Abstract
Aims
Despite significant morbidity and mortality, recent advances in cardiogenic shock (CS) management have been associated with increased survival. However, little is known regarding the management of patients who survive CS with heart failure (HF) with reduced left ventricular ejection fraction (LVEF, HFrEF), and the utilization of guideline‐directed medical therapy (GDMT) in these patients has not been well described. To fill this gap, we investigated the use of GDMT during an admission for CS and short‐term outcomes using the Inova single‐centre shock registry.
Methods
We investigated the implementation of GDMT for patients who survived an admission for CS with HFrEF using data from our single‐centre shock registry from January 2017 to December 2019. Baseline characteristics, discharge clinical status, data on GDMT utilization and 30 day, 6 month and 12 month patient outcomes were collected by retrospective chart review.
Results
Among 520 patients hospitalized for CS during the study period, 185 (35.6%) had HFrEF upon survival to discharge. The median age was 64 years [interquartile range (IQR) 56, 70], 72% (n = 133) were male, 22% (n = 40) were Black and 7% (n = 12) were Hispanic. Forty‐one per cent of patients (n = 76) presented with shock related to acute myocardial infarction (AMI), while 59% (n = 109) had HF‐related CS (HF‐CS). The median length of hospital stay was 12 days (IQR 7, 18). At discharge, the proportions of patients on beta‐blockers, angiotensin‐converting enzyme inhibitors (ACEis)/angiotensin receptor blockers (ARBs)/angiotensin receptor/neprilysin inhibitors (ARNIs) and mineralocorticoid receptor antagonists (MRAs) were 78% (n = 144), 58% (n = 107) and 55% (n = 101), respectively. Utilization of three‐drug GDMT was 33.0% (n = 61). Ten per cent of CS survivors with HFrEF (n = 19) were not prescribed any component of GDMT at discharge. Multivariable logistic regression adjusted for baseline GDMT use revealed that patients with lower LVEF and those who transferred to our centre from an outside hospital were more likely to experience GDMT addition (P < 0.05). Patients prescribed at least one additional class of GDMT during admission had higher odds of 6 month and 1 year survival (P < 0.01): On average, 6 month survival odds were 7.1 times greater [confidence interval (CI) 1.9, 28.5] and 1 year survival odds were 6.0 times greater than those who did not have at least one GDMT added (CI 1.9, 20.5).
Conclusions
Most patients who survived CS admission with HFrEF in this single‐centre CS registry were not prescribed all classes or goal doses of GDMT at hospital discharge. These findings highlight an urgent need to augment multidisciplinary efforts to enhance the post‐discharge medical management and outcomes of patients who survive CS with HFrEF.
Keywords: cardiogenic shock, critical care, guideline‐directed medical therapy, heart failure
Background
Cardiogenic shock (CS) is a leading cause of admission to cardiac intensive care units (CICUs), with a short‐term mortality rate ranging from 35% to 50%. 1 , 2 , 3 , 4 The incidence of CS continues to increase, with heart failure (HF)‐related CS (HF‐CS) comprising the largest proportion of CS cases. 5 , 6 Recently, multidisciplinary, standardized, team‐based approaches to the management of CS have been associated with reductions in short‐term mortality, resulting in a growing cohort of CS survivors who must be appropriately transitioned to outpatient management, including guideline‐directed medical therapy (GDMT). 7 , 8 , 9
The 2022 American Heart Association (AHA)/American College of Cardiology (ACC)/Heart Failure Society of America (HFSA) Guidelines for the Management of Heart Failure recommend four classes of medications for patients with chronic HF with reduced left ventricular ejection fraction (LVEF) ≤ 40% (HFrEF). 10 , 11 These include beta‐adrenergic receptor antagonists (‘beta‐blockers’ or BBs) effective for HF, angiotensin‐converting enzyme inhibitors (ACEis), angiotensin receptor blockers (ARBs), angiotensin receptor/neprilysin inhibitors (ARNIs), mineralocorticoid receptor antagonists (MRAs) and sodium/glucose cotransporter‐2 inhibitors (SGLT2is), each of which significantly reduces the risk of mortality and hospitalizations for patients with HFrEF. 12 Despite these recommendations, contemporary registries and clinical trial data demonstrate under‐utilization of these life‐prolonging medications for outpatients and inpatients with HFrEF. 13 , 14 , 15
The utilization of GDMT for patients who survive admission for CS with HFrEF has not been well described. To fill this gap, we investigated the use of GDMT during an admission for CS and short‐term outcomes using the Inova single‐centre shock registry.
