Krishna Pundi, MD is a Fellow in Cardiovascular Medicine at Stanford University. He received his MD from Mayo Medical school and completed internal medicine residency at Stanford University. Following internal medicine residency, Dr. Pundi received a combined appointment as a clinical instructor in hospital medicine and a post-doctoral research fellow for the ENHANCE-AF clinical trial as part of the AHA’s Strategically Focused Research Networks. Dr. Pundi then started Cardiovascular Medicine Fellowship at Stanford University in July 2020.
Dr. Pundi’s research interest is in combining traditional epidemiologic approaches of understanding disease with novel methods of data acquisition to define clinical, demographic, and arrhythmia morphology features that predict cardiovascular events and death. He was recently awarded an ACC/Bristol Myers Squibb Research Fellowship Award to study the practice variation and treatment outcomes for patients with non-sustained ventricular tachycardia.
Honors & Awards
Dr. Scholl SURF Scholar, Mayo Clinic (2011)
Magna Cum Laude for Outstanding Educational Presentation, Radiologic Society of North America (2015)
Case Competition Award, International Dead Sea Symposium (2022)
Edwin Alderman Award for Excellence in Clinical Research, Stanford University (2022)
Member, Alpha Omega Alpha Honor Medical Society (2022)
Research Fellowship Award, American College of Cardiology (ACC)/Bristol Myers Squibb (2022)
Doctor of Medicine, Mayo Graduate School (2016)
Bachelor of Science, University of Minnesota Twin Cities (2012)
Fellowship, Stanford University, Cardiovascular Medicine (2023)
Board Certification, American Board of Internal Medicine, Internal Medicine (2019)
Residency, Stanford University, Internal Medicine (2019)
M.D., Mayo Medical School (2016)
B.S., University of Minnesota, Twin Cities, Neuroscience (2012)
Community and International Work
Healthcare Volunteer, Dominican Republic
International Medical Alliance
Opportunities for Student Involvement
Global Health Scholar, Rwanda
Johnson and Johnson
Opportunities for Student Involvement
University of Guadalajara Brigades, Guadalajara, Mexico
Developing sustainable microenterprise, local level public health initiatives
University of Guadalajara
Rural and farm communities
Opportunities for Student Involvement
Design and development of a digital shared decision-making tool for stroke prevention in atrial fibrillation.
2023; 6 (1): ooad003
Shared decision-making (SDM) is an approach in which patients and clinicians act as partners in making medical decisions. Patients receive the information needed to decide and are encouraged to balance risks, benefits, and preferences. Informative materials are vital to SDM. Atrial fibrillation (AF) is the most common cardiac arrhythmia and responsible for 10% of ischemic strokes, however 1/3 of patients are not on appropriate anticoagulation. Decision sharing may facilitate treatment acceptance, improving outcomes.To develop a framework of the components needed to create novel SDM tools and to provide practical examples through a case-study of stroke prevention in AF.We analyze the design values of a web-based SDM tool created to better inform AF patients about anticoagulation. The tool was developed in partnership with patient advocates, multi-disciplinary investigators, and private design firms. It was refined through iterative, recursive testing in patients with AF. Its effectiveness is being evaluated in a multisite clinical trial led by Stanford University and sponsored by the American Heart Association.The main components considered when creating the Stanford AFib tool included: design and software; content identification; information delivery; inclusive communication, user engagement; patient feedback; clinician experience; and anticipation of implementation and dissemination. We also highlight the ethical principles underlying SDM; matters of diversity and inclusion, linguistic variety, accessibility, and health literacy. The Stanford AFib Guide patient tool is available at: https://afibguide.com and the clinician tool at https://afibguide.com/clinician.Attention to a range of vital development and design factors can facilitate tool adoption and information acquisition by diverse cultural, educational, and socioeconomic subpopulations. With thoughtful design, digital tools may decrease decision regret and improve treatment outcomes across many decision-making situations in healthcare.
View details for DOI 10.1093/jamiaopen/ooad003
View details for PubMedID 36751465
View details for PubMedCentralID PMC9893868
Warfarin Time in Therapeutic INR Range and Direct Oral Anticoagulant Adherence for Venous Thromboembolism Across the Spectrum of Weight and Body Mass Index: Findings from Veterans Health Administration.
Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis
2023; 29: 10760296231152474
The evidence of direct oral anticoagulants (DOACs) usage for venous thromboembolism (VTE) in patients at extremes of body weight or mass index is limited. In such situations, warfarin may be more frequently used. We investigated warfarin time in the therapeutic international normalized ratio range (TTR) and DOAC adherence based on the calculated proportion of days covered (PDC) by pill coverage from a DOAC prescription in patients with VTE across all body sizes. Using data from the Veterans Health Administration (VA), we identified first-time patients with VTE between 2013 and 2018 treated with warfarin or DOACs. We analyzed 28,245 patients with warfarin TTR (N=10,167) or DOAC PDC(N=18,078). For warfarin-treated patients after index VTE, mean TTR was lower over shorter treatment durations (TTR 30 vs TTR 180 [mean±SD]: 43.8%±33.5% vs 58.8%±23.5%). Mean TTR over 180 days after VTE was lowest for patients <60 kg (TTR 180 [mean±SD]: <60kg: 49.3%±24.2% vs ≥60 to <100 kg: 57.8%±23.4%; P<.0001). For DOAC-treated patients over 180 days after index VTE, mean PDC was lowest for patients <60 kg (PDC 180 [mean±SD]:<60kg: 76.9%±33.2% vs≥60 to <100 kg: 83.6%±27.7%; P<.0001).Most DOAC-treated patients attained sufficient adherence across the body size spectrum while warfarin-treated patients <60kg were at risk for low TTR.
