V.K. Topkara

Coronary Artery Bypass Grafting in Patients With Low Ejection Fraction

Background—Patients with low ejection fraction (EF) are at a higher risk for postoperative complications and mortality. Our objective was to assess the effect of low EF on clinical outcomes after coronary artery bypass grafting (CABG). Methods and Results—We analyzed 55,515 patients from New York State database who underwent CABG between 1997 and 1999. Patients were stratified into 1 of the 4 EF groups: Group I (EF≤20%), Group II (EF 21% to 30%), Group III (EF 31% to 40%), and Group IV (EF>40%). History of previous myocardial infarction, renal failure, and congestive heart failure were higher in patients with low EF (all P<0.001). Group I experienced a higher incidence of postoperative respiratory failure (10.1% versus 2.9%), renal failure (2.5% versus 0.6%), and sepsis (2.5% versus 0.6%) compared with Group IV. In-hospital mortality was significantly higher in Group I (6.5% versus 1.4%; P<0.001). Multivariate analysis showed hepatic failure [odds ratio (OR), 11.2], renal failure (OR, 4.1), previous myocardial infarction (OR, 3.4), reoperation (OR, 3.4), emergent procedures (OR, 3.2), female gender (OR, 1.7), congestive heart failure (OR, 1.6), and age (OR, 1.04) as independent predictors of in-hospital mortality in the low EF group. The discharges to home rate were significantly lower in Group I versus Group IV (73.1% and 87.7%, respectively; P<0.001). Conclusions—Patients with low EF are sicker at baseline and have >4 times higher mortality than patients with high EF. However, outcomes are improving over time and are superior to historical data. Therefore, CABG remains a viable option in selected patients with low EF.

The Cytoprotective Effects of Tumor Necrosis Factor Are Conveyed Through Tumor Necrosis Factor Receptor–Associated Factor 2 in the Heart

Background—Activation of both type 1 and type 2 tumor necrosis factor (TNF) receptors (TNFR1 and TNFR2) confers cytoprotection in cardiac myocytes. Noting that the scaffolding protein TNF receptor–associated factor 2 (TRAF2) is common to both TNF receptors, we hypothesized that the cytoprotective responses of TNF were mediated through TRAF2. Methods and Results—Mice with cardiac-restricted overexpression of low levels of TNF (MHCsTNF3) and TRAF2 (MHC-TRAF2LC) and mice lacking TNFR1, TNFR2, and TNFR1/TNFR2 were subjected to ischemia (30 minutes) reperfusion (30 minutes) injury ex vivo using a Langendorff apparatus. MHCsTNF3 mice were protected against ischemia-reperfusion injury as shown by a significant ≈30% greater left ventricular developed pressure, ≈80% lower creatine kinase release, and Evans blue dye uptake compared with littermates. The extent of ischemia-reperfusion induced injury was similar in wild-type, TNFR1, and TNFR2 deficient mice; however, mice lacking TNFR1/TNFR2 had a significant ≈40% lower left ventricular developed pressure, a ≈65% greater creatine kinase release, and ≈40% greater Evans blue dye uptake compared with littermates. Interestingly, MHC-TRAF2LC mice had a significant ≈50% lower left ventricular developed pressure, a ≈70% lower creatine kinase release, and ≈80% lower Evans blue dye uptake compared with littermate controls after ischemia-reperfusion injury. Biochemical analysis of the MHC-TRAF2LC hearts showed that there was activation of nuclear factor-kappaB but not c-Jun N-terminal kinase activation. Conclusion—Taken together, these results suggest that TNF confers cytoprotection in the heart through TRAF2-mediated activation of nuclear factor-&kgr;B.

Fatty acid synthase modulates homeostatic responses to myocardial stress.

Fatty acid synthase (FAS) promotes energy storage through de novo lipogenesis and participates in signaling by the nuclear receptor PPARα in noncardiac tissues. To determine if de novo lipogenesis is relevant to cardiac physiology, we generated and characterized FAS knockout in the myocardium (FASKard) mice. FASKard mice develop normally, manifest normal resting heart function, and have normal cardiac PPARα signaling as well as fatty acid oxidation. However, they decompensate with stress. Most die within 1 h of transverse aortic constriction, probably due to arrhythmia. Voltage clamp measurements of FASKard cardiomyocytes show hyperactivation of L-type calcium channel current that could not be reversed with palmitate supplementation. Of the classic regulators of this current, Ca2+/calmodulin-dependent protein kinase II (CaMKII) but not protein kinase A signaling is activated in FASKard hearts, and knockdown of FAS in cultured cells activates CaMKII. In addition to being intolerant of the stress of acute pressure, FASKard hearts were also intolerant of the stress of aging, reflected as persistent CaMKII hyperactivation, progression to dilatation, and premature death by ∼1 year of age. CaMKII signaling appears to be pathogenic in FASKard hearts because inhibition of its signaling in vivo rescues mice from early mortality after transverse aortic constriction. FAS was also increased in two mechanistically distinct mouse models of heart failure and in the hearts of humans with end stage cardiomyopathy. These data implicate a novel relationship between FAS and calcium signaling in the heart and suggest that FAS induction in stressed myocardium represents a compensatory response to protect cardiomyocytes from pathological calcium flux.

Effect of Donor Age on Long-Term Survival Following Cardiac Transplantation

Abstract  Background and Aim: The current shortage of donor hearts has forced the criteria of organ procurement to be extended, leading to increased use of older donor hearts to bridge the gap between demand and availability. Our objective was to analyze the effect of donor age on outcomes after cardiac transplantation. Methods: We retrospectively studied 864 patients who underwent cardiac transplantation at New York Presbyterian Hospital – Columbia University between 1992 and 2002. Patients were divided into two groups; donor age <40 years (Group A, n = 600) and donor age ≥40 years (Group B, n = 264). Results: Characteristics including gender, body mass index, and cytomegalovirus (CMV) status were significantly different between the two donor age groups. Race, CMV status, toxoplasmosis status, left ventricular assist device prior to transplant, diabetes mellitus, and retransplantation were similar in both the recipient groups, while age, gender, and BMI were different. Early mortality was lower in Group A, 5%, versus 9.5% in Group B. Multivariate analysis revealed recipient female gender (odd ratio (OR) = 1.71), retransplantation (OR = 1.63), and increased donor age (OR = 1.02) as significant predictors of poor survival in the recipient population. Actuarial survival at 1 year (86.7% vs 81%), 5 years (75% vs 65%), and 10 years (56% vs 42%) was significantly different as well with a log rank p = 0.002. Conclusions: These findings suggest that increased donor age is an independent predictor of long‐term survival. However, the shortage of organs makes it difficult to follow strict guidelines when placing hearts; therefore, decisions need to be made on a relative basis.

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.

Continuous-flow left ventricular assist devices and usefulness of a standardized strategy to reduce drive-line infections

BACKGROUND Drive-line infection (DLI) is a common complication of left ventricular assist device (LVAD) support, leading to significant morbidity that jeopardizes the benefits of these devices. It has been reported that DLI incidence is related to drive-line dressing strategies. The aim of this study was to determine whether implementation of a standardized drive-line care kit would reduce the incidence of DLIs. METHODS DLI data were collected prospectively on all LVAD patients implanted between 2009 and 2013 at Columbia University Medical Center. Drive-line care was altered on June 1, 2011, from a dry sterile dressing without a standard anchoring device to a standardized kit, which included silver gauze dressing and a standard anchoring device. The silver dressing was used until the wound incorporated, with a minimum of 1 month. RESULTS During the study period, 107 patients were implanted with LVADs before implementation of a standardized kit (Group A) and 159 thereafter (Group B). Median follow-up time (censoring at June 2011) for Group A was 8.73 (IQR 3.51 to 17.47) months and 11.65 (IQR 6.66 to 35.20) months for Group B (p = 0.17). DLI event rate improved from 0.18 to 0.07 event per patient-year, corresponding to a relative risk reduction of 62.5%. In addition, the 1-year freedom from infection was significantly increased in Group B (92.46%) compared with Group A (81.94%) (log rank = 0.036). CONCLUSION The use of a standardized kit, including silver dressing and a standard anchoring device, leads to decrease in DLI with an absolute risk reduction of 11%. Routine use of these dressing techniques is warranted based on our findings, and may lead to reduction of complications related to infections.

