Women often experience heart disease differently than men. The FDA Office of Women's Health (OWH) supports research to help the FDA learn more about sex differences in the safety and efficacy of FDA-regulated medical products for the diagnosis and treatment of heart disease. The projects listed on this page have been completed. Publications highlighting the projects results are listed after the name of the project.
Completed Projects listed by Funding Year
PK analysis of the samples for a study funded by CDER Critical Pathways titled, “A double-blind, randomized, placebo-controlled single-dose, five-period crossover study of the electrocardiographic effects of ranolazine, dofetilide, verapamil and quinidine in healthy subjects” – David Strauss, MD, PhD, CDRH and Norman Stockbridge, MD, PhD, CDER
- Johannesen L, Vicente J, Mason J, et al. Differentiating drug-induced multi-channel block on the electrocardiogram: Randomized study of dofetilide, quinidine, ranolazine, and verapamil. Clin Pharmacol Ther 2014 Nov;96(5):549-58.
- Vicente J, Johannesen L, Mason JW, et al. Comprehensive T wave morphology assessment in a randomized clinical study of dofetilide, quinidine, ranolazine, and verapamil. J Am Heart Assoc. 2015 Apr 13;4(4).
Novel Electrocardiogaphic Device Algroithms to Assess Cardiac Safety of Investigational Drugs – David Strauss, MD, PhD, CDRH
- Johannesen L, Vicente J, Galeotti L and Strauss DG. “ECGlib: Library for Processing Electrocardiograms”. In: Comput Cardiol; 2013: IEEE; 2013. p. 951-954.
- Vincente J, Johannesen L, Galeotti L, Strauss DG. ECGlab: User friendly ECG/VCG analysis tool for research environments. In: Comput Cardiol; 2013: IEEE; Sept 2013. p. 775-778.
- Johannesen L, Vicente J, Gray RA, et al. Improving the Assessment of Heart Toxicity for all New Drugs Through Translational Regulatory Science. Clin Pharmacol Ther 2014; May; 95(5):501-8.
- Vicente J, Johannesen L, Galeotti L, Strauss DG. Mechanisms of sex and age differences in ventricular repolarization in humans. American Heart Journal 2014 Nov;168(5):749-56.
Gender-Specific Predictors of Heart Failure Hospitalization and Death in Cardiac Resynchronization Therapy - David Strauss, MD, PhD, CDRH
- D Strauss. Filling Information Gaps for Women in Medical Device Trials. FDA Voice Blog: June 2014.
- Zusterzeel R, Spatz ES, Curtis JP, et al. Cardiac resynchronization therapy in women versus men: Observational comparative effectiveness study from the national cardiovascular data registry. Circ Cardiovasc Qual Outcomes. 2015 Mar;8(2 Suppl 1):S4-11.
- Zusterzeel R, Curtis JP, Canos DA, et al. Sex-specific mortality risk by QRS morphology and duration in patients receiving CRT: Results from the NCDR. Journal of the American College of Cardiology 2014; 64 (9):887-894.
- Zusterzeel R., Selzman KA., Sanders WE., Canos DA., O’Callaghan KM., Carpenter JL., Pina IL., Strauss DG. Cardiac resynchronization therapy in women: US Food and Drug Administration meta-analysis of patient-level data. JAMA Intern Med 2014;174(8):1340-1348.
- Z Loring, D Strauss, G Gerstenblith, G Tomaselli, R Weiss, K Wu. Cardiac MRI scar patterns differ by gender in an implantable cardioverter defibrillator and cardiac resynchronization cohort, Heart Rhythm 2013; 10(5):659–665.
