Cardiovascular comorbidities in hospitalized patients with hypertrophic cardiomyopathy and factors associated with a higher case-fatality rate

ABSTRACT

Background

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disorder, with rising hospitalization rates and high comorbidity burden, yet the impact of cardiovascular comorbidities (CVC) on mortality among hospitalized HCM patients remains poorly defined.

Methods

Queried the 2016 to 2020 National Inpatient Sample (NIS) to identify hospitalizations with diagnosed HCM.

Results

Among 278,995 HCM hospitalizations (mean age 64.3 ± 18.4 years; 55.7% female), in-hospital mortality rose from 16.4% to 22.9% throughout the study. Cardiac arrest (41.00%), tamponade (13.70%), and ST-segment elevation myocardial infarction (STEMI) (10.20%) had the highest mortality rates. Atrial fibrillation (AF) (42.10%), heart failure with preserved ejection fraction (HFpEF) (28.10%), and cardiorenal syndrome (16.60%) were the most prevalent comorbidities. Predictors of case-fatality included increasing age (aOR: 1.02, 95% CI: 1.02–1.03, p < 0.0001), Asian/Pacific Islander race (aOR: 1.70, 95% CI: 1.10–2.40, p = 0.007), CVA (aOR: 2.30, 95% CI: 1.70–3.06, p < 0.0001), NSTEMI (aOR: 1.80, 95% CI: 1.30–2.40, p < 0.0001), cardiorenal syndrome (aOR: 1.40, 95% CI: 1.20–1.80, p < 0.001), and cardiac arrest (aOR: 26.60, 95% CI: 20.90–33.90, p < 0.001).

Conclusion

Mortality rate among hospitalized HCM patients has shown a mild upward trend and is driven by age, race, NSTEMI, and cardiorenal syndrome.

Plain Language Summary

Our study reveals that individuals with hypertrophic cardiomyopathy which is a lifelong heart condition who are older, belong to certain racial groups, or have additional health issues like stroke, heart attack, or kidney problems are more likely to die during hospitalization, with cardiac arrest being the most serious complication, which underscores the importance of early identification of high-risk patients and the development of personalized treatment plans to enhance survival and to support this goal, future research should track patients over time and include detailed information from imaging, genetics, and treatment records, while also assessing tailored care strategies, such as managing accompanying health conditions and referring patients to specialized centers that offer integrated care.

1. Introduction

Hypertrophic cardiomyopathy (HCM), the most common inherited heart condition, is an autosomal dominant disorder marked by left ventricular (LV) thickening and disorganized myocardial structure [1–4]. Epidemiologic studies estimate that hypertrophic cardiomyopathy affects around 0.2% of the general population, with evidence suggesting a growing prevalence over time [5,6]. Symptoms typically include exertional dyspnea, syncope, angina, palpitations atypical chest pain, and fatigue, and a notable fraction of patients remain symptom-free for their lives, with diagnosis often occurring incidentally due to abnormal electrocardiography (ECG) findings or the detection of a cardiac murmur and the disease’s progression is highly variable, as many patients have a normal life expectancy, while others may experience worsening symptoms [7,8]. Individuals with HCM are known to face an elevated risk of sudden cardiac death (SCD), ventricular arrhythmias, stroke, atrial fibrillation (AF), and heart failure (HF) [9–11]. The majority of HCM patients have cardiovascular comorbidities (CVC), with approximately 75% having at least one, and half having two or more, the most common being obesity, followed by new-onset AF [12]. Comorbidities influence the clinical progression of HCM mainly by worsening outflow obstruction and contributing to the development of progressive HF [13–19]. More than one in four patients with HCM experience AF, highlighting its prevalence as a common arrhythmic complication in this population [20], as nationwide inpatient data show that HCM hospitalizations involving arrhythmias have markedly longer stays and higher inpatient mortality [21]. In a random sample of 53 117 HCM admissions across the United States, race, sex, social risk factors and geography were each independently linked with notable disparities in care and outcomes, with Black patients with obstructive HCM markedly less likely than White individuals to receive septal myectomy or alcohol septal ablation, Medicaid recipients undergoing both septal interventions and implantable cardioverter-defibrillator (ICD) therapy at substantially lower rates than privately insured patients, and women as well as residents of small towns or rural areas experiencing disproportionately higher in-hospital mortality [22]. Although CVC profoundly shapes HCM outcomes, their prevalence and impact on in-hospital mortality among HCM admissions remain poorly defined, so we analyzed the 2016 to 2020 National Inpatient Sample (NIS) to evaluate the comorbidities and identify demographic and clinical predictors of case-fatality and we aim to describe comorbidity patterns among hospitalized adults with hypertrophic cardiomyopathy using the National Inpatient Sample 2016 to 2020, and identify demographic and clinical predictors of in-hospital mortality.

