Abstract
Aim: Right ventricular failure (RVF) complicates 30–50% of cases with inferior wall myocardial infarctions (IWMI). Large-scale studies exploring the recent trends in morbidity and mortality of IWMI with RVF in the context of improved reperfusion strategies are currently lacking.
Materials & methods: The International Classification of Diseases, Tenth Revision, Clinical Modification codes were used to query the National Inpatient Sample of 2018–2019 to yield IWMI admissions and stratified based on presence of RVF. The primary outcome was in-hospital mortality.
Results: Out of the 182,485 weighed hospital admissions for IWMI, 1005 patients (0.6%) also had RVF. Patients with both IWMI and RVF had significantly higher mortality than patients with IWMI and no RVF (p < 0.001).
Conclusion: RVF in patients with IWMI is an independent predictor of poor outcomes.
Plain Language Summary
What is this article about?
Right ventricular failure (RVF) refers to a condition in which the right ventricle is unable to pump blood to the left side of the heart. Up to 30–50% of patients with heart attacks, commonly known as acute myocardial infarction, affecting the back or the inferior wall of the heart (IWMI) can develop RVF. Research studies assessing the outcomes of patients with IWMI and RVF were done either in a small number of patients or done during the time when the current standard of acute myocardial infarction care was not the standard of care. Therefore, we conducted a study to assess the clinical outcomes of patients with IWMI and RVF in contemporary times.
What are the results?
We found that among all patients with IWMI, only about 0.6% had evidence of RVF. However, these patients were older and much more likely to have a higher burden of chronic medical problems and were less likely to have received angioplasty to open blocked arteries when compared with patients with IWMI and no RVF. Patients with IWMI and RVF were noticed to have a higher rate of death during hospitalization.
What do the results mean?
Patients with IWMI and RVF, when compared with patients with IWMI and no RVF, had significantly higher rates of various complications and death.
1. Background
Right ventricular failure (RVF) refers to the inability of the right ventricle (RV) to generate an adequate forward flow of blood into the pulmonary circulation, which in turn impairs left ventricular (LV) filling [1]. It is associated with poor outcomes in acute myocardial infarction (AMI) [2]. RVF complicates up to 30–50% of cases with inferior wall myocardial infarctions (IWMI), among which about 10% of the patients develop hemodynamically significant right ventricular dysfunction [3–7]. Several prior studies have highlighted the poor outcomes in patients with IWMI by itself [8–10]. Among patients with AMI complicated by hemodynamic instability and arrhythmias, RV dysfunction is associated with a significantly increased risk of death and irreversible congestive failure [11–14]. However, while most of these studies were designed and executed well, they were with limitations. Many studies were performed in an era when percutaneous coronary intervention (PCI) was not the standard of care for revascularization, and thrombolysis was still widely used.
In contrast, others had a relatively smaller sample size [3,5,6]. Among some studies, the diagnostic accuracy of RVMI and RV function could have been more precise, given the complex geometry and inclusion criteria. Over the past several years, as revascularization strategies have undergone robust changes, reperfusion times have reduced significantly, dramatically improving the overall outcomes of AMI [15–19]. However, there is a lack of large-scale studies exploring the recent trends in morbidity and mortality of IWMI with RVF in the context of advances in the techniques of reperfusion strategies [20], and we thus decided to undertake a study to explore the same. We hypothesized that compared with patients without RVF, patients with RVF admitted to the hospital with IWMI had worse outcomes.
2. Materials & methods
The data source for this study used the National Inpatient Sample (NIS) database records for the years 2018 and 2019. The NIS, a part of the HealthCare Utilization Project (HCUP), is the nation’s most comprehensive database, which contains information about more than 7 million unweighted and 35 million weighted hospitalizations annually [21]. The International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) was used to identify diseases and procedures linked with each unique hospital admission [22]. Additional information, including de-identified demographic details, length of stay and hospitalization costs, is available for each patient. Each hospitalization has one unique primary and several secondary diagnoses with ICD-10-CM codes.
Using the ICD-10-CM code I21.1, we identified patients aged 18 or above who had been admitted with a primary diagnosis of IWMI between 2018 and 2019. Hospitalization with information missing on age, race, gender, length of stay, cost of stay or in-hospital death were excluded. We then used ICD-10-CM code I50.810 to identify admissions with a secondary diagnosis of RVF and stratified the population into two cohorts: IWMI with RVF and IWMI without RVF. Finally, propensity score matching (PSM) was performed with the unmatched cohort to adjust the differences in sociodemographic and comorbid conditions.