View details for DOI 10.1177/10760296231152474
View details for PubMedID 36694957
Clinical Trial to Evaluate an Atrial Fibrillation Stroke Prevention Shared DecisionMaking Pathway
LIPPINCOTT WILLIAMS & WILKINS. 2022: E582-E583
View details for Web of Science ID 000928164500042
A Randomized Clinical Trial to Evaluate an Atrial Fibrillation Stroke Prevention Shared Decision-Making Pathway.
Journal of the American Heart Association
Background Oral anticoagulation (OAC) reduces stroke and disability in atrial fibrillation (AF) but is underutilized. We evaluated the effects of a novel patient-clinician shared decision-making (SDM) tool in reducing OAC patient's decisional conflict as compared to usual care. Methods and Results We designed and evaluated a new digital decision aid in a multicenter, randomized, comparative effectiveness trial, ENHANCE-AF (Engaging Patients to Help Achieve Increased Patient Choice and Engagement for AF Stroke Prevention). The digital AF SDM Toolkit was developed using patient-centered design with clear health communication principles (e.g. meaningful images, limited text). Available in English and Spanish, the toolkit included the following: 1) a brief animated video; 2) interactive questions with answers; 3) a quiz to check on understanding; 4) a worksheet to be used by the patient during the encounter; and 5) an online guide for clinicians. The study population included English or Spanish speakers with non-valvular AF and a CHA2DS2-VASc stroke score ≥1 for men or ≥2 for women. Participants were randomized in a 1:1 ratio to either Usual Care (UC) or the SDM Toolkit. The primary endpoint was the validated 16-item Decisional Conflict Scale (DCS) at 1 month. Secondary outcomes included DCS at 6 months and the 10-item Decision Regret Scale (DRS) at 1 and 6 months as well as a weighted average of Mann-Whitney U-statistics for both DCS and DRS. A total of 1001 participants were enrolled and followed at 5 different sites in the United States between 12/18/19 and 8/17/22. The mean patient age was 69 ±10years (40% females, 16.9% Black, 4.5% Hispanic, 3.6% Asian), and 50% of participants had CHA2DS2-VASc scores ≥3 (M) or ≥4 (F). The primary endpoint at 1 month showed a clinically meaningful reduction in decisional conflict: a 7-point difference in median scores between the two arms (16.4 v 9.4; Mann-Whitney U-statistics=0.550; p-value=0.007). For the secondary endpoint of 1-month DRS, the difference in median scores between arms was 5 points in the direction of less decisional regret (p-value of 0.078). The treatment effects lessened over time: at 6 months the difference in medians was 4.7 points for DCS (p-value=0.060) and 0 points for DRS (p-value=0.35). Conclusions Implementation of a novel, Shared Decision-Making Toolkit (afibguide.com; afibguide.com/clinician) achieved significantly lower decisional conflict compared to usual care in patients with AF.
View details for DOI 10.1161/JAHA.122.028562
View details for PubMedID 36342828
Atrial fibrillation bleeding risk and prediction while treated with direct oral anticoagulants in warfarin-naive or warfarin-experienced patients.
BACKGROUND: In patients with atrial fibrillation (AF) treated with direct oral anticoagulants (DOAC), bleeding risk scores provide only modest discrimination for major or intracranial bleeding. However, warfarin experience may impact HAS-BLED (Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile international normalized ratio, Elderly (>65 years), Drugs/alcohol concomitantly) score performance in patients evaluated for DOACs, as HAS-BLED was derived and validated in warfarin cohorts.METHODS: We performed a retrospective cohort study of patients prescribed DOAC for AF in the Veterans Health Administration between 2010 and 2017. We determined modified HAS-BLED score discrimination and calibration for bleeding, for patients treated with DOAC, stratified by prior warfarin exposure. We also determined the association betweenDOAC-warfarin-naive status to bleeding (nonintracranial and intracranial) with DOAC-warfarin-experienced patients as reference.RESULTS: The DOAC analysis cohort included 100,492 patients with AF (age [mean±SD]: 72.9±9.6 years; 1.7% female; 90.1% White), of which 26,760 patients (26.6%) and 73,732 patients (73.4%) were warfarin experienced or naive, respectively. HAS-BLED discrimination for bleeds was modest for patients treated with DOAC, regardless of prior warfarin experience (concordancestatistics: 0.53-0.59). For DOAC-warfarin-naive patients, as compared to DOAC-warfarin-experienced patients, adjusted risk of intracranial bleeding was lower, while risk of nonintracranial bleeding was higher (intracranial bleeding propensity adjusted with inverse probability of treatment weights [IPTWs]: hazard ratio [HR]: 0.86, 95% confidence interval [CI]: 0.78-0.95, p=.0040) (nonintracranial bleeding propensity adjusted with IPTW: HR: 1.15, 95% CI: 1.11-1.19, p<.0001).CONCLUSION: Patients' modified HAS-BLED score at the time of DOAC initiation, regardless of prior warfarin use, provided only modest discrimination for intracranial and nonintracranial bleeds. These data argue against maintaining DOAC eligible patients on warfarin therapy regardless of modified HAS-BLED score.