2. Methods

2.1. Data source and population of the study

A retrospective cohort study using the NIS database from 1 January 2016, to 31 December 2020, was conducted. The NIS, maintained by the Agency for Healthcare Research and Quality (AHRQ), is a component of the Healthcare Cost and Utilization Project (HCUP), which represents the largest publicly available all-payer inpatient dataset in the U.S. which samples approximately 20% of inpatient discharges from U.S. community hospitals and provides weighted estimates for over 35 million hospitalizations annually [23]. Access to the NIS data was granted following the completion of the Data Use Agreement training and submission of the signed agreement, in accordance with the guidelines.

Hospitalizations for adult patients (≥18 years) confirmed to have HCM were determined through International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM) codes I42.1 and I42.2. After applying sampling weights, the final analytic cohort represented 278,995 HCM hospitalizations.

2.2. Variable definitions

Patient demographics included age, sex, race (White, Black, Hispanic, Asian/Pacific Islander, Native American, Other), insurance type (Medicare, Medicaid, Private insurance, Self-Pay, No-Charge, Other), median household income quartile, and patient location based on hospital urban/rural code. Clinical coexisting conditions were identified by ICD-10-CM codes and included I48.91 for AF, I63.9 for cerebrovascular accident (CVA), I35.9 for aortic valve disease (AVD), I21.3 for ST-elevation myocardial infarction (STEMI), I21.4 for non-ST-elevation myocardial infarction (NSTEMI), I50.2 for heart failure with reduced ejection fraction (HFrEF), I50.3 for heart failure with preserved ejection fraction (HFpEF), E11.8 for diabetes with complications, E11.9 for diabetes without complications, F19.20 for drug use disorder, I13.10 for hypertension (HTN) with complications, I10 for HTN without complications, J44.9 for chronic lung disease, E66.9 for obesity, I73.9 for peripheral vascular disease (PVD), I13.2 for cardiorenal syndrome, I31.4 for tamponade, and I46.9 for cardiac arrest.

For individuals hospitalized with acute myocardial infarction (AMI), procedures including Z95.5 for percutaneous coronary intervention (PCI) and Z95.1 for coronary artery bypass grafting (CABG) were identified by ICD-10-CM codes.

2.3. Outcomes

The main outcome was all-cause mortality during hospitalization. Secondary outcomes included cause-specific case-fatality rates, including mortality associated with specific cardiovascular events such as cardiac arrest, tamponade, cardiorenal syndrome, CVA, AVD, HFpEF, HFrEF, NSTEMI, STEMI, AF, diabetes with complications, diabetes without complications, drug use disorder, HTN with complications, HTN without complications, chronic lung diseases, obesity, and PVD. For patients undergoing coronary revascularization, we compared mortality rates between the PCI and CABG groups.

2.4. Statistical analysis

All analyses incorporated the NIS sampling weights to produce nationally representative estimates. Continuous variables were summarized as means ± standard deviations (SD) or medians with interquartile ranges, and categorical variables were reported as counts and weighted percentages. Temporal trends in in-hospital mortality and comorbidity prevalence were assessed using weighted linear regression.

We used univariate logistic regression to screen variables associated with in-hospital mortality (p < 0.05 threshold), followed by multivariate logistic regression to estimate adjusted odds ratios (aORs) with 95% confidence intervals (CIs), controlling for age, sex, race, insurance type, household income percentile, and all clinical comorbidities. Significance was assessed as a two-sided p-value < 0.05, and analyses were conducted using Stata statistical software version 19 (StataCorp LLC, College Station, TX).

