Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

PET and SPECT in cardiovascular molecular imaging

Abstract

The current focus of cardiovascular medicine is on early detection and prevention of disease, to control the escalating costs of health care. To achieve this goal, novel imaging approaches that allow for early detection of disease and risk stratification are needed. Traditionally, the diagnosis, monitoring, and prognostication of cardiovascular disease were based on techniques that measured changes in metabolism, blood flow, and biological function. Molecular imaging is emerging as a new tool for the noninvasive detection of biological processes that can differentiate and characterize tissues before manifestation of gross anatomical features or physiological consequences. Leading the way are techniques involving high-sensitivity radiotracers that could revolutionize current diagnostic paradigms. This Review provides an overview of selected molecular-based single photon emission CT (SPECT) and PET imaging strategies for the evaluation of cardiovascular disease—including the evaluation of myocardial metabolism and neurohumoral activity of the heart—and potential future targeted methods of evaluating critical molecular processes, such as atherosclerosis, ventricular remodeling after myocardial infarction, and ischemia-associated angiogenesis.

Key Points

  • With the growth of genomics and proteomics has come a requirement for new diagnostic molecular imaging approaches that advance health care through early detection of disease processes

  • Noninvasive targeted radiotracer-based SPECT and PET approaches are evolving through both preclinical imaging studies, involving transgenic animals, and advances in imaging technology

  • Both SPECT and PET, as nuclear techniques, have unique advantages including high sensitivity and selectivity, which make these approaches particularly suitable for cardiovascular molecular imaging

  • The introduction of hybrid SPECT–CT and PET–CT imaging systems has greatly enhanced the performance and accuracy of nuclear imaging

  • The examples of targeted radiotracer imaging with SPECT and PET presented in this Review provide insight into the future of noninvasive cardiovascular imaging

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Reporter gene technology.
Figure 2: Representative PET time–activity curves of L-3-11C-lactate and corresponding myocardial images obtained 5–10 min after tracer injection and depicting primarily early tracer uptake.
Figure 3: Representative midventricular short-axis slices of myocardial sympathetic innervation imaged with 11C-epinephrine PET, in the healthy human, pig, and rat heart.
Figure 4: Myocardial origin of 64Cu-DOTA-VEGF121 PET signal after myocardial infarction (MI).
Figure 5: Noninvasive PET–CT images of angiogenesis induced by hindlimb ischemia in a murine model.
Figure 6: MicroSPECT–CT 99mTc-RP805 images were acquired by use of a high resolution SPECT detector after the administration of X-ray contrast, a | at 1 week and b | 3 weeks after myocardial infarction.

Similar content being viewed by others

References

  1. National Academy of Engineering. Greatest Engineering Achievements of the 20th Century [online], (2009).

  2. Brumley, C. L. & Kuhn, J. A. Radiolabeled monoclonal antibodies. Aorn J. 62, 343–350 (1995).

    CAS  PubMed  Google Scholar 

  3. Inubushi, M. & Tamaki, N. Radionuclide reporter gene imaging for cardiac gene therapy. Eur. J. Nucl. Med. Mol. Imaging 34 (Suppl. 1), S27–S33 (2007).

    CAS  PubMed  Google Scholar 

  4. Sun, N., Lee, A. & Wu, J. C. Long term non-invasive imaging of embryonic stem cells using reporter genes. Nat. Protoc. 4, 1192–1201 (2009).

    CAS  PubMed Central  PubMed  Google Scholar 

  5. Willmann, J. K. et al. Imaging gene expression in human mesenchymal stem cells: from small to large animals. Radiology 252, 117–127 (2009).

    PubMed Central  PubMed  Google Scholar 

  6. Hiona, A. & Wu, J. C. Noninvasive radionuclide imaging of cardiac gene therapy: progress and potential. Nat. Clin. Pract. Cardiovasc. Med. 5 (Suppl. 2), S87–S95 (2008).

    CAS  PubMed  Google Scholar 

  7. Nahrendorf, M. et al. Multimodality cardiovascular molecular imaging, part II. Circ. Cardiovasc. Imaging 2, 56–70 (2009).

