Discriminatory performance of positive urine hemoglobin for detection of significant hemolysis in patients with continuous-flow left ventricular assist devices.

BACKGROUND: Serum lactate dehydrogenase (LDH) is the standard measure for detection of hemolysis and thus surveillance for device thrombosis in patients on continuous-flow left ventricular assist device (CF-LVAD) support. Significant hemolysis has been defined as LDH ≥600 IU/L. However, LDH testing requires phlebotomy, precluding frequent home monitoring. Simple dipstick urinalysis (UA) for urine hemoglobin (U-Hb) overcomes this limitation. This study correlated U-Hb and LDH levels and evaluated the performance of UA for detection of significant hemolysis in patients with CF-LVADs. METHODS: U-Hb and LDH were measured concurrently 956 times in 221 patients with CF-LVADs. Statistics were computed to determine accuracy of UA in detecting LDH ≥600 IU/L, with a positive result being any detected U-Hb. All analyses were performed with and without excluding for 1) conditions associated with tissue damage, which are known to increase LDH, and 2) suspected or confirmed urinary tract infections or hematuria, which are known to cause hemoglobinuria for reasons other than hemolysis. RESULTS: Mean LDH for absent/mild/severe U-Hb was 360 IU/L/467 IU/L IU/L/777 IU/L without exclusions, 354 IU/L/444 IU/L IU/L/651 IU/L after excluding non-hemolytic LDH elevations, 370 IU/L/513 IU/L IU/L/1,357 IU/L after excluding urinary tract infections and hematuria, and 367 IU/L/470 IU/L IU/L/1,217 IU/L when both exclusions applied (all p < 0.001). Absent U-Hb had a negative predictive value for LDH ≥600 IU/L of >90% for all analyses. CONCLUSIONS: Serum LDH is significantly associated with U-Hb levels. Absence of U-Hb appears to efficiently exclude significant hemolysis in patients with CF-LVADs. Because it can be performed by patients at home, hemoglobinuria monitoring may enable more intense surveillance and earlier diagnosis of device thrombosis.

Advanced cardiovascular life support algorithm for the management of the hospitalized unresponsive patient on continuous flow left ventricular assist device support outside the intensive care unit.

Over the past decade, continuous flow left ventricular assist devices (CF-LVADs) have become the mainstay of therapy for end stage heart failure. While the number of patients on support is exponentially growing, at present there are no American Heart Association or European Society of Cardiology Advanced Cardiovascular Life Support guidelines for the management of this unique patient population. We propose an algorithm for the hospitalized unresponsive CF-LVAD patient outside of the intensive care unit setting. Key elements of this algorithm are: creation of a dedicated LVAD code pager and LVAD code team; early assessment and correction of LVAD malfunction; early determination of blood flow using Doppler technique in carotid and femoral arteries; prompt administration of external chest compressions in the absence of Doppler flow; bedside veno-arterial extracorporeal membranous oxygenation support if no response to resuscitation measures; and early consideration for stroke.

Atrial Fibrillation in Patients With Left Ventricular Assist Devices: Incidence, Predictors, and Clinical Outcomes.

OBJECTIVES: This study sought to determine the prevalence of atrial fibrillation (AF) and its association with cardiac outcomes in patients with left ventricular assist devices (LVADs). BACKGROUND: LVADs are pivotal treatments for end-stage heart failure and a critical bridge to heart transplantation. METHODS: Medical records of 249 consecutive patients who received an LVAD at Columbia University Medical Center were reviewed. Patient demographics, clinical variables, medications, and outcomes were recorded. Descriptive statistics were generated, and multivariable logistic regression was performed to assess the independent association of clinical variables with the presence of AF. RESULTS: Overall, AF was documented in 80 patients (32%) following LVAD placement. Before LVAD placement, 182 patients had no history of AF, whereas 67 patients had documented AF. Among these 67 patients, 56 (84%) continued to have AF following LVAD placement; 24 patients without a history of AF (13%) developed AF after LVAD placement. Patients manifesting AF after LVAD placement were more likely to have had AF before LVAD insertion (p < 0.001). There were no significant differences in risk of stroke or death for patients with AF before or following LVAD insertion. CONCLUSIONS: AF is common in patients with LVADs, with 32% manifesting AF after placement of their LVAD, including 13% without a prior documented history of AF. The presence of AF was not associated with increased risk of death or stroke.