View details for DOI 10.1002/clc.23887
View details for PubMedID 35946047
THE 2017 ACC/AHA HYPERTENSION GUIDELINES AND CHA2DS2-VASC UP-SCORING IN PATIENTS WITH ATRIAL FIBRILLATION: INSIGHTS FROM THE NCDR (R) PINNACLE (R) REGISTRY
ELSEVIER SCIENCE INC. 2022: 12
View details for Web of Science ID 000781026600013
The ENHANCE-AF Clinical Trial to Evaluate an Atrial Fibrillation Shared Decision-Making Pathway: Rationale and Study Design.
American heart journal
Shared decision making (SDM) may result in treatment plans that best reflect the goals and wishes of patients, increasing patient satisfaction with the decision-making process. There is a knowledge gap to support the use of decision aids in SDM for anticoagulation therapy in patients with atrial fibrillation (AF). We describe the development and testing of a new decision aid, including a multicenter, randomized, controlled, 2-arm, open-label ENHANCE-AF clinical trial (Engaging Patients to Help Achieve Increased Patient Choice and Engagement for AF Stroke Prevention) to evaluate its effectiveness in 1,200 participants.Participants will be randomized to either usual care or to a shared decision-making pathway incorporating a digital tool designed to simplify the complex concepts surrounding AF in conjunction with a clinician tool and a non-clinician navigator to guide the participants through each step of the tool. The participant-determined primary outcome for this study is the Decisional Conflict Scale, measured at 1 month after the index visit during which a decision was made regarding anticoagulation use. Secondary outcomes at both 1 and 6 months will include other decision making related scales as well as participant and clinician satisfaction, oral anticoagulation adherence, and a composite rate of major bleeding, death, stroke, or transient ischemic attack. The study will be conducted at four sites selected for their ability to enroll participants of varying racial and ethnic backgrounds, health literacy, and language skills. Participants will be followed in the study for 6 months.The results of the ENHANCE-AF trial will determine whether a decision aid facilitates high quality shared decision making in anticoagulation discussions for stroke reduction in AF. An improved shared decision-making experience may allow patients to make decisions better aligned with their personal values and preferences, while improving overall AF care.
View details for DOI 10.1016/j.ahj.2022.01.013
View details for PubMedID 35092723
Shared Decision-Making in Cardiac Electrophysiology Procedures and Arrhythmia Management.
Circulation. Arrhythmia and electrophysiology
Shared decision-making (SDM) has been advocated to improve patient care, patient decision acceptance, patient-provider communication, patient motivation, adherence, and patient reported outcomes. Documentation of SDM is endorsed in several society guidelines and is a condition of reimbursement for selected cardiovascular and cardiac arrhythmia procedures. However, many clinicians argue that SDM already occurs with clinical encounter discussions or the process of obtaining informed consent and note the additional imposed workload of using and documenting decision aids without validated tools or evidence that they improve clinical outcomes. In reality, SDM is a process and can be done without decision tools, although the process may be variable. Also, SDM advocates counter that the low-risk process of SDM need not be held to the high bar of demonstrating clinical benefit and that increasing the quality of decision-making should be sufficient. Our review leverages a multidisciplinary group of experts in cardiology, cardiac electrophysiology, epidemiology, and SDM, as well as a patient advocate. Our goal is to examine and assess SDM methodology, tools, and available evidence on outcomes in patients with heart rhythm disorders to help determine the value of SDM, assess its possible impact on electrophysiological procedures and cardiac arrhythmia management, better inform regulatory requirements, and identify gaps in knowledge and future needs.
View details for DOI 10.1161/CIRCEP.121.007958
View details for PubMedID 34865518
Anticoagulation Treatment and Outcomes of Venous Thromboembolism by Weight and Body Mass Index: Insights From the Veterans Health Administration.