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.

Implantation of a left ventricular assist device and the hub-and-spoke system in treating acute cardiogenic shock: Who survives?

We have established a regional referral network that facilitates the transfer of patients in cardiogenic shock to our center for definitive management. This “hub-and-spoke” network has proven to be effective in treating this critically ill population. Postcardiotomy shock complicates 2% to 6% of cardiac procedures. 1 The incidence of cardiogenic shock following acute myocardial infarction (AMI) is 5% to 15%. 2 Medical management composed of inotropes and pressors with or without intra-aortic balloon pump support represents the standard of care in treating these patients. The advent of left ventricular assist devices (LVADs) introduced a surgical option for cases refractory to medical management. This study delineates who survives in this population and how the postcardiotomy setting impacts device placement. Methods

Incidence and predictors of myocardial recovery on long-term left ventricular assist device support: Results from the United Network for Organ Sharing database

BACKGROUND Mechanical circulatory support (MCS) leads to favorable changes in the failing heart at the molecular, cellular, and structural levels. However, myocardial recovery leading to device explantation is rare. We reasoned that the multicenter United Network for Organ Sharing (UNOS) registry might provide insights into clinical predictors and outcomes of the recovery process. METHODS The MCS device data set of the UNOS registry was queried for patients with long-term continuous-flow left ventricular assist devices (CF-LVADs) that were explanted for heart transplantation or indication of recovery. Analysis was restricted to adult patients (≥18 years old) who were listed for an initial heart transplantation. Patients with CF-LVADs that were explanted because of recovery were compared with patients with CF-LVADs who underwent transplantation. RESULTS We identified 594 patients with HeartMate II devices and 92 patients with HeartWare devices. Duration of support was on average 500.4 ± 325.3 days. In 34 (5.0%) patients, devices were explanted secondary to myocardial recovery. Univariate predictors of recovery in patients with long-term LVADs included younger age (40 years vs 53 years), female sex, lower body mass index (25.7 kg/m(2) vs 27.9 kg/m(2)), non-ischemic etiology (91% vs 59%), lack of implantable cardioverter defibrillator at the time of listing (44% vs 79%), and lower serum creatinine (0.97 mg/dl vs 1.28 mg/dl) (all p < 0.05). In the post-explantation period, freedom from death or transplantation was 66% at 1 year. CONCLUSIONS The incidence of recovery on device support is low in the current MCS era and limited to a select cohort of predominantly young patients with non-ischemic myopathy. Given the high incidence of disease recurrence, patients should be closely followed after device explantation.

Outcomes of contemporary mechanical circulatory support device configurations in patients with severe biventricular failure

OBJECTIVES Severe right ventricular failure often is considered a contraindication for left ventricular assist device (LVAD) therapy and necessitates use of biventricular assist devices (BiVADs). Available options for BiVADs are limited, and comparative outcomes are largely unknown. METHODS Heart transplant candidates who were registered on the United Network for Organ Sharing waitlist and underwent long-term contemporary LVAD (n = 3195) or BiVAD (n = 408) implantation, from January 2010 through June 2014, were retrospectively analyzed. We evaluated clinical characteristics and outcomes of patients requiring a BiVAD, as well as regional differences in utilization of this technology. RESULTS Patients requiring a BiVAD were younger (48.9 vs 53.3 years), had a higher proportion of nonischemic disease (69.1% vs 58.2%), a higher bilirubin level (0.9 vs 0.7 mg/dL), and a lower 6-month survival rate (68.1% vs 92.7%) after device implantation (all P < .05). Postimplantation and posttransplantation survival was comparable for commonly used BiVAD configurations, including total artificial heart, continuous flow BiVAD, a continuous-flow LVAD coupled with a right-sided device, and pulsatile flow. Significant variation was found in regional utilization of these devices, regardless of differences in transplantation waitlist times. A large body surface area was an independent predictor of mortality on a BiVAD (hazard ratio = 2.12, P = .017). CONCLUSIONS Outcomes of patients requiring a BiVAD remain poor in the contemporary device era, regardless of the configuration used. Among other clinical factors, body surface area should be incorporated into decision making for device selection in these patients.