Pat Pappas

Prospective, Multicenter Study of Ventricular Assist Device Infections

Background— Ventricular assist devices (VADs) improve survival and quality of life in patients with advanced heart failure, but their use is frequently complicated by infection. There are limited data on the microbiology and epidemiology of these infections. Methods and Results— One hundred fifty patients scheduled for VAD implantation were enrolled (2006–2008) at 11 US cardiac centers and followed prospectively until transplantation, explantation for recovery, death, or for 1 year. Eighty-six patients (57%) received HeartMate II devices. Data were collected on potential preoperative, intraoperative, and postoperative risk factors for infection. Clinical, laboratory, and microbiological data were collected for suspected infections and evaluated by an infectious diseases specialist. Thirty-three patients (22%) developed 34 VAD-related infections with an incidence rate of 0.10 per 100 person-days (95% confidence interval, 0.073–0.142). The median time to infection was 68 days. The driveline was the most commonly infected site (n=28); 18 (64%) were associated with invasive disease. Staphylococci were the most common pathogen (47%), but pseudomonas or other Gram-negative bacteria caused 32% of infections. A history of depression and elevated baseline serum creatinine were independent predictors of VAD infection (adjusted hazard ratio=2.8 [P=0.007] and 1.7 [P=0.023], respectively). The HeartMate II was not associated with a decreased risk of infection. VAD infection increased 1-year mortality (adjusted hazard ratio=5.6; P<0.0001). Conclusions— This prospective, multicenter study demonstrates that infection frequently complicates VAD placement and is a continuing problem despite the use of newer, smaller devices. Depression and renal dysfunction may increase the risk of VAD infection. VAD infection is a serious consequence because it adversely affects patient survival. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01471795.

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.

Staphylococcus epidermidis Colonization Is Highly Clonal Across US Cardiac Centers

BACKGROUND Little is known about the clonality of Staphylococcus epidermidis in the United States, although it is the predominant pathogen in infections involving prosthetic materials, including ventricular assist devices (VADs). METHODS Seventy-five VAD recipients at 4 geographically diverse US cardiac centers were prospectively followed up to 1 year of VAD support. The anterior nares, sternum, and (future) driveline exit site were cultured for S. epidermidis before VAD insertion and at 7 times after surgery. Infection isolates were also collected. Isolates were typed by pulsed-field gel electrophoresis. A subset underwent susceptibility testing and staphylococcal chromosomal cassette mec and multilocus sequence typing. RESULTS A total of 1559 cultures yielded 565 S. epidermidis isolates; 254 of 548 typed isolates (46%) belonged to 1 of 7 clonal types as defined by pulsed-field gel electrophoresis. These clones were identified in up to 27 people distributed across all 4 cardiac centers. They caused 3 of 6 VAD-related infections. Disseminated clones were more antibiotic resistant than were less prevalent isolates (eg, 79% vs 54% methicillin resistant; P = .0021). CONCLUSIONS This study revealed that healthcare-associated S. epidermidis infection is remarkably clonal. We describe S. epidermidis clones that are highly resistant to antibiotics distributed across US cardiac centers. These clones may have determinants that enhance transmissibility, persistence, or invasiveness. Clinical Trials Registration. NCT01471795.

Experience with noncardiac surgery in destination therapy left ventricular assist devices patients.

Continuous flow left ventricular assist devices (CF-LVAD) are increasing the life expectancy of patients with advanced heart failure, with these patients undergoing more noncardiac operations after implantation. The purpose of this study was to determine the safety of noncardiac operations in destination therapy CF-LVAD patients. In a retrospective study of 110 CF-LVAD patients, we reviewed 36 patients who underwent 63 noncardiac operations 315.1 ± 333.5 days after LVAD placement. Fifty-four (84%) operations were elective and 10 were emergent. The mean age of the cohort was 61.4 ± 11.4 years, with the majority (81%) being men. Most patients (n = 24, 38%) underwent total abdominal operation. Of the 36 patients in the study, 23 (63.8%) patients required one surgical procedure, and 13(36.1%) patients underwent more than one procedure. Six critically ill patients (16%) of 37 expired within 30 days after emergent operation. Our study demonstrates overall good clinical outcomes with minimal intraoperative complications in LVAD patients undergoing noncardiac surgeries, except an increased propensity for intra- and postoperative transfusion of blood products because of complex coagulopathies.

Racial differences in patients with left ventricular assist devices.

We examined clinical outcomes based on ethnicity in patients undergoing left ventricular assist device (LVAD) implantation. We hypothesized that treatment in a specialized, comprehensive heart failure program results in similar survival between African Americans and whites. We retrospectively reviewed patient data implanted with HeartMate II (HM-II) LVAD over 2 years. There were 79 patients: 34 (43%) whites, 33 (42%) African Americans, and 12 (15%) patients belonging to other ethnicities there was no difference in demographics. The etiology of cardiomyopathy was more commonly ischemic in white patients compared to nonischemic in African American patients (p = 0.01). The mean left ventricular ejection fraction was 22.21 ± 10.66% in African American patients and 15.21 ± 5.54% in white patients (p = 0.008). The left ventricular end-diastolic (p = 0.06) and end-systolic (p = 0.03) diameters were greater in white patients compared to African American patients. Hypertension was seen in 79% of African American patients compared to 56% in white patients (p = 0.07). Survival by Kaplan–Meier analysis revealed an unadjusted survival advantage in African American patients (p = 0.04 by log-rank test), but this survival advantage was lost in multivariable Cox regression analysis after adjustment for other covariates. There was no difference in readmissions (p = 0.36). In patients with advanced heart failure undergoing HM-II LVAD implantation, African American patients had a similar survival and no difference in readmissions when compared with white patients despite significant differences in baseline clinical characteristics.

Thoracic bioimpedence accurately determines cardiac output in patients with left ventricular assist devices

potentially long periods of subclinical status and then by periods of insidious and progressive advancing signs and symptoms. There are increasingly useful pharmacologic methods to treat many patients, but for those with very advanced heart failure, the approaches are generally more limited. Among the approaches being utilized to support patients with advanced heart failure, surgical therapies such as implantable left ventricular assist devices (LVAD) are of great promise because of their ability to substantially alter heart size, structure and function. Lessons learned from patients receiving LVAD include the fact that even greatly impaired muscle may recover biochemically and functionally following device support, and this information, in turn, has raised the promise of using LVAD to support patients until a period of recovery is attained.