Origins and Evolution of Extracorporeal Circulation: JACC Historical Breakthroughs in Perspective.

Midway through the 20th century, direct open-heart operations were not yet a reality, awaiting safe methods to support the cardiopulmonary circulation during cardiac surgery. The scientific advancements collectively leading to safe cardiopulmonary bypass are considered some of the most impactful advances of modern medicine. Stimulated by the work of physiologists and engineers in the late 19th century, primitive pump and oxygenator designs were the forerunners of major work by DeBakey and others in roller pump design and by Gibbon in oxygenator development. Following Gibbon's historic successful closure of an atrial septal defect in 1953 with his heart-lung machine, it was left to Lillehei and Kirklin to first successfully repair large series of cardiac malformations. The history leading to these historic events and the subsequent evolution of cardiopulmonary bypass machines for short- and longer-term support is filled with engineering and surgical brilliance, daring innovations, and serendipity.

Cardiothoracic Surgery at the University of Alabama at Birmingham (UAB): A Legacy of Innovation, Education, and Contributions.

Cardiothoracic Surgery at the University of Alabama at Birmingham (UAB) represents a transformative enterprise whose origins lie in local practice and education in a Southern state with a challenging history, transformed by the visions of a few to become a dominant force in the historical fabric of regional, national, and international cardiothoracic surgery. Throughout its history, numerous individuals have participated in important innovations, education, and contributions to a consistent theme of surgical excellence. This review will recapitulate a sample of relevant historical events and the impact of the leaders of cardiothoracic surgery at UAB.

Clinical characteristics and outcomes of patients requiring prolonged inotropes after left ventricular assist device implantation.

Limited data exist regarding patients with continuous-flow left ventricular assist device (LVAD) support who require long-term inotropes. Our primary objective was to evaluate the clinical characteristics and all-cause mortality of LVAD recipients with prolonged inotrope use (PIU). Secondary endpoints were to compare predictors of PIU, mortality, risk of late re-initiation of inotropes, time to gastrointestinal bleed (GIB), infection, and arrhythmias. Retrospective cohort study was conducted on adult patients with primary continuous-flow LVADs implanted from January 2008 to February 2017 and the patients were followed up through February 2018. We defined PIU as ≥14 days of inotrope support. Kaplan-Meier method, competing risk models and Cox proportional hazard models were used. Final analytic sample was 203 patients, 58% required PIU, and 10% were discharged on inotropes. There was no difference in preimplant characteristics. One-year survival rate was 87% if no PIU required, 74% if PIU required, and 72% if discharged on inotropes. PIU was associated with longer length of stay and higher incidence of GIB. We found no association between PIU and late re-initiation of inotropes, infection or arrhythmias. Adjusted hazard risk of death was increased in patients with PIU (HR = 1.66, P = .046), older age (HR = 1.28, P = .031), and higher creatinine levels (HR = 1.60, P = .007). Prolonged inotrope use is frequently encountered following LVAD implantation and is associated with adverse prognosis but remains a therapeutic option. Inability to wean inotropes prior to hospital discharge is a marker of patients at particularly higher risk of mortality following LVAD implantation.

Utility of nuclear stress imaging in predicting long-term outcomes one-year post CABG Surgery.

BACKGROUND: Early MPI after CABG is currently considered rarely appropriate in asymptomatic patients. This study aimed to identify prognostic value of nuclear stress-imaging post-CABG. METHODS: This was a single center prospective study looking at long-term outcomes post-CABG. Per protocol participants underwent SPECT-MPI stress testing and coronary angiogram on the same day, 1-year following CABG. Defect size was semi-quantified. The primary outcomes were the composite of death and congestive heart failure. RESULTS: Eighty-four participants underwent nuclear stress-imaging and angiography, with a median follow-up of 11.1 years. Three separate stress findings predicted the primary outcome: inability to reach stage 3 of a Bruce protocol (OR 7.3, CI 2.4-22.1, P < 0.001), LVEF < 45% (OR 4.0, CI 1.1-15.3, P = 0.041) and a moderate-large stress defect size (HR 2.31, CI 1.1-1.5, P = 0.04). These findings appear to be additive and strongest among patients who underwent exercise stress testing (HR 10.6, CI 3.6-30.6, P < 0.001). Graft disease was identified in 39 (46%) patients and compared to those individuals with no graft disease, did not predict long-term adverse outcomes (P = 0.29). CONCLUSION: In clinically stable patients early after revascularization with CABG, SPECT-MPI can identify patients at higher risk of heart failure and death.

Innovation in Medical Devices-Lessons from the Past, Planning for the Future: Hastings Lecture 2019.

