function of severely injured murine myocardium in vivo. Microarray analysis of the EVs revealed significantly enriched expression of the miR-106a-363 cluster (miR cluster) in hEVs vs. nEVs. This miR cluster preserved survival and contractility of hypoxia-injured iCMs and maintained murine left-ventricular (LV) chamber size, improved LV ejection fraction, and reduced myocardial fibrosis of the injured myocardium. RNA-Seq analysis identified Jag1-Notch3-Hes1 as a target intracellular pathway of the miR cluster. Moreover, the study found that the cell cycle activator and cytokinesis genes were significantly up-regulated in the iCMs treated with miR cluster and Notch3 siRNA. Together, these results suggested that the miR cluster in the EVs stimulated cardiomyocyte cell cycle re-entry by repressing Notch3 to induce cell proliferation and augment myocardial self-repair. The miR cluster may represent an effective therapeutic approach for ischemic cardiomyopathy.

STratification risk analysis in OPerative management (STOP score) for drug-induced endocarditis.

BACKGROUND: The opioid epidemic has seen a drastic increase in the incidence of drug-associated infective endocarditis (IE). No clinical tool exists to predict operative morbidity and mortality in patients undergoing surgery. METHODS: A multi-institutional database was reviewed between 2011 and 2018. Multivariate logistic regression was fitted in an automated stepwise fashion. The STratification risk analysis in OPerative management of drug-associated IE (STOP) score was constructed. Morbidity was defined as reintubation, prolonged ventilation, pneumonia, renal failure, dialysis, stroke, reoperation for bleeding, and a permanent pacemaker. Cross-validation provided an unbiased estimate of out-of-sample performance. RESULTS: A total of 1181 patients underwent surgery for drug-associated IE (median age, 39; interquartile range [IQR], 30-54, 386 women [32.7%], 341 reoperations for prosthetic valve endocarditis [28.9%], 316 patients with multivalve disease [26.8%]). Operative morbidity and mortality were 41.1% and 5.9%, respectively. Predictors of morbidity were dialysis (95% confidence interval [CI], 1.16-2.82), emergent intervention (1.83-4.73), multivalve procedure (1.01-1.98), causative organisms other than Streptococcus (1.09-2.02), and type of valve procedure performed [aortic valve procedure (1.07-2.15), mitral valve replacement (1.03-2.05), tricuspid valve replacement (1.21-2.60)]. Predictors of mortality were dialysis (1.29-5.74), active endocarditis (1.32-83), lung disease (1.25-5.43), emergent intervention (1.69-6.60), prosthetic valve endocarditis (1.24-3.69), aortic valve procedure (1.49-5.92) and multivalve disease (1.00-2.95). Variables maximizing explanatory power were translated into a scoring system. Each point increased odds of morbidity and mortality by 22.0% and 22.4% with an accuracy of 94.0% and 94.1%, respectively. CONCLUSION: Drug-related IE is associated with significant morbidity and mortality. An easily-applied risk stratification score may aid in clinical decision-making.

Rationale and design of the Fractional Flow Reserve versus Angiography for Multivessel Evaluation (FAME) 3 Trial: a comparison of fractional flow reserve-guided percutaneous coronary intervention and coronary artery bypass graft surgery in patients with multivessel coronary artery disease.

