Baran, David A.

Peripartum cardiomyopathy (PPCM) is an idiopathic form of pregnancy-induced heart failure associated with preeclampsia. Circulating factors in late pregnancy are thought to contribute to both diseases, suggesting a common underlying pathophysiological process. However, what drives this process remains unclear. Using serum proteomics, we identified the senescence-associated secretory phenotype (SASP), a marker of cellular senescence associated with biological aging, as the most highly up-regulated pathway in young women with PPCM or preeclampsia. Placentas from women with preeclampsia displayed multiple markers of amplified senescence and tissue aging, as well as overall increased gene expression of 28 circulating proteins that contributed to SASP pathway enrichment in serum samples from patients with preeclampsia or PPCM. The most highly expressed placental SASP factor, activin A, was associated with cardiac dysfunction or heart failure severity in women with preeclampsia or PPCM. In a murine model of PPCM induced by cardiomyocyte-specific deletion of the gene encoding peroxisome proliferator–activated receptor γ coactivator-1α, inhibiting activin A signaling in the early postpartum period with a monoclonal antibody to the activin type II receptor improved heart function. In addition, attenuating placental senescence with the senolytic compound fisetin in late pregnancy improved cardiac function in these animals. These findings link senescence biology to cardiac dysfunction in pregnancy and help to elucidate the pathogenesis underlying cardiovascular diseases of pregnancy.

Introduction: A single assessment of the SCAI shock classification robustly predicts mortality, and a repeat assessment may improve prognostication. Hypothesis: We hypothesized that frequent serial assignment of the SCAI shock stage could further improve risk stratification. Methods: Unique AHA Level 1 cardiac intensive care unit (CICU) admissions at a single center from 2015 to 2018 were reviewed retrospectively. Time-stamped electronic health record data were used to assign the SCAI shock stage in each 4-hour block during the first 24 hours of CICU admission. Shock was defined as SCAI shock stage C, D, or E. In-hospital mortality was evaluated using logistic regression. Results: Among 2,918 CICU patients, 1,537 (52.7%) met criteria for shock during >=1 block and 266 (9.1%) died in hospital. The SCAI shock stage on admission was: A, 37.6%; B, 31.5%; C, 25.9%; D, 1.8%; E, 3.3%. Patients with worsening SCAI shock stage after admission (first 4 hours) were at higher risk of mortality ( Figure A ), as were patients who met SCAI criteria for shock (particularly those with shock on admission, Figure B ). The pattern was consistent in patients with acute coronary syndromes, heart failure, or cardiac arrest (who had very high mortality). Each higher admission (aOR 1.36, 95% CI 1.18-1.56, AUC 0.70), maximum (aOR 1.59, 95% CI 1.37-1.85, AUC 0.73) and 24 hour mean (aOR 2.42, 95% CI 1.99-2.95, AUC 0.78) SCAI shock stage were incrementally associated with increasing in-hospital mortality. Discrimination was highest for the mean SCAI shock stage (p <0.05). Each additional 4 hour block meeting SCAI criteria for shock was associated with higher mortality (aOR 1.15, 95% CI 1.07-1.24). Conclusions: Dynamic assessment of shock using serial SCAI shock classification assignment can improve mortality risk stratification in CICU patients. Cumulative time in shock was a strong mortality risk indicator, highlighting the area under the curve of shock severity as an important determinant of outcomes.

Background One‐time assessment of the Society for Cardiovascular Angiography and Interventions (SCAI) shock classification robustly predicts mortality in the cardiac intensive care unit (CICU). We sought to determine whether serial SCAI shock classification could improve risk stratification. Methods and Results Unique admissions to a single academic level 1 CICU from 2015 to 2018 were included in this retrospective cohort study. Electronic health record data were used to assign the SCAI shock stage during 4‐hour blocks of the first 24 hours of CICU admission. Shock was defined as hypoperfusion (SCAI shock stage C, D, or E). In‐hospital death was evaluated using logistic regression. Among 2918 unique CICU patients, 1537 (52.7%) met criteria for shock during ≥1 block, and 266 (9.1%) died in the hospital. The SCAI shock stage on admission was: A, 37.6%; B, 31.5%; C, 25.9%; D, 1.8%; and E, 3.3%. Patients who met SCAI criteria for shock on admission (first 4 hours) and those with worsening SCAI shock stage after admission were at higher risk for in‐hospital death. Each higher admission (adjusted odds ratio, 1.36 [95% CI, 1.18–1.56]; area under the receiver operating characteristic curve, 0.70), maximum (adjusted odds ratio, 1.59 [95% CI, 1.37–1.85]; area under the receiver operating characteristic curve, 0.73) and mean (adjusted odds ratio, 2.42 [95% CI, 1.99–2.95]; area under the receiver operating characteristic curve, 0.78) SCAI shock stage was incrementally associated with a higher in‐hospital mortality rate. Discrimination was highest for the mean SCAI shock stage ( P <0.05). Each additional 4‐hour block meeting SCAI criteria for shock predicted a higher mortality rate (adjusted odds ratio, 1.15 [95% CI, 1.07–1.24]). Conclusions Dynamic assessment of shock using serial SCAI shock classification assignment can improve mortality risk stratification in CICU patients by quantifying the magnitude and duration of shock.

