Burden of Arrhythmias in Acute Myocardial Infarction Complicated by Cardiogenic Shock

Abstract

There are limited data on arrhythmias in acute myocardial infarction with cardiogenic shock (AMI-CS). Using a 17-year AMI-CS population from the National Inpatient Sample, we identified common arrhythmias – atrial fibrillation (AF), atrial flutter, supraventricular tachycardia, ventricular tachycardia (VT), ventricular fibrillation (VF), and atrioventricular blocks (AVB). Admissions with concomitant cardiac surgery were excluded. Outcomes of interest included temporal trends, predictors, in-hospital mortality, and resource utilization in cohorts with and without arrhythmias. Of the 420,319 admissions with AMI-CS during 2000–2016, arrhythmias were noted in 213,718 (51%). AF (45%), VT (35%) and VF (30%) were the most common arrhythmias. Compared to those without, the cohort with arrhythmias was more often male, of white race, with ST-segment elevation AMI-CS presentation, and had higher rates of cardiac arrest and acute organ failure (all p<0.001). Temporal trends of prevalence revealed a stable trend of atrial and ventricular arrhythmias and declining trend in AVB. The cohort with arrhythmias had higher unadjusted (42% vs. 41%; odds ratio [OR] 1.03 [95% confidence interval 1.02–1.05]; p<0.001), but not adjusted (OR 1.01 [95% CI 0.99–1.03]; p=0.22) in-hospital mortality compared to those without. The cohort with arrhythmias had longer hospital stay (9±10 vs 7±9 days; p<0.001) and higher hospitalization costs ($124,000±146,000 vs $91,000±115,000; p<0.001). In the cohort with arrhythmias, older age, female sex, non-white race, higher comorbidity, presence of acute organ failure, and cardiac arrest, predicted higher in-hospital mortality. In conclusion, cardiac arrhythmias in AMI-CS are a marker of higher illness severity and are associated with greater resource utilization.

INTRODUCTION

Arrhythmias are a frequent complication in patients with acute myocardial infarction (AMI).^1–4 Multiple studies have associated various arrhythmias with poor prognosis and a higher risk of mortality in patients with AMI.^1–9 Patients with cardiogenic shock (CS) constitute the sickest spectrum of AMI, and have nearly 30% in-hospital mortality.^10–23 The ischemic changes and metabolic derangements resulting from AMI-CS can precipitate arrhythmias, which is probably a reflection of LV dysfunction, higher filling pressures and worsening heart failure.² Conversely, high ventricular rates can result in hemodynamic compromise, further worsening myocardial function and hemodynamic instability.^4,24,25 The use of vasopressors and inotropes in this population is associated with a pro-arrhythmic state resulting in higher atrial and potentially ventricular arrhythmias.²⁶ Despite this known risk of arrhythmias, there are limited contemporary data related to arrhythmias in patients with AMI-CS.^7–9 Using a nationally-representative population, we sought to assess the burden of arrhythmias in admissions with AMI-CS. In addition, we evaluated the temporal trends, prevalence, clinical outcomes of cohorts with and without arrhythmias with further sub-group analyses of atrial and ventricular arrhythmias.

METHODS

The National (Nationwide) Inpatient Sample (NIS) is the largest all-payer database of hospital inpatient stays in the United States. NIS contains discharge data from a 20% stratified sample of community hospitals and is a part of the Healthcare Quality and Utilization Project (HCUP), sponsored by the Agency for Healthcare Research and Quality.²⁷ Information regarding each discharge includes patient demographics, primary payer, hospital characteristics, principal diagnosis, up to 24 secondary diagnoses, and procedural diagnoses. The HCUP-NIS does not capture individual patients but captures all information for a given admission. Institutional Review Board approval was not sought due to the publicly available nature of this de-identified database. These data are available to other authors via the HCUP-NIS database with the Agency for Healthcare Research and Quality.¹⁶