Circulation. Cardiovascular quality and outcomes
BACKGROUND: Consensus statements have recommended against the use of direct oral anticoagulants (DOACs) in venous thromboembolism (VTE) for patients ≥120 kg and ≥40 kg/m2. We sought to determine use and outcomes of DOACs for VTE across weight and body mass index (BMI).METHODS: We performed a retrospective cohort study of patients with first-time VTE 2013 to 2018 that were treated with DOAC or warfarin in the Veterans Health Administration. The Veterans Health Administration has implemented system-wide guidance for patient selection and shared decision-making for use of DOACs in VTE at extremes of weight. We stratified patients by weight and BMI and assessed (1) association of weight and BMI category to outcomes in those prescribed DOAC; and (2) association of DOAC, as compared to warfarin, to outcomes by weight and BMI categories. Outcomes of interest included major bleeding, clinically relevant nonmajor bleeding, and recurrent VTE.RESULTS: The analysis cohort included 51 871 patients prescribed DOAC or warfarin within 30 days of index VTE diagnosis (age 64.5±13.1 years; 6.0% female; median weight 93.4 kg [25th-75th: 80.5-108.6 kg]). For patients ≥120 kg (N=6934 patients), 38.4% were treated with DOAC, as compared to 45.4% of those ≥60 to <100 kg (N=30 645; P<0.0001). DOAC prescription was not associated with major bleeds, clinically relevant nonmajor bleeds, or recurrent VTE for those in higher weight and BMI categories as compared to those in average weight and BMI categories. DOAC prescription, as compared to warfarin, was not associated with increased recurrent VTE in any weight or BMI category.CONCLUSIONS: Patients ≥120 kg and ≥40 kg/m2 with VTE are frequently prescribed DOAC by the Veterans Health Administration, without an increase in bleeding or recurrent VTE. These findings suggest DOACs can be safe and effective in this population and may argue for broader adoption of pharmacy policies that promote careful patient selection and shared decision making.
View details for DOI 10.1161/CIRCOUTCOMES.121.008005
View details for PubMedID 34724801
Direct Oral Anticoagulant Adherence of Patients With Atrial Fibrillation Transitioned from Warfarin.
Journal of the American Heart Association
Background Reduced time in international normalized ratio therapeutic range (TTR) limits warfarin safety and effectiveness. In patients switched from warfarin to direct oral anticoagulants (DOACs), patient factors associated with low TTR could also increase risk of DOAC nonadherence. We investigated the relationship between warfarin TTR and DOAC adherence in warfarin-treated patients with atrial fibrillation switched to DOAC. Methods and Results Using data from the Veterans Health Administration, we identified patients with atrial fibrillation switched from warfarin to DOAC (switchers) or treated with warfarin alone (non-switchers). Logistic regression was used to evaluate association between warfarin TTR and DOAC adherence. We analyzed 128 605 patients (age, 71±9; 1.6% women; CHA2DS2-VASc 3.5±1.6); 32 377 switchers and 96 228 non-switchers. In 8016 switchers with international normalized ratio data to calculate 180-day TTR before switch, TTR was low (median 0.45; IQR, 0.26-0.64). Patients with TTR <0.5 were more likely to be switched to DOAC (odds ratio [OR],1.68 [95% CI,1.62-1.74], P<0.0001), as were those with TTR <0.6 or TTR <0.7. Proportion of days covered ≥0.8 was achieved by 76% of switchers at 365 days. In low-TTR individuals, proportion of days covered ≥0.8 was achieved by 70%, 72%, and 73% of switchers with TTR <0.5, 0.6, and 0.7, respectively. After multivariable adjustment, TTR <0.5 decreased odds of achieving 365-day proportion of days covered ≥0.8 (OR, 0.49; 0.43-0.57, P<0.0001), with similar relationships for TTR <0.6 and TTR <0.7. In non-switchers with TTR <0.5, long-term TTR remained low. Conclusions In patients with atrial fibrillation switched from warfarin to DOAC, most achieved adequate DOAC adherence despite low pre-switch TTRs. However, TTR trajectories remained low in non-switchers. Patients with low warfarin TTR more consistently achieved treatment targets after switching to DOACs, although adherence-oriented interventions may be beneficial.
View details for DOI 10.1161/JAHA.121.020904
View details for PubMedID 34779243
Blood Thinners for Atrial Fibrillation Stroke Prevention.
Circulation. Arrhythmia and electrophysiology
View details for DOI 10.1161/CIRCEP.120.009389
View details for PubMedID 34111936
Association of kidney function and atrial fibrillation progression to clinical outcomes in patients with cardiac implantable electronic devices.
American heart journal
Kidney function may promote progression of AF.We evaluated the association of kidney function to AF progression and resultant clinical outcomes in patients with cardiac implantable electronic devices (CIED).We performed a retrospective cohort study using national clinical data from the Veterans Health Administration linked to CIED data from the Carelink® remote monitoring data warehouse (Medtronic Inc, Mounds View, MN). All devices had atrial leads and at least 75% of remote monitoring transmission coverage. Patients were included at the date of the first AF episode lasting ≥6 minutes, and followed until the occurrence of persistent AF in the first year, defined as ≥7 consecutive days with continuous AF. We used Cox regression analyses with persistent AF as a time-varying covariate to examine the association to stroke, myocardial infarction, heart failure and death.Of, 10,323 eligible patients, 1,771 had a first CIED-detected AF (mean age 69 ± 10 years, 1.2% female). In the first year 355 (20%) developed persistent AF. Kidney function was not associated with persistent AF after multivariable adjustment including CHA2DS2-VASc variables and prior medications. Only higher age increased the risk (HR: 1.28 per 10 years; 1.07-1.52). Persistent AF was associated to higher risk of heart failure (HR: 2.27; 95% CI: 1.88-2.74) and death (HR: 1.60; 95% CI: 1.30-1.96), but not stroke (HR: 1.28; 95% CI: 0.62-2.62) or myocardial infarction (HR: 1.43; 95% CI: 0.91-2.25).Kidney function was not associated to AF progression, whereas higher age was. Preventing AF progression could reduce the risk of heart failure and death.