Methods
Patients admitted to the Inova quaternary care centre with a diagnosis of CS between 3 January 2017 and 31 December 2019 were prospectively identified and retrospectively reviewed. The shock team's inclusion and exclusion criteria, composition and standardized, team‐based protocol have been described previously. 16 We included patients who were hospitalized with a diagnosis of CS due to either acute myocardial infarction (AMI) or HF. Briefly, clinical criteria for CS diagnosis included a systolic blood pressure (SBP) < 90 mmHg for ≥30 min (or vasopressors to maintain SBP ≥ 90 mmHg) and evidence of end‐organ hypoperfusion. 17 We excluded patients who expired, transitioned to hospice care, transferred to another health system, left against medical advice, underwent a heart transplant or durable left ventricular assist device (LVAD) placement during admission or had an LVEF > 40%.
This study was approved by the Inova Health System's local institutional review board. Demographic, co‐morbidities at presentation, clinical characteristics (including LVEF and heart rhythm during admission) and haemodynamic parameters were manually collected via retrospective chart review of all available electronic medical records. In addition, transfer status and clinical outcomes, including discharge status (laboratory values and vital signs), clinical management decisions (including HF medication prescriptions and a documented plan for follow‐up with an HF cardiologist) and clinical outcomes (including readmission within 30 days and 30 day, 6 month and 1 year mortality), were collected.
Using methodology developed by the Heart Failure Collaboratory (HFC), an ‘optimal medical therapy (OMT) score’ was calculated for each patient at the time of discharge. 18 The frequency and dosage of each of the three available classes of GDMT medications were captured for each patient, and point values were assigned using the maximum recommended daily doses outlined in the 2017 HF guidelines, the most current guidelines at the time of these encounters. 10 Because the first SGLT2i was approved for HFrEF by regulators in May 2020, after the period of study, SGLT2i use was not included in this analysis.
The maximum OMT score was 7 points. The OMT scoring methodology was as follows (Figure 1):
BBs: Patients were assigned 0 points if not on a BB, 1 point if on <50% of the maximum daily dose and 2 points for ≥50% of the maximum daily dose.
ACEis/ARBs/ARNIs: Patients were assigned 0 points if not on an ACEi/ARB/ARNI, 1 point if on <50% of the maximum daily dose, 2 points for ≥50% of the maximum daily dose and 3 points for sacubitril/valsartan (any dose).
MRAs: Patients were assigned 0 points if not on an MRA or 2 points for being on any dose of MRA.
Figure 1.
Point assignments for various doses of guideline‐directed medical therapies (GDMTs) used in the calculation of the ‘optimal medical therapy score’, developed by the Heart Failure Collaboratory and based off the maximum daily doses of GDMT from the 2017 heart failure (HF) management guidelines. 10 , 18 Because sodium/glucose cotransporter‐2 inhibitors were not yet a part of the HF recommendations, they were not included in this analysis. ACEi, angiotensin‐converting enzyme inhibitor; ARB, angiotensin receptor blocker; ARNI, angiotensin receptor/neprilysin inhibitor; MRA, mineralocorticoid receptor antagonist.
A discharge OMT score of 6 or 7 indicated a patient who was discharged on any dose of MRA, ≥50% maximum dose of BBs and an ARNI or ≥50% maximum daily dose of an ACEi or ARB. Laboratory and clinical exclusion criteria used in contemporary clinical trials of BBs, ARNIs and MRAs were collected at discharge to identify overt GDMT contraindications.
Summary statistics are presented as medians [quartiles (Q1, Q3)] or frequencies (percentage). We compared patients who experienced the addition of at least one class of GDMT to those who did not via the Kruskal–Wallis test for medians and Fisher's exact test for proportions. Multivariable logistic regression models were constructed to determine the potential association between clinical and baseline variables and the addition of one or more classes of GDMT at discharge, while adjusting for baseline use of GDMT. 19 Results were summarized using forest plots of the calculated odds ratios.
Multivariable logistic regression models were also used to describe the relationship between HF medication management, readmission within 30 days and mortality at 6 months and 1 year. Models were adjusted for key clinical and demographic variables including patient sex, age, length of stay, outside transfer status, diabetes, discharge status (SBP, sodium, log creatinine and LVEF), mitral regurgitation and number of GDMT classes at admission. Variance inflation factors (VIFs) were computed to examine multicollinearity in clinical variables. 20 The VIF is a metric used to assess the magnitude of multicollinearity, or the correlation between the covariates, in a multivariate regression model. High multicollinearity can result in inflated standard errors and difficulty testing the statistical significance of the estimated regression coefficients. VIF values < 4.0 suggested that multicollinearity was not significant in this study. All covariates in our models had VIF values under 2. All analyses were performed using R (4.0.2) software for statistical computing and RStudio™ Version 2022.12.0 (Posit, PBC).
