Celeste T. Williams

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.

LVAD destination therapy: applying what we know about psychiatric evaluation and management from cardiac failure and transplant

Left ventricular assist devices (LVADs) have evolved into long-term use as destination therapy for those with severe end-stage heart failure due to other medical risks. Success with LVAD depends on adherence to a complicated mechanical regimen, and acceptance of a life that is far from normal. Patients with LVADs share characteristics with other end-stage cardiac failure patients and those waiting for or receiving heart transplants. Understanding the more thoroughly studied issues of psychiatric disorders, adherence, and behavioral correlates of success in heart failure and transplantation may identify feasible strategies for optimizing care of LVAD patients and suggest directions for future research. Depression and distress complicate post-transplant care. Psychiatric morbidity is associated with poor outcomes, including graft rejection, non-adherence, hospitalizations, infection, and death. With a high risk of embolic neurological events, patients’ ability for self-care may be compromised. Psychiatric symptoms are underdiagnosed and undertreated, which may impact overall survival and quality of life.

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.

Stroke while on long-term left ventricular assist device support: incidence, outcome, and predictors.

Development of stroke while on left ventricular assist device (LVAD) support can be a source of significant morbidity and mortality. From March 2006 through November 2011, one hundred patients with chronic heart failure underwent implantation of a HeartMate II (HM II) LVAD (Thoratec Corp.) as a bridge to transplant (BTT; n = 65) or destination therapy (DT; n = 35). Records were reviewed to determine the prevalence and type of postimplant stroke, anatomic cerebral location of strokes, and associated morbidity and mortality. Cox multivariate logistic regression analysis was conducted to identify independent predictors of postoperative stroke. Strokes occurred in 12 patients (12.0%): four embolic and eight hemorrhagic. Median duration of support at the time of stroke was 281.0 days for embolic strokes and 380.5 days for hemorrhagic strokes (p = 0.028). Stroke patients had a significantly higher incidence of diabetes (66.7% vs. 40.9%; p = 0.024), history of preimplant stroke (16.7% vs. 4.5%; p = 0.046), and aortic cross-clamping with cardioplegic arrest during their LVAD implant (50.0% vs. 20.2%; p = 0.034) compared with patients without postoperative strokes. Mean international normalized ratio (INR) at the time of stroke was subtherapeutic in all four patients with embolic strokes (mean: 1.5 ± 0.1 IU; range 1.3–1.6 IU) and supratherapeutic in four of eight patients with hemorrhagic strokes (mean: 3.2 ± 2.2 IU, range: 1.4–7.0 IU; p = 0.024). There was a 25.0% 30 day mortality after stroke. Diabetes (odds ratio [OR] 6.36; p = 0.029), aortic cross-clamping with cardioplegic arrest (OR 4.75; p = 0.025), duration of LVAD support (OR 1.00; p = 0.008), and INR (OR 4.42; p = 0.020) were independent predictors of stroke in multivariate analysis with a trend toward significance for history of stroke (OR 6.25; p = 0.075). Stroke represented an important source of morbidity and mortality for patients on HM II LVAD support. As long-term device therapy continues to gain popularity for both BTT and DT, a better understanding of the predictors of stroke, more strict control of postoperative anticoagulation, and the establishment of a risk stratification model may aid in minimizing its occurrence.

Left ventricular reverse remodeling with a continuous flow left ventricular assist device measured by left ventricular end-diastolic dimensions and severity of mitral regurgitation.

Pulsatile flow left ventricular assist devices (LVADs) maximally unload the left ventricle (LV), leading to reverse remodeling of the myopathic LV that manifests as decreased LV end-diastolic dimension (LVEDD) and decreased severity of mitral regurgitation (MR). There is a paucity of data, however, regarding the ability of continuous flow (CF) pumps to adequately decompress the LV to induce similar reverse remodeling. We sought to evaluate the effects of CF-LVADs on LV reverse remodeling. From March 2006 through July 2011, one hundred patients with chronic heart failure underwent implantation of CF-LVAD (93 HeartMate II LVADs and seven HeartWare LVADs) as bridge-to-transplant (n = 68) and destination therapies (n = 32). Echocardiograms and right heart catheterizations were reviewed preoperatively and at 1 and 6 months post-LVAD implantation. Mean age was 52.1 ± 12.1 years; etiology of heart failure was ischemic cardiomyopathy in 34 patients and nonischemic dilated cardiomyopathy in 66 patients. Median LVAD support time was 378.3 days; 371.5 days for patients who received bridge-to-transplant therapy and 422.2 days for patients who underwent destination therapy. Left ventricular end-diastolic dimension significantly decreased at 1 month post-LVAD implantation from 71.6 ± 12.4 to 58.3 ± 13.8 mm (p < 0.001). Severity of MR also significantly decreased from 76.0% of patients having moderate or severe MR preoperatively to 8.0% with moderate or severe MR at 1 month post-LVAD (p < 0.001). These reductions were maintained at 6 months. These data demonstrate the ability of a CF-LVAD to significantly decompress the LV, leading to significant reductions in LVEDD and severity of MR. This reverse remodeling was apparent in the early postoperative period and was sustained at 6 months. Further studies are warranted to investigate whether this correlates with clinical LV recovery.