The primary outcome was in-hospital mortality within 30 days of hospital admission. Secondary outcomes included conditions that developed as sequelae of myocardial dysfunction and interventions deemed necessary for adequate patient care. Our study defined secondary outcomes as cardiogenic shock, acute kidney injury (AKI), use of vasopressor agents and mechanical circulatory support devices.
We used IBM SPSS version 12.2 (IBM Corp, Armonk, NY) for statistical analysis. Categorical variables are expressed as numbers and percentages, and continuous variables are expressed as mean standard deviation. We used Pearson’s Chi-square test to assess differences in categorical variables between patients with and without RVF. However, to compare continuous variables, we used a student’s t-test and a one-way analysis of variance. Cox-proportional logistic regression models were applied to estimate the hazard ratios of the primary outcome and various secondary outcomes and interventions. We used multiple covariates in our linear regression model, including age, gender, race, income, insurance status, hospital type, size, location and the Elixhauser comorbidity index. The Elixhauser comorbidity accounts for up to 29 chronic comorbidities present upon admission [23]. Given the difference in the baseline characteristics, we used PSM by applying a logistic regression model accounting for various demographic and clinical variables. The p-values reported for all analyses were two-sided with a significant threshold of less than 0.05.
3. Results
We found 182,485 weighted hospital admissions for IWMIs between 2018 and 2019. A total of 1005 patients (0.6%) also had RVF. Table 1 shows the baseline demographic and clinical variables among the two groups of patients. Compared with patients with IWMI and no RVF, patients with IWMI and RVF were more likely to be males (68.9 vs 66.7%), older (Mean age: 68.4 vs. 63.9 years, p < 0.001), and have a higher burden of comorbidities (Table 1).
Table 1.
Baseline characteristics of patients admitted with inferior wall myocardial infarction.
| Without RVF N (%) |
With RVF N (%) |
p-value | |
|---|---|---|---|
| Weighted population (N) | 181480 (99.4) | 1005 (0.6) | |
| Age, mean (SD) (years) | 63.9 (12.7) | 68.4 (11.8) | <0.001 |
| Female N (%) | 56370 (31.1) | 335 (33.3) | 0.5155 |
| Insurance | <0.001 | ||
| Medicare | 84535 (46.6) | 650 (64.7) | |
| Medicaid | 18875 (10.4) | 90 (9.0) | |
| Private | 59295 (32.7) | 185 (18.4) | |
| Self-pay | 5800 (3.2) | 35 (3.5) | |
| Location | 0.0624 | ||
| Rural | 11780 (6.5) | 30 (3.0) | |
| Urban nonteaching | 34140 (6.5) | 165 (16.4) | |
| Urban teaching | 135560 (74.7) | 810 (80.6) | |
| Hospital bed size | 0.0158 | ||
| Small | 29940 (16.5) | 95 (9.5) | |
| Medium | 53880 (29.7) | 290 (28.9) | |
| Large | 97660 (53.8) | 620 (61.7) | |
| Disposition | <0.001 | ||
| Routine | 131875 (72.7) | 270 (26.9) | |
| Transfer to short term hospital | 6660 (3.7) | 120 (11.9) | |
| SNF | 13920 (7.7) | 145 (14.4) | |
| Home healthcare | 13870 (7.6) | 120 (11.9) | |
| Elixhauser score | <0.001 | ||
| 0 | 9145 (5.0) | 0 (0.0) | |
| 1–3 | 100840 (55.6) | 130 (12.9) | |
| 4–5 | 45185 (24.9) | 280 (27.9) | |
| ≥6 | 26310 (14.5) | 595 (59.2) | |
| Atrial fibrillation | 75580 (41.6) | 750 (74.6) | <0.001 |
| Arrhythmia | 12015 (6.6) | 35 (3.5) | <0.001 |
