Walter Droogne

Proof of concept: hemodynamic response to long-term partial ventricular support with the synergy pocket micro-pump

OBJECTIVES The purpose of this study was to test the hemodynamic effects of partial ventricular support in patients with advanced heart failure. BACKGROUND The use of current left ventricular assist devices (VADs) that provide full circulatory support is restricted to critically ill patients because of associated risks. Smaller, less-invasive devices could expand VAD use to a larger pool of less-sick patients but would pump less blood, providing only partial support. METHODS The Synergy Pocket Micro-pump device (CircuLite, Inc., Saddle Brook, New Jersey) pumps approximately 3.0 l/min, is implanted (off pump) via a mini-thoracotomy, and is positioned in a right subclavicular subcutaneous pocket (like a pacemaker). The inflow cannula inserts into the left atrium; the outflow graft connects to the right subclavian artery. RESULTS A total of 17 patients (14 men), age 53 +/- 9 years with ejection fraction 21 +/- 6%, mean arterial pressure 73 +/- 7 mm Hg, pulmonary capillary wedge pressure 29 +/- 6 mm Hg, and cardiac index 1.9 +/- 0.4 l/min/m(2) received an implant. Duration of support ranged from 6 to 213 (median 81) days. In addition to demonstration of significant acute hemodynamic improvements in the first day of support, 9 patients underwent follow-up right heart catheterization at 10.6 +/- 6 weeks. These patients showed significant increases in arterial pressure (67 +/- 8 mm Hg vs. 80 +/- 9 mm Hg, p = 0.01) and cardiac index (2.0 +/- 0.4 l/min/m(2) vs. 2.8 +/- 0.6 l/min/m(2), p = 0.01) with large reductions in pulmonary capillary wedge pressure (30 +/- 5 mm Hg vs. 18 +/- 5 mm Hg, p = 0.001). CONCLUSIONS Partial support appears to interrupt the progressive hemodynamic deterioration typical of late-stage heart failure. If proven safe and durable, this device could be used in a relatively large population of patients with severe heart failure who are not sick enough to justify use of currently available full support VADs. (Safety and Performance Evaluation of CircuLite Synergy; NCT00878527).

Quantitative dobutamine stress echocardiography for the early detection of cardiac allograft vasculopathy in heart transplant recipients

Background: A non-invasive method to detect the presence of cardiac allograft vasculopathy (CAV) remains an important goal in clinical cardiology. Objective: To assess the value of quantitative dobutamine stress echocardiography (DSE) for the early detection of CAV. Methods: 42 heart transplant recipients underwent DSE with acquisition of both conventional two-dimensional and colour tissue Doppler data. All studies were analysed conventionally and quantitatively using regional deformation parameters—that is, peak systolic longitudinal strain (∊peak sys), strain rate (SRpeak sys) and post-systolic strain index. Myocardial segments were classified as normal, mildly abnormal or severely abnormal based on correlative angiographic findings. Results: At baseline, ∊peak sys was significantly lower in severely abnormal segments than in normal ones. However, at peak stress, ∊peak sys was able to separate three groups of segments. Receiver operating characteristic analysis showed an SRpeak sys response of <0.5/s to identify patients with CAV with a sensitivity of 88%, specificity of 85% and a negative predictive value of 92%. Conclusion: Regional myocardial function is impaired in heart transplant recipients with CAV even when the disease is considered to be non-significant on conventional angiography. Systolic deformation parameters tended to detect the existence of CAV more accurately than conventional visual DSE assessment. Strain rate imaging during stress can therefore safely be used as a non-invasive screening test for detecting CAV in heart transplant recipients.

Different evolutions in heart rate variability after heart transplantation: 10-year follow-up

Background. After heart transplantation, the donor heart is extrinsically denervated. No input of sympathetic or vagal nerves can influence the heart rate, resulting in a flat power spectrum of the beat-to-beat variability. The occurrence and the significance of reinnervation remain controversial. Methods and Results. We monitored the evolution of heart rate variability (HRV) after heart transplantation, starting from a few weeks postoperatively up to 10 years after surgery. Twenty–four-hour Holter recordings of 216 heart-transplant patients were analyzed using time and frequency domain analysis of HRV. Analysis of all data revealed an increase in 24-hour and night-time total power starting from 2 years after transplantation. Low-frequency oscillations calculated over the total 24 hours, day- and nighttime increased significantly starting from year 4 and onward (year 4–8: P<0.005). No evolution was found in high-frequency power. Subgroup analysis revealed a group with a clear spectral component (n=16), a group with a small component (n=124), and a group with a flat spectrum (n=76). Only the first group revealed an evolution in both high- and low-frequency power. Conclusion. These results indicate three different types of evolution in HRV, with reinnervating patterns present in only a minority of the patients. The vast majority of the patients show no signs of reinnervation.

Differences in psychosocial and behavioral profiles between heart failure patients admitted to cardiology and geriatric wards

Heart failure represents a growing epidemic, primarily in the elderly. Development and implementation of management programs designed for use in daily clinical practice remains a major challenge.

