H. Todd Massey

Extended Mechanical Circulatory Support With a Continuous-Flow Rotary Left Ventricular Assist Device

OBJECTIVES This study sought to evaluate the use of a continuous-flow rotary left ventricular assist device (LVAD) as a bridge to heart transplantation. BACKGROUND LVAD therapy is an established treatment modality for patients with advanced heart failure. Pulsatile LVADs have limitations in design precluding their use for extended support. Continuous-flow rotary LVADs represent an innovative design with potential for small size and greater reliability by simplification of the pumping mechanism. METHODS In a prospective, multicenter study, 281 patients urgently listed (United Network of Organ Sharing status 1A or 1B) for heart transplantation underwent implantation of a continuous-flow LVAD. Survival and transplantation rates were assessed at 18 months. Patients were assessed for adverse events throughout the study and for quality of life, functional status, and organ function for 6 months. RESULTS Of 281 patients, 222 (79%) underwent transplantation, LVAD removal for cardiac recovery, or had ongoing LVAD support at 18-month follow-up. Actuarial survival on support was 72% (95% confidence interval: 65% to 79%) at 18 months. At 6 months, there were significant improvements in functional status and 6-min walk test (from 0% to 83% of patients in New York Heart Association functional class I or II and from 13% to 89% of patients completing a 6-min walk test) and in quality of life (mean values improved 41% with Minnesota Living With Heart Failure and 75% with Kansas City Cardiomyopathy questionnaires). Major adverse events included bleeding, stroke, right heart failure, and percutaneous lead infection. Pump thrombosis occurred in 4 patients. CONCLUSIONS A continuous-flow LVAD provides effective hemodynamic support for at least 18 months in patients awaiting transplantation, with improved functional status and quality of life. (Thoratec HeartMate II Left Ventricular Assist System [LVAS] for Bridge to Cardiac Transplantation; NCT00121472).

Renal and Hepatic Function Improve in Advanced Heart Failure Patients During Continuous-Flow Support With the HeartMate II Left Ventricular Assist Device

Background— The effects of continuous blood flow and reduced pulsatility on major organ function have not been studied in detail. Methods and Results— We evaluated renal (creatinine and blood urea nitrogen) and hepatic (aspartate transaminase, alanine transaminase, and total bilirubin) function in 309 (235 male, 74 female) advanced heart failure patients who had been supported with the HeartMate II continuous-flow left ventricular assist device for bridge to transplantation. To determine whether patients with impaired renal and hepatic function improve over time with continuous-flow left ventricular assist device support or whether there are any detrimental effects in patients with normal organ function, we divided patients into those with above-normal and normal laboratory values before implantation and measured blood chemistry over time during left ventricular assist device support. There were significant improvements over 6 months in all parameters in the above-normal groups, with values in the normal groups remaining in the normal range over time. Mean blood urea nitrogen and serum creatinine in the above-normal groups decreased significantly from 37±14 to 23±10 mg/dL (P<0.0001) and from 1.8±0.4 to 1.4±0.8 mg/dL (P<0.01), respectively. There were decreases in aspartate transaminase and alanine transaminase in the above-normal groups from 121±206 and 171±348 to 36±19 and 31±22 IU (P<0.001), respectively. Total bilirubin for the above-normal group was 2.1±0.9 mg/dL at baseline; after an acute increase at week 1, it decreased to 0.9±0.5 mg/dL by 6 months (P<0.0001). Both renal and liver values from patients in the normal groups remained normal during support with the left ventricular assist device. Conclusions— The HeartMate II continuous-flow left ventricular assist device improves renal and hepatic function in advanced heart failure patients who are being bridged to transplantation, without evidence of detrimental effects from reduced pulsatility over a 6-month time period. Clinical Trial Registration Information— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00121472.

Intensive surveillance of femoropopliteal-tibial autogenous vein bypasses improves long-term graft patency and limb salvage

