M. Yuzefpolskaya

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 patients 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.

Ventricular arrhythmias and implantable cardioverter-defibrillator therapy in patients with continuous-flow left ventricular assist devices: Need for primary prevention?

OBJECTIVES This study sought to evaluate the prevalence and significance of ventricular arrhythmia (VA) and the role of an implantable cardioverter-defibrillator (ICD) in patients supported by a continuous-flow left ventricular assist device (CF-LVAD). BACKGROUND VAs are common in patients supported by CF-LVADs but prospective data to support the routine use of ICDs in these patients are lacking. METHODS All patients supported by long-term CF-LVAD receiving care at our institution were enrolled. The ICDs were interrogated at baseline and throughout prospective follow-up. The VA was defined as ventricular tachycardia/fibrillation lasting >30 s or effectively terminated by appropriate ICD tachytherapy. The primary outcome was the occurrence of VA >30 days after CF-LVAD implantation. RESULTS Ninety-four patients were enrolled; 77 had an ICD and 17 did not. Five patients with an ICD had it deactivated or a depleted battery not replaced during the study. Twenty-two patients had a VA >30 days after LVAD implantation. Pre-operative VA was the major predictor of post-operative arrhythmia. Absence of pre-operative VA conferred a low risk of post-operative VA (4.0% vs. 45.5%; p < 0.001). No patients discharged from the hospital without an ICD after CF-LVAD implantation died during 276.2 months of follow-up (mean time without ICD, 12.7 ± 12.3 months). CONCLUSIONS Patients with pre-operative VA are at risk of recurrent VA while on CF-LVAD support and should have active ICD therapy to minimize sustained VA. Patients without pre-operative VA are at low risk and may not need active ICD therapy.

Prevalence, Significance, and Management of Aortic Insufficiency in Continuous Flow Left Ventricular Assist Device Recipients

Background— Aortic insufficiency (AI) is increasingly recognized as a complication of continuous flow left ventricular assist device support; however, its long-term prevalence, clinical significance, and efficacy of potential interventions are not well known. Methods and Results— We studied the prevalence and management of AI in 232 patients with continuous flow left ventricular assist device at our institution. Patients with aortic valve (AV) surgery before left ventricular assist device implantation were excluded from analysis. To examine the prevalence of de novo AI, patients without preoperative AI were divided into a retrospective and a prospective cohort based on whether a dedicated speed optimization study had been performed at the time of discharge. Forty-three patients underwent AV repair at the time of implant, and 3 subsequently developed greater than mild AI. In patients without surgical AV manipulation and no AI at the time of implant, Kaplan–Meier analysis revealed that freedom from greater than mild de novo AI at 1 year was 77.6±4.2%, and that at least moderate AI is expected to develop in 37.6±13.3% after 3 years. Nonopening of the AV was strongly associated with de novo AI development in patients without prospective discharge speed optimization. Seven of 21 patients with at least moderate AI developed symptomatic heart failure requiring surgical intervention. Conclusions— AI is common in patients with continuous flow left ventricular assist devices and may lead to clinical decompensation requiring surgical correction. The prevalence of AI is substantially less in patients whose AV opens, and optimized loading conditions may reduce AI prevalence in those patients in whom AV opening cannot be achieved.

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.

Incidence and clinical significance of late right heart failure during continuous-flow left ventricular assist device support

BACKGROUND Right heart failure (RHF) is an unresolved issue during continuous-flow left ventricular assist device (LVAD) support. Little is known about the incidence and clinical significance of late RHF during LVAD support. METHODS Between May 2004 and December 2013, 336 patients underwent continuous-flow LVAD implantation. Of these, 293 patients (87%) discharged with isolated LVAD support were included in this study. Late RHF was defined as HF requiring re-admission and medical or surgical intervention after initial surgery. RESULTS Late RHF occurred in 33 patients (11%) at a median of 99 days after discharge (range 19 to 1,357 days). Freedom from late RHF rates were 87%, 84% and 79% at 1, 2 and 3 years, respectively. RHF recurred in 15 patients. Three patients required right ventricular assist device insertion. Univariable Cox proportional hazards regression model showed diabetes mellitus (HR 2.05, 95% CI 1.03 to 4.06, p = 0.04), body mass index >29 (HR 2.47, 95% CI 1.24 to 4.94, p = 0.01) and blood urea nitrogen level >41 mg/dl (HR 2.19; 95% CI 1.10 to 4.36; p = 0.025) as significant predictors for late RHF. Estimated on-device survival rates at 2 years were 73% in the RHF group and 82% in the non-RHF group (p = 0.20). However, overall survival at 2 years was significantly worse in patients who developed late RHF (60% vs 85%, p = 0.016). This reduction was mostly attributed to worse overall outcomes in the bridge-to-transplant (BTT) population. CONCLUSIONS Late RHF is common after continuous-flow LVAD implantation, but does not affect survival during LVAD support. However, it is associated with worse overall outcomes in the BTT population.