Validity and reliability of a novel slow cuff-deflation system for noninvasive blood pressure monitoring in patients with continuous-flow left ventricular assist device.

BACKGROUND: Doppler ultrasound is the clinical gold standard for noninvasive blood pressure (BP) measurement among continuous-flow left ventricular assist device patients. The relationship of Doppler BP to systolic BP (SBP) and mean arterial pressure (MAP) is uncertain and Doppler measurements require a clinic visit. We studied the relationship between Doppler BP and both arterial-line (A-line) SBP and MAP. Validity and reliability of the Terumo Elemano BP Monitor, a novel slow cuff-deflation device that could potentially be used by patients at home, were assessed. METHODS AND RESULTS: Doppler and Terumo BP measurements were made in triplicate among 60 axial continuous-flow left ventricular assist device (HeartMate II) patients (30 inpatients and 30 outpatients) at 2 separate exams (360 possible measurements). A-line measures were also obtained among inpatients. Mean absolute differences (MADs) and correlations were used to determine within-device reliability (comparison of second and third BP measures) and between-device validity. Bland-Altman plots assessed BP agreement between A-line, Doppler BP, and Terumo Elemano. Success rates for Doppler and Terumo Elemano were 100% and 91%. Terumo Elemano MAD for repeat SBP and MAP were 4.6±0.6 and 4.2±0.6 mm Hg; repeat Doppler BP MAD was 2.9±0.2 mm Hg. Mean Doppler BP was lower than A-line SBP by 4.1 (MAD=6.4±1.4) mm Hg and higher than MAP by 9.5 (MAD=11.0±1.2) mm Hg; Terumo Elemano underestimated A-line SBP by 0.3 (MAD=5.6±0.9) mm Hg and MAP by 1.7 (MAD=6.0±1.0) mm Hg. CONCLUSIONS: Doppler BP more closely approximates SBP than MAP. Terumo Elemano was successful, reliable, and valid when compared with A-line and Doppler.

Matrix metalloproteinase-9 deficiency phenocopies features of preeclampsia and intrauterine growth restriction.

The pregnancy complication preeclampsia (PE), which occurs in approximately 3% to 8% of human pregnancies, is characterized by placental pathologies that can lead to significant fetal and maternal morbidity and mortality. Currently, the only known cure is delivery of the placenta. As the etiology of PE remains unknown, it is vital to find models to study this common syndrome. Here we show that matrix metalloproteinase-9 (MMP9) deficiency causes physiological and placental abnormalities in mice, which mimic features of PE. As with the severe cases of this syndrome, which commence early in gestation, MMP9-null mouse embryos exhibit deficiencies in trophoblast differentiation and invasion shortly after implantation, along with intrauterine growth restriction or embryonic death. Reciprocal embryo transfer experiments demonstrated that embryonic MMP9 is a major contributor to normal implantation, but maternal MMP9 also plays a role in embryonic trophoblast development. Pregnant MMP9-null mice bearing null embryos exhibited clinical features of PE as VEGF dysregulation and proteinuria accompanied by preexisting elevated blood pressure and kidney pathology. Thus, our data show that fetal and maternal MMP9 play a role in the development of PE and establish the MMP9-null mice as a much-needed model to study the clinical course of this syndrome.

Prevalence and timing of bend relief disconnection in patients supported by the late version HeartMate II left ventricular assist device.

