Geetha Bhat

Impact of symptom prevalence and symptom burden on quality of life in patients with heart failure

Background: Heart failure is an escalating health problem around the world. Despite significant scientific advances, heart failure patients experience multiple physical and psychological symptoms that can impact the quality of life. Aims: To determine the (1) symptom prevalence, severity, distress and symptom burden in patients with heart failure; (2) impact of age and gender on symptom prevalence, severity, distress and symptom burden; and (3) impact of symptom prevalence and symptom burden on health-related quality of life (HRQOL) in patients with heart failure. Methods: A convenience sample of 53 heart failure patients participated in this descriptive, cross-sectional design. Symptoms and HRQOL were measured using the Memorial Symptom Assessment Scale—Heart Failure and the Minnesota Living with Heart Failure Questionnaire. Results: Patients experienced a mean of 15.1 ± 8.0 symptoms. Shortness of breath and lack of energy were the most prevalent. Difficulty sleeping was the most burdensome symptom. Lower age, worse functional status, total symptom prevalence and total symptom burden predicted 67% of the variance in HRQOL. Conclusion: Patients with heart failure experience a high level of symptoms and symptom burden. Nurses should target interventions to decrease frequency, severity, distress and overall symptom burden and improve HRQOL.

An analysis of pump thrombus events in patients in the HeartWare ADVANCE bridge to transplant and continued access protocol trial

BACKGROUND The HeartWare left ventricular assist device (HVAD, HeartWare Inc, Framingham, MA) is the first implantable centrifugal continuous-flow pump approved for use as a bridge to transplantation. An infrequent but serious adverse event of LVAD support is thrombus ingestion or formation in the pump. In this study, we analyze the incidence of pump thrombus, evaluate the comparative effectiveness of various treatment strategies, and examine factors pre-disposing to the development of pump thrombus. METHODS The analysis included 382 patients who underwent implantation of the HVAD as part of the HeartWare Bridge to Transplant (BTT) and subsequent Continued Access Protocol (CAP) trial. Descriptive statistics and group comparisons were generated to analyze baseline characteristics, incidence of pump thrombus, and treatment outcomes. A multivariate analysis was performed to assess significant risk factors for developing pump thrombus. RESULTS There were 34 pump thrombus events observed in 31 patients (8.1% of the cohort) for a rate of 0.08 events per patient-year. The incidence of pump thrombus did not differ between BTT and CAP. Medical management of pump thrombus was attempted in 30 cases, and was successful in 15 (50%). A total of 16 patients underwent pump exchange, and 2 underwent urgent transplantation. Five patients with a pump thrombus died after medical therapy failed, 4 of whom also underwent a pump exchange. Survival at 1 year in patients with and without a pump thrombus was 69.4% and 85.5%, respectively (p = 0.21). A multivariable analysis revealed that significant risk factors for pump thrombus included a mean arterial pressure > 90 mm Hg, aspirin dose ≤ 81 mg, international normalized ratio ≤ 2, and Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profile level of ≥ 3 at implant. CONCLUSIONS Pump thrombus is a clinically important adverse event in patients receiving an HVAD, occurring at a rate of 0.08 events per patient-year. Significant risk factors for pump thrombosis include elevated blood pressure and sub-optimal anti-coagulation and anti-platelet therapies. This suggests that pump thrombus event rates could be reduced through careful adherence to patient management guidelines.

Predicting Survival in Patients Receiving Continuous Flow Left Ventricular Assist Devices The HeartMate II Risk Score