2.5. Ethical considerations

Since NIS data are anonymized, this study did not require approval from the institutional review board, consistent with prior database studies.

3. Results

3.1. Demographics, socioeconomic status, and cohort characteristics

During the study period from 2016 to 2020, we analyzed weighted data encompassing 174,776,205 hospital admissions, identifying 278,955 patients with HCM, representing an overall prevalence of 0.16%. The annual prevalence steadily increased over the years, recorded at 0.14% in 2016, 0.15% in 2017, 0.16% in 2018, 0.17% in 2019, and 0.17% in 2020. From 2016 to 2020, unadjusted in-hospital mortality rose substantially from 16.4% to 22.9%.

As detailed in Table 1, among 278,995 HCM admissions, the mean age was 64.3 ± 18.4 years; 55.7% were female. Racial distribution was 67.3% White, 20.6% Black, 6.3% Hispanic, 2.8% Asian/Pacific Islander, 0.3% Native American, and 2.5% Other. The large portion of hospitalized individuals with HCM were under Medicare, accounting for 60.5% of the cohort, followed by 22.4% with private insurance and 12.5% with Medicaid, while a small fraction of patients were self-pay (2.4%), had no charge (0.2%), or other (2%). Regarding socioeconomic distribution based on ZIP code – linked income quartiles, 27.1% of patients resided in areas within the lowest income quartile (0–25%), while 24.7%, 24.4%, and 23.8% were from ZIP codes in the 26–50%, 51–75%, and 76–100% income quartiles, respectively. A substantial proportion of hospitalized patients with HCM were admitted to hospitals located in central counties of metropolitan areas with populations of one million or more, comprising 29.6% of the cohort, closely followed by 26.9% in fringe counties of similarly large metropolitan regions, while 20.6% received care in hospitals within metro areas of 250,000 to 999,999 residents, 8.7% in those with populations between 50,000 and 249,999, 8.2% in micropolitan counties, and 6% in non-metropolitan or non-micropolitan areas.

Table 1.

Demographics, socioeconomic status, clinical characteristics, and cardiovascular comorbidities of hospitalized patients with hypertrophic cardiomyopathy, 2016–2020.

Age, mean ± standard deviation (SD) years	64.3 ± 18.4
Gender, n (%)
Male	123,530 (44.3%)
Female	155,425 (55.7%)
Race/ethnicity, n (%)
White	182,069 (67.3%)
Black	55,795 (20.6%)
Hispanic	17,145 (6.3%)
Asian or Pacific Islander	7,685 (2.8%)
Native American	849 (0.3%)
Other	6,865 (2.5%)
Primary payer, n (%)
Medicare	168,710 (60.5%)
Medicaid	34,870 (12.5%)
Private insurance	62,335 (22.4%)
Self-pay	6,640 (2.4%)
No charge	580 (0.2%)
Other	5,570 (2%)
Median household income for patient’s ZIP Code (based on current year), n (%)
[0–25%]	74,495 (27.1%)
[26%-50%]	67,760 (24.7%)
[51%-75%]	66,915 (24.4%)
[76%-100%]	65,325 (23.8%)
Patient location based on hospital urban/rural code, (N, %)
“Central” counties of metro areas of ≥ 1 million population	82,400 (29.6%)
“Fringe” counties of metro areas of ≥ 1 million population	74,725 (26.9%)
Counties in metro areas of 250,000–999,999 population	57,150 (20.6%)
Counties in metro areas of 50,000–249,999 population	24,150 (8.7%)
Micropolitan counties	22,790 (8.2%)
Not metropolitan or micropolitan counties	16,780 (6%)
Comorbidity and Clinical CharacteristicsPrevalence, n (%)
Hypertension	16,829 (30.20%)
Diabetes mellitus	7,395 (13.20%)
Alcohol use disorder	831 (3.50%)
HIV	140 (0.25%)
AIDS	117 (0.50%)

HIV = Human immunodeficiency virus; AIDS = Acquired immunodeficiency syndrome.