The development of devices for cardiac and pulmonary support is an example of innovation that opened important therapeutic options for patients with life-limiting diseases. The history of this important advance provides guidance for future developments in the field. Integrity is fundamental to maintaining the trust necessary for success.

Use of Computed Tomography in Preoperative Planning for Heartware Left Ventricular Assist Device Placement.

Optimal left ventricular assist device (LVAD) cannula position is important for adequate ventricular unloading and LVAD function. Poor inflow cannula position predisposes to pump thrombosis, inotrope dependence, and mortality. We describe a novel technique of preoperative left ventricular apex marking using CT guidance and demonstrate in three cases the use of this method to achieve optimal inflow cannula positioning for lateral thoracotomy Heartware LVAD implantation.

Evaluation of flow-modulation approaches in ventricular assist devices using an in-vitro endothelial cell culture model.

BACKGROUND: Continuous-flow ventricular assist devices (CF-VADs) produce non-physiologic flow with diminished pulsatility, which is a major risk factor for development of adverse events, including gastrointestinal (GI) bleeding and arteriovenous malformations (AVMs). Introduction of artificial pulsatility by modulating CF-VAD flow has been suggested as a potential solution. However, the levels of pulsatility and frequency of CF-VAD modulation necessary to prevent adverse events are currently unknown and need to be evaluated. METHODS: The purpose of this study was to use human aortic endothelial cells (HAECs) cultured within an endothelial cell culture model (ECCM) to: (i) identify and validate biomarkers to determine the effects of pulsatility; and (ii) conclude whether introduction of artificial pulsatility using flow-modulation approaches can mitigate changes in endothelial cells seen with diminished pulsatile flow. Nuclear factor erythroid 2-related factor 2 (Nrf-2)-regulated anti-oxidant genes and proteins and the endothelial nitric oxide synthase/endothelin-1 (eNOS/ET-1) signaling pathway are known to be differentially regulated in response to changes in pulsatility. RESULTS: Comparison of HAECs cultured within the ECCM (normal pulsatile vs CF-VAD) with aortic wall samples from patients (normal pulsatile [n = 5] vs CF-VADs [n = 5]) confirmed that both the Nrf-2-activated anti-oxidant response and eNOS/ET-1 signaling pathways were differentially regulated in response to diminished pulsatility. Evaluation of 2 specific CF-VAD flow-modulation protocols to introduce artificial pulsatility, synchronous (SYN, 80 cycles/min, pulse pressure 20 mm Hg) and asynchronous (ASYN, 40 cycles/min, pulse pressure 45 mm Hg), suggested that both increased expression of Nrf-2-regulated anti-oxidant genes and proteins along with changes in levels of eNOS and ET-1 can potentially be minimized with ASYN and, to a lesser extent, with SYN. CONCLUSIONS: HAECs cultured within the ECCM can be used as an accurate model of large vessels in patients to identify biomarkers and select appropriate flow-modulation protocols. Pressure amplitude may have a greater effect in normalizing anti-oxidant response compared with frequency of modulation.

INTERMACS Analysis of Stroke During Support With Continuous-Flow Left Ventricular Assist Devices: Risk Factors and Outcomes.

OBJECTIVES: This study sought to evaluate predictors of stroke during left ventricular assist device (LVAD) support from data available prior to implantation, and quantify stroke-related morbidity and mortality. BACKGROUND: Stroke is a major complication after LVAD. Pre-implant factors that influence stroke are not well understood. METHODS: We evaluated all patients in INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) who were implanted with continuous flow LVADs from May 1, 2012, to March 31, 2015. Pre-operative risk factors for stroke and stroke incidence, morbidity, and mortality were analyzed. RESULTS: During the study period, 7,112 patients underwent continuous flow LVAD placement. Median follow-up was 9.79 months (range 0.02 to 34.96 months). Of all patients, 752 (10.57%) had at least 1 stroke, with an incidence rate of 0.123 strokes per patient-year. A total of 447 (51.38%) strokes were ischemic and 423 (48.62%) were hemorrhagic. Patients with hemorrhagic stroke had worse survival than those with ischemic strokes (30-day survival: 45.3% vs. 80.7%; p < 0.001). Of patients with a first stroke, 13% had a second stroke. Pre-implant predictors of stroke were female sex (hazard ratio [HR]: 1.51; 95% confidence interval [CI]: 1.25 to 1.82; p < 0.001), pre-implant systolic blood pressure (HR: 1.01; 95% CI: 1.00 to 1.01; p = 0.002), heparin-induced thrombocytopenia (HR: 3.68; 95% CI: 1.60 to 8.47; p = 0.002), intra-aortic balloon pump (HR: 1.21; 95% CI: 1.01 to 1.46; p = 0.043), and primary cardiac diagnosis (ischemic/other/unknown) (p = 0.040). CONCLUSIONS: Despite improvements in LVAD technology, stroke-related morbidity and mortality is substantial. Further investigation is necessary to decrease the risk of this devastating complication.

