Integrated Sudden Cardiac Death Risk Prediction Model For Patients With Hypertrophic Cardiomyopathy

HomeCirculationVol. 147, No. 4Integrated Sudden Cardiac Death Risk Prediction Model For Patients With Hypertrophic Cardiomyopathy Free AccessArticle CommentaryPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessArticle CommentaryPDF/EPUBIntegrated Sudden Cardiac Death Risk Prediction Model For Patients With Hypertrophic Cardiomyopathy Emanuele Monda and Giuseppe Limongelli Emanuele MondaEmanuele Monda https://orcid.org/0000-0001-9304-988X Inherited and Rare Cardiovascular Diseases, Department of Translational Medical Sciences, University of Campania "Luigi Vanvitelli," Naples, Italy (E.M., G.L.) and Giuseppe LimongelliGiuseppe Limongelli Correspondence to: Giuseppe Limongelli, MD, PhD, Inherited and Rare Cardiovascular Disease Clinic, Department of Translational Medical Sciences, University of Campania "Luigi Vanvitelli," Via L. Bianchi 1 c/o Monaldi Hospital, AORN Colli, 80135, Naples, Italy. Email E-mail Address: [email protected] https://orcid.org/0000-0002-8291-9517 Inherited and Rare Cardiovascular Diseases, Department of Translational Medical Sciences, University of Campania "Luigi Vanvitelli," Naples, Italy (E.M., G.L.) Institute of Cardiovascular Sciences, University College of London and St. Bartholomew's Hospital, United Kingdom (G.L.). Originally published23 Jan 2023https://doi.org/10.1161/CIRCULATIONAHA.122.063019Circulation. 2023;147:281–283Hypertrophic cardiomyopathy (HCM) is one of the leading causes of sudden cardiac death (SCD) in young and otherwise healthy individuals.1 Although an implantable cardioverter defibrillator (ICD) is the standard of care for individuals with HCM at high risk for SCD, the identification of patients who most likely benefit from device implantation is challenging. The discrepancy between international clinical guideline approaches1,2 is responsible for a wide gap in risk stratification algorithms and creates uncertainty among physicians, thereby enhancing this challenge in everyday clinical practice.The debate began in 2014, when the European Society of Cardiology (ESC) proposed a new approach for risk prediction using a clinical risk tool (HCM Risk-SCD [Clinical Risk Prediction Model for Sudden Cardiac Death in Hypertrophic Cardiomyopathy]) to estimate a 5-year risk of SCD.2 HCM Risk-SCD is a decision-making risk score derived from a multivariable logistic regression model that estimates SCD based on a formula comprising 7 variables. Despite initial enthusiasm related to its prognostic accuracy, the HCM Risk-SCD score has been advocated as a "rigid mathematical model" with low sensitivity, theoretically leaving many patients unprotected without ICDs, and potentially with poor flexibility to evolve as new evidence emerges.The observation that some patients could theoretically be left unprotected from an SCD event led to the active search for additional risk factors. Thus, extensive late gadolinium enhancement (LGE), presence of left ventricular (LV) apical aneurysm, and systolic dysfunction (ie, LV ejection fraction ≤50%) have been associated with increased risk for future life-threatening ventricular arrhythmias. According to this evidence, an enhanced version of the 2011 American College of Cardiology/American Heart Association (ACC/AHA) model for SCD risk prediction was developed and then recommended by the 2020 ACC/AHA guidelines as the model of choice for predicting arrhythmic events.1The enhanced ACC/AHA algorithm demonstrated high sensitivity in identifying high-risk patients. However, its ability to identify low-risk patients is not high, potentially leading to an excessive device implantation rate. Data from the International Sarcomeric Human Cardiomyopathy Registry shows that patients in the United States are more frequently implanted compared with patients at non-US sites, and that there are fewer appropriate ICD therapy among patients implanted in the United States.3 In contrast, the HCM Risk-SCD score exhibits a high negative predictive value but fails to correctly identify high-risk patients in some cases. Moreover, it does not take into account the impact of newer markers of SCD risk.To overcome these limitations, a new SCD risk algorithm was discussed and proposed in the 2022 ESC guidelines for the management of patients with ventricular arrhythmias and the prevention of SCD2 (Figure). The new algorithm gives a central role to the HCM Risk-SCD score as a tool statistically capable of calculating the individual risk of each patient, which facilitates shared decision-making for ICD implantation.Download figureDownload PowerPointFigure. Comparison between different international society guidelines on implantable cardioverter defibrillator implantation for primary prevention in patients with HCM. AHA/ACC indicates American Heart Association/American College of Cardiology; BP, blood pressure; CMR, cardiac magnetic resonance; ESC, European Society of Cardiology; FH HCM, family history of hypertrophic cardiomyopathy; HCM Risk-SCD, Clinical Risk Prediction Model for Sudden Cardiac Death in Hypertrophic Cardiomyopathy; LGE, late gadolinium enhancement; LVEF, left ventricular ejection fraction; LVH, left ventricular hypertrophy; NSVT, nonsustained ventricular tachycardia; and SCD, sudden cardiac death. *Based on the HCM Risk-SCD ( https://doc2do.com/hcm/webHCM.html). †Usually ≥15% of left ventricular mass. ‡Defined as failure to increase systolic pressure by at least 20 mm Hg from rest to peak exercise, or a fall of 20 mm Hg from peak pressure.As in previous ESC guidelines, an ICD placement in primary prevention is recommended in adult patients with an estimated 5-year risk of SCD ≥6% (class IIa). In patients with an estimated 5-year risk of SCD <4% (traditionally considered low risk), an ICD should not be placed unless there is ≥1 major risk factor, including significant LGE, LV ejection fraction ≤50%, or apical aneurysm (class IIb). This new recommendation is supported by different retrospective studies that show some patients classified