Michele Esposito

Effects of a percutaneous mechanical circulatory support device for medically refractory right ventricular failure

BACKGROUND Medically refractory right ventricular failure (MR-RVF) is associated with high in-hospital mortality and is managed with surgical assist devices, atrial septostomy, or extracorporeal membrane oxygenation. This study explored the hemodynamic effect associated with a percutaneous RV support device (pRVSD) for MR-RVF. METHODS Between 2008 and 2010, 9 patients with MR-RVF, defined as cardiogenic shock despite maximal medical therapy, were treated with a pRVSD. Medical records were reviewed for demographics, hemodynamic and laboratory data, and details of pRVSD implantation. RESULTS MR-RVF was due to severe sepsis in 1 patient (11.1%), post-cardiotomy syndrome in 2 (22.2%), and acute inferior wall myocardial infarction (IWMI) in 6 (66.7%). Five patients underwent right internal jugular-to-femoral cannulation, and 4 required bifemoral cannulation. No intra-procedural deaths or major vascular complications requiring surgical or peripheral intervention occurred. Time from admission to pRVSD implantation was 2.9 ± 3.3 days, with an average of 6516 ± 698 rotations/min, providing flow at 3.3 ± 0.4 liters/min. Mean duration of pRVSD activation was 3.1 ± 1.8 days. Compared with pre-procedural values, mean arterial pressure (57 ± 7 vs 75 ± 19 mm Hg, p < 0.05), right atrial pressure (22 ± 3 vs 15 ± 6 mm Hg, p < 0.05), cardiac index (1.5 ± 0.4 vs 2.3 ± 0.5 liters/min/m(2), p < 0.05), mixed venous oxygen saturation (40 ± 14 vs 58 ± 4 percent, p < 0.05), and RV stroke work (3.4 ± 3.9 vs 9.7 ± 6.8 g · m/beat, p < 0.05) improved significantly within 24 hours of pRVSD implantation. In-hospital mortality was 44% (n = 4). Time from admission to pRVSD placement was lower in patients who survived to hospital discharge (0.9 ± 0.8 days) vs non-survivors (4.8 ± 3.5 days; p = 0.04). All survivors presented with IWMI. CONCLUSION Use of a pRVSD for MR-RVF is feasible and associated with improved hemodynamics. Algorithms promoting earlier pRVSD use in MR-RVF warrant further investigation.

Hemodynamic Support with Percutaneous Devices in Patients with Heart Failure

The use of surgically implanted durable mechanical circulatory support (MCS) in high-risk patients with heart failure is declining and short-term, nondurable MCS device use is growing. Percutaneously delivered MCS options for advanced heart failure include the intra-aortic balloon pump, Impella axial flow catheter, TandemHeart centrifugal pump, and venoarterial extracorporeal membrane oxygenation. Nondurable MCS devices have unique implantation characteristics and hemodynamic effects. Algorithms and guidelines for optimal nondurable MCS device selection do not exist. Emerging technologies and applications will address the need for improved left ventricular unloading using lower-profile devices, longer-term ambulatory support, and the potential for myocardial recovery.

Hemodynamic effects of left atrial or left ventricular cannulation for acute circulatory support in a bovine model of left heart injury.

Our objective was to examine the hemodynamic effects of a trans-aortic axial flow catheter (Impella CP) in the left ventricle (LV) versus left atrial (LA) to femoral artery bypass using a centrifugal pump (TandemHeart: TH) in a bovine model of acute LV injury. In three male calves, we performed sequential activation of a CP then TH device in each animal. After 60 minutes of left anterior descending artery ligation, a CP was activated at maximal power. The CP was then removed and the TH activated at 5,500 then a maximum of 7,500 rotations per minute (RPM). The CP generated a maximum 3.1 ± 0.2 L/minute (LPM) of flow, whereas the TH at 5,500 and 7,500 RPM generated 3.1 ± 0.4 and 4.4 ± 0.3 LPM. At 3.1 LPM, the CP and TH reduced LV stroke work (LVSW) similarly. The TH reduced stroke volume, whereas the CP did not. The CP reduced end-systolic pressure, whereas the TH did not. At a maximum flow of 4.4 LPM, the TH provided a greater reduction in LVSW than maximal CP activation. This is the first report to compare the hemodynamic effects of trans-aortic LV unloading versus LA-to-femoral artery (FA) bypass.