- Loring Z, Caños DA, Selzman K, Herz ND, Silverman H, MaCurdy TE, Worrall CM, Kelman J, Richey ME, Piña IL, Strauss DG. Left Bundle Branch Block Predicts Better Survival in Women than Men Receiving Cardiac Resynchronization Therapy: Long Term Follow-Up of 145,000 Patients. J Am Coll Cardiol HF 2013; 1:237-44
Investigate the mechanisms of trastuzumab-induced cardiotoxicity and cardiotoxicity and cardio protective role of antioxidants in trastuzumab-mediated cardiac dysfunction - Wen Jin Wu, MD, PhD, CDER
- ElZarrad MK, Mukhopadhyay P, Mohan N, et al. Trastuzumab alters the expression of genes essential for cardiac function and induces ultrastructural changes of cardiomyocytes in mice. PLoS One Nov 2013; 8:e79543
- Wu W, Dokmanovic M. (2012) Trastuzumab. In Schwab M. (Ed.) Encyclopedia of Cancer(pp.3776). Springer-Verlag Berlin Heidelberg. http://link.springer.com/referenceworkentry/10.1007/978-3-642-16483-5_5962
Preclinical Test Methods for Percutaneously Implanted Heart Valves: Effect of Non-Circular Valve Configuration After Implantation On Valve Leaflet Dynamics – Terry Woods, NCTR
Genetic and epigenetic mechanisms for sex differences in the kidney of a rat model system: developing safety biomarkers for FDA regulated products – James Fuscoe, PhD, NCTR
- Kwekel JC, Desai VG, Moland CL, Vikrant V, Fuscoe JC. Life cycle analysis of kidney gene expression in male F344 rats. PloS One 2013; 8(10):e75305
- Kwekel JC, Desai VG, Moland CL, Vikrant V, Fuscoe JC. Sex differences in kidney gene expression during the life cycle of F344 rats. Biol of Sex Differ 2013; 4(14)
- Marti HP, Fuscoe JC, Kwekel JC, Anagnostopoulu A, Scherer A. Metzincins and related genes in experimental renal ageing: towards a unifying fibrosis classifier across species. Nephrol Dial Transplant 2014; doi: 10.1093/ndt/gfu027.
- Yu Y, Fuscoe JC, Zhao C, et al. A rat RNA-Seq transcriptomic BodyMap across 11 organs and 4 developmental stages. Nat Commun 2014; 5:3230.
- Kwekel JC, Vijay V, Desai VG, Moland CL, Fuscoe JC. Age and sex differences in kidney microRNA expression during the life span of F344 rats. Biol Sex Differ. 2015 Jan;6(1):1.
Prospective assessment of clinical and patients-reported outcomes for female patients undergoing Percutaneous Coronary Intervention (PCI) procedures via femoral and radial access - Katie O’Callaghan, CDRH
- Hess CN, Krucoff MW, Sheng S, et al. Comparison of quality-of-life measures after radial versus femoral artery access for cardiac catheterization in women: Results of the Study of Access Site for Enhancement of Percutaneous Coronary Intervention for Women quality-of-life substudy. Am Heart J. 2015 Aug;170(2):371-9.
Addressing the unmet medical needs for cardioproctection in women receiving chemotherapy – Rao, Ashutosh, CDER
Sex-based differences in the molecular mechanisms of polymer degradation in drug eluting stents (DES) - Patwardhan, Dinesh, PhD, CDRH
- J Guo, D Saylor, E Glaser, D Patwardhan. Impact of artificial plaque composition on drug transport. J Pharm Sci, 2013 Jun;102(6):1905-14.
- McDermott MK, Kim CS, Saylor DM, Patwardhan DV. Impact of copolymer ratio on drug distribution in styrene-isobutylene-styrene block copolymers. J Biomed Mater Res B Appl Biomater. 2013 Oct;101(7):1191-9
Sex-Specific Left Bundle Branch Block Criteria and ECG Scar Quantification to Predict Benefit from Cardiac Resynchronization Therapy (CRT) – David Strauss MD, PhD, CDRH
- Loring Z, Chelliah S, Selvester R, Wagner G, Strauss D. A detailed guide for quantification of myocardial scar with the Selvester QRS score in the presence of electrocardiogram confounders. Journal of Electrocardiology 2011; 44:544–554.
Atrial Fibrillation Ablation Registry Study (SAFARI) - Ellen Pinnow, MPH, CDRH (10)
Assessment of outcomes and bleeding complications following implantation of drug eluting stents (DES) and dual anti-platelet therapy (DAPT) - Hesha Duggirala, Ph.D, CDRH
- Hess CN, McCoy LA, Duggirala HJ, et al. Sex-based differences in outcomes after percutaneous coronary intervention for acute myocardial infarction: A report from TRANSLATE-ACS. J Am Heart Assoc 2014; 3(1):e000523.
