Longitudinal assessment of the platelet transcriptome in advanced heart failure patients following mechanical unloading.

Patients with heart failure (HF) and left ventricular assist devices (LVAD) have dysregulated thrombo-inflammatory responses, mediated in part by platelets. While studies of platelet activation have been undertaken in HF, changes in the platelet transcriptome in HF patients following mechanical unloading with an LVAD have not been investigated. We prospectively enrolled and longitudinally followed advanced HF patients (n = 32) for a mean of 57 months post-LVAD implantation. For comparison, healthy donors were also enrolled (n = 20). Platelets were hyperactive in HF, as evidenced by significantly increased formation of circulating platelet-monocyte aggregate formation. Platelet transcriptome interrogation by next-generation RNA-sequencing identified that the expression of numerous genes (n = 588) was significantly (FDR < 0.05) altered in HF patients prior to LVAD implantation. Differentially expressed genes were predicted to have roles in angiogenesis, immune and inflammatory responses, apoptosis, and cardiac muscle contraction. 90 days following LVAD implantation, the majority (80%) of differentially expressed genes in HF patients normalized, as compared to the platelet transcriptomes of healthy donors. In conclusion, advanced HF is associated with marked alterations in the platelet transcriptome. While LVAD implantation to off load the failing heart results in resolution in the majority of differentially expressed genes, a subset of the platelet transcriptome remains persistently altered.

Provider Perspectives on the Feasibility and Utility of Routine Patient-Reported Outcomes Assessment in Heart Failure: A Qualitative Analysis.

Background Patient-reported outcomes (PROs) objectively measure health-related quality of life and provide prognostic information. Advances in technology now allow for rapid, patient-friendly PRO assessment and scoring, yet the adoption of PROs in clinic has been slow. We conducted a multicenter qualitative study of diverse providers to describe the barriers and facilitators of routine PRO use in heart failure clinics. Methods and Results Sixty heart failure providers from 5 institutions participated in 8 focus groups to explore provider perspectives on the use of heart failure-specific and generic PROs in clinical practice. A qualitative editing approach was used to analyze the data, whereby a coding dictionary was iteratively developed and applied using the qualitative software program Altas.ti. Three main themes, supporting and impeding PRO use, emerged: (1) data collection; (2) presentation and interpretation; and (3) utility and value. For each construct, we identified perspectives that highlighted both barriers and facilitators. Providers identified burden, survey fatigue, and language/health literacy barriers as potentially impeding data collection. Optimal workflow, PRO frequency and length, use of PRO translations, and assistance of a patient's proxy were suggested as facilitators. Focus group discussions provided insight on how to display PROs to support its interpretability and sharing. Furthermore, the need to educate providers on the utility and value PROs over and above current clinical approaches emerged. Conclusions Overcoming the barriers and supporting facilitators of PRO adoption could potentially lead to more successful adoption of PROs in heart failure clinics.

Value-driven cardiac surgery: Achieving "perfect care" after coronary artery bypass grafting.

OBJECTIVE: The objective of this study was to determine if the implementation of a value-driven outcomes tool comprising modifiable quality and utilization metrics lowers cost and improves value of coronary artery bypass grafting (CABG) postoperative care. METHODS: Ten metrics were defined for CABG patients in 2 temporally separated phases. Clinical care protocols were designed and implemented to increase compliance with these metrics. Clinical outcomes and cost data were harvested from the electronic medical record using a proprietary value-driven outcomes tool and verified by a data management team. "Perfect care" was defined as achieving all 10 metrics per patient episode. RESULTS: Over a 45-month period, data of 467 consecutive patients who underwent isolated CABG were analyzed. "Perfect care" was successfully achieved in 304 patients (65.1%). There were no observed differences in mortality between patient groups. Linear regression analysis showed a negative correlation between percent compliance with "perfect care" and mean cost. When multivariate analysis was used to adjust for preoperative risk score, mean cost for patients with "perfect care" was 37.0% less than for those without "perfect care." CONCLUSIONS: In the context of focused institution-specific interventions to target quality and utilization metrics for CABG care, clinical care pathways and protocols informed by innovative tools that link automated tracking of these metrics to cost data might simultaneously promote quality and decrease costs, thereby enhancing value. This descriptive study provides preliminary support for a systematic approach to define, measure, and modulate the drivers of value for cardiothoracic surgery patients.