    PubMed Central  PubMed  Google Scholar 

  8. Sinusas, A. J. et al. Multimodality cardiovascular molecular imaging, part I. Circ. Cardiovasc. Imaging 1, 244–256 (2008).

    PubMed  Google Scholar 

  9. Dobrucki, L. W. & Sinusas, A. J. Molecular imaging. A new approach to nuclear cardiology. Q. J. Nucl. Med. Mol. Imaging 49, 106–115 (2005).

    CAS  PubMed  Google Scholar 

  10. Dobrucki, L. W. & Sinusas, A. J. Molecular cardiovascular imaging. Curr. Cardiol. Rep. 7, 130–135 (2005).

    PubMed  Google Scholar 

  11. Dobrucki, L. W. & Sinusas, A. J. Cardiovascular molecular imaging. Semin. Nucl. Med. 35, 73–81 (2005).

    PubMed  Google Scholar 

  12. Dobrucki, L. W. & Sinusas, A. J. Imaging angiogenesis. Curr. Opin. Biotechnol. 18, 90–96 (2007).

    CAS  PubMed  Google Scholar 

  13. Blankenberg, F. G. Molecular imaging: The latest generation of contrast agents and tissue characterization techniques. J. Cell. Biochem. 90, 443–453 (2003).

    CAS  PubMed  Google Scholar 

  14. Sinusas, A. J. Imaging of angiogenesis. J. Nucl. Cardiol. 11, 617–633 (2004).

    PubMed  Google Scholar 

  15. Morrison, A. R. & Sinusas, A. J. New molecular imaging targets to characterize myocardial biology. Cardiol. Clin. 27, 329–344 (2009).

    PubMed Central  PubMed  Google Scholar 

  16. Kim, H. et al. SemiSPECT: a small-animal single-photon emission computed tomography (SPECT) imager based on eight cadmium zinc telluride (CZT) detector arrays. Med. Phys. 33, 465–474 (2006).

    CAS  PubMed  Google Scholar 

  17. Wagenaar, D. J., Kapusta, M., Li, J. & Patt, B. E. Rationale for the combination of nuclear medicine with magnetic resonance for pre-clinical imaging. Technol. Cancer Res. Treat. 5, 343–350 (2006).

    PubMed  Google Scholar 

  18. Tawakol, A. et al. In vivo 18F-fluorodeoxyglucose positron emission tomography imaging provides a noninvasive measure of carotid plaque inflammation in patients. J. Am. Coll. Cardiol. 48, 1818–1824 (2006).

    PubMed  Google Scholar 

  19. Dilsizian, V. et al. Metabolic imaging with beta-methyl-p-[(123)I]-iodophenyl-pentadecanoic acid identifies ischemic memory after demand ischemia. Circulation 112, 2169–2174 (2005).

    PubMed  Google Scholar 

  20. Kida, K., Akashi, Y. J., Yoneyama, K., Shimokawa, M. & Musha, H. 123I-BMIPP delayed scintigraphic imaging in patients with chronic heart failure. Ann. Nucl. Med. 22, 769–775 (2008).

    PubMed  Google Scholar 

  21. Nakamura, A. et al. Ability of (201)Tl and (123)I-BMIPP mismatch to diagnose myocardial ischemia in patients with suspected coronary artery disease. Ann. Nucl. Med. doi: 10.1007/s12149-009-0307–0308

  22. Nanasato, M. et al. Restored cardiac conditions and left ventricular function after parathyroidectomy in a hemodialysis patient. Parathyroidectomy improves cardiac fatty acid metabolism assessed by 123I-BMIPP. Circ. J. 73, 1956–1960 (2009).

    PubMed  Google Scholar 

  23. Shi, C. Q. et al. Correlation of myocardial p-(123)I-iodophenylpentadecanoic acid retention with (18)F-FDG accumulation during experimental low-flow ischemia. J. Nucl. Med. 43, 421–431 (2002).

    PubMed  Google Scholar 

  24. Verani, M. S. et al. 123I-IPPA SPECT for the prediction of enhanced left ventricular function after coronary bypass graft surgery. Multicenter IPPA Viability Trial Investigators. 123I-iodophenylpentadecanoic acid. J. Nucl. Med. 41, 1299–1307 (2000).

