Nancy K Sweitzer

Interests

Research

Heart failure clinical trials, drug and device treatment of heart failure, heart failure with preserved ejection fraction physiology, heart failure genetics, proteomics, biomarkers and metabolomics

Courses

Scholarly Contributions

Books

• Sweitzer, N. K. (2011). Braunwald’s Heart Disease: Review and Assessment, 6th edition. Philadelphia, PA: WB Saunders Co.
• Sweitzer, N. K. (2007). Risk Factor Management and Lifestyle Modification in Heart Failure. Philadelphia, PA: Elsevier Saunders.
• Sweitzer, N. K. (2003). Braunwald’s Heart Disease: Cardiovascular Disease in Women,. Philadelphia, PA: WB Saunders Co./Elsevier Health Sciences.
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  ContributorWith 35 new chapters as well as comprehensive updates throughout, the New Edition of the cardiology masterwork represents the most complete revision to date. Hundreds of world authorities synthesize all of the developments that are revolutionizing practice—from the newest findings in molecular biology and genetics to the latest imaging modalities, interventional
• Sweitzer, N. K. (2001). Braunwald’s Heart Disease: Review and Assessment, 6th edition. Philadelphia, PA: WB Saunders Co./Elsevier Health Sciences.
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  Contributor : The New Edition of this incontrovertible champion among cardiology references brings all of the clinical know-how you need. World authorities synthesize all of the remarkable developments that are revoluntionizing cardiology practice*from the newest findings in molecular genetics through the latest imaging modalities, interventional procedures, and

Chapters

• Sweitzer, N. K. (2013). Hemodynamic Optimization in the Patient with Refractory Systolic Heart Failure. In Heart Failure: A Case-Based Approach. New York, NY: Demos Medical Publishing.
• Sweitzer, N. K. (2009). Pathophysiology of Heart Failure. In Device Therapy in Heart Failure. Totowa, NJ: Humana Press. doi:10.1007/978-1-59745-424-7