Implementation of Real-Time Assessment of Patient-Reported Outcomes in a Heart Failure Clinic: A Feasibility Study.

BACKGROUND: Patient-reported outcomes (PROs) quantify, from patients' perspectives, their symptoms, function, and quality of life. Our aim was to determine the feasibility of integrating PRO capture into routine clinical practice at a large heart failure (HF) clinic. METHODS: We examined the practicality of PRO completion at the time of clinic visit, the time required to complete the selected instruments, the completion rate, and the feasibility of immediate PRO scoring and integration of the results into the electronic health record (EHR). We deployed a computer program to capture PROs (Kansas City Cardiomyopathy Questionnaire, Patient-Reported Outcomes Measurement Information System) on a portable computer platform at the time of a clinic visit. An automated algorithm identified patients scheduled for appointments at the HF clinic at registration, provided a portable tablet computer with which to complete the appropriate PRO instruments and then scored and immediately integrated the results in the patient's EHR. RESULTS: In a 12-month period, 862 unique patients completed 1,320 PRO assessments. The mean age of this cohort was 60.1 ± 16.3 years and 66% were male. The average time for PRO assessment was 6.7 minutes and the completion rate among eligible patients was 58%, with 91% of started assessments completed in full. CONCLUSIONS: These preliminary data support the feasibility of serial PRO assessment with real-time integration into the EHR in a large outpatient population of patients with HF. We identified critical steps that should enhance adoption of this approach by clinicians and render PRO results meaningful and actionable in routine clinical care.

Patient-Reported Health-Related Quality of Life Is a Predictor of Outcomes in Ambulatory Heart Failure Patients Treated With Left Ventricular Assist Device Compared With Medical Management: Results From the ROADMAP Study (Risk Assessment and Comparative Effectiveness of Left Ventricular Assist Device and Medical Management).

BACKGROUND: The prospective observational ROADMAP study (Risk Assessment and Comparative Effectiveness of Left Ventricular Assist Device and Medical Management) demonstrated that ambulatory advanced heart failure patients selected for left ventricular assist device (LVAD) were more likely to be alive at 1 year on original therapy with ≥75-m improvement in 6-minute walk distance compared with patients assigned to optimal medical management. Whether baseline health-related quality of life (hrQoL) resulted in a heterogeneity of this treatment benefit is unknown. METHODS AND RESULTS: Patient-reported hrQoL was assessed with EuroQol questionnaire and visual analogue scale (VAS). We aimed to identify predictors of event-free survival and survival with acceptable hrQoL (VAS≥60). LVAD patients had significant improvement in 3 of 5 EuroQol dimensions (P<0.05), but no significant changes were observed with optimal medical management. Among patients with baseline VAS<55, survival on original treatment was lower for optimal medical management patients compared with those assigned to LVAD (58±7% versus 82±5%; P=0.004). No such difference was seen if baseline VAS was ≥55 (70±7% versus 75±9%; P=0.79). Survival on original therapy with acceptable quality of life was also more likely with LVAD versus optimal medical management if baseline VAS was <55, whereas outcomes in patients with higher baseline VAS scores were similar regardless of treatment assignment (P=0.046 for treatment arm and baseline VAS interaction). CONCLUSIONS: LVAD therapy resulted in improvement of patient health status in heart failure patients with low self-reported hrQoL, but not in patients with acceptable quality of life at the time of LVAD implantation. Patient-reported hrQoL should be integrated into decision making concerning the use and timing of LVAD therapy in heart failure patients who are symptom limited but remain ambulatory. CLINICAL TRIAL REGISTRATION: URL: http://www.ClinicalTrials.gov. Unique identifier: NCT01452802.

Risk Assessment and Comparative Effectiveness of Left Ventricular Assist Device and Medical Management in Ambulatory Heart Failure Patients: The ROADMAP Study 2-Year Results.

