MS, Stanford University, School of Medicine, Epidemiology and Clinical Research (2017)
MD, Columbia University, College of Physicians & Surgeons, Medicine (2012)
BA, Yale College, History (2007)
Randomized control trials are extraordinarily expensive in cardiac surgery. As such, many management decisions are made with incomplete or potentially anachronistic information. My research is focused on applying causal inference techniques to observational data in order to better evaluate the comparative effectiveness of competing treatment methods in the treatment of cardiovascular disease.
Department of Surgery and Department of Cardiothoracic Surgery
Department of Cardiothoracic Surgery
Department of Cardiothoracic Surgery
In patients undergoing aortic-valve or mitral-valve replacement, either a mechanical or biologic prosthesis is used. Biologic prostheses have been increasingly favored despite limited evidence supporting this practice.We compared long-term mortality and rates of reoperation, stroke, and bleeding between inverse-probability-weighted cohorts of patients who underwent primary aortic-valve replacement or mitral-valve replacement with a mechanical or biologic prosthesis in California in the period from 1996 through 2013. Patients were stratified into different age groups on the basis of valve position (aortic vs. mitral valve).From 1996 through 2013, the use of biologic prostheses increased substantially for aortic-valve and mitral-valve replacement, from 11.5% to 51.6% for aortic-valve replacement and from 16.8% to 53.7% for mitral-valve replacement. Among patients who underwent aortic-valve replacement, receipt of a biologic prosthesis was associated with significantly higher 15-year mortality than receipt of a mechanical prosthesis among patients 45 to 54 years of age (30.6% vs. 26.4% at 15 years; hazard ratio, 1.23; 95% confidence interval [CI], 1.02 to 1.48; P=0.03) but not among patients 55 to 64 years of age. Among patients who underwent mitral-valve replacement, receipt of a biologic prosthesis was associated with significantly higher mortality than receipt of a mechanical prosthesis among patients 40 to 49 years of age (44.1% vs. 27.1%; hazard ratio, 1.88; 95% CI, 1.35 to 2.63; P<0.001) and among those 50 to 69 years of age (50.0% vs. 45.3%; hazard ratio, 1.16; 95% CI, 1.04 to 1.30; P=0.01). The incidence of reoperation was significantly higher among recipients of a biologic prosthesis than among recipients of a mechanical prosthesis. Patients who received mechanical valves had a higher cumulative incidence of bleeding and, in some age groups, stroke than did recipients of a biologic prosthesis.The long-term mortality benefit that was associated with a mechanical prosthesis, as compared with a biologic prosthesis, persisted until 70 years of age among patients undergoing mitral-valve replacement and until 55 years of age among those undergoing aortic-valve replacement. (Funded by the National Institutes of Health and the Agency for Healthcare Research and Quality.).
View details for DOI 10.1056/NEJMoa1613792
View details for PubMedID 29117490
Management of the aortic root is a challenge for surgeons treating acute type A aortic dissection.We performed a retrospective review of the acute type A aortic dissection experience at Stanford Hospital between 2005 and 2015 and identified patients who underwent either limited root repair or aortic root replacement. Differences in baseline characteristics were balanced with inverse probability weighting to estimate the average treatment effect on the controls. Weighted logistic regression was used to evaluate in-hospital mortality. Weighted Cox proportional hazards regression was used to evaluate differences in the hazard for mid-term death. Reoperation was evaluated with death as a competing risk with the Fine-Gray subdistribution hazard.After we excluded patients managed either nonoperatively or with definitive endovascular repair, there were 293 patients without connective tissue disease who underwent either limited root repair or aortic root replacement. There was no difference in weighted perioperative mortality, odds ratio 0.89 (95% confidence interval [CI], 0.44-1.76, P = .7), and there was no difference in weighted survival, hazard ratio 1.12 (95% CI, 0.54-2.31, P = .8). Risk of reoperation was greater in limited root repair (11.8%, 95% CI, 0.0%-23.8%) than for root replacement (0%), P < .001.Limited root repair was associated with increased risk of late reoperation after repair of acute type A aortic dissection. Surgeons with adequate experience may consider aortic root replacement in well-selected patients. However, given good outcomes after limited root repair, surgeons should not feel compelled to perform this more-complex operation.