OBJECTIVES The aim of this study was to derive and validate a model to predict survival in candidates for HeartMate II (HMII) (Thoratec, Pleasanton, California) left ventricular assist device (LVAD) support. BACKGROUND LVAD mortality risk prediction is important for candidate selection and communicating expectations to patients and clinicians. With the evolution of LVAD support, prior risk prediction models have become less valid. METHODS Patients enrolled into the HMII bridge to transplantation and destination therapy trials (N = 1,122) were randomly divided into derivation (DC) (n = 583) and validation cohorts (VC) (n = 539). Pre-operative candidate predictors of 90-day mortality were examined in the DC with logistic regression, from which the HMII Risk Score (HMRS) was derived. The HMRS was then applied to the VC. RESULTS There were 149 (13%) deaths within 90 days. In the DC, mortality (n = 80) was higher in older patients (odds ratio [OR]: 1.3, 95% confidence interval [CI]: 1.1 to 1.7 per 10 years), those with greater hypoalbuminemia (OR: 0.49, 95% CI: 0.31 to 0.76 per mg/dl of albumin), renal dysfunction (OR: 2.1, 95% CI: 1.4 to 3.2 per mg/dl creatinine), coagulopathy (OR: 3.1, 95% CI: 1.7 to 5.8 per international normalized ratio unit), and in those receiving LVAD support at less experienced centers (OR: 2.2, 95% CI: 1.2 to 4.4 for <15 trial patients). Mortality in the DC low, medium, and high HMRS groups was 4%, 16%, and 29%, respectively (p < 0.001). In the VC, corresponding mortality was 8%, 11%, and 25%, respectively (p < 0.001). HMRS discrimination was good (area under the receiver-operating characteristic curve: 0.71, 95% CI: 0.66 to 0.75). CONCLUSIONS The HMRS might be useful for mortality risk stratification in HMII candidates and may serve as an additional tool in the patient selection process.

Results of the Destination Therapy Post-Food and Drug Administration Approval Study With a Continuous Flow Left Ventricular Assist Device: A Prospective Study Using the INTERMACS Registry (Interagency Registry for Mechanically Assisted Circulatory Support)

OBJECTIVES A post-approval (PA) study for destination therapy (DT) was required by the Food and Drug Administration (FDA) to determine whether results with the HeartMate (HM) II (Thoratec, Pleasanton, California) left ventricular assist device (LVAD) in a commercial setting were comparable to results during the DT multicenter pivotal clinical trial. BACKGROUND New device technology developed in the clinical research setting requires validation in a real-world setting. METHODS The PA study was a prospective evaluation of the first 247 HM II patients identified pre-operatively as eligible for DT in the national INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) registry. Patients were enrolled from January to September 2010 at 61 U.S. centers and followed for 2 years. A historical comparison group included patients (n = 133 at 34 centers) enrolled in the primary data cohort in the DT pivotal trial (TR). Survival rates and adverse events for the PA group were obtained from the INTERMACS registry. RESULTS Baseline characteristics were similar for PA versus TR. Forty-five percent of PA patients were in INTERMACS profiles 1 to 2 and 28% were in profile 3. Adverse events in the PA group were similar or lower than those in the TR group, including improvements in device-related infection (0.22 vs. 0.47) and post-operative bleeding requiring surgery (0.09 vs. 0.23) events per patient-year. Kaplan-Meier survival at 2 years was 62% (PA group) versus 58% (TR group). PA group survival at 1 and 2 years was 82 ± 5% and 69 ± 6% for INTERMACS profiles 4 to 7 (n = 63) versus 72 ± 3% and 60 ± 4% for profiles 1 to 3 (n = 184). The median length of stay after surgery was reduced by 6 days in the PA group versus the TR group. CONCLUSIONS Results in a commercial patient care setting for the DT population supported the original pivotal clinical trial findings regarding the efficacy and risk profile of the HM II LVAD. Survival was best in patients who were not inotrope-dependent (INTERMACS profiles 4 to 7).

Intrapericardial Left Ventricular Assist Device for Advanced Heart Failure.

Background Mechanical circulatory support with a left ventricular assist device (LVAD) is an established treatment for patients with advanced heart failure. We compared a newer LVAD design (a small intrapericardial centrifugal‐flow device) against existing technology (a commercially available axial‐flow device) in patients with advanced heart failure who were ineligible for heart transplantation. Methods We conducted a multicenter randomized trial involving 446 patients who were assigned, in a 2:1 ratio, to the study (centrifugal‐flow) device or the control (axial‐flow) device. Adults who met contemporary criteria for LVAD implantation for permanent use were eligible to participate in the trial. The primary end point was survival at 2 years free from disabling stroke or device removal for malfunction or failure. The trial was powered to show noninferiority with a margin of 15 percentage points. Results The intention‐to treat‐population included 297 participants assigned to the study device and 148 participants assigned to the control device. The primary end point was achieved in 164 patients in the study group and 85 patients in the control group. The analysis of the primary end point showed noninferiority of the study device relative to the control device (estimated success rates, 55.4% and 59.1%, respectively, calculated by the Weibull model; absolute difference, 3.7 percentage points; 95% upper confidence limit, 12.56 percentage points; P=0.01 for noninferiority). More patients in the control group than in the study group had device malfunction or device failure requiring replacement (16.2% vs. 8.8%), and more patients in the study group had strokes (29.7% vs. 12.1%). Quality of life and functional capacity improved to a similar degree in the two groups. Conclusions In this trial involving patients with advanced heart failure who were ineligible for heart transplantation, a small, intrapericardial, centrifugal‐flow LVAD was found to be noninferior to an axial‐flow LVAD with respect to survival free from disabling stroke or device removal for malfunction or failure. (Funded by HeartWare; ENDURANCE ClinicalTrials.gov number, NCT01166347.)

