Erin M. Schumer

Rotary pump speed modulation for generating pulsatile flow and phasic left ventricular volume unloading in a bovine model of chronic ischemic heart failure

BACKGROUND Rotary blood pumps operate at a constant speed (rpm) that diminishes vascular pulsatility and variation in ventricular end-systolic and end-diastolic volumes, which may contribute to adverse events, including aortic insufficiency and gastrointestinal bleeding. In this study, pump speed modulation algorithms for generating pulsatility and variation in ventricular end-systolic and end-diastolic volumes were investigated in an ischemic heart failure (IHF) bovine model (n = 10) using a clinically implanted centrifugal-flow left ventricular assist device (LVAD). METHODS Hemodynamic and hematologic measurements were recorded during IHF baseline, constant pumps speeds, and asynchronous (19-60 cycles/min) and synchronous (copulse and counterpulse) pump speed modulation profiles using low relative pulse speed (±25%) of 3,200 ± 800 rpm and high relative pulse speed (±38%) of 2,900 ± 1,100 rpm. End-organ perfusion, hemodynamics, and pump parameters were measured to characterize pulsatility, myocardial workload, and LVAD performance for each speed modulation profile. RESULTS Speed modulation profiles augmented aortic pulse pressure, surplus hemodynamic energy, and end-organ perfusion (p < 0.01) compared with operation at constant speed. Left ventricular external work and myocardial oxygen consumption were significantly reduced compared with IHF baseline (p < 0.01) but at the expense of higher LVAD power consumption. CONCLUSIONS Pump speed modulation increases pulsatility and improves cardiac function and end-organ perfusion, but the asynchronous mode provides the technologic advantage of sensorless control. Investigation of asynchronous pump speed modulation during long-term support is warranted to test the hypothesis that operating an LVAD with speed modulation will minimize adverse events in patients supported by an LVAD that may be associated with long-term operation at a constant pump speed.

Left ventricular assist devices: current controversies and future directions

Advanced heart failure is a growing epidemic that leads to significant suffering and economic losses. The development of left ventricular assist devices (LVADs) has led to improved quality of life and long-term survival for patients diagnosed with this devastating condition. This review briefly summarizes the short history and clinical outcomes of LVADs and focuses on the current controversies and issues facing LVAD therapy. Finally, the future directions for the role of LVADs in the treatment of end-stage heart failure are discussed.

Quantitative analysis of exhaled carbonyl compounds distinguishes benign from malignant pulmonary disease

OBJECTIVES The analysis of exhaled breath is a promising noninvasive tool for the diagnosis of lung cancer, but its clinical relevance has yet to be established. We report the analysis of exhaled volatile carbonyl compounds for the identification of specific carbonyl cancer markers to differentiate benign pulmonary disease from early-stage lung cancer and to compare its diagnostic accuracy with positron emission tomography (PET) scans. METHODS Aminooxy-coated silicon microchips were used for the selective capture of exhaled carbonyls by an oximation reaction. Breath samples were collected then directed through the silicon chips by applying a vacuum. Carbonyl adducts were analyzed by Fourier transform mass spectrometry. Eighty-eight control subjects, 107 patients with lung cancer (64 stage 0, I, or II), 40 patients with benign pulmonary disease, and 7 patients with a solitary pulmonary metastasis participated. Analysis of cancer markers was performed blinded to the pathologic results. RESULTS Four carbonyls were defined as cancer markers with significantly higher concentrations in patients with lung cancer. The number of increased cancer markers distinguished benign disease from both early and stage III and IV lung cancer. For early-stage disease, defining greater than 2 increased markers as diagnostic of lung cancer resulted in 83% sensitivity and 74% specificity. PET scans for this same cohort resulted in 90% sensitivity but only 39% specificity. Markers normalized for 3 of the 4 markers after resection of the lung cancer. CONCLUSIONS Analysis of specific exhaled carbonyls can differentiate early lung cancer from benign pulmonary disease. Breath analysis was more specific than PET for a lung cancer diagnosis. Judicious use of these data may expedite the care of patients with lung cancer.

Left ventricular volume unloading with axial and centrifugal rotary blood pumps.