| Prior CVA | 24395 (13.4) | 105 (10.4) | 0.0697 |
| Prior MI | 1910 (1.1) | 15 (1.5) | 0.2128 |
| Prior PCI | 9570 (5.3) | 20 (2.0) | 0.5386 |
| Prior CABG | 2010 (1.1) | 5 (0.5) | 0.0378 |
| Prior PPM | 29440 (16.2) | 250 (24.9) | 0.4077 |
| COPD | 134115 (73.9) | 790 (78.6) | 0.0007 |
| Hypertension | 60180 (33.2) | 360 (35.8) | 0.128 |
| Diabetes mellitus | 33335 (18.4) | 160 (15.9) | 0.4208 |
| Obesity | 24810 (13.7) | 250 (24.9) | 0.3733 |
| CKD-ESRD | 4235 (2.3) | 20 (2.0) | <0.001 |
| Anemia | 14545 (8.0) | 95 (9.5) | 0.7466 |
| PVD | 8620 (4.7) | 340 (33.8) | 0.4539 |
| Liver disease | 16350 (9.0) | 110 (10.9) | <0.001 |
| Hypothyroidism | 62520 (34.5) | 240 (23.9) | 0.3403 |
| Smoking | 5530 (3.0) | 50 (5.0) | 0.0015 |
| Alcohol use disorder | 84535 (46.6) | 650 (64.7) | 0.1198 |
CABG: Coronary artery bypass grafting; CKD-ESRD: Chronic kidney disease-end stage renal disease; COPD: Chronic obstructive pulmonary disease; CVA: Cerebrovascular accidents; MI: Myocardial infarction; PCI: Percutaneous coronary intervention; PPM: Permanent pacemaker; PVD: Peripheral vascular disease; RVF: Right ventricular failure.
Table 2 illustrates the event rates for primary and secondary outcomes among IWMI patients with and without RVF, respectively. Compared with patients hospitalized with IWMI but without RVF, patients with IWMI and RVF had increased mortality (p < 0.001), increased prevalence of cardiogenic shock (p < 0.001) and AKI (p < 0.001), and increased use of vasopressor agents (p < 0.001), and mechanical circulatory support devices (p < 0.001). The length and costs of hospitalization were also higher in patients with RVF (p < 0.001). However, among patients with IWMI and RVF, we found that the rates of PCI were significantly lower compared with patients with IWMI and no RVF (p < 0.001). Here we have considered both primary and delayed PCI during the same admission.
Table 2.
Length of stay, cost of stay and clinical outcomes in patients with inferior wall myocardial infarction.
| Outcomes | Without RVF N (%) |
With RVF N (%) |
p-value |
|---|---|---|---|
| In-hospital mortality | 13615 (7.5) | 345 (34.3) | <0.001 |
| Length of stay, mean (SD) (days) | 4.7 (8.8) | 6.0 (8.2) | <0.001 |
| PPM insertion | 2150 (1.2) | 15 (1.5) | 0.6867 |
| Cardiac arrest | 9580 (5.3) | 110 (10.9) | 0.0003 |
| Cardiogenic shock | 22605 (12.5) | 735 (73.1) | <0.001 |
| VT | 22165 (12.2) | 2.65 (0.3) | <0.001 |
| AKI | 31585 (17.4) | 655 (65.2) | <0.001 |
| AKI requiring HD | 2135 (1.2) | 110 (10.9) | <0.001 |
| Vasopressor | 6245 (3.4) | 235 (23.4) | <0.001 |
| Mechanical circulatory support | |||
| IABP | 10595 (5.8) | 250 (24.9) | <0.001 |
| Impella | 3235 (1.8) | 150 (14.9) | <0.001 |
| ECMO | 770 (0.4) | 100 (10.0) | <0.001 |
| PCI | 143975 (79.3) | 590 (58.7) | <0.001 |
| CABG | 8290 (4.6) | 120 (11.9) | <0.001 |
| IVUS | 9515 (5.2) | 40 (4.0) | 0.4227 |
| FFR | 3180 (1.8) | 15 (1.5) | 0.7791 |
| Cost of hospitalization, mean (SD) (US dollar) | 26396 (26236) | 64916 (60448) | <0.001 |
AKI: Acute kidney injury; CABG: Coronary artery bypass grafting; ECMO: Extra corporeal membrane oxygenation; FFR: Fractional flow reserve; HD: Hemodialysis; IABP: Intra-aortic balloon pump; IVUS: Intravascular ultrasound; PCI: Percutaneous coronary intervention; PPM: Permanent pacemaker; VT: Ventricular tachycardia.
