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1. Zilucoplan in immune-mediated necrotising myopathy: a phase 2, randomised, double-blind, placebo-controlled, multicentre trial.

Author

Mammen, Andrew, Amato, Anthony, Dimachkie, Mazen, Chinoy, Hector, Hussain, Yessar, Lilleker, James, Pinal-Fernandez, Iago, Allenbach, Yves, Boroojerdi, Babak, Vanderkelen, Mark, Delicha, Eumorphia, Koendgen, Harold, Farzaneh-Far, Ramin, Duda, Petra, Sayegh, Camil, and Benveniste, Olivier

Abstract

BACKGROUND: Immune-mediated necrotizing myopathy (IMNM) is an autoimmune myopathy characterised by proximal muscle weakness, high creatine kinase (CK) values, and autoantibodies recognizing 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) or the signal recognition particle (SRP). There are currently no approved therapies for IMNM and many patients experience active disease despite off-label treatment with intravenous immunoglobulin, glucocorticoids, and immunosuppressants. Detection of complement-activating anti-HMGCR and anti-SRP autoantibodies and the presence of complement deposition on the sarcolemma of non-necrotic myofibers led to the hypothesis that complement activation may be pathogenic in IMNM, therefore zilucoplan, a complement component 5 (C5) inhibitor, could be a potential therapy. METHODS: IMNM01, a phase 2, multicenter, randomised, double-blind, placebo-controlled study (NCT04025632) at 15 sites (four countries) evaluated efficacy, safety, and tolerability of zilucoplan in adult participants with anti-HMGCR or anti-SRP autoantibody-positive IMNM. Participants were randomised 1:1 to receive daily subcutaneous zilucoplan (0·3mg/kg) or placebo for eight weeks; with optional enrolment in the study open-label extension. Primary efficacy endpoint was percent change from baseline to Week 8 in CK levels. Secondary endpoints included safety. FINDINGS: Between 07 November 2019 and 07 January 2021, 27 participants (13 female and 14 male) received zilucoplan (n=12) or placebo (n=15) and completed the 8-week main study. At Week 8 there were no clinically relevant or statistically significant differences, despite target engagement based on mode of action, between treatment arms in mean percent change (standard deviation) of CK levels versus baseline (-9·86% [26·06] versus -20·72% [31·22] in zilucoplan [n=10] and placebo arms [n=14], p=0·46, respectively) and no clinically relevant improvement over time within the treatment arm. There were no unexpected adverse safety or tolerability findings. Treatment emergent adverse events (TEAEs) and serious TEAEs were reported in n=9 (75·0%) vs n=13 (86·7%) and n=0 (0%) and n=3 (20·0%) participants, respectively. The most frequent TEAEs were headache (n=4 in both groups [33·3% and 26·7%, respectively]) and nausea (n=3 in both groups [25·0% and 20·0%, respectively]). INTERPRETATION: C5 inhibition does not appear to be an effective treatment modality for IMNM. Rather than driving myofiber necrosis, complement activation may be secondary to muscle injury. FUNDING: Study funded by Ra Pharmaceuticals (now part of UCB Pharma).

Published
2023

2. Zilucoplan in immune-mediated necrotising myopathy: a phase 2, randomised, double-blind, placebo-controlled, multicentre trial

Author

Amato, Anthony A., Benveniste, Olivier, Biliciler, Suur, Chinoy, Hector, Dimachkie, Mazen M., Edmundson, Christyn, Freimer, Miriam, Geraci, Anthony, Hussain, Yessar, Machado, Pedro, Mammen, Andrew L., Mozaffar, Tahseen, Soltanzadeh, Payam, Suresh, Niraja, van der Kooi, Anneke, Allenbach, Yves, Appleby, Matthew, Barohn, Richard J, Champtiaux, Nicolas, Doughty, Christopher, Farias, Jerrica, Farmakidis, Constantine, Habib, Ali A., Karam, Chafic, Lilleker, James, Lorusso, Samantha, Pasnoor, Mamatha, Pinal-Fernandez, Iago, Querin, Giorgia, Raaphorst, Joost, Ransley, George, Saba, Sami, Sheikh, Kazim, Snedden, Andrew, Statland, Jeffrey, Vu, Tuan, Mammen, Andrew L, Amato, Anthony A, Dimachkie, Mazen M, Lilleker, James B, Boroojerdi, Babak, Vanderkelen, Mark, Delicha, Eumorphia Maria, Koendgen, Harold, Farzaneh-Far, Ramin, Duda, Petra W, and Sayegh, Camil

Published
2023
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3. Correction: Change in Leukocyte Telomere Length Predicts Mortality in Patients with Stable Coronary Heart Disease from the Heart and Soul Study

Author

Goglin, Sarah E, Farzaneh-Far, Ramin, Epel, Elissa S, Lin, Jue, Blackburn, Elizabeth H, and Whooley, Mary A

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Health Sciences, Cardiovascular, Good Health and Well Being, General Science & Technology
Abstract

[This corrects the article DOI: 10.1371/journal.pone.0160748.].

