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.

  • Viewpoint
  • Published:

Exploring unknowns in cardiology

Nature Reviews Cardiology volume 11, pages 664–670 (2014)Cite this article

Subjects

This article has been updated

Abstract

To mark the 10th anniversary of Nature Reviews Cardiology in November 2014, five of our Advisory Board members were invited to consider a topic within cardiology about which we know too little. A diverse range of subjects are highlighted in this Perspectives article, including preoperative assessment of right ventricular function, the burden of cardiomyopathies in Africa, the measurement of fractional flow reserve to guide coronary intervention, the interaction between genes and environment in cardiovascular disease, and the difficulty of predicting atherosclerotic plaque rupture. The five key opinion leaders from around the globe also suggest ways in which future research could be targeted to address the deficits in our understanding, with the aim of preventing cardiovascular disease, improving patient care, and reducing morbidity and mortality.

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

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

Figure 1: Assessment of right ventricular dimensions and volume.
Figure 2: Cardiomyopathy is a major cause of acute heart failure in Africa.
Figure 3: Kaplan–Meier curves showing clinical outcomes before and after the routine use of FFR.
Figure 4: Morphological features of atherothrombosis.

Similar content being viewed by others

Change history

  • 25 September 2014

    In the version of this article initially published online, Seung-Jung Park’s name was misspelled in the contributors’ biographies on page 2. The error has been corrected for the print, HTML, and PDF versions of the article.

References

  1. Kaul, T. K. & Fields, B. L. Postoperative acute refractory right ventricular failure: incidence, pathogenesis, management and prognosis. Cardiovasc. Surg. 8, 1–9 (2000).

    Article  CAS  Google Scholar 

  2. Haddad, F., Doyle, R., Murphy, D. J. & Hunt, S. A. Right ventricular function in cardiovascular disease, part II: pathophysiology, clinical importance, and management of right ventricular failure. Circulation 117, 1717–1731 (2008).

    Article  Google Scholar 

  3. Reichert, C. L. et al. Prognostic value of biventricular function in hypotensive patients after cardiac surgery as assessed by transesophageal echocardiography. J. Cardiothorac. Vasc. Anesth. 6, 429–432 (1992).

    Article  CAS  Google Scholar 

  4. Pinzani, A. et al. Pre- and postoperative right cardiac insufficiency in patients with mitral or mitral-aortic valve diseases [French]. Arch. Mal. Coeur Vaiss. 86, 27–34 (1993).

    CAS  PubMed  Google Scholar 

  5. Maslow, A. D. et al. Precardiopulmonary bypass right ventricular function is associated with poor outcome after coronary artery bypass grafting in patients with severe left ventricular systolic dysfunction. Anesth. Analg. 95, 1507–1158 (2002).

    Article  Google Scholar 

  6. Haddad, F. et al. Right ventricular myocardial performance index predicts perioperative mortality or circulatory failure in high-risk valvular surgery. J. Am. Soc. Echocardiogr. 20, 1065–1072 (2007).

    Article  Google Scholar 

  7. Ochiai, Y. et al. Predictors of severe right ventricular failure after implantable left ventricular assist device insertion: analysis of 245 patients. Circulation 106 (Suppl. 1), I198–I202 (2002).

    PubMed  Google Scholar 

  8. Mertens, L. L. & Friedberg, M. K. Imaging the right ventricle—current state of the art. Nat. Rev. Cardiol. 7, 551–563 (2010).

    Article  Google Scholar 

  9. Friedberg, M. K. & Redington, A. N. Right versus left ventricular failure: differences, similarities, and interactions. Circulation 129, 1033–1034 (2014).

    Article  Google Scholar 

  10. Vahanian, A. et al. Guidelines on the management of valvular heart disease (version 2012). Joint Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS). Eur. Heart J. 33, 2451–2496 (2012).

    Article  Google Scholar 

  11. Akinkugbe, O. O., Nicholson, G. D. & Cruickshank, J. K. Heart disease in blacks of Africa and the Caribbean. Cardiovasc. Clin. 21, 377–391 (1991).

    CAS  PubMed  Google Scholar 

  12. Damasceno, A. et al. The causes, treatment, and outcome of acute heart failure in 1006 Africans from 9 countries: results of the Sub-Saharan Africa Survey of Heart Failure. Arch. Intern. Med. 172, 1386–1394 (2012).

    Article  CAS  Google Scholar 

  13. Sliwa, K. & Mayosi, B. M. Recent advances in the epidemiology, pathogenesis and prognosis of acute heart failure and cardiomyopathy in Africa. Heart 99, 1317–1322 (2013).