Time course of acquired von Willebrand disease associated with two types of continuous-flow left ventricular assist devices: HeartMate II and CircuLite Synergy Pocket Micro-pump

BACKGROUND Bleeding complications are frequent adverse events in patients supported with axial continuous-flow pumps. Previous retrospective studies demonstrated that bleeding events in patients with the HeartMate II (Thoratec Corp, Pleasanton, CA) were attributed to acquired von Willebrand syndrome. We sought to analyze the von Willebrand factor (VWF) profile in patients receiving a HeartMate II or a CircuLite (Saddle Brook, NJ,) device (Synergy Pocket Micro-pump) prospectively. METHODS Prospectively analyzed were 34 patients supported with left ventricular assist device (LVAD; 26 with HeartMate II and 8 with CircuLite). The control group comprised 20 patients who underwent heart transplantation (HTx). Blood samples were taken pre-operatively and at 14 days and 3, 6, 9, and 12 months post-operatively. RESULTS Patients with LVADs had a high incidence of bleeding complications. From the immediate post-operative phase throughout the entire observation, the VWF ristocetin cofactor activity (Rco)/antigen (Ag) ratio of patients with HeartMate II and CircuLite devices was consistently lower compared with HTx patients. No correlation was found between the individual VWF:Rco/Ag ratio and bleeding events or transfusion requirements. The VWF:Rco/Ag ratio normalized immediately in patients who received HTx. CONCLUSIONS Acquired von Willebrand syndrome was confirmed to occur immediately after the implantation of both types of LVAD and persisted up to 12 months. A lower VWF:Rco/Ag ratio was associated with larger transfusion requirements. Acquired von Willebrand syndrome resolves after LVAD explantation.

Incremental Prognostic Value of Myocardial Fibrosis in Patients With Non–Ischemic Cardiomyopathy Without Congestive Heart Failure

Background—We conducted a prospective longitudinal study to investigate the yet unknown clinical significance of myocardial fibrosis in patients with non–ischemic cardiomyopathy without history of congestive heart failure (CHF). Methods and Results—At 3 tertiary referral centers, 228 patients with non–ischemic cardiomyopathy without history of CHF were studied with cardiovascular magnetic resonance for late gadolinium enhancement (LGE) detection and quantification and prospectively followed up for a median of 23 months. The end point was a composite of cardiac death, onset of CHF, and aborted sudden cardiac death. LGE was detected in 61 (27%) patients. Thirty-one of 61 (51%) patients with LGE reached combined end point when compared with 18 of 167 (11%) patients without LGE (hazard ratio, 5.10 [2.78–9.36]; P<0.001). Patients with LGE had greater risk of developing CHF than patients without LGE (hazard ratio, 5.23 [2.61–10.50]; P<0.001) and higher rate of aborted sudden cardiac death (hazard ratio, 8.31 [1.66–41.55]; P=0.010). Multivariate analysis showed that LGE was associated with high likelihood of composite end point independent of other prognostic determinants, including age; duration of cardiomyopathy; and left ventricular volumes, mass, and ejection fraction (hazard ratio, 4.02 [2.08–7.76]; P<0.001). Improvement &khgr;2 analysis disclosed that LGE addition to models, including clinical data alone or in combination with parameters of left ventricular remodeling and function, yielded an improvement in outcome prediction (P<0.001). Addition of LGE to age and left ventricular ejection fraction improved risk stratification for composite end point (net reclassification improvement, 29.6%) and onset of CHF (net reclassification improvement, 25.4%; both P<0.001). Conclusions—In patients with non–ischemic cardiomyopathy without history of CHF, myocardial fibrosis is a strong and independent predictor of outcome, providing incremental prognostic information and improvement in risk stratification beyond clinical data and degree of left ventricular dysfunction.

Circulating apoptotic endothelial cells and apoptotic endothelial microparticles independently predict the presence of cardiac allograft vasculopathy.

OBJECTIVES Maintenance of endothelial homeostasis may prevent the development of cardiac allograft vasculopathy (CAV). This study investigated whether biomarkers related to endothelial injury and endothelial repair discriminate between CAV-negative and CAV-positive heart transplant recipients. BACKGROUND CAV is the most important determinant of cardiac allograft survival and a major cause of death after heart transplantation. METHODS Fifty-two patients undergoing coronary angiography between 5 and 15 years after heart transplantation were recruited in this study. Flow cytometry was applied to quantify endothelial progenitor cells (EPCs), circulating endothelial cells (CECs), and endothelial microparticles. Cell culture was used for quantification of circulating EPC number and hematopoietic progenitor cell number and for analysis of EPC function. RESULTS The EPC number and function did not differ between CAV-negative and CAV-positive patients. In univariable models, age, creatinine, steroid dose, granulocyte colony-forming units, apoptotic CECs, and apoptotic endothelial microparticles discriminated between CAV-positive and CAV-negative patients. The logistic regression model containing apoptotic CECs and apoptotic endothelial microparticles as independent predictors provided high discrimination between CAV-positive and CAV-negative patients (C-statistic 0.812; 95% confidence interval: 0.692 to 0.932). In a logistic regression model with age and creatinine as covariates, apoptotic CECs (p = 0.0112) and apoptotic endothelial microparticles (p = 0.0141) were independent predictors (C-statistic 0.855; 95% confidence interval: 0.756 to 0.953). These 2 biomarkers remained independent predictors when steroid dose was introduced in the model. CONCLUSIONS The high discriminative ability of apoptotic CECs and apoptotic endothelial microparticles is a solid foundation for the development of clinical prediction models of CAV.