Ventricular Assist Device in Acute Myocardial Infarction.

BACKGROUND: Patients with acute myocardial infarction (AMI) complicated by acute heart failure or cardiogenic shock have high mortality with conventional management. OBJECTIVES: This study evaluated outcomes of patients with AMI who received durable ventricular assist devices (VAD). METHODS: Patients in the INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) registry who underwent VAD placement in the setting of AMI were included and compared with patients who received VAD for non-AMI indications. RESULTS: VAD were implanted in 502 patients with AMI: 443 left ventricular assist devices; 33 biventricular assist devices; and 26 total artificial hearts. Median age was 58.3 years, and 77.1% were male. At implantation, 66% were INTERMACS profile 1. A higher proportion of AMI than non-AMI patients had pre-operative intra-aortic balloon pumps (57.6% vs. 25.3%; p < 0.01), intubation (58% vs. 8.3%; p < 0.01), extracorporeal membrane oxygenation (17.9% vs. 1.7%, p < 0.01), cardiac arrest (33.5% vs. 3.3%, p < 0.01), and higher-acuity INTERMACS profiles. At 1 month post-VAD, 91.8% of AMI patients were alive with ongoing device support, 7.2% had died on device, and 1% had been transplanted. At 1-year post-VAD, 52% of AMI patients were alive with ongoing device support, 25.7% had been transplanted, 1.6% had left VAD explanted for recovery, and 20.7% had died on device. The AMI group had higher unadjusted early phase hazard (hazard ratio [HR]: 1.24; p = 0.04) and reduced late-phase hazard of death (HR: 0.57; p = 0.04) than the non-AMI group did. After accounting for established risk factors, the AMI group no longer had higher early mortality hazard (HR: 0.89; p = 0.30), but it had lower late mortality hazard (HR: 0.55; p = 0.02). CONCLUSIONS: Patients with AMI who receive VAD have outcomes similar to other VAD populations, despite being more critically ill pre-implantation. VAD therapy is an effective strategy for patients with AMI and acute heart failure or shock in whom medical therapy is failing.

Benefits of a novel percutaneous ventricular assist device for right heart failure: The prospective RECOVER RIGHT study of the Impella RP device.

BACKGROUND: Right ventricular failure (RVF) increases morbidity and mortality. The RECOVER RIGHT study evaluated the safety and efficacy of a novel percutaneous right ventricular assist device, the Impella RP (Abiomed, Danvers, MA), in a prospective, multicenter trial. METHODS: Thirty patients with RVF refractory to medical treatment received the Impella RP device at 15 United States institutions. The study population included 2 cohorts: 18 patients with RVF after left ventricular assist device (LVAD) implantation (Cohort A) and 12 patients with RVF after cardiotomy or myocardial infarction (Cohort B). The primary end point was survival to 30 days or hospital discharge (whichever was longer). Major secondary end points included indices of safety and efficacy. RESULTS: The patients (77% male) were a mean age of 59 ± 15 years, 53% had diabetes, 88.5% had a history of congestive heart failure, and 37.5% had renal dysfunction. Patients were on an average of 3.2 inotropes/pressors. Device delivery was achieved in all but 1 patient. Hemodynamics improved immediately after initiation of Impella RP support, with an increase in cardiac index from 1.8 ± 0.2 to 3.3 ± 0.23 liters/min/m(2) (p < 0.001) and a decrease in central venous pressure from 19.2 ± 4 to 12.6 ± 1 mm Hg (p < 0.001). Patients were supported for an average of 3.0 ± 1.5 days (range, 0.5-7.8 days). The overall survival at 30 days was 73.3%. All patients discharged were alive at 180 days. CONCLUSIONS: In patients with life-threatening RVF, the novel percutaneous Impella RP device was safe, easy to deploy, and reliably resulted in immediate hemodynamic benefit. These data support its probable benefit in this gravely ill patient population.

Assessment and management of right ventricular failure in left ventricular assist device patients.

Mechanical circulatory support devices, including ventricular assist devices (VADs) and the total artificial heart, have evolved to become accepted therapeutic options for patients with severe congestive heart failure. Continuous-flow left VADs are the most prevalent option for mechanical circulatory assistance and reliably provide years of support. However, problems related to acute and chronic right heart failure in patients with left VADs continue to cause important mortality and morbidity. This review discusses the assessment and management of right ventricular failure in left VAD patients. The goal is to summarize current knowledge and suggest new approaches to managing this problem.