Prognostic value of cardiopulmonary exercise testing in heart failure with preserved ejection fraction. The Henry Ford HospITal CardioPulmonary EXercise Testing (FIT-CPX) project

BACKGROUND Although cardiopulmonary exercise (CPX) testing in patients with heart failure and reduced ejection fraction is well established, there are limited data on the value of CPX variables in patients with HF and preserved ejection fraction (HFpEF). We sought to determine the prognostic value of select CPX measures in patients with HFpEF. METHODS This was a retrospective analysis of patients with HFpEF (ejection fraction ≥ 50%) who performed a CPX test between 1997 and 2010. Selected CPX variables included peak oxygen uptake (VO2), percent predicted maximum oxygen uptake (ppMVO2), minute ventilation to carbon dioxide production slope (VE/VCO2 slope) and exercise oscillatory ventilation (EOV). Separate Cox regression analyses were performed to assess the relationship between each CPX variable and a composite outcome of all-cause mortality or cardiac transplant. RESULTS We identified 173 HFpEF patients (45% women, 58% non-white, age 54 ± 14 years) with complete CPX data. During a median follow-up of 5.2 years, there were 42 deaths and 5 cardiac transplants. The 1-, 3-, and 5-year cumulative event-free survival was 96%, 90%, and 82%, respectively. Based on the Wald statistic from the Cox regression analyses adjusted for age, sex, and β-blockade therapy, ppMVO2 was the strongest predictor of the end point (Wald χ(2) = 15.0, hazard ratio per 10%, P < .001), followed by peak VO2 (Wald χ(2) = 11.8, P = .001). VE/VCO2 slope (Wald χ(2)= 0.4, P = .54) and EOV (Wald χ(2) = 0.15, P = .70) had no significant association to the composite outcome. CONCLUSION These data support the prognostic utility of peak VO2 and ppMVO2 in patients with HFpEF. Additional studies are needed to define optimal cut points to identify low- and high-risk patients.

Muscular strength and cardiorespiratory fitness are associated with health status in patients with recently implanted continuous-flow LVADs.

INTRODUCTION: Patient health status (PHS) and peak oxygen uptake ( O2) are important predictors of clinical outcomes in individuals with heart failure. Preliminary studies of individuals with left ventricular assist devices (LVADs) show improvements in both PHS and peak O2. However, the relationship between peak O2 and PHS in this population is not well described. Likewise, data regarding muscular strength are also lacking in this population. We sought to describe the association between peak O2, muscular strength, and PHS in patients with continuous-flow LVADs. METHODS: Subjects (n = 26; 7 women) completed a symptom-limited graded exercise test within an average of 82 days (range, 33-167 days) of LVAD implant. In addition, subjects underwent a 6-Minute Walk Test and an isokinetic knee extension strength test and completed the Kansas City Cardiomyopathy Questionnaire (KCCQ). Spearman correlation coefficients were performed, adjusting for body weight and gender, to examine relationships between variables. RESULTS: Muscular strength, as measured by peak torque, and peak O2 were both moderately associated with the KCCQ (r = 0.58, P = .006; r = 0.51, P = .019). A subanalysis revealed that muscular strength and peak O2 were related to different domains within the KCCQ. CONCLUSIONS: Leg muscle strength and peak O2 appear to be important factors related to PHS in patients with continuous-flow LVADs. This is likely partially a result of deconditioning due to recent hospitalization, as well as persistent heart failure–related peripheral maladaptations in skeletal muscle. Incorporating both a cardiovascular as well as strength training program before and after LVAD implant surgery may be beneficial.

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.