Table 3 depicts the hazard ratios of primary and secondary outcomes after applying PSM. Patients with IWMI and RVF had an 83% higher risk of in-hospital mortality than patients with IWMI and no RVF. In addition, RVF in patients admitted to the hospital with IWMI was associated with an increased incidence of cardiogenic shock, AKI, utilization of vasopressor agents and mechanical circulatory support devices such as IABP, Impella and extracorporeal membrane oxygenation (ECMO).
Table 3.
Propensity score matched hazards of outcomes.
| Outcomes | Hazard ratio | 95% C.I. | p-value |
|---|---|---|---|
| In-hospital mortality | 1.83 | 1.19–2.81 | 0.006 |
| PPM insertion | 1.00 | 0.19–5.34 | 0.999 |
| Cardiac arrest | 0.91 | 0.50–1.64 | 0.743 |
| Cardiogenic shock | 5.08 | 3.36–7.68 | <0.001 |
| VT | 1.06 | 0.67–1.66 | 0.816 |
| AKI | 2.42 | 1.63–3.59 | <0.001 |
| AKI requiring HD | 1.45 | 0.75–2.79 | 0.267 |
| Vasopressor | 4.09 | 2.21–7.54 | <0.001 |
| Mechanical circulatory support | |||
| IABP | 1.82 | 1.12–2.96 | 0.016 |
| Impella | 4.24 | 1.91–9.39 | <0.001 |
| ECMO | 3.40 | 1.31–8.79 | 0.012 |
AKI: Acute kidney injury; ECMO: Extra corporeal membrane oxygenation; HD: Hemodialysis; IABP: Intra-aortic balloon pump; PPM: Permanent pacemaker; VT: Ventricular tachycardia.
4. Discussion
RVF was reported in 0.6% of individuals in our study of more than 180,000 hospital admissions with inferior wall myocardial infarction from the NIS database of 2018 and 2019. We found that among patients admitted with IWMI, those with RVF were predominantly males, older, and had a significantly higher burden of various comorbid conditions than IWMI patients without RVF.
The RV is a thin-walled chamber that outputs into a low-pressure, high-capacitance vascular bed. The RV is extremely sensitive to acute changes in preload compared with the left ventricle. IWMI leads to increased end-diastolic RV volume and increased diastolic pressure. The RV pressure overload results in a leftward shift of the interventricular septum. The shift decreases LV end-diastolic volume, compliance and filling. These effects can ultimately lead to underfilling of the left side of the heart and cardiogenic shock. So, the management of RVF is essential to ensure a positive outcome for the affected individual [24].
Our analysis found that among patients hospitalized with inferior wall myocardial infarction, the presence of RVF was associated with an 83% higher risk of in-hospital mortality. These patients also had higher odds of developing cardiogenic shock, AKI and requiring vasopressors and mechanical circulatory support devices.
Limited guidelines exist regarding the use of vasopressors and inotropes associated with RVF in IWMI. This use is relevant for patients with end-organ hypoperfusion, including cardiogenic shock. Hypotension may aggravate RV ischemia by further affecting coronary perfusion. Therefore, maintaining an optimum perfusion pressure in RVF in patients with IWMI is important. If, after increasing preload or fluid therapy, the blood pressure does not improve, vasopressor therapy should be considered [25].
To the best of our knowledge, our study was the first to compare IWMI patients with and without RVF in an era of efficient and timely reperfusion. Many prior reports on outcomes of patients with IWMI were limited by relatively smaller sample sizes [26], conducted when PCI was still becoming readily and widely available [3,11] and thrombolysis was the standard of care for acute coronary syndromes. Furthermore, several studies focused on myocardial infarctions with either different wall involvement or combined IWMI with myocardial infarction of other segments [5,17]. In contrast to earlier studies conducted during the pre-reperfusion or thrombolysis era, mortality in IWMI patients with right heart failure has significantly decreased due to improving trends of timely reperfusion using highly effective PCI techniques [11,15]. Our study showed an 83% higher risk of in-hospital mortality, which, albeit high, is still significantly lower than several previously reported values [11]. A recent study has shown that tricuspid annular velocities by tissue doppler index are important in evaluating RV diastolic dysfunction. The study revealed that E/E′ >6 and E′ velocity ≤6 cm/s were associated with more major adverse cardiac events in patients with IWMI involving RV [27].