3.2. Comorbidity prevalence and case-fatality

As demonstrated in Figure 1, AF was most prevalent (42.10%), followed by HFpEF (28.10%), cardiorenal syndrome (16.60%), HFrEF (6.10%), NSTEMI (5.40%), AVD (5.40%), CVA (3.60%), cardiac arrest (1.6%), STEMI (0.44%), and tamponade (0.30%). The highest case-fatality rate occurred in patients admitted for cardiac arrest (41.00%), next came cardiac tamponade (13.70%), STEMI (10.20%), and CVA (8.30%). Admissions for NSTEMI, cardiorenal syndrome, HFrEF, HFpEF, AVD, and AF carried lower risks of mortality (5.50%, 5.40%, 4.70%, 4.20%, 4.20%, and 3.90%, respectively).

Figure 1.

Prevalence of cardiovascular morbidities and case-fatality rate among hospitalized patients with HCM.

3.3. Multivariate predictors of mortality

As detailed in Table 2 factors affecting case-fatality rate in hospitalized HCM were age (aOR: 1.02, 95% CI: 1.02–1.03, p < 0.0001), Asian/Pacific Islander race (aOR: 1.70, 95% CI: 1.10–2.40, p = 0.007), CVA (aOR: 2.30, 95% CI: 1.70–3.06, p < 0.0001), NSTEMI (aOR: 1.80, 95% CI: 1.30–2.40, p < 0.0001), PVD (aOR: 1.30, 95% CI: 1.03–1.60, p = 0.03), cardiorenal syndrome (aOR:1.40, 95% CI: 1.20–1.80, p < 0.0001), and cardiac arrest (aOR:26.60, 95% CI: 20.90–33.90, p < 0.0001). Furthermore, HTN with complications (aOR: 0.70, 95% CI: 0.60–0.90, p = 0.001) and HTN without complications (aOR: 0.40, 95% CI: 0.30–0.50, p < 0.0001) were both associated with lower in-hospital mortality, which might stem from residual confounding or coding bias. Other factors did not show significant associations with case-fatality rates in hospitalized HCM patients.

Table 2.

Multivariate logistic regression demonstrating factors affecting case-fatality rate among hospitalized patients with hypertrophic cardiomyopathy.

Variable	Adjusted Odds Ratio	p	95% Confidence Interval (Lower)	95% Confidence Interval (Upper)
Age	1.02	<0.0001	1.02	1.03
Female vs. Male	0.9	0.3	0.7	1.1
Race (vs. White race)
Black	0.9	0.3	0.7	1.1
Hispanic	0.9	0.6	0.6	1.3
Asian or Pacific Islander	1.7	0.007	1.1	2.4
Native American	0.9	0.9	0.2	3.8
Other	1.4	0.2	0.8	2.1
Insurance Type (vs. Medicare)
Medicaid	1.04	0.8	0.8	1.4
Private Insurance	0.8	0.05	0.6	0.9
Self-Pay	0.76	0.41	0.4	1.4
No charge	1
Other	0.8	0.4	0.4	1.4
Household Income Percentile (vs. 1st Quartile [≤$49,999])
2nd Quartile [$50,000–$64,999]	0.9	0.2	0.7	1.1
3rd Quartile [$65,000–$85,999]	0.9	0.3	0.7	1.1
4th Quartile [$86,000+]	0.8	0.1	0.7	1.04
Atrial Fibrillation	1.03	0.7	0.9	1.2
Cerebrovascular Accident	2.3	<0.0001	1.7	3.06
Aortic Valve Diseases	0.8	0.3	0.6	1.2
STEMI	1.5	0.3	0.7	3.6
NSTEMI	1.8	<0.0001	1.3	2.4
HFrEF	0.9	0.6	0.7	1.25
HFpEF	1.02	0.8	0.9	1.2
Diabetes with Complications	0.9	0.4	0.8	1.1
Diabetes without Complications	1.01	0.9	0.8	1.3
Drug Use Disorder	0.6	0.076	0.3	1.06
Hypertension with Complications	0.7	0.001	0.6	0.9
Hypertension without Complications	0.4	<0.0001	0.3	0.5
Chronic Lung Diseases	0.9	0.8	0.8	1.1
Obesity	0.9	0.2	0.7	1.1
Peripheral Vascular Diseases	1.3	0.03	1.03	1.6
Cardiorenal Syndrome	1.4	0.000	1.2	1.8
Cardiac Arrest	26.6	0.000	20.9	33.9

STEMI = ST-segment Elevation Myocardial Infarction; NSTEMI = Non-ST-segment Elevation Myocardial Infarction; HFrEF = Heart Failure with Reduced Ejection Fraction; HFpEF = Heart Failure with Preserved Ejection Fraction.