Assessment of Risk Factors Associated with Exposure to Proton Pump inhibitors and Fracture and CV outcomes in post-menopausal osteoporosis woman - Antonio Paredes, CDER
Risk of Adverse Events Following Cardiac Catheterization by Hemostasis Device Use – Phase III - Dale Tavris, MD, MPH, CDRH
- Tavris DR, Wang Y, Jacobs S, et al. Bleeding and vascular complications at the femoral access site following percutaneous coronary intervention (PCI): an evaluation of hemostasis strategies. J Invasive Cardiol 2012 124: 328-34.
The swan-ganz balloon flotation pulmonary artery catheter: possible racial and sex discrepancies - Daniel Canos, Ph.D, CDRH
- Iantorno M, Panza JA, Cook NL, et al. Gender-and race-based utilization and outcomes of pulmonary artery catheterization in the setting of full-time intensivist staffing. Acute Card Care 2012; 14:125-30.
- Cooper HA, Najafi AH, Ghafourian K, et al. Diagnosis of cardiogenic shock without the use of a pulmonary artery catheter. Eur Heart J Acute Cardiovasc Care. 2015 Feb;4(1):88-95.
Sex- and age- related differences in baseline QT, QT prolongation, and TdP risk - Christine Garnett, Pharm D, CDRH
Analysis of sex-differences in cardiac resynchronization therapy devices: inclusion, adverse events, and outcomes - Kathryn O’Callaghan, CDRH
Sex-based differences in the safety of drug-eluting stents containing bioresorbable materials - Dinesh Patwardhan, Ph.D., CDRH
Publications from this project:
- McDermott MK, Saylor DM, Casas R, et al. Microstructure and elution of tetracycline from block copolymer coatings. J Pharm Sci. 2010 Jun;99(6):2777-85.
Workshop: Guidance for the Study and Analysis of Sex Differences in the Clinical Evaluation of Cardiovascular Medical Devices - Kathryn O’Callaghan, CDRH
- Guidance developed: Draft Guidance for Industry and Food and Drug Administration Staff - Evaluation of Sex Differences in Medical Device Clinical Studies. Issued: December 19, 2011. http://www.fda.gov/medicaldevices/deviceregulationandguidance/guidancedocuments/ucm283453.htm
Gender-Related Differences in QT Effects and Torsade de Pointes Potential of Drugs - Christine Garnett, PharmD/ Phillip Dinh, PhD, CDER
Publication from this project:
- Dinh P, Sun J, Bai S, Kordzakhia G. Sex-Related Differences in QTc Effects Potential of Drugs. Rev Recent Clin Trials 2011; 6(3): 220-227.
Factors Accelerating the Progression of Heart Failure (HF) in Women: Implications for Drug Interactions with Medical Devices - Soma Kalb, PhD, CDRH (07)
Evaluation of Availability and Quality of Information Available on Females Included in Mechanical device Implant Trials - Kathryn O’Callaghan, CDRH
ECG Warehouse - Mortara Instruments Inc., Justin Mortara, PhD, Mortara Instruments Inc.
Publication from this project:
- Sarapa N, Mortara JL, Brown BD, Isola L, Badilini F. Quantitative performance of e-scribe warehouse in detecting quality issues with digital annotated ECG data from healthy subjects. J Clin Pharmacol 2008; 48:538-546.
ECG Warehouse - Duke Clinical Research Institute and Duke University - Christopher Cabell, M.D., MHS, Duke Clinical Research Institute (DCRI)
Assessment of the Accuracy of the Troponin Assay and the Diagnosis of Myocardial Infarction by Gender - Azadeh Shoaibi, PhD/ Dale Tavris, MD, MPh, CDRH (05)
- Shoaibi A, Tavris DR, McNulty S. Gender differences in correlates of troponin assay in diagnosis of myocardial infarction. Translational Research 2009; 154:250–256.
- Tavris DR, Shoaibi A, Chen AY, Uchida T, Roe, Chen J. Gender differences in the treatment of non–ST-segment elevation myocardial infarction. Clin. Cardiol 2010; 33(2):99–103.
Systems Biology Approach to Evaluate Sex Differences in Heart of a Rat Model - James C. Fuscoe, Ph.D., NCTR
Implications of Gender-based Differences in Cardiovascular Disease on Imaging for Treatment and Diagnosis - Iacovos Kyprianou, Ph.D., CDRH
Use and Outcomes of Coronary Stents in Women: Use of a National Medicare Database - Karen Freund, MD, Boston Univ
Fruend KM, Jacobs AK, Pechacek JA, White HF, Ash AS. Disparities by Race, Ethnicity, and Sex in Treating Acute Coronary Syndromes. Journal of Women's Health 2012; 21(2): 126-131.