Journals/Publications

• Barac, Y. D., Jawitz, O. K., Klapper, J., Schroder, J., Daneshmand, M. A., Patel, C., Hartwig, M. G., Sweitzer, N. K., & Milano, C. A. (2019). Heart Transplantation Survival and the Use of Traumatically Brain-Injured Donors: UNOS Registry Propensity-Matched Analysis. Journal of the American Heart Association, 8(17), e012894.
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  Background The transplantation of hearts from traumatically brain-injured (TBI) donors has been associated with inferior long-term survival in single-center analyses. However, in a more recent analysis, death caused by cerebrovascular accident was associated with worse posttransplant survival in recipients. The purpose of this study was to explore the outcomes of heart transplantation in recipients receiving donor hearts from TBI and non-TBI donors in a large national registry. Methods and Results We performed a retrospective cohort analysis of the UNOS (United Network of Organ Sharing) Registry Organ Procurement and Transplantation Network between 2006 and 2018 for adult candidates wait-listed for isolated heart transplantation. Recipients were stratified into 2 groups, TBI and non-TBI donors. Propensity score matching was performed. Kaplan-Meier analysis was used to estimate survival posttransplant. A total of 24 894 candidates met inclusion criteria. TBI was the leading cause of death in the donor population. Recipients of TBI donor hearts (N=13 07) were younger (median age, 55 versus 57 years; P
• Breathett, K., Yee, E., Pool, N., Hebdon, M., Crist, J. D., Knapp, S., Larsen, A., Solola, S., Luy, L., Herrera-Theut, K., Zabala, L., Stone, J., McEwen, M. M., Calhoun, E., & Sweitzer, N. K. (2019). Does Race Influence Decision Making for Advanced Heart Failure Therapies?. Journal of the American Heart Association, 8(22), e013592.
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  Background Race influences medical decision making, but its impact on advanced heart failure therapy allocation is unknown. We sought to determine whether patient race influences allocation of advanced heart failure therapies. Methods and Results Members of a national heart failure organization were randomized to clinical vignettes that varied by patient race (black or white man) and were blinded to study objectives. Participants (N=422) completed Likert scale surveys rating factors for advanced therapy allocation and think-aloud interviews (n=44). Survey results were analyzed by least absolute shrinkage and selection operator and multivariable regression to identify factors influencing advanced therapy allocation, including interactions with vignette race and participant demographics. Interviews were analyzed using grounded theory. Surveys revealed no differences in overall racial ratings for advanced therapies. Least absolute shrinkage and selection operator regression selected no interactions between vignette race and clinical factors as important in allocation. However, interactions between participants aged ≥40 years and black vignette negatively influenced heart transplant allocation modestly (-0.58; 95% CI, -1.15 to -0.0002), with adherence and social history the most influential factors. Interviews revealed sequential decision making: forming overall impression, identifying urgency, evaluating prior care appropriateness, anticipating challenges, and evaluating trust while making recommendations. Race influenced each step: avoiding discussing race, believing photographs may contribute to racial bias, believing the black man was sicker compared with the white man, developing greater concern for trust and adherence with the black man, and ultimately offering the white man transplantation and the black man ventricular assist device implantation. Conclusions Black race modestly influenced decision making for heart transplant, particularly during conversations. Because advanced therapy selection meetings are conversations rather than surveys, allocation may be vulnerable to racial bias.
• Hill, J. A., Agewall, S., Baranchuk, A., Booz, G. W., Borer, J. S., Camici, P. G., Chen, P. S., Dominiczak, A. F., Erol, ., Grines, C. L., Gropler, R., Guzik, T. J., Heinemann, M. K., Iskandrian, A. E., Knight, B. P., London, B., Lüscher, T. F., Metra, M., Musunuru, K., , Nallamothu, B. K., et al. (2019). Medical Misinformation. Circulation, 139(5), 571-572.
• Hill, J. A., Agewall, S., Baranchuk, A., Booz, G. W., Borer, J. S., Camici, P. G., Chen, P. S., Dominiczak, A. F., Erol, ., Grines, C. L., Gropler, R., Guzik, T. J., Heinemann, M. K., Iskandrian, A. E., Knight, B. P., London, B., Lüscher, T. F., Metra, M., Musunuru, K., , Nallamothu, B. K., et al. (2019). Medical Misinformation. Hypertension (Dallas, Tex. : 1979), 73(3), 506-507.
• Hill, J. A., Agewall, S., Baranchuk, A., Booz, G. W., Borer, J. S., Camici, P. G., Chen, P. S., Dominiczak, A. F., Erol, C., Grines, C., Gropler, R. J., Guzik, T. J., Heinemann, M. K., Iskandrian, A. E., Knight, B. P., London, B., Lüscher, T. F., Metra, M., Musunuru, K., , Nallamothu, B. K., et al. (2019). Medical Misinformation: Vet the Message!. Circulation.
• McMurray, J. J., Jackson, A. M., Lam, C. S., Redfield, M. M., Anand, I. S., Ge, J., Lefkowitz, M. P., Maggioni, A. P., Martinez, F., Packer, M., Pfeffer, M. A., Pieske, B., Rizkala, A. R., Sabarwal, S. V., Shah, A. M., Shah, S. J., Shi, V. C., van Veldhuisen, D. J., Zannad, F., , Zile, M. R., et al. (2019). Effects of Sacubitril-Valsartan, versus Valsartan, in Women Compared to Men with Heart Failure and Preserved Ejection Fraction: Insights from PARAGON-HF. Circulation.
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  Unlike heart failure with reduced ejection fraction, there is no approved treatment for heart failure with preserved ejection fraction (HFpEF), the predominant phenotype in women. Therefore, there is a greater heart failure therapeutic deficit in women, compared with men. In a pre-specified subgroup analysis, we examined outcomes according to sex in the PARAGON-HF trial which compared sacubitril-valsartan and valsartan in patients with HFpEF. The primary outcome was a composite of first and recurrent hospitalizations for heart failure and death from cardiovascular causes. We also report secondary efficacy and safety outcomes. Overall, 2479 women (51.7%) and 2317 men (48.3%) were randomized. Women were older, had more obesity, less coronary disease, and lower estimated glomerular filtration rate and NT-proBNP levels than men. For the primary outcome, the rate ratio for sacubitril-valsartan versus valsartan was 0.73 (95% CI 0.59-0.90) in women and 1.03 (0.84-1.25) in men; P interaction=0.017. The benefit from sacubitril-valsartan was due to reduction in heart failure hospitalization. The improvement in NYHA class and renal function with sacubitril-valsartan was similar in women and men, whereas the improvement in KCCQ-CSS was less in women than in men. The difference in adverse events, between sacubitril-valsartan and valsartan, was similar in women and men. As compared with valsartan, sacubitril-valsartan seemed to reduce the risk of heart failure hospitalization more in women than in men. While the possible sex-related modification of the effect of treatment has several potential explanations, the present study does not provide a definite mechanistic basis for this finding. URL: https://clinicaltrials.gov Unique Identifier: NCT01920711.
• Merrill, M., Sweitzer, N. K., Lindenfeld, J., & Kao, D. P. (2019). Sex Differences in Outcomes and Responses to Spironolactone in Heart Failure With Preserved Ejection Fraction: A Secondary Analysis of TOPCAT Trial. JACC. Heart failure, 7(3), 228-238.
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  This study sought to investigate sex differences in outcomes and responses to spironolactone in patients with heart failure with preserved ejection fraction (HFpEF).
• Minamisawa, M., Seidelmann, S. B., Claggett, B., Hegde, S. M., Shah, A. M., Desai, A. S., Lewis, E. F., Shah, S. J., Sweitzer, N. K., Fang, J. C., Anand, I. S., O'Meara, E., Rouleau, J. L., Pitt, B., & Solomon, S. D. (2019). Impact of Malnutrition Using Geriatric Nutritional Risk Index in Heart Failure With Preserved Ejection Fraction. JACC. Heart failure, 7(8), 664-675.
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  This study sought to investigate the relationship between malnutrition and adverse cardiovascular (CV) events in heart failure with preserved ejection fraction (HFpEF).
• Myhre, P. L., Vaduganathan, M., Claggett, B. L., Lam, C. S., Desai, A. S., Anand, I. S., Sweitzer, N. K., Fang, J. C., O'Meara, E., Shah, S. J., Shah, A. M., Lewis, E. F., Rouleau, J., Pitt, B., & Solomon, S. D. (2019). Application of the H FPEF score to a global clinical trial of patients with heart failure with preserved ejection fraction: the TOPCAT trial. European journal of heart failure, 21(10), 1288-1291.
• Ramalho, S. H., Claggett, B. L., Sweitzer, N. K., Fang, J. C., Shah, S. J., Anand, I. S., Pitt, B., Lewis, E. F., Pfeffer, M. A., Solomon, S. D., & Shah, A. M. (2019). Impact of pulmonary disease on the prognosis in heart failure with preserved ejection fraction: the TOPCAT trial. European journal of heart failure.