Incidence and Management of Gastrointestinal Bleeding With Continuous Flow Assist Devices

BACKGROUND Continuous flow left ventricular assist devices (CF-LVADs) have emerged as the standard of care for patients in advanced heart failure (HF) requiring long-term mechanical circulatory support. Gastrointestinal (GI) bleeding has been frequently reported within this population. METHODS A retrospective analysis of 101 patients implanted with the Heart Mate II from January 2005 to August 2011 was performed to identify incidence, etiology, and management of GI bleeding. Univariate and multivariate regression analysis was conducted to identify related risk factors. RESULTS A significant incidence of GI bleeding (22.8%) occurred in our predominantly destination therapy (DT) (93%) population. Fifty-seven percent of the patients with bleeding episodes bled from the upper GI (UGI) tract (with 54% bleeding from gastric erosions and 37% from ulcers/angiodysplasias), whereas 35% of patients bled from the lower GI (LGI) tract. Previous history of GI bleeding (odds ratio [OR], 22.7; 95% CI, 2.2-228.6; p=0.008), elevated international normalized ratio (INR) (OR, 3.9; CI, 1.2-12.9; p=0.02), and low platelet count (OR, -0.98; CI, 0.98 -0.99; p=0.001) were independent predictors of GI hemorrhage. Recurrent bleeding was more common in older patients (mean, 70 years; p=0.01). The majority of bleeders (60%) rebled from the same site. Management strategies included temporarily withholding anticoagulation, decreasing the speed of LVADs, and using octreotide. Octreotide did not impact the amount of packed red blood cells used, rebleeding rates, length of hospital stay, or all-cause mortality. Only 1 patient died as a direct consequence of GI bleeding. CONCLUSIONS Multiple factors account for GI bleeding in patients on CF-VADs. A previous history of bleeding increases risk significantly and warrants careful monitoring.

The Development of Aortic Insufficiency in Continuous-Flow Left Ventricular Assist Device–Supported Patients

BACKGROUND Significant aortic insufficiency (AI) after left ventricular assist device (LVAD) placement affects device performance and end-organ perfusion. This study examined the development and progression of AI after implantation of continuous-flow LVAD. METHODS Seventy-nine patients undergoing Heart Mate II (Thoratec Corp, Pleasanton, CA) LVAD implantation for predominantly destination therapy (n = 69 [87%]) were examined. Preoperative and postoperative echocardiograms for all patients were reviewed at the intervals of 0 to 3, 3 to 6, 6 to 12, 12 to 18, and 18 to 24 months. AI was graded on an interval scale of 0, none; 0.5, trivial; 1, mild; 1.5, mild to moderate; 2, moderate; 2.5, moderate to severe; and 3, severe. Development and progression of AI were analyzed. RESULTS The incidence of significant AI (mild or greater) was 52% (n = 41). Median time to AI development was 187 days. The median duration of VAD support was 761 days. Mild AI developed in 41 patients (52%). No severe AI developed. In the Cox regression model (hazard ratio [95% confidence interval]), aortic valve closure (2.51 [1.06 to 5.89]; p = 0.03), and age (1.04 [1.008 to 1.08]; p = 0.01) were independent predictors of AI development. There was no difference in mortality rates in the two groups (p = 0.40 by log-rank test). A mixed-model linear regression analysis showed a significant overall progression of AI over time (β ± standard error, 0.06 ± 0.02; p = 0.006). CONCLUSIONS AI develops over time in a significant number of Heart Mate II LVAD patients. AI is more common in patients with closed aortic valves and in the older age group. As more patients require long-term VAD support, the development of AI will need careful attention and monitoring.