    Article  Google Scholar 

  14. Mocumbi, A. O., Ferreira, M. B., Sidi, D. & Yacoub, M. H. A population study of endomyocardial fibrosis in a rural area of Mozambique. N. Engl. J. Med. 359, 43–49 (2008).

    Article  CAS  Google Scholar 

  15. Khogali, S. S. et al. A common mitochondrial DNA variant associated with susceptibility to dilated cardiomyopathy in two different populations. Lancet 357, 1265–1267 (2001).

    Article  CAS  Google Scholar 

  16. Ntusi, N. B., Wonkam, A., Shaboodien, G., Badri, M. & Mayosi, B. M. Frequency and clinical genetics of familial dilated cardiomyopathy in Cape Town: implications for the evaluation of patients with unexplained cardiomyopathy. S. Afr. Med. J. 101, 394–398 (2011).

    PubMed  Google Scholar 

  17. Shaboodien, G. et al. Prevalence of myocarditis and cardiotropic virus infection in Africans with HIV-associated cardiomyopathy, idiopathic dilated cardiomyopathy and heart transplant recipients: a pilot study. Cardiovasc. J. Afr. 23, 1–6 (2013).

    Google Scholar 

  18. Hilfiker-Kleiner, D. et al. A cathepsin D-cleaved 16 kDa form of prolactin mediates postpartum cardiomyopathy. Cell 128, 589–600 (2007).

    Article  CAS  Google Scholar 

  19. Sliwa, K. et al. Evaluation of bromocriptine in the treatment of acute severe peripartum cardiomyopathy: a proof-of-concept pilot study. Circulation 121, 1465–1473 (2010).

    Article  CAS  Google Scholar 

  20. Batchelder, K. & Mayosi, B. M. Pentoxifylline for heart failure: a systematic review. S. Afr. Med. J. 95, 171–175 (2005).

    CAS  PubMed  Google Scholar 

  21. Ntusi, N. B., Badri, M., Gumedze, F., Wonkam, A. & Mayosi, B. M. Clinical characteristics and outcomes of familial and idiopathic dilated cardiomyopathy in Cape Town: a comparative study of 120 cases followed up over 14 years. S. Afr. Med. J. 101, 399–404 (2011).

    PubMed  Google Scholar 

  22. D'Arbela, P. G., Mutazindwa, T., Patel, A. K. & Somers, K. Survival after first presentation with endomyocardial fibrosis. Br. Heart J. 34, 403–407 (1972).

    Article  CAS  Google Scholar 

  23. Blauwet, L. A. et al. Predictors of outcome in 176 South African patients with peripartum cardiomyopathy. Heart 99, 308–313 (2013).

    Article  CAS  Google Scholar 

  24. Karthikeyan, G. et al. Rationale and design of a Global Rheumatic Heart Disease Registry: the REMEDY study. Am. Heart J. 163, 535–540 (2012).

    Article  Google Scholar 

  25. Mayosi, B. M. et al. Rationale and design of the Investigation of the Management of Pericarditis (IMPI) trial: a 2 × 2 factorial randomized double-blind multicenter trial of adjunctive prednisolone and Mycobacterium w immunotherapy in tuberculous pericarditis. Am. Heart J. 165, 109–115.e3 (2013).

    Article  CAS  Google Scholar 

  26. Mayosi, B. M. The 10 'Best Buys' to combat heart disease, diabetes and stroke in Africa. Heart 99, 973–974 (2013).

    Article  Google Scholar 

  27. Gould, K. L., Lipscomb, K. & Hamilton, G. W. Physiologic basis for assessing critical coronary stenosis. Instantaneous flow response and regional distribution during coronary hyperemia as measures of coronary flow reserve. Am. J. Cardiol. 33, 87–94 (1974).

    Article  CAS  Google Scholar 

  28. White, C. W. et al. Does visual interpretation of the coronary arteriogram predict the physiologic importance of a coronary stenosis? N. Engl. J. Med. 310, 819–824 (1984).

    Article  CAS  Google Scholar 

  29. Wijns, W. et al. Guidelines on myocardial revascularization: Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS). Eur. Heart J. 31, 2501–2555 (2010).

    Article  Google Scholar 

  30. Tonino, P. A. et al. Fractional flow reserve versus angiography for guiding percutaneous coronary intervention. N. Engl. J. Med. 360, 213–224 (2009).