as low risk via the HCM Risk-SCD score could be at risk for SCD because of the presence of risk markers not incorporated into the risk score.For patients classified as intermediate risk (with an estimated 5-year risk of SCD ≥4% and <6%), 2 recommendations are provided: (1) ICD implantation may be considered (class IIb); and (2) ICD implantation should be considered in the presence of ≥1 risk factor, including significant LGE, LV ejection fraction ≤50%, apical aneurysm, abnormal blood pressure response to exercise, and presence of sarcomeric pathogenic mutations (class IIa).The new algorithm gives clinicians a ready-to-use solution to apply to difficult clinical questions regarding HCM risk stratification. Nevertheless, we have some concerns regarding the specific risk markers of abnormal blood pressure response to exercise and presence of sarcomeric pathogenic mutation.Abnormal blood pressure response to exercise has been associated with a higher risk for SCD in patients ≤40 years of age. However, the absence of studies demonstrating its independent association with SCD in multivariable survival analyses4 and the identification of new risk markers have resulted in the removal of abnormal blood pressure response to exercise as a routine part of the SCD risk estimation. Furthermore, its complementary role when added to the HCM Risk-SCD score is unknown.In addition, although we acknowledge that specific mutations in sarcomeric genes may potentially confer increased risk of SCD, we believe that the inclusion of sarcomeric mutation as an additional risk factor is premature and not sufficiently supported by solid evidence. It seems that the recommendation was based on the results of SHaRe (Sarcomeric Human Cardiomyopathy Registry),5 which showed that the presence of a sarcomeric mutation was associated with a >2-fold increased risk for ventricular arrhythmias and SCD after controlling for proband status, sex, and race. However, in that study, patients with sarcomeric mutation were significantly younger and had a greater maximal LV wall thickness compared with those without sarcomeric mutation. Thus, because the authors did not show the results of the analysis adjusted for these covariates, it is not possible to exclude a significant overestimation of the SCD risk in this subgroup of patients, which may be already covered by actual risk estimation scores.In conclusion, the algorithm proposed by the 2022 ESC guidelines for the management of patients with ventricular arrhythmias and the prevention of SCD tries to fill the gap between the US model, which is based on major risk factors, and the European model, which is based on an individualized risk calculator. However, further studies designed to evaluate the performance of the new ESC model are required.In clinical practice, risk stratification is critical for patient management because risk underestimation can lead to unexpected life-threatening events; however, its overestimation may result in unnecessary ICD implantation with the potential for future complications. The decision to place an ICD in primary prevention is an actuarial exercise and is based on the predicted risk for SCD- and ICD-related complications and costs; however, the latter may change significantly in the future with the introduction of new device options. Therefore, even if we seem to be getting closer to an appropriate model, the challenge and the debate on how to stratify SCD risk in patients with HCM is likely to continue.Article InformationThis article reflects the views of the authors and does not necessarily represent the views of a scientific society or authoritative body.AcknowledgmentsThe authors would like to thank Dr Marta Rubino (University of Campania "Luigi Vanvitelli") and Dr Michele Lioncino (University of Campania "Luigi Vanvitelli") for helpful discussions on this topic.Sources of FundingNone.Disclosures None.FootnotesCirculation is available at www.ahajournals.org/journal/circThe opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.For Sources of Funding and Disclosures, see page 283.Correspondence to: Giuseppe Limongelli, MD, PhD, Inherited and Rare Cardiovascular Disease Clinic, Department of Translational Medical Sciences, University of Campania "Luigi Vanvitelli," Via L. Bianchi 1 c/o Monaldi Hospital, AORN Colli, 80135, Naples, Italy. Email limongelligiuseppe@libero.itREFERENCES1. Ommen SR, Mital S, Burke MA, Day SM, Deswal A, Elliott P, Evanovich LL, Hung J, Joglar JA, Kantor P, et al. 2020 AHA/ACC guideline for the diagnosis and treatment of patients with hypertrophic cardiomyopathy: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.Circulation. 2020; 142:e558–e631. doi: 10.1161/CIR.0000000000000937LinkGoogle Scholar2. Zeppenfeld K, Tfelt-Hansen J, de Riva M, Winkel BG, Behr ER, Blom NA, Charron P, Corrado D, Dagres N, de Chillou C, et al. 2022 ESC guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death.Eur Heart J. 2022; 26:ehac262.Google Scholar3. Nauffal V, Marstrand P, Han L, Parikh VN, Helms AS, Ingles J, Jacoby D, Lakdawala NK, Kapur S, Michels M, et al. Worldwide differences in primary prevention implantable cardioverter defibrillator utilization and outcomes in hypertrophic cardiomyopathy.Eur Heart J. 2021; 42:3932–3944. doi: 10.1093/eurheartj/ehab598CrossrefMedlineGoogle Scholar4. Rodrigues T, Raposo SC, Brito D, Lopes LR. Prognostic relevance of exercise testing in hypertrophic cardiomyopathy. A systematic review.Int J Cardiol. 2021; 339:83–92. doi: 10.1016/j.ijcard.2021.06.051CrossrefMedlineGoogle Scholar5. Ho CY, Day SM, Ashley EA, Michels M, Pereira AC, Jacoby D, Cirino AL, Fox JC, Lakdawala NK, Ware JS, et al. Genotype and lifetime burden of disease in hypertrophic cardiomyopathy: insights from the Sarcomeric Human Cardiomyopathy Registry (SHaRe).Circulation. 2018; 138:1387–1398. doi: 10.1161/CIRCULATIONAHA.117.033200LinkGoogle Scholar eLetters(0) eLetters should relate to an article recently published in the journal and are not a forum for providing unpublished data. 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