3.4. Prevalence of other comorbidities

As demonstrated in Table 1, HTN was the most common coexisting condition among hospitalized individuals with HCM, affecting 16,829 individuals (30.20%). Diabetes mellitus was also commonly observed, present in 7,395 patients (13.20%), followed by alcohol use disorder in 831 patients (3.50%). Less frequently, there were Human Immunodeficiency Virus (HIV) and acquired immunodeficiency syndrome (AIDS) in 140 (0.25%) and 117 (0.50%) patients, respectively.

3.5. Revascularization outcomes

As demonstrated in Figure 2, among HCM patients admitted with STEMI or NSTEMI who underwent revascularization, PCI was linked with meaningfully lesser mortality than CABG for both STEMI (8.50% vs. 37.50%, p = 0.008) and NSTEMI (1.80% vs. 4.90%, p = 0.04).

Figure 2.

Mortality rate among HCM patients with AMI undergoing revascularization procedures.

4. Discussion

Using a nationwide cohort of 278,995 hospitalized patients with HCM from 2016 to 2020, based on the leading publicly obtainable inpatient dataset in the U.S., we observed that Cardiac arrest, tamponade, and myocardial infarction had the highest fatality rates. Factors of case-fatality included older age, Asian/Pacific Islander race, CVA, NSTEMI, PVD, and cardiorenal syndrome. PCI was linked to better survival among patients undergoing revascularization compared to CABG.

4.1. HCM hospitalizations, In-hospital mortality trends, and comorbidity-associated mortality

Over recent decades, findings from various HCM cohorts have shown that progress in managing the disease has led to marked improvements in patient outcomes and a notable decline in mortality [24–27]. However, our results demonstrate that crude in-hospital mortality among all HCM admissions remained alarmingly high, rising from 16.4% to 22.9% over the study period. This difference may stem from variations in study populations, geographical settings, and methodological approaches. Furthermore, in the context of total hospital admissions, a previous NIS analysis reported 242,172 HCM hospitalizations over eight years from 2011–2018, reflecting a lower hospitalization rate compared to our five-year study, which identified 278,995 hospitalizations which indicates a rising trend in HCM-related admissions [28], and may reflect increased disease recognition, improved diagnostic accuracy, or a growing population of patients with complex comorbidities. In our study, cardiac arrest exhibited the highest mortality rates and was significantly associated with case-fatality. Our analysis further demonstrated that PVD, cardiorenal syndrome and NSTEMI were also significantly linked to increased case-fatality rates, in line with previous research, as the majority of HCM patients died from cardiovascular events [29–31]. Moreover, we identified cardiorenal syndrome as the third most prevalent cardiovascular comorbidity, significantly associated with increased case-fatality rates, which contrasts with previous research, that described cardiorenal syndrome as a rare complication in patients with HCM, suggesting that discrepancies may stem from differences in study design, analytical methods, or patient population characteristics and need for further investigations [26].

4.2. Patient demographics

Hospitalized patients with HCM tend to be older adults, as reflected in this analysis, where the mean age was 64.3 ± 18.4 years. Advancing age emerged as an independent predictor of in-hospital mortality, aligning with findings from a previous NIS study in which most individuals were aged 65 years or older [22]. Females are more regularly seen represented in hospitalized HCM cohorts, as shown in a U.S. study of 53,117 HCM admissions, where 57.7% were women [22], which aligns with our findings, where the majority of hospitalized patients were also female, accounting for 55.7% of the cohort. Moreover, consistent with these observations, another US-based analysis found that among individuals with AMI, those with coexisting HCM were significantly more likely to be female and older versus AMI individuals without HCM [26], further reinforcing the demographic patterns observed in our study.