Purpose of review Cardiogenic shock (CS) has been recognized for >50 years, most commonly in the setting of myocardial infarction. This review covers recent advances in the definitions, epidemiology and severity assessment of cardiogenic shock. Recent findings In this review, the authors discuss the evolving definitions of cardiogenic shock, detailing the early approaches as well as more contemporary ideas. The epidemiology of CS is reviewed and then granular detail on the assessment of shock severity is provided including the role of lactate measurement and invasive hemodynamic assessment. The development of the Society for Cardiac Angiography and Intervention (SCAI) consensus statement on Classification of Cardiogenic Shock is reviewed by the principal authors. The revised SCAI Shock document is reviewed as well and the future directions for assessment of shock along with clinical applications are reviewed. Summary Cardiogenic shock mortality has not changed in a significant way in many years. Recent advances such as more granular assessment of shock severity have the potential to improve outcomes by allowing research to separate the patient groups which may respond differently to various therapies.

Abstract Aims Shock severity predicts mortality in patients with cardiogenic shock (CS). We evaluated the association between pre-cannulation Society for Cardiovascular Angiography and Intervention (SCAI) shock classification and mortality among patients receiving venoarterial (VA) extracorporeal membrane oxygenation (ECMO) support for CS. Methods and results We included Extracorporeal Life Support Organization (ELSO) Registry patients from 2010 to 2020 who received VA ECMO for CS. SCAI shock stage was assigned based on hemodynamic support requirements prior to ECMO initiation. In-hospital mortality was analyzed using multivariable logistic regression. We included 12 106 unique VA ECMO patient runs with a median age of 57.9 (interquartile range: 46.8, 66.1) years and 31.8% were females; 3472 (28.7%) were post-cardiotomy. The distribution of SCAI shock stages at ECMO initiation was: B, 821 (6.8%); C, 7518 (62.1%); D, 2973 (24.6%); and E, 794 (6.6%). During the index hospitalization, 6681 (55.2%) patients died. In-hospital mortality increased incrementally with SCAI shock stage (adjusted OR: 1.24 per SCAI shock stage, 95% CI: 1.17–1.32, P &lt; 0.001): B, 47.5%; C, 52.8%; D, 60.8%; E, 65.1%. A higher SCAI shock stage was associated with increased in-hospital mortality in key subgroups, although the SCAI shock classification was only predictive of mortality in non-surgical (medical) CS and not in post-cardiotomy CS. Conclusion The severity of shock prior to cannulation is a strong predictor of in-hospital mortality in patients receiving VA ECMO for CS. Using the pre-cannulation SCAI shock classification as a risk stratification tool can help clinicians refine prognostication for ECMO recipients and guide future investigations to improve outcomes.

AbstractBackgroundRandomized studies of intra‐aortic balloon pump (IABP) in cardiogenic shock (CS) have only included on patients with acute coronary syndromes (ACS) without stratification according to shock severity. We examined the association between IABP and mortality in CS patients across the Society for Cardiovascular Angiography and Intervention (SCAI) shock stages.MethodsWe included cardiac intensive care unit patients admitted from 2007 to 2015 with CS from any etiology. In‐hospital mortality associated with IABP was examined in each SCAI shock stage. Multivariable logistic regression was performed using inverse probability of treatment weighting (IPTW) to determine the association between IABP and in‐hospital mortality.ResultsWe included 934 patients, with a mean age of 68 ± 14 years; 60% had ACS. The distribution of SCAI shock stages was: B, 41%; C, 13%; D, 38%; E, 8%. In‐hospital mortality was lower in the 39% of patients who received IABP (27% vs. 43%, adjusted OR with IABP after IPTW 0.53, 95% CI 0.40–0.72, p < .0001). IABP use was associated with lower crude in‐hospital mortality in each SCAI shock stage (all p < .05, except p = .08 in SCAI shock stage E). We did not observe any significant heterogeneity in the association between IABP use and in‐hospital mortality as a function of SCAI shock stage.ConclusionsPatients with CS who were selected to receive an IABP had lower in‐hospital mortality, without differences in this effect across the SCAI shock stages. Future studies should account for the severity and etiology of shock when evaluating the efficacy of IABP for CS.

AbstractBackgroundAmong acute myocardial infarction patients with cardiogenic shock (AMICS), a number of key variables predict mortality, including cardiac arrest (CA) and shock classification as proposed by Society for Cardiovascular Angiography and Intervention (SCAI). Given this prognostic importance, we examined the frequency of reporting of high risk variables in published randomized controlled trials (RCTs) of AMICS patients.MethodsWe identified 15 RCTs enrolling 2,500 AMICS patients and then reviewed rates of CA, baseline neurologic status, right heart catheterization data, lactate levels, inotrope and vasopressor requirement, hypothermia, mechanical ventilation, left ventricular ejection fraction (LVEF), mechanical circulatory support, and specific cause of death based on the primary manuscript and Data in S1.ResultsA total of 2,500 AMICS patients have been enrolled in 15 clinical trials over 21 years with only four trials enrolling >80 patients. The reporting frequency and range for key prognostic factors was: neurologic status (0% reported), hypothermia (28% reported, prevalence 33–75%), specific cause of death (33% reported), cardiac index and wedge pressure (47% reported, range 1.6–2.3 L min−1 m−2 and 15–24 mmHg), lactate (60% reported, range 4–7.7 mmol/L), LVEF (73% reported, range 25–45%), CA (80% reported, prevalence 0–92%), MCS (80% reported, prevalence 13–100%), and mechanical ventilation (93% reported, prevalence 35–100%). This variability was reflected in the 30‐day mortality which ranged from 20–73%.ConclusionsIn a comprehensive review of seminal RCTs in AMICS, important predictors of outcome were frequently not reported. Future efforts to standardize CS trial data collection and reporting may allow for better assessment of novel therapies for AMICS.

Background: Previous studies have defined preshock as isolated hypotension or isolated hypoperfusion, whereas shock has been variably defined as hypoperfusion with or without hypotension. We aimed to evaluate the mortality risk associated with hypotension and hypoperfusion at the time of admission in a cardiac intensive care unit population. Methods: We analyzed Mayo Clinic cardiac intensive care unit patients admitted between 2007 and 2015. Hypotension was defined as systolic blood pressure <90 mm Hg or mean arterial pressure <60 mm Hg, and hypoperfusion as admission lactate >2 mmol/L, oliguria, or rising creatinine. Associations between hypotension and hypoperfusion with hospital mortality were estimated using multivariable logistic regression. Results: Among 10 004 patients with a median age of 69 years, 43.1% had acute coronary syndrome, and 46.1% had heart failure. Isolated hypotension was present in 16.7%, isolated hypoperfusion in 15.3%, and 8.7% had both hypotension and hypoperfusion. Stepwise increases in hospital mortality were observed with hypotension and hypoperfusion compared with neither hypotension nor hypoperfusion (3.3%; all P <0.001): isolated hypotension, 9.3% (adjusted odds ratio, 1.7 [95% CI, 1.4–2.2]); isolated hypoperfusion, 17.2% (adjusted odds ratio, 2.3 [95% CI, 1.9–3.0]); both hypotension and hypoperfusion, 33.8% (adjusted odds ratio, 2.8 [95% CI, 2.1–3.6]). Adjusted hospital mortality in patients with isolated hypoperfusion was higher than in patients with isolated hypotension ( P =0.02) and not significant different from patients with both hypotension and hypoperfusion ( P =0.18). Conclusions: Hypotension and hypoperfusion are both associated with increased mortality in cardiac intensive care unit patients. Hospital mortality is higher with isolated hypoperfusion or concomitant hypotension and hypoperfusion (classic shock). We contend that preshock should refer to isolated hypotension without hypoperfusion, while patients with hypoperfusion can be considered to have shock, irrespective of blood pressure.

Background: The systemic inflammatory response syndrome (SIRS) frequently occurs in patients with cardiogenic shock and may aggravate shock severity and organ failure. We sought to determine the association of SIRS with illness severity and survival across the spectrum of shock severity in cardiac intensive care unit (CICU) patients. Methods: We retrospectively analyzed 8995 unique patients admitted to the Mayo Clinic CICU between 2007 and 2015. Patients with ≥2/4 SIRS criteria based on admission laboratory and vital sign data were considered to have SIRS. Patients were stratified by the 2019 Society for Cardiovascular Angiography and Interventions (SCAI) shock stages using admission data. The association between SIRS and mortality was evaluated across SCAI shock stage using logistic regression and Cox proportional-hazards models for hospital and 1-year mortality, respectively. Results: The study population had a mean age of 67.5±15.2 years, including 37.2% women. SIRS was present in 33.9% of patients upon CICU admission and was more prevalent in advanced SCAI shock stages. Patients with SIRS had higher illness severity, worse shock, and more organ failure, with an increased risk of mortality during hospitalization (16.8% versus 3.8%; adjusted odds ratio, 2.1 [95% CI, 1.7–2.5]; P <0.001) and at 1 year (adjusted hazard ratio, 1.4 [95% CI, 1.3–1.6]; P <0.001). After multivariable adjustment, SIRS was associated with higher hospital and 1-year mortality among patients in SCAI shock stages A through D (all P <0.01) but not SCAI shock stage E. Conclusions: One-third of CICU patients meet clinical criteria for SIRS at the time of admission, and these patients have higher illness severity and worse outcomes across the spectrum of SCAI shock stages. The presence of SIRS identified CICU patients at increased risk of short-term and long-term mortality. Further study is needed to determine whether systemic inflammation truly drives SIRS in this population and whether patients with SIRS respond differently to supportive therapies for shock.

Abstract Aims Age is an important risk factor for mortality among patients with cardiogenic shock and heart failure (HF). We sought to assess the extent to which age modified the performance of the Society for Cardiovascular Angiography and Interventions (SCAI) shock stage for in-hospital and 1 year mortality in cardiac intensive care unit (CICU) patients with and without HF. Methods and results We retrospectively reviewed unique admissions to the Mayo Clinic CICU during 2007–2015 and stratified patients by age and SCAI shock stage. The association between age and in-hospital mortality was analysed using multivariable logistic regression, and 1 year mortality was analysed using Cox proportional hazards analysis, both in the entire cohort and among patients with an admission diagnosis of HF or acute coronary syndrome (ACS). The final study population included 10 004 unique patients with a mean age of 67 ± 15 years, including 46.1% with HF and 43.1% with ACS. Older patients more frequently had HF and had more extensive co-morbidities, higher illness severity, more organ failure, and differential use of critical care therapies. The percentage of patients with SCAI shock stages A, B, C, D, and E were 46%, 30%, 16%, 7%, and 1%, respectively. Patients with HF were older, had greater severity of illness and higher SCAI shock stage, and had higher rates of death at all time points. In-hospital mortality occurred in 908 (9%) patients, including 549 (12%) patients with HF (61% of all hospital deaths). Age was independently associated with hospital mortality (adjusted odds ratio per 10 years 1.3, 95% confidence interval 1.2–1.4, P &lt; 0.001) and 1 year mortality (adjusted hazard ratio per 10 years 1.2, 95% confidence interval 1.2–1.3, P &lt; 0.001) in the overall cohort. The associations of age with both hospital mortality (adjusted odds ratio 1.6 vs. 1.3 per 10 years older) and 1 year mortality (adjusted hazard ratio 1.5 vs. 1.3 per 10 years older) were higher for patients with ACS compared with patients with HF. Older age was associated with higher adjusted hospital mortality and 1 year mortality in each SCAI shock stage (all P &lt; 0.05). Additive increases in both hospital mortality and 1 year mortality were observed with increasing age and SCAI shock stage. Conclusions Age is an independent risk factor for mortality that modifies the relationship between the SCAI shock stage and mortality risk in CICU patients, providing robust risk stratification for in-hospital and 1 year mortality. Although patients with HF had a higher risk of dying, age was more strongly associated with mortality among patients with ACS.