Objectives. There is renewed interest in intra-aortic balloon pump (IABP) use in chronic systolic heart failure (HF) patients with acute decompensation and cardiogenic shock (CS). We sought to identify predictors of early IABP response to guide optimal use in this population. Methods. We retrospectively analyzed records of chronic systolic HF patients presenting to our center between 2011-2018 with acute decompensated HF who received IABP for CS. An IABP responder was defined as having both an early cardiac output (CO) increase and mean pulmonary artery pressure (MPAP) decrease above the cohort median values. Results. During this period, a total of 218 chronic systolic HF patients received IABP for acute decompensation with CS. The average CO increase was 0.57 ± 0.85 L/min and MPAP reduction was 5.1 ± 7.6 mm Hg. Fifty-six patients (25.7%) were identified as IABP responders, with mean CO increase of 1.21 ± 0.87 L/min and MPAP reduction of 12.1 ± 5.9 mm Hg. Systemic vascular resistance (SVR) >1300 dynes/sec/cm−5 (odds ratio [OR], 5.04; 95% confidence interval [CI], 1.86-13.6; P<.01) and moderate-severe mitral regurgitation (OR, 2.42; 95% CI, 1.25-4.66; P<.01) predicted robust hemodynamic response. Conclusions. A subset of chronic systolic HF patients had robust hemodynamic response to IABP with significant CO augmentation and MPAP reduction. Higher SVR and moderate-severe mitral regurgitation predicted early hemodynamic response to IABP.
J INVASIVE CARDIOL 2021;33(4):E275-E280. Epub 2021 March 12.
Key words: cardiogenic shock, heart failure, intra-aortic balloon pump, mechanical circulatory support
Cardiogenic shock (CS) is broadly defined as a state of insufficient cardiac output (CO) with clinical and biochemical evidence of tissue hypoperfusion. While there have been recent advances in therapy for patients with CS, in-hospital mortality can be as high as 50%-60% depending upon the etiology, and the prevalence of patients admitted to intensive care units with CS continues to increase.1-3 CS exists as a spectrum of phenotypes from multiple primary cardiac etiologies. Historically, management of CS includes vasoactive infusions and mechanical circulatory support devices. The intra-aortic balloon pump (IABP) has been the most widely used percutaneous circulatory support device to have been implemented in CS and currently remains the most commonly utilized, likely in part due to its ease of implantation and low complication rate.4 Nonetheless, despite decades of IABP use, its clinical indications in CS remain poorly defined. Only recently, the neutral results of the landmark IABP-SHOCK II trial have led to a shift away from routine IABP use in cases of CS complicating acute myocardial infarction (AMI), and subsequently European guidelines have downgraded IABP use in this group to a class IIIB recommendation.5,6
Although AMI remains the most well-studied cause of CS, acute decompensation of chronic systolic heart failure (HF) is estimated to represent up to 30% of CS cases,7,8 and this proportion will only continue to increase. It is estimated that by 2030, more than 8 million people (1 in 33) in the United States will have HF.9 Few studies have examined the efficacy of IABP in non-AMI patients, although there is renewed interest in utilization of counterpulsation in this patient population, particularly as a bridge to durable left ventricular assist device (LVAD) or heart transplant.10-14 We recently reported promising results with IABP support in chronic HF patients with evidence of CS and highlighted a subset of this population exhibiting robust hemodynamic response to counterpulsation.15 Long-term survival in this population often depends on overall candidacy for heart replacement therapies (HRTs) such as durable LVAD or heart transplant; therefore, this outcome may not accurately reflect the specific effects of counterpulsation therapy. As such, the objective of this study was to expand our prior dataset of IABP patients with acute decompensation of chronic systolic HF complicated by CS to determine predictors of early hemodynamic response to IABP therapy.
Study population. Patients who presented to New York Presbyterian-Columbia University Irving Medical Center from January 2011 to September 2018 and underwent IABP placement for acute on chronic systolic HF with evidence of CS were considered for this study. Electronic medical records were retrospectively reviewed for eligibility. All patients were over 18 years old and had documented systolic HF with left ventricular ejection fraction <40% by transthoracic echocardiogram. Clinically, patients were either stage C or early stage D according to Society of Cardiovascular Angiography and Interventions (SCAI) shock classification. Hemodynamic evidence of CS was obtained via pulmonary artery (PA) catheter-derived data in conjunction with systolic blood pressure <90 mm Hg or need for a vasopressor/inotrope to maintain this blood pressure. Patients were excluded from the study if IABP placement was for any indication other than acute on chronic systolic HF (eg, AMI, fulminant myocarditis); if there was another mechanical circulatory support device prior to initiation of IABP therapy (eg, venoarterial extracorporeal membrane oxygenation [VA-ECMO] used concurrently); and if there were incomplete hemodynamic data or hemodynamics inconsistent with CS. The study was approved by the institutional review board of Columbia University.