Using the HCUP-NIS data from 2000–2016, a retrospective cohort study of admissions with AMI in the primary diagnosis field (International Classification of Diseases 9.0 Clinical Modification [ICD–9CM] 410.x and ICD–10CM I21.x–22.x) and a secondary diagnosis of CS (ICD–9CM 785.51, ICD–10CM R57.0) were identified. Similar to prior literature, we identified AF, atrial flutter (AFlut), supraventricular tachycardia (SVT), VT, VF, 1° atrioventricular block (AVB), 2° AVB (type II), 3° AVB and permanent pacemaker (PPM) implantation.²⁸ We excluded admissions that received cardiac surgery (coronary artery bypass grafting, valve repair/replacement, durable left ventricular assist device placement and orthotopic heart transplant) since they have a distinctly different arrhythmic profile. The Deyo’s modification of the Charlson Comorbidity Index was used to identify the burden of co-morbid diseases (Supplementary Table 1).²⁹ Demographic characteristics, hospital characteristics, acute organ failure, mechanical circulatory support, cardiac procedures, and non-cardiac organ support use were identified for all admissions using previously used methodologies from our group.^{10–16,20–22,28,30–36}

The primary outcome was the in-hospital mortality and resource utilization in AMI-CS admissions with and without arrhythmias. Secondary outcomes included temporal trends, predictors of arrhythmias in AMI-CS, and clinical outcomes, resource utilization and predictors of in-hospital mortality in the arrhythmia cohort.

As recommended by HCUP-NIS, survey procedures using discharge weights provided with HCUP-NIS database were used to generate national estimates.³⁷ Using the trend weights provided by the HCUP-NIS, samples from 2000–2011 were re-weighted to adjust for the 2012 HCUP-NIS re-design.³⁷ Chi-square/one-way analysis of variance and t-tests were used to compare 2/≥2 categorical and continuous variables, respectively. Multivariable logistic regression was used to analyze trends over time (referent year 2000). The inherent restrictions of the HCUP-NIS database related to research design, data interpretation, and data analysis were reviewed and addressed.^37,38 Pertinent considerations include not assessing individual hospital-level volumes (due to changes to sampling design detailed above), treating each entry as an ‘admission’ as opposed to individual patients, restricting the study details to inpatient factors since the HCUP-NIS does not include outpatient data, and limiting administrative codes to those previously validated and used for similar studies. Univariable analysis for trends and outcomes was performed and was represented as odds ratio (OR) with 95% confidence interval (CI). Multivariable logistic regression analysis incorporating age, sex, race, primary payer status, socio-economic stratum, hospital characteristics, comorbidities, acute organ failure, AMI-type, cardiac procedures, and non-cardiac procedures was performed for assessing temporal trends of prevalence and in-hospital mortality. For the multivariable modeling, regression analysis with purposeful selection of statistically (liberal threshold of p<0.20 in univariate analysis) and clinically relevant variables was conducted. Two-tailed p<0.05 was considered statistically significant. All statistical analyses were performed using SPSS v25.0 (IBM Corp, Armonk NY).

RESULTS

In the period from January 1, 2000 to December 31, 2016, there were over 10 million AMI admissions, of which 513,288 had concomitant CS (5.1%). Of these, 92,969 (18.5%) received concomitant cardiac surgery and were excluded. In the final cohort of 420,319, arrhythmias were noted in 213,718 (50.8%) of the admissions, with AF, VT and VF being the most common arrhythmias (Figure 1). The cohort with arrhythmias was more often male, of white race, with higher rates of acute organ failure, cardiac arrest, and greater use of cardiac and non-cardiac organ support devices (Tables 1 and 2).

Figure 1. Arrhythmias in AMI-CS.

Cumulative arrhythmias in AMI-CS showing overlap and relative percentages between different arrhythmia categories and types in the arrhythmia cohort (N=213,718)

Abbreviations: AF: atrial fibrillation; AFlut: atrial flutter; AMI: acute myocardial infarction; AVB: atrio-ventricular block; CS: cardiogenic shock; SVT: supraventricular tachycardia; VF: ventricular fibrillation; VT: ventricular tachycardia

Table 1.

