Cristina Tita

Gastrointestinal bleeding with the HeartMate II left ventricular assist device.

BACKGROUND Continuous flow left ventricular assist devices (CF-LVADs) have yielded improved outcomes compared with pulsatile flow devices for patients on long-term support. However, significant rates of gastrointestinal bleeding (GIB) have been observed during CF-LVAD support. METHODS From March 2006 through March 2011, 86 patients with chronic heart failure underwent implantation of a CF-LVAD (HeartMate II; Thoratec Corp., Pleasanton, CA). Records were reviewed to determine the prevalence of post-implant GIB, location of the bleeding site and associated morbidity and mortality. Uni- and multivariate analyses were conducted to identify independent predictors of GIB. RESULTS GIB occurred in 19 patients (22.1%) with a duration of support that ranged from 5 to 456 days. Sources of GIB included small bowel and rectum in 6 patients each, large bowel in 2 patients and stomach in 1 patient. No definite source was identified in 4 patients. There were no deaths referable to GIB. Recurrent GIB occurred in 4 patients. History of a GIB prior to LVAD implant was the only variable significantly different between patients with and without post-implant GIB (21.1% vs 10.4%, p = 0.016), and was the only independent predictor of GIB (OR = 2.24, 95% CI 2.121 to 2.435, p = 0.004). CONCLUSIONS Gastrointestinal bleeding is a frequent source of morbidity for patients on HeartMate II LVAD support but does not significantly impact survival. As implantation of CF-LVADs with non-pulsatile flow gains popularity for both bridge-to-transplant and destination therapy, a better understanding of the pathophysiology of GIB in these patients will be needed for minimizing this complication.

Impact of continuous-flow left ventricular assist device support on right ventricular function

BACKGROUND Continuous-flow (CF) pumps have yielded improvements in short- and long-term survival and quality of life, and have reduced the number of left ventricular assist device (LVAD)-related complications. However, their ability to unload the right ventricle (RV) and improve RV function has not been as clearly defined. We evaluated the short- and mid-term effects of CF-LVADs on central venous pressure (CVP), pulmonary artery pressures (PAP), pulmonary capillary wedge pressure (PCWP), cardiac index (CI), RV ejection fraction (RVEF), RV end-diastolic dimension (RVEDD), RV stroke work index (RVSWI), tricuspid annular plane systolic excursion (TAPSE) and severity of tricuspid regurgitation (TR). METHODS From March 2006 through June 2012, 130 patients with chronic heart failure underwent implantation of a CF-LVAD (122 HeartMate II and 8 HeartWare devices) as a bridge to transplant (n = 76) or as destination therapy (n = 54). Patients with pre-operative long-term LVADs (n = 4) and patients who underwent concomitant tricuspid valve repairs during their LVAD implant (n = 21) were excluded from the analysis. Echocardiograms and right heart catheterizations of the remaining 105 patients were reviewed pre-operatively and at 1 and 6 months post-LVAD implantation. RESULTS At 1 month post-LVAD implantation, CVP decreased from 12.4 ± 5.9 mm Hg to 8.7 ± 4.5 mm Hg (p < 0.001), systolic PAP decreased from 52.3 ± 14.1 mm Hg to 36.8 ± 11.3 mm Hg (p < 0.001), PCWP decreased from 23.0 ± 9.4 mm Hg to 12.9 ± 8.0 mm Hg (p < 0.001), CI index increased from 1.8 ± 0.5 liters/min m2 to 2.4 ± 0.5 liters/min m2 (p < 0.001), RVEF increased from 33.1 ± 4.9% to 40.4 ± 6.2% (p < 0.001), RVEDD decreased from 36 mm to 31 mm (p = 0.020), RVSWI improved from 408.6 ± 144.6 mm Hg ml m2 to 614.4 ± 196.2 mm Hg ml m2 (p < 0.001), and mean TAPSE increased from 1.1 ± 0.4 cm to 1.9 ± 0.4 cm (p = 0.004). Similarly, qualitative RV function on echocardiography improved from 57.1% moderately or severely reduced pre-operatively to 38.1% at 1 month (p = 0.008). Severity of TR decreased from 11.4% moderate or severe pre-operatively to 4.8% at 1 month (p < 0.001). These improvements were maintained at 6 months post-LVAD. CONCLUSIONS CF-LVAD support significantly decreased CVP and RVEDD, with concomitant improvement in RV function, as measured by increases in RVEF, RVSWI and TAPSE, as well as improvements in the qualitative echocardiographic appearance of RV contractility and a reduction in TR.