    CAS  PubMed  Google Scholar 

  25. Volokh, L., Lahat, C. & Blevis, I. Myocardial perfusion imaging with an ultra-fast cardiac SPECT camera: a phantom study. Nuclear Science Symposium Conference Record 19–25 October 4636–4639 (2008).

  26. Levy, M. N. Cardiac sympathetic-parasympathetic interactions. Fed. Proc. 43, 2598–2602 (1984).

    CAS  PubMed  Google Scholar 

  27. Sunagawa, K., Kawada, T. & Nakahara, T. Dynamic nonlinear vago-sympathetic interaction in regulating heart rate. Heart Vessels 13, 157–174 (1998).

    CAS  PubMed  Google Scholar 

  28. Zemaityte, D. J., Varoneckas, G. A. & Sokolov, E. N. Interaction between the parasympathetic and sympathetic divisions of the autonomic nervous system in cardiac rhythm regulation. Hum. Physiol. 11, 208–215 (1985).

    CAS  PubMed  Google Scholar 

  29. Henneman, M. M., Bengel, F. M., van der Wall, E. E., Knuuti, J. & Bax, J. J. Cardiac neuronal imaging: application in the evaluation of cardiac disease. J. Nucl. Cardiol. 15, 442–455 (2008).

    PubMed  Google Scholar 

  30. Higuchi, T. & Schwaiger, M. Noninvasive imaging of heart failure: neuronal dysfunction and risk stratification. Heart Fail. Clin. 2, 193–204 (2006).

    PubMed  Google Scholar 

  31. Carrio, I. Cardiac neurotransmission imaging. J. Nucl. Med. 42, 1062–1076 (2001).

    CAS  PubMed  Google Scholar 

  32. Cleland, J. G., Coletta, A. P., Clark, A. L. & Cullington, D. Clinical trials update from the American College of Cardiology ADMIRE-HF, PRIMA, STICH, REVERSE, IRIS, partial ventricular support, FIX-HF-5, vagal stimulation, REVIVAL-3, pre-RELAX-AHF, ACTIVE-A, HF-ACTION, JUPITER, AURORA, and OMEGA. Eur. J. Heart Fail. 11, 622–630 (2009).

    PubMed  Google Scholar 

  33. Link, J. M. et al. PET measures of pre- and post-synaptic cardiac beta adrenergic function. Nucl. Med. Biol. 30, 795–803 (2003).

    CAS  PubMed  Google Scholar 

  34. Tseng, H., Link, J. M., Stratton, J. R. & Caldwell, J. H. Cardiac receptor physiology and its application to clinical imaging: present and future. J. Nucl. Cardiol. 8, 390–409 (2001).

    CAS  PubMed  Google Scholar 

  35. Accuracy of radiolabeled fatty acid analog, BMIPP, in the late detection of decreased blood flow to the heart (ZEUSS-ACS). NCT00585663. ClinicalTrials.gov [online] (2009).

  36. Cardiac sympathetic activity in patients with the apical ballooning syndrome. NCT00586183. ClinicalTrials.gov [online] (2007).

  37. Battegay, E. J. Angiogenesis: mechanistic insights, neovascular diseases, and therapeutic prospects. J. Mol. Med. 73, 333–346 (1995).

    CAS  PubMed  Google Scholar 

  38. Carmeliet, P. Angiogenesis in health and disease. Nat. Med. 9, 653–660 (2003).

    CAS  PubMed  Google Scholar 

  39. Brack, S. S., Dinkelborg, L. M. & Neri, D. Molecular targeting of angiogenesis for imaging and therapy. Eur. J. Nucl. Med. Mol. Imaging 31, 1327–1341 (2004).

    PubMed  Google Scholar 

  40. Miller, J. C., Pien, H. H., Sahani, D., Sorensen, A. G. & Thrall, J. H. Imaging angiogenesis: applications and potential for drug development. J. Natl Cancer Inst. 97, 172–187 (2005).