UNLABELLED: Guidelines recommend coronary artery bypass graft (CABG) surgery over percutaneous coronary intervention (PCI) for the treatment of 3-vessel coronary artery disease (3-VD). The inferior results of PCI demonstrated by previous large randomized trials comparing PCI and CABG might be explained by the use of suboptimal stent technology and by the lack of fractional flow reserve (FFR) guidance of PCI. TRIAL DESIGN: The objective of this investigator-initiated, multicenter, randomized clinical trial is to investigate whether FFR-guided PCI with new-generation stents is noninferior to CABG in patients with 3-VD, not including the left main coronary artery. Eligible patients must have ≥50% coronary stenoses in all 3 major epicardial vessels or major side branches. Patients with a nondominant right coronary artery may be included only if the left anterior descending artery and left circumflex have ≥50% stenoses. Consecutive patients who meet all of the inclusion criteria and none of the exclusion criteria will be randomized in a 1:1 fashion to either CABG or FFR-guided PCI. Coronary artery bypass graft will be performed based on the angiogram as per clinical routine. Patients assigned to FFR-guided PCI will have FFR measured in each diseased vessel and only undergo stenting if the FFR is ≤0.80. The primary end point of the study is a composite of major adverse cardiac and cerebrovascular events, including death, myocardial infarction, repeat coronary revascularization, and stroke at 1 year. Key secondary end point will be a composite of death, myocardial infarction, and stroke at 3-year follow-up. Other secondary end points include the individual adverse events, cost-effectiveness, and quality of life at 2-year, 3-year, with up to 5-year follow-up. CONCLUSION: The FAME 3 study will compare in a multicenter, randomized fashion FFR-guided PCI with contemporary drug-eluting stents to CABG in patients with 3-VD.

Model analysis of secondary organic aerosol formation by glyoxal in laboratory studies: the case for photoenhanced chemistry.

The reactive uptake of glyoxal by atmospheric aerosols is believed to be a significant source of secondary organic aerosol (SOA). Several recent laboratory studies have been performed with the goal of characterizing this process, but questions remain regarding the effects of photochemistry on SOA growth. We applied GAMMA (McNeill et al. Environ. Sci. Technol. 2012, 46, 8075-8081), a photochemical box model with coupled gas-phase and detailed aqueous aerosol-phase chemistry, to simulate aerosol chamber studies of SOA formation by the uptake of glyoxal by wet aerosol under dark and irradiated conditions (Kroll et al. J. Geophys. Res. 2005, 110 (D23), 1-10; Volkamer et al. Atmos. Chem. Phys. 2009, 9, 1907-1928; Galloway et al. Atmos. Chem. Phys. 2009, 9, 3331- 306 3345 and Geophys. Res. Lett. 2011, 38, L17811). We find close agreement between simulated SOA growth and the results of experiments conducted under dark conditions using values of the effective Henry's Law constant of 1.3-5.5 × 10(7) M atm(-1). While irradiated conditions led to the production of some organic acids, organosulfates, and other oxidation products via well-established photochemical mechanisms, these additional product species contribute negligible aerosol mass compared to the dark uptake of glyoxal. Simulated results for irradiated experiments therefore fell short of the reported SOA mass yield by up to 92%. This suggests a significant light-dependent SOA formation mechanism that is not currently accounted for by known bulk photochemistry, consistent with recent laboratory observations of SOA production via photosensitizer chemistry.

"At the End I Have a Say": Engaging the Chinese Community in Advance Care Planning.

CONTEXT: Despite the association of advance care planning (ACP) with improved patient and caregiver outcomes, Chinese American elders have low rates of ACP. OBJECTIVES: Assess ACP facilitators/barriers in the San Francisco (SF) Chinese community and codesign, implement, and test community-based ACP-promoting pilot events. METHODS: A Chinese Community Committee (N = 19 community-based organization leaders, health system representatives, community members) conducted focus groups in Cantonese and English with Chinese older adults (age ≥55), caregivers, and community leaders. The Committee designed and implemented pilot events in-person and online. We analyzed focus group data using thematic analysis; assessed pre-to-post-event readiness to engage in ACP (validated survey; 14 scale, 4 = most ready); and assessed event acceptability. RESULTS: A total of 34 people participated in six focus groups. Themes described Chinese community-specific importance of ACP (e.g., reduces family burden), barriers (e.g., younger generations lack tools to discuss ACP with elders and vice versa), and facilitators (e.g., intergenerational events, culturally/linguistically appropriate materials). Based on focus groups findings, the Committee developed a novel ACP tool and designed intergenerational events. A total of 195 participants attended 10 events; 95% were Chinese, 90% spoke Chinese languages, 80% were women. ACP readiness increased significantly (1.66 [SD 0.84] vs. 2.03 [SD 0.85]; P < 0.001); 94% of participants were comfortable attending and 96% would recommend events. CONCLUSION: Community-developed intergenerational events that highlight the value of ACP and address barriers are acceptable and increase ACP engagement in the Chinese community.