Published
2016

4. Change in Leukocyte Telomere Length Predicts Mortality in Patients with Stable Coronary Heart Disease from the Heart and Soul Study.

Author

Goglin, Sarah E, Farzaneh-Far, Ramin, Epel, Elissa S, Lin, Jue, Blackburn, Elizabeth H, and Whooley, Mary A

Subjects
Leukocytes, Telomere, Humans, Creatinine, Waist-Hip Ratio, Exercise, Proportional Hazards Models, Cohort Studies, Follow-Up Studies, Prospective Studies, Age Factors, Sex Factors, Ventricular Function, Left, Aged, Middle Aged, Female, Male, Coronary Artery Disease, Interviews as Topic, Kaplan-Meier Estimate, Telomere Shortening, Ventricular Function, Left, General Science & Technology
Abstract

BackgroundShort telomere length independently predicts mortality in patients with coronary heart disease. Whether 5-year change in telomere length predicts subsequent mortality in patients with coronary heart disease has not been evaluated.MethodsIn a prospective cohort study of 608 individuals with stable coronary artery disease, we measured leukocyte telomere length at baseline and after five years of follow-up. We divided the sample into tertiles of telomere change: shortened, maintained or lengthened. We used Cox survival models to evaluate 5-year change in telomere length as a predictor of mortality.ResultsDuring an average of 4.2 years follow-up, there were 149 deaths. Change in telomere length was inversely predictive of all-cause mortality. Using the continuous variable of telomere length change, each standard deviation (325 base pair) greater increase in telomere length was associated with a 24% reduction in mortality (HR 0.76, 95% CI 0.61-0.94; p = 0.01), adjusted for age, sex, waist to hip ratio, exercise capacity, LV ejection fraction, serum creatinine, and year 5 telomere length. Mortality occurred in 39% (79/203) of patients who experienced telomere shortening, 22% (45/203) of patients whose telomere length was maintained, and 12% (25/202) of patients who experienced telomere lengthening (p

Published
2016

5. Phase II trials of zilucoplan in paroxysmal nocturnal hemoglobinuria

Author

Kulasekararaj, Austin G., primary, Lehtinen, Anna-Elina, additional, Forsyth, Cecily, additional, Gandhi, Shreyans, additional, Griffin, Morag, additional, Körper, Sixten, additional, Mikala, Gabor, additional, Muus, Petra, additional, Overgaard, Ulrik, additional, Patriquin, Christopher J., additional, Pullon, Humphrey, additional, Shen, Yu-Min, additional, Spearing, Ruth, additional, Szer, Jeff, additional, De la Borderie, Guillemette, additional, Duda, Petra W., additional, Farzaneh-Far, Ramin, additional, Ragunathan, Sharan, additional, Sayegh, Camil E., additional, Vadysirisack, Douangsone D., additional, and Schrezenmeier, Hubert, additional

Published
2023
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6. Prognostic value of electrocardiographic detection of unrecognized myocardial infarction in persons with stable coronary artery disease: data from the Heart and Soul Study

Author

Kehl, Devin W, Farzaneh-Far, Ramin, Na, Beeya, and Whooley, Mary A

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Clinical Research, Atherosclerosis, Cardiovascular, Heart Disease - Coronary Heart Disease, Heart Disease, 4.1 Discovery and preclinical testing of markers and technologies, Detection, screening and diagnosis, 4.2 Evaluation of markers and technologies, Aged, Cohort Studies, Coronary Artery Disease, Electrocardiography, Female, Follow-Up Studies, Humans, Male, Middle Aged, Myocardial Infarction, Prevalence, Prognosis, Prospective Studies, Q wave, Unrecognized myocardial infarction, Electrocardiogram, Coronary artery disease, Cardiorespiratory Medicine and Haematology, Cardiovascular System & Hematology, Cardiovascular medicine and haematology
Abstract