    CAS  PubMed  Google Scholar 

  41. Ferrara, N. & Davis-Smyth, T. The biology of vascular endothelial growth factor. Endocr. Rev. 18, 4–25 (1997).

    CAS  PubMed  Google Scholar 

  42. Ferrara, N., Gerber, H. P. & LeCouter, J. The biology of VEGF and its receptors. Nat. Med. 9, 669–676 (2003).

    CAS  PubMed  Google Scholar 

  43. Shweiki, D., Itin, A., Soffer, D. & Keshet, E. Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis. Nature 359, 843–845 (1992).

    CAS  PubMed  Google Scholar 

  44. Brooks, P. C., Clark, R. A. & Cheresh, D. A. Requirement of vascular integrin alpha v beta 3 for angiogenesis. Science 264, 569–571 (1994).

    CAS  PubMed  Google Scholar 

  45. Brooks, P. C. et al. Integrin alpha v beta 3 antagonists promote tumor regression by inducing apoptosis of angiogenic blood vessels. Cell 79, 1157–1164 (1994).

    CAS  PubMed  Google Scholar 

  46. Haas, T. L. & Madri, J. A. Extracellular matrix-driven matrix metalloproteinase production in endothelial cells: implications for angiogenesis. Trends Cardiovasc. Med. 9, 70–77 (1999).

    CAS  PubMed  Google Scholar 

  47. Haas, T. L. et al. Matrix metalloproteinase activity is required for activity-induced angiogenesis in rat skeletal muscle. Am. J. Physiol. Heart Circ. Physiol. 279, H1540–H1547 (2000).

    CAS  PubMed  Google Scholar 

  48. Lu, E. et al. Targeted in vivo labeling of receptors for vascular endothelial growth factor: approach to identification of ischemic tissue. Circulation 108, 97–103 (2003).

    CAS  PubMed  Google Scholar 

  49. Cai, W. et al. PET of vascular endothelial growth factor receptor expression. J. Nucl. Med. 47, 2048–2056 (2006).

    CAS  PubMed  Google Scholar 

  50. Rodriguez-Porcel, M. et al. Imaging of VEGF receptor in a rat myocardial infarction model using PET. J. Nucl. Med. 49, 667–673 (2008).

    PubMed  Google Scholar 

  51. Wagner, B. et al. Noninvasive characterization of myocardial molecular interventions by integrated positron emission tomography and computed tomography. J. Am. Coll. Cardiol. 48, 2107–2115 (2006).

    PubMed  Google Scholar 

  52. Sipkins, D. A. et al. Detection of tumor angiogenesis in vivo by alphaVbeta3-targeted magnetic resonance imaging. Nat. Med. 4, 623–626 (1998).

    CAS  PubMed  Google Scholar 

  53. Haubner, R. et al. Glycosylated RGD-containing peptides: tracer for tumor targeting and angiogenesis imaging with improved biokinetics. J. Nucl. Med. 42, 326–336 (2001).

    CAS  PubMed  Google Scholar 

  54. Haubner, R. et al. Radiolabeled alpha(v)beta3 integrin antagonists: a new class of tracers for tumor targeting. J. Nucl. Med. 40, 1061–1071 (1999).

    CAS  PubMed  Google Scholar 

  55. Haubner, R. et al. Noninvasive imaging of alpha(v)beta3 integrin expression using 18F-labeled RGD-containing glycopeptide and positron emission tomography. Cancer Res. 61, 1781–1785 (2001).

    CAS  PubMed  Google Scholar 

  56. Pfaff, M. et al. Selective recognition of cyclic RGD peptides of NMR defined conformation by alpha IIb beta 3, alpha V beta 3, and alpha 5 beta 1 integrins. J. Biol. Chem. 269, 20233–20238 (1994).

    CAS  PubMed  Google Scholar 

  57. Harris, T. D. et al. Design, synthesis, and evaluation of radiolabeled integrin alpha v beta 3 receptor antagonists for tumor imaging and radiotherapy. Cancer Biother. Radiopharm. 18, 627–641 (2003).

    CAS  PubMed  Google Scholar 

  58. Sadeghi, M. M. et al. Imaging αvβ3 integrin in vascular injury: does this reflect increased integrin expression or activation? Circulation 108 (17 Suppl.), 1868 (2003).