Results
Cohort selection and baseline demographics
The cohort included 520 consecutive patients admitted for CS during the study period. Patients who expired (n = 157), had an LVEF > 40% (n = 79) at discharge, underwent durable LVAD placement (n = 31) or heart transplantation (n = 28), transitioned to hospice (n = 29), transferred to another health system (n = 10) or left against medical advice (n = 1) were excluded; the primary analysis included the remaining patients alive with HFrEF that could potentially qualify for GDMT use (Figure 2).
Figure 2.
Consort diagram of patient selection for this analysis. CS, cardiogenic shock; HFrEF, heart failure with reduced left ventricular ejection fraction; LVAD, left ventricular assist device; LVEF, left ventricular ejection fraction.
Table 1 outlines the baseline characteristics and clinical presentation of the 185 patients who survived CS with HFrEF. The median age was 64 years [interquartile range (IQR) 56, 70], 72% (n = 133) were men, 43% (n = 80) were non‐White patients [including 22% (n = 40) Black patients], 41% (n = 75) had diabetes mellitus and 55% (n = 101) were transferred to this centre from an outside hospital. Forty‐one per cent (n = 76) presented with shock related to AMI‐CS, while 59% (n = 109) had HF‐CS. Baseline clinical characteristics included median creatinine of 1.4 mg/dL (IQR 1.0, 1.8) and lactate of 2.2 mg/dL (IQR 1.4, 3.7). CS severity at presentation by the Society for Cardiovascular Angiography and Intervention (SCAI) criteria included 65% (n = 120) stage C, 30% (n = 56) stage D and 5% (n = 9) stage E CS. 21
Table 1.
Demographics and baseline characteristics for 185 survivors of CS with LVEF ≤ 40%, stratified by GDMT addition during admission.
| Demographics and baseline characteristics | Overall (n = 185) | GDMT classes added ≥1 (n = 108) | GDMT classes added <1 (n = 77) | P‐value |
|---|---|---|---|---|
| Age, years | 64 (56, 70) | 64.5 (56, 70) | 63 (57, 69) | 0.96 |
| Male | 133 (71.9%) | 74 (68.5%) | 59 (76.6%) | 0.25 |
| Race | ||||
| White | 96 (51.2%) | 57 (52.7%) | 39 (50.6%) | 0.52 |
| Black | 40 (21.6%) | 23 (21.3%) | 17 (22.1%) | |
| Hispanic | 12 (6.5%) | 5 (4.6%) | 7 (9.1%) | |
| Asian | 28 (15.1%) | 19 (17.6%) | 9 (11.7%) | |
| BMI, kg/m2 | 28.4 (24.4, 32.5) | 28.2 (24.3, 32.3) | 28.6 (24.4, 33.3) | 0.73 |
| Diabetes mellitus | 75 (40.5%) | 39 (36.1%) | 36 (46.8%) | 0.17 |
| AMI‐CS | 76 (41.1%) | 51 (47.2%) | 25 (32.5%) | 0.05 |
| HF‐CS | 109 (58.9%) | 57 (52.8%) | 52 (67.5%) | |
| Transferred from another hospital? | 101 (54.6%) | 71 (65.7%) | 30 (39.0%) | <0.01 |
| Baseline creatinine, mg/dL | 1.4 (1.0, 1.8) | 1.3 (1.0, 1.7) | 1.4 (1.0, 2.0) | 0.49 |
| Baseline lactate, mg/dL | 2.2 (1.4, 3.7) | 2.1 (1.4, 3.2) | 2.4 (1.3, 4.2) | 0.50 |
| Baseline SCAI classification | ||||
| C | 120 (64.9%) | 73 (67.6%) | 47 (61.0%) | 0.21 |
| D | 56 (30.3%) | 28 (25.9%) | 28 (36.4%) | |
| E | 9 (4.9%) | 7 (6.5%) | 2 (2.6%) | |
Note: The values presented are frequency (percentage) or median (Q1, Q3), where appropriate.
