Hypertrophic cardiomyopathy (HCM) is characterized by abnormal thickening of the myocardium in the absence of identifiable causes of hypertrophy and hypercontractility,1 and is often inherited.2

Obstructive HCM (oHCM) is defined by the presence of a left ventricular outflow tract gradient of ≥ 30 mm Hg, observed under basal conditions in up to one-third of HCM patients or under provocation in another one-third of patients.3,4 This condition leads to a range of physiological abnormalities beyond left ventricular outflow tract obstruction and diastolic dysfunction, including myocardial ischemia, mitral valve dysfunction, and arrhythmias.5 oHCM is also associated with a higher risk of heart failure, cardiovascular, and all-cause mortality compared with the general population.5,6 Patients aged <35 years have a higher risk of sudden cardiac death (SCD) and obstruction is an independent predictor of adverse outcomes.3,4

SCD risk assessment is essential to determine the need for primary prevention with an implantable cardioverter-defibrillator (ICD). Tools such as the HCM Risk-SCD score7,8 or individual clinical factors combined with shared decision-making9 are used for risk estimates. Common symptoms include dyspnea, chest pain, and syncope, which usually worsen with advancing age.3,4,7

Prevalence estimates of HCM vary among studies and countries. Reported global prevalence rates range from 2 to 23 cases per 10 000 people worldwide.10 A US study estimated a prevalence of 1.6 to 1.7 cases per 10 000 population.11 Higher annual prevalence rates have been reported in the UK and Germany (2.8 and 4.2 per 10 000, respectively).12 The proportion of oHCM is estimated to range from 22% to approximately 70% of total HCM cases.13,14 However, these figures may be underestimated due to suboptimal diagnostic practices.15,16

Diagnosis involves a comprehensive clinical evaluation confirmed with imaging techniques.3,4 Assessing the presence and severity of obstruction is essential to guide medical treatment and conduct individualized SCD risk stratification.4

The primary aim of oHCM treatment is to alleviate symptoms through pharmacological or interventional approaches. The 2023 European Society of Cardiology (ESC) and the 2024 American Heart Association (AHA)/American College of Cardiology (ACC) guidelines recommend nonvasodilating beta-blockers (BBs) as first-line therapy.7,9 When contraindicated or ineffective, nondihydropyridine calcium-channel blockers (CCBs) are advised as an alternative.7,9 In HCM patients not achieving adequate symptom control, the guidelines suggest escalating therapy to include disopyramide or mavacamten.7,9

Among patients with persistent, severe symptoms (New York Heart Association [NYHA] functional class III-IV), and ≥ 50 mmHg outflow obstruction despite maximally tolerated medical therapy—or in those with exertional or unexplained recurrent syncope unresponsive to maximally tolerated pharmacological treatments, the guidelines recommend considering septal reduction therapies (SRT).7,9 These include surgical septal myectomy (SM), a highly specialized procedure with a risk of complications,17 and, in selected patients, percutaneous alcohol septal ablation, which is the primary alternative to surgical myectomy.17–19 Both procedures should be performed in high-volume HCM centers as the risks of complications and mortality increase exponentially in lower-volume settings.3,20

Despite its significant prevalence and impact on patients’ quality of life, morbidity, and mortality, data on the clinical and economic burden of oHCM for health care systems in Spain are limited or lacking. This study aimed to investigate the patient characteristics, therapeutic trends, health care resource utilization (HCRU), and costs associated with oHCM in real-world settings, stratified by symptom burden according to NYHA functional class.21

To our knowledge, this is the first Spanish study to evaluate the management of oHCM and its impact on HCRU and costs using real-world data. We found a higher prevalence of oHCM in Spain compared to international reports, although its relative frequency among HCM patients was lower, more in line with data from Sweden.14 Approximately one-third of NYHA class III/IV patients who underwent SRT improved to a lower NYHA class. Higher NYHA classification was associated with increased hospitalization rates, cardiovascular events, mortality, HCRU, and costs (figure 5).

Figure 5.

Central illustration. Study summary. HCM, hypertrophic cardiomyopathy; oHCM, obstructive hypertrophic cardiomyopathy; NYHA, New York Heart Association; SD, standard deviation.