    Google Scholar 

  59. Meoli, D. F. et al. Noninvasive imaging of myocardial angiogenesis following experimental myocardial infarction. J. Clin. Invest. 113, 1684–1691 (2004).

    CAS  PubMed Central  PubMed  Google Scholar 

  60. Kalinowski, L. et al. Targeted imaging of hypoxia-induced integrin activation in myocardium early after infarction. J. Appl. Physiol. 104, 1504–1512 (2008).

    CAS  PubMed  Google Scholar 

  61. Bach-Gansmo, T. et al. Integrin receptor imaging of breast cancer: a proof-of-concept study to evaluate 99mTc-NC100692. J. Nucl. Med. 47, 1434–1439 (2006).

    CAS  PubMed  Google Scholar 

  62. Edwards, D. et al. 99mTc-NC100692--a tracer for imaging vitronectin receptors associated with angiogenesis: a preclinical investigation. Nucl. Med. Biol. 35, 365–375 (2008).

    CAS  PubMed  Google Scholar 

  63. Indrevoll, B. et al. NC-100717: a versatile RGD peptide scaffold for angiogenesis imaging. Bioorg. Med. Chem. Lett. 16, 6190–6193 (2006).

    CAS  PubMed  Google Scholar 

  64. Kenny, L. M. et al. Phase I trial of the positron-emitting Arg-Gly-Asp (RGD) peptide radioligand 18F-AH111585 in breast cancer patients. J. Nucl. Med. 49, 879–886 (2008).

    PubMed  Google Scholar 

  65. Hua, J. et al. Noninvasive imaging of angiogenesis with a 99mTc-labeled peptide targeted at alphavbeta3 integrin after murine hindlimb ischemia. Circulation 111, 3255–3260 (2005).

    CAS  PubMed  Google Scholar 

  66. Lindsey, M. L. et al. Matrix metalloproteinase-9 gene deletion facilitates angiogenesis after myocardial infarction. Am. J. Physiol. Heart Circ. Physiol. 290, H232–H239 (2006).

    CAS  PubMed  Google Scholar 

  67. Dobrucki, L. W. et al. Serial noninvasive targeted imaging of peripheral angiogenesis: validation and application of a semiautomated quantitative approach. J. Nucl. Med. 50, 1356–1363 (2009).

    PubMed  Google Scholar 

  68. Almutairi, A. et al. Biodegradable dendritic positron-emitting nanoprobes for the noninvasive imaging of angiogenesis. Proc. Natl Acad. Sci. USA 106, 685–690 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Haubner, R. et al. Noninvasive visualization of the activated alphavbeta3 integrin in cancer patients by positron emission tomography and [18F]Galacto-RGD. PLoS Med. 2, e70 (2005).

    PubMed Central  PubMed  Google Scholar 

  70. Liu, S. Radiolabeled multimeric cyclic RGD peptides as integrin alphavbeta3 targeted radiotracers for tumor imaging. Mol. Pharm. 3, 472–487 (2006).

    CAS  PubMed  Google Scholar 

  71. Jaffer, F. A., Libby, P. & Weissleder, R. Molecular imaging of cardiovascular disease. Circulation 116, 1052–1061 (2007).

    PubMed  Google Scholar 

  72. Sutton, M. G. & Sharpe, N. Left ventricular remodeling after myocardial infarction: pathophysiology and therapy. Circulation 101, 2981–2988 (2000).

    CAS  PubMed  Google Scholar 

  73. Chung, G. & Sinusas, A. J. Imaging of matrix metalloproteinase activation and left ventricular remodeling. Curr. Cardiol. Rep. 9, 136–142 (2007).

    PubMed  Google Scholar 

  74. Su, H. et al. Noninvasive targeted imaging of matrix metalloproteinase activation in a murine model of postinfarction remodeling. Circulation 112, 3157–3167 (2005).

    CAS  PubMed  Google Scholar 

  75. Liu, Y. H. et al. Hotspot quantification of myocardial focal tracer uptake from molecular targeted SPECT/CT images: experimental validation - art. no. 69150N. Proceedings—SPIE (The International Society for Optical Engineering) 6915 (Part 1), 69150N–69150N-8 (2008).