Abbreviations: AMI, acute myocardial infarction; BMI, body mass index; CS, cardiogenic shock; GDMT, guideline‐directed medical therapy; HF, heart failure; LVEF, left ventricular ejection fraction; SCAI, Society for Cardiovascular Angiography and Intervention.
Discharge characteristics and GDMT prescription rates
The median length of hospital stay was 12 days (IQR 7, 18). At the time of discharge, the included patients had an LVEF of 20% (IQR 15, 30) and creatinine of 1.2 mg/dL (IQR 0.9, 1.7). The median heart rate (HR) was 82 b.p.m. (IQR 72, 93), with an SBP of 106 mmHg (IQR 98, 118). Echocardiography documented mitral regurgitation worse than ‘mild’ in 37% of patients (n = 69); 67% (n = 123) were in sinus rhythm on their most recent electrocardiogram, while 14% (n = 26) were in atrial fibrillation or flutter (Table 2). The median time between the most recent echocardiogram and discharge was 9 days (IQR 6, 14), and the median time between discharge and a 12‐lead electrocardiogram was 6 days (IQR 3, 11).
Table 2.
Discharge clinical characteristics for 185 survivors of CS with LVEF ≤ 40%, stratified by GDMT class addition during admission.
| Discharge clinical characteristics | Overall (n = 185) | GDMT classes added ≥1 (n = 108) | GDMT classes added <1 (n = 77) | P‐value |
|---|---|---|---|---|
| Length of stay (days) | 12 (7, 18) | 12 (7, 18) | 12 (7, 20) | 0.92 |
| LVEF, % | 20 (15, 30) | 20 (15, 30) | 20 (15, 30) | 0.56 |
| Mitral regurgitation? (Worse than mild) | 69 (37.4%) | 43 (39.8%) | 26 (33.8%) | 0.54 |
| Serum creatinine, mg/dL | 1.2 (0.9, 1.7) | 1.1 (0.8, 1.5) | 1.3 (1.0, 1.9) | <0.01 |
| Serum sodium, mEq/L | 136 (133, 138) | 136 (133, 138) | 135 (133, 137) | 0.04 |
| BUN, mg/dL | 25.0 (17.0, 37.0) | 23.5 (16.0, 33.0) | 27.0 (18.0, 41.0) | 0.04 |
| Haemoglobin, g/dL | 10.7 (9.1, 12.6) | 11.0 (9.2, 11.1) | 10.7 (9.0, 12.2) | 0.39 |
| Heart rate, b.p.m. | 82 (72, 93) | 84 (72, 94) | 80 (72, 89) | 0.28 |
| SBP (mmHg) | 106 (98, 118) | 106 (97.0, 115.5) | 106 (99, 123) | 0.39 |
| DBP (mmHg) | 64 (58, 70) | 63.5 (58.0, 70.0) | 64 (59, 69) | 0.76 |
| Mean arterial pressure (mmHg) | 78.3 (72.7, 84.0) | 78.3 (72.3, 83.8) | 78 (73.7, 85.3) | 0.40 |
| Heart rhythm | <0.01 | |||
| Sinus | 123 (66.5%) | 82 (75.9%) | 41 (53.2%) | |
| Atrial fibrillation or flutter | 26 (14.1%) | 15 (13.9%) | 11 (14.3%) | |
| Paced | 26 (14.1%) | 7 (6.5%) | 19 (24.7%) | |
| Other | 10 (5.4%) | 4 (3.7%) | 6 (7.8%) | |
| ICD | 62 (33.5%) | 24 (22.2%) | 38 (49.4%) | <0.01 |
| Cardiac resynchronization therapy | 25 (13.5%) | 6 (5.6%) | 19 (24.7%) | <0.01 |
| Plan for AHF follow‐up | ||||
| Plan for specialist heart failure (HF) follow‐up? | 83 (44.9%) | 45 (41.7%) | 38 (49.4%) | 0.37 |
| Median time until AHF follow‐up, days? | 7 (6.25, 14.0) | 7 (6.0, 14.0) | 7 (7.0, 14.0) | 0.94 |
Note: The values presented are frequency (percentage) or median (Q1, Q3), where appropriate.
Abbreviations: AHF, advanced heart failure; BUN, blood urea nitrogen; CS, cardiogenic shock; DBP, diastolic blood pressure; GDMT, guideline‐directed medical therapy; ICD, implantable cardiac defibrillator; LVEF, left ventricular ejection fraction; SBP, systolic blood pressure.