Mechanical Circulatory Support Devices for Acute Right Ventricular Failure

Right ventricular (RV) failure remains a major cause of global morbidity and mortality for patients with advanced heart failure, pulmonary hypertension, or acute myocardial infarction and after major cardiac surgery. Over the past 2 decades, percutaneously delivered acute mechanical circulatory support pumps specifically designed to support RV failure have been introduced into clinical practice. RV acute mechanical circulatory support now represents an important step in the management of RV failure and provides an opportunity to rapidly stabilize patients with cardiogenic shock involving the RV. As experience with RV devices grows, their role as mechanical therapies for RV failure will depend less on the technical ability to place the device and more on improved algorithms for identifying RV failure, patient monitoring, and weaning protocols for both isolated RV failure and biventricular failure. In this review, we discuss the pathophysiology of acute RV failure and both the mechanism of action and clinical data exploring the utility of existing RV acute mechanical circulatory support devices.

Elevated Soluble fms-Like Tyrosine Kinase-1 Levels in Acute Coronary Occlusion

Objective—Early recognition of an acute coronary occlusion (ACO) improves clinical outcomes. Soluble fms-like tyrosine kinase-1 (sFLT1) is an endothelium-derived protein induced by hypoxia. We tested whether sFLT1 levels are elevated in ACO. Methods and Results—Serum sFLT1 levels were measured by enzyme-linked immunosorbent assay in patients with ST-segment elevations and angiographically confirmed ACO, unstable angina/non ST-segment elevation myocardial infarction, and 2 control groups. To further explore sFLT1 release, a mouse model of ACO and in vitro human coronary artery endothelial cell injury were used. sFLT1 levels were increased in ACO compared with unstable angina/non-ST-elevation myocardial infarction, catheterized controls, or healthy volunteers (200.7±15.5 versus 70.7±44.0 versus 10.2±4.0 versus 11.7±1.7 pg/mL respectively, P<0.001 versus ACO). At presentation, all ACO patients had elevated sFLT1 levels (>15 pg/mL, 99th percentile in controls), whereas 57% had levels of the MB isoform of creatine kinase levels >10 ng/mL (P<0.01) and 85% had ultrasensitive troponin I levels >0.05 ng/mL (P<0.05). Within 60 minutes after symptom onset, sFLT1 was more sensitive than the MB isoform of creatine kinase or ultrasensitive troponin I for ACO (100% versus 20% versus 20% respectively; P≤0.01 for each). Within 60 minutes of ACO in mice, sFLT1 levels were elevated. Hypoxia and thrombin increased sFLT1 levels within 15 minutes in human coronary artery endothelial cells. Conclusion—sFLT1 levels may be an early indicator of endothelial hypoxia in ACO.

Distinct effects of unfractionated heparin versus bivalirudin on circulating angiogenic peptides.

Background Human studies of therapeutic angiogenesis, stem-cell, and progenitor-cell therapy have failed to demonstrate consistent clinical benefit. Recent studies have shown that heparin increases circulating levels of anti-angiogenic peptides. Given the widely prevalent use of heparin in percutaneous and surgical procedures including those performed as part of studies examining the benefit of therapeutic angiogenesis and cell-based therapy, we compared the effects of unfractionated heparin (UFH) on angiogenic peptides with those of bivalirudin, a relatively newer anticoagulant whose effects on angiogenic peptides have not been studied. Methodology/Principal Findings We measured soluble fms-like tyrosine kinase-1 (sFLT1), placental growth factor (PlGF), vascular endothelial growth factor (VEGF), and soluble Endoglin (sEng) serum levels by enzyme linked immunosorbent assays (ELISA) in 16 patients undergoing elective percutaneous coronary intervention. Compared to baseline values, sFLT1 and PlGF levels increased by 2629±313% and 253±54%, respectively, within 30 minutes of UFH therapy (p<0.01 for both; n = 8). VEGF levels decreased by 93.2±5% in patients treated with UFH (p<0.01 versus baseline). No change in sEng levels were observed after UFH therapy. No changes in sFLT1, PlGF, VEGF, or sEng levels were observed in any patients receiving bivalirudin (n = 8). To further explore the direct effect of anticoagulation on circulating angiogenic peptides, adult, male wild-type mice received venous injections of clinically dosed UFH or bivalirudin. Compared to saline controls, sFLT1 and PlGF levels increased by >500% (p<0.01, for both) and VEGF levels increased by 221±101% (p<0.05) 30 minutes after UFH treatment. Bivalirudin had no effect on peptide levels. To study the cellular origin of peptides after anticoagulant therapy, human coronary endothelial cells were treated with UFH and demonstrated increased sFLT1 and PlGF levels (ANOVA p<0.01 for both) with reduced VEGF levels (ANOVA p<0.05). Bivalirudin had no effect on peptide levels in vitro. Conclusions/Significance Circulating levels of sFLT1, PlGF, and VEGF are significantly altered by UFH, while bivalirudin therapy has no effect. These findings may have significant implications for clinical studies of therapeutic angiogenesis, stem-cell and progenitor-cell therapy.