IWMI often occurs due to an acute occlusion of the right coronary artery or left circumflex artery [28]. The RV is supplied by the RV branches of the right coronary artery, which explains the frequent association of RV involvement with IWMI. In our study, IWMI patients with RVF had significantly lower PCI rates than those without RVF, reflecting lower rates of revascularization, which has been associated with poor outcomes in multiple prior studies [29–31]. The lower PCI rate can be associated with already poor prognosis of the patients with RVF who could not get PCI due to the deteriorating clinical picture. The finding may explain the higher rates of cardiogenic shock, AKI and usage of mechanical circulatory support in patients with RVF.
As NIS is a discharge diagnosis-based database without any patient-level objective data, it is difficult to comment on why there is a significant difference between these two groups regarding PCI. Whether the patients with RVF were too sick to get PCI or the PCI failed due to the already deteriorated clinical status of the affected patients is a matter of discussion and further study. Also, it is beyond the scope of the analysis to comment on the effect of medical management on the outcomes.
Contrary to the prior notion about the relative unimportance of RV in maintaining normal circulation, emerging data in the last decade has brought on a new focus on the vitality of the overall functional and prognostic value of the RV [32,33]. Our study corroborates multiple prior studies highlighting the prognostic significance of RVF and emphasizes the need for its early recognition and prompt evaluation.
The prevalence of RVF in our patient population is lower than reported in previous literature [8,11]. This discrepancy may be explained by the relative limitation of the administrative database to account for various conditions from incomplete or inaccurate coding. Conversely, the lower rates of RVF may result from effective supportive and reperfusion therapy, leading to a potential recovery of the RV function.
As mentioned before, robust data is yet to be available on IWMI patients with and without RVF to show the efficacy of efficient and timely reperfusion. A recent study was done to show whether the addition of revascularization by PCI results in a lower incidence of death from any cause or hospitalization for heart failure in patients with ischemic LV dysfunction. Interestingly, compared with optimal medical management, only the addition of PCI did not result in a lower incidence of death or hospitalization at a median of 3.4 years. It would be interesting to know similar study results on patients with IVMI and RVF [34].
5. Limitations
There are several limitations in our retrospective study using an administrative database. RVF is a complex clinical condition requiring high clinical suspicion and careful laboratory and imaging data assessment, making its diagnosis challenging. Since administrative databases utilize diagnosis codes associated with each hospitalization, which are used originally for billing purposes, there exists a potential for the loss of important clinical information. The inherent nature of ICD-10-CM coding makes it hard to differentiate new-onset RVF from chronic RVF. Given that the data source of this study was an extensive administrative database, there is a potential for several unaccounted confounding factors that may influence the results. Finally, since the NIS only includes inpatient outcomes for the duration of the hospitalization, long-term outcomes, particularly the ones that occur beyond hospitalization and are often of crucial clinical information, cannot be evaluated.
6. Conclusion
In conclusion, RVF in the setting of IWMI is associated with a worse outcome, including a higher rate of in-hospital mortality, cardiogenic shock and AKI, along with higher use of vasopressor agents and mechanical circulatory devices like IABP, Impella and ECMO. Therefore, physicians approaching IWMI should be aware of the presence of RVF and institute appropriate clinical, laboratory and imaging investigations for a prompt diagnosis and robust treatment to mitigate the associated adverse outcomes.
Author contributions
Conceptualization: S Mukhopadhyay, D Rai, D Bandyopadhyay. Data curation: R Srivastav, A Malik, A Hajra, A Goel. Writing—original draft preparation: A Hajra, A Goel, A Mandal. Review and editing: R Srivastav, A Malik, S Mukhopadhyay, D Rai, D Bandyopadhyay. Supervision: S Mukhopadhyay, D Bandyopadhyay.
Financial disclosure
The authors have no 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.
Competing interests disclosure
The authors have no competing interests or relevant affiliations with any organization or entity 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.
Writing disclosure
No writing assistance was utilized in the production of this manuscript.
Ethical conduct of research
Permission to use information from a database/repository is not required as we used the NIS database which is publicly available information.
References
Papers of special note have been highlighted as: • of interest; •• of considerable interest
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