• Selvaraj, S., Claggett, B., Shah, S. J., Anand, I. S., Rouleau, J. L., Desai, A. S., Lewis, E. F., Vaduganathan, M., Wang, S. Y., Pitt, B., Sweitzer, N. K., Pfeffer, M. A., & Solomon, S. D. (2019). Utility of the Cardiovascular Physical Examination and Impact of Spironolactone in Heart Failure With Preserved Ejection Fraction. Circulation. Heart failure, 12(7), e006125.
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  The prognostic value of physical examination, its relation to quality of life, and influence of therapy in heart failure with preserved ejection fraction is not well known.
• Slater, R. E., Strom, J. G., Methawasin, M., Liss, M., Gotthardt, M., Sweitzer, N., & Granzier, H. L. (2019). Metformin improves diastolic function in an HFpEF-like mouse model by increasing titin compliance. The Journal of general physiology, 151(1), 42-52.
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  Heart failure with preserved ejection fraction (HFpEF) is a complex syndrome characterized by a preserved ejection fraction but increased diastolic stiffness and abnormalities of filling. Although the prevalence of HFpEF is high and continues to rise, no effective therapies exist; however, the diabetic drug metformin has been associated with improved diastolic function in diabetic patients. Here we determine the therapeutic potential of metformin for improving diastolic function in a mouse model with HFpEF-like symptoms. We combine transverse aortic constriction (TAC) surgery with deoxycorticosterone acetate (DOCA) supplementation to obtain a mouse model with increased diastolic stiffness and exercise intolerance. Echocardiography and pressure-volume analysis reveal that providing metformin to TAC/DOCA mice improves diastolic function in the left ventricular (LV) chamber. Muscle mechanics show that metformin lowers passive stiffness of the LV wall muscle. Concomitant with this improvement in diastolic function, metformin-treated TAC/DOCA mice also demonstrate preserved exercise capacity. No metformin effects are seen in sham operated mice. Extraction experiments on skinned ventricular muscle strips show that the metformin-induced reduction of passive stiffness in TAC/DOCA mice is due to an increase in titin compliance. Using phospho-site-specific antibodies, we assay the phosphorylation of titin's PEVK and N2B spring elements. Metformin-treated mice have unaltered PEVK phosphorylation but increased phosphorylation of PKA sites in the N2B element, a change which has previously been shown to lower titin's stiffness. Consistent with this result, experiments with a mouse model deficient in the N2B element reveal that the beneficial effect of metformin on LV chamber and muscle stiffness requires the presence of the N2B element. We conclude that metformin offers therapeutic benefit during HFpEF by lowering titin-based passive stiffness.
• Solomon, S. D., McMurray, J. J., Anand, I. S., Ge, J., Lam, C. S., Maggioni, A. P., Martinez, F., Packer, M., Pfeffer, M. A., Pieske, B., Redfield, M. M., Rouleau, J. L., van Veldhuisen, D. J., Zannad, F., Zile, M. R., Desai, A. S., Claggett, B., Jhund, P. S., Boytsov, S. A., , Comin-Colet, J., et al. (2019). Angiotensin-Neprilysin Inhibition in Heart Failure with Preserved Ejection Fraction. The New England journal of medicine, 381(17), 1609-1620.
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  The angiotensin receptor-neprilysin inhibitor sacubitril-valsartan led to a reduced risk of hospitalization for heart failure or death from cardiovascular causes among patients with heart failure and reduced ejection fraction. The effect of angiotensin receptor-neprilysin inhibition in patients with heart failure with preserved ejection fraction is unclear.
• Solomon, S. D., Vaduganathan, M., Claggett, B. L., Packer, M., Zile, M., Swedberg, K., Rouleau, J., Pfeffer, M. A., Desai, A., Lund, L. H., Koeber, L., Anand, I., Sweitzer, N. K., Linssen, G., Merkely, B., Arango, J. L., Vinereanu, D., Chen, C. H., Senni, M., , Sibulo, A., et al. (2019). Sacubitril/Valsartan Across the Spectrum of Ejection Fraction in Heart Failure. Circulation.
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  While disease modifying therapies exist for heart failure (HF) with reduced left ventricular ejection fraction (LVEF), few options are available for patients in the higher range of LVEF (>40%). Sacubitril/valsartan has been compared with a renin-angiotensin- system (RAS) inhibitor alone in two similarly designed clinical trials of patients with reduced and preserved LVEF, permitting examination of its effects across the full spectrum of LVEF. We combined data from PARADIGM-HF (LVEF eligibility≤40%; n=8,399) and PARAGON-HF (LVEF eligibility≥45%; n=4,796) in a prespecified pooled analysis. We divided randomized patients into LVEF categories:≤22.5% (n=1269), >22.5% to 32.5% (n=3987), >32.5% to 42.5% (n=3143), > 42.5% to 52.5% (n=1427), > 52.5% to 62.5% (n=2166), >62.5% (n=1202). We assessed time to first cardiovascular death and HF hospitalization, its components, and total heart failure hospitlizations, all-cause mortality and non-cardiovascular mortality. Incidence rates and treatment effects were examined across categories of LVEF. Among 13,195 randomized patients, we observed lower rates of cardiovascular death and HF hospitalization, but similar rates of non-cardiovascular death, among patients in the highest vs. lowest groups. Overall sacubitril/valsartan was superior to RAS inhibition for first cardiovascular death or heart failure hospitalization (HR 0.84, 95% CI 0.78, 0.90), cardiovascular death (HR 0.84, 95% CI 0.76, 0.92), heart failure hospitalization (HR 0.84, 95% CI 0.77, 0.91), and all-cause mortality (HR 0.88, 95% CI 0.81, 0.96). The effect of sacubitril/valsartan was modified by LVEF (treatment-by-continuous LVEF interaction p=0.02), and benefit appeared to be present for individuals with EF primarily below the normal range, although the treatment benefit for cardiovascular death diminished at a lower ejection fraction. We observed effect modification by LVEF on the efficacy of sacubitril/valsartan in both men and women with respect to composite total HF hospitalizations and cardiovascular death, although women derived benefit to higher ejection fractions. The therapeutic effects of sacubitril/valsartan, compared with a RAS inhibitor alone, vary by LVEF, with treatment benefits, particularly for heart failure hospitalization, that appear to extend to patients with heart failure and mildly reduced ejection fraction. These therapeutic benefits appeared to extend to a higher LVEF range in women compared with men. URL: https://clinicaltrials.gov PARAGON-HF Unique Identifier: NCT01920711. PARADIGM-HF Unique Identifier: NCT01035255.
• Sweitzer, N. K. (2019). Choosing a Career in Heart Failure. Circulation. Heart failure, 12(7), e006139.
• Vardeny, O., Claggett, B., Vaduganathan, M., Beldhuis, I., Rouleau, J., O'Meara, E., Anand, I. S., Shah, S. J., Sweitzer, N. K., Fang, J. C., Desai, A. S., Lewis, E. F., Pitt, B., Pfeffer, M. A., Solomon, S. D., & , T. I. (2019). Influence of Age on Efficacy and Safety of Spironolactone in Heart Failure. JACC. Heart failure, 7(12), 1022-1028.
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  The authors examined efficacy and safety of spironolactone by age in the Americas region (N = 1,767) of the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist) trial.
• Abraham, I. L., Abraham, I. L., Sweitzer, N. K., Sweitzer, N. K., Klimecki, W., Klimecki, W., Karnes, J. H., Karnes, J. H., Erstad, B. L., Erstad, B. L., Slack, M. K., Slack, M. K., Gharaibeh, M., Gharaibeh, M., Ramos, K., Ramos, K., Alkhatib, N., & Alkhatib, N. (2018). Economic evaluation of genetic testing for Arg389 in the management of stage III/IV heart failure.. Expert Review of Precision Medicine and Drug Development, 3, 319-329.
• Breathett, K., Maffett, S., Foraker, R. E., Sturdivant, R., Moon, K., Hasan, A., Franco, V., Smith, S., Lampert, B. C., Emani, S., Haas, G., Kahwash, R., Hershberger, R. E., Binkley, P. F., Helmkamp, L., Colborn, K., Peterson, P. N., Sweitzer, N., & Abraham, W. T. (2018). Pilot Randomized Controlled Trial to Reduce Readmission for Heart Failure Using Novel Tablet and Nurse Practitioner Education. The American journal of medicine, 131(8), 974-978.
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  Heart failure education programs are not standardized. The best form of education is unclear. We evaluated whether addition of a novel tablet application to nurse practitioner (NP) education was superior to NP education alone in reducing 30-day readmission after heart failure hospitalization.
• van Diepen, S., Katz, J. N., Albert, N. M., Henry, T. D., Jacobs, A. K., Kapur, N. K., Kilic, A., Menon, V., Ohman, E. M., Sweitzer, N. K., Thiele, H., Washam, J. B., Cohen, M. G., & , A. H. (2017). Contemporary Management of Cardiogenic Shock: A Scientific Statement From the American Heart Association. Circulation, 136(16), e232-e268.
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  Cardiogenic shock is a high-acuity, potentially complex, and hemodynamically diverse state of end-organ hypoperfusion that is frequently associated with multisystem organ failure. Despite improving survival in recent years, patient morbidity and mortality remain high, and there are few evidence-based therapeutic interventions known to clearly improve patient outcomes. This scientific statement on cardiogenic shock summarizes the epidemiology, pathophysiology, causes, and outcomes of cardiogenic shock; reviews contemporary best medical, surgical, mechanical circulatory support, and palliative care practices; advocates for the development of regionalized systems of care; and outlines future research priorities.