Axial (AX) and centrifugal (CFG) rotary blood pumps have gained clinical acceptance for the treatment of advanced heart failure. Differences between AX and CFG designs and mechanism of blood flow delivery may offer clinical advantages. In this study, pump characteristics, and acute physiologic responses during support with AX (HeartMate II) and CFG (HVAD) left ventricular assist devices (LVAD) were investigated in mock loop and chronic ischemic heart failure bovine models. In the mock loop model, pump performance was characterized over a range of pump speeds (HeartMate II: 7,000–11,000 rpm, HVAD: 2,000–3,600 rpm) and fluid viscosities (2.7 cP, 3.2 cP, 3.7 cP). In the ischemic heart failure bovine model, hemodynamics, echocardiography, and end-organ perfusion were investigated. CFG LVAD had a flatter HQ curve, required less power, and had a more linear flow estimation relation than AX LVAD. The flow estimation error for the AX LVAD (±0.9 L/min at 2.7 cP, ±0.7 L/min at 3.2 cP, ±0.8 L/min at 3.7 cP) was higher than the CFG LVAD (±0.5 L/min at 2.7 cP, ±0.2 L/min at 3.2 cP, ±0.5 L/min at 3.7 cP). No differences in acute hemodynamics, echocardiography, or end-organ perfusion between AX and CFG LVAD over a wide range of support were statistically discernible. These findings suggest no pronounced acute differences in LV volume unloading between AX and CFG LVAD.

High sensitivity for lung cancer detection using analysis of exhaled carbonyl compounds.

OBJECTIVE Several volatile carbonyl compounds in exhaled breath have been identified as cancer-specific markers. The potential for these markers to serve as a screening test for lung cancer is reported. METHODS Patients with computed tomography-detected intrathoracic lesions and healthy control participants were enrolled from 2011 onward. One liter of breath was collected from a single exhalation from each participant. The contents were evacuated over a silicon microchip, captured by oximation reaction, and analyzed by mass spectrometry. Concentrations of 2-butanone, 3-hydroxy-2-butanone, 2-hydroxyacetaldehyde, and 4-hydroxyhexanal were measured. The overall population was divided into 3 groups: those with lung cancer, benign disease, and healthy controls. An elevated cancer marker was defined as ≥1.5 SDs above the mean concentration of the control population. One or more elevated cancer markers constituted a positive breath test. RESULTS In all, 156 subjects had lung cancer, 65 had benign disease, and 194 were healthy controls. A total of 103 (66.0%) lung cancer patients were early stage (stage 0, I, and II). For ≥1 elevated cancer marker, breath analysis showed a sensitivity of 93.6%, and a specificity of 85.6% for lung cancer patients. Additionally, 83.7% of stage I tumors ≤2 cm were detected; whereas only 14% of the control population tested positive. In a comparison of cancer to benign disease, specificity was proportional to the number of elevated cancer markers present. CONCLUSIONS Screening using a low-dose CT scan is associated with high cost, repeated radiation exposure, and low accrual. The high sensitivity, convenience, and low cost of breath analysis for carbonyl cancer markers suggests that it has the potential to become a primary screening modality for lung cancer.

The association of pretransplant HeartMate II left ventricular assist device placement and heart transplantation mortality.

Previous United Network for Organ Sharing (UNOS) analysis has shown an increase in posttransplant mortality with pretransplant pulsatile-flow left ventricular assist device (LVAD). Recent studies evaluating continuous-flow LVAD demonstrated improved durability, excellent survival, and improved quality of life. This study investigates the association of preheart transplant continuous-flow LVAD placement and posttransplant mortality using the UNOS database. Heart transplant patients listed after April 2004 (N = 48,090) during the era of HeartMate (HM) II LVAD usage were investigated. Patients with UNOS 1A and 1B status with (n = 1,435) and without HMII (n = 16,379) placement before the heart transplantation were evaluated. Preliminary descriptive statistics suggested an extensive heterogeneity in patient characteristics between HMII LVAD recipients and nonrecipients. Propensity scores (1:2) were used to match HMII LVAD recipients and nonrecipients characteristics and donor characteristics. This resulted in a final sample of 2,265 patients (758 with HMII pretransplant placement and 1,507 without HMII pretransplant placement). The Kaplan–Meier curves were evaluated for the differences in postheart transplant mortality in patients with and without HMII pretransplant placement. A time-dependent Cox regression model was used to study the hazard ratios (HRs) for the association between HMII pretransplant placement and posttransplant survival. The mean age of the study group was 51.9 years old (standard deviation: 12.3). HeartMate II pretransplant placement was associated with no statistically significant difference in the risk of 30 days (HR = 1.23, 95% confidence interval [CI]: 0.79–1.95, p = 0.36) and 1 year posttransplant mortality (HR = 1.31, 95% CI: 0.85–2.01, p = 0.22) compared with non-HMII recipients. The use of HMII LVAD before heart transplantation, however, was associated with a statistically significant 64% lower risk (HR = 0.36, 95% CI: 0.16–0.77, p = 0.01) of mortality among heart transplant patients who survived beyond the first year of transplantation. Continuous-flow LVAD pretransplant placement is associated with improved long-term (>1 year) survival after heart transplantation.

Hemodynamic changes and retrograde flow in LVAD failure.