Two-Year Outcomes with a Magnetically Levitated Cardiac Pump in Heart Failure

Background In an early analysis of this trial, use of a magnetically levitated centrifugal continuous‐flow circulatory pump was found to improve clinical outcomes, as compared with a mechanical‐bearing axial continuous‐flow pump, at 6 months in patients with advanced heart failure. Methods In a randomized noninferiority and superiority trial, we compared the centrifugal‐flow pump with the axial‐flow pump in patients with advanced heart failure, irrespective of the intended goal of support (bridge to transplantation or destination therapy). The composite primary end point was survival at 2 years free of disabling stroke (with disabling stroke indicated by a modified Rankin score of >3; scores range from 0 to 6, with higher scores indicating more severe disability) or survival free of reoperation to replace or remove a malfunctioning device. The noninferiority margin for the risk difference (centrifugal‐flow pump group minus axial‐flow pump group) was ‐10 percentage points. Results Of 366 patients, 190 were assigned to the centrifugal‐flow pump group and 176 to the axial‐flow pump group. In the intention‐to‐treat population, the primary end point occurred in 151 patients (79.5%) in the centrifugal‐flow pump group, as compared with 106 (60.2%) in the axial‐flow pump group (absolute difference, 19.2 percentage points; 95% lower confidence boundary, 9.8 percentage points [P<0.001 for noninferiority]; hazard ratio, 0.46; 95% confidence interval [CI], 0.31 to 0.69 [P<0.001 for superiority]). Reoperation for pump malfunction was less frequent in the centrifugal‐flow pump group than in the axial‐flow pump group (3 patients [1.6%] vs. 30 patients [17.0%]; hazard ratio, 0.08; 95% CI, 0.03 to 0.27; P<0.001). The rates of death and disabling stroke were similar in the two groups, but the overall rate of stroke was lower in the centrifugal‐flow pump group than in the axial‐flow pump group (10.1% vs. 19.2%; hazard ratio, 0.47; 95% CI, 0.27 to 0.84, P=0.02). Conclusions In patients with advanced heart failure, a fully magnetically levitated centrifugal‐flow pump was superior to a mechanical‐bearing axial‐flow pump with regard to survival free of disabling stroke or reoperation to replace or remove a malfunctioning device. (Funded by Abbott; MOMENTUM 3 ClinicalTrials.gov number, NCT02224755.)

Outcomes after stroke complicating left ventricular assist device

BACKGROUND Stroke is one of the leading complications during continuous flow-left ventricular assist device (CF-LVAD) support. Risk factors have been well described, although less is known regarding treatment and outcomes. We present a large single-center experience on stroke outcome and transplant eligibility by stroke sub-type and severity in CF-LVAD patients. METHODS Between January 1, 2008, and April 1, 2015, 301 patients underwent CF-LVAD (266 HeartMate II [HM I], Thoratec Corp, Pleasanton, CA; 35 HeartWare [HVAD], HeartWare International Inc, Framingham, MA). Stroke was defined as a focal neurologic deficit with abnormal neuroimaging. Intracerebral hemorrhage (ICH) definition excluded sub-dural hematoma and hemorrhagic conversion of an ischemic stroke (IS). Treatment in IS included intra-arterial embolectomy when appropriate; treatment in ICH included reversal of coagulopathy. Stroke severity was measured using the National Institutes of Health Stroke Scale (NIHSS). Outcomes were in-hospital mortality and transplant status. RESULTS Stroke occurred in 40 patients: 8 ICH (4 HM II, 4 HVAD) and 32 IS (26 HM II, 6 HVAD). Among 8 ICH patients, there were 4 deaths (50%), with NIHSS of 18.8 ± 13.7 vs 1.8 ± 1.7 in survivors (p = 0.049). Among 32 IS patients, 12 had hemorrhagic conversion and 5 were treated with intra-arterial embolectomy. There were 9 deaths (28%), with NIHSS of 16.2 ± 10.8 vs 7.0 ± 7.6 in survivors (p = 0.011). Among the 32 IS patients, 12 underwent transplant, and 1 is awaiting transplant. No ICH patients received a transplant. CONCLUSIONS In-hospital mortality after stroke is significantly affected by the initial neurologic impairment. Patients with IS appear to benefit the most from in-hospital treatment and often make sufficient recovery to be able to progress to transplant.