Data collection. Medical records were reviewed for data collection, which included demographic data, baseline echocardiogram results obtained at admission, and pertinent laboratory data, such as creatinine and lactate. Hemodynamic measurements by PA catheterization that were obtained immediately prior to and at the earliest measurement after IABP insertion were used to assess hemodynamic IABP response. Postdevice insertion hemodynamics were collected either while the patient was in the cardiac catheterization laboratory or while the patient was in the intensive care unit if the IABP was placed at bedside, with a time interval requirement between predevice and postdevice hemodynamics <12 hours. CO and cardiac index (CI) were calculated using the Fick method.
Outcomes of interest. The primary outcome was early hemodynamic response to IABP therapy. An IABP responder was defined as having an increase in CO and a decrease in mean pulmonary artery pressure (MPAP) above the median values of the cohort at the first hemodynamic assessment following insertion. This definition was selected based on a preliminary analysis of the cohort, which revealed that reduction in intracardiac filling pressures correlated better with survival or the need for addition of another short-term circulatory support device than change in CO. Secondary outcomes included death and need for escalation to another mechanical circulatory support device, as well as successful bridge to HRT and hospital discharge without the requirement for another short-term or long-term circulatory support device.
Statistical analysis. Continuous variables were analyzed using paired Student’s t-test or rank-sum tests, where appropriate. Categorical variables were analyzed using Chi-square tests. Continuous variables are reported as means ± standard deviations, while categorical variables are reported as frequencies (%). Logistic regression was used to identify clinical predictors of hemodynamic response. Multivariable logistic regression was performed on variables with P-value <.20 in univariable analysis with continuous variables dichotomized. Collinear variables were excluded from multivariable analysis. P-values <.05 were considered statistically significant. All analyses were performed using STATA, version 15.0 (StataCorp LP).
A total of 1070 patients underwent IABP insertion between 2011 and 2018, of which 218 met the study inclusion criteria. The primary indications for IABP insertion were ischemia including an acute coronary syndrome or high-risk coronary anatomy in the perirevascularization period (602 patients; 56.3%); acute HF such as following cardiac arrest, acute valvular dysfunction, or fulminant myocarditis (151 patients; 14.1%); and acute on chronic systolic HF (317 patients, 29.6%). Of the 317 patients who underwent IABP insertion for acute on chronic systolic HF, 99 were excluded due to prior heart transplant, concomitant or preceding mechanical circulatory support device, incomplete charting of hemodynamic data, or preimplant hemodynamics inconsistent with CS. The final data analysis cohort consisted of 218 patients.
Baseline characteristics. The baseline characteristics of the study cohort grouped by IABP response are depicted in Table 1. The mean age of the cohort was 59.4 ± 13.4 years, 79.8% were men, and 38.5% had a history of chronic ischemic cardiomyopathy (ICM). The mean CI was 1.59 ± 0.39 L/min/m2, mean creatinine was 1.96 ± 1.15 mg/dL, and mean lactate was 2.53 ± 2.67 mg/dL. Compared with IABP non-responders, IABP responders were less likely to have a history of ICM (26.8% vs 42.6%; P=.03) and more likely to have severe mitral regurgitation (MR; 30.4% vs 17.3%; P=.04), elevated preimplant MPAP (43.2 ± 10.2 mm Hg vs 35.3 ± 8.7 mm Hg; P<.001), and lower CI (1.48 ± 0.36 L/min/m2 vs 1.62 ± 0.39 L/min/m2; P=.01). There was no significant difference between groups with regard to number of preimplant inotrope or vasopressor support (Table 1).
Clinical outcomes. Among the 218 patients in the final cohort, 19 patients (8.7%) were escalated to either VA-ECMO or short-term ventricular assist device (ie, CentriMag; Abbott). A total of 160 patients (73.4%) were either bridged to HRT (132 patients) or discharged without requiring another short- or long-term mechanical circulatory support device (28 patients). In the escalation cohort, 5 of the 12 patients who were bridged to durable LVAD died in the hospital. Among the 132 patients bridged to HRT without need for another short-term device, 7 died in the hospital. Thirty-nine patients (17.9%) died without escalation.