    Article  CAS  Google Scholar 

  31. De Bruyne, B. et al. Fractional flow reserve-guided PCI versus medical therapy in stable coronary disease. N. Engl. J. Med. 367, 991–1001 (2012).

    Article  CAS  Google Scholar 

  32. Dattilo, P. B., Prasad, A., Honeycutt, E., Wang, T. Y. & Messenger, J. C. Contemporary patterns of fractional flow reserve and intravascular ultrasound use among patients undergoing percutaneous coronary intervention in the United States: insights from the National Cardiovascular Data Registry. J. Am. Coll. Cardiol. 60, 2337–2339 (2012).

    Article  Google Scholar 

  33. Tonino, P. A. et al. Angiographic versus functional severity of coronary artery stenoses in the FAME study fractional flow reserve versus angiography in multivessel evaluation. J. Am. Coll. Cardiol. 55, 2816–2821 (2010).

    Article  Google Scholar 

  34. Kang, S. J. et al. Usefulness of minimal luminal coronary area determined by intravascular ultrasound to predict functional significance in stable and unstable angina pectoris. Am. J. Cardiol. 109, 947–953 (2012).

    Article  Google Scholar 

  35. Park, S. J. et al. Trends in the outcomes of percutaneous coronary intervention with the routine incorporation of fractional flow reserve in real practice. Eur. Heart J. 34, 3353–3361 (2013).

    Article  Google Scholar 

  36. Joseph, P. G., Pare, G. & Anand, S. S. Exploring gene–environment relationships in cardiovascular disease. Can. J. Cardiol. 29, 37–45 (2013).

    Article  Google Scholar 

  37. O'Donnell, C. J. & Nabel, E. G. Genomics of cardiovascular disease. N. Engl. J. Med. 365, 2098–2109 (2011).

    Article  CAS  Google Scholar 

  38. Heath, A. C. et al. Zygosity diagnosis in the absence of genotypic data: an approach using latent class analysis. Twin Res. 6, 22–26 (2003).

    Article  Google Scholar 

  39. Hunter, D. J. Gene–environment interactions in human diseases. Nat. Rev. Genet. 6, 287–298 (2005).

    Article  CAS  Google Scholar 

  40. Kullo, I. J. & Ding, K., Mechanisms of disease: the genetic basis of coronary heart disease. Nat. Clin. Pract. Cardiovasc. Med. 4, 558–569 (2007).

    Article  CAS  Google Scholar 

  41. Manly, K. F. Reliability of statistical associations between genes and disease. Immunogenetics 57, 549–558 (2005).

    Article  Google Scholar 

  42. Reich, D. & Patterson, N. Will admixture mapping work to find disease genes? Philos. Trans. R. Soc. Lond. B Biol. Sci. 360, 1605–1607 (2005).

    Article  CAS  Google Scholar 

  43. Do, R. et al. The effect of chromosome 9p21 variants on cardiovascular disease may be modified by dietary intake: evidence from a case/control and a prospective study. PLoS Med. 8, e1001106 (2011).

    Article  CAS  Google Scholar 

  44. Ordovas, J. M., Robertson, R. & Cleirigh, E. N. Gene–gene and gene–environment interactions defining lipid-related traits. Curr. Opin. Lipidol. 22, 129–136 (2011).

    Article  CAS  Google Scholar 

  45. Serre, D. et al. Correction of population stratification in large multi-ethnic association studies. PLoS ONE 3, e1382 (2008).

    Article  Google Scholar 

  46. Deitz, A. C. et al. Impact of misclassification in genotype-exposure interaction studies: example of N-acetyltransferase 2 (NAT2), smoking, and bladder cancer. Cancer Epidemiol. Prev. 13, 1543–1546 (2004).

    CAS  Google Scholar 

  47. Kilpelainen, T. O. et al. Physical activity attenuates the influence of FTO variants on obesity risk: a meta-analysis of 218,166 adults and 19,268 children. PLoS Med. 8, e1001116 (2011).

    Article  Google Scholar 

  48. Marteau, T. M. et al. Effects of communicating DNA-based disease risk estimates on risk-reducing behaviours. Cochrane Database Systematic Reviews, Issue 10. Art. No.: CD007275. http://dx.doi.org/10.1002/14651858.CD007275.pub2.

  49. Guttmacher, A. E. et al. The family history more important than ever. N. Engl. J. Med. 351, 2333–2336 (2004).

    Article  CAS  Google Scholar 

  50. Fletcher, B. J. et al. Global cardiovascular disease prevention: a call to action for nursing, community-based and public health prevention initiatives. J. Cardiovasc. Nurs. 26 (Suppl.), S35–S45 (2011).