OBJECTIVES: The authors sought to provide the pre-specified primary endpoint of the ROADMAP (Risk Assessment and Comparative Effectiveness of Left Ventricular Assist Device and Medical Management in Ambulatory Heart Failure Patients) trial at 2 years. BACKGROUND: The ROADMAP trial was a prospective nonrandomized observational study of 200 patients (97 with a left ventricular assist device [LVAD], 103 on optimal medical management [OMM]) that showed that survival with improved functional status at 1 year was better with LVADs compared with OMM in a patient population of ambulatory New York Heart Association functional class IIIb/IV patients. METHODS: The primary composite endpoint was survival on original therapy with improvement in 6-min walk distance ≥75 m. RESULTS: Patients receiving LVAD versus OMM had lower baseline health-related quality of life, reduced Seattle Heart Failure Model 1-year survival (78% vs. 84%; p = 0.012), and were predominantly INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) profile 4 (65% vs. 34%; p < 0.001) versus profiles 5 to 7. More LVAD patients met the primary endpoint at 2 years: 30% LVAD versus 12% OMM (odds ratio: 3.2 [95% confidence interval: 1.3 to 7.7]; p = 0.012). Survival as treated on original therapy at 2 years was greater for LVAD versus OMM (70 ± 5% vs. 41 ± 5%; p < 0.001), but there was no difference in intent-to-treat survival (70 ± 5% vs. 63 ± 5%; p = 0.307). In the OMM arm, 23 of 103 (22%) received delayed LVADs (18 within 12 months; 5 from 12 to 24 months). LVAD adverse events declined after year 1 for bleeding (primarily gastrointestinal) and arrhythmias. CONCLUSIONS: Survival on original therapy with improvement in 6-min walk distance was superior with LVAD compared with OMM at 2 years. Reduction in key adverse events beyond 1 year was observed in the LVAD group. The ROADMAP trial provides risk-benefit information to guide patient- and physician-shared decision making for elective LVAD therapy as a treatment for heart failure. (Risk Assessment and Comparative Effectiveness of Left Ventricular Assist Device and Medical Management in Ambulatory Heart Failure Patients [ROADMAP]; NCT01452802).

Evaluation of autologous platelet rich plasma for cardiac surgery: outcome analysis of 2000 patients.

BACKGROUND: Deep and superficial sternal wound infections (DSWI & SWI) following cardiac surgery increase morbidity, mortality and cost. Autologous platelet rich plasma (PRP) derived from the patient's own blood has been used in other surgical settings to promote successful wound healing. The goal of this study was to analyze the addition of PRP using a rapid point of care bedside system to standard wound care in all patients undergoing sternotomy for cardiac surgical procedures. METHODS: Over a 7 year period, 2000 patients undergoing open cardiac operations requiring sternotomy were enrolled. One thousand patients received standard of care sternal closure. The other 1000 patients received standard of care sternal closure plus PRP applied to the sternum at the time of closure. The outcomes related to wound healing, infection, readmissions, and costs were analyzed. RESULTS: In the 2000 patients, there were more ventricular assist device implants/heart transplants and emergency operations in the PRP group; otherwise there were no significant differences. The use of PRP reduced the incidence of DSWI from 2.0 to 0.6 %, SWI from 8.0 to 2.0 %, and the readmission rate from 4.0 to 0.8 %. The use of PRP reduced the costs associated with the development of deep and superficial wound complications from $1,256,960 to $593,791. CONCLUSIONS: The use of PRP decreases the incidence and costs of sternal wound complications following cardiac surgery. The routine use of platelet rich plasma should be considered for all patients undergoing sternotomy for cardiac surgical procedures. TRIAL REGISTRATION: Clinicaltrials.gov ( NCT00130377 ) for the data registry.

Risk Assessment and Comparative Effectiveness of Left Ventricular Assist Device and Medical Management in Ambulatory Heart Failure Patients: Results From the ROADMAP Study.