(0.74MB).

There is a substantial scarcity of real-world data regarding Spanish oHCM patients’ demographics, clinical management, HCRU, and economic impact. This study estimated the prevalence of oHCM in Spain to be 7 cases per 10 000 individuals, which exceeds the 2.8-4.1 cases per 10 000 individuals reported in the UK and Germany.12 These differences may stem from methodological discrepancies, genetic background variations, aging demographics, or differences in diagnostic outreach and criteria. Only 25% of HCM patients in Spain were diagnosed with oHCM, compared with 68% in the UK and 49% in Germany. This disparity may be due to the different data sources and coding systems: our analysis used the BIG-PAC database and ICD-9 codes, in contrast to the broader diagnostic coding and databases applied in other studies. Furthermore, our study used stricter diagnostic criteria than those used in the German study,12 which could account for the lower observed prevalence.

In our cohort, NYHA class II and III predominated among oHCM patients, with consistent diagnostic frequencies over the 9-year recruitment period. The mean age and comorbidity burden increased progressively with NYHA classification, consistent with disease severity.

Therapeutic interventions varied significantly by NYHA class, with the mean number of prescribed medications rising from 1.6 in NYHA-I to 3.1 in NYHA-IV, reflecting the limitations of pre-myosin inhibitor pharmacological options in fully addressing disease complexity.31,32

In Spain, BBs and CCBs are the most commonly prescribed medications for oHCM, in line with American and European guidelines.7,31 However, evidence supporting their efficacy remains limited.31 Disopyramide use was rare, likely due to limited clinical experience and concerns about adverse effects.33 A notable minority of patients continued to receive dihydropyridine CCBs and renin-angiotensin system inhibitors (3.5% and 36.7% of patients, respectively), despite guidelines advising against their use in oHCM.31 This suggests that many patients are treated preferentially in nonreferral hospitals or by specialists who may not be up to date with guideline recommendations. The recent introduction of novel therapeutic agents, such as cardiac myosin inhibitors, represents a paradigm shift in the management of oHCM. However, real-world studies evaluating their effectiveness, safety, and cost-effectiveness in routine clinical practice are still needed to fully understand their impact on patient care and health care systems.

Only 8.2% of the study cohort underwent SRT, mainly patients in NYHA classes III (13.1%) and IV (47.7%). SSM, a definitive procedure for alleviating obstruction, was performed in only 7.3% of class III/IV patients, reflecting its selective use. Instead, a larger proportion underwent PTSMA (13.2%), likely due to the limited availability of specialized centers for SM and the preference for a less invasive approach in elderly patients, consistent with earlier recommendations.34 This preference likely influenced this distribution pattern.

As expected, cardiovascular events and mortality increased with disease severity.35 Patients in NYHA classes III and IV had significantly higher rates of adverse events and death. Despite interventions, most patients remained in the same or a worse NYHA class at follow-up: 90% of those initially in NYHA-III and 69% of those in NYHA-IV did not improve. About one-third of patients undergoing SRT or device implantation showed improvement, which may appear modest. However, it is important to note that device implantation alone may not yield the same functional improvement as SRT. Moreover, these findings are subject to limitations of administrative data, where improvements may be captured in open text fields but not updated in structured classification fields. Prospective studies are warranted to validate these observations.

HCRU and costs rose markedly with increasing disease severity. Differences were particularly pronounced in ER visits, cardiology consultations, hospitalizations, and length of hospital stays among NYHA classes. The low frequency of monitoring tests may reflect inconsistent application of clinical guidelines in real-life practice, regardless of the care setting. Patients with NYHA-III and -IV who underwent SRT or device implantation exclusively incurred the highest healthcare costs. The mean healthcare cost for NYHA-IV patients was €17 545.2 (95% CI, €16 213.9-€18 876.5), compared with €4430.3 (95% CI, €3690.7-€5170.0) for those in NYHA-I. These findings are consistent with existing literature,36,37 highlighting the economic burden of managing advanced oHCM.