View details for DOI 10.1016/j.jtcvs.2017.08.137
View details for PubMedID 29042100
Allosensitization has been shown to negatively affect post-heart transplant (HTx) survival even with a negative crossmatch. Whether allosensitization related to mechanical circulatory support (MCS) is associated with worse post-HTx survival remains controversial.Adult HTx recipients listed in the United Network for Organ Sharing database (July 2006-December 2012) were identified. Multivariate Cox regression assessed the effect of allosensitization on survival. Propensity matching was performed to compare patients who were and were not allosensitized. Kaplan-Meier survival analysis compared matched and unmatched patients in the MCS and medically managed cohorts.We identified 11,840 HTx recipients, of whom 4,167 had MCS. MCS was associated with allosensitization in multivariate logistic regression. Each different MCS device was associated with worse post-HTx survival in multivariate Cox regression. Allosensitization did not predict post-HTx mortality in MCS patients (hazard ratio, 1.07; 95% confidence interval, 0.89-1.28; p = 0.48. Among patients without MCS, allosensitization was associated with post-HTx mortality (hazard ratio, 1.19; 95% confidence interval, 1.03-1.39; p = 0.02). Kaplan-Meier analysis revealed equivalent survival in unmatched and matched cohorts when MCS patients who were allosensitized were compared with non-allosensitized MCS patients. Among non-MCS patients, allosensitization was associated with worse survival in unmatched and matched analysis.MCS was associated with allosensitization. For MCS patients, allosensitization did not independently predict worse post-HTx outcome. Among non-MCS patients, allosensitization was associated with worse post-HTx survival. Allosensitization appears to be a heterogeneous process influenced by presence of MCS.
View details for DOI 10.1016/j.healun.2015.12.023
View details for PubMedID 26856669
Medical treatment of initially uncomplicated acute Stanford type-B aortic dissection is associated with a high rate of late adverse events. Identification of individuals who potentially benefit from preventive endografting is highly desirable.The association of computed tomography imaging features with late adverse events was retrospectively assessed in 83 patients with acute uncomplicated Stanford type-B aortic dissection, followed over a median of 850 (interquartile range 247-1824) days. Adverse events were defined as fatal or nonfatal aortic rupture, rapid aortic growth (>10 mm/y), aneurysm formation (≥6 cm), organ or limb ischemia, or new uncontrollable hypertension or pain. Five significant predictors were identified using multivariable Cox regression analysis: connective tissue disease (hazard ratio [HR] 2.94, 95% confidence interval [CI]: 1.29-6.72; P=0.01), circumferential extent of false lumen in angular degrees (HR 1.03 per degree, 95% CI: 1.01-1.04, P=0.003), maximum aortic diameter (HR 1.10 per mm, 95% CI: 1.02-1.18, P=0.015), false lumen outflow (HR 0.999 per mL/min, 95% CI: 0.998-1.000; P=0.055), and number of intercostal arteries (HR 0.89 per n, 95% CI: 0.80-0.98; P=0.024). A prediction model was constructed to calculate patient specific risk at 1, 2, and 5 years and to stratify patients into high-, intermediate-, and low-risk groups. The model was internally validated by bootstrapping and showed good discriminatory ability with an optimism-corrected C statistic of 70.1%.Computed tomography imaging-based morphological features combined into a prediction model may be able to identify patients at high risk for late adverse events after an initially uncomplicated type-B aortic dissection.