BACKGROUND: On April 4, 2012, the U.S. Food and Drug Administration issued a Class 1R recall of the HeartMate II (Thoratec Corporation, Pleasanton, CA) left ventricular assist device (LVAD) due to spontaneous detachment of the bend relief from its intended position in patients implanted with the most recent version of the HM II. This study examined the incidence and timing of outflow graft bend relief disconnection in patients implanted with the HM II LVAD. METHODS: All patients supported with the modified version of the HM II LVAD were asked to report for dedicated abdominal X-ray imaging to assess the position of the bend relief. Also performed was a retrospective review of X-ray images of all patients who had previously been supported with this version but had since received a transplant, undergone LVAD explant, or died. RESULTS: Between March 9, 2011, and April 9, 2012, 59 patients underwent primary implant with the modified version HM II. Follow up X-ray images were available for 56 patients (95%). The bend relief was found fully disconnected in 6 of 56 (11%) and partially disconnected in 13 (23%). Two of 6 patients (33%) with full bend relief disconnection and 1 of 13 of the initially partially disconnected patients (7.7%) required urgent surgical intervention due to symptoms of hemolysis and/or heart failure. CONCLUSIONS: Bend relief disconnection is common and may be observed immediately after implant but may also develop over time. Full bend relief disconnect may present with hemolysis and/or heart failure symptoms and often requires surgical revision. Surveillance abdominal X-ray imaging should be performed routinely on all patients who were implanted with the modified version HM II.

Development of a novel echocardiography ramp test for speed optimization and diagnosis of device thrombosis in continuous-flow left ventricular assist devices: the Columbia ramp study.

OBJECTIVES: This study sought to develop a novel approach to optimizing continuous-flow left ventricular assist device (CF-LVAD) function and diagnosing device malfunctions. BACKGROUND: In CF-LVAD patients, the dynamic interaction of device speed, left and right ventricular decompression, and valve function can be assessed during an echocardiography-monitored speed ramp test. METHODS: We devised a unique ramp test protocol to be routinely used at the time of discharge for speed optimization and/or if device malfunction was suspected. The patient's left ventricular end-diastolic dimension, frequency of aortic valve opening, valvular insufficiency, blood pressure, and CF-LVAD parameters were recorded in increments of 400 rpm from 8,000 rpm to 12,000 rpm. The results of the speed designations were plotted, and linear function slopes for left ventricular end-diastolic dimension, pulsatility index, and power were calculated. RESULTS: Fifty-two ramp tests for 39 patients were prospectively collected and analyzed. Twenty-eight ramp tests were performed for speed optimization, and speed was changed in 17 (61%) with a mean absolute value adjustment of 424 ± 211 rpm. Seventeen patients had ramp tests performed for suspected device thrombosis, and 10 tests were suspicious for device thrombosis; these patients were then treated with intensified anticoagulation and/or device exchange/emergent transplantation. Device thrombosis was confirmed in 8 of 10 cases at the time of emergent device exchange or transplantation. All patients with device thrombosis, but none of the remaining patients had a left ventricular end-diastolic dimension slope >-0.16. CONCLUSIONS: Ramp tests facilitate optimal speed changes and device malfunction detection and may be used to monitor the effects of therapeutic interventions and need for surgical intervention in CF-LVAD patients.

Changing trends in mechanical circulatory assistance:.