• Rich, M. W., Kitzman, D. W., , P. O., & , P. I. (2016). Third pivotal research in cardiology in the elderly (PRICE-III) symposium: heart failure in the elderly: mechanisms and management. The American journal of geriatric cardiology, 14(5), 250-61.
• Rich, M. W., Kitzman, D. W., , P. O., & , P. I. (2015). Third pivotal research in cardiology in the elderly (PRICE-III) symposium: heart failure in the elderly: mechanisms and management. The American journal of geriatric cardiology, 14(5), 250-61.
• Albrecht, C. M., Sweitzer, N. K., Johnson, M. R., & Vardeny, O. (2014). Lack of persistence of influenza vaccine antibody titers in patients with heart failure. Journal of cardiac failure, 20(2), 105-9.
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  Patients with heart failure (HF) have lower initial antibody responses to the influenza vaccine compared with healthy individuals. Whether antibody titers wane faster in this population remains unknown.
• Basuray, A., French, B., Ky, B., Vorovich, E., Olt, C., Sweitzer, N. K., Cappola, T. P., & Fang, J. C. (2014). Heart failure with recovered ejection fraction: clinical description, biomarkers, and outcomes. Circulation, 129(23), 2380-7.
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  We hypothesized that patients with heart failure (HF) who recover left ventricular function (HF-Recovered) have a distinct clinical phenotype, biology, and prognosis compared with patients with HF with reduced ejection fraction (HF-REF) and those with HF with preserved ejection fraction (HF-PEF).
• Pitt, B., Pfeffer, M. A., Assmann, S. F., Boineau, R., Anand, I. S., Claggett, B., Clausell, N., Desai, A. S., Diaz, R., Fleg, J. L., Gordeev, I., Harty, B., Heitner, J. F., Kenwood, C. T., Lewis, E. F., O'Meara, E., Probstfield, J. L., Shaburishvili, T., Shah, S. J., , Solomon, S. D., et al. (2014). Spironolactone for heart failure with preserved ejection fraction. The New England journal of medicine, 370(15), 1383-92.
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  Mineralocorticoid-receptor antagonists improve the prognosis for patients with heart failure and a reduced left ventricular ejection fraction. We evaluated the effects of spironolactone in patients with heart failure and a preserved left ventricular ejection fraction.
• Shah, A. M., Claggett, B., Sweitzer, N. K., Shah, S. J., Anand, I. S., O'Meara, E., Desai, A. S., Heitner, J. F., Li, G., Fang, J., Rouleau, J., Zile, M. R., Markov, V., Ryabov, V., Reis, G., Assmann, S. F., McKinlay, S. M., Pitt, B., Pfeffer, M. A., & Solomon, S. D. (2014). Cardiac structure and function and prognosis in heart failure with preserved ejection fraction: findings from the echocardiographic study of the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) Trial. Circulation. Heart failure, 7(5), 740-51.
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  Abnormalities in cardiac structure and function in heart failure with preserved ejection fraction may help identify patients at particularly high risk for cardiovascular morbidity and mortality.
• Shah, A. M., Shah, S. J., Anand, I. S., Sweitzer, N. K., O'Meara, E., Heitner, J. F., Sopko, G., Li, G., Assmann, S. F., McKinlay, S. M., Pitt, B., Pfeffer, M. A., Solomon, S. D., & , T. I. (2014). Cardiac structure and function in heart failure with preserved ejection fraction: baseline findings from the echocardiographic study of the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist trial. Circulation. Heart failure, 7(1), 104-15.
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  Heart failure with preserved ejection fraction (HFpEF) is associated with substantial morbidity and mortality. Existing data on cardiac structure and function in HFpEF suggest significant heterogeneity in this population.
• Vorovich, E., French, B., Ky, B., Goldberg, L., Fang, J. C., Sweitzer, N. K., & Cappola, T. P. (2014). Biomarker predictors of cardiac hospitalization in chronic heart failure: a recurrent event analysis. Journal of cardiac failure, 20(8), 569-76.
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  Identification of heart failure (HF) patients at risk for hospitalization may improve care and reduce costs. We evaluated 9 biomarkers as predictors of cardiac hospitalization in chronic HF.
• Zhang, K. W., French, B., May Khan, A., Plappert, T., Fang, J. C., Sweitzer, N. K., Borlaug, B. A., Chirinos, J. A., St John Sutton, M., Cappola, T. P., & Ky, B. (2014). Strain improves risk prediction beyond ejection fraction in chronic systolic heart failure. Journal of the American Heart Association, 3(1), e000550.
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  The utility of longitudinal, circumferential, and radial strain and strain rate in determining prognosis in chronic heart failure is not well established.
• Givertz, M. M., Teerlink, J. R., Albert, N. M., Westlake Canary, C. A., Collins, S. P., Colvin-Adams, M., Ezekowitz, J. A., Fang, J. C., Hernandez, A. F., Katz, S. D., Krishnamani, R., Stough, W. G., Walsh, M. N., Butler, J., Carson, P. E., Dimarco, J. P., Hershberger, R. E., Rogers, J. G., Spertus, J. A., , Stevenson, W. G., et al. (2013). Acute decompensated heart failure: update on new and emerging evidence and directions for future research. Journal of cardiac failure, 19(6), 371-89.
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  Acute decompensated heart failure (ADHF) is a complex clinical event associated with excess morbidity and mortality. Managing ADHF patients is challenging because of the lack of effective treatments that both reduce symptoms and improve clinical outcomes. Existing guideline recommendations are largely based on expert opinion, but several recently published trials have yielded important data to inform both current clinical practice and future research directions. New insight has been gained regarding volume management, including dosing strategies for intravenous loop diuretics and the role of ultrafiltration in patients with heart failure and renal dysfunction. Although the largest ADHF trial to date (ASCEND-HF, using nesiritide) was neutral, promising results with other investigational agents have been reported. If these findings are confirmed in phase III trials, novel compounds, such as relaxin, omecamtiv mecarbil, and ularitide, among others, may become therapeutic options. Translation of research findings into quality clinical care can not be overemphasized. Although many gaps in knowledge exist, ongoing studies will address issues around delivery of evidence-based care to achieve the goal of improving the health status and clinical outcomes of patients with ADHF.
• Ky, B., French, B., May Khan, A., Plappert, T., Wang, A., Chirinos, J. A., Fang, J. C., Sweitzer, N. K., Borlaug, B. A., Kass, D. A., St John Sutton, M., & Cappola, T. P. (2013). Ventricular-arterial coupling, remodeling, and prognosis in chronic heart failure. Journal of the American College of Cardiology, 62(13), 1165-72.
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  The objective of this study was to compare the physiological determinants of ejection fraction (EF)-ventricular size, contractile function, and ventricular-arterial (VA) interaction-and their associations with clinical outcomes in chronic heart failure (HF).
• Shah, S. J., Heitner, J. F., Sweitzer, N. K., Anand, I. S., Kim, H., Harty, B., Boineau, R., Clausell, N., Desai, A. S., Diaz, R., Fleg, J. L., Gordeev, I., Lewis, E. F., Markov, V., O'Meara, E., Kobulia, B., Shaburishvili, T., Solomon, S. D., Pitt, B., , Pfeffer, M. A., et al. (2013). Baseline characteristics of patients in the treatment of preserved cardiac function heart failure with an aldosterone antagonist trial. Circulation. Heart failure, 6(2), 184-92.
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  Treatment of Preserved Cardiac Function with an Aldosterone Antagonist (TOPCAT) is an ongoing randomized controlled trial of spironolactone versus placebo for heart failure with preserved ejection fraction (HFpEF). We sought to describe the baseline clinical characteristics of subjects enrolled in TOPCAT relative to other contemporary observational studies and randomized clinical trials of HFpEF.
• Sweitzer, N. K., Hetzel, S. J., Skalski, J., Velez, M., Eggleston, K., & Mitchell, G. F. (2013). Left ventricular responses to acute changes in late systolic pressure augmentation in older adults. American journal of hypertension, 26(7), 866-71.
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  Changes in the cardiovascular system with age may predispose older persons to development of heart failure with preserved ejection fraction. Vascular stiffening, aortic pressure augmentation, and ventricular-vascular coupling have been implicated. We explored the potential for acute reductions in late systolic pressure augmentation to impact left ventricular relaxation in older persons without heart failure.
• Van Ermen, A., Hermanson, M. P., Moran, J. M., Sweitzer, N. K., Johnson, M. R., & Vardeny, O. (2013). Double dose vs. standard dose influenza vaccination in patients with heart failure: a pilot study. European journal of heart failure, 15(5), 560-4.