Transmission Attenuation Correction for Female Patients Undergoing Myocardial Perfusion Imaging: Correction for Confounding Breast Tissue Artifact - Michelle Dew, MD, Univ. of Arizona
Pilot Study: Combined Beta1 Arg 389 and Alpha 2c Del 322-325 Adrenergic Receptor Polymorphisms and Heart Failure with Preserved Left Ventricular Ejection Fraction in African American Women - Thierry LeJemtel, MD, Tulane Univ
Are Women at Higher risk from Proarrhythmic Drugs? - Jogarao Gobburu, PhD, CDER (03)
- International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). E14 Guidance on Clinical Evaluation of QT/QTc Interval Prolongation and Proarrhythic Potential for Non-Antiarrthmic Drugs 2005. Available from: http://www.fda.gov/downloads/RegulatoryInformation/Guidances/ucm129357.pdf
Discovery and Evaluation of Interspecies Biomarkers to Monitor the Early Onset and the Progression of Cardiovascular Toxicity Associated with Thiazolidinedione Compounds Used in the Treatment of Type 2 Diabetes - Eugene Herman, PhD, CDER
Cardiovascular Effects Of Ultrasound Contrast Agents in Intact and Ovariectomized Female Animals - Melvin Stratmeyer, PhD, CDRH
Electrophysiological Characterization of Several Torsadogenic Drugs in Isolated Rabbit Hearts - John Koerner, PhD, CDER
- Katchman AN, Koerner J, Tosaka T, Woosley RL, Ebert SN. Comparative evaluation of HERG currents and QT intervals following challenge with suspected torsadogenic and nontorsadogenic drugs. J Pharmacol Exp Ther. Epub 2006; 316:1098–1106.
Pharmacokinetics and Pharmacodynamics (PK/PD) of Atenolol in Pregnancy - Mary Hebert, PharmD, University of Washington, Dept of Pharmacy
- Hebert MF, Carr DB, Anderson GD, Blough D, Green GE, Brateng DA, Kantor E, Benedetti TJ, Easterling TR. Pharmacokinetics and pharmacodynamics of atenolol during pregnancy and postpartum. J Clin Pharmacol 2005; 45(1):25-33.
- Eyal S, Kim JD, Anderson GD, et al. Atenolol Pharmacokinetics and Excretion in Breast Milk During the First 6 to 8 Months Postpartum. J Clin Pharmacol 2010; 50:1301-309
Incidence and attributable risk of serious adverse events and death associated with the use of homeostasis devices by gender – Dale Tavris MD, MPH, CDRH
- Tavris DR, Gallauresi B, Rich S, Bell B, Relative risks of reported serious injury and death associated with hemostasis devices by gender. Pharmacoepidemiology and Drug Safety 2003; 12(3):237-241
- Tavris DR, Gallauresi BA, Lin B, Rich SE, Shaw RE, Weintraub WS, Brindis RG, Hewitt K. Risk of local adverse events following cardiac catheterization by hemostasis device use and gender. J Invasive Cardiol 2004; 16(9):459-64.
- Tavris DR, Dey S, Gallauresi BA, Brindis RG, Shaw R, Weintraub W, Mitchel K. Risk Of local adverse events following cardiac catheterization by hemostasis device use: phase II. J Invasive Cardiol 2005; 17(12):644-50
- Tavris DR Md, Gallauresi BA, Dey S, Brindis R, Mitchel K. Risk of local adverse events by gender following cardiac catheterization. Pharmacoepidemiology And Drug Safety 2007; 16:125–131.
Discovery and evaluation of interspecies biomarkers to identify and characterize the cardiotoxic effects of Transtuzumab (Herceptin), a novel antibody used in the treatment of breast cancer - Eugene Herman, PhD, CDER
Labetalol and Hypertension in Pregnancy: Pharmacokinetics and Pharmacodynamics - James Fischer, Ph.D. University of Illinois, Chicago
Publications from this project:
- Fischer JH, Sarto GE, Hardman J, et al. Influence of gestational age and body weight on the pharmacokinetics of labetalol in pregnancy. Clin Pharmacokinet 2014 Apr;53(4):373-83
- JH. Fischer, GE. Sarto, M Habibi, SJ. Kilpatrick, RE. Tuomala, JM. Shier, L Wollett, PA. Fischer, KS. Khorana, KA. Rodvold. Influence of Body Weight, Ethnicity, Oral Contraceptives, and Pregnancy on the Pharmacokinetics of Azithromycin in Women of Childbearing Age. Antimicrob. Agents Chemother 2012; 56(2):715-724.
