CONTENT

To the Editor,

The recent article by Babur Güler et al¹ entitled “Phenotypic, Epidemiologic, and Imaging Features of Hypertrophic Cardiomyopathy: A Single-Center Experience” was read with great interest. The authors reported a comprehensive cohort of 701 patients, providing valuable real-world insight into the phenotypic spectrum of hypertrophic cardiomyopathy (HCM) in Türkiye where data about this subject remain limited. The study was designed as a single-center, cross-sectional, retrospective, and observational study. The study’s strengths include its large sample size, systematic phenotypic classification (including the under-recognized latent obstructive subgroup), and extensive use of multimodality imaging, particularly cardiac magnetic resonance (CMR). The high utilization rate of CMR (84%) and the detailed assessment of late gadolinium enhancement (LGE) widely enhance the power of phenotypic characterization. Moreover, the inclusion of genetic data (even in a subset (32%)) adds important translational relevance, especially with the predominance of MYBPC3 and MYH7 mutations aligning with worldwide literature.^2-4

However, we would like to highlight several points that may further enrich the interpretation and clinical applicability of the findings: First, the relatively short median follow-up duration (13 months) limits the ability to draw conclusions regarding long-term outcomes, particularly sudden cardiac death (SCD) risk and progression toward advanced heart failure.^3-5 Given the evolving paradigm in HCM (where heart failure-related morbidity may increasingly exceed arrhythmic mortality), longitudinal data from this cohort would be of high value. Second, while the study provides detailed phenotypic comparisons, the absence of multivariable analyses limits the ability to identify independent predictors of adverse outcomes. For instance, the observed higher NT-proBNP levels and mitral regurgitation prevalence in the resting-obstructive group are clinically meaningful, but their independent prognostic significance remains unclear. Future analyses incorporating Cox regression or competing-risk models would strengthen causal inference.^5-7 Third, the findings related to apical HCM and the lack of data about the mid-ventricular obstruction phenotype HCM deserve particular emphasis. The high prevalence of LGE (95%) and extensive LGE burden, along with increased apical aneurysm rates, raise important questions regarding current risk stratification models.² These observations support the growing notion that apical HCM may not be as benign as historically perceived and may warrant phenotype-specific risk algorithms beyond the current ESC HCM Risk-SCD model. Furthermore, patients with the mid-ventricular obstruction phenotype HCM have not been mentioned in the paper who are shown to be presented with apical aneurysms, arrhythmic complications of HCM, and major adverse cardiac outcomes compared to other phenotypes.^8-10 There was also no data about the patients with the dilated phase (burn-out) of HCM in which the prognosis is generally poorer compared to standard HCM.^11,12 Fourth, the relatively low rate of genetic testing reflects real-world limitations; however, it also introduces potential selection bias in genotype–phenotype correlations. Expanding genetic screening and incorporating polygenic or modifier analyses could help clarify the unexpectedly similar mutation rates observed across phenotypes, particularly in apical HCM and response to medical therapy.¹³ Finally, an important trending consideration is the absence of patients treated with cardiac myosin inhibitors. As these agents are increasingly integrated into clinical practice, future studies from this cohort may provide valuable insights into their impact on phenotype expression, symptom burden, and biomarker profiles.

In conclusion, this study represents a significant contribution to regional HCM literature and provides a solid basis for future prospective, multicenter, and longitudinal investigations. Further integration of advanced statistical modeling, extended follow-up, and emerging therapies will be essential to fully clarify phenotype-specific risk and optimize personalized management strategies.

Footnotes

Declaration of Interests: The author has no conflict of interest to declare.

References

1. Babur Güler G, Güler A, Tanboğa İH. Phenotypic, Epidemiologic, and Imaging Features of Hypertrophic Cardiomyopathy: A Single-Center Experience. Anatol J Cardiol. 2026;30(5):321-332.
2. Arbelo E, Protonotarios A, Gimeno JR. 2023 ESC Guidelines for the management of cardiomyopathies. Eur Heart J. 2023;44(37):3503-3626.
3. Ho CY, Day SM, Ashley EA. Genotype and lifetime burden of disease in hypertrophic cardiomyopathy: insights from the sarcomeric human cardiomyopathy registry (SHaRe). Circulation. 2018;138(14):1387-1398.
4. Marian AJ, Braunwald E. Hypertrophic cardiomyopathy: genetics, pathogenesis, clinical manifestations, diagnosis, and therapy. Circ Res. 2017;121(7):749-770.
5. Kalenderoğlu K, Hayıroğlu Mİ, Pay L. The long-term mortality predictors in hypertrophic cardiomyopathy patients with low risk of sudden cardiac death. Turk Kardiyol Dern Ars. 2025;53(5):312-318.
6. Balaban İ, Tanyeri S, Karaduman A. Electrophysiological markers in hypertrophic cardiomyopathy: enhancing sudden cardiac death risk prediction with index of cardiac electrophysiological balance and its corrected variant. Anatol J Cardiol. 2025;():-.
7. Liu L, Zheng Y, Ma H. Association between triglyceride-glucose index and prognosis of patients with hypertrophic cardiomyopathy and heart failure with preserved ejection fraction. Anatol J Cardiol. 2025;29(11):619-629.
8. Ates AH, Kivrak A, Canpolat U. Polidocanol ablation in midventricular obstructive cardiomyopathy: novel approach and early outcomes. J Invasive Cardiol. 2025;37(10):-.
9. Maron MS, Finley JJ, Bos JM. Prevalence, clinical significance, and natural history of left ventricular apical aneurysms in hypertrophic cardiomyopathy. Circulation. 2008;118(15):1541-1549.
10. Sherrid MV, Bernard S, Tripathi N. Apical aneurysms and mid-left ventricular obstruction in hypertrophic cardiomyopathy. JACC Cardiovasc Imaging. 2023;16(5):591-605.
11. Canpolat U, Şahiner L, Kaya EB. Melting heart: dilated phase of hypertrophic cardiomyopathy. Anadolu Kardiyol Derg. 2012;12(7):E36-E37.
12. Ishihara K, Kubota Y, Matsuda J. Predictive factors for decreasing left ventricular ejection fraction and progression to the dilated phase of hypertrophic cardiomyopathy. J Clin Med. 2023;12(15):5137-.
13. Raimoglou D, İzgi C, Enar R. Structural and functional impact of adrenoceptor Beta-1 gene polymorphism in patients with hypertrophic cardiomyopathy and response to beta-blocker therapy. Anatol J Cardiol. 2024;28(3):150-157.