View details for DOI 10.1016/j.ahj.2021.06.002
View details for PubMedID 34118202
WARFARIN TIME IN THERAPEUTIC RANGE TRAJECTORIES IN POTENTIAL SWITCHERS TO DIRECT ORAL ANTICOAGULANTS
ELSEVIER SCIENCE INC. 2020: 416
View details for Web of Science ID 000522979100406
DETERMINANTS OF ATRIAL FIBRILLATION PROGRESSION IN CHRONIC KIDNEY DISEASE PATIENTS WITH CARDIAC IMPLANTABLE ELECTRONIC DEVICES (DATA FROM THE MEDTRONIC CARELINK DATABASE)
ELSEVIER SCIENCE INC. 2020: 488
View details for Web of Science ID 000522979100477
Characteristics and Strength of Evidence of COVID-19 Studies Registered on ClinicalTrials.gov.
JAMA internal medicine
View details for DOI 10.1001/jamainternmed.2020.2904
View details for PubMedID 32730617
Multiphase Computed Tomographic Enterography: Diagnostic Yield and Efficacy in Patients With Suspected Small Bowel Bleeding.
Mayo Clinic proceedings. Innovations, quality & outcomes
2019; 3 (4): 438–47
Objective: To estimate the diagnostic yield and efficacy of multiphase computed tomographic enterography (mpCTE) for suspected small bowel bleeding in routine clinical practice.Patients and Methods: All mpCTEs performed between January 1, 2006, and December 31, 2014, for suspected small bowel bleeding were included and classified by a gastroenterologist and an abdominal radiologist. The reference standard for a definitive diagnosis was balloon-assisted enteroscopic, angiographic, surgical, or pathologic results. Overall and lesion-specific diagnostic yield (DY), sensitivity, and positive predictive value were calculated. The relationship of mpCTE diagnosis and continued bleeding or iron supplementation was examined using logistic regression in patients with at least 1 year of follow-up.Results: We identified 1087 patients who had an initial mpCTE indication of small bowel bleeding. The overall DY was 31.6% (344 of 1087 patients; 95% CI, 29.0%-35.0%), higher for an indication of small bowel bleeding that was overt or occult with heme-positive stool vs occult with only iron-deficiency anemia (DY, 35.0% [170 of 486] and 35.3% [66 of 187] vs 26.1% [108 of 414]; P=.004 and P=.02, respectively). The highest sensitivity and positive predictive value were for small bowel masses (90.2% [55 of 61] and 98.2% [55 of 56], respectively). Higher risk of future bleeding and iron supplementation was seen with a negative result on mpCTE (odds ratio [OR], 1.91; 95% CI, 1.28-2.86), lack of surgical intervention (OR, 4.37; 95% CI, 2.31-8.29), or discrepant balloon-assisted enteroscopic findings (OR, 2.50; 95% CI, 1.03-6.09).Conclusion: Multiphase computed tomographic enterography has a higher rate of detection in patients with overt bleeding or heme-positive stool. The procedure provides actionable targets for further intervention and leads to substantially reduced rates of rebleeding in long-term follow-up.
View details for DOI 10.1016/j.mayocpiqo.2019.09.001
View details for PubMedID 31993562
IMPACT OF PATIENT FRAILTY ON ONE-YEAR MORTALITY ACROSS CHA2DS2-VASC SCORES: FROM THE TREAT-AF STUDY
ELSEVIER SCIENCE INC. 2019: 539
View details for Web of Science ID 000460565900539
CHA2DS2VASC and HAS-BLED Scores Predict Frailty in Non-Valvular Atrial Fibrillation
LIPPINCOTT WILLIAMS & WILKINS. 2018
View details for Web of Science ID 000528619406362
Yield of theRYR2Genetic Test in Suspected Catecholaminergic Polymorphic Ventricular Tachycardia and Implications for Test Interpretation.