Table 3 outlines GDMT utilization by medication class. On admission, 44% (n = 82) of patients with CS were not prescribed any GDMT, while 12% (n = 23) were on all three GDMT therapies recommended for HFrEF at the time (Central Figure 1).
Table 3.
Frequency of prescriptions for various medications in CS survivors at admission versus discharge, stratified by cause of CS (AMI‐CS vs. HF‐CS).
| Admission | Discharge | Absolute increase | ||
|---|---|---|---|---|
| AMI‐CS (N = 76) | Loop diuretics | 9 (12%) | 37 (49%) | ↑ 37% |
| Beta‐blockers | 15 (20%) | 54 (71%) | ↑ 51% | |
| ACEis/ARBs/ARNIs | 23 (30%) | 50 (66%) | ↑ 36% | |
| MRAs | 4 (5%) | 32 (42%) | ↑ 37% | |
| 3‐drug GDMT | 4 (5%) | 25 (33%) | ↑ 28% | |
| HF‐CS (N = 109) | Loop diuretics | 64 (59%) | 87 (80%) | ↑ 21% |
| Beta‐blockers | 63 (58%) | 90 (83%) | ↑ 27% | |
| ACEis/ARBs/ARNIs | 48 (44%) | 57 (52%) | ↑ 9% | |
| MRAs | 29 (27%) | 69 (63%) | ↑ 40% | |
| 3‐drug GDMT | 19 (17%) | 36 (33%) | ↑ 17% |
Abbreviations: ACEis, angiotensin‐converting enzyme inhibitors; AMI, acute myocardial infarction; ARBs, angiotensin receptor blockers; ARNIs, angiotensin receptor/neprilysin inhibitors; CS, cardiogenic shock; GDMT, guideline‐directed medical therapy; HF, heart failure; MRAs, mineralocorticoid receptor antagonists.
Central Figure 1.
(A) Frequency of guideline‐directed medical therapy (GDMT) utilization in cardiogenic shock (CS) survivors at both admission and discharge. (B) Calculated optimal medical therapy (OMT) scores for CS survivors at both admission and discharge. (C) Table of OMT scores of patients that were on one, two or three forms of GDMT at discharge.
At time of discharge, 33% (n = 61) of patients who survived CS with HFrEF were prescribed three‐drug GDMT (Table 3), and there were increases in prescriptions for all three medication classes. The proportions of patients on BBs, ACEis/ARBs/ARNIs and MRAs were 78% (n = 144), 58% (n = 107) and 55% (n = 101), respectively. Notably, 10% of patients (n = 19) were not prescribed any GDMT at discharge, and 9% (n = 17) were discharged on BBs not approved for the treatment of HF. Loop diuretic use rose from 40% (n = 73) to 67% (n = 124), and the median furosemide equivalent dose doubled from 40 mg (IQR 40, 80) to 80 mg (IQR 40, 160) from pre‐admission to discharge.
OMT scores for each individual medication class increased, and 7% (n = 5) of patients with no new GDMT class addition experienced an overall OMT score increase because of dose changes. The median OMT score for the overall cohort was 1 point (IQR 0, 3) at admission, which increased to a median OMT score of 3 (IQR 1, 4) at discharge (P < 0.001 by paired Wilcoxon signed rank test). Only 8% of patients (n = 15) achieved an ‘optimal’ OMT score of 6 or 7 points. Of patients prescribed one GDMT at discharge (n = 41), the majority (71%, n = 29) achieved an OMT score of 1 point (Central Figure 1).
Characteristics associated with GDMT addition versus no GDMT addition
Patients who experienced the addition of one or more classes of GDMT were more likely to have AMI‐CS and to have transferred to our centre from another hospital. Among patients with AMI‐CS (n = 76), 67% (n = 51) experienced GDMT additions, compared with only 52% (n = 57) of those with HF‐CS (P < 0.05). Among patients who transferred (n = 101), 70% (n = 71) had GDMT additions, while 30% (n = 30) did not (P < 0.01). At discharge, patients prescribed at least one additional GDMT class had a lower median serum creatinine (1.1 vs. 1.3 mg/dL, P < 0.01), lower median blood urea nitrogen (BUN) (23.5 vs. 27 mg/dL, P < 0.05) and higher median serum sodium (136 vs. 135 mEq/L, P < 0.05). They were also less likely to be discharged with an implantable cardiac defibrillator (ICD) (22% vs. 49%, P < 0.01).
Multivariable logistic regression adjusted for baseline GDMT use revealed that patients with lower LVEF and those who transferred to this centre from an outside hospital were more likely to experience the addition of at least one class of GDMT (P < 0.05) (Figure 3).