Aqueous-phase secondary organic aerosol and organosulfate formation in atmospheric aerosols: a modeling study.

We have examined aqueous-phase secondary organic aerosol (SOA) and organosulfate (OS) formation in atmospheric aerosols using a photochemical box model with coupled gas-phase chemistry and detailed aqueous aerosol chemistry. SOA formation in deliquesced ammonium sulfate aerosol is highest under low-NO(x) conditions, with acidic aerosol (pH = 1) and low ambient relative humidity (40%). Under these conditions, with an initial sulfate loading of 4.0 µg m(-3), 0.9 µg m(-3) SOA is predicted after 12 h. Low-NO(x) aqueous-aerosol SOA (aaSOA) and OS formation is dominated by isoprene-derived epoxydiol (IEPOX) pathways; 69% or more of aaSOA is composed of IEPOX, 2-methyltetrol, and 2-methyltetrol sulfate ester. 2-Methyltetrol sulfate ester comprises >99% of OS mass (66 ng m(-3) at 40% RH and pH 1). In urban (high-NO(x)) environments, aaSOA is primarily formed via reversible glyoxal uptake, with 0.12 µg m(-3) formed after 12 h at 80% RH, with 20 µg m(-3) initial sulfate. OS formation under all conditions studied is maximum at low pH and lower relative humidities (<60% RH), i.e., when the aerosol is more concentrated. Therefore, OS species are expected to be good tracer compounds for aqueous aerosol-phase chemistry (vs cloudwater processing).

Impact of thoracotomy approach on right ventricular failure and length of stay in left ventricular assist device implants: an intermacs registry analysis.

INTRODUCTION: Traditionally, implantation of Left Ventricular Assist Devices (LVADs) is performed via median sternotomy. Recently, less invasive thoracotomy approaches are growing in popularity as they involve less surgical trauma, potentially less bleeding, and may preserve right ventricular function. We hypothesized implantation of LVADs via thoracotomy has less perioperative right ventricular failure (RVF) and shorter postoperative length of stay (LOS). METHODS: Continuous flow LVAD implants from Intermacs between February 6, 2014 - December 31, 2018 were identified. Patients implanted via thoracotomy were propensity matched in a 1:1 ratio with patients implanted via sternotomy. Outcomes were compared between sternotomy and thoracotomy approach and by device type (axial, centrifugal-flow with hybrid levitation (CF-HL), centrifugal-flow with full magnetic levitation devices (CF-FML)). The primary outcome was time to first moderate or severe RVF. Secondary outcomes included survival and LOS. RESULTS: Overall 978 thoracotomy patients were matched with 978 sternotomy patients. Over the study period, 242 thoracotomy patients and 219 sternotomy patients developed RVF with no significant difference in time to first moderate to severe RVF by surgical approach overall (p = 0.27) or within CF-HL (p = 0.36) or CF-FML devices (p = 0.25). Survival did not differ by implant technique (150 deaths in thoracotomy group, 154 deaths in sternotomy group; p = 0.58). However, sternotomy approach was associated with a significantly shorter LOS (17 Vs 18 days, p = 0.009). CONCLUSION: As compared to sternotomy, implantation of continuous flow LVADs via thoracotomy approach does not reduce moderate to severe RVF or improve survival but does reduce post-operative LOS. Device type did not influence outcomes and most centers did a small volume of thoracotomy implants.

Risk of reoperative valve surgery for endocarditis associated with drug use.