Circulation. Genomic and precision medicine
2018; 11 (2): e001424
PathogenicRYR2variants account for ≈60% of clinically definite cases of catecholaminergic polymorphic ventricular tachycardia. However, the rate of rare benignRYR2variants identified in the general population remains a challenge for genetic test interpretation. Therefore, we examined the results of theRYR2genetic test among patients referred for commercial genetic testing and examined factors impacting variant interpretability.Frequency and location comparisons were made forRYR2variants identified among 1355 total patients of varying clinical certainty and 60 706 Exome Aggregation Consortium controls. The impact of the clinical phenotype on the yield ofRYR2variants was examined. Six in silico tools were assessed using patient- and control-derived variants.A total of 18.2% (218/1200) of patients referred for commercial testing hosted rareRYR2variants, statistically less than the 59% (46/78) yield among clinically definite cases, resulting in a much higher potential genetic false discovery rate among referrals considering the 3.2% background rate of rare, benignRYR2variants. Exclusion of clearly putative pathogenic variants further complicates the interpretation of the next novelRYR2variant. Exonic/topologic analyses revealed overrepresentation of patient variants in exons covering only one third of the protein. In silico tools largely failed to show evidence toward enhancement of variant interpretation.Current expert recommendations have resulted in increased use ofRYR2genetic testing in patients with questionable clinical phenotypes. Using the largest to date catecholaminergic polymorphic ventricular tachycardia patient versus control comparison, this study highlights important variables in the interpretation of variants to overcome the 3.2% background rate that confoundsRYR2variant interpretation.
View details for PubMedID 29453246
Sudden cardiac death and late arrhythmias after the Fontan operation.
Congenital heart disease
2017; 12 (1): 17-23
We sought to examine the incidence and predictors of arrhythmias and sudden cardiac death (SCD) after Fontan operation.Arrhythmias and SCD have been reported following operations for congenital heart disease, but the incidence and risk factors have not been well defined in patients after a Fontan operation.We reviewed records of all patients who had a Fontan operation from 1973 to 2012 (n = 1052) at our institution. A questionnaire was mailed to patients who were not known to be deceased at the initiation of the study. Late arrhythmias were classified as bradyarrhythmias or tachyarrhythmias requiring treatment >30 days after operation.We included 996/1052 (95%) patients with no arrhythmia diagnosis prior to Fontan. Overall 10-, 20-, and 30-year freedom from arrhythmias was 71%, 42%, and 24%, respectively. Of 864 patients who survived >30 days after Fontan, 304 (35%) had atrial flutter, 161 (19%) had atrial fibrillation, 108 (13%) had atrial tachycardia, 37 (4%) had reentrant supraventricular tachycardia, 40 (5%) had ventricular tachycardia, and 113 (13%) had sinus node dysfunction. Predictors of late arrhythmias included an atriopulmonary Fontan, age at operation (>16 years) or atrial arrhythmias postoperatively. During follow-up, 52/1052 (5%) patients had SCD, with 51 having documentation available; 8 patients died suddenly within 30 days and the remaining 43 had an average time to SCD of 6.9 ± 6.7 years (median was 3.8 years). Arrhythmias were documented in 28/43 (65%) patients prior to SCD. Predictors of SCD included atrioventricular valve replacement and post-bypass Fontan pressures >20 mm Hg; preoperative sinus rhythm was protective.Arrhythmias and SCD are significant concerns among Fontan patients and specific risk factors may warrant closer follow-up and earlier consideration for therapy.
View details for DOI 10.1111/chd.12401
View details for PubMedID 27545004
Heart transplantation after Fontan: Results from a surgical Fontan cohort.
2016; 20 (8): 1087-1092
We performed a retrospective review of outcomes after heart transplantation during long-term follow-up of a surgical cohort of 1138 Fontan patients who were followed at the Mayo Clinic. Follow-up information was obtained from medical records and a clinical questionnaire that was mailed to patients not known to be deceased at the initiation of the study. Forty-four of 1138 Fontan patients with initial or subsequent evaluation at Mayo had cardiac transplantation between 1988 and 2014 (mean age at transplantation was 23.2 ± 12 yr, median was 19.8 yr; mean interval between Fontan and transplantation was 13.0 ± 7.7 yr, median was 13.1 yr). Two patients had combined organ transplantation (one heart-lung, one heart-liver). Twelve of the 44 (27%) patients had PLE prior to transplantation. There was no difference in post-bypass Fontan pressures or incidence of late reoperations for AVV repair/replacement between transplanted and non-transplanted patients. There were 16 (36%) deaths in the transplantation cohort; seven occurred within 30 days of transplantation. Overall one, five, 10, and 15 yr post-transplantation survival was 80%, 72%, 69%, and 55%, respectively. Although this is a challenging group of patients, intermediate-term results suggest that cardiac transplantation remains a reasonable option for patients with a failed Fontan circulation.