OBJECTIVE The authors determined the impact of an intensive surveillance program of autogenous vein bypasses on patency and limb salvage. SUMMARY BACKGROUND DATA Surveillance protocols of vein bypasses can identify graft-threatening lesions to permit elective revisions before thrombosis. The authors compared follow-up based on clinically indicated procedures with intensive surveillance. METHODS From 1985 to 1994, 615 autogenous vein bypasses (454 in situ, 161 reversed/composite) to popliteal (n = 169) and tibial (n = 446) arteries were performed for critical limb ischemia (n = 507), claudication (n = 88), and popliteal aneurysm (n = 20). Intensive surveillance of autogenous vein bypasses consisted of ankle brachial index and duplex scan with graft velocities measured at 1 month, 3 months, 6 months, and every 6 months subsequently. After surgery 317 bypasses had intensive surveillance, 222 bypasses were clinically indicated for follow-up, and 76 bypasses were excluded because follow-up or patency was less than 31 days. RESULTS Primary patency at 5 years was similar for bypasses treated by intensive surveillance (56%) and those treated with clinically indicated procedures (67%). Secondary patency and limb salvage at 5 years was significantly improved (p < 0.02) for bypasses followed by intensive surveillance (80% and 94%) compared with clinically indicated procedures (67% and 73%). Revision of patent bypasses was higher (p < 0.000001) for bypasses treated by intensive surveillance (61 of 70, 87%) compared with those treated with clinically indicated procedures (9 of 34, 26%). Secondary patency at 2 years was significantly higher (p < 0.02) for revision of patent bypasses (79%) compared with thrombosed bypasses (55%). CONCLUSIONS Long-term autogenous vein bypass patency and limb salvage is significantly improved by intensive surveillance, permitting identification and correction of graft threatening lesions before thrombosis.

Pedal or peroneal bypass: Which is better when both are patent?

PURPOSE We compared autogenous vein pedal and peroneal bypasses, focusing on extremities that could have a bypass to either artery. METHODS From 1985 to 1993 we performed a total of 175 pedal and 77 peroneal autogenous vein bypasses for rest pain (n = 75, 30%) and tissue loss (n = 177, 70%). One hundred ninety-six (78%) in situ saphenous vein and 56 (22%) reversed or composite vein bypasses were performed. One hundred fifty-two of these 252 bypasses were performed in extremities with both the pedal and peroneal arteries patent by arteriography. The vascular surgeon chose to perform 99 pedal and 53 peroneal vein bypasses in these 152 extremities. RESULTS The angiogram score of the outflow arteries were similar for pedal and peroneal bypasses with the Society for Vascular Surgery and the International Society for Cardiovascular Surgery and modified scoring systems. At 2 years the primary and secondary patency rates for pedal bypasses (70% and 77%) were not significantly different compared with those for peroneal bypasses (60% and 72%). Limb salvage rates at 2 years were similar for pedal and peroneal bypasses for all patients (74% and 73%), patients with both pedal and peroneal arteries patent (83% and 72%), diabetics (76% and 66%), and patients with tissue necrosis (77% and 71%). CONCLUSIONS Pedal and peroneal artery bypasses with equivalent angiogram scores have similar long-term graft patency and limb salvage. The choice between pedal or peroneal artery bypass should be based on the quality of vein and the surgeons preference.

Evaluation and treatment of pump thrombosis and hemolysis

Ventricular assist devices (VADs) are not fully biocompatible, and are therefore predisposed to device thrombosis and subsequent pump dysfunction. Clinically significant hemolysis in VADs most often occurs as a result of device thrombosis, but can also be caused by other factors. Herein we describe the evaluation and management of VAD thrombosis and hemolysis.

Clinical implications of physiological flow adjustment in continuous-flow left ventricular assist devices.

There is increasing evidence for successful management of end-stage heart failure with continuous-flow left ventricular assist device (CF-LVAD) technology. However, passive flow adjustment at fixed CF-LVAD speed is susceptible to flow balancing issues as well as adverse hemodynamic effects relating to the diminished arterial pulse pressure and flow. With current therapy, flow cannot be adjusted with changes in venous return, which can vary significantly with volume status. This limits the performance and safety of CF-LVAD. Active flow adjustment strategies have been proposed to improve the synchrony between the pump and the native cardiovascular system, mimicking the Frank–Starling mechanism of the heart. These flow adjustment strategies include modulation by CF-LVAD pump speed by synchrony and maintenance of constant flow or constant pressure head, or a combination of these variables. However, none of these adjustment strategies have evolved sufficiently to gain widespread attention. Herein we review the current challenges and future directions of CF-LVAD therapy and sensor technology focusing on the development of a physiologic, long-term active flow adjustment strategy for CF-LVADs.

