Eleni Maneta

The renin-angiotensin-aldosterone system (RAAS) is essential to cardiovascular homeostasis, particularly in heart failure (HF) and cardiogenic shock states. Relative angiotensin II depletion is a potential mechanism for postoperative hypotension and may be potentiated by pre-existing HF. The availability of exogenous AT2 allows for tailored vasoplegia management in a state of RAAS dysregulation. This prospective, single-institution pilot study aimed to characterize the expected reduction in angiotensin II (AT2) and angiotensin I (AT1) levels following cardiopulmonary bypass (CPB) in patients with and without chronic systolic HF, with enrollment of 10 patients in each arm. Preoperative AT2 and AT1 levels were significantly higher in patients with HF and remained so following cardiac surgery. A lower postoperative AT2 correlated with lower mean arterial pressure and a trend toward higher pressor requirements in HF patients only. No association was seen in HF or non-HF patients between CPB time and the change in AT1, AT2, or their ratio. Taken together, this pilot study suggests a role for characterizing RAAS function in patients with HF undergoing cardiac surgery for prediction and treatment of postcardiotomy vasoplegia.

Background: Whether preleft ventricular assist device (LVAD) kidney function relates to myocardial recovery and LVAD‐related adverse events remains uncertain. We evaluated the association of baseline estimated glomerular filtration rate (eGFR) with recovery and adverse events after LVAD implantation. Methods: We studied participants who underwent LVAD implantation between 2008 and 2021 at any of the 3 institutions comprising the Utah Cardiac Recovery Program. eGFR at implant was categorized as 2 . Myocardial recovery was defined after ≥3 months of support as LV ejection fraction ≥40% and LV internal diameter in diastole ≤6.0 cm. Logistic regression was used to estimate the odds of myocardial recovery, and log‐linear models to estimate incidence rate ratios for adverse events. Results: Among 385 patients (mean age 56 years, 84% men, 44% ischemic cardiomyopathy), 50 (13%) achieved recovery. Median time to echocardiogram with maximum LV ejection fraction was 120 (IQR, 71–199) days. Preimplant eGFR2 was not significantly associated with recovery (odds ratio [OR], 0.61 [95% CI, 0.34–1.11]). Lower eGFR was associated with a higher rate of major bleeding but did not reach statistical significance (incidence rate ratio, 1.41 [95% CI, 0.99–2.01]). There were no significant associations between lower eGFR and neurologic or device complications. Conclusions: Pre‐LVAD low eGFR was not associated with lower rates of myocardial recovery. As the population of patients with concomitant advanced heart failure and cardiorenal syndrome continues to grow, these findings may help guide the management of these challenging patients.

BACKGROUND: The left atrium (LA) maintains a dynamic interaction with the left ventricle (LV). LA forward and reverse remodeling affect prognosis in patients with chronic heart failure. We examined LA reverse remodeling in patients supported with LV assist devices (LVADs) and investigated a potential impact on clinical outcomes. METHODS: Consecutive patients with advanced heart failure receiving durable, continuous-flow LVADs were prospectively evaluated (n=263). After excluding patients with unavailable echocardiographic data, 241 patients were studied. Echocardiographic assessment was performed pre- and serially post-LVAD implantation. We assessed LA and LV structure and function and their association, and the impact of LA reverse remodeling on all-cause mortality, LVAD-related adverse events, and atrial fibrillation (AF). RESULTS: Most patients were male, White, with a mean age of 56±15 years. Forty-four percent had underlying ischemic cardiomyopathy, and 65% were profile 1 to 3 as per the Interagency Registry for Mechanically Assisted Circulatory Support, with a mean LV ejection fraction of 19±7%, and end-diastolic diameter of 6.7±1.1 cm pre-LVAD. LA structure and function improved by 1 month on LVAD support and remained improved by 12 months, as evidenced by LA volumes, emptying volumes, emptying fractions, and strain parameters. LA changes were shown to be associated with LV structural and functional changes. The magnitude of LA reverse remodeling was associated with all-cause mortality, but not cerebrovascular accident/transient ischemic attack, LVAD thrombosis, or late right heart failure rates by 12 months on LVAD support. Of 46 patients with AF pre-LVAD, 28 (61%) converted to sinus rhythm, and 18 (39%) remained in AF during serial echocardiographic assessment. CONCLUSIONS: LA structure and function improved early post-LVAD support, showed stability of improvement during follow-up, and were associated with simultaneous LV changes. Implications on all-cause mortality and AF might inform the care of heart failure patients being considered for advanced therapies, as well as the broader population of patients with heart failure and concomitant AF undergoing pharmacological unloading.