Non-cardiac surgery in patients on long-term left ventricular assist device support

BACKGROUND An increasing number of patients on left ventricular assist device (LVAD) support are requiring non-cardiac surgical (NCS) procedures. We reviewed our experience with the management of patients on continuous flow (CF) LVAD support undergoing NCS. METHODS From March 2006 through March 2011, 86 patients with chronic heart failure underwent implantation of a HeartMate II (Thoratec Corp, Pleasanton, CA) LVAD. Clinical records of these patients were reviewed to identify patients who underwent NCS while on LVAD support, with a focus on peri-operative death, bleeding, thrombosis, and device malfunction, as well as management of pre-operative anti-coagulation. RESULTS While on CF-LVAD support, 20 patients underwent 25 NCSs, comprising 13 major and 12 minor procedures. Operations were performed electively in 22 and as emergencies in 3. No peri-operative deaths, thromboembolic complications, or device malfunctions occurred. The incidence of bleeding requiring transfusion of packed red blood cells was 36.0%, including 25% of patients undergoing minor NCSs and 46.2% undergoing major NCSs (p = 0.004). All bleeding complications occurred in patients on both warfarin and aspirin pre-operatively. The only significant differences between patients who did and did not require transfusion were pre-operative warfarin use and significantly higher pre-operative international normalized ratio in the transfused group (1.9 ± 0.4 vs 1.4 ± 0.3; p = 0.008). CONCLUSIONS Non-cardiac operations can be performed safely in patients with CF-LVADs. It may possible to reduce peri-operative bleeding by lowering pre-operative anti-coagulation goals, especially before major surgery. However, additional analysis is required to determine if this can be performed safely.

Management of Aortic Valve Insufficiency in Patients Supported By Long-Term Continuous Flow Left Ventricular Assist Devices

Continuous flow (CF) left ventricular assist devices (LVADs) have yielded improved outcomes in patient survival and quality of life compared with first-generation pulsatile pumps; however, they have been associated with an increased incidence of postimplant aortic valve insufficiency (AI), which can have can have serious clinical consequences if not diagnosed and treated expeditiously. We reviewed our experience with AI after LVAD since the start of our CF LVAD program. From March 2006 through July 2011, 94 patients with chronic heart failure underwent implantation of a HeartMate II (HM II) LVAD. Severe AI developed in three patients after CF LVAD implantation. The clinical records of these patients were reviewed to analyze the presenting signs and symptoms of AI, identify the duration of LVAD support when the AI occurred, how the AI was treated, and the outcomes.

Short term effects of milrinone on biomarkers of necrosis, apoptosis, and inflammation in patients with severe heart failure

IntroductionInotropes are associated with adverse outcomes in heart failure (HF), raising concern they may accelerate myocardial injury. Whether biomarkers of myocardial necrosis, inflammation and apoptosis change in response to acute milrinone administration is not well established.MethodsTen patients with severe HF and reduced cardiac output who were to receive milrinone were studied. Blood samples were taken just before initiation of milrinone and after 24 hours of infusion. Dosing was at the discretion of the patients attending physician (range 0.25–0.5 mcg/kg/min). Plasma measurements of troponin, myoglobin, N-terminal-pro-BNP, interleukin-6, tumor necrosis factor-α, soluble Fas, and soluble Fas-ligand were performed at both time points.ResultsTroponin was elevated at baseline in all patients (mean 0.1259 ± 0.17 ng/ml), but there was no significant change after 24 hours of milrinone (mean 0.1345 ± 0.16 ng/ml, p = 0.44). There were significant improvements in interleukin-6, tumor necrosis factor-α, soluble Fas, and soluble Fas-ligand (all p < 0.05) indicative of reduced inflammatory and apoptotic signaling compared to baseline.ConclusionIn conclusion, among patients with severe HF and low cardiac output, ongoing myocardial injury is common, and initiation of milrinone did not result in exacerbation of myocardial injury but instead was associated with salutary effects on other biomarkers.