Are Blood Stream Infections Associated With an Increased Risk of Hemorrhagic Stroke in Patients With a Left Ventricular Assist Device

Blood stream infections (BSIs) are an important cause of morbidity and mortality in patients with left ventricular assist devices (LVADs). The aim of this study was to examine the correlation between hemorrhagic cerebrovascular accident (CVA) and BSI after implantation of LVAD for advanced heart failure (HF). This was a retrospective descriptive review of 87 patients with end-stage HF, who underwent implantation of HeartMate II continuous-flow LVAD over a 4 year period. Blood stream infections were diagnosed by serial blood cultures, and suspected neurological complications including CVAs were confirmed by neuroimaging. Extensive patient chart review was performed, and descriptive characteristics were analyzed using SPSS statistical software. The mean age of our study population was 62.3 ± 12.8 years, and the majority of our patients were males (n = 75, 86.2%). The baseline characteristics were comparable in the patients with and without CVAs. Patients with BSI had a much greater incidence of CVA compared to patients without BSI (n = 13, 43.3% vs. n = 5, 10.0%; p < 0.0001). There was an increased mortality in patients with BSI than those without (n = 57, 65.5% vs. n = 30, 34.5%; p = 0.003). The risk of all CVAs (hemorrhagic/ischemic) was eightfold (odds ratio [OR] = 7.9; 95% confidence interval [CI] = 2.4–25.5; p = 0.001] in patients with BSI. Patients with BSI had a >20-fold risk of hemorrhagic CVA (OR = 24; 95% CI = 2.8–201.1; p = 0.03). Advanced HF patients with LVAD support who developed BSI need urgent evaluation and close monitoring for suspected neurological complications, particularly hemorrhagic CVA.

Nutrition assessment in advanced heart failure patients evaluated for ventricular assist devices or cardiac transplantation.

BACKGROUND Malnutrition has been shown to affect clinical outcomes in patients with heart failure. The aim of this study was to analyze the incidence of malnutrition and to assess its prognostic significance in patients with advanced heart failure (AHF) (being evaluated for left ventricular assist device [LVAD] or cardiac transplant) based on nutrition status as assessed by the Mini Nutritional Assessment (MNA). METHODS A retrospective analysis was conducted on 154 patients. During evaluation, a complete nutrition assessment was performed, and diagnosis of malnutrition and risk of malnutrition was done with the MNA. Its possible independent association with mortality was assessed. RESULTS The mean (SD) age of the patients was 59.3 (14.1) years, with 76% men. Twenty-two percent were classified as malnourished, 68% at risk of malnutrition, and 10% well nourished. The mortality in the 3 groups was 26.5%, 42.0%, and 6.7%, respectively (P = .02). In the multivariate logistic regression analysis, the undernutrition state (malnourished + at risk) was an independent predictor of mortality (odds ratio, 7.9; confidence interval, 1.01-62.30; P = .04). CONCLUSIONS The state of undernutrition is an independent predictor of mortality in patients with AHF. Early recognition of undernutrition through use of the MNA may affect the long-term prognosis of these patients by enabling early intervention.

How effective are continuous flow left ventricular assist devices in lowering high pulmonary artery pressures in heart transplant candidates

BACKGROUND Pulmonary hypertension (PH) is considered a risk factor for morbidity and mortality in patients undergoing heart transplantation. Medical therapy with oral and pharmacologic agents is not always effective in reducing pulmonary artery (PA) pressures. Left ventricular assist devices (LVADs) have been used to reduce PA pressures in cases of PH unresponsive to medical therapy. METHODS AND RESULTS Our study sought to evaluate the effectiveness of axial- and centrifugal- continuous flow LVADs in reversing PH in heart transplant candidates. Hemodynamics were assessed pre- and post-operatively in nine patients undergoing HeartMate II and six patients undergoing HeartWare continuous flow LVADs. Mean PA pressures were reduced from 31.9 ± 10.6 mm Hg to 22.1 ± 6.6 mm Hg (p = 0.001), and pulmonary vascular resistance was reduced from 3.08 ± 1.6 mm Hg to 1.8 ± 1.0 mm Hg (p = 0.007). This improvement was seen within seven days of LVAD implantation. Three of 15 patients were successfully transplanted, with 100% survival at an average of 199 days post-transplant. CONCLUSIONS The results of this study suggest that both axial- and centrifugal-continuous flow LVADs are effective in immediately lowering PA pressures in heart transplant candidates with PH.