Mammalian enabled (Mena) is a critical regulator of cardiac function

Mammalian enabled (Mena) of the Drosophila enabled/vasodilator-stimulated phosphoprotein gene family is a cytoskeletal protein implicated in actin regulation and cell motility. Cardiac Mena expression is enriched in intercalated discs (ICD), the critical intercellular communication nexus between adjacent muscle cells. We previously identified Mena gene expression to be a key predictor of human and murine heart failure (HF). To determine the in vivo function of Mena in the heart, we assessed Mena protein expression in multiple HF models and characterized the effects of genetic Mena deletion on cardiac structure and function. Immunoblot analysis revealed significant upregulation of Mena protein expression in left ventricle tissue from patients with end-stage HF, calsequestrin-overexpressing mice, and isoproterenol-infused mice. Characterization of the baseline cardiac function of adult Mena knockout mice (Mena(-/-)) via echocardiography demonstrated persistent cardiac dysfunction, including a significant reduction in percent fractional shortening compared with wild-type littermates. Electrocardiogram PR and QRS intervals were significantly prolonged in Mena(-/-) mice, manifested by slowed conduction on optical mapping studies. Ultrastructural analysis of Mena(-/-) hearts revealed disrupted organization and widening of ICD structures, mislocalization of the gap junction protein connexin 43 (Cx43) to the lateral borders of cardiomyoycytes, and increased Cx43 expression. Furthermore, the expression of vinculin (an adherens junction protein) was significantly reduced in Mena(-/-) mice. We report for the first time that genetic ablation of Mena results in cardiac dysfunction, highlighted by diminished contractile performance, disrupted ICD structure, and slowed electrical conduction.

Comparison of total artificial heart and biventricular assist device support as bridge-to-transplantation

The use of left ventricular assist devices (LVAD) has increased significantly in the last decade. However, right heart dysfunction remains a problem despite the improved outcomes with continuous‐flow LVADs. Surgical options for bridge to transplantation (BTT) in patients with biventricular failure are total artificial heart (TAH) or biventricular support (BiVAD). This study examines the differences in pre‐ and post‐transplantation outcomes and survival in patients with TAH or BiVAD support as BTT.

Anticoagulation Reversal Strategies for Left Ventricular Assist Device Patients Presenting with Acute Intracranial Hemorrhage

The safety of alternative vitamin K antagonist (VKA) reversal strategies in patients with left ventricular assist devices (LVAD’s) who present with intracranial hemorrhage (ICH) are not well known. A review of LVAD patients with ICH from May 2008 to 2015 was conducted, comparing the safety and efficacy of 4-factor prothrombin complex concentrate-assisted VKA reversal (4F-PCC group, n = 10) to reversal with traditional agents alone (no-PCC group, n = 10). An analysis of a no-reversal strategy in selected patients (n = 11) with ICH was additionally performed. Thirty-one cases of ICH on LVAD support were reviewed. The rate of post reversal thromboembolic events was not significantly different between 4F-PCC and no-PCC patients (0% vs. 10%, p = 1.0); however, the time to VKA reversal was shorter (474 vs. 945 minutes, p = 0.02) and fresh frozen plasma (FFP) requirements lower (1.9 vs. 3.6 units, p = 0.05) in 4F-PCC patients, with no difference in mortality between groups (p = 1.0). Eleven patients (mean ICH volume: 0.4 cm3) were successfully managed without active VKA reversal, with no increased hemorrhage noted on neuroimaging. These results suggest that 4F-PCC-assisted reversal in LVAD patients is safe and may improve the efficacy of VKA reversal. Our findings also indicate that carefully selected patients with small ICH volumes may be safely managed by discontinuing anticoagulation and allowing the international normalized ratio (INR) to normalize physiologically.

Temporary mechanical circulatory support after orthotopic heart transplantation: a single-centre experience

OBJECTIVES There are various strategies in the use of temporary mechanical circulatory support following orthotopic heart transplant (OHT). We sought to examine the outcomes following different temporary mechanical circulatory support strategies for acute graft failure. METHODS Patients who received an OHT between 2001 and 2015 at a single institution were retrospectively reviewed. Patients were divided into 2 groups based on the need for temporary mechanical circulatory support (TMCS). RESULTS A total of 9.9% (19 of 192) of patients required TMCS following OHT. There were no significant differences in the preoperative demographics between groups. Six patients (32%) required a biventricular assist device, 9 patients (47%) required a right ventricular assist device and 4 patients (21%) required a veno-arterial extracorporeal membrane oxygenator. Perioperative morbidity was comparable between all groups. Our entire TMCS cohort had 94.7% 30-day and 61.1% 1-year survival. When compared with the OHT patients with no TMCS (97.1% at 30 days and 92.8% at 1 year), survival was inferior in TMCS patients ( P  = 0.01 at 30 days, P  < 0.001 at 1 year, P  < 0.001 overall). CONCLUSIONS Acute graft failure requiring TMCS has inferior overall survival. Larger, multi-institutional studies are needed to further elucidate these differences and identify the best TMCS mode.