Baseline characteristics of AMI-CS stratified by arrhythmias

Variable		AMI-CS cohort (N=420,319)			Arrhythmia cohort (N=213,718)
		Arrhythmia (N=213,718)	No Arrhythmias (N=206,601)	P	Atrial (N=72,264)	Ventricular (N=80,388)	AVB (N=18,123)	≥2 types (N=42,943)	P
Age (years)		69.8±13.1	69.8±13.4	0.27	75.7±11.4	64.4±12.9	69.6±13.0	70.0±12.1	<0.001
Women		37.1%	43.4%	<0.001	43.7%	30.3%	46.5%	34.8%	<0.001
White		79.6%	75.5%	<0.001	81.7%	77.1%	76.1%	82.1%	<0.001
Black		6.8%	8.2%		5.6%	8.0%	8.2%	6.1%
Othera		13.6%	16.3%		12.71%	14.90%	15.67%	11.77%
Primary payer	Medicare	62.9%	63.7%	<0.001	78.1%	48.8%	61.8%	64.1%	<0.001
	Medicaid	6.1%	6.8%		3.8%	8.1%	6.9%	6.0%
	Private	23.5%	21.6%		14.0%	32.4%	23.0%	22.9%
	Othersb	7.5%	7.9%		4.1%	10.8%	8.3%	7.1%
Hospital teaching status and location	Rural	6.7%	9.5%	<0.001	8.4%	5.7%	7.2%	5.7%	<0.001
	Urban non-teaching	38.7%	40.6%		39.7%	37.6%	40.2%	38.5%
	Urban teaching	54.5%	49.9%		52.0%	56.7%	52.5%	55.8%
Hospital bed-size	Small	8.4%	9.4%	<0.001	9.3%	8.1%	8.5%	7.5%	<0.001
	Medium	23.7%	24.0%		24.5%	22.9%	24.1%	23.6%
	Large	67.9%	66.6%		66.2%	69.1%	67.4%	68.9%
Hospital region	Northeast	18.5%	18.6%	<0.001	20.4%	17.9%	17.5%	17.1%	<0.001
	Midwest	23.1%	22.7%		22.4%	22.9%	23.6%	24.7%
	South	37.5%	39.1%		35.9%	38.9%	38.4%	37.0%
	West	20.8%	19.7%		21.3%	20.3%	20.5%	21.3%
Charlson Comorbidity Index	0–3	24.5%	23.2%	<0.001	9.6%	38.2%	26.7%	23.0%	<0.001
	4–6	53.3%	53.7%		56.2%	48.8%	55.5%	55.7%
	≥7	22.2%	23.1 %		34.2%	12.9%	17.8%	21.2%
Prior pacemaker		2.1%	1.7%	<0.001	3.7%	1.0%	1.4%	1.7%	<0.001
Prior implantable cardioverter-defibrillator		1.4%	1.1%	<0.001	1.5%	1.5%	0.4%	1.6%	<0.001

Represented as percentage or mean ± standard deviation;

^aHispanic, Asian, Native American, Others;

^bUninsured, No Charge, Others

Abbreviations: AMI: acute myocardial infarction; AVB: atrioventricular block; CS: cardiogenic shock

Table 2.