View details for DOI 10.1111/petr.12753
View details for PubMedID 27397767
Evaluation of Patient Tolerance and Small-Bowel Distention With a New Small-Bowel Distending Agent for Enterography
AMERICAN JOURNAL OF ROENTGENOLOGY
2016; 206 (5): 994-1002
The objective of our study was to compare a flavored beverage containing a thickening agent for enterography with a low-Hounsfield-value barium suspension for side effects, taste, subjects' willingness to repeat the drinking protocol, and small-bowel distention.The following five drinking protocols were administered to 10 volunteers: 1000 mL of flavored beverage followed by 350 mL of water, 1500 mL of flavored beverage, 900 mL of low-Hounsfield-value barium suspension followed by 450 mL of water, 1350 mL of low-Hounsfield-value barium suspension followed by 150 mL of water, and 1500 mL of water. MR images were obtained 50 and 60 minutes after initiation of drinking. Subjects completed a questionnaire evaluating the side effects, the taste of the drink, and their willingness to repeat the drinking protocol. Reviewers assigned scores evaluating small-bowel distention and ranked the examinations in order of preference.There was no significant difference in nausea or vomiting among the protocols (p = 0.20 and 0.42, respectively), but larger volumes of flavored beverage and low-Hounsfield-value barium suspension resulted in more cramping and diarrhea (p = 0.001 and 0.002, respectively). The taste of the low-Hounsfield-value barium suspension was rated the worst (p < 0.0001). The subjects' willingness to repeat the drinking protocol was highest for the 1000 mL of flavored beverage or water alone (p < 0.05). There were no significant differences in subjective small-bowel distention except that water was rated the worst by two of the three readers (p < 0.02). There was no significant difference in the diameter of the most dis-tended small bowel for any segment or reader (p > 0.23).A flavored beverage containing a thickening agent has a similar side effect profile and results in equivalent small-bowel distention compared with a low-Hounsfield-value barium suspension, but subjects rate taste and their willingness to repeat the drinking protocol higher for this new agent.
View details for DOI 10.2214/AJR.15.15260
View details for Web of Science ID 000374860500020
View details for PubMedID 26998661
Liver Disease in Patients After the Fontan Operation
AMERICAN JOURNAL OF CARDIOLOGY
2016; 117 (3): 456-460
We reviewed records of all patients with an initial Fontan operation or revision from 1973 to 2012 at our institution (n = 1,138); 195 patients had postoperative liver data available. Cirrhosis was identified by histopathology or characteristic findings on imaging with an associated diagnosis of cirrhosis by a hepatologist. Of 195 patients with biopsy or imaging, 10-, 20-, and 30-year freedom from cirrhosis was 99%, 94%, and 57%, respectively. There were 40 of 195 patients (21%) diagnosed with cirrhosis (mean age at Fontan 10.7 ± 8 years). On multivariate analysis, hypoplastic left heart syndrome was associated with increased risk of cirrhosis (n = 2 of 16, p = 0.0133), whereas preoperative sinus rhythm was protective (p = 0.009). Survival after diagnosis of cirrhosis was 57% and 35%, at 1, and 5 years, respectively. The cause of death was known for 9 patients (5 multiorgan failure, 2 liver failure, and 2 heart failure). In conclusion, there is an incremental occurrence of cirrhosis after the Fontan, which should be considered when designing follow-up protocols for patients after Fontan operation.
View details for DOI 10.1016/j.amjcard.2015.11.014
View details for Web of Science ID 000369194200023
View details for PubMedID 26704027
Contraception Practices and Pregnancy Outcome in Patients after Fontan Operation
CONGENITAL HEART DISEASE
2016; 11 (1): 63-70
The feasibility and safety of pregnancy after the Fontan operation is not well understood. We sought to determine contraception practices and early and late outcomes of pregnancy after the Fontan operation.We performed a retrospective review of medical records to identify women of childbearing age from the Mayo Clinic Fontan database. A follow-up questionnaire was mailed to all patients not known to be deceased at the time of study. Patients with available contraception and pregnancy data were included in the study.Of the 138 women with available contraception data, 44% used no contraception, 12% each used barrier methods, combination hormone therapy or sterilization, 8% used Depo-Provera, 7% had intrauterine devices, 4% had a partner with a vasectomy and 1% used progestin pills. Six women had thrombotic complications (only one using oral contraceptives). Thirty-five women had pregnancy data available. Prior to the Fontan operation there were 10 pregnancies (8 miscarriages, 2 therapeutic abortions, and no live births). After the Fontan operation there were 70 pregnancies resulting in 35 miscarriages (50%), 29 live births (41%), and 6 therapeutic abortions (9%). There were no maternal deaths during pregnancy. During long-term follow up (26 ± 6 years since the Fontan), 1 death, and 1 cardiac transplant occurred. Mean gestational age of the newborns (n = 22/29) was 33.1 ± 4.0 weeks; mean birth weight (n = 20/29) was 2086 ± 770 g. There was 1 neonatal death because of prematurity and two children were born with congenital heart disease (one patent ductus arteriosus and one membranous ventricular septal defect).Pregnancy after the Fontan operation is associated with a high rate of miscarriages, preterm delivery, and low birth weight. Further studies are needed to identify specific variables influencing risk stratification of pregnancy in this patient population.
View details for DOI 10.1111/chd.12291
View details for Web of Science ID 000371241800010
View details for PubMedID 26239864
40-Year Follow-Up After the Fontan Operation Long-Term Outcomes of 1,052 Patients
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
2015; 66 (15): 1700-1710
There are limited long-term, single-cohort, follow-up studies available about patients after the Fontan operation.This study sought to determine the long-term outcome of all patients who had a Fontan operation at the Mayo Clinic.Records of all patients who had a modified Fontan operation between 1973 and 2012 were reviewed. A follow-up questionnaire was mailed to all patients alive at the time of the study.Overall, 10-, 20-, and 30-year survival for 1,052 patients was 74%, 61%, and 43%, respectively. Factors associated with decreased overall or late survival in multivariate analysis included pre-operative diuretic use, longer cardiopulmonary bypass time, operation prior to 1991, atrioventricular valve (AVV) replacement at the time of Fontan operation, elevated post-bypass Fontan (>20 mm Hg) or left atrial (>13 mm Hg) pressures, prolonged chest tube drainage (>21 days), post-operative ventricular arrhythmias, renal insufficiency, and development of protein-losing enteropathy (PLE). Pre-operative and intraoperative sinus rhythm were associated with improved survival. Long-term survival was similar for patients regardless of ventricular morphology. The most common reoperations were pacemaker insertion/revision in 212 patients (20%), Fontan revision/conversion in 117 patients (11%), and AVV repair/replacement in 66 patients (5%). Clinically significant late atrial or ventricular arrhythmias occurred in 468 patients (44%). Ninety-five patients (9%) developed PLE, and 5-, 10-, and 20-year survival after diagnosis of PLE was 50%, 35%, and 19%, respectively.As the surgical techniques for the Fontan operation have changed over the last 40 years, survival has improved. However, development of PLE and arrhythmias and the need for reoperation during long-term follow-up pose significant management challenges.
View details for DOI 10.1016/j.jacc.2015.07.065
View details for Web of Science ID 000363329200009
View details for PubMedID 26449141
40 YEARS OF THE FONTAN OPERATION: LONG-TERM OUTCOME OF 1,052 PATIENTS
64th Annual Scientific Sessions and Expo of the American-College-of-Cardiology (ACC)
ELSEVIER SCIENCE INC. 2015: A506–A506
View details for DOI 10.1016/S0735-1097(15)60506-X
View details for Web of Science ID 000375328800507
Forequarter amputation for recurrent breast cancer.
International journal of surgery case reports
2015; 11: 24-28
Localized excision combined with radiation and chemotherapy represents the current standard of care for recurrent breast cancer. However, in certain conditions a forequarter amputation may be employed for these patients.We present a patient with recurrent breast cancer who had a complicated treatment history including multiple courses of chemotherapy, radiation, and local surgical excision. With diminishing treatment options, she opted for a forequarter amputation in an attempt to limit the spread of cancer.In our patient the forequarter amputation was utilized as a last resort to slow disease progression after she had failed multiple rounds of chemotherapy and received maximal radiation. Unfortunately, while she had symptomatic relief in the short-term, she had cutaneous recurrence of metastatic adenocarcinoma within 2 months of the procedure. In comparing this case with other reported forequarter amputations, patients with non-metastatic disease showed a mean survival of approximately two years. Furthermore, among patients who had significant pain prior to surgery, all patients reported pain relief, indicating a significant palliative benefit. This seems to indicate that our patient's unfortunate outcome was anomalous compared to that of most patients undergoing forequarter amputation for recurrent breast cancer.Forequarter amputation can be judiciously used for patients with recurrent or metastatic breast cancer. Patients with recurrent disease without evidence of distant metastases may be considered for curative amputation, while others may receive palliative benefit; disappointingly our patient achieved neither of these outcomes. In the long term, these patients may still have significant psychological problems.
View details for DOI 10.1016/j.ijscr.2015.04.018
View details for PubMedID 25898339
Coordination of Hand Shape
JOURNAL OF NEUROSCIENCE
2011; 31 (10): 3757-3765
The neural control of hand movement involves coordination of the sensory, motor, and memory systems. Recent studies have documented the motor coordinates for hand shape, but less is known about the corresponding patterns of somatosensory activity. To initiate this line of investigation, the present study characterized the sense of hand shape by evaluating the influence of differences in the amount of grasping or twisting force, and differences in forearm orientation. Human subjects were asked to use the left hand to report the perceived shape of the right hand. In the first experiment, six commonly grasped items were arranged on the table in front of the subject: bottle, doorknob, egg, notebook, carton, and pan. With eyes closed, subjects used the right hand to lightly touch, forcefully support, or imagine holding each object, while 15 joint angles were measured in each hand with a pair of wired gloves. The forces introduced by supporting or twisting did not influence the perceptual report of hand shape, but for most objects, the report was distorted in a consistent manner by differences in forearm orientation. Subjects appeared to adjust the intrinsic joint angles of the left hand, as well as the left wrist posture, so as to maintain the imagined object in its proper spatial orientation. In a second experiment, this result was largely replicated with unfamiliar objects. Thus, somatosensory and motor information appear to be coordinated in an object-based, spatial-coordinate system, sensitive to orientation relative to gravitational forces, but invariant to grasp forcefulness.
View details for DOI 10.1523/JNEUROSCI.5158-10.2011
View details for Web of Science ID 000288160500025
View details for PubMedID 21389230