This study has several strengths, including its detailed analysis of HCRU and costs among NYHA classes, and its use of a large, nationally representative dataset (BIG-PAC), which provides valuable insights into the clinical and economic burdens of oHCM. The longitudinal design allows for assessment of trends over time and understanding of disease progression and management outcomes.

However, the study also has limitations inherent to administrative data, such as missing variables and selection bias.38 Such limitations highlight the need for cautious interpretation of the study results and suggest an avenue for future research to incorporate more comprehensive data collection methods, possibly through multicenter collaborations. Heterogeneity among participating centers (referral vs nonreferral) and the exclusion of private centers must be considered when interpreting the findings. Patients were categorized by baseline NYHA class, and changes over time were not reassigned in the analysis. Furthermore, mortality rates associated with SRT/medical devices procedures and the percentage of patients who underwent heart transplantation were not retrieved. Moreover, costs related to SRT or device implantation may be under or overestimated since some sources did not specify whether the cost was solely due to the intervention or to the intervention and subsequent visits (ie, follow-up visits). Out-of-pocket costs borne by patients or families were not captured, potentially underestimating the total economic impact. Finally, unadjusted confounders—such as age or sex—may introduce additional biases that merit exploration in future research.

This investigation provides critical insights into the real-world management of oHCM patients in Spain. Individuals with advanced symptomatic oHCM (NYHA-III and -IV) have a less favorable prognosis and generate substantially higher HCRU and associated costs compared with those with less severe disease (NYHA-I and -II). The standard of care prior to the availability of cardiac myosin inhibitors fell short in managing the full complexity of the underlying pathophysiology of the disease. The broader adoption of these novel therapeutic agents is likely to reshape the treatment paradigm for oHCM. In parallel, continued efforts are needed to expand our understanding of optimal management strategies to improve patient outcomes.

This study was funded by Bristol-Myers Squibb. The sponsor was involved in all aspects of the study, in the drafting of the manuscript, and in the decision to submit the manuscript for publication.

Data anonymization was rigorously carried out at the originating center in accordance with Organic Law 3/2018 of December 5 on the Protection of Personal Data and Guarantee of Digital Rights.39 Atrys Health-RLD, the study sponsor, did not have access to the primary data sources. As anonymization was completed prior to data inclusion in the database, written informed consent was not required. The study was conducted in accordance with the principles of the Declaration of Helsinki and was approved by the Comité de Ética de Investigación con Medicamentos del Consorci Sanitari de Terrassa (CEIm code 02-23-188-027) on November 24, 2022. The SAGER guidelines were considered and applied where possible; however, data were not disaggregated by patient sex.

No artificial intelligence was used during the preparation and drafting of this study.

Conceptualization: R. Barriales-Villa, L. Escobar-López, J. R. Gimeno; Methodology: I. Hernández; Validation: I. Hernández, D. Vilanova-Larena; Formal analysis: I. Hernández; Investigation: R. Barriales-Villa, L. Escobar-López, J. R. Gimeno, E. Rebollo-Gómez; Data Curation: I. Hernández; Writing—Original Draft: L. Escobar-López, E. Rebollo-Gómez; Writing—Review and Editing: R. Barriales-Villa, L. Escobar-López, D. Vilanova-Larena, J. Salazar-Mendiguchía, A. Echeto, I. Hernández, E. Rebollo-Gómez, J. R. Gimeno; Visualization: R. Barriales-Villa, L. Escobar-López, D. Vilanova-Larena, J. Salazar-Mendiguchía, A. Echeto, I. Hernández, E. Rebollo-Gómez, J. R. Gimeno; Supervision: L. Escobar-López; Funding acquisition: D. Vilanova-Larena, J. Salazar-Mendiguchía, A. Echeto.

R. Barriales-Villa declares that he has been part of advisory boards and received speaker fees from Bristol Myers Squibb, Sanofi, Cytokinetics, Alnylam, and Pfizer. J. R. Gimeno declares that he has been part of advisory boards and received speaker fees from Bristol Myers Squibb and Sanofi.

L. Escobar-López, D. Vilanova-Larena, J. Salazar-Mendiguchía, and A. Echeto are employees of Bristol Myers Squibb. I. Hernández and E. Rebollo-Gómez are employees of Atrys Health S.A.