Relationship of tricuspid repair at the time of left ventricular assist device implantation and survival

Purpose Tricuspid regurgitation contributes to right ventricular failure (RVF) and is associated with worse clinical outcomes in patients undergoing left ventricular assist device (LVAD) treatment. However, whether tricuspid valve repair (TVR) at the time of LVAD implantation improves outcomes is not clear. Methods We identified all patients undergoing initial implantation of a long-term continuous-flow LVAD at our institution from March 2006 to August 2011. We assessed the impact of TVR on survival and incidence of RVF using Kaplan-Meier curves and proportional hazards regression adjusted for age, gender, baseline tricuspid regurgitation, RV function, MELD score, albumin, and indication (bridge vs. destination). Results A total of 101 patients were included in the analysis, of which 14 patients underwent TVR concomitant LVAD. All TVR patients had moderate or severe baseline regurgitation. Crude survival was not different between groups. In multivariable models adjusted for confounding factors, TVR showed a significant association with improved survival (HR = 0.1, p = 0.049). Adjusted models showed no difference in RVF. Conclusions In this cohort of patients, TVR at the time of LVAD implantation appears associated with better survival. Additional larger studies are needed to verify the effect of TVR at the time of LVAD implantation, and whether it should be utilized more frequently.

A Phase 2a dose-escalation study of the safety, tolerability, pharmacokinetics and haemodynamic effects of BMS-986231 in hospitalized patients with heart failure with reduced ejection fraction

This study was designed to evaluate the safety, tolerability and haemodynamic effects of BMS‐986231, a novel second‐generation nitroxyl donor with potential inotropic, lusitropic and vasodilatory effects in patients hospitalized with decompensated heart failure and reduced ejection fraction (HFrEF).

Assessing the Potential of E-mail for Communicating Drug Therapy Recommendations to Physicians in Patients With Heart Failure and Ventricular-Assist Devices

Purpose: This project explores electronic mail (e-mail) as a potential medium for pharmacists to communicate pharmacotherapy interventions to prescribers. Methods: This retrospective descriptive analysis was conducted at an urban, academic teaching hospital. The pharmacist attempted a drug therapy intervention via e-mail when unable to make face-to-face contact with the attending physician. Eligible patients for this project were admitted to the advanced heart failure (HF) team between December 1, 2010, and July 31, 2011, and had at least 1 attempted e-mail intervention. The primary outcome was the number of accepted interventions, while the secondary end point was the time until a physician e-mail response. Results: A total of 51 e-mail interventions were attempted on 29 patients (mean age = 53, 24% caucasian, 59% male, 69% left ventricular-assist device [VAD]). Overall, of the total 51 interventions,44 (86.3%) were accepted. The average time to a physician e-mail response was 41 minutes. Initiation of drug therapy and changing dose and route or frequency accounted for the most frequent intervention (33%). The most common drug classes involved in the e-mail interventions were angiotensin-converting enzyme inhibitors (15.7%), loop diuretics (9.8%), and antiplatelet agents (7.8%). Conclusion: Clinical pharmacists with well-established physician relationships can effectively implement timely drug therapy recommendations using e-mail communications in patients with advanced HF or VADs.

DOING THE RIGHT THING: ACUTE RIGHT VENTRICULAR FAILURE POST LEFT VENTRICULAR ASSIST DEVICE IMPLANTATION

Acute right ventricular failure (RVF) is a serious complication post left ventricular assist device (LVAD) implantation. Multiple contributory factors are involved and management with a right ventricular assist device (RVAD) may be essential. A 68-year-old woman with non-ischemic cardiomyopathy and