    Article  Google Scholar 

  51. Burke, A. P. et al. Coronary risk factors and plaque morphology in men with coronary disease who died suddenly. N. Engl. J. Med. 336, 1276–1282 (1997).

    Article  CAS  Google Scholar 

  52. Heron, M. Deaths: leading causes for 2008. Natl Vital Stat. Rep. 60, 1–94 (2012).

    PubMed  Google Scholar 

  53. Finn, A. V., Nakano, M., Narula, J., Kolodgie, F. D. & Virmani, R. Concept of vulnerable/unstable plaque. Arterioscler. Thromb. Vasc. Biol. 30, 1282–1292 (2010).

    Article  CAS  Google Scholar 

  54. Stone, G. W. et al. A prospective natural-history study of coronary atherosclerosis. N. Engl. J. Med. 364, 226–235 (2011).

    Article  CAS  Google Scholar 

  55. Greenland, P. et al. 2010 ACCF/AHA guideline for assessment of cardiovascular risk in asymptomatic adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J. Am. Coll. Cardiol. 56, e50–e103 (2010).

    Article  Google Scholar 

  56. Kong, M. H. et al. Systematic review of the incidence of sudden cardiac death in the United States. J. Am. Coll. Cardiol. 57, 794–801 (2011).

    Article  Google Scholar 

  57. WHO. Cardiovascular disease. The atlas of heart disease and stroke. Deaths from coronary heart disease [online], (2004).

  58. Gerber, Y. et al. Secular trends in deaths from cardiovascular diseases: a 25-year community study. Circulation 113, 2285–2292 (2006).

    Article  Google Scholar 

  59. Ng, M. et al. Global, regional, and national prevalence of overweight and obesity in children and adults during 1980–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet http://dx.doi.org/10.1016/S0140-6736(14)60460-8.

  60. Virmani, R., Kolodgie, F. D., Burke, A. P., Farb, A. & Schwartz, S. M. Lessons from sudden coronary death: a comprehensive morphological classification scheme for atherosclerotic lesions. Arterioscler. Thromb. Vasc. Biol. 20, 1262–1275 (2000).

    Article  CAS  Google Scholar 

  61. Bentzon, J. F., Otsuka, F., Virmani, R. & Falk, E. Mechanisms of plaque formation and rupture. Circ. Res. 114, 1852–1866 (2014).

    Article  CAS  Google Scholar 

  62. Otsuka, F., Sakakura, K., Yahagi, K., Joner, M. & Virmani, R. Has our understanding of calcification in human coronary atherosclerosis progressed? Arterioscler. Thromb. Vasc. Biol. 34, 724–736 (2014).

    Article  CAS  Google Scholar 

  63. Rader, D. J. & Daugherty, A. Translating molecular discoveries into new therapies for atherosclerosis. Nature 451, 904–913 (2008).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

N.S. acknowledges the University of British Columbia School of Population and Public Health, Vancouver, BC, Canada where she was undertaking a sabbatical while writing this manuscript.

Author information

Authors and Affiliations

  1. Cardiac Surgery Department, San Raffaele Scientific Institute, Via Olgettina, 58, Milan, 20132, Italy

    Ottavio Alfieri

  2. Department of Medicine, J Floor, Old Groote Schuur Hospital, Groote Schuur Drive, Observatory, Cape Town, 7925, South Africa

    Bongani M. Mayosi

  3. Asan Medical Center, 86 Asanbyeongwon-gil, Songpa-gu, Seoul, 138-736, South Korea

    Seung-Jung Park

  4. Isfahan Cardiovascular Research Centre, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Khorram Avenue, Isfahan, PO Box 81465-1148, Iran

    Nizal Sarrafzadegan

  5. CVPath Institute Inc., 19 Firstfield Road, Gaithersburg, 20878, MD, USA

    Renu Virmani

Authors
  1. Ottavio Alfieri
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bongani M. Mayosi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Seung-Jung Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Nizal Sarrafzadegan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Renu Virmani
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Ottavio Alfieri, Bongani M. Mayosi, Seung-Jung Park, Nizal Sarrafzadegan or Renu Virmani.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

PowerPoint slides

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Alfieri, O., Mayosi, B., Park, SJ. et al. Exploring unknowns in cardiology. Nat Rev Cardiol 11, 664–670 (2014). https://doi.org/10.1038/nrcardio.2014.123

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrcardio.2014.123

This article is cited by

Search

Advanced 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