Unrecognized myocardial infarction (MI) carries a poor prognosis in the general population, but its prognostic value is less clear in high-risk patients. We sought to determine whether Q waves on electrocardiogram (ECG), suggestive of unrecognized MI, predict cardiovascular events in patients with stable coronary artery disease (CAD), but without a prior history of MI. We studied 462 patients enrolled in the Heart and Soul Study with stable CAD but without a prior history of MI. All patients had baseline ECGs. The baseline prevalence of unrecognized myocardial infarction was 36%. After a mean of 6.3 years of follow-up, there were a total of 141 cardiovascular events. The presence of Q waves in any ECG lead territory predicted cardiovascular events before (unadjusted HR 1.41, 95% CI 1.01-1.97) and after adjustment for demographics, medical history, diastolic function, and ejection fraction (HR 1.55, 95% CI 1.06-2.26). This association was partly attenuated after adjustment for the presence of inducible ischemia at baseline (HR 1.43, 95% CI 0.96-2.12). When specific territories were analyzed separately, Q waves in anterior leads were predictive of cardiovascular events in both unadjusted and adjusted models (adjusted HR 1.85, 95% CI 1.14-3.00), and this association was partly attenuated after adjustment for inducible ischemia. In conclusion, in patients with CAD but no history of prior MI, the presence of any Q waves or anterior Q waves alone is independently predictive of adverse cardiovascular events.

Published
2011

7. A functional polymorphism in renalase (Glu37Asp) is associated with cardiac hypertrophy, dysfunction, and ischemia: data from the heart and soul study.

Author

Farzaneh-Far, Ramin, Desir, Gary V, Na, Beeya, Schiller, Nelson B, and Whooley, Mary A

Subjects
Humans, Cardiomegaly, Myocardial Ischemia, Monoamine Oxidase, Aspartic Acid, Glutamic Acid, Prospective Studies, Polymorphism, Single Nucleotide, Aged, Middle Aged, Female, Male, Polymorphism, Single Nucleotide, General Science & Technology
Abstract

BackgroundRenalase is a soluble enzyme that metabolizes circulating catecholamines. A common missense polymorphism in the flavin-adenine dinucleotide-binding domain of human renalase (Glu37Asp) has recently been described. The association of this polymorphism with cardiac structure, function, and ischemia has not previously been reported.MethodsWe genotyped the rs2296545 single-nucleotide polymorphism (Glu37Asp) in 590 Caucasian individuals and performed resting and stress echocardiography. Logistic regression was used to examine the associations of the Glu37Asp polymorphism (C allele) with cardiac hypertrophy (LV mass>100 g/m2), systolic dysfunction (LVEF

Published
2010

8. Telomere length trajectory and its determinants in persons with coronary artery disease: longitudinal findings from the heart and soul study.

Author

Farzaneh-Far, Ramin, Lin, Jue, Epel, Elissa, Lapham, Kyle, Blackburn, Elizabeth, and Whooley, Mary A

Subjects
Telomere, Humans, DNA Primers, Multivariate Analysis, Cohort Studies, Longitudinal Studies, Base Sequence, Coronary Artery Disease, General Science & Technology
Abstract

BackgroundLeukocyte telomere length, an emerging marker of biological age, has been shown to predict cardiovascular morbidity and mortality. However, the natural history of telomere length in patients with coronary artery disease has not been studied. We sought to investigate the longitudinal trajectory of telomere length, and to identify the independent predictors of telomere shortening, in persons with coronary artery disease.Methodology/principal findingsIn a prospective cohort study of 608 individuals with stable coronary artery disease, we measured leukocyte telomere length at baseline, and again after five years of follow-up. We used multivariable linear and logistic regression models to identify the independent predictors of leukocyte telomere trajectory. Baseline and follow-up telomere lengths were normally distributed. Mean telomere length decreased by 42 base pairs per year (p

Published
2010

15. Zilucoplan: An Investigational Complement C5 Inhibitor for the Treatment of Acetylcholine Receptor Autoantibody–Positive Generalized Myasthenia Gravis

Author

Kimiaki Utsugisawa, Maria Isabel Leite, James F. Howard, Hiroyuki Murai, Duda Petra, Farzaneh-Far Ramin, John Vissing, Heinz Wiendl, and Nils Erik Gilhus

Subjects
0301 basic medicine, Autoimmune diseases, membrane attack complex, Neuromuscular junction, corticosteroids, 03 medical and health sciences, 0302 clinical medicine, Myasthenia Gravis, Animals, Humans, Medicine, Receptors, Cholinergic, Pharmacology (medical), generalized myasthenia gravis, Generalized myasthenia, Autoantibodies, Randomized Controlled Trials as Topic, Acetylcholine receptor, Pharmacology, Complement component 5, complement activation, neuromuscular junction, business.industry, Autoantibody, complement C5, Complement C5, Muscle weakness, General Medicine, Complement system, Complement Inactivating Agents, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Immunology, medicine.symptom, business, Complement membrane attack complex
Abstract

Introduction: Generalized myasthenia gravis (gMG) is an autoimmune disorder in which pathogenic autoantibodies damage the neuromuscular junction, causing disabling or life-threatening muscle weakness. Most treatments nonspecifically inhibit aspects of the immune system, do not directly address the causal mechanisms of tissue damage, and often have side-effect profiles that negatively impact patients. Understanding of the central pathogenic role of the complement cascade in gMG is advancing, and a new complement-targeting treatment is under investigation. Areas covered: We provide an overview of gMG etiology, the complement cascade, current treatments, and the investigational gMG therapy zilucoplan. Zilucoplan is a small, subcutaneously administered, macrocyclic peptide that inhibits cleavage of complement component C5 and the subsequent formation of the membrane attack complex. Expert opinion: In a randomized, double-blind, placebo-controlled, phase 2 clinical trial, zilucoplan demonstrated clinically meaningful complement inhibition in patients with acetylcholine receptor-positive gMG. Zilucoplan, a first-of-its-kind cyclic peptide targeting C5, appears to be a therapeutic option for the treatment of gMG based on available pharmacokinetic/pharmacodynamic data and phase 1 and 2 efficacy, safety, and tolerability data with limited long-term follow-up. Zilucoplan use earlier in the treatment paradigm would be suitable in this population should phase 3 efficacy and safety data be equally favorable.

Published
2021

19. Association of marine omega-3 fatty acid levels with telomeric aging in patients with coronary heart disease

Author

Farzaneh-Far, Ramin, Jue Lin, Epel, Elissa S., Harris, William S., Blackburn, Elizabeth H., and Whooley, Mary A.

Subjects
Coronary heart disease -- Care and treatment, Aged patients -- Health aspects, Omega-3 fatty acids -- Health aspects, Telomeres -- Health aspects
Abstract

A study was conducted to evaluate the relationship between marine omega-3 fatty acid blood levels and telomeric aging in patients with coronary heart disease. Results indicated that an inverse relationship exists between the two.

Published
2010

20. Thinking outside the box

Author

Farzaneh-Far, Ramin, Schwarzberg, Talya, and Mushlin, Stuart B.

Subjects
Pulmonary embolism -- Diagnosis, Pulmonary embolism -- Case studies
Abstract

The case of a 35-year-old man with advanced acquired immunodeficiency syndrome (AIDS) is used to highlight the challenges clinicians face in the diagnosis of acute pulmonary embolism. The case illustrates the importance of 'thinking outside the box' in order to avoid missing this diagnosis, particularly in patients whose underlying diseases might otherwise suggest alternative explanations for presenting symptoms.

Published
2006

24. Use of ranolazine in patients with incomplete revascularization after percutaneous coronary intervention: Design and rationale of the Ranolazine for Incomplete Vessel Revascularization Post–Percutaneous Coronary Intervention (RIVER-PCI) trial

Author

Weisz, Giora, Farzaneh-Far, Ramin, Ben-Yehuda, Ori, DeBruyne, Bernard, Montalescot, Gilles, Lerman, Amir, Mahmud, Ehtisham, Alexander, Karen P., Ohman, Magnus E., White, Harvey D., Olmsted, Ann, Walker, Gennyne A., and Stone, Gregg W.

Published
2013
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25. Correlation of Quantitative Myasthenia Gravis and Myasthenia Gravis Activities of Daily Living scales in the MGTX study.

Author

McPherson, Tarrant, Aban, Inmaculada, Duda, Petra W., Farzaneh‐Far, Ramin, Wolfe, Gil I., Kaminski, Henry J., Cutter, Gary, Lee, Ikjae, Farzaneh-Far, Ramin, and of the MGTX Study Group

Subjects
THERAPEUTIC use of glucocorticoids, MYASTHENIA gravis treatment, RESEARCH, MYASTHENIA gravis, CLINICAL trials, THORACIC surgery, RESEARCH methodology, ACTIVITIES of daily living, EVALUATION research, MEDICAL cooperation, COMPARATIVE studies, RESEARCH funding, PREDNISONE, COMBINED modality therapy
Abstract

Introduction: Quantitative Myasthenia Gravis (QMG) and Myasthenia Gravis Activities of Daily Living (MG-ADL) scales were compared using the data from the Thymectomy Trial in Non-Thymomatous Myasthenia Gravis Patients Receiving Prednisone Therapy (MGTX) study.Methods: Correlation between QMG and MG-ADL raw and change-from-baseline scores was calculated every 3 months for 60 months based on treatment groups and minimal manifestation status (MMS).Results: QMG and MG-ADL change-from-baseline scores correlated significantly, with increasing strength of correlation over time, in both treatment groups. QMG and MG-ADL raw scores correlated significantly in both treatment groups, with increasing correlation only in the prednisone-alone group. Correlation between raw scores was weaker in patients who were in MMS, demonstrating a "floor effect" on the MG-ADL scale. Raw QMG scores could be modeled assuming a normal distribution, whereas raw MG-ADL scores could not be modeled this way.Discussion: The floor effect and skewed distribution of the MG-ADL measure should be taken into account in the design of myasthenia gravis clinical trials. [ABSTRACT FROM AUTHOR]

Published
2020
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29. Clinical Effects of the Self-administered Subcutaneous Complement Inhibitor Zilucoplan in Patients With Moderate to Severe Generalized Myasthenia Gravis: Results of a Phase 2 Randomized, Double-Blind, Placebo-Controlled, Multicenter Clinical Trial

Author

Howard, James F., Nowak, Richard J., Wolfe, Gil I., Freimer, Miriam L., Vu, Tuan H., Hinton, John L., Benatar, Michael, Duda, Petra W., MacDougall, James E., Farzaneh-Far, Ramin, Kaminski, Henry J., Barohn, Richard, Dimachkie, Mazen, Pasnoor, Mamatha, Farmakidis, Constantine, Liu, Tina, Colgan, Samantha, Benatar, Michael G., Bertorini, Tulio, Pillai, Rekha, Henegar, Robert, Bromberg, Mark, Gibson, Summer, Janecki, Teresa, Freimer, Miriam, Elsheikh, Bakri, Matisak, Paige, Genge, Angela, Guidon, Amanda, David, William, Habib, Ali A., Mathew, Veena, Mozaffar, Tahseen, Hinton, John L., Hewitt, William, Barnett, Deborah, Sullivan, Patricia, Ho, Doreen, Howard, James F., Traub, Rebecca E., Chopra, Manisha, Kaminski, Henry J., Aly, Radwa, Bayat, Elham, Abu-Rub, Mohammad, Khan, Shaida, Lange, Dale, Holzberg, Shara, Khatri, Bhupendra, Lindman, Emily, Olapo, Tayo, Sershon, Lisa M., Lisak, Robert P., Bernitsas, Evanthia, Jia, Kelly, Malik, Rabia, Lewis-Collins, Tiffany D., Nicolle, Michael, Nowak, Richard J., Sharma, Aditi, Roy, Bhaskar, Nye, Joan, Pulley, Michael, Berger, Alan, Shabbir, Yasmeen, Sachdev, Amit, Patterson, Kimberly, Siddiqi, Zaeem, Sivak, Mark, Bratton, Joan, Small, George, Kohli, Anem, Fetter, Mary, Vu, Tuan, Lam, Lucy, Harvey, Brittany, Wolfe, Gil I., Silvestri, Nicholas, Patrick, Kara, Zakalik, Karen, Duda, Petra W., MacDougall, James, Farzaneh-Far, Ramin, Pontius, Angela, and Hoarty, Michelle

Abstract

IMPORTANCE: Many patients with generalized myasthenia gravis (gMG) have substantial clinical disability, persistent disease burden, and adverse effects attributable to chronic immunosuppression. Therefore, there is a significant need for targeted, well-tolerated therapies with the potential to improve disease control and enhance quality of life. OBJECTIVE: To evaluate the clinical effects of zilucoplan, a subcutaneously (SC) self-administered macrocyclic peptide inhibitor of complement component 5, in a broad population of patients with moderate to severe gMG. DESIGN, SETTING, AND PARTICIPANTS: This randomized, double-blind, placebo-controlled phase 2 clinical trial at 25 study sites across North America recruited participants between December 2017 and August 2018. Fifty-seven patients were screened, of whom 12 did not meet inclusion criteria and 1 was lost to follow-up after randomization but before receiving study drug, resulting in a total of 44 acetylcholine receptor autoantibody (AChR-Ab)–positive patients with gMG with baseline Quantitative Myasthenia Gravis (QMG) scores of at least 12, regardless of treatment history. INTERVENTIONS: Patients were randomized 1:1:1 to a daily SC self-injection of placebo, 0.1-mg/kg zilucoplan, or 0.3-mg/kg zilucoplan for 12 weeks. MAIN OUTCOMES AND MEASURES: The primary and key secondary end points were the change from baseline to week 12 in QMG and MG Activities of Daily Living scores, respectively. Significance testing was prespecified at a 1-sided α of .10. Safety and tolerability were also assessed. RESULTS: The study of 44 patients was well balanced across the 3 treatment arms with respect to key demographic and disease-specific variables. The mean age of patients across all 3 treatment groups ranged from 45.5 to 54.6 years and most patients were white (average proportions across 3 treatment groups: 78.6%-86.7%). Clinically meaningful and statistically significant improvements in primary and key secondary efficacy end points were observed. Zilucoplan at a dose of 0.3 mg/kg SC daily resulted in a mean reduction from baseline of 6.0 points in the QMG score (placebo-corrected change, –2.8; P = .05) and 3.4 points in the MG Activities of Daily Living score (placebo-corrected change, –2.3; P = .04). Clinically meaningful and statistically significant improvements were also observed in other secondary end points, the MG Composite and MG Quality-of-Life scores. Outcomes for the 0.1-mg/kg SC daily dose were also statistically significant but slower in onset and less pronounced than with the 0.3-mg/kg dose. Rescue therapy (intravenous immunoglobulin or plasma exchange) was required in 3 of 15, 1 of 15, and 0 of 14 participants in the placebo, 0.1-mg/kg zilucoplan, and 0.3-mg/kg zilucoplan arms, respectively. Zilucoplan was observed to have a favorable safety and tolerability profile. CONCLUSIONS AND RELEVANCE: Zilucoplan yielded rapid, meaningful, and sustained improvements over 12 weeks in a broad population of patients with moderate to severe AChR-Ab–positive gMG. Near-complete complement inhibition appeared superior to submaximal inhibition. The observed safety and tolerability profile of zilucoplan was favorable. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03315130.

Published
2020
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31. Glomerular membrane attack complex is not a reliable marker of ongoing C5 activation in lupus nephritis

Author

Wilson, Hannah R., primary, Medjeral-Thomas, Nicholas R., additional, Gilmore, Alyssa C., additional, Trivedi, Pritesh, additional, Seyb, Kathleen, additional, Farzaneh-Far, Ramin, additional, Gunnarsson, Iva, additional, Zickert, Agneta, additional, Cairns, Thomas D., additional, Lightstone, Liz, additional, Cook, H. Terence, additional, and Pickering, Matthew C., additional

Published
2019
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32. Body mass index is negatively associated with telomere length: a collaborative cross-sectional meta-analysis of 87 observational studies

Author

Gielen, Marij, primary, Hageman, Geja J, additional, Antoniou, Evangelia E, additional, Nordfjall, Katarina, additional, Mangino, Massimo, additional, Balasubramanyam, Muthuswamy, additional, de Meyer, Tim, additional, Hendricks, Audrey E, additional, Giltay, Erik J, additional, Hunt, Steven C, additional, Nettleton, Jennifer A, additional, Salpea, Klelia D, additional, Diaz, Vanessa A, additional, Farzaneh-Far, Ramin, additional, Atzmon, Gil, additional, Harris, Sarah E, additional, Hou, Lifang, additional, Gilley, David, additional, Hovatta, Iiris, additional, Kark, Jeremy D, additional, Nassar, Hisham, additional, Kurz, David J, additional, Mather, Karen A, additional, Willeit, Peter, additional, Zheng, Yun-Ling, additional, Pavanello, Sofia, additional, Demerath, Ellen W, additional, Rode, Line, additional, Bunout, Daniel, additional, Steptoe, Andrew, additional, Boardman, Lisa, additional, Marti, Amelia, additional, Needham, Belinda, additional, Zheng, Wei, additional, Ramsey-Goldman, Rosalind, additional, Pellatt, Andrew J, additional, Kaprio, Jaakko, additional, Hofmann, Jonathan N, additional, Gieger, Christian, additional, Paolisso, Giuseppe, additional, Hjelmborg, Jacob B H, additional, Mirabello, Lisa, additional, Seeman, Teresa, additional, Wong, Jason, additional, van der Harst, Pim, additional, Broer, Linda, additional, Kronenberg, Florian, additional, Kollerits, Barbara, additional, Strandberg, Timo, additional, Eisenberg, Dan T A, additional, Duggan, Catherine, additional, Verhoeven, Josine E, additional, Schaakxs, Roxanne, additional, Zannolli, Raffaela, additional, dos Reis, Rosana M R, additional, Charchar, Fadi J, additional, Tomaszewski, Maciej, additional, Mons, Ute, additional, Demuth, Ilja, additional, Molli, Andrea Elena Iglesias, additional, Cheng, Guo, additional, Krasnienkov, Dmytro, additional, D'Antono, Bianca, additional, Kasielski, Marek, additional, McDonnell, Barry J, additional, Ebstein, Richard Paul, additional, Sundquist, Kristina, additional, Pare, Guillaume, additional, Chong, Michael, additional, and Zeegers, Maurice P, additional

Published
2018
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33. RA101495, A Subcutaneously Administered Peptide Inhibitor of Complement Component 5 (C5) for the Treatment of Generalized Myasthenia Gravis (gMG): Phase 1 Results and Phase 2 Design (S31.006)

Author

Howard, James F., primary, Kaminski, Henry J., additional, Nowak, Richard J., additional, Wolfe, Gil I., additional, Benatar, Michael G., additional, Ricardo, Alonso, additional, Hoarty, Michelle D., additional, DeMarco, Steven J., additional, Farzaneh-Far, Ramin, additional, and Duda, Petra W., additional

Published
2018
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34. The spectrum of complement C9 staining in lupus nephritis

Author

Wilson, Hannah R., primary, Gilmore, Alyssa, additional, Medjeral-Thomas, Nicholas R., additional, Trivedi, Pritesh, additional, Seyb, Kathleen, additional, Farzaneh-Far, Ramin, additional, Cairns, Thomas, additional, Lightstone, Liz, additional, Pickering, Matthew C., additional, and Cook, H. Terence, additional

Published
2017
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35. Association of cardiorespiratory fitness with left ventricular remodeling and diastolic function: the Cooper Center Longitudinal Study

Author

Brinker, Stephanie K, Pandey, Ambarish, Ayers, Colby R, Barlow, Carolyn E, DeFina, Laura F, Willis, Benjamin L, Radford, Nina B, Farzaneh-Far, Ramin, de Lemos, James A, Drazner, Mark H, and Berry, Jarett D

Subjects
Male, Heart Failure, Diastolic, Ventricular Remodeling, Cardiac Volume, Myocardium, Stroke Volume, Organ Size, Middle Aged, Article, Ventricular Dysfunction, Left, Cross-Sectional Studies, Echocardiography, Physical Fitness, Exercise Test, Humans, Female, Heart Atria, Longitudinal Studies
Abstract

This study sought to compare the cross-sectional associations between fitness and echocardiographic measures of cardiac structure and function.Cardiorespiratory fitness is inversely associated with heart failure risk. However, the mechanism through which fitness lowers heart failure risk is not fully understood.We included 1,678 men and 1,247 women from the Cooper Center Longitudinal Study who received an echocardiogram from 1999 to 2011. Fitness was estimated by Balke protocol (in metabolic equivalents) and also categorized into age-specific quartiles, with quartile 1 representing low fitness. Cross-sectional associations between fitness (in metabolic equivalents) and relative wall thickness, left ventricular end-diastolic diameter indexed to body surface area, left atrial volume indexed to body surface area, left ventricular systolic function, and E/e' ratio were determined using multivariable linear regression analysis.Higher levels of mid-life fitness (metabolic equivalents) were associated with larger indexed left atrial volume (men: beta = 0.769, p0.0001; women: beta = 0.879, p value ≤0.0001) and indexed left ventricular end-diastolic diameter (men: beta = 0.231, p0.001; women: beta = 0.264, p0.0001). Similarly, a higher level of fitness was associated with a smaller relative wall thickness (men: beta = -0.002, p = 0.04; women: beta = -0.005, p0.0001) and E/e' ratio (men: beta = -0.11, p = 0.003; women: beta = -0.13, p = 0.01). However, there was no association between low fitness and left ventricular systolic function (p = NS).Low fitness is associated with a higher prevalence of concentric remodeling and diastolic dysfunction, suggesting that exercise may lower heart failure risk through its effect on favorable cardiac remodeling and improved diastolic function.

Published
2013

38. Effects of Ranolazine on Angina and Quality of Life After Percutaneous Coronary Intervention With Incomplete Revascularization

Author

Alexander, Karen P., primary, Weisz, Giora, additional, Prather, Kristi, additional, James, Stefan, additional, Mark, Daniel B., additional, Anstrom, Kevin J., additional, Davidson-Ray, Linda, additional, Witkowski, Adam, additional, Mulkay, Angel J., additional, Osmukhina, Anna, additional, Farzaneh-Far, Ramin, additional, Ben-Yehuda, Ori, additional, Stone, Gregg W., additional, and Ohman, E. Magnus, additional

Published
2016
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39. Effects of Ranolazine in Patients With Chronic Angina in Patients With and Without Percutaneous Coronary Intervention for Acute Coronary Syndrome: Observations From the MERLIN-TIMI 36 Trial

Author

Gutierrez, Jorge A., primary, Karwatowska-Prokopczuk, Ewa, additional, Murphy, Sabina A., additional, Belardinelli, Luiz, additional, Farzaneh-Far, Ramin, additional, Walker, Gennyne, additional, Morrow, David A., additional, and Scirica, Benjamin M., additional

Published
2015
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40. Development of an echocardiographic risk-stratification index to predict heart failure in patients with stable coronary artery disease: the Heart and Soul study

Author

Stevens, Steven M., Farzaneh-Far, Ramin, Na, Beeya, Whooley, Mary A., and Schiller, Nelson B.

Subjects
Male, Time Factors, Heart Ventricles, risk stratification, Coronary Artery Disease, Risk Assessment, Severity of Illness Index, Article, California, Ventricular Dysfunction, Left, Predictive Value of Tests, Risk Factors, echocardiography, Humans, Heart Atria, Prospective Studies, Aged, Proportional Hazards Models, Heart Failure, prognostic index, Mitral Valve Insufficiency, Length of Stay, Middle Aged, Prognosis, Echocardiography, Doppler, Disease Progression, Female, Follow-Up Studies
Abstract

ObjectivesWe sought to determine which transthoracic echocardiographic (TTE) measurements most strongly predict heart failure (HF) and to develop an index for risk stratification in outpatients with coronary artery disease (CAD).BackgroundMany TTE measurements have been shown to be predictive of HF, and they might be useful if aggregated into a risk-prediction index.MethodsWe performed TTE in 1,024 outpatients with stable CAD enrolled in the Heart and Soul study and followed them for 4.4 years. With Cox proportional hazard models, we evaluated the association of 15 TTE measurements with subsequent HF hospital stay. Those measurements that independently predicted HF were combined into an index. Variables were defined as normal or abnormal on the basis of dichotomous cutoffs determined from the American Society of Echocardiography. Abnormal variables in each measurement were assigned points on the basis of strength of association with HF.ResultsOf the 15 variables, 5 measurements were independent predictors of HF: left ventricular mass index (LVMI), left atrial volume index (LAVI), mitral regurgitation (MR), left ventricular outflow tract velocity-time integral (VTILVOT), and diastolic dysfunction (DD). In multivariate analysis, each of the 5 measurements independently predicted HF: LVMI >90 g/m2 (hazard ratio [HR]: 4.1; 95% confidence interval [CI]: 2.3 to 7.2, p < 0.0001); pseudo-normal or restrictive DD (HR: 2.9; 95% CI: 1.8 to 4.5, p < 0.0001); VTILVOT 29 ml/m2 (HR: 1.6; 95% CI: 1.0 to 2.5, p < 0.06). Combining these measurements, the Heart Failure Index ranged from 0 to 8, representing risk as follows: 3 points for LVMI, 2 points for DD, and 1 point for VTILVOT, MR, and LAVI. Among participants with 0 to 2 points: 4% had HF hospital stays (reference); 3 to 4 points: 10% (HR: 2.4; 95% CI: 1.3 to 4.4, p = 0.003); 5 to 6 points: 24% (HR: 6.2; 95% CI: 3.6 to 10.6, p < 0.0001); 7 to 8 points: 48% (HR: 13.7; 95% CI: 7.2 to 25.9, p < 0.0001).ConclusionsWe identified 5 TTE measurements that independently predict HF in patients with stable CAD and combined them as an index that might be useful for risk stratification and serial observations.

Published
2008

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