BACKGROUND: We aimed to quantify incidence and operative risks associated with reoperative valve surgeries (RVS) in patients with drug-associated infective endocarditis in a multi-center setting. METHODS: We formed a registry of patients with drug-associated infective endocarditis who underwent valve surgeries at 8 US centers between 2011 and 2017. Outcomes of first-time valve surgery (FVS) and RVS were compared. Multivariable logistic regression models related RVS to 30-day mortality. Poisson regression models were fitted to evaluate temporal trends in overall case volume and proportions of patients undergoing RVS. RESULTS: The cohort consisted of 925 patients with drug-associated infective endocarditis who underwent a valve surgery, of which 652 were FVS and 273 were RVS. Patients undergoing FVS had fewer comorbidities than those undergoing RVS. Overall case volume increased from 108 in 2012 to 229 cases in 2017 (P < .001). The proportion of redo valve cases increased from 19% in 2012 to 28% in 2017 (P < .001). The 30-day mortality in RVS was higher compared with FVS (8.1% vs 4.8%; P = .049). An increase in unadjusted mortality rates were observed as the number of prior cardiac surgeries increased, from 4.8% in FVS to 11.8% in ≥3 RVS. Multivariable model demonstrated that RVS was associated with an increased risk of 30-day mortality (odds ratio, 2.22; 95% confidence interval, 1.22-4.06; P = .010). CONCLUSIONS: An increasing proportion of valve surgery for drug-associated infective endocarditis is for RVS. Despite being young and harboring few comorbidities, the RVS cohort is still susceptible to increased risk of 30-day mortality compared with those undergoing FVS.

Mode-specific study of nanoparticle-mediated optical interactions in an absorber/metal thin film system.

We present an experimental and theoretical study of the electromagnetic interaction between a single gold nanoparticle and a thin gold substrate separated by a sub-50 nm-thick optically absorptive polythiophene spacer layer. Single-particle dark-field scattering spectra show distinct resonance features assigned to four different modes: a horizontal image dipole coupling mode, a vertical image dipole coupling mode and horizontal and vertical coupling modes between localized surface plasmon resonances (LSPRs) and surface plasmon polaritons (SPPs). Relatively broadband spectral tuning of the modes can be achieved by modification of the thickness of either the absorptive spacer or the underlying metal film. Dark-field images also reveal the existence of particles for which the signal of the horizontal image dipole coupling mode is suppressed. This is attributed to partial-embedding of gold nanoparticles into the polythiophene spacer and leads to higher scattered light intensities at longer wavelengths. Full-field electromagnetic simulations show good agreement with the experimental results for the various sample conditions. Strong local electric field confinement at longer wavelengths in the polythiophene spacer, due to the vertical image dipole coupling mode and a LSPR-SPP coupling mode, is also observed in simulations and contributes to absorption enhancement in the spacer. Furthermore, we find absorption enhancement in the semiconducting polythiophene spacer increases with decreasing thickness, indicating the increased light trapping ability of the gold nanoparticles for ultra-thin semiconductor layers. The need for ever-thinner semiconductor layers in optoelectronic devices requires effective light trapping at deeply-subwavelength scales. This work demonstrates that light trapping in sub-50 nm-thick semiconductor layers is possible using a "sphere-on-plane" system and offers insight into how coupling modes can be manipulated in this system.

Long-term outcomes of septal reduction for obstructive hypertrophic cardiomyopathy.