In terms of racial and social factors, our study noted that most hospitalized patients were white, aligning with previous research [22]. While our analysis, based on data from 2016 to 2020, showed that Asian/Pacific Islander individuals had an elevated mortality risk compared to other racial populations, and that Hispanic patients had a lower mortality rate than white patients, a separate study using NIS data from 2012 to 2018 reported higher in-hospital mortality among Hispanic individuals compared to white patients [22]. This discrepancy might be due to variability in the research periods and analytical approaches, reflecting possible changes in healthcare access, quality, or population health characteristics over time. Moreover, similar socioeconomic patterns were observed, as the majority of individuals in both our research and the study by Johnson et al. [22] were covered by Medicare, followed by private insurance, despite differences in study durations and periods covered. In our study, most of hospitalized individuals with HCM were in large metropolitan areas, with central and fringe counties of major metro regions accounting for the largest proportions, a pattern that closely mirrors insights from a past NIS study [22], which indicates a shared trend of care delivery and emphasizes the need to address potential access disparities for patients residing in less populated, rural areas.

4.3. Comorbidity profile

Consistent with prior studies, our cohort of hospitalized HCM patients bore a high burden of CVC, with over 34% diagnosed with HF, reflecting the similarly elevated rate reported by Ismail et al. [25], where over 45% of HCM admissions involved HF, though this variation may stem from differing study periods and the disruptive consequences of the COVID-19 pandemic on hospital utilization and in named study, individuals with HCM were more likely to present with additional comorbidities such as diabetes mellitus (DM), a trend consistent with our findings, as both DM and HTN were prevalent among the patients in our cohort. Moreover, studies indicate that up to 20% of HCM patients have coexistent CAD [27], which is likely reflected in our cohort’s MI prevalence and aligns with these findings. Among individuals with HCM, AF is the most prevalent arrhythmia [24,28] as studies have estimated that individuals with HCM face a 20% lifetime risk of developing AF, with the prevalence rising to as high as 40% among patients over the age of 70 [29–33]. In our study, AF was observed in more than 42% of HCM patients, which is notably greater than the 18% prevalence reported in the Mayo Clinic study [34], as the variation might stem from variability in research population characteristics and the periods. While previous research has reported that MI in HCM patients is not significantly associated with case fatality, our analysis found a different pattern, as in our analysis, NSTEMI was not only more prevalent than STEMI, consistent with earlier prevalence trends [35], but NSTEMI was also significantly associated with increased case fatality.

4.4. Revascularization outcomes

Research has demonstrated that individuals with AMI who also have HCM receive notably fewer coronary interventions, such as stenting and CABG surgery, and experience lower rates of in-hospital mortality compared to patients without HCM [36]. However, a Korean nationwide population-based cohort study demonstrated that HCM individuals who underwent revascularization had an elevated risk of all-cause mortality, cardiovascular death, sudden cardiac death, and ischemic stroke [37]. As shown in the previous research, patients with STEMI exhibit higher fatality rates compared to those with NSTEMI [38], which contrasts with our findings and may be due to differences in analytical methods, population size, and patient characteristics. Furthermore, our research revealed that PCI was linked to reduced mortality rate compared to CABG, a finding that contrasts with earlier research which either reported the superiority of CABG over PCI in terms of clinical outcomes and mortality rates or found no meaningful differences between the two, as the variation may be explained by differences in study populations, research methodologies, and the periods the studies were carried out [39–44] and prior evidence also suggest that CABG and PCI show comparable rates of long-term mortality and myocardial infarction [45], or the difference could originate from multiple factors, including individuals undergoing CABG, were more likely to have heightened risk characteristics than others [46], while other research resulted that CABG offers superior protection against myocardial infarction and reduces the likelihood of repeat revascularization, PCI is associated with a lower risk of cerebrovascular accident [45] which together emphasize the importance of tailoring revascularization strategies to each patient’s unique risk profile and clinical circumstances.