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  Influenza infection leads to increased morbidity and mortality in those with heart failure, and individuals with heart failure exhibit reduced antibody responses to influenza vaccine. We hypothesized that patients with heart failure randomized to double dose (DD) influenza vaccine will mount more vigorous humoral immune responses compared with those given standard dose (SD) vaccine.
• Butler, J., Ezekowitz, J. A., Collins, S. P., Givertz, M. M., Teerlink, J. R., Walsh, M. N., Albert, N. M., Westlake Canary, C. A., Carson, P. E., Colvin-Adams, M., Fang, J. C., Hernandez, A. F., Hershberger, R. E., Katz, S. D., Rogers, J. G., Spertus, J. A., Stevenson, W. G., Sweitzer, N. K., Tang, W. H., , Stough, W. G., et al. (2012). Update on aldosterone antagonists use in heart failure with reduced left ventricular ejection fraction. Heart Failure Society of America Guidelines Committee. Journal of cardiac failure, 18(4), 265-81.
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  Aldosterone antagonists (or mineralocorticoid receptor antagonists [MRAs]) are guideline-recommended therapy for patients with moderate to severe heart failure (HF) symptoms and reduced left ventricular ejection fraction (LVEF), and in postmyocardial infarction patients with HF. The Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS-HF) trial evaluated the MRA eplerenone in patients with mild HF symptoms. Eplerenone reduced the risk of the primary endpoint of cardiovascular death or HF hospitalization (hazard ratio [HR] 0.63, 95% confidence interval [CI] 0.54-0.74, P < .001) and all-cause mortality (adjusted HR 0.76, 95% CI 0.62-0.93, P < .008) after a median of 21 months. Based on EMPHASIS-HF, an MRA is recommended for patients with New York Heart Association (NYHA) Class II-IV symptoms and reduced LVEF (55 years, QRS duration >130 msec [if LVEF between 31% and 35%], HF hospitalization within 6 months or elevated B-type natriuretic peptide level). Renal function and serum potassium should be closely monitored. Dose selection should consider renal function, baseline potassium, and concomitant drug interactions. The efficacy of eplerenone in patients with mild HF symptoms translates into a unique opportunity to reduce morbidity and mortality earlier in the course of the disease.
• Ky, B., French, B., Levy, W. C., Sweitzer, N. K., Fang, J. C., Wu, A. H., Goldberg, L. R., Jessup, M., & Cappola, T. P. (2012). Multiple biomarkers for risk prediction in chronic heart failure. Circulation. Heart failure, 5(2), 183-90.
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  Prior studies have suggested using a panel of biomarkers that measure diverse biological processes as a prognostic tool in chronic heart failure. Whether this approach improves risk prediction beyond clinical evaluation is unknown.
• Stevenson, W. G., Hernandez, A. F., Carson, P. E., Fang, J. C., Katz, S. D., Spertus, J. A., Sweitzer, N. K., Tang, W. H., Albert, N. M., Butler, J., Westlake Canary, C. A., Collins, S. P., Colvin-Adams, M., Ezekowitz, J. A., Givertz, M. M., Hershberger, R. E., Rogers, J. G., Teerlink, J. R., Walsh, M. N., , Stough, W. G., et al. (2012). Indications for cardiac resynchronization therapy: 2011 update from the Heart Failure Society of America Guideline Committee. Journal of cardiac failure, 18(2), 94-106.
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  Cardiac resynchronization therapy (CRT) improves survival, symptoms, quality of life, exercise capacity, and cardiac structure and function in patients with New York Heart Association (NYHA) functional class II or ambulatory class IV heart failure (HF) with wide QRS complex. The totality of evidence supports the use of CRT in patients with less severe HF symptoms. CRT is recommended for patients in sinus rhythm with a widened QRS interval (≥150 ms) not due to right bundle branch block (RBBB) who have severe left ventricular (LV) systolic dysfunction and persistent NYHA functional class II-III symptoms despite optimal medical therapy (strength of evidence A). CRT may be considered for several other patient groups for whom evidence of benefit is clinically significant but less substantial, including patients with a QRS interval of ≥120 to
• Cappola, T. P., Matkovich, S. J., Wang, W., van Booven, D., Li, M., Wang, X., Qu, L., Sweitzer, N. K., Fang, J. C., Reilly, M. P., Hakonarson, H., Nerbonne, J. M., & Dorn, G. W. (2011). Loss-of-function DNA sequence variant in the CLCNKA chloride channel implicates the cardio-renal axis in interindividual heart failure risk variation. Proceedings of the National Academy of Sciences of the United States of America, 108(6), 2456-61.
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  Common heart failure has a strong undefined heritable component. Two recent independent cardiovascular SNP array studies identified a common SNP at 1p36 in intron 2 of the HSPB7 gene as being associated with heart failure. HSPB7 resequencing identified other risk alleles but no functional gene variants. Here, we further show no effect of the HSPB7 SNP on cardiac HSPB7 mRNA levels or splicing, suggesting that the SNP marks the position of a functional variant in another gene. Accordingly, we used massively parallel platforms to resequence all coding exons of the adjacent CLCNKA gene, which encodes the K(a) renal chloride channel (ClC-K(a)). Of 51 exonic CLCNKA variants identified, one SNP (rs10927887, encoding Arg83Gly) was common, in linkage disequilibrium with the heart failure risk SNP in HSPB7, and associated with heart failure in two independent Caucasian referral populations (n = 2,606 and 1,168; combined P = 2.25 × 10(-6)). Individual genotyping of rs10927887 in the two study populations and a third independent heart failure cohort (combined n = 5,489) revealed an additive allele effect on heart failure risk that is independent of age, sex, and prior hypertension (odds ratio = 1.27 per allele copy; P = 8.3 × 10(-7)). Functional characterization of recombinant wild-type Arg83 and variant Gly83 ClC-K(a) chloride channel currents revealed ≈ 50% loss-of-function of the variant channel. These findings identify a common, functionally significant genetic risk factor for Caucasian heart failure. The variant CLCNKA risk allele, telegraphed by linked variants in the adjacent HSPB7 gene, uncovers a previously overlooked genetic mechanism affecting the cardio-renal axis.
• Halbe, J. K., & Sweitzer, N. K. (2011). Determinants of exercise intolerance in heart failure with preserved ejection fraction. Journal of the American College of Cardiology, 58(24), 2547-8; author reply 2548-9.
• Ky, B., French, B., McCloskey, K., Rame, J. E., McIntosh, E., Shahi, P., Dries, D. L., Tang, W. H., Wu, A. H., Fang, J. C., Boxer, R., Sweitzer, N. K., Levy, W. C., Goldberg, L. R., Jessup, M., & Cappola, T. P. (2011). High-sensitivity ST2 for prediction of adverse outcomes in chronic heart failure. Circulation. Heart failure, 4(2), 180-7.
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  Soluble ST2 reflects activity of an interleukin-33-dependent cardioprotective signaling axis and is a diagnostic and prognostic marker in acute heart failure. The use of ST2 in chronic heart failure has not been well defined. Our objective was to determine whether plasma ST2 levels predict adverse outcomes in chronic heart failure in the context of current approaches.
• Ky, B., French, B., Ruparel, K., Sweitzer, N. K., Fang, J. C., Levy, W. C., Sawyer, D. B., & Cappola, T. P. (2011). The vascular marker soluble fms-like tyrosine kinase 1 is associated with disease severity and adverse outcomes in chronic heart failure. Journal of the American College of Cardiology, 58(4), 386-94.
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  We sought to evaluate placental growth factor (PlGF) and soluble Fms-like tyrosine kinase 1 (sFlt-1) as clinical biomarkers in chronic heart failure (HF).
• Lanktree, M. B., Guo, Y., Murtaza, M., Glessner, J. T., Bailey, S. D., Onland-Moret, N. C., Lettre, G., Ongen, H., Rajagopalan, R., Johnson, T., Shen, H., Nelson, C. P., Klopp, N., Baumert, J., Padmanabhan, S., Pankratz, N., Pankow, J. S., Shah, S., Taylor, K., , Barnard, J., et al. (2011). Meta-analysis of Dense Genecentric Association Studies Reveals Common and Uncommon Variants Associated with Height. American journal of human genetics, 88(1), 6-18.
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  Height is a classic complex trait with common variants in a growing list of genes known to contribute to the phenotype. Using a genecentric genotyping array targeted toward cardiovascular-related loci, comprising 49,320 SNPs across approximately 2000 loci, we evaluated the association of common and uncommon SNPs with adult height in 114,223 individuals from 47 studies and six ethnicities. A total of 64 loci contained a SNP associated with height at array-wide significance (p < 2.4 × 10(-6)), with 42 loci surpassing the conventional genome-wide significance threshold (p < 5 × 10(-8)). Common variants with minor allele frequencies greater than 5% were observed to be associated with height in 37 previously reported loci. In individuals of European ancestry, uncommon SNPs in IL11 and SMAD3, which would not be genotyped with the use of standard genome-wide genotyping arrays, were strongly associated with height (p < 3 × 10(-11)). Conditional analysis within associated regions revealed five additional variants associated with height independent of lead SNPs within the locus, suggesting allelic heterogeneity. Although underpowered to replicate findings from individuals of European ancestry, the direction of effect of associated variants was largely consistent in African American, South Asian, and Hispanic populations. Overall, we show that dense coverage of genes for uncommon SNPs, coupled with large-scale meta-analysis, can successfully identify additional variants associated with a common complex trait.
