John M. Stulak

Readmissions after implantation of axial flow left ventricular assist device.

OBJECTIVES The purpose of this study was to determine the occurrence and causes of readmissions after implantation of axial flow left ventricular assist device (LVAD). BACKGROUND Based on the REMATCH (Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure) study experience, readmissions after LVAD implantation are thought to be frequent. METHODS We retrospectively analyzed admissions to our facility in a cohort of 115 patients implanted between January 2008 and July 2011 with the HeartMate II axial flow LVAD, of whom 42 were bridged to transplant. To account for repeated events, Andersen-Gill models were used to determine possible predictors. RESULTS The patients were followed for 1.4 ± 0.9 years. There were 224 readmissions in 83 patients. The overall readmission rate was 1.64 ± 1.97 per patient-year of follow-up. The readmission rate for the first 6 months was 2.0 ± 2.3 and decreased to 1.2 ± 2.1 during subsequent follow-up. Leading causes were bleeding (66 readmissions in 34 patients), mostly gastrointestinal bleed (51 in 27 patients), cardiac (51 in 36 patients, most for HF or arrhythmia), infections (32 in 25 patients) of which 6 were pump related, and thrombosis (20 in 15 patients) including 13 readmissions due to hemolysis. Preoperative variables associated with (fewer) readmissions in a multivariate model include residence within our hospital-extended referral zone of Minnesota and the neighboring states (hazard ratio: 0.66; 95% confidence interval: 0.48 to 0.91; p = 0.011), hemoglobin (hazard ratio: 0.91, 95% confidence interval: 0.84 to 0.99; p = 0.027) and N-terminal pro-B-type natriuretic peptide (hazard ratio: 0.98; 95% confidence interval: 0.96 to 1.0 per 1,000-unit increase, p = 0.022). C-statistic for the model: 0.63. CONCLUSIONS Readmission rates after axial flow LVAD implantation decrease during the first 6 months and then stabilize. The leading causes are bleeding, cardiac (heart failure and arrhythmia), infections, and thrombosis.

Multiple arterial grafts improve late survival of patients undergoing coronary artery bypass graft surgery: analysis of 8622 patients with multivessel disease.

Background— Use of the left internal mammary artery (LIMA) in multivessel coronary artery disease improves survival after coronary artery bypass graft surgery; however, the survival benefit of multiple arterial (MultArt) grafts is debated. Methods and Results— We reviewed 8622 Mayo Clinic patients who had isolated primary coronary artery bypass graft surgery for multivessel coronary artery disease from 1993 to 2009. Patients were stratified by number of arterial grafts into the LIMA plus saphenous veins (LIMA/SV) group (n=7435) or the MultArt group (n=1187). Propensity score analysis matched 1153 patients. Operative mortality was 0.8% (n=10) in the MultArt and 2.1% (n=154) in the LIMA/SV (P=0.005) group, which was not statistically different (P=0.996) in multivariate analysis or the propensity-matched analysis (P=0.818). Late survival was greater for MultArt versus LIMA/SV (10- and 15-year survival rates were 84% and 71% versus 61% and 36%, respectively [P<0.001], in unmatched groups and 83% and 70% versus 80% and 60%, respectively [P=0.0025], in matched groups). MultArt subgroups with bilateral internal mammary artery/SV (n=589) and bilateral internal mammary artery only (n=271) had improved 15-year survival (86% and 76%; 82% and 75% at 10 and 15 years [P<0.001]), and patients with bilateral internal mammary artery/radial artery (n=147) and LIMA/radial artery (n=169) had greater 10-year survival (84% and 78%; P<0.001) versus LIMA/SV. In multivariate analysis, MultArt grafts remained a strong independent predictor of survival (hazard ratio, 0.79; 95% confidence interval, 0.66–0.94; P=0.007). Conclusions— In patients undergoing isolated coronary artery bypass graft surgery with LIMA to left anterior descending artery, arterial grafting of the non–left anterior descending vessels conferred a survival advantage at 15 years compared with SV grafting. It is still unproven whether these results apply to higher-risk subgroups of patients.

