Impact of amyloidosis on the outcomes of percutaneous coronary intervention recipients: a nationwide analysis

Introduction

Amyloidosis is a medical condition characterized by the irregular accumulation of amyloid protein in various organs, including the heart. Cardiac amyloidosis, which can be categorized into transthyretin (ATTR) and light chain (AL) amyloidosis, is the primary cause of restrictive cardiomyopathy. This condition can lead to myocardial ischemia and heart failure, similar to atherosclerotic disease. When combined with atherosclerosis and heart failure, cardiac amyloidosis can further exacerbate coronary artery disease and interstitial amyloidosis.¹ Coronary artery disease is the most prevalent form of heart disease and a leading cause of mortality. In 2020, it was responsible for the death of 382,820 individuals, with 20% of these deaths occurring in people under the age of 65.²

The formation of amyloid fibrils in amyloidosis involves different precursor proteins. Protein misfolding and aggregation occur due to factors such as abnormal proteolysis, point mutations, and posttranslational modifications like phosphorylation, oxidation, and glycation.^3,4 Research conducted in Germany examined trends in hospitalizations for heart failure and found that improved outcomes were partially attributed to the utilization of percutaneous coronary interventions.⁵ Another investigation focused on patients diagnosed with cardiac amyloidosis and revealed that individuals with ST-elevation myocardial infarction and cardiac amyloidosis had higher rates of signs and symptoms, including ventricular tachycardia/ventricular fibrillation, cardiogenic shock, acute kidney injury requiring dialysis, and admissions to the intensive care unit, compared to those without ST-elevation myocardial infarction.⁶

The present study aimed to investigate predictors of in-patient mortality after percutaneous coronary intervention (PCI), compare PCI recipients with and without amyloidosis and identify risk factors for post-PCI complications in amyloidosis patients. Notably, there is a lack of dedicated studies specifically addressing the immediate complications of PCI in patients with coronary amyloidosis, such as coronary artery perforation, coronary artery dissection, coronary artery aneurysm, failure of stent deployment, and patient-stent mismatch, when compared to patients without coronary amyloidosis.⁷ Evaluating the demographics and hospital outcomes of patients undergoing PCI is essential for enhancing patient care and outcomes. In our investigation, we analyzed variables such as age, gender, household income, and comorbidities, with a specific focus on assessing main risk factors, including acute kidney injury, complications of surgical care/injury, and complications of cardiovascular implant/graft.

Methods

We conducted a cross-sectional study using the publicly available registry database nationwide inpatient sample (NIS, 2018 and 2019). The NIS dataset covers hospitalized patients from more than 4,400 non-federal community hospitals across 48 states and the District of Columbia in the United States. The clinical classifications software refined (CCSR) for international classification of diseases, tenth revision (ICD-10)-coded diagnoses classifies diagnoses into clinical categories. According to the agency for healthcare research and quality (AHRQ) and the Department of Health and Human Services (HHS), our study was based on the de-identified dataset of the NIS and does not require approval from an institutional review board. The data can be obtained from the website of the Healthcare Cost and Utilization Project, AHRQ.⁸

We included 457,730 adult inpatients (age ≥18 years, mean age 65.9) hospitalized with a primary discharge diagnosis of coronary atherosclerosis and other heart diseases (CCSR code: CIR011) and managed with the primary procedure of percutaneous coronary intervention (PCI). We used the term coronary artery disease (CAD) for “coronary atherosclerosis and other heart diseases” in this study. The study sample was further grouped by the co-diagnosis of amyloidosis (identified by CCSR code END016).

The variable of interest included demographic characteristics: age at admission, sex, race, and median household income. The following comorbidities were obtained from the data using CCSR codes in parenthesis: diabetes (END004, END005), hypertension (CIR007, CIR008), and obesity (END009). Acute complications during the hospitalization included acute kidney injury (AKI), complications of surgical care/injury, and complications of cardiovascular implant/graft. The hospitalization outcomes of interest include the severity of illness, which was measured using the all-patient refined DRG (APR-DRGs), length of stay (LOS), total charges, and disposition status, including all-cause in-hospital mortality.

We used descriptive statistics with Pearson’s chi-square test for categorical data and independent-sample T-test for continuous data (age, LOS, and total charges) to measure the differences between PCI recipients by co-diagnosis of amyloidosis. The binomial logistic regression model was used to evaluate the odds ratio (OR) of predictors associated with in-hospital mortality in PCI recipients. A P value <0.05 was used to detect the statistical significance, and all analyses were conducted using the Statistical Package for the social sciences (SPSS) version 27 (IBM Corp., Armonk, NY).

Results

426,825 patients admitted with a primary diagnosis of coronary artery disease received percutaneous coronary intervention. 30,905 (7.24%) of those had amyloidosis. Amyloidosis prevalence was significantly greater among males (64.4%) compared to females (35.6%). The mean age at admission was relatively higher in patients with concurrent amyloidosis. The prevalence of both CAD (52.5%) and CAD with concurrent amyloidosis (54.2%) was significantly greater among patients over 65 years. While studying ethnicities, the prevalence of CAD with coexisting amyloidosis was higher in Caucasian patients (72.4%), followed by African American patients (9.6%) and Hispanic patients (8.2%). The most significant comorbid conditions among patients with amyloidosis were complicated diabetes (40.8%), complicated hypertension (51.1%), and obesity (26.5%). It was also noted that patients with coexisting amyloidosis often had other statistically significant complications like acute kidney injury, seen in 29.9% of patients, post-surgical complications occurred in 1.7% of patients, and graft-related complications in 9.5%. Patients with amyloidosis were also reported to have a longer in-hospital admission duration, increasing the mean total expenditure. Patients with concurrent amyloidosis were also reported to have moderate (31.2%) to major (54.7%) loss of function post-procedure. Although most patients resumed routine life immediately following discharge, a considerable number of patients with amyloidosis were required to transfer to a skilled nursing care facility (13.2%) or home health care (13.9%). Our study also found that concurrent amyloidosis was much more prevalent among people with a median household income below the 50th percentile, as shown in Table 1.