• Norman, H. S., Oujiri, J., Larue, S. J., Chapman, C. B., Margulies, K. B., & Sweitzer, N. K. (2011). Decreased cardiac functional reserve in heart failure with preserved systolic function. Journal of cardiac failure, 17(4), 301-8.
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  Heart failure in patients with preserved left ventricular systolic function (HFpEF) is a prevalent disease characterized by exercise intolerance with poorly understood pathophysiology. We hypothesized that recruitable contractility is impaired in HFpEF, accounting for the appearance of symptoms with exertion.
• Sweitzer, N. K. (1999). Hospitalization for Heart Failure in the Elderly. American Journal of Geriatric Cardiology, 276-281.
• Vardeny, O., Moran, J. J., Sweitzer, N. K., Johnson, M. R., & Hayney, M. S. (2010). Decreased T-cell responses to influenza vaccination in patients with heart failure. Pharmacotherapy, 30(1), 10-6.
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  To determine whether T-cell immune responses to influenza vaccination in patients with chronic heart failure (CHF) are less vigorous than the responses of healthy control subjects.
• Garster, N. C., Palta, M., Sweitzer, N. K., Kaplan, R. M., & Fryback, D. G. (2009). Measuring health-related quality of life in population-based studies of coronary heart disease: comparing six generic indexes and a disease-specific proxy score. Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation, 18(9), 1239-47.
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  To compare HRQoL differences with CHD in generic indexes and a proxy CVD-specific score in a nationally representative sample of U.S. adults.
• Ky, B., Kimmel, S. E., Safa, R. N., Putt, M. E., Sweitzer, N. K., Fang, J. C., Sawyer, D. B., & Cappola, T. P. (2009). Neuregulin-1 beta is associated with disease severity and adverse outcomes in chronic heart failure. Circulation, 120(4), 310-7.
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  Neuregulin-1 (NRG-1) is a paracrine factor released by microvascular endothelial cells that has cardioprotective effects in animal models of heart failure. However, circulating NRG-1 has not been studied in human heart disease. We used a novel immunoassay to test whether circulating NRG-1beta is associated with disease severity and clinical outcomes in chronic heart failure.
• Vardeny, O., Sweitzer, N. K., Detry, M. A., Moran, J. M., Johnson, M. R., & Hayney, M. S. (2009). Decreased immune responses to influenza vaccination in patients with heart failure. Journal of cardiac failure, 15(4), 368-73.
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  Heart failure (HF) patients are at risk for influenza despite widespread vaccination. Both humoral (antibody) and cytotoxic T-lymphocyte (CTL) responses are important for protection. We explored antibody- and CTL-mediated responses to the influenza vaccine in HF patients compared with healthy controls.
• Sweitzer, N. K., Lopatin, M., Yancy, C. W., Mills, R. M., & Stevenson, L. W. (2008). Comparison of clinical features and outcomes of patients hospitalized with heart failure and normal ejection fraction (> or =55%) versus those with mildly reduced (40% to 55%) and moderately to severely reduced (<40%) fractions. The American journal of cardiology, 101(8), 1151-6.
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  Heart failure (HF) with normal ejection fraction (EF) is an increasingly common presentation of acute decompensated HF. Differences between patients with HF and truly normal EF and those with mildly impaired EF have not been described. The Acute Decompensated Heart Failure Registry (ADHERE) contains information on >100,000 HF hospitalizations and may provide insight into this distinction. The ADHERE database was used to investigate differences between patients hospitalized with HF and severely ( or =55%). The group with normal EF was 69% women with a mean age of 74 years (p or =55% had increased pulse pressure, suggesting a role for arterial stiffening. Treatment differed by EF. Creatinine increased > or =0.5 mg/dl more often in the group with HF and normal EF than in the group with HF and severely decreased EF. In-hospital mortality and length of stay in the intensive care unit varied inversely with EF; overall length of stay was similar. In conclusion, patients with HF and normal EF are more likely to be women, have a history of high pulse pressure hypertension, less coronary artery disease, and a lower risk of inpatient death but a higher likelihood of deterioration in renal function during hospitalization. These observations may be important considerations in the design of future clinical trials.
• Vardeny, O., Detry, M. A., Moran, J. J., Johnson, M. R., & Sweitzer, N. K. (2008). The beta2 adrenergic receptor Gln27Glu polymorphism affects insulin resistance in patients with heart failure: possible modulation by choice of beta blocker. Journal of cardiovascular pharmacology, 52(6), 500-6.
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  Insulin resistance is prevalent in heart failure (HF) patients, and beta2 adrenergic receptors (beta2-AR) are involved in glucose homeostasis. We hypothesized that beta2-AR Gln27Glu and Arg16Gly polymorphisms affect insulin resistance in HF patients, and we explored if effects of beta2-AR polymorphisms on glucose handling are modified by choice of beta blocker. We studied 30 nondiabetic adults with HF and a history of systolic dysfunction; 15 were receiving metoprolol succinate, and 15 were receiving carvedilol. We measured fasting glucose, insulin, and insulin resistance, and we determined beta2-AR genotypes at codons 27 and 16. The cohort was insulin resistant with a mean HOMA-IR score of 3.4 (95% CI, 2.3 to 4.5; normal value, 1.0). Patients with the Glu27Glu genotype exhibited higher insulin and HOMA-IR compared to individuals carrying a Gln allele (P = 0.019). Patients taking carvedilol demonstrated lower insulin resistance if also carrying a wild-type allele at codon 27 (fasting insulin, 9.8 +/- 10.5 versus 20.5 +/- 2.1 for variant, P = 0.072; HOMA-IR, 2.4 +/- 2.7 versus 5.1 +/- 0.6, P = 0.074); those on metoprolol succinate had high insulin resistance irrespective of genotype. The beta2-AR Glu27Glu genotype may be associated with higher insulin concentrations and insulin resistance in patients with HF. Future studies are needed to confirm whether treatment with carvedilol may be associated with decreased insulin and insulin resistance in beta2-AR codon 27 Gln carriers.
• Sweitzer, N. K., Shenoy, M., Stein, J. H., Keles, S., Palta, M., LeCaire, T., & Mitchell, G. F. (2007). Increases in central aortic impedance precede alterations in arterial stiffness measures in type 1 diabetes. Diabetes care, 30(11), 2886-91.
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  Increased pulse pressure has been associated with increased cardiovascular risk in individuals with diabetes. Changes in central aortic properties can increase central pulse pressure and may adversely affect microvascular perfusion and cardiac performance. This study was performed to define early changes in central arterial properties in a group of young individuals with type 1 diabetes.
• Sweitzer, N. K. (2003). Cardiology patient page. What is an angiotensin converting enzyme inhibitor?. Circulation, 108(3), e16-8.
• Ho, C. Y., Sweitzer, N. K., McDonough, B., Maron, B. J., Casey, S. A., Seidman, J. G., Seidman, C. E., & Solomon, S. D. (2002). Assessment of diastolic function with Doppler tissue imaging to predict genotype in preclinical hypertrophic cardiomyopathy. Circulation, 105(25), 2992-7.
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  Unexplained left ventricular hypertrophy (LVH) is considered diagnostic of hypertrophic cardiomyopathy (HCM) but fails to identify all genetically affected individuals. Altered diastolic function has been hypothesized to represent an earlier manifestation of HCM before the development of LVH; however, data regarding the clinical utility of imaging techniques that assess this parameter are limited.
• Dries, D. L., Sweitzer, N. K., Drazner, M. H., Stevenson, L. W., & Gersh, B. J. (2001). Prognostic impact of diabetes mellitus in patients with heart failure according to the etiology of left ventricular systolic dysfunction. Journal of the American College of Cardiology, 38(2), 421-8.
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  We sought to determine the relative impact of diabetes mellitus on prognosis in ischemic compared with nonischemic cardiomyopathy.
• Oh, W. K., Lee, B. H., & Sweitzer, N. K. (2000). Nonmalignant diagnoses in patients. Case 3. Right atrial thrombus associated with a central venous catheter in a patient with metastatic adrenocortical carcinoma. Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 18(13), 2638-9.