View details for DOI 10.1161/CIRCIMAGING.116.005709
View details for Web of Science ID 000399574300007
View details for PubMedID 28360261
Aortic root aneurysm formation and subsequent dissection and/or rupture remain the leading cause of death in patients with Marfan syndrome. Our laboratory has reported that miR-29b participates in aortic root/ascending aorta extracellular matrix remodeling during early aneurysm formation in Fbn1(C1039G/+) Marfan mice. Herein, we sought to determine whether miR-29b suppression can reduce aneurysm formation long-term. Fbn1(C1039G/+) Marfan mice were treated with retro-orbital LNA-anti-miR-29b inhibitor or scrambled-control-miR before aneurysms develop either (1) a single dose prenatally (pregnant Fbn1(C1039G/+) mice at 14.5 days post-coitum) (n = 8-10, each group) or (2) postnatally every other week, from 2 to 22 weeks of age, and sacrificed at 24 weeks (n = 8-10, each group). To determine if miR-29b blockade was beneficial even after aneurysms develop, a third group of animals were treated every other week, starting at 8 weeks of age, until sacrificed (n = 4-6, each group). miR-29b inhibition resulted in aneurysm reduction, increased elastogenesis, decreased matrix metalloproteinase activity and decreased elastin breakdown. Prenatal LNA-anti-miR-29b inhibitor treatment decreased aneurysm formation up to age 32 weeks, whereas postnatal treatment was effective up to 16 weeks. miR-29b blockade did not slow aortic growth once aneurysms already developed. Systemic miR-29b inhibition significantly reduces aneurysm development long-term in a Marfan mouse model. Drug administration during aortic wall embryologic development appears fundamental. miR-29b suppression could be a potential therapeutic target for reducing aneurysm formation in Marfan syndrome patients.
View details for DOI 10.14814/phy2.13257
View details for PubMedID 28455451
Lymphovenous malformations of the heart are rare, and optimal management is uncertain. We present a case of a 39-year-old gentleman with a giant symptomatic lymphovenous malformation involving the right atrium, ventricle, and coronary artery. Radical resection was performed with replacement of the tricuspid valve and bovine pericardial reconstruction of the atrium and ventricle. Additional coronary artery bypass grafting was performed to the acute marginal and distal right coronary artery. Radical resection for this benign process is feasible and may be considered given the possibility of recurrence seen with lymphatic malformations of other parts of the body.
View details for DOI 10.1016/j.athoracsur.2017.04.052
View details for PubMedID 28838522
Patients with Stanford type B aortic dissections (ADs) are at risk of long-term disease progression and late complications. The aim of this study was to evaluate the natural course and evolution of acute type B AD and intramural hematomas (IMHs) in patients who presented without complications during their initial hospital admission and who were treated with optimal medical management (MM).Databases from 2 aortic centers in Europe and the United States were used to identify 136 patients with acute type B AD (n = 92) and acute type B IMH (n = 44) who presented without complications during their index admission and were treated with MM. Computed tomography angiography scans were available at onset (≤14 days) and during follow-up for those patients. Relevant data, including evidence of adverse events during follow-up (AE; defined according to current guidelines), were retrieved from medical records and by reviewing computed tomography scan images. Aortic diameters were measured with dedicated 3-dimensional software.The 1-, 2-, and 5-year event-free survival rates of patients with type B AD were 84.3% (95% confidence interval [CI], 74.4-90.6), 75.4% (95% CI, 64.0-83.7), and 62.6% (95% CI, 68.9-73.6), respectively. Corresponding estimates for IMH were 76.5% (95% CI, 57.8-87.8), 76.5% (95% CI, 57.8-87.8), and 68.9% (95% CI, 45.2-83.9), respectively. In patients with type B AD, risk of an AE increased with aortic growth within the first 6 months after onset. A diameter increase of 5 mm in the first half year was associated with a relative risk for AE of 2.29 (95% CI, 1.70-3.09) compared with the median 6 months' growth of 2.4 mm. In approximately 60% of patients with IMH, the abnormality resolved within 12 months and in the patients with nonresolving IMH, risk of an adverse event was greatest in the first year after onset and remained stable thereafter.More than one third of patients with initially uncomplicated type B AD suffer an AE under MM within 5 years of initial diagnosis. In patients with nonresolving IMH, most adverse events are observed in the first year after onset. In patients with type B AD an early aortic growth is associated with a greater risk of AE.