The overall in-hospital mortality after PCI is 2.7%, of which 4.7% of patients had coexisting amyloidosis. Patients over 65 years were at 2.79 times higher mortality risk after PCI than other groups (OR 2.79 95% CI 1.88-4.12). Patients with AKI had a six-fold higher mortality (OR 6.49 95% CI 6.24-6.77). Post-procedure complications also led to a three-fold increase in mortality (OR 3.02 95% CI 2.70-3.37). The most important comorbid conditions that lead to in-hospital mortality after PCI include amyloidosis (OR 1.30 95% CI 1.23-1.39) and complicated hypertension (OR 1.13 95% CI 1.09-1.18) followed by complicated diabetes (OR 0.86 95% CI 0.82-0.89) and obesity (OR 0.69 95% CI 0.65-0.72). Other statistically significant risk factors for in-hospital mortality after PCI include female sex (OR 1.34 95% CI 1.28-1.39), African American ethnicity (OR 0.77 95% CI 0.72-0.83), and low socioeconomic status (OR 1.08 95% CI 1.04-1.12) as shown in Table 2. We also found that post-PCI complications such as AKI (OR 1.89 95% CI 1.83-1.94) and complications of surgical care/injury (OR 2.05 95% CI 1.87-2.26) are higher in patients with amyloidosis, but complications of cardiovascular implant/graft were similar in patients with or without amyloidosis (OR 1.01 95% CI 0.97-1.05) as shown in Table 3.

Discussion

In this study, we investigated the impact of amyloidosis on in-hospital mortality and outcomes among patients who underwent percutaneous coronary intervention (PCI). Our findings revealed that amyloidosis was an independent risk factor for in-hospital mortality. Patients with amyloidosis had a higher incidence of AKI, complications of surgical care, complications of cardiovascular implant, major loss of function, length of stay in days, and total charges.

Amyloidosis is characterized by the deposition of misfolded protein subunits, forming insoluble amyloid fibrils in various tissues. This abnormal protein aggregation can disrupt normal tissue function and contribute to several diseases.⁹ Cardiac involvement is common in amyloidosis, which can be systemic or localized, primary or secondary, and varying in incidence rarity.^10–12 Although cardiac amyloidosis is a recognized risk factor, its association with complications during PCI is often overlooked.¹³ Sometimes, the patient may not improve after revascularization.¹⁴ Therefore, it is clinically significant to identify amyloidosis as a risk factor and understand its association with other established risk factors, such as AKI.

In contrast to the general population in this study, patients with amyloidosis showed a higher association with the African American population and below 50th percentile household income. The prevalence of obesity, hypertension, and diabetes with chronic complications was significantly higher, as were complications such as major loss of function, acute kidney injury, complications of surgical care, and cardiovascular implant. Notably, acute kidney injury and complications of surgical care exhibited the strongest association with in-hospital mortality in this study.

Although there are limited studies specifically addressing amyloidosis as an independent risk factor for PCI, cardiac amyloidosis (CA) has been identified as an independent risk factor for in-hospital mortality in patients with myocardial infarction (MI).¹⁵ However, CA was not found to be a risk factor for mortality during transcatheter aortic valve replacement.¹⁶ Many amyloidosis patients undergoing PCI may need intravascular ultrasound, which increases the cost of the hospitalization.¹⁷

This study determined that amyloidosis was an independent factor associated with in-hospital mortality, with an odds ratio of 1.3 (1.23-1.39). This increased mortality risk can be attributed to several factors, including the higher incidence of acute kidney injury in patients with amyloidosis (odds ratio 1.89, p<0.001). Acute kidney injury itself exhibited the strongest association with mortality, consistent with published data.¹⁸ Heart failure readmissions and the need for left ventricular assist devices may arise in these patients, which increase the length of stay, contributes to loss of function, and increases the total cost of hospitalization.^19,20 In patients with cancer and amyloidosis, there could be racial differences in the cardiovascular outcomes as well.²¹ Amyloidosis was also associated with a higher incidence of complications of surgical care/injury (odds ratio 2.05, p<0.001). Considering the higher incidence of hypertension, diabetes, and obesity in this patient group, it is expected to observe a greater occurrence of surgical complications, in-hospital mortality, and major loss of function.

Furthermore, this study observed a significant difference in intervention timing. Patients without amyloidosis had a routine PCI in 80.6% of cases, whereas only 65.3% of amyloidosis patients underwent a routine PCI. Emergency and urgent PCIs were significant risk factors for in-hospital mortality regardless of the presence of shock.²² Therefore, further studies are necessary to assess the significance of amyloidosis as an independent risk factor in both emergency and urgent scenarios.

Based on our findings, we believe that clinicians should consider amyloidosis as a risk factor when performing PCI on patients. Although not currently included in existing risk calculation tools, amyloidosis increases the risk of procedure complications, either independently or possibly due to its association with other patient comorbidities. Moreover, it may be associated with a greater need for urgent procedures, leading to worse outcomes. This risk factor can be modified by implementing changes in clinical practice, such as closer follow-up or a lower threshold for elective PCI.

Conclusions

Amyloidosis is associated with higher in-hospital mortality and worse outcomes in PCI recipients. This could be related to the increased incidence of complications of PCI in amyloidosis as a result of the low flow state. Further research is indicated to precisely define the etiologies behind the worse outcomes and mitigate the increased risk. This will also help address the unresolved question of the management of stable angina with stable CAD in patients with amyloidosis.