Early hemodynamic response. The average hemodynamic changes following IABP insertion for the entire cohort are consistent with previous studies that have assessed IABP hemodynamic response.16 Overall, there was a mean CO increase of 0.57 ± 0.85 L/min and a MPAP reduction of 5.1 ± 7.6 mm Hg. Mean CI increased by 0.29 ± 0.42 L/min/m2 (P<.001), while average MAP minimally decreased by 1.6 ± 13.1 mm Hg (P=.08). There was no significant difference in number of vasoactive infusions post device insertion.
Fifty-six patients (25.7%) in the entire cohort were identified as IABP responders, predefined as demonstrating both a CO increase and a MPAP reduction above the median values of the entire cohort. IABP responders had a mean CO increase of 1.21 ± 0.87 L/min and a MPAP reduction of 12.1 ± 5.9 mm Hg (Figures 1 and 2).
IABP responders had additional differences in postdevice insertion hemodynamics compared with IABP non-responders; specifically, they were more likely to have greater reduction in systemic vascular resistance (SVR) (-527 ± 431 dynes/sec/cm-5 vs -143 ± 458 dynes/sec/cm-5; P<.001). IABP responders also consistently demonstrated greater improvement in hemodynamics after adjusting for patient size, as represented by the CI and cardiac power index. There were no significant between-group differences with regard to change in MAP and number of vasoactive infusions (Table 2).
Predictors of hemodynamic response. In univariable analysis, predictors of favorable IABP response were higher heart rate (odds ratio [OR], 1.02; 95% confidence interval [95% CI], 1.00-1.03; P=.04), higher SVR (OR, 1.00; 95% CI, 1.00-1.00; P=.04), and presence of moderate or severe mitral regurgitation (MR) (OR, 2.32; 95% CI, 1.22-4.36; P<.01). Multivariable logistic regression identified SVR >1300 dynes/sec/cm-5 (OR, 5.04; 95% CI, 1.86-13.6; P<.01) and the presence of moderate or severe MR (OR, 2.42; 95% CI, 1.25-4.66; P<.01) as independent predictors of early hemodynamic response to IABP therapy (Table 3).
Guidelines on the use of IABP in CS in the non-AMI setting remain poorly defined. To our knowledge, this is the largest study to date examining the hemodynamic response to aortic counterpulsation in chronic HF patients with acute decompensation complicated by CS. Similar to the results from our prior work,15 data from this expanded cohort demonstrate that a subgroup of patients has robust early hemodynamic response to IABP therapy with substantial improvements in both CO augmentation and MPAP reduction. We identified key variables that predicted robust hemodynamic improvements, thus helping to describe the profile of the “super responder” to aortic counterpulsation therapy.
Given the medical complexities of our study cohort, we wished to focus on predictors of hemodynamic response to IABP therapy rather than clinical outcomes such as mortality and the proportion of patients bridged to HRT. Clinical outcomes in an advanced HF population often depend on the individual patient’s overall candidacy for therapies such as HRT, which does not necessarily correlate with hemodynamic response to IABP. Indeed, many of the previous studies evaluating IABP use in non-AMI patients noted lack of strict correlation between hemodynamic response and clinical stabilization and/or outcomes.10-12,17
Our prior work has demonstrated that the rate of complications with IABP in this patient population is low.15 Identification of the patient who will have a robust early hemodynamic response to aortic counterpulsation allows the clinician to select a temporary device that may provide adequate circulatory support to the patient in CS and is a lower-risk option compared with other temporary support devices used for this population. As a corollary, the clinician may choose an alternative circulatory support device to the IABP (eg, percutaneous LVAD or ECMO) for the patient who is not expected to have a robust response to aortic counterpulsation. Refining patient selection for this technology will become increasingly important with the advent of a durable aortic counterpulsation device in investigational phases and the increasing use of the IABP to bridge patients to cardiac transplantation.18,19
The criteria for IABP responder in this current study differ from that of our first study, which identified the top quartile of patients with robust CO augmentation as IABP “super responders.”15 In the present study, we included MPAP reduction and CO augmentation in our definition of IABP responders in light of an observation that MPAP reduction correlated better with overall survival than augmentation of CO. This definition also highlights the role of IABP counterpulsation as a primary afterload-reducing intervention, and as such, the increase in CO stems from a more optimal loading condition for the left ventricle. Therefore, we felt this classification of IABP responder fit well with observations in other HF populations and better matched the anticipated hemodynamic effects of the IABP. For example, in an analysis of the ESCAPE trial, intracardiac pressures were more predictive of overall outcomes in HF patients than CO measured by PA catheter.20,21
Our study identified higher SVR and the presence of moderate or severe MR as key predictors of early hemodynamic response to IABP therapy. These findings correspond with the mechanism of action of the device, namely afterload reduction. The patient with higher SVR and more MR would be expected to have greater forward improvement in response to an afterload-reducing intervention. However, it is notable that patients benefited from afterload reduction even when the SVR was not considered significantly elevated. While afterload reduction has been a mainstay in the management of decompensated HF, it is notable that the change in MAP was minimal with IABP. In other words, counterpulsation was capable of augmenting CO by reducing afterload without substantially lowering MAP. Such an intervention is optimal for the patient with relative hypotension at presentation. In this manner, the benefit of the device is similar to that achieved with intravenous vasodilator therapy,22,23 although the clinician may be more inclined to use the device for the hypotensive patient because of its minimal effect on MAP.