View details for DOI 10.1016/j.jtcvs.2017.04.064
View details for PubMedID 28668458
View details for PubMedCentralID PMC5603396
Acute type A aortic dissection (AcA-AoD) is a surgical emergency associated with very high morbidity and mortality. Unfortunately, the early outcome of emergency surgical repair has not improved substantially over the last 20 years. Many of the same debates occur repeatedly regarding operative extent and optimal conduct of the operation. The question remains: are patients suffering from too large an operation or too small? The pendulum favoring routine aortic valve resuspension, when feasible, has swung towards frequent aortic root replacement. This already aggressive approach is now being challenged with the even more extensive valve-sparing aortic root replacement (V-SARR) in selected patients. Distally, open replacement of most of the transverse arch is best in most patients. The need for late aortic re-intervention has not been shown to be affected by more extensive distal operative procedures, but the contemporary enthusiasm for a distal frozen elephant trunk (FET) only seems to build. It must be remembered that the first and foremost goal of the operation is to have an operative survivor; additional measures to reduce late morbidity are secondary aspirations. With increasing experience, true contraindications to emergency surgical operation have dwindled, but patients with advanced age, multiple comorbidities, and major neurological deficits do not fare well. The endovascular revolution, moreover, has spawned innovative options for modern practice, including ascending stent graft and adaptations of the old flap fenestration technique. Despite the increasingly complex operations and ever expanding therapies, this life-threatening disease remains a stubborn challenge for all cardiovascular surgeons. Development of specialized thoracic aortic teams and regionalization of care for patients with AcA-AoD offers the most promise to improve overall results.
View details for DOI 10.21037/acs.2016.05.05
View details for PubMedID 27563541
View details for PubMedCentralID PMC4973128
We describe a patient who presented in profound cardiogenic shock due to bioprosthetic aortic valve stenosis requiring salvage Extracorporeal Membrane Oxygenation followed by a "bridge" valve-in-valve transcatheter aortic valve replacement. doi: 10.1111/jocs.12750 (J Card Surg 2016;31:403-405).
View details for DOI 10.1111/jocs.12750
View details for PubMedID 27109017
View details for PubMedCentralID PMC4951207
Despite increasing use of left ventricular devices for the surgical treatment of heart failure, there is limited experience with implantation of devices in the setting of challenging left apical anatomy. We report the case of a 68-year-old man with a chronic post-infarction calcified apical pseudoaneurysm, who underwent pseudoaneurysmectomy, ventricular myoplasty, and left ventricular assist device implantation. A review of the literature and operative strategies are presented.
View details for DOI 10.1177/0218492315579555
View details for PubMedID 25834125
Although controlled donation after circulatory determination of death (cDCDD) could increase the supply of donor lungs within the United States, the yield of lungs from cDCDD donors remains low compared with donation after neurologic determination of death (DNDD). To explore the reason for low lung yield from cDCDD donors, Scientific Registry of Transplant Recipient data were used to assess the impact of donor lung quality on cDCDD lung utilization by fitting a logistic regression model. The relationship between center volume and cDCDD use was assessed, and the distance between center and donor hospital was calculated by cDCDD status. Recipient survival was compared using a multivariable Cox regression model. Lung utilization was 2.1% for cDCDD donors and 21.4% for DNDD donors. Being a cDCDD donor decreased lung donation (adjusted odds ratio 0.101, 95% confidence interval [CI] 0.085-0.120). A minority of centers have performed cDCDD transplant, with higher volume centers generally performing more cDCDD transplants. There was no difference in center-to-donor distance or recipient survival (adjusted hazard ratio 1.03, 95% CI 0.78-1.37) between cDCDD and DNDD transplants. cDCDD lungs are underutilized compared with DNDD lungs after adjusting for lung quality. Increasing transplant center expertise and commitment to cDCDD lung procurement is needed to improve utilization.