Background: Multidisciplinary teams and regionalized care systems have been suggested to improve cardiogenic shock (CS) outcomes. We sought to identify clinical factors associated with successful outcomes for patients developing CS at an outside healthcare facility (spoke) and being transferred to a quaternary medical center (hub). Methods and Results: Consecutive patients with CS were evaluated (N=1162). Our study cohort comprised 412 patients developing CS at a spoke. Our primary end point was native heart survival (NHS) defined as survival to discharge without receiving advanced heart failure therapies. Secondary end points were survival to discharge, 30‐day and 1‐year survival after discharge, and adverse events. Association of clinical data with NHS was analyzed using logistic regression. Overall, 246 (59.7%) patients achieved NHS, 125 (30.3%) died, and 41 (10.0%) were discharged after advanced heart failure therapies. Of the 287 patients who were discharged (69.7%), 276 (67.0%) were alive at 30 days, and 250 (60.7%) at 1 year. Patients with NHS less commonly had bleeding or vascular complications or acute kidney injury requiring renal replacement therapy compared with patients who died or received advanced heart failure therapies. Significant multivariable factors associated with NHS likelihood included younger age; shorter length of stay and transfer from a secondary compared with a tertiary/quaternary level of care spoke; absence of cardiac arrest, intubation, or type 3 bleeding; lower vasoactive–inotropic score; higher left ventricular ejection fraction at admission to the hub; and shorter CS onset‐to‐temporary mechanical circulatory support deployment time. Conclusions: We identified clinical factors reflecting disease severity and management practices including length of stay and spoke level of care, inotrope/vasopressor utilization, and CS onset‐to‐temporary mechanical circulatory support deployment time, that might inform the management of patients developing CS at a spoke.

Ischemic heart disease and acute myocardial infarction (AMI) is a leading cause of morbidity and mortality. Improvements have been made in coronary interventions to restore blood flow, but ischemia/reperfusion (I/R) injury significantly impacts clinical outcomes. We previously reported that activation of percutaneous mechanical unloading of the left ventricle (LV) with a transvalvular axial-flow device simultaneously with reperfusion improves myocardial salvage. However, the underlying mechanisms, potential adjuvant pharmacological interventions and the timing of the use of LV unloading as a cardioprotective approach in AMI are not well understood. This study investigated a) the mechanisms associated with improved myocardial salvage, b) a pharmacological intervention, and c) the timing of LV unloading. Following 90 minutes of ischemia, adult swine were subjected to reperfusion alone, simultaneous unloading with reperfusion, upfront unloading with delayed reperfusion, upfront reperfusion with delayed unloading, or reperfusion with concurrent use of esmolol and milrinone. Compared to controls, the simultaneous group had a 47% increase in myocardial salvage following AMI. This was associated with increased expression of neutrophil degranulation, macrophage activation, iNOS signaling, wound healing, and PPAR signaling. From these pathways, PPARG (peroxisome proliferator-activated receptor gamma) emerged as a potential cardioprotective gene that was uniquely overexpressed in the simultaneously unloaded and reperfused myocardium. Next, we showed PPARG agonism with rosiglitazone reduces mitochondrial oxygen demand in cardiomyocytes and in vivo, improves myocardial salvage following I/R injury in C57BL6/J mice. Thiazolidinediones (TZDs), such as rosiglitazone could be investigated as therapies combined with simultaneous LV unloading and coronary interventions to mitigate reperfusion injury. GRAPHICAL

BACKGROUND: Cardiogenic shock (CS) can stem from multiple causes and portends poor prognosis. Prior studies have focused on acute myocardial infarction-CS; however, acute decompensated heart failure (ADHF)-CS accounts for most cases. We studied patients suffering ADHF-CS to identify clinical factors, early in their trajectory, associated with a higher probability of successful outcomes. METHODS: Consecutive patients with CS were evaluated (N=1162). We studied patients who developed ADHF-CS at our hospital (N=562). Primary end point was native heart survival (NHS), defined as survival to discharge without receiving advanced HF therapies. Secondary end points were adverse events, survival, major cardiac interventions, and hospital readmissions within 1 year following index hospitalization discharge. Association of clinical data with NHS was analyzed using logistic regression. RESULTS: Overall, 357 (63.5%) patients achieved NHS, 165 (29.2%) died, and 41 (7.3%) were discharged post advanced HF therapies. Of 398 discharged patients (70.8%), 303 (53.9%) were alive at 1 year. Patients with NHS less commonly suffered cardiac arrest, underwent intubation or pulmonary artery catheter placement, or received temporary mechanical circulatory support, had better hemodynamic and echocardiographic profiles, and had a lower vasoactive-inotropic score at shock onset. Bleeding, hemorrhagic stroke, hemolysis in patients with mechanical circulatory support, and acute kidney injury requiring renal replacement therapy were less common compared with patients who died or received advanced HF therapies. After multivariable adjustments, clinical variables associated with NHS likelihood included younger age, history of systemic hypertension, absence of cardiac arrest or acute kidney injury requiring renal replacement therapy, lower pulmonary capillary wedge pressure and vasoactive-inotropic score, and higher tricuspid annular plane systolic excursion at shock onset (all P <0.05). CONCLUSIONS: By studying contemporary patients with ADHF-CS, we identified clinical factors that can inform clinical management and provide future research targets. Right ventricular function, renal function, pulmonary artery catheter placement, and type and timing of temporary mechanical circulatory support warrant further investigation to improve outcomes of this devastating condition.