Lastly, it is important to recognize that many of the patients who were not classified as IABP responders still had overall hemodynamic benefit from the device, with an increase in CO and a reduction in MPAP. Many of these patients were sufficiently stabilized with IABP to be bridged to either durable LVAD implantation or cardiac transplantation. The goal of our study is not to suggest pre-emptive initiation of a more powerful (and potentially higher-risk) mechanical circulatory support device in patients not identified as “responders.” Instead, the results of this study should be used to help identify those patients who might have an early robust hemodynamic response to IABP therapy, particularly in light of the emerging role of IABP in advanced HF either as a bridge to HRT or as a destination device for selected patients.24,25
Study limitations. Our study has several important limitations. First, it is a single-center, retrospective study limited to a specific patient population and a specific pattern of clinical practice where unmeasured variables could confound these findings. Second, there was no control group included in the study, which confers possible selection bias. Additionally, escalation of therapy to a more advanced mechanical circulatory support device was performed according to clinical judgment. Third, while this is the largest in-depth study evaluating the hemodynamic effects of IABP therapy in patients with advanced HF, not all patients had complete echocardiographic and laboratory data. Fourth, patients with severe refractory CS (SCAI stage E) who were initially stabilized with a more powerful device from presentation were not included in the study cohort. We focused only on patients with chronic HF, and predictors of response may differ for AMI-related CS.26 Finally, this study did not assess predictors of clinical outcomes such as mortality, need for device escalation, and duration of IABP therapy. However, as previously discussed, we purposely focused on predictors of hemodynamic response given the complex variables that affect clinical outcomes in this patient population.
Overall, IABP insertion in patients with acute decompensation of chronic systolic HF complicated by CS provided a modest increase in CO and reduction in MPAP without significantly affecting MAP. A subset of chronic systolic HF patients had a robust response to IABP therapy with both substantial CO augmentation and MPAP reduction. Higher SVR and the presence of moderate or severe MR were identified as predictors of early hemodynamic response following device insertion. These parameters may be used to identify patients who will be well stabilized by aortic counterpulsation instead of a more powerful (but higher-risk) device.
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From the 1Division of Cardiology, Department of Medicine and 2Cardiothoracic Surgery, Department of Surgery, New York Presbyterian-Columbia University Irving Medical Center, New York, New York; 3Division of Cardiology, Department of Medicine, The Mount Sinai Hospital, New York, New York; and 4the Division of Cardiology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Colombo reports grant support and non-compensated advisor to Abbott Vascular. Dr Garan reports research support from Abbott Vascular; non-compensated advisor to Abiomed. Dr Pinto reports personal fees from NuPulseCV and Abiomed. Dr Kirtane reports grants and non-financial support from Medtronic, Abbott Vascular/St. Jude, Boston Scientific, Abiomed, Siemens/Corindus, Philips/Spectranetics, ReCor Medical, Cardiovascular Systems, Inc; grant support from CathWorks; non-financial support from Chiesi, Opsens, Zoll, and Regeneron. The remaining authors report no conflicts of interest regarding the content herein.
Manuscript accepted July 27, 2020.
Address for correspondence: A. Reshad Garan, MD, MS, Section Chief, Advanced Heart Failure and Mechanical Circulatory Support, Beth Israel Deaconess Medical Center, 185 Pilgrim Road, Boston, MA 02215. Email: email@example.com