Door to Unload: a New Paradigm for the Management of Cardiogenic Shock

Cardiogenic shock (CS) remains the most common cause of in-hospital mortality in the setting of acute myocardial infarction (AMI). Recent data have identified several concerning trends in the field of AMI-CS that include an overall increase in mortality, an increase in patient complexity, minimal use of acute mechanical circulatory support (AMCS) devices with the majority being implanted as a bailout option. In this review, we will discuss recent trends in CS and the rationale for the use of acute mechanical circulatory support pumps early in the clinical treatment of CS.

Acute mechanical circulatory support for cardiogenic shock: the “door to support” time

Cardiogenic shock (CS) remains a major cause of in-hospital mortality in the setting of acute myocardial infarction. CS begins as a hemodynamic problem with impaired cardiac output leading to reduced systemic perfusion, increased residual volume within the left and right ventricles, and increased cardiac filling pressures. A critical step towards the development of future algorithms is a clear understanding of the treatment objectives for CS. In this review, we introduce the “door to support” time as an emerging target of therapy to improve outcomes associated with CS, define four key treatment objectives in the management of CS, discuss the importance of early hemodynamic assessment and appropriate selection of acute mechanical circulatory support (AMCS) devices for CS, and introduce a classification scheme that identifies subtypes of CS based on cardiac filling pressures.

Acute Biventricular Mechanical Circulatory Support for Cardiogenic Shock

Background Biventricular failure is associated with high in‐hospital mortality. Limited data regarding the efficacy of biventricular Impella axial flow catheters (BiPella) support for biventricular failure exist. The aim of this study was to explore the clinical utility of percutaneously delivered BiPella as a novel acute mechanical support strategy for patients with cardiogenic shock complicated by biventricular failure. Methods and Results We retrospectively analyzed data from 20 patients receiving BiPella for biventricular failure from 5 tertiary‐care hospitals in the United States. Left ventricular support was achieved with an Impella 5.0 (n=8), Impella CP (n=11), or Impella 2.5 (n=1). All patients received the Impella RP for right ventricular (RV) support. BiPella use was recorded in the setting of acute myocardial infarction (n=11), advanced heart failure (n=7), and myocarditis (n=2). Mean flows achieved were 3.4±1.2 and 3.5±0.5 for left ventricular and RV devices, respectively. Total in‐hospital mortality was 50%. No intraprocedural mortality was observed. Major complications included limb ischemia (n=1), hemolysis (n=6), and Thrombolysis in Myocardial Infarction major bleeding (n=7). Compared with nonsurvivors, survivors were younger, had a lower number of inotropes or vasopressors used before BiPella, and were more likely to have both devices implanted simultaneously during the same procedure. Compared with nonsurvivors, survivors had lower pulmonary artery pressures and RV stroke work index before BiPella. Indices of RV afterload were quantified for 14 subjects. Among these patients, nonsurvivors had higher pulmonary vascular resistance (6.8; 95% confidence interval [95% CI], 5.5–8.1 versus 1.9; 95% CI, 0.8–3.0; P<0.01), effective pulmonary artery elastance (1129; 95% CI, 876–1383 versus 458; 95% CI, 263–653; P<0.01), and lower pulmonary artery compliance (1.5; 95% CI, 0.9–2.1 versus 2.7; 95% CI, 1.8–3.6; P<0.05). Conclusions This is the largest, retrospective analysis of BiPella for cardiogenic shock. BiPella is feasible, reduces cardiac filling pressures and improves cardiac output across a range of causes for cardiogenic shock. Simultaneous left ventricular and RV device implantation and lower RV afterload may be associated with better outcomes with BiPella. Future prospective studies of BiPella for cardiogenic shock are required.

Quantity Over Quality: How the Rise in Quality Measures is Not Producing Quality Results

Over the past decade, quality measures (QMs) have been implemented nationally in order to establish standards aimed at improving the quality of care. With the expansion of their role in the Affordable Care Act and pay-for-performance, QMs have had an increasingly significant impact on clinical practice. However, adverse patient outcomes have resulted from adherence to some previously promulgated performance measures. Several of these QMs with unintended consequences, including the initiation of perioperative beta-blockers in noncardiac surgery and intensive insulin therapy for critically ill patients, were instituted as QMs years before large randomized trials ultimately refuted their use. The future of quality care should emphasize the importance of evidence-based, peer-reviewed measures.