Figure 3.
Forest plot of covariates' logarithmic odds ratios for the addition of at least one class of guideline‐directed medical therapy (GDMT) during hospital admission for cardiogenic shock (CS), adjusted for baseline GDMT use at admission. Models included serum creatinine at hospital discharge (mg/dL), cause of CS [acute myocardial infarction (AMI) vs. heart failure], length of hospital stay (days), systolic blood pressure (BP) at discharge (mmHg), patient age (years), patient sex, presence of diabetes mellitus, sodium at discharge (mEq/L), presence of mitral regurgitation worse than mild at discharge and whether the patient transferred to our centre from an outside hospital. CI, confidence interval; LVEF, left ventricular ejection fraction.
At time of discharge, 75 (41%) patients met one or more exclusion criteria from contemporary clinical trials of GDMT—with SBP < 100 mmHg (n = 54), resting HR < 60 b.p.m. (n = 4) or creatinine > 2.5 mg/dL (n = 20). 22 , 23 , 24 , 25 However, none of these variables were significantly associated with a lack of GDMT addition during admission by logistic regression. GDMT prescriptions at discharge for patients that met one or more of the aforementioned criteria are presented in Table S2.
Clinical outcomes for patients who survived CS admission with HFrEF
Within 30 days of hospital discharge, 42 (23%) patients who survived CS admission with HFrEF were readmitted, and 7 (4%) had died. At 6 and 12 months, 26 (15%) and 39 (23%) patients who survived their CS hospitalization had died, respectively (Table 4). Post‐discharge outcomes by SCAI classification are available in Table S3. Survival outcomes at 6 and 12 months did not differ by CS aetiology (P = 0.67 and P = 0.34, respectively). Outcomes were not available for 10 (5%) patients at 6 months and 14 (8%) patients at 12 months. Multivariable logistic regression modelling showed no statistically significant relationship between overall in‐hospital GDMT implementation and readmission within 30 days. However, patients who were prescribed at least one additional class of GDMT had higher odds of 6 month and 1 year survival (P < 0.01): On average, 6 month survival odds were 7.1 times greater [confidence interval (CI) 1.9, 28.5] and 1 year survival odds were 6.0 times greater than those who did not have at least one GDMT added (CI 1.9, 20.5). Fewer than half (45%, n = 83) of discharged CS survivors with HFrEF had a documented plan for follow‐up with a specialist HF clinician (Table 2).
Table 4.
Patient outcomes at 30 days, 6 months and 1 year for 185 survivors of CS with LVEF ≤ 40%, stratified by GDMT class addition during admission.
| Long‐term outcomes of CS survivors | Overall (n = 185) | GDMT classes added ≥1 (n = 108) | GDMT classes added <1 (n = 77) | P‐value |
|---|---|---|---|---|
| Readmission within 30 days | 42 (22.7%) | 20 (18.5%) | 22 (28.6%) | 0.11 |
| Death within 30 days | 7 (3.8%) | 3 (2.8%) | 4 (5.2%) | 0.45 |
| Death within 6 months a | 26 (14.9%) | 8 (7.9%) | 18 (24.3%) | <0.01 |
| Death within 1 year a | 39 (22.8%) | 13 (13.3%) | 26 (35.6%) | <0.01 |
Note: The values presented are frequency (percentage) or median (Q1, Q3), where appropriate.
Abbreviations: CS, cardiogenic shock; GDMT, guideline‐directed medical therapy; LVEF, left ventricular ejection fraction.
Missing values were excluded for % calculations.
Discussion
This is a large, multidisciplinary effort to characterize the implementation of GDMT in patients who survive CS hospitalization with HFrEF. In this single‐centre, retrospective, observational cohort of patients with CS and reduced LVEF, we observed the following findings:
There was higher use of BBs and MRAs but lower use of ACEis, ARBs and ARNIs in patients who survived CS with HFrEF as compared with observed usage for these GDMTs in contemporary HF registries.
Despite eligibility, a treatment gap exists: Only one third of CS survivors with HFrEF received three‐drug therapy at the time of discharge, and <10% achieved ‘optimal’ GDMT.
Patients who were prescribed at least one new class of GDMT had significantly higher odds of 6 month and 1 year survival but no reduction in 30 day readmission.