BACKGROUND: Data for left ventricular assist devices (LVADs) in patients with noninotrope-dependent heart failure (HF) are limited. OBJECTIVES: The goal of this study was to evaluate HeartMate II (HMII) LVAD support versus optimal medical management (OMM) in ambulatory New York Heart Association functional class IIIB/IV patients meeting indications for LVAD destination therapy but not dependent on intravenous inotropic support. METHODS: This was a prospective, multicenter (N = 41), observational study of 200 patients (97 LVAD, 103 OMM). Entry criteria included ≥1 hospitalization for HF in the last 12 months and 6-min walk distance (6MWD) <300 m. The primary composite endpoint was survival on original therapy with improvement in 6MWD ≥75 m at 12 months. RESULTS: LVAD patients were more severely ill, with more patients classified as Interagency Registry for Mechanically Assisted Circulatory Support profile 4 (65% LVAD vs. 34% OMM; p < 0.001) than 5 to 7. More LVAD patients met the primary endpoint (39% LVAD vs. 21% OMM; odds ratio: 2.4 [95% confidence interval: 1.2 to 4.8]; p = 0.012). On the basis of as-treated analysis, 12-month survival was greater for LVAD versus OMM (80 ± 4% vs. 63 ± 5%; p = 0.022) patients. Adverse events were higher in LVAD patients, at 1.89 events/patient-year (EPPY), primarily driven by bleeding (1.22 EPPY), than with OMM, at 0.83 EPPY, primarily driven by worsening HF (0.68 EPPY). Most patients (80% LVAD vs. 62% OMM; p < 0.001) required hospitalizations. Health-related quality of life (HRQol) and depression improved from baseline more significantly with LVADs than with OMM (Δ visual analog scale: 29 ± 25 vs. 10 ± 22 [p < 0.001]; Δ Patient Health Questionnaire-9: -5 ± 7 vs. -1 ± 5 [p < 0.001]). CONCLUSIONS: Survival with improved functional status was better with HMII LVAD compared with OMM. Despite experiencing more frequent adverse events, LVAD patients improved more in HRQol and depression. The results support HMII use in functionally limited, noninotrope-dependent HF patients with poor HRQoL. (Risk Assessment and Comparative Effectiveness of Left Ventricular Assist Device [LVAD] and Medical Management [ROADMAP]; NCT01452802).

Characterization of diffuse fibrosis in the failing human heart via diffusion tensor imaging and quantitative histological validation.

Non-invasive imaging techniques are highly desirable as an alternative to conventional biopsy for the characterization of the remodeling of tissues associated with disease progression, including end-stage heart failure. Cardiac diffusion tensor imaging (DTI) has become an established method for the characterization of myocardial microstructure. However, the relationships between diffuse myocardial fibrosis, which is a key biomarker for staging and treatment planning of the failing heart, and measured DTI parameters have yet to be investigated systematically. In this study, DTI was performed on left ventricular specimens collected from patients with chronic end-stage heart failure as a result of idiopathic dilated cardiomyopathy (n = 14) and from normal donors (n = 5). Scalar DTI parameters, including fractional anisotropy (FA) and mean (MD), primary (D1 ), secondary (D2 ) and tertiary (D3 ) diffusivities, were correlated with collagen content measured by digital microscopy. Compared with hearts from normal subjects, the FA in failing hearts decreased by 22%, whereas the MD, D2 and D3 increased by 12%, 14% and 24%, respectively (P < 0.01). No significant change was detected for D1 between the two groups. Furthermore, significant correlation was observed between the DTI scalar indices and quantitative histological measurements of collagen (i.e. fibrosis). Pearson's correlation coefficients (r) between collagen content and FA, MD, D2 and D3 were -0.51, 0.59, 0.56 and 0.62 (P < 0.05), respectively. The correlation between D1 and collagen content was not significant (r = 0.46, P = 0.05). Computational modeling analysis indicated that the behaviors of the DTI parameters as a function of the degree of fibrosis were well explained by compartmental exchange between myocardial and collagenous tissues. Combined, these findings suggest that scalar DTI parameters can be used as metrics for the non-invasive assessment of diffuse fibrosis in failing hearts.

Current status of the total artificial heart.

Although heart transplantation remains the gold standard for patients who remain in advanced heart failure despite optimal medical therapy, limited donor supplies allows for just >2000 transplant each year in the United States. Recent enthusiasm has developed for the role of mechanical circulatory support for this ever-growing population of sick patients. Although much attention has been directed toward ventricular assist devices, less information is available regarding the role of the total artificial heart. Indeed, efforts in this latter technology have allowed the relatively recent deployment of a variety of complete circulatory assist devices. The purpose of this article is to review the historical development, current use, and future role of total artificial hearts.