• Sweitzer, N. K., & Stevenson, L. W. (2000). Diastolic heart failure: miles to go before we sleep. The American Journal of medicine, 109(8), 683-5.
• Sweitzer, N. K., Frishman, W. H., & Stevenson, L. W. (2000). Drug therapy of heart failure caused by systolic dysfunction in the elderly. Clinics in geriatric medicine, 16(3), 513-34.
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  The presence of multiple medical illnesses often distinguishes elderly patients with heart failure and can make pharmacologic management of symptomatic heart failure challenging in this population. Physiologic changes that occur with normal aging may complicate clinical assessment. Limited data from large clinical trials of heart failure therapy are applicable to aged patients. Available data suggest that elderly patients should be treated with the same regimen as younger patients but that more careful attention should be paid to dosing, especially when initiating a new drug. History and physical examination techniques can be used to uncover evidence of congestion and inadequate perfusion and are critical adjuncts when making therapeutic decisions. The objectives of therapy for elderly patients with heart failure must be individualized within the larger context of patients' goals and stage of life.
• Sweitzer, N., & Warner Stevenson, L. (1999). Hospitalization for Heart Failure in the Elderly. The American journal of geriatric cardiology, 8(6), 276-281.
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  People over 65 years account for more than 80% of heart failure hospitalizations, with almost half in patients morer than 75. Heart failure hospitalizations accounted for 21% of the annual health care budget for a representative senior program. Heart failure with preserved ejection fraction accounts for over half of heart failure hospitalizations in the elderly. Current therapy for the elderly is directed to relieve congestion by reducing volume overload and hypertension, while addressing exacerbating factors such as ischemia and anemia. Heart rate reduction is critical when sinus rhythm cannot be maintained but can also improve diastolic filling during sinus rhythm. While cardiac transplantation is rarely indicated, other interventions should be actively considered. Most elderly patients admitted with heart failure wish resuscitation. As heart failure progresses, decisions regarding implantable defibrillators or dialysis require careful consideration, and the risk/benefit balance may shift toward therapies to improve quality of life. (c)1999 by CVRR, Inc.
• Strang, K. T., Sweitzer, N. K., Greaser, M. L., & Moss, R. L. (1994). Beta-adrenergic receptor stimulation increases unloaded shortening velocity of skinned single ventricular myocytes from rats. Circulation research, 74(3), 542-9.
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  In vitro biochemical experiments have suggested that stimulation of beta-adrenergic receptor may increase the rate of crossbridge cycling in mammalian myocardium, but recent attempts to demonstrate a mechanical correlate have yielded conflicting results. To investigate this issue, we measured the effect of isoproterenol (ISO) and cAMP-dependent protein kinase (PKA) on unloaded shortening velocity (Vo). Vo is thought to be determined by the rate-limiting step of the crossbridge cycle, ie, the rate of crossbridge detachment from actin, and is therefore an index of the cycling rate. Single rat ventricular myocytes were enzymatically isolated, incubated in Ringer's solution without (control) or with 0.1 mumol/L ISO, and then rapidly skinned. Some control cells were subsequently treated with 3 micrograms/mL PKA for 40 minutes. Vo was then measured during maximal activation (pCa 4.5) in control, ISO-treated, and PKA-treated cells using the slack-test method. To test the efficacy of the agonist treatments, Ca2+ sensitivity of isometric tension was also assessed for each treatment by determining the [Ca2+] required for half-maximal tension (ie, pCa50). Both ISO and PKA treatment reduced the Ca2+ sensitivity of isometric tension compared with same-day control cells, in agreement with previous studies in intact and in skinned preparations. Vo was increased 38% by ISO treatment and 41% by PKA treatment compared with same-day control cells. 32P autoradiography showed that troponin I and C protein were the principal proteins phosphorylated by PKA treatment. We conclude that beta-adrenergic stimulation increases the rate of crossbridge release from actin, by a mechanism that most likely involves the phosphorylation of troponin I and/or C protein by PKA.
• Sweitzer, N. K., & Moss, R. L. (1993). Determinants of loaded shortening velocity in single cardiac myocytes permeabilized with alpha-hemolysin. Circulation research, 73(6), 1150-62.
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  Force-velocity relations were obtained from single cardiac myocytes isolated by enzymatic digestion of rat myocardium and permeabilized with the pore-forming staphylococcal toxin alpha-hemolysin. Single cardiac myocytes were attached to a force transducer and piezoelectric translator and viewed with an inverted microscope to allow periodic monitoring of sarcomere length during experiments. Permeabilized cells were activated by immersion in a bath of known [Ca2+]. We report that the Ca2+ sensitivity of cells obtained by enzymatic digestion and permeabilized using alpha-hemolysin is similar to that reported previously for mechanically disrupted ventricular myocardium; however, the tension-pCa relation is less steep in the new preparation. During isotonic measurements, force was clamped to various loads using a rapid-response servo system. All recordings of shortening under load were distinctly curvilinear, and analysis of data involved fitting each shortening recording with a single exponential curve and calculating the value of the slope at the initial time of the load clamp. In addition, the presence of significant resting force at initial sarcomere lengths in these cells required that the possibility of alteration of velocity due to the presence of resting force be addressed. The maximum shortening velocity in fully Ca(2+)-activated single ventricular myocytes studied by this method was 2.83 muscle lengths per second on average. The basis for curvilinear shortening is postulated to be multifactorial in cardiac muscle, involving a combination of shortening inactivation and one or more passive elasticities that resist stretch or compression depending on sarcomere length. Shortening velocity shows a dependence on myosin isoform content when cells from a single heart are compared; however, this relation does not hold when cells from different hearts are compared. The behavior of single alpha-hemolysin-permeabilized myocyte shortening under loaded conditions at lower levels of Ca2+ is also described. During submaximal Ca2+ activation, initial shortening velocities are faster than those observed in maximally activated cells. This may be due to contributions of high passive force to increase shortening velocity under conditions of low active force generation, when passive force in the cell is a greater proportion of the total force and there are fewer bound crossbridges.
• Sweitzer, N. K., & Moss, R. L. (1990). The effect of altered temperature on Ca2(+)-sensitive force in permeabilized myocardium and skeletal muscle. Evidence for force dependence of thin filament activation. The Journal of general physiology, 96(6), 1221-45.
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  The effect of changes in temperature on the calcium sensitivity of tension development was examined in permeabilized cellular preparations of rat ventricle and rabbit psoas muscle. Maximum force and Ca2+ sensitivity of force development increased with temperature in both muscle types. Cardiac muscle was more sensitive to changes in temperature than skeletal muscle in the range 10-15 degrees C. It was postulated that the level of thin filament activation may be decreased by cooling. To investigate this possibility, troponin C (TnC) was partially extracted from both muscle types, thus decreasing the level of thin filament activation independent of temperature and, at least in skeletal muscle fibers, decreasing cooperative activation of the thin filament as well. TnC extraction from cardiac muscle reduced the calcium sensitivity of tension less than did extraction of TnC from skeletal muscle. In skeletal muscle the midpoint shift of the tension-pCa curve with altered temperature was greater after TnC extraction than in control fibers. Calcium sensitivity of tension development was proportional to the maximum tension generated in cardiac or skeletal muscle under all conditions studied. Based on these results, we conclude that (a) maximum tension-generating capability and calcium sensitivity of tension development are related, perhaps causally, in fast skeletal and cardiac muscles, and (b) thin filament activation is less cooperative in cardiac muscle than in skeletal muscle, which explains the differential sensitivity of the two fiber types to temperature and TnC extraction. Reducing thin filament cooperativity in skeletal muscle by TnC extraction results in a response to temperature similar to that of control cardiac cells. This study provides evidence that force levels in striated muscle influence the calcium binding affinity of TnC.