In-hospital characteristics of AMI-CS stratified by arrhythmias

Variable		AMI-CS cohort (N=420,319)			Arrhythmia cohort (N=213,718)
		Arrhythmia (N=213,718)	No Arrhythmias (N=206,601)	P	Atrial (N=72,264)	Ventricular (N=80,388)	AVB (N=18,123)	≥2 types (N=42,943)	P
AMI type	STEMI	71.8%	67.0%	<0.001%	58.3%	79.3%	81.8%	76.2%	<0.001
	NSTEMI	28.2%	33.0%		41.7%	20.7%	18.2%	23.8%
Acute organ failure	Respiratory	51.9%	42.6%	<0.001	46.6%	57.2%	39.8%	55.9%	<0.001
	Renal	38.2%	34.1%	<0.001	43.5%	34.0%	33.8%	39.3%	<0.001
	Hepatic	10.6%	6.9%	<0.001	9.0%	11.9%	8.5%	11.7%	<0.001
	Hematologic	9.9%	7.8%	<0.001	10.0%	9.7%	7.4%	11.0%	<0.001
	Neurologic	18.9 %	11.1%	<0.001	11.6%	26.6%	10.0%	20.4%	<0.001
Out of hospital cardiac arrest		40.6%	13.3%	<0.001	11.9%	65.5%	15.7%	53.0%	<0.001
Coronary angiography		72.8%	64.7%	<0.001	58.7%	80.9%	77.8%	79.1%	<0.001
Percutaneous coronary intervention		58.8%	49.6%	<0.001	43.9%	67.4%	64.7%	65.1%	<0.001
Invasive hemodynamic monitoringa		19.8%	17.8%	<0.001	19.5%	20.5%	15.6%	20.8%	<0.001
Mechanical circulatory support	Total	43.0%	36.9%	<0.001	31.7%	52.4%	39.0%	46.2%	<0.001
	IABP	40.6%	35.3%	<0.001	30.1%	49.2%	37.4%	43.7%	<0.001
	pLVAD	2.8%	1.8%	<0.001	1.9 %	3.6%	2.0%	3.0%	<0.001
	ECMO	0.7%	0.3%	<0.001	0.3%	1.1%	0.4%	0.9%	<0.001
Invasive mechanical ventilation		49.1%	39.2%	<0.001	40.8%	56.4%	37.4%	54.6%	<0.001
Hemodialysis		3.2%	2.6%	<0.001	3.8%	2.6%	2.9%	3.4%	<0.001

Represented as percentage or mean ± standard deviation;

^apulmonary artery catheterization or right heart catheterization

Abbreviations: AMI: acute myocardial infarction; AVB: atrioventricular block; CS: cardiogenic shock; ECMO: extracorporeal membrane oxygenation; IABP: intra-aortic balloon pump; NSTEMI: non-ST-segment elevation myocardial infarction; pLVAD: percutaneous left ventricular assist device; STEMI: ST-segment elevation myocardial infarction

Among the 213,718 admissions with arrhythmias, the temporal trends of atrial arrhythmias (AF, AFlut, and SVT), ventricular arrhythmias (VT, VF) and AVB–related admissions are presented in Figure 2. There was a temporal increase of all arrhythmia sub-groups in the unadjusted analysis; however the adjusted analysis showed relatively stable trends of atrial and ventricular arrhythmias and decreasing trend in AVB. The cohort with ventricular arrhythmias on average had higher rates of ST-segment elevation myocardial infarction with cardiogenic shock (STEMI-CS), cardiac arrest, neurological failure, and mechanical circulatory support use (Table 2). PPM was implanted in 6,837 (1.6%) of the admissions and the temporal trends showed a relatively steady rate of implantation during the study period (Figure 2C).

Figure 2. Trends in the prevalence of atrial, ventricular and AVB arrhythmias in AMI-CS.

17-year unadjusted trends in the prevalence of atrial arrhythmias (A), ventricular arrhythmias (B), AVB and PPM (C); all p<0.001 for trend over time; D: Adjusted multivariate logistic regression for prevalence of atrial, ventricular and AVB arrhythmias temporal trends with 2000 as referent year; adjusted for age, sex, race, comorbidity, primary payer, socio-economic stratum, hospital characteristics, comorbidities, AMI type, acute organ failure, cardiac arrest, cardiac and non-cardiac procedures (p<0.001 for trend over time).

Abbreviations: AF: atrial fibrillation; AFlut: atrial flutter; AMI: acute myocardial infarction; AVB: atrio-ventricular block; CS: cardiogenic shock; PPM: permanent pacemaker; SVT: supraventricular tachycardia; VF: ventricular fibrillation; VT: ventricular tachycardia

The all-cause in-hospital mortality in admissions with arrhythmias was higher than those without (42.1% vs. 41.3%; OR 1.03 [95% CI 1.02–1.05]; p<0.001). There was a consistent decrease in in-hospital mortality across both categories during this 17-year study period (Figure 3). In a multivariable logistic regression for in-hospital mortality, the cohort arrhythmias had comparable mortality to those without (OR 1.01 [95% CI 0.99–1.03]; p=0.22) (Supplementary Table 2). The cohort with arrhythmias had longer hospital stay, higher hospitalization costs, and fewer discharges to home (Table 3).