BACKGROUND: Cardiogenic shock (CS) mortality remains near 40%. In addition to inadequate cardiac output, patients with severe CS may exhibit vasodilation. We aimed to examine the prevalence and consequences of vasodilation in CS. METHODS: We analyzed all patients hospitalized at a CS referral center who were diagnosed with CS stages B to E and did not have concurrent sepsis or recent cardiac surgery. Vasodilation was defined by lower systemic vascular resistance (SVR), higher norepinephrine equivalent dose, or a blunted SVR response to pressors. Threshold SVR values were determined by their relation to 14-day mortality in spline models. The primary outcome was death within 14 days of CS onset in multivariable-adjusted Cox models. RESULTS: This study included 713 patients with a mean age of 60 years and 27% females; 14-day mortality was 28%, and 38% were vasodilated. The median SVR was 1308 dynes•s•cm ⁻⁵ (interquartile range, 870–1652), median norepinephrine equivalent was 0.11 µg/kg per minute (interquartile range, 0–0.2), and 28% had a blunted pressor response. Each 100-dynes•s•cm ⁻⁵ decrease in SVR below 800 was associated with 20% higher mortality (adjusted hazard ratio, 1.23; P =0.004). Each 0.1-µg/kg per minute increase in norepinephrine equivalent dose was associated with 15% higher mortality (adjusted hazard ratio, 1.12; P P =0.003). CONCLUSIONS: Pathophysiologic vasodilation is prevalent in CS and independently associated with an increased risk of death. CS vasodilation can be identified by SVR −5 , high doses of pressors, or a blunted SVR response to pressors. Additional studies exploring mechanisms and treatments for CS vasodilation are needed.

Background: Type 2 diabetes is prevalent in cardiovascular disease and contributes to excess morbidity and mortality. We sought to investigate the effect of glycemia on functional cardiac improvement, morbidity, and mortality in durable left ventricular assist device (LVAD) recipients. Methods and Results: Consecutive patients with an LVAD were prospectively evaluated (n=531). After excluding patients missing pre‐LVAD glycated hemoglobin (HbA1c) measurements or having inadequate post‐LVAD follow‐up, 375 patients were studied. To assess functional cardiac improvement, we used absolute left ventricular ejection fraction change (ΔLVEF: LVEF post‐LVAD−LVEF pre‐LVAD). We quantified the association of pre‐LVAD HbA1c with ΔLVEF as the primary outcome, and all‐cause mortality and LVAD‐related adverse event rates (ischemic stroke/transient ischemic attack, intracerebral hemorrhage, gastrointestinal bleeding, LVAD‐related infection, device thrombosis) as secondary outcomes. Last, we assessed HbA1c differences pre‐ and post‐LVAD. Patients with type 2 diabetes were older, more likely men suffering ischemic cardiomyopathy, and had longer heart failure duration. Pre‐LVAD HbA1c was inversely associated with ΔLVEF in patients with nonischemic cardiomyopathy but not in those with ischemic cardiomyopathy, after adjusting for age, sex, heart failure duration, and left ventricular end‐diastolic diameter. Pre‐LVAD HbA1c was not associated with all‐cause mortality, but higher pre‐LVAD HbA1c was shown to increase the risk of intracerebral hemorrhage, LVAD‐related infection, and device thrombosis by 3 years on LVAD support ( P P <0.001). Conclusions: Type 2 diabetes and pre‐LVAD glycemia modify the potential for functional cardiac improvement and the risk for adverse events on LVAD support. The degree and duration of pre‐LVAD glycemic control optimization to favorably affect these outcomes warrants further investigation.