Early post-operative ventricular arrhythmias in patients with continuous-flow left ventricular assist devices

BACKGROUND Ventricular arrhythmias (VAs) are common in patients with a continuous-flow left ventricular assist device (CF-LVAD). The causes and clinical significance of early post-operative VAs have not previously been characterized in these patients. The purpose of this study was to assess the incidence, precipitants, and clinical impact of early VAs in patients supported by CF-LVADs. METHODS Patients with a long-term CF-LVAD receiving care between January 1, 2012, and March 1, 2014, were enrolled and followed prospectively. Implantable cardioverter-defibrillators (ICDs) were interrogated at baseline and throughout the follow-up period. VA was defined as ventricular tachycardia or ventricular fibrillation lasting >30 seconds or effectively terminated by appropriate ICD tachytherapy or external defibrillation. The primary end-point was the occurrence of early VAs (within 30 days of surgery). Secondary end-points were right ventricular (RV) failure and need for VA ablation. RESULTS There were 162 patients enrolled, and 38 (23.5%) experienced at least 1 early VA. Predictors of early VA were a history of pre-operative VAs, non-ischemic cardiomyopathy, and older age. Several conditions frequently encountered in the early post-operative period were identified as possible precipitants for VA episodes. Early VAs were associated with post-operative RV failure, particularly when patients received shocks instead of anti-tachycardia pacing. CONCLUSIONS Early VAs are common and are associated with RV failure. ICD shocks, but not anti-tachycardia pacing, for early VAs are associated with acute worsening of RV failure.

Outcome of cardiac transplantation in patients requiring prolonged continuous-flow left ventricular assist device support

OBJECTIVE This study assessed the early and late outcomes after cardiac transplantation in patients receiving long-term continuous-flow left ventricular assist device (CF-LVAD) support. METHODS Between April 2004 and September 2013, 192 patients underwent HeartMate II (Thoratec, Pleasanton, CA) CF-LVAD placement as a bridge to transplant at our center. Of these, 122 (63%) successfully bridged patients were retrospectively reviewed. Patients were stratified into 2 groups according to their waiting time with CF-LVAD support of <1 year or ≥1 year. RESULTS The study cohort was a mean age of 54 ± 13 years, 79% were male, and 35% had an ischemic etiology. The mean duration of CF-LVAD support before transplantation was 296 days (range, 27-1,413 days). The overall 30-day mortality was 4.1%. Overall post-transplant survival was 88%, 84%, 78% at 1, 3, and 5 years, respectively. The 32 patients (26%) with ≥1 year of CF-LVAD support (mean, 635 days) were more likely to have blood type O, a larger body size, and to have been readmitted due to recurrent heart failure and device failure requiring exchange than those with <1 year of CF-LVAD support. Patients who required prolonged support time also had worse in-hospital mortality (16% vs 6.7%, p = 0.12) and significantly lower survival at 3 years after transplantation (68% vs 88%, p = 0.049). CONCLUSIONS The overall short-term and long-term cardiac transplant outcomes of patients supported with CF-LVAD are satisfactory. However, patients who require prolonged CF-LVAD support may have diminished post-transplant survival due to adverse events occurring during device support.

Device exchange in HeartMate II recipients: long-term outcomes and risk of thrombosis recurrence.

Successful long-term use of the HeartMate II (HM II) left ventricular assist device has become commonplace but may be complicated by mechanical failure, infection, or thrombosis necessitating device exchange (DE). A subcostal approach to device exchange with motor exchange only is less traumatic, but long-term outcomes have not been reported. A retrospective chart review of all patients who required HM II to HM II device exchange at our institution was conducted. Of the 232 HM II patients implanted between January 2008 and July 2013, 28 required 36 device exchanges during a follow-up of 33.72 ± 17.25 months. The Kaplan–Meier 1 year survival was 63% for sternotomy exchanges and 100% for subcostal exchanges. Twenty-one exchanges were performed for initial or recurring device thrombosis. Although there was no difference in the risk of subsequent thrombosis after subcostal versus sternotomy exchange, the overall risk of recurring device thrombosis after device exchange for the same was high (31%). HM II device exchange via the subcostal approach has excellent short- and long-term outcomes. Device exchange performed for thrombosis is associated with a high recurrence risk irrespective of surgical approach