Figure 3. Trends of in-hospital mortality in AMI-CS admissions with and without arrhythmias.

A: Unadjusted in-hospital mortality in AMI-CS by year of admission, stratified by arrhythmias (p<0.001 for trend over time); D: Adjusted multivariate logistic regression for in-hospital mortality temporal trends stratified by arrhythmias with 2000 as referent year; adjusted for age, sex, race, comorbidity, primary payer, socio-economic stratum, hospital characteristics, comorbidities, AMI type, acute organ failure, cardiac arrest, cardiac and non-cardiac procedures (p<0.001 for trend over time).

Abbreviations: AMI: acute myocardial infarction; CS: cardiogenic shock

Table 3.

Clinical outcomes of AMI-CS stratified by arrhythmias

Clinical Outcomes		AMI-CS cohort (N=420,319)			Arrhythmia cohort (N=213,718)
		Arrhythmia (N=213,718)	No Arrhythmias (N=206,601)	P	Atrial (N=72,264)	Ventricular (N=80,388)	AVB (N=18,123)	≥2 types (N=42,943)	P
In-hospital mortality		42.1%	41.3%	<0.001	43.0%	42.7%	38.7%	40.8%	<0.001
Length of stay (days)		9.1±9.9	7.4±8.7	<0.001	9.0±9.2	9.1±10.9	7.1±7.7	9.9±9.9	<0.001
Hospitalization costs (x1000 USD)		124±146	91±115	<0.001	107±135	134±156	101±110	142±156	<0.001
Disposition	Home	44.3%	46.8 %	<0.001	32.8%	52.2%	54.1%	44.2%	<0.001
	Transfer	11.5%	15.5%		12.4%	11.5%	10.8%	10.1%
	SNF	29.4 %	24.0%		37.5%	23.3%	22.2%	30.7%
	Home with HHC	14.3%	13.1%		16.9%	12.3%	12.6%	14.7%
	AMA	0.4%	0.6%		0.3%	0.7%	0.3%	0.3%

Represented as percentage or mean ± standard deviation

Abbreviations: AMA: against medical advice; AMI: acute myocardial infarction; AVB: atrio-ventricular block; CS: cardiogenic shock; HHC: home health care; SNF: skilled nursing facility; USD: United States Dollars

In the cohort with arrhythmias, the cohort with atrial (43.0%) and ventricular (42.7%) arrhythmias had higher in-hospital mortality compared to those with AVB (38.7%) and with more than one category of arrhythmias (40.8%), p<0.001. In the cohort with arrhythmias, older age, female sex, lack of insurance, non-white race, higher comorbidity, presence of acute organ failure, cardiac arrest, and non-cardiac organ support were predictive of higher in-hospital mortality (Figure 4).

Figure 4. Adjusted odds ratio for in-hospital mortality in AMI admissions with arrhythmias.

Odds ratio with 95% confidence interval using multivariable regression analysis for prediction of in-hospital mortality; for cohorts with multiple categories (i.e. age, sex, race, primary payer, CCI, SES, AMI type) the first category was used as reference category for calculating odds ratios

Abbreviations: AMI: acute myocardial infarction; CCI: Charlson comorbidity index; CS: cardiogenic shock; IHDM: invasive hemodynamic monitoring; IMV: invasive mechanical ventilation; MCS: mechanical circulatory support; NSTEMI: non-ST-elevation myocardial infarction; PCI: percutaneous coronary intervention; SES: socio-economic status; STEMI: ST-elevation myocardial infarction

DISCUSSION

In this nationally representative study of over 400,000 AMI-CS admissions, nearly half the admissions had arrhythmias, with AF, VT and VF being the most commonly noted ones. During this 17-year study period, there was a steady temporal trend across all arrhythmic categories after adjusting for comorbidity and illness severity. Though the cohort with arrhythmias had longer hospital stay and greater resource utilization, they had comparable in-hospital mortality to the cohort without arrhythmias. The cohort with arrhythmias expectedly had greater acuity of illness, and higher use of cardiac and non-cardiac organ support.