Gastrointestinal bleeding and subsequent risk of thromboembolic events during support with a left ventricular assist device

BACKGROUND Modern left ventricular assist devices (LVAD) require anti-coagulation (AC) with warfarin and anti-platelet therapy to prevent thromboembolic complications in patients. Gastrointestinal bleeding (GI) is a significant adverse event in these patients and treatment typically requires reduction or elimination of AC or anti-platelet therapy. It is not known whether alterations in AC to treat GI bleeding influence subsequent risk of thromboembolic (TE) events during LVAD support. METHODS Between July 2003 and September 2011, 389 patients (308 male) underwent implantation of a continuous-flow LVAD at the University of Michigan Health System and the Mayo Clinic. Median age at implant was 60 years (range 18 to 79 years). Outcomes were analyzed for the association of GI bleeding events and subsequent TE events, defined as stroke, transient ischemic attack, hemolysis or suspected or confirmed pump thrombosis. RESULTS Median survival was 10 months (maximum 7.2 years, total 439 patient-years). TE events occurring within the first 30 days were not counted. Overall survival and freedom from an outcome event were assessed using the Kaplan-Meier method. Associations between GI bleeding and subsequent TE events and survival impact were analyzed as time-dependent covariates. One hundred ninety-nine GI bleeding episodes occurred in 116 of 389 patients (30%) for an event rate of 0.45 GI bleed/patient-year of support. One hundred thirty-eight TE events occurred in 97 of 389 patients (25%) for an event rate of 0.31 TE event/patient-year of support. Median time from LVAD implant to first GI bleed was 5 months (range 1 to 116 months) and to first TE event was 6 months (range 1 to 29 months). For patients who had a TE event after GI bleed, the median interval was 5 months (range 0.5 to 25 months). TE events were 7.4-fold more likely in patients who had a prior GI bleed (range 4.9- to 11.1-fold) (p < 0.001); however, neither the presence of GI bleeding (0.7 to 1.2) nor a TE event (0.8 to 2.0) portended a lower overall survival. CONCLUSIONS Patients who had GI bleeding were at significantly higher risk for a subsequent TE event. Although the exact cause of this relationship is unknown, it suggests that a reduction in anti-coagulation and anti-platelet management to treat GI bleeds may contribute to this risk.

Frailty and outcomes after implantation of left ventricular assist device as destination therapy

BACKGROUND Frailty is recognized as a major prognostic indicator in heart failure. There has been interest in understanding whether pre-operative frailty is associated with worse outcomes after implantation of a left ventricular assist device (LVAD) as destination therapy. METHODS Patients undergoing LVAD implantation as destination therapy at the Mayo Clinic, Rochester, Minnesota, from February 2007 to June 2012, were included in this study. Frailty was assessed using the deficit index (31 impairments, disabilities and comorbidities) and defined as the proportion of deficits present. We divided patients based on tertiles of the deficit index (>0.32 = frail, 0.23 to 0.32 = intermediate frail, <0.23 = not frail). Cox proportional hazard regression models were used to examine the association between frailty and death. Patients were censored at death or last follow-up through October 2013. RESULTS Among 99 patients (mean age 65 years, 18% female, 55% with ischemic heart failure), the deficit index ranged from 0.10 to 0.65 (mean 0.29). After a mean follow-up of 1.9 ± 1.6 years, 79% of the patients had been rehospitalized (range 0 to 17 hospitalizations, median 1 per person) and 45% had died. Compared with those who were not frail, patients who were intermediate frail (adjusted HR 1.70, 95% CI 0.71 to 4.31) and frail (HR 3.08, 95% CI 1.40 to 7.48) were at increased risk for death (p for trend = 0.004). The mean (SD) number of days alive out of hospital the first year after LVAD was 293 (107) for not frail, 266 (134) for intermediate frail and 250 (132) for frail patients. CONCLUSIONS Frailty before destination LVAD implantation is associated with increased risk of death and may represent a significant patient selection consideration.

Spectrum and Outcome of Reoperations After the Ross Procedure

Background— Proposed advantages to the Ross procedure included presumed increased freedom from reoperation and simpler reoperation for pulmonary conduit replacement if needed. It is increasingly apparent, however, that reoperations are frequent after the Ross procedure and that when required, they may be more complex than previously thought. Methods and Results— Between September 1991 and August 2008, 56 patients underwent reoperation at our institution after a Ross procedure performed by ourselves (n=13) or elsewhere (n=43). Median age at first reoperation at our institution was 26 years (range 1 to 69 years). The 4 most common indications for reoperation were isolated autograft (neoaortic) regurgitation in 11 cases (20%), isolated pulmonary conduit regurgitation/stenosis in 9 (16%), combined autograft regurgitation/dilatation in 8 (14%), and combined autograft regurgitation and pulmonary conduit regurgitation/stenosis in 6 (11%). A total of 144 procedures were performed in these 56 patients during first reoperation at our institution. The autograft valve required replacement in 21 cases (38%) and aortic root replacement in 21 (38%), with ascending aortic/arch reconstruction in 13 (23%) and mitral valve surgery in 5 (9%). The pulmonary valve was replaced in 33 cases (59%) and the tricuspid valve was repaired/replaced in 10 (18%). Early mortality was 1.8% (1 of 56 patients), and morbidity included 6 patients with respiratory failure and 3 who required postcardiotomy extracorporeal membrane oxygenation. There were 4 late deaths during the median follow-up of 8 months (range 1 to 179 months). Conclusions— A broad spectrum of complex reoperations may be required after the Ross procedure. Patients and family members considering the procedure should be informed of the potential for associated morbidity should reoperation be necessary.

Driveline Infections in Left Ventricular Assist Devices: Implications for Destination Therapy

BACKGROUND Infection is one of the major limitations to successful long-term support after ventricular assist device implantation. There are limited data specifically examining the incidence and predictors of driveline infections (DLI), with a changing treatment paradigm toward destination therapy (DT) and longer duration of support. METHODS Between January 2007 and 2011, 143 patients underwent HeartMate II (Thoratec, Pleasanton, CA) implantation, with 87 (61%) as DT. Driveline maintenance strategy included sterile dressing changes with chlorhexidine and saline application, without prophylactic oral antibiotics. RESULTS DLI developed in 18 patients (12%) at a median of 182 days (range, 26 to 1,138 days) after implantation, among which 12 (66%) were from the DT cohort. Infections were superficial in 15 (82%) and deep in 3 (18%). Trauma was documented in 6 patients (33%). Seven patients (38%) needed readmission for DLI. Surgical debridement was needed in 3 (17%). All patients were managed successfully, without the need for device explantation or urgent cardiac transplantation. No patient required continuous antibiotic prophylaxis after the infection subsided. Risk factor analysis identified duration of support as the only independent predictor of infection (mean. 600 vs 390 days; p = 0.03). The odds of having a DLI rose by 4% for every month of support. CONCLUSIONS Longer duration of support significantly increased the risk of DLI and hence increased the risk of DLI in patients with DT. DLI may be successfully managed with antibiotics and local wound care. Most of the infections were superficial, and progression to deep pocket or pump infection is rare in our experience.

PREVENtion of HeartMate II Pump Thrombosis Through Clinical Management: The PREVENT multi-center study

BACKGROUND Recommended structured clinical practices including implant technique, anti-coagulation strategy, and pump speed management (PREVENT [PREVENtion of HeartMate II Pump Thrombosis Through Clinical Management] recommendations) were developed to address risk of early (<3 months) pump thrombosis (PT) risk with HeartMate II (HMII; St. Jude Medical, Inc. [Thoratec Corporation], Pleasanton, CA). We prospectively assessed the HMII PT rate in the current era when participating centers adhered to the PREVENT recommendations. METHODS PREVENT was a prospective, multi-center, single-arm, non-randomized study of 300 patients implanted with HMII at 24 participating sites. Confirmed PT (any suspected PT confirmed visually and/or adjudicated by an independent assessor) was evaluated at 3 months (primary end-point) and at 6 months after implantation. RESULTS The population included 83% men (age 57 years ± 13), 78% destination therapy, and 83% Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) Profile 1-3. Primary end-point analysis showed a confirmed PT of 2.9% at 3 months and 4.8% at 6 months. Adherence to key recommendations included 78% to surgical recommendations, 95% to heparin bridging, and 79% to pump speeds ≥9,000 RPMs (92% >8,600 RPMs). Full adherence to implant techniques, heparin bridging, and pump speeds ≥9,000 RPMs resulted in a significantly lower risk of PT (1.9% vs 8.9%; p < 0.01) and lower composite risk of suspected thrombosis, hemolysis, and ischemic stroke (5.7% vs 17.7%; p < 0.01) at 6 months. CONCLUSIONS Adoption of all components of a structured surgical implant technique and clinical management strategy (PREVENT recommendations) is associated with low rates of confirmed PT.

Device exchange after primary left ventricular assist device implantation: Indications and outcomes

BACKGROUND Patients are being supported for longer periods with implantable left ventricular assist devices (LVADs) owing to longer transplantation wait times and approval of LVADs for destination therapy. This comes with an increased potential need for device exchange when complications arise. There are few data examining this patient population. METHODS Between August 1998 and January 2012, 45 patients (34 men) underwent 57 device exchanges after primary pulsatile or continuous-flow LVAD implantation. The median age at the initial LVAD implantation was 58 years (range, 28-78 years) and the median time to first device exchange was 15 months (range, immediate-56 months). Indications for primary LVAD included bridge to transplantation in all but 10 patients, and devices included the HeartMate I (Thoratec, Pleasanton, CA) in 16 patients, the HeartMate II (Thoratec) in 21 patients, the HeartWare HVAD (HeartWare, Framingham, MA) in 2 patients, the DuraHeart I (Terumo Heart, Ann Arbor, MI) in 1 patient, and other devices in 5 patients. Indications for reoperation included device/component failure (n=24), major driveline infection (n=15), pump thrombus (n=15), and other indications (n=2). RESULTS Pumps implanted in 57 reoperations included the HeartMate I in 15 patients, the HeartMate II in 35 patients, the HeartWare HVAD in 2 patients, the DuraHeart I in 2 patients, and other devices in 3 patients. Early mortality occurred in 2/57 (3.5%) patients. Median follow-up was 18 months (range, 1-113 months); median length of LVAD therapy after the first device exchange was 13 months (range, 1-59 months). Actuarial 1-year survival and freedom from repeated device exchange after the first exchange was 89% and 79%, respectively. CONCLUSIONS Device exchange may be required after LVAD implantation. This can be performed with low early mortality and no adverse effect on late survival. Multiple reoperations may be required in some patients.

Adverse events in contemporary continuous-flow left ventricular assist devices: A multi-institutional comparison shows significant differences

OBJECTIVES We review differences in the incidence and timing of adverse events in patients implanted with continuous-flow left ventricular assist devices (LVADs), using the Mechanical Circulatory Support Research Network registry. METHODS From May 2004 to September 2014, a total of 734 patients (591 men; median age: 59 years) underwent primary continuous-flow LVAD implantation at our institutions. Patients implanted with the HeartMate II (HMII) (560 [76%] patients), compared with the HeartWare ventricular assist device (HVAD; 174 [24%]) were more often receiving destination therapy (47% vs 20%; P < .01), had a lower preoperative creatinine level (1.2 vs 1.3; P = .01), and had less median preoperative right ventricular dysfunction (mild vs moderate; P < .01). Ischemic etiology, prior sternotomy, and median INTERMACS profile were similar. RESULTS Overall mortality was 54 of 734 (7.4%); 41 of 560 (7.3%) in the HMII group, and 13 of 174 (7.5%) in the HVAD group (P = .95). Follow-up was available in 100% of early survivors for a median of 1 year (max: 10 years) and a total of 1120 patient-years of support (HMII: 940 patient-years [median: 1.1 years, max: 5.3 years] and HVAD: 180 patient-years [median: 0.6 year, max: 10.4 years]). On multivariable analysis, GI bleeding (P = .63), any infection (P = .32), driveline infection (P = .10), and pump thrombus (P = .64) were similar between devices while HeartWare HVAD was associated with higher risk of stroke (HR: 1.8, [1.25, 2.5], P = .003). CONCLUSIONS In this pooled analysis, a trend was found for higher incidence of percutaneous driveline infections in patients treated with the HMII; a higher incidence of stroke and time-related cumulative risk of any infection and stroke was found in patients treated with the HVAD, which was independently associated with higher stroke risk.

Restoration of Sinus Rhythm by the Maze Procedure Halts Progression of Tricuspid Regurgitation After Mitral Surgery

BACKGROUND Tricuspid regurgitation (TR) is common in patients undergoing mitral valve surgery, and atrial fibrillation (AF) can cause progression of TR. This study examined the hypothesis that correction of AF with the Maze procedure can prevent the late progression of TR after mitral valve surgery. METHODS We compared severity of TR in 33 patients (January 1, 1993, to January 1, 2003) who underwent concomitant Maze procedure plus mitral valve surgery and converted to normal sinus rhythm postoperatively with case-matched control patients who underwent mitral valve surgery alone and remained in AF postoperative. Matched variables were age, sex, diabetes mellitus, left ventricular ejection fraction, and hypertension. Preoperative TR grade was similar between groups (Maze 2.2 +/- 0.8 versus no-Maze 2.3 +/- 0.8, p = 0.67). Patients with permanent transvenous pacemakers, organic tricuspid valve disease, and prior tricuspid valve surgery were excluded from this comparison. RESULTS Before hospital dismissal, average TR grade improved to 1.9 +/- 0.9 in both groups; TR improved in 42% of patients in the Maze group and 36% of patients with preoperative AF and no Maze. At last follow-up, average TR grade remained stable at 1.9 +/- 0.9 in the Maze group (p = 0.078 versus preoperative) with TR progression in only 9% of patients (3 of 33). In contrast, TR grade worsened to 2.7 +/- 0.9 in the no-Maze group (p = 0.04 versus preoperative, p < 0.001 versus postoperative, p < 0.001 versus groups), and TR worsened in 45% of patients (15 of 33). In a multivariable model, performance of a Maze procedure was protective against the progression of TR. CONCLUSIONS Continued AF after mitral valve surgery can predispose a patient to progression of TR, and this progression is prevented in patients having successful concomitant Maze procedure.