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  • Review Article
  • Published:

Update on hypertrophic cardiomyopathy and a guide to the guidelines

Nature Reviews Cardiology volume 13, pages 651–675 (2016)Cite this article

Subjects

Key Points

  • Although the ACC Foundation (ACCF)/AHA and ESC guidelines show widespread concordance, the ESC definition of hypertrophic cardiomyopathy (HCM) includes nonsarcomeric disease states associated with load-independent left ventricular hypertrophy (LVH)

  • Relatives of patients with HCM should be offered screening; autosomal dominant inheritance is typical, and a range of electrocardiographic and imaging features are recognized to precede the development of LVH

  • Prognostic assessment at baseline and follow-up is recommended for all patients with HCM; despite recognizing many of the same predictors of sudden death, the ACCF/AHA and ESC adopt distinct approaches to risk profiling

  • Specialist HCM centres promote implementation of best-practice guidelines by offering facilities and skills for investigations such as exercise stress echocardiography, cardiovascular magnetic resonance (CMR), and genetic analysis, in addition to high-volume programmes for invasive septal reduction

  • Patients referred to specialist HCM centres also benefit from multidisciplinary support systems and clinical experience in interpreting equivocal clinical findings, adjudicating borderline risk profiles, and managing complex cases

  • Advances in the evaluation of HCM include CMR-based T1 mapping for demonstrating diffuse and interstitial fibrosis; in the therapeutic arena, several putative substrate-modulating agents are progressing from preclinical to clinical trials

Abstract

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disorder, affecting 1 in 500 individuals worldwide. Existing epidemiological studies might have underestimated the prevalence of HCM, however, owing to limited inclusion of individuals with early, incomplete phenotypic expression. Clinical manifestations of HCM include diastolic dysfunction, left ventricular outflow tract obstruction, ischaemia, atrial fibrillation, abnormal vascular responses and, in 5% of patients, progression to a 'burnt-out' phase characterized by systolic impairment. Disease-related mortality is most often attributable to sudden cardiac death, heart failure, and embolic stroke. The majority of individuals with HCM, however, have normal or near-normal life expectancy, owing in part to contemporary management strategies including family screening, risk stratification, thromboembolic prophylaxis, and implantation of cardioverter–defibrillators. The clinical guidelines for HCM issued by the ACC Foundation/AHA and the ESC facilitate evaluation and management of the disease. In this Review, we aim to assist clinicians in navigating the guidelines by highlighting important updates, current gaps in knowledge, differences in the recommendations, and challenges in implementing them, including aids and pitfalls in clinical and pathological evaluation. We also discuss the advances in genetics, imaging, and molecular research that will underpin future developments in diagnosis and therapy for HCM.

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Figure 1: Cine cardiovascular magnetic resonance (CMR) images of hypertrophic cardiomyopathy (HCM) cases with TNNI3 mutations.
Figure 2: Apical hypertrophy missed by echocardiography.
Figure 3: T1 mapping and late gadolinium enhancement (LGE) in differentiating archetypal hypertrophic cardiomyopathy (HCM) from phenotypic mimics.
Figure 4: Doppler echocardiographic assessment of left ventricular outflow tract obstruction (LVOTO)93,94,95,96.
Figure 5: Genotype-positive hypertrophic cardiomyopathy (HCM) without left ventricular hypertrophy (LVH)116,117,118,119,120,121,122,123,124.
Figure 6: Risk stratification in hypertrophic cardiomyopathy (HCM)13,14,15,134,135.
Figure 7: Calcium handling and the actin myosin crossbridge cycle in cardiac muscle.
Figure 8: Relationship between calcium concentration (pCa) and active force generation in hypertrophic cardiomyopathy (HCM).
Figure 9: Assessing force production, velocity, and power output of the cardiac sarcomere.
Figure 10: The energy depletion hypothesis.

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Acknowledgements

S.S.-C. is supported by the BHF Intermediate Clinical Research Fellowship (FS/10/011/27881). W.J.M. is supported by the Fondation Leducq Transatlantic Networks of Excellence Program.

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Authors and Affiliations

  1. Institute of Cardiovascular Science, University College London, Gower Street, London, WC1E 6BT, UK

    Srijita Sen-Chowdhry & James C. Moon

  2. Department of Epidemiology, Imperial College, St Mary's Campus, Norfolk Place, London, W2 1NY, UK

    Srijita Sen-Chowdhry

  3. Section of Cardiovascular Medicine, Yale School of Medicine, 333 Cedar Street, New Haven, 06520, Connecticut, USA

    Daniel Jacoby

  4. Barts Heart Centre, St Bartholomew's Hospital, West Smithfield, London, EC1A 7BE, UK

    James C. Moon

  5. Heart Hospital, Hamad Medical Corporation, Al Rayyan Road, Doha, Qatar

    William J. McKenna

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All the authors researched data for the article and reviewed and edited the manuscript before submission. D.J., J.C.M., and W.J.M. substantially contributed to discussion of content. S.S.-C. and D.J. wrote the manuscript.

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Sen-Chowdhry, S., Jacoby, D., Moon, J. et al. Update on hypertrophic cardiomyopathy and a guide to the guidelines. Nat Rev Cardiol 13, 651–675 (2016). https://doi.org/10.1038/nrcardio.2016.140

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