Women's participation in clinical drug trials for unstable angina and myocardial infarction - Ann Farrell, MD, CDER (00)
Surveillance of Sex-specific Utilization, Morbidity, and Mortality Associated with Transmyocardial Revascularization - Ronald Kaczmarek, MD, MPH, CDRH (00)
Publication from this project:
- Peterson ED, Kaul P, Kaczmarek RG, Hammill BG, Armstrong PW, Bridges CR, Ferguson TB. From controlled trials to clinical practice: monitoring transmyocardial revascularization use and outcomes. J Am Coll Cardiol 2003; 42(9):1611-6.
Flow studies and the use of a waveguide in cardiovascular devices - Harvey Rudolf, PhD, CDRH
Ovarian steroids and cardiovascular disease: The role of gender in the effectiveness of interventional medical devices - James Karanian, PhD, CDRH
Variations in the drug-induced QT interval prolongation during the menstrual cycle - Ana Szarfman, MD, PhD, Raymond L. Woosley, MD, PhD, CDER (co-funded by NIH ORWH, 98)
Publication from this project:
- Rodriguez J, Kilborn MJ, Liu, XK, Pezzullo JC, Woosley RL. Drug-Induced QT prolongation in women during the menstrual cycle. JAMA 2001; 285:1322-1326.
Epidemiology of medical devices in women - Danica Marinac-Dabic, MD, CDRH (97)
A comparison of gender specific utilization of implantable cardioverter defibrillator therapy and post-implantation survivability - Steven Lascher, DVM, MPH, CDRH (97)
Administration of thrombolytic therapy to women with acute myocardial infarction. Is it too late? - Emily B. Shacter, PhD, CBER (96)
- Rieves D, Wright G, Gupta G, Shacter E. Clinical Trial (GUSTO-1 and INJECT) Evidence of Earlier Death for Men than Women After Acute Myocardial Infarction. Am J Cardiol 2000; 85:147–153.
Gender differences in early and long-term results of coronary angioplasty with the Palmaz/Schatz stent - Danica Marinac-Dabic, MD, CDRH (95, 96, 97)
Comparison of the beta-adrenergic antagonist actions of propranolol in men and women - David Flockhart, MD, PhD, CDER (94)
Comparison of the potassium channel blocking actions of quinidine in men and women - Raymond L. Woosley, MD, PhD, CDER (94)
- Benton RE, Sale M, Flockhart DA, Woosley RL. Greater quinidine-induced QTc interval prolongation in women. Clin Pharmacol Ther 2000; 67:413-8.
Terfenadine/Oral contraceptive study - Lou Cantillina, MD, CDER (94)
- Douglas PS, Brennan JM, Anstrom KA, Sedrakyan A, Eisenstein EL, Haque G, Dai D, Kong DF, Hammill B, Curtis L, Matchar D, Brindis R, Peterson RD, Clinical Effectiveness of Coronary Stents in Elderly Persons - Results From 262,700 Medicare Patients in the American College of Cardiology–National Cardiovascular Data Registry, J Am C Cardiol 2009; 53(18):1629-41.
- Guo L, Dial S, Shi L, Branham W, Liu J, Fang JL, Green B, Deng h, Kaput J, Ning B. Similarities and Differences in the Expression of Drug Metabolizing Enzymes between Human Hepatic Cell Lines and Primary Human Hepatocytes. Drug Metab Dispos, 2011; 39(3):528-38.
- Yang L, Yan L, Hong H, Chang C-W, Guo L-W, Lyn-Cook B, Shi L, Ning B. Sex difference in the expression of drug metabolizing and transporter genes in human liver. J. Drug Metab. & Toxicol. 2012; 3:119. doi:10.4172/2157-7609.1000119.
- Kim CS, Saylor DM, McDermott MK, Patwardhan DV, Warren JA. Modeling solvent evaporation during the manufacture of controlled drug-release coatings and the impact on release kinetics. J Biomed Mater Res B Appl Biomater. 2009 Aug;90(2):688-99.