In the event of left ventricular assist device (LVAD) failure, we hypothesized that rotary blood pumps will experience significant retrograde flow and induce adverse physiologic responses. Catastrophic LVAD failure was investigated in computer simulation with pulsatile, axial, and centrifugal LVAD, mock flow loop with pulsatile (PVAD) and centrifugal (ROTAFLOW), and healthy and chronic ischemic heart failure bovine models with pulsatile (PVAD), axial (HeartMate II), and centrifugal (HVAD) pumps. Simulated conditions were LVAD “off” with outflow graft clamped (baseline), LVAD “off” with outflow graft unclamped (LVAD failure), and LVAD “on” (5 L/min). Hemodynamics (aortic and ventricular blood pressures, LVAD flow, and left ventricular volume), echocardiography (cardiac volumes), and end-organ perfusion (regional blood flow microspheres) were measured and analyzed. Retrograde flow was observed with axial and centrifugal rotary pumps during LVAD failure in computer simulation (axial = -3.4 L/min, centrifugal = -2.8 L/min), mock circulation (pulsatile = -0.1 L/min, centrifugal = -2.7 L/min), healthy (pulsatile = -1.2 ± 0.3 L/min, axial = -2.2 ± 0.2 L/min, centrifugal = -1.9 ± 0.3 L/min), and ischemic heart failure (centrifugal = 2.2 ± 0.7 L/min) bovine models for all test conditions (p < 0.05). Differences between axial and centrifugal LVAD were statistically indiscernible. Retrograde flow increased ventricular end-systolic and end-diastolic volumes and workload, and decreased myocardial and end-organ perfusion during LVAD failure compared with baseline, LVAD support, and pulsatile LVAD failure.

Minimally invasive esophagectomy for esophageal cancer: evolution and review.

Esophageal cancer remains one of the most deadly cancers with a low overall 5-year survival rate of 17%. Surgical options for esophageal cancer are varied, and debate exists on the best option. The literature was searched for articles discussing minimally invasive esophagectomy (MIE) compared with open esophagectomy (OE), and articles were chosen at the discretion of the authors. Several studies have shown that MIE has a statistically significant rate of decreased blood loss, increased length of operative time, shorter hospital stay, and overall decreased morbidity. Anastomotic leak, stricture rate, and survival benefit have also been demonstrated to be similar between OE and MIE. As is made apparent by the small amount of literature on MIE, further research must be done to determine outcomes. Although it is likely that MIE does offer benefits when compared with open surgery, it has not been shown in any large-scale comparative studies.

Double Lung Transplants Have Significantly Improved Survival Compared With Single Lung Transplants in High Lung Allocation Score Patients

BACKGROUND Historically, double lung transplantation survival rates are higher than those of single lung transplantation, but in critically ill patients a single lung transplant, with less associated operative morbidity, could afford a better outcome. This article evaluates how survival is affected in patients who have a high lung allocation score (LAS) and receive a single versus a double lung transplant. METHODS The UNOS Thoracic Transplant Database for lung transplants from January 2005 to June 2012 was used for analysis. Propensity matching was used to minimize differences between the high and low LAS groups and between single and double lung transplants in the high LAS group. RESULTS Within this database, there were 8,778 patients, of whom 8,050 had an LAS less than 75 and 728 had an LAS greater than or equal to 75. Kaplan-Meier survival curves stratified by high and low LAS, and by single versus double lung transplants, showed a marked decrease in survival (p<0.001) in those with a high LAS who received a single lung transplant when compared with those with a high LAS who received a double lung transplant. This was a much greater difference in survival than was present in the low LAS patient population. CONCLUSIONS Despite a higher operative morbidity, patients who had a high LAS did substantially better in terms of survival if two lungs were transplanted rather than only one, with a larger difference in survival than for patients with a lower LAS.

Normalization of Exhaled Carbonyl Compounds After Lung Cancer Resection

Background Quantitative analysis of specific exhaled carbonyl compounds (ECCs) has shown promise for the detection of lung cancer. The purpose of this study is to demonstrate the normalization of ECCs in patients after lung cancer resection. Methods Patients from a single center gave consent and were enrolled in the study from 2011 onward. Breath analysis was performed on lung cancer patients before and after surgical resection of their tumors. One liter of breath from a single exhalation was collected and evacuated over a silicon microchip. Carbonyls were captured by oximation reaction and analyzed by mass spectrometry. Concentrations of four cancer-specific ECCs were measured and compared by using the Wilcoxon test. A given cancer marker was considered elevated at 1.5 or more standard deviations greater than the mean of the control population. Results There were 34 cancer patients with paired samples and 187 control subjects. The median values after resection were significantly lower for all four ECCs and were equivalent to the control patient values for three of the four ECCs. Conclusions The analysis of ECCs demonstrates reduction to the level of control patients after surgical resection for lung cancer. This technology has the potential to be a useful tool to detect disease after lung cancer resection. Continued follow-up will determine whether subsequent elevation of ECCs is indicative of recurrent disease.