View details for DOI 10.1111/ajt.13599
View details for Web of Science ID 000373075400021
Giant coronary aneurysms are rare. We present a 25-year-old woman with a known history of non-Kawasaki/nonatherosclerotic bilateral coronary aneurysms. She was transferred to our facility with acute coronary syndrome complicated by cardiogenic shock. Angiography demonstrated giant bilateral coronary aneurysms and complete occlusion of the left anterior descending (LAD) artery. Emergent coronary artery bypass grafting was performed. Coronary artery bypass grafting is the preferred approach for addressing giant coronary aneurysms. Intervention on the aneurysm varies in the literature. Aggressive revascularization is recommended in the non-Kawasaki/nonatherosclerotic aneurysm patient, and ligation should be performed in patients with thromboembolic phenomena.
View details for DOI 10.1016/j.athoracsur.2015.06.104
View details for PubMedID 27000621
OHT is the definitive therapy in end-stage heart failure. Elevated PVRI is considered a relative contraindication to isolated OHT; this assumption is re-evaluated using data from the UNOS database. A retrospective review of de-identified data from the UNOS dataset was performed. There were 1943 pediatric OHT recipients between 10/87 and 12/11 with sufficient data for analysis. Cox regression was performed to examine the effect of baseline characteristics on post-transplant survival. Patients were propensity matched, and Kaplan-Meier survival analysis was performed comparing cohorts of patients using thresholds of 6 and 9 WU × m(2) . PVRI was not a significant predictor of post-transplant outcomes in either univariate or multivariate Cox regression. Kaplan-Meier analysis revealed no difference in survival between both unmatched and propensity-matched OHT recipients. In conclusion, elevated PVRI was not associated with post-transplant mortality in pediatric OHT recipients. A prospective study assessing the current use of PVRI ≥6 as a threshold to contraindicate isolated OHT should be undertaken. Removing this potentially unnecessary restriction on transplant candidacy may make this life-saving therapy available to a greater number of patients.
View details for DOI 10.1111/petr.12550
View details for Web of Science ID 000358688400018
Transaortic interventions on the mitral valve are rarely performed, but offer advantages over traditional approaches in certain circumstances, including either extensive involvement of the aortomitral junction with endocarditis or the patient requiring reoperation for aortic and mitral disease. Herein is presented a case of recurrent endocarditis involving aortomitral continuity, reconstructed using a transaortic mitral valve repair and reconstruction of the aortic and mitral annuli with a pericardial patch, followed by aortic root replacement.
View details for Web of Science ID 000369045500006
View details for PubMedID 26204680
Cardiac sarcomas are rare and have a poor prognosis. The details are presented of a patient with a right atrial angiosarcoma who underwent radical resection with reconstruction of the right atrium with a bovine pericardial patch, tricuspid valve replacement, and bypass of the right coronary artery. Survival is improved in patients who successfully undergo total (R0) resection. For this reason, an aggressive approach to resection is recommended, with extensive reconstruction for all patients with cardiac sarcoma.
View details for PubMedID 26901916
Combined heart-liver transplant (HLT) is a viable therapy for patients with concomitant end-stage heart and liver failure. Using data from the United Network for Organ Sharing database, we examined the cumulative incidences of transplant and mortality in waitlisted candidates for HLT, isolated heart transplant (HRT) and isolated liver transplant (LIV) in the Model for End-Stage Liver Disease era. The incidence of waitlist mortality was higher in HLT candidates than in HRT candidates (p = 0.001, 26% vs. 12% at 1 year) or LIV candidates (p = 0.005, 26% vs. 14% at 1 year). These differences persisted after stratifying by disease severity. Posttransplant survival was not significantly different between HLT and HRT recipients or between HLT and LIV recipients. In a multivariable model, undergoing HLT was associated with enhanced survival for HLT candidates (hazard ratio, 0.41; confidence interval, 0.21-0.79; p = 0.008), but undergoing HRT alone was not. Interestingly, 90% of HLT recipients were allocated an organ locally, compared to 60% of HRT candidates and 73% of LIV candidates (both p < 0.001). These data suggest that the current cardiac and liver allocation systems may underestimate the risk of death for patients with concomitant end-stage heart and liver failure on the HLT waitlist.