Our observations regarding implementation of GDMT during CS hospitalization are comparable with increases reported from the Get With The Guidelines Heart Failure Registry (GWTG), in which in‐hospital BB usage increased by 46%, ACEi/ARB/ARNI by 27% and MRA by 10%. 26 Together, these data suggest that inpatient hospitalization remains a valuable opportunity to add, titrate and optimize HF medications, even in patients who initially present in a shock state.
We found higher prescriptions of BBs and MRAs in patients who survived CS with HFrEF than rates observed in the Change the Management of Patients with Heart Failure (CHAMP‐HF) Registry, which reported 67% utilization for BB and 33% for MRA during the study period of 2015–2017. 13 Interestingly, ACEi, ARB and ARNI prescription in the current analysis was lower than observed in both the CHAMP‐HF registry and in clinical trial data, possibly related to concerns of hyperkalaemia or of exacerbation of kidney dysfunction caused by hypoperfusion in CS. The lower median serum creatinine in patients who had GDMT added supports this notion. Furthermore, this cohort of CS patients likely had greater illness severity than all‐comers in CHAMP, as evidenced by a lower overall LVEF and SBP. 13
Despite eligibility, only one third of CS survivors with HFrEF received three‐drug GDMT by hospital discharge, and <10% achieved ‘optimal’ GDMT by OMT score. These data are consistent with data from patients with HFrEF without CS. 27 The reasons for under‐utilization and under‐optimization of GDMT appear multifactorial and include financial costs, stagnant ‘clinical inertia’ and concerns for medication intolerance (including hypotension or renal dysfunction). 15 , 28 , 29 The severity of CS may lead clinicians to exercise an over‐abundance of caution when balancing the risks and benefits of medical therapy: That is, patients admitted with CS may have high potential for benefit from GDMT, but their potential for deterioration may lead to prescription hesitancy. Given the association between GDMT prescription and beneficial outcomes, under‐implementation of GDMT following CS admission is a treatment gap that merits further study and rectification.
This patient cohort had 30 day hospital readmission rates and 1 year mortality rates similar to recent data from Canada, which included patients with AMI‐CS and demonstrated 30 day readmission rates of 19% and 1 year mortality rates of 15% among CS hospital survivors. 30
GDMT implementation was associated with improved patient outcomes following a CS admission. Patients who had at least one class of GDMT added had 6 month survival odds seven times greater and 1 year survival odds six times greater than those who did not have a GDMT addition. However, it is likely that these associations are confounded by illness severity: The sickest group of patients—those with grim clinical prognoses and whose conditions were deteriorating—may not have been able to tolerate GDMT or required other advanced therapeutic interventions and therefore exaggerated a mortality difference compared with patients who had GDMT added. 31
Our data suggest the need for better implementation of GDMT for patients who survive CS with HFrEF. Multiple strategies may assist, such as ‘discharge GDMT checklists’, automated electronic health record provider alerts or through protocols used in the Safety, tolerability and efficacy of up‐titration of guideline‐directed medical therapies for acute heart failure (STRONG‐HF) study, which demonstrated the safety and efficacy of rapid GDMT up‐titration within a few weeks of discharge for patients hospitalized with acute HF, leading to a significantly reduced risk of readmission and death within 180 days. 32 , 33 , 34 A post hoc analysis from STRONG‐HF indicated that the benefits of high‐intensity GDMT up‐titration were independent of baseline SBP, suggesting benefits for CS survivors with HFrEF despite clinician concern for hypotension. 35
A smooth transition of care to outpatient clinicians is also crucial to ensuring successful outcomes following a critical illness. 36 Fewer than half of CS survivors with HFrEF had a documented plan for follow‐up with a specialist HF clinician, despite the poor prognosis associated with this condition. 36 , 37 , 38 Outpatient follow‐up—particularly within 7 days of discharge—has been associated with lower rates of readmission, and higher proportions of patients with HFrEF followed in an advanced HF (AHF) clinic achieve target doses of GDMT. 39 , 40 It remains to be determined whether dedicated ‘post‐shock’ or ‘ICU recovery’ clinics with multidisciplinary collaboration may help facilitate GDMT titration and optimization and hopefully reduce rehospitalization and mortality in this patient population.