Previous studies looking at the impact of arrhythmias in the AMI-CS population have limited their evaluation to a single type of arrhythmia.^7,39 Sub-studies from large clinical trials in the AMI-CS population have looked at the prognostic impact of AF in AMI-CS,³⁹ and others have evaluated incidence and burden of ventricular arrhythmias in this population.⁷ Unlike these studies, we evaluated the prognostic impact of all types of arrhythmias among in-hospital admissions of AMI-CS. We found higher rates and a relatively stable trend for ventricular arrhythmias in contrast to other contemporary studies. A single-center study evaluating trends over 25 years reported a decline in the incidence of VT and VF from 1986 to 2011.⁷ In comparison to this prior study, our cohort was a national sample, included only AMI-CS patients and spanned a greater time period during which early revascularization techniques and vasoactive medications were increasingly used for the AMI-CS population. Therefore it is possible to surmise that arrhythmias associated with reperfusion and use of vasopressors could have contributed to the higher and stable incidence rates of ventricular arrhythmias.⁹ A decline in the incidence of atrioventricular block is in line with evidence from the reperfusion era.⁴⁰

In our study STEMI-CS, acute organ failure, and use of circulatory support devices were independently associated with arrhythmias. Patients with STEMI have a higher likelihood of developing arrhythmias, especially ventricular arrhythmias due to the acuity of onset, larger myocardial involvement and higher rates of coronary revascularization.⁴¹ We also noted a significant percentage of acute organ failure in this population with a greater incidence in the arrhythmia cohort.¹¹ Arrhythmias rapidly alter atrial and ventricular hemodynamics affecting loading conditions thereby inducing further damage to an already compromised cardiac status in AMI-CS and worsening end-organ perfusion.¹¹ Therefore acute organ failure bears a bidirectional relationship to arrhythmias in AMI-CS. The use of contemporary mechanical circulatory support devices to provide higher hemodynamic support and reduce transmyocardial strain,^{10,12,14,17–19} could result in electrolyte imbalances in the myocardium and mechanical irritation potentially increasing incidence of arrhythmias in patients using these devices.⁴² In addition, patients with AMI-CS are subject to a greater utilization of inotropes and vasoactive medications that potentially precipitate arrhythmias.^12,26

Similar to our results, studies from the IABP-SHOCK (Intraaortic Balloon Pump in Cardiogenic Shock) trial and CULPRIT-SHOCK (Culprit Lesion Only PCI versus Multivessel PCI in Cardiogenic Shock) trial also reported no association of AF with mortality.^43,44 Nonetheless, results from the Bremen STEMI registry showed that AF was associated with a higher one-year mortality in STEMI-CS.⁴⁵ The Bremen STEMI registry had patients that were less sick and less likely to have utilized vasoactive medications, circulatory support devices compared to former studies, which could explain the differences. Ventricular arrhythmias, both VT and VF were also found to not have any impact on the mortality in AMI-CS.⁷ The increase in understanding of the pathophysiology associated with AMI-CS and the advancement of care for these patients, early identification of arrhythmias and prompt access to defibrillation has likely resulted in earlier termination of malignant arrhythmias.

This study has several limitations, some of which are inherent to the analysis of a large administrative database. The HCUP-NIS attempts to mitigate potential errors by using internal and external quality control measures. The lack of information on the duration of arrhythmia, management strategies including rate control, defibrillation and use of anticoagulation limit the generalized ability of our findings. Though we have previously demonstrated that admission with AMI-CS have become sicker over time,¹¹ it is possible that the increase in prevalence of arrhythmias may be attributable to improvements in recognition and coding practices.

In conclusion, development of cardiac arrhythmias during admission for AMI-CS is a marker of higher illness severity and is associated with worse acute organ failure. Though the cohort with arrhythmias did not have higher in-hospital mortality, they had greater resource utilization.