  76. Nahrendorf, M. et al. Factor XIII deficiency causes cardiac rupture, impairs wound healing, and aggravates cardiac remodeling in mice with myocardial infarction. Circulation 113, 1196–1202 (2006).

    CAS  PubMed Central  PubMed  Google Scholar 

  77. Nahrendorf, M. et al. Transglutaminase activity in acute infarcts predicts healing outcome and left ventricular remodelling: implications for FXIII therapy and antithrombin use in myocardial infarction. Eur. Heart J. 29, 445–454 (2008).

    CAS  PubMed  Google Scholar 

  78. Shirani, J. & Dilsizian, V. Imaging left ventricular remodeling: targeting the neurohumoral axis. Nat. Clin. Pract. Cardiovasc. Med. 5 (Suppl. 2), S57–S62 (2008).

    CAS  PubMed  Google Scholar 

  79. Dilsizian, V., Eckelman, W. C., Loredo, M. L., Jagoda, E. M. & Shirani, J. Evidence for tissue angiotensin-converting enzyme in explanted hearts of ischemic cardiomyopathy using targeted radiotracer technique. J. Nucl. Med. 48, 182–187 (2007).

    CAS  PubMed  Google Scholar 

  80. Shirani, J., Narula, J., Eckelman, W. C., Narula, N. & Dilsizian, V. Early imaging in heart failure: exploring novel molecular targets. J. Nucl. Cardiol. 14, 100–110 (2007).

    PubMed  Google Scholar 

  81. Trivedi, R. A. et al. Identifying inflamed carotid plaques using in vivo USPIO-enhanced MR imaging to label plaque macrophages. Arterioscler. Thromb. Vasc. Biol. 26, 1601–1606 (2006).

    CAS  PubMed  Google Scholar 

  82. Nahrendorf, M. et al. Nanoparticle PET-CT imaging of macrophages in inflammatory atherosclerosis. Circulation 117, 379–387 (2008).

    CAS  PubMed  Google Scholar 

  83. Hyafil, F. et al. Noninvasive detection of macrophages using a nanoparticulate contrast agent for computed tomography. Nat. Med. 13, 636–641 (2007).

    CAS  PubMed  Google Scholar 

  84. Schafers, M. et al. Scintigraphic imaging of matrix metalloproteinase activity in the arterial wall in vivo. Circulation 109, 2554–2559 (2004).

    PubMed  Google Scholar 

  85. Zhang, J. et al. Molecular imaging of activated matrix metalloproteinases in vascular remodeling. Circulation 118, 1953–1960 (2008).

    CAS  PubMed Central  PubMed  Google Scholar 

  86. Sadeghi, M. M. et al. Detection of injury-induced vascular remodeling by targeting activated alphavbeta3 integrin in vivo. Circulation 110, 84–90 (2004).

    CAS  PubMed  Google Scholar 

  87. Matter, C. M. et al. Molecular imaging of atherosclerotic plaques using a human antibody against the extra-domain B of fibronectin. Circ. Res. 95, 1225–1233 (2004).

    CAS  PubMed  Google Scholar 

  88. von Lukowicz, T. et al. Human antibody against C domain of tenascin-C visualizes murine atherosclerotic plaques ex vivo. J. Nucl. Med. 48, 582–587 (2007).

    CAS  PubMed  Google Scholar 

  89. Lederman, R. J. et al. Detection of atherosclerosis using a novel positron-sensitive probe and 18-fluorodeoxyglucose (FDG). Nucl. Med. Commun. 22, 747–753 (2001).

    CAS  PubMed  Google Scholar 

  90. Zhu, Q., Piao, D., Sadeghi, M. M. & Sinusas, A. J. Simultaneous optical coherence tomography imaging and beta particle detection. Opt. Lett. 28, 1704–1706 (2003).

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Albert J. Sinusas.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Dobrucki, L., Sinusas, A. PET and SPECT in cardiovascular molecular imaging. Nat Rev Cardiol 7, 38–47 (2010). https://doi.org/10.1038/nrcardio.2009.201

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrcardio.2009.201

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing