Henry, Timothy D.

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.

Abstract The concept that cell-based repair of myocardial injury might be possible was introduced almost two decades ago; however, the field of cardiovascular reparative medicine has been criticized as translation to clinically effective approaches has been slow. The recent retraction of a series of papers has further impacted perception of this area of research. As researchers, clinicians, and teachers in this field, we felt it incumbent to critically appraise the current state of cardiac cell repair, determine what can be learned from past mistakes, and formulate best practices for future work. This special communication summarizes an introspective assessment of what has fallen short, how to prevent similar issues, and how the field might best move forward in the service of science and patients.

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 This study aims to explore long-term clinical outcomes of cardiopoiesis-guided stem cell therapy for ischaemic heart failure assessed in the Congestive Heart Failure Cardiopoietic Regenerative Therapy (CHART-1) trial. Methods and results CHART-1 is a multinational, randomized, and double-blind trial conducted in 39 centres in heart failure patients (n = 315) on standard-of-care therapy. The ‘active’ group received cardiopoietic stem cells delivered intramyocardially using a retention-enhanced catheter. The ‘control’ group underwent patient-level sham procedure. Patients were followed up to 104 weeks. In the entire study population, results of the primary hierarchical composite outcome were maintained neutral at Week 52 [Mann–Whitney estimator 0.52, 95% confidence interval (CI) 0.45–0.59, P = 0.51]. Landmark analyses suggested late clinical benefit in patients with significant left ventricular enlargement receiving adequate dosing. Specifically, beyond 100 days of follow-up, patients with left ventricular end-diastolic volume of 200–370 mL treated with ≤19 injections of cardiopoietic stem cells showed reduced risk of death or cardiovascular hospitalization (hazard ratio 0.38, 95% CI 0.16–0.91, P = 0.031) and cardiovascular death or heart failure hospitalization (hazard ratio 0.28, 95% CI 0.09–0.94, P = 0.040). Cardiopoietic stem cell therapy was well tolerated long term with no difference in safety readouts compared with sham at 2 years. Conclusions Longitudinal follow-up documents that cardiopoietic stem cell therapy is overall safe, and post hoc analyses suggest benefit in an ischaemic heart failure subpopulation defined by advanced left ventricular enlargement on tolerable stem cell dosing. The long-term clinical follow-up thus offers guidance for future targeted trials.

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.

AbstractBackgroundPatients with concomitant cardiac arrest (CA) and shock are at increased risk of mortality, even when stratified according to shock severity. We sought to determine whether the presence of ventricular fibrillation (VF) modified the relationship between CA and mortality in cardiac intensive care unit (CICU) patients.MethodsWe retrospectively analyzed unique Mayo Clinic CICU patients admitted between 2007 and 2015. Society for Cardiovascular Angiography and Intervention (SCAI) shock stages A through E were classified at admission. Hospital mortality in each SCAI shock stage was stratified by the presence of CA, VF CA, or non‐VF CA.ResultsWe included 9,898 patients with a mean age of 68 years (38% females). CA was present in 12%, including 53% with VF CA and 47% with non‐VF CA. Hospital mortality was higher in patients with CA compared to patients without CA (34% vs. 6%; adjusted odds ratio [OR] = 3.1, 95% CI [2.4, 4.0],p < .001), and patients with non‐VF CA had higher hospital mortality than patients with VF CA (44% vs. 25%; adjusted OR = 2.1, 95% CI [1.4, 3.0],p < .001). After adjustment, patients with any CA or non‐VF CA had higher hospital mortality at each SCAI stage, except stage E (all otherp < .05), whereas patients with VF CA did not (allp > .1).ConclusionsCA rhythm modifies the relationship between CA and mortality in CICU patients, when accounting for coma, shock, and organ failure. Outcome studies examining CA in patients with cardiogenic shock need to account for important differences such as CA rhythm.

AbstractCD34+ cells are haematopoietic stem cells used therapeutically in patients undergoing radiation or chemotherapy due to their regenerative potential and ability to restore the haematopoietic system. In animal models, CD34+ cells have been associated with therapeutic angiogenesis in response to ischaemia. Several trials have shown the potential safety and efficacy of CD34+ cell delivery in various cardiovascular diseases. Moreover, Phase III trials have now begun to explore the potential role of CD34+ cells in treatment of both myocardial and peripheral ischaemia. CD34+ cells have been shown to be safe and well-tolerated in the acute myocardial infarction (AMI), heart failure, and angina models. Several studies have suggested potential benefit of CD34+ cell therapy in patients with coronary microvascular disease as well. In this review, we will discuss the therapeutic potential of CD34+ cells, and describe the pertinent trials that have used autologous CD34+ cells in no-options refractory angina, AMI, and heart failure. Lastly, we will review the potential utility of autologous CD34+ cells in coronary endothelial and microvascular dysfunction.