BACKGROUND: The success of long-term implantable ventricular assist devices has led to their increased use in patients previously thought to be unsuitable for mechanical support. As a result, the demographic profile of patients presenting for LVAD support has changed over time. We reviewed our institutional experience to identify emerging risk factors and changing trends in patients who received the HeartMate VE LVAD. METHODS: The clinical records were reviewed of 131 consecutive LVAD recipients between 1996 and 2001. All perioperative data were collected prospectively and entered into an institutional database. All patients received a preoperative risk stratification score based upon published criteria. The cohort was arbitrarily divided into early (n = 45), mid (n = 45), and late groups (n = 41). RESULTS: Overall operative mortality was 25% with no difference between groups. The mean risk score increased significantly over time (early 3.5 +/- 0.4 vs. late 5.3 +/- 0.3, p < 0.05). The proportion of patients at high risk for mortality (score >5) was significantly higher in the late group (51% vs. 29%, p < 0.05). Although ventilation time and ICU stay was similar for all groups, hospital stay was longer in the late group (43 days vs. 23 days, p < 0.05). Mean duration of support fell from 90 to 59 days, but this failed to achieve statistical significance. Out-patient therapy decreased from 73% in the early group to 15% in the late group (p < 0.001). Multivariate analysis identified right heart failure (odds ratio 4.1, 95% CI 2-11) and risk score (OR 1.4, 95% CI 1.2-1.6) as independent predictors of death. CONCLUSIONS: Despite an increasingly high risk patient population, the mortality associated with LVAD therapy has remained constant. Duration of LVAD support has decreased with a trend toward transplantation before hospital discharge. These data continue to support the aggressive institution of mechanical assistance for acute or chronic heart failure.

Effects of changes in UNOS policy regarding left ventricular assist devices.

Over the last 6 years, 161 patients underwent implantation of HeartMate single-lead vented electric (SLVE) devices as a bridge to transplantation. SLVE patients were retrospectively analyzed before and after United Network for Organ Sharing (UNOS) policy changes, and designated SLVE-1 and SLVE-2, respectively. Mean support time decreased significantly from 79.7 +/- 72.0 days to 55.3 +/- 60.5 days (p = 0.022). Although not statistically significant, rate of successful bridging to transplant increased from 70.3% to 74.7%, and post-transplant 1- and 3-year survival increased from 90.0% and 86.0%, respectively, to 92.9% and 87.3%, respectively.

Bridging to transplant with the HeartMate left ventricular assist device: The Columbia Presbyterian 12-year experience.

OBJECTIVE: Implantation of a left ventricular assist device as a bridge to transplantation has become an acceptable approach for patients with end-stage heart failure. Our long-term results with 3 Thoratec HeartMate devices are presented to outline improvements in successful bridging to transplantation and post-transplant survival. METHODS: From August 1990 through January 2003, 243 patients underwent implantation of Thoratec HeartMate devices as a bridge to transplantation. This included 52 (21.4%) pneumatic devices, 17 (7.0%) dual-lead vented electric devices, and 174 (71.6%) single-lead vented electric devices. RESULTS: Mean age was 49.7 +/- 13.7 years. Mean support time was 78.1 +/- 82.9 days (0-541). Bridging success increased from 63.5% (n = 33) for pneumatic devices to 64.7% (n = 11) for dual-lead vented electric devices and 72.4% (n = 126) for single-lead vented electric devices (P =.005). Posttransplant 1-, 3-, and 5-year actuarial survival increased from 87.5%, 78.1%, and 71.9% in patients with pneumatic devices to 91.5%, 86.9%, and 81.3%, respectively, for patients with single-lead vented electric devices. Device infection and malfunction occurred in 17.7% (n = 43) and 12.8% (n = 31) of patients, respectively. CONCLUSIONS: Successful bridging to transplantation and posttransplant survival has improved over time. Left ventricular assist devices have become increasingly more effective in bridging patients with end-stage heart failure to transplantation. This is likely due to a combination of better patient selection, improvements in clinical practice, and evolution in device design.

Revised screening scale to predict survival after insertion of a left ventricular assist device.