BACKGROUND: Surgical myectomy and alcohol septal ablation (ASA) aim to decrease left ventricular outflow tract (LVOT) gradient in hypertrophic cardiomyopathy (HCM). Outcome of myectomy beyond 10 years has rarely been described. We describe 20 years of follow-up of surgical myectomy and 5 years of follow-up for ASA performed for obstructive HCM. METHODS: We studied 171 patients who underwent myectomy for symptomatic LVOT obstruction between 1972 and 2006. In addition, we studied 52 patients who underwent ASA for the same indication and who declined surgery. Follow-up of New York Heart Association (NYHA) functional class, echocardiographic data, and vital status were obtained from patient records. Mortality rates were compared with expected mortality rates of age- and sex-matched populations. RESULTS: Surgical myectomy improved NYHA class (2.74±0.65 to 1.54±0.74, p<0.001), reduced resting gradient (67.4±43.4mmHg to 11.2±16.4mmHg, p<0.001), and inducible LVOT gradient (98.1±34.7mmHg to 33.6±34.9mmHg, p<0.001). Similarly, ASA improved functional class (2.99±0.35 to 1.5±0.74, p<0.001), resting gradient (67.1±26.9mmHg to 23.9±29.4mmHg, p<0.001) and provoked gradient (104.4±34.9mmHg to 35.5±38.6mmHg, p<0.001). Survival after myectomy at 5, 10, 15, and 20 years of follow-up was 92.9%, 81.1%, 68.9%, and 47.5%, respectively. Of note, long-term survival after myectomy was lower than for the general population [standardized mortality ratio (SMR)=1.40, p<0.005], but still compared favorably with historical data from non-operated HCM patients. Survival after ASA at 2 and 5 years was 97.8% and 94.7%, respectively. Short-term (5 year) survival after ASA (SMR=0.61, p=0.48) was comparable to that of the general population. CONCLUSION: Long-term follow-up of septal reduction strategies in obstructive HCM reveals that surgical myectomy and ASA are effective for symptom relief and LVOT gradient reduction and are associated with favorable survival. While overall prognosis for the community HCM population is similar to the general population, the need for surgical myectomy may identify a sub-group with poorer long-term prognosis. We await long-term outcomes of more extensive myectomy approaches adopted in the past 10 years at major institutions.

Aqueous aerosol SOA formation: impact on aerosol physical properties.

Organic chemistry in aerosol water has recently been recognized as a potentially important source of secondary organic aerosol (SOA) material. This SOA material may be surface-active, therefore potentially affecting aerosol heterogeneous activity, ice nucleation, and CCN activity. Aqueous aerosol chemistry has also been shown to be a potential source of light-absorbing products ("brown carbon"). We present results on the formation of secondary organic aerosol material in aerosol water and the associated changes in aerosol physical properties from GAMMA (Gas-Aerosol Model for Mechanism Analysis), a photochemical box model with coupled gas and detailed aqueous aerosol chemistry. The detailed aerosol composition output from GAMMA was coupled with two recently developed modules for predicting a) aerosol surface tension and b) the UV-Vis absorption spectrum of the aerosol, based on our previous laboratory observations. The simulation results suggest that the formation of oligomers and organic acids in bulk aerosol water is unlikely to perturb aerosol surface tension significantly. Isoprene-derived organosulfates are formed in high concentrations in acidic aerosols under low-NO(x) conditions, but more experimental data are needed before the potential impact of these species on aerosol surface tension may be evaluated. Adsorption of surfactants from the gas phase may further suppress aerosol surface tension. Light absorption by aqueous aerosol SOA material is driven by dark glyoxal chemistry and is highest under high-NO(x) conditions, at high relative humidity, in the early morning hours. The wavelength dependence of the predicted absorption spectra is comparable to field observations and the predicted mass absorption efficiencies suggest that aqueous aerosol chemistry can be a significant source of aerosol brown carbon under urban conditions.

Anesthetic considerations during minimally invasive mitral valve surgery.

Advances in instruments and visualization tools as well as circulatory systems for cardiopulmonary bypass during the late 1990s have stimulated widespread adoption of minimally invasive mitral valve surgery (MIMVS). Today, MIMVS is the standard approach for many surgeons and institutions. There are multiple benefits of MIMVS. Patient satisfaction and improved cosmesis are important. Additionally, studies have consistently shown faster recovery times and less associated pain with MIMVS. Statistically significant improvement in bleeding, transfusion, incidence of atrial fibrillation, and time to resumption of normal activities with MIMVS has also been shown when comparing MIMVS with conventional mitral surgery. Most important, these benefits have been achieved without sacrificing perioperative safety or durability of surgical repair. Although a steep learning curve still exists given the high level of case complexity, continued development fueled by increasing patient demand may allow for even further expansion in the use of minimal invasive techniques.