Limitations
This study included a relatively small sample of 185 patients. All data collection was retrospective and may be subject to biased reporting and confounding. This study was conducted using data from a quaternary care centre, which may limit generalizability to patients treated at secondary or tertiary centres. However, this analysis included both patients who presented directly to the emergency department and those who were transferred from another hospital. 41 The retrospective nature of this study prevented the inclusion of additional variables of interest, including natriuretic peptides and the New York Heart Association (NYHA) functional class, as they were not consistently collected or updated prior to hospital discharge. Additionally, reliable data on established patient histories of HF prior to admission were not available. While diagnosis of HF prior to CS admission would provide valuable insight into clinical management decisions, the cohort of interest in this study are those who survived their admission for CS and have LVEF ≤ 40% and therefore are indicated for GDMT use, irrespective of a history of HF prior to CS admission. While we compared the laboratory results and clinical characteristics of this cohort to identify exclusionary criteria for clinical trials, it is possible that some patients met other exclusion criteria for GDMT or had other GDMT contraindications, resulting in an over‐estimation of patients eligible for GDMT at the time of discharge. The study was conducted prior to the implementation of the SGLT2i drug class for HFrEF.
Conclusions
Most patients who survived CS admission with HFrEF in this single‐centre CS registry were not prescribed all classes or goal doses of GDMT at hospital discharge. The addition and up‐titration of GDMT during CS admission remains an opportunity for improvement in the management of HF and in the post‐discharge care of CS, as there remains a high rate of rehospitalization and mortality following CS admission. These findings are consistent with contemporaneous decompensated HF registries and clinical trial data. Concerted multidisciplinary efforts are needed to improve the post‐discharge medical management of CS survivors with HFrEF. This study establishes a baseline‐level use of GDMT in survivors of CS with HFrEF. Further research is needed to determine whether GDMT utilization has increased following the implementation of the 2022 HF clinical guidelines, which placed increased emphasis on the importance of inpatient initiation of GDMT.
Conflict of interest statement
PS receives unrelated grant support paid to the institution from Merck, Bayer, Roche and Abbott and consulting fees from Natera, Merck and Procyrion. AGT is part of the Consultant/Speakers Bureau, Abiomed Inc. and Speakers Bureau, Shockwave Inc. AAD receives research funding from the Pepper Scholars Program of the Johns Hopkins University Claude D. Pepper Older Americans Independence Center funded by the National Institute on Aging (P30‐AG021334) and receives a mentored patient‐oriented research career development award from the National Heart, Lung, and Blood Institute (K23‐HL153771‐01). CMO has received grant or research support from Merck and consulting fees from Merck, Bayer and Abiomed. All other authors report no relevant disclosures.
Funding
The statistical analysis for this manuscript was supported by grant funding from iTHRIV: National Center for Advancing Translational Science of the National Institutes of Health Award UL1TR003015/KL2TR003016. NIH K23 Career Development Award 1K23HL143179 was awarded to PS.
Supporting information
Table S1. Frequency of prescriptions for various medications in the overall CS survivor cohort at admission vs. discharge. ACEi = angiotensin‐converting enzyme inhibitor, ARB = angiotensin receptor blocker, ARNI = angiotensin receptor/neprilysin inhibitor, MRA = mineralocorticoid receptor antagonist.
Table S2. Number of GDMT classes prescribed at hospital discharge, stratified by patients that met or did not meet exclusion criteria from contemporary clinical trials of HF medications.
Table S3. Post‐discharge patient outcomes, stratified by SCAI shock stage.
Dimond, M. G. , Rosner, C. M. , Lee, S. B. , Shakoor, U. , Samadani, T. , Batchelor, W. B. , Damluji, A. A. , Desai, S. S. , Epps, K. C. , Flanagan, M. C. , Moukhachen, H. , Raja, A. , Sherwood, M. W. , Singh, R. , Shah, P. , Tang, D. , Tehrani, B. N. , Truesdell, A. G. , Young, K. D. , Fiuzat, M. , O'Connor, C. M. , Sinha, S. S. , and Psotka, M. A. (2025) Guideline‐directed medical therapy implementation during hospitalization for cardiogenic shock. ESC Heart Failure, 12: 60–70. 10.1002/ehf2.14863.
Shashank S. Sinha and Mitchell A. Psotka contributed equally to this work.
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Associated Data
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Supplementary Materials
Table S1. Frequency of prescriptions for various medications in the overall CS survivor cohort at admission vs. discharge. ACEi = angiotensin‐converting enzyme inhibitor, ARB = angiotensin receptor blocker, ARNI = angiotensin receptor/neprilysin inhibitor, MRA = mineralocorticoid receptor antagonist.
Table S2. Number of GDMT classes prescribed at hospital discharge, stratified by patients that met or did not meet exclusion criteria from contemporary clinical trials of HF medications.
Table S3. Post‐discharge patient outcomes, stratified by SCAI shock stage.