BACKGROUND: We previously calculated a risk factor summation score that successfully predicted survival after insertion of a left ventricular assist device. We sought to validate our previous score by using a single center's clinical experience and to determine emerging risk factors for mortality after device insertion. METHODS: The clinical records of 130 consecutive patients who received the HeartMate VE left ventricular assist device (Thoratec Corp, Pleasanton, Calif) at our institution between June 1996 and March 2001 as a bridge to transplantation were reviewed. Univariate and multivariable analyses were performed to determine the predictors of operative mortality after device insertion. Using the relative risks for each identified variable, we devised a new risk factor summation score. The new and old scores were then compared by using linear regression analyses to determine whether the revised score improved statistical accuracy. RESULTS: Overall operative mortality was 25% (n = 33). The old score successfully predicted operative mortality in the current patient population (operative mortality of 38% for score >5 vs 13% for score < or =5). However, the revised score improved risk discrimination (operative mortality of 46% for a score >5 vs 12% for a score < or = to 5). Statistical accuracy was comparable between scores, but the relationship between observed and predicted outcomes was improved with the revised score. CONCLUSIONS: The changing demographic profile and management of patients presenting for mechanical circulatory support has led to a change in the predictors of mortality after device insertion. Periodic remodeling and recalibration of risk indices helps to accurately predict outcomes in high-risk patient groups and identifies emerging risk factors for mortality.

Assessment of myocardial recovery in a patient with acute myocarditis supported with a left ventricular assist device: a case report.

Acute myocarditis may present with profound hemodynamic compromise; however, spontaneous resolution of the inflammatory process may occur in up to half of such patients. In patients with fulminant myocarditis, mechanical circulatory support may serve as a bridge to myocardial recovery. In this report we describe a 35-year-old man with acute myocarditis who required left ventricular assist device support as a bridge to recovery, and suggest a method for determining the suitability and timing of device explantation. A combination of echocardiography, right heart catheterization, exercise testing and serial endomyocardial biopsies was used to determine the resolution of myocarditis, recovery of myocardial function and timing for device explantation. Successful device explantation was performed after 37 days of device support. Further study is required to assess the role of ventricular assist devices in combination with immunosuppressive therapy in the management of fulminant myocarditis.

Right ventricular dysfunction and organ failure in left ventricular assist device recipients: a continuing problem.

BACKGROUND: Although right ventricular assist device (RVAD) use has declined with the introduction of inhaled nitric oxide and phosphodiesterase inhibitors (type III), right ventricular dysfunction (RVD) is still a serious problem in patients receiving left ventricular assist devices (LVAD). METHODS: We retrospectively analyzed Thoratec Vented Electrical LVAD recipients between June 1996 and September 1999. RVD was defined as inotropic requirement 14 days or more or need for RVAD postoperatively, or both. RESULTS: Sixty-nine LVAD recipients were analyzed. Twenty-one patients (30.4%) had RVD, with 1 patient requiring RVAD insertion, and there were 48 non-RVD patients. There were no significant differences between both groups for age, sex, etiology of congestive heart failure, days of support, and preoperative hemodynamics. Preoperative right ventricle stroke work index (mm Hg x m(-2) x L(-1)) had a trend toward being lower in the RVD group (4.1+/-3.2 versus 6.1+/-3.7, p = 0.06). A higher preoperative total bilirubin (mg/dL) was noticed in the RVD group (4.0+/-5.2 versus 2.1+/-1.7). The RVD group had a higher postoperative creatinine (2.2+/-1.4 mg/dL versus 1.5+/-0.8 mg/dL), incidence of continuous venovenous hemofiltration dialysis (73% versus 26%), transfusion of packed red blood cells (43.2+/-28.6 units versus 24.7+/-18.9 units), platelets (58.6+/-46.1 units versus 30.2+/-20.4 units), with longer intensive care unit length of stay (33.6+/-34.7 days versus 9.1+/-6.9) and higher mortality (42.8% versus 14.5%). When deaths were excluded, both intensive care unit and postoperative length of stay were significantly longer in the RVD group. CONCLUSIONS: RVD in LVAD recipients remains poorly identified and is associated with a high transfusion rate and end organ failure that results in increased intensive care unit and hospital length of stay, and a high mortality rate. Preoperative identification of risk factors for RVD may select patients who would benefit from a biventricular assist device and prevent the subsequent end organ failure.