Surgical ablation of refractory ventricular tachycardia in patients with nonischemic cardiomyopathy.

BACKGROUND: The surgical approach for the treatment of ventricular tachycardia (VT) has been largely replaced by percutaneous, catheter-based techniques. However, some VT circuits, particularly in patients with nonischemic cardiomyopathy, remain inaccessible to percutaneous ablation. Surgical therapy of these VTs is an alternative approach; however, its methodology has not been well defined. The purpose of this study was to evaluate the efficacy of preoperative electroanatomic and electrophysiological characterization of the VT substrate and circuit to guide surgical ablation. METHODS AND RESULTS: Eight patients with recurrent sustained VT refractory to antiarrhythmic drugs underwent endocardial and/or epicardial ablation procedures. Electroanatomic mapping was performed, and the VT substrate and circuit(s) were defined using voltage, activation, entrainment, and pace mapping. All 8 patients underwent detailed endocardial mapping; 6 patients also underwent epicardial mapping. Radiofrequency ablation was performed with the use of an open-irrigation catheter. After the unsuccessful percutaneous approach, surgical cryoablation was applied to the sites previously identified and targeted during the percutaneous procedure. There were no significant perioperative complications. During a mean follow-up period of 23 ± 6 months (range, 15 to 34 months), 6 patients had significant reduction in VT burden as evident by a reduced number of implantable cardioverter-defibrillator shocks after ablation (6.6 to 0.6 shocks per patient; P = 0.026). Two patients died, one of progressive heart failure and one of sepsis. CONCLUSIONS: VT circuits inaccessible to percutaneous ablation techniques are rare but can be encountered in patients with nonischemic cardiomyopathy. These VTs can be successfully targeted by surgical cryoablation guided by preoperative electroanatomic and electrophysiological mapping.

Clinically silent cerebral ischemic events after cardiac surgery: their incidence, regional vascular occurrence, and procedural dependence.

BACKGROUND: The reported frequency of stroke after coronary artery bypass grafting varies between 1.5% and 6%, approaches 10% after aortic valve replacement, and may occur in between 40 to 70% in high-risk groups. Clinically silent infarction may be far more frequent and could contribute to long-term cognitive dysfunction in patients after cardiac procedures. Using diffusion-weighted magnetic resonance imaging we document the occurrence, vascular distribution, and procedural dependence of silent infarction after cardiac surgery with cardiopulmonary bypass. We also document the association of preexisting white matter lesions with new postoperative ischemic lesions. METHODS: Thirty-four patients underwent T2-weighted fluid attenuated inversion recovery and diffusion-weighted magnetic resonance imaging before and after cardiac surgery with cardiopulmonary bypass for coronary artery bypass grafting, aortic valve replacement, and mitral valve repair or replacement surgery. Images were evaluated by experienced neuroradiologists for number, size, and vascular distribution of lesions. RESULTS: Mean age of participants was 67 +/- 15 years. Imaging occurred before and 6 +/- 2 days after surgery. New cerebral infarctions were evident in 6 of 34 patients (18%), were often multiple, and in 67% of patients were clinically silent. The occurrence of new infarctions by surgical procedure was as follows: aortic valve replacement (2 of 6), coronary artery bypass grafting and aortic valve replacement (3 of 8), aortic valve replacement with root replacement (1 of 1), coronary artery bypass grafting and mitral valve repair or replacement (0 of 4), mitral valve repair or replacement (0 of 2), and isolated coronary artery bypass grafting (0 of 13). New infarction occurred in 6 of 15 (40%) of all procedures involving aortic valve replacement. The severity of preexisting white matter lesions trended toward predicting the occurrence of new lesions (p = 0.055). CONCLUSIONS: Diffusion-weighted imaging reveals new cerebral infarctions in nearly 40% of patients after aortic valve replacement.