4.5. Clinical implications and future directions

Our findings highlight the need for proactive identification of high-risk subgroups, particularly older adults and certain racial populations who appear disproportionately vulnerable, and targeted risk stratification incorporating demographic, comorbidity, and acute event profiles could facilitate earlier interventions, optimize resource allocation, and guide procedural decision-making. Future research should focus on prospective studies integrating detailed clinical, imaging, and genetic data to better elucidate the interplay between HCM severity and comorbidity burden, while also assessing the effectiveness of tailored treatment pathways as well as development of targeted interventions, such as comorbidity-specific management algorithms and enhanced referral to multidisciplinary HCM centers, which has the potential to reduce mortality and improve overall outcomes in this population.

5. Limitations of the study

Limitations of this study stem from its retrospective nature and dependence on administrative coding, which may cause misclassification and lack detailed clinical information such as disease severity, echocardiographic findings, and treatment strategies. Additionally, because the data reflect hospitalizations rather than individual patients, repeat admissions may be counted more than once. Despite adjusting for multiple confounders, unmeasured variables may still influence the results, limiting the ability to draw more definitive causal conclusions. Furthermore, we acknowledge that while direct validation against clinical records would be ideal, such validation presents significant challenges as the NIS is a de-identified national database that prohibits patient-level linkage to clinical records by design [47], and large-scale validation studies of administrative databases typically require substantial additional resources and infrastructure beyond the scope of a single research study. The multivariate logistic regression model accounted for age, sex, race, insurance type, household income percentile, and all identified clinical comorbidities to adjust for potential confounding. However, the NIS lacks direct measures of HCM severity, such as echocardiographic findings and New York Heart Association (NYHA) functional class, limiting our ability to fully assess the influence of disease severity on comorbidity prevalence and mortality outcomes and the absence of detailed clinical parameters, including left ventricular outflow tract gradient, wall thickness, EF, and medication use that restricts the clinical interpretability of our results and represents a known limitation of the NIS, which relies solely on administrative coding and without such information, surveillance bias may affect observed associations, potentially producing invalid protective effects, since differences in diagnostic testing or treatment practices cannot be evaluated or controlled for as well as that NIS does not differentiate between the acuity or severity of diagnoses or distinguish chronic comorbidities from complications, further constraining causal inference. We acknowledge that while the study could benefit from subgroup analyses of comorbidity patterns, these were not performed to preserve statistical stability, avoid over-stratification of smaller subgroups, and future research should explore the probable benefit of such stratifications to better elucidate demographic differences in comorbidity burden and outcomes.

6. Conclusion

This study demonstrates that in-hospital mortality among patients with HCM has edged upward slightly, driven by age, race, and comorbid conditions such as CVA, NSTEMI, and cardiorenal syndrome, with cardiac arrest being the most fatal complication. These findings underscore the need for identification of high-risk patients, particularly among older adults and certain racial groups who appear more vulnerable. Furthermore, in cases requiring revascularization, our findings suggest that PCI is associated with better survival compared to CABG. Although this remains open to debate, and emphasizes the need to choose revascularization strategies based on each patient’s risk factors and clinical condition.

Funding Statement

This paper was not funded.

Article highlights

• Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac condition with increasing hospitalization rates and a high comorbidity burden.

• In-hospital mortality increased from 16.4% in 2016 to 22.9% in 2020.

• Cardiac arrest, tamponade, and ST-elevation myocardial infarction (STEMI) were associated with the highest mortality rates.

• Atrial fibrillation (AF), heart failure with preserved ejection fraction (HFpEF), and cardiorenal syndrome were the most prevalent comorbidities.

• Independent predictors of mortality in this population included older age, Asian/Pacific Islander race, cerebrovascular accident (CVA), non-ST-segment elevation myocardial infarction (NSTEMI), cardiorenal syndrome, and cardiac arrest.

• Cardiac arrest carries the highest odds of death in this population.

• Findings highlight the need for early identification and targeted management of high-risk patients.

• Our findings emphasize the importance of a multidisciplinary management for HCM cases.

Authors contributions

Reza Khademi participated in data interpretation, drafted the manuscript, and critically revised it for important intellectual content. Saeed Shoar contributed to the study conception and design, performed statistical analysis, interpreted the data, and critically revised the manuscript for important intellectual content. Both authors reviewed and approved the final version of the manuscript and agreed to be accountable for all aspects of the work, ensuring the accuracy and integrity of the study.

Disclosure statement

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.