View details for DOI 10.1111/ajt.12595
View details for PubMedID 24517245
In patients with end-stage heart failure (ESHF) who are candidates for isolated heart transplant (HRT), dialysis dependence (DD) is considered an indication for combined heart-kidney transplantation (HKT). HKT remains controversial in ESHF transplant candidates with nondialysis-dependent renal insufficiency (NDDRI). Using United Network for Organ Sharing data, we examined the cumulative incidences of transplant and mortality in patients with DD and NDDRI waitlisted for HKT or HRT. In all groups, 3-month waitlist mortality was dismal: 31% and 21% for HRT- and HKT-listed patients with DD and 12% and 7% for HRT- and HKT-listed patients with NDDRI. Five-year posttransplant survival was improved in HKT recipients compared with HRT recipients for both patients with DD (73% vs. 51%, p < 0.001) and NDDRI (80% vs. 69%, p < 0.001). Likewise, multivariable analysis associated HKT with better outcomes than HRT in HKT-listed patients, although both improved survival. These data argue strongly for HKT in ESHF transplant candidates with DD. However, in patients with NDDRI, HKT must be weighed against the possibility of renal recovery with isolated HRT. Whether HRT (followed by a staged kidney transplant in patients who do not recover renal function after HRT), as opposed to HKT, maximizes organ benefit for patients with NDDRI and ESHF requires assessment. Nevertheless, given their dismal waitlist outcomes and excellent posttransplant results, we suggest that patients with DD and NDDRI with ESHF be considered for early listing and transplant.
View details for DOI 10.1111/ajt.12522
View details for PubMedID 24279876
Currently, pulmonary vascular resistance index (PVRI) >6 WU × m(2) (indexed units) is generally considered a contraindication to isolated orthotopic heart transplantation (OHT). However, this has been questioned in the literature.A retrospective review was performed on all patients <18 years old who underwent primary OHT for cardiomyopathy. Data were collected with regard to demographics, pre-operative hemodynamics, need for pre-operative mechanical circulatory support, vasodilator reactivity and 30-day mortality (30dM). A receiver operating characteristic (ROC) curve was used to establish an optimal threshold. Uni- and multivariate logistic regressions were performed to assess the influence of PVRI on 30dM.Complete data were available for 158 cardiomyopathy patients <18 years of age, who underwent primary OHT between June 1984 and November 2010. The ROC curve yielded a threshold of 9.290 indexed units. Four of 19 patients (21.1%) with PVRI >9 died in the first 30 days. In patients with PVRI <9, there was only 1 death among 139 patients (0.7%). Odds of mortality increased incrementally with PVRI as a continuous variable, with an odds ratio (OR) of 1.35 per indexed unit (95% confidence interval 1.12 to 1.63). PVRI was dichomotomized (PVRId) using the previously established threshold and revealed an increasing risk of mortality, OR 36.80 (95% confidence interval 3.86 to 350.90), with a PVRI of >9 indexed units.Using a PVRI >6 as a contraindication to isolated OHT may be too restrictive. Patients with PVRI ≤9 do not appear to be at increased risk of early mortality. In patients with PVRI >9, 30-day survival was 78.9% in this study. This represents a viable alternative to heart-lung transplantation.
View details for DOI 10.1016/j.healun.2011.08.021
View details for Web of Science ID 000298442200008
View details for PubMedID 22019236