Presentations

• Desai, A., Sprissler, R. S., Sotak, S., Granzier, H. L., Tardiff, J. C., Khalpey, Z. I., Sweitzer, N. K., Gupta, A., Nai, V., & Whitaker, M. E. (2015, November). dult Onset Non-Ischemic Dilated Cardiomyopathy: A Novel Titin Mutation and a Case of Complex Inheritance. American College of Physicians (Arizona Chapter) Scientific Meeting. Phoenix, AZ: American College of Physicians (Arizona Chapter).

Poster Presentations

• Kazui, T., Khalpey, Z. I., Lick, S. D., Sweitzer, N. K., Avery, R., Cook, J., Juneman, E. B., Juneman, E. B., Cook, J., Avery, R., Sweitzer, N. K., Lick, S. D., Khalpey, Z. I., & Kazui, T. (2017, Oct). Minimally invasive off-pump HVAD vs full sternotomy on-pump LVAD placement: comparison of clinical outcomes. The 2017 ISMCS Conference. Tucson: ISMCS.
• Khalpey, Z. I., Sweitzer, N. K., Cook, J., Juneman, E. B., Avery, R., Lick, S. D., & Kazui, T. (2017, Oct). The effectiveness of minimally invasive off pump HVAD placement in redo patients. The 2017 ISMCS Conference. Tucson: ISMCS.
• Sweitzer, N. K. (2017, August 29). Prognostic Importance of Pulmonary Pressure in Heart Failure with Preserved Ejection Fraction. European Society of Cardiology.

Reviews

• Sweitzer, N. K. (2010. review of book : Management of Heart Failure.

Others

• Sweitzer, N. K. (2011, March). Optimal Management of the Decompensated CHF Patient. Audio-Digest CME/CE Program Internal Medicine.
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  Audio-Digest CME/CE Program: Optimal Management of the Decompensated CHF Patient, Audio-Digest Internal Medicine Volume 58 Issue 11, March 21, 2011