Are right ventricular risk scores useful

OBJECTIVES Left ventricular assist device (LVAD) implantation can be complicated by right ventricular (RV) failure. Several scores have been proposed to predict this event. Our aim was to validate three of these scores in a population which had received a rotary blood pump LVAD. METHODS In a consecutive series of 59 full LVAD implantations, preoperative clinical, echocardiographic, laboratory and haemodynamic values were retrospectively collected. Three previously published predictive scores were calculated for all the patients. A logistic regression analysis was used to identify the predictors of RV support after LVAD implantation. RESULTS Fourteen patients (23.7%) needed additional temporary RV support. The three scores did not present any significant difference between patients treated with LVAD plus right ventricular assist device or LVAD only (45.86 ± 14.02 vs 42.1 ± 17.34, P = 0.46; 4.57 ± 3.37 vs 4.94 ± 2.87, P = 0.69; 2.71 ± 2.11 vs 2.92 ± 2.99m P = 0.81) and they were not predictive for RV failure. High pulmonary vascular resistance and the presence of non-ischaemic cardiomyopathy were the only significant predictors in logistic regression. CONCLUSIONS The use of risk scores failed to predict the need of RV support after LVAD. Stratification of the hazard with these scores should occur with extreme caution.

Comparison of a computer assisted learning program to standard education tools in hospitalized heart failure patients

Background: Education, coaching and guidance of patients are important components of heart failure management. Aim: The aim of this study was to compare a computer assisted learning (CAL) program with standard education (brochures and oral information from nurses) on knowledge and self-care in hospitalized heart failure patients. Satisfaction with the CAL program was also assessed in the intervention group. Methods: A quasi-experimental design was used, with a convenience sample of in-hospital heart failure patients. Knowledge and self-care were measured using the Dutch Heart Failure Knowledge Scale and the European Heart Failure Self-care Behaviour Scale at hospital admission, at discharge and after a 3-month follow-up. Satisfaction with the CAL program was assessed at hospital discharge using a satisfaction questionnaire. Within and between groups, changes in knowledge and self-care over time were tested using a mixed regression model. Results: Of 65 heart failure patients screened, 37 were included in the study: 21 in the CAL group and 16 in the usual care group. No significant differences in knowledge (p = 0.65) or self-care (p = 0.40) could be found between groups. However, both variables improved significantly over time in each study group (p<0.0001). Conclusions: Both educational strategies increased knowledge and improved self-care. The design did not allow isolation of the effects of standard education usual care from CAL. Economic and clinical outcomes of both methods should be evaluated in further research.

Matricellular proteins and matrix metalloproteinases mark the inflammatory and fibrotic response in human cardiac allograft rejection

Aims The cardiac extracellular matrix is highly involved in regulating inflammation, remodelling, and function of the heart. Whether matrix alterations relate to the degree of inflammation, fibrosis, and overall rejection in the human transplanted heart remained, until now, unknown. Methods and results Expression of matricellular proteins, proteoglycans, and metalloproteinases (MMPs) and their inhibitors (TIMPs) were investigated in serial endomyocardial biopsies (n = 102), in a cohort of 39 patients within the first year after cardiac transplantation. Out of 15 matrix-related proteins, intragraft transcript and protein levels of syndecan-1 and MMP-9 showed a strong association with the degree of cardiac allograft rejection (CAR), the expression of pro-inflammatory cytokines tumour necrosis factor (TNF)-α, interleukin (IL)-6 and transforming growth factor (TGF)-β, and with infiltrating CD3+T-cells and CD68+monocytes. In addition, SPARC, CTGF, TSP-2, MMP-14, TIMP-1, Testican-1, TSP-1, Syndecan-1, MMP-2, -9, and -14, as well as IL-6 and TGF-β transcript levels and inflammatory infiltrates all strongly relate to collagen expression in the transplanted heart. More importantly, receiver operating characteristic curve analysis demonstrated that syndecan-1 and MMP-9 transcript levels had the highest area under the curve (0.969 and 0.981, respectively), thereby identifying both as a potential decision-making tool to discriminate rejecting from non-rejecting hearts. Conclusion Out of 15 matrix-related proteins, we identified synd-1 and MMP-9 intragraft transcript levels of as strong predictors of human CAR. In addition, a multitude of non-structural matrix-related proteins closely associate with collagen expression in the transplanted heart. Therefore, we are convinced that these findings deserve further investigation and are likely to be of clinical value to prevent human CAR.