Ricardo Bello

Increased Incidence of Gastrointestinal Bleeding Following Implantation of the HeartMate II LVAD

Abstract  Background: The HeartMate II (HMII) Left Ventricular Assist System (Thoratec Corporation, Pleasanton, CA, USA), an axial continuous‐flow left ventricular assist device (LVAD), has been approved for use in bridge‐to‐transplant patients and is under investigation for destination therapy. To avoid device‐related thromboembolic complications, antiplatelet, and anticoagulation therapy are routinely administered. A worrisome frequency of gastrointestinal (GI) bleeding events has been observed. Methods: A retrospective review of all 33 patients undergoing long‐term LVAD implantation between June 1, 2006 and July 31, 2008 at our institution for any indication was conducted. Anticoagulation consisted of heparin (intravenous or subcutaneous) followed by transition to Coumadin therapy to a target INR of two to three. Antiplatelet therapy consisted of low‐dose aspirin and dipyridamole. Results: Twenty patients received the HMII and 13 patients received other devices. Eight (40%) HMII recipients suffered at least one episode of GI bleeding while no GI bleeding occurred in recipients of other devices (p = 0.012). Of 17 total bleeding episodes, no definitive source could be identified in 11 instances (65%). Conclusions: Although definitive source identification remains elusive, we believe that the majority of bleeding arises in the small bowel, possibly due to angiodysplasias, similar to the pathophysiology encountered in patients with aortic stenosis and GI bleeding. As we move toward wider use of the HMII and other axial continuous‐flow devices in both bridge‐to‐transplant patients and for destination therapy, more studies will be necessary to understand the mechanisms of this obscure GI bleeding and develop treatment strategies to minimize its development. (J Card Surg 2010;25:352‐356)

Demonstration of left ventricular outflow tract eccentricity by real time 3D echocardiography: Implications for the determination of aortic valve area

Background: Determination of the left ventricular outflow tract cross‐sectional area (ALVOT) is necessary for calculating aortic valve area (AVA) by echocardiography using the continuity equation (CE). In the commonly applied form of CE, πr2 is used to estimate ALVOT utilizing the assumptions that LVOT is round and the parasternal long axis (PLAX) plane bisects LVOT. Imaging LVOT using real time 3D echocardiography (RT3DE) eliminates the need for these assumptions. We tested the hypothesis that LVOT is round based on a formula for eccentricity. Methods and Results: In 53 patients, 2D echocardiography (2DE) and RT3DE were acquired. ALVOT was calculated by 2DE using πr2 (ALVOT‐2D). Using RT3DE, ALVOT planimetry was performed immediately beneath the aortic valve (ALVOT‐3Dplan). Eccentricity Index (EI) was calculated using the shortest and longest LVOT diameters. The long axis was measured to be larger by 0.53 cm ± 0.36 (P < 0.005). The median EI was 0.20 (0.00–0.54), indicating that half the subjects had at least a 20% difference between the major and minor diameters. ALVOT‐3Dplan was larger than ALVOT‐2D (3.73 ± 0.95 cm2 vs. 3.18 ± 0.73 cm2; P < 0.001) by paired analysis. Using the equation of an ellipse (πab), ALVOT‐3Dellip was 3.57 ± 0.95 resulting in improved agreement with ALVOT‐3Dplan. Conclusions: In our small patient sample with normal aortic valves, we showed the LVOT shape is usually not round and frequently, elliptical. Incorrectly assuming a round LVOT underestimated the ALVOT‐3Dplan and consequently the AVA by 15%. Investigating the LVOT in aortic stenosis is warranted to evaluate whether RT3DE may improve measurement of AVA.

The use of the Berlin heart EXCOR in patients with functional single ventricle

INTRODUCTION The frequency and successful use of pediatric ventricular assist devices (VADs) as a bridge to cardiac transplantation have been steadily increasing since 2003, but the experience in patients with complex congenital heart disease has not been well described. Using a large prospectively collected dataset of children supported with the Berlin Heart EXCOR VAD, we have reviewed the experience in children with single ventricular anatomy or physiology (SV), and compared the results with those supported with biventricular circulation (BV) over the same time period. METHODS The EXCOR Investigational Device Exemption study database was retrospectively reviewed. VAD implants under the primary cohort and compassionate use cohort between May 2007 and December 2011 were included in this review. RESULTS Twenty-six of 281 patients supported with a VAD were SV. The most common diagnosis was hypoplastic left heart syndrome (15 of 26). Nine patients were supported after neonatal palliative surgery (Blalock-Taussig shunt or Sano), 12 after a superior cavopulmonary connection (SCPC), and 5 after total cavopulmonary connection (TCPC). Two patients received biventricular assist devices, 1 after stage I surgery and 1 after stage II. SV patients were supported for a median time of 10.5 days (range, 1-363 days) versus 39 days (range, 0-435 days) for BV (P = .01). The ability to be bridged to transplant or recovery in SV patients is lower than for BV patients (11 of 26 [42.3%] vs 185 of 255 [72.5%]; P = .001). Three of 5 patients with TCPC were successfully bridged to transplant and were supported with 1 VAD. Seven of 12 patients with SCPC were bridged to transplant, and only 1 of 9 patients supported after a stage I procedure survived. CONCLUSIONS The EXCOR Pediatric VAD can provide a bridge to transplant for children with SV anatomy or physiology, albeit less successfully than in children with BV. In this small series, results are better in patients with SCPC and TCPC. VAD support for patients with shunted sources of pulmonary blood flow should be applied with caution.

Readmissions After Ventricular Assist Device: Etiologies, Patterns, and Days Out of Hospital

BACKGROUND Scarce literature exists describing the patterns of readmission after continuous flow left ventricular assist device (CF-LVAD) implantation. These carry significant cost and quality of life implications. We sought to describe the etiology and pattern of readmission among patients receiving CF-LVADs. METHODS Frequency, reason, urgency, and duration of readmission as well as freedom from readmission were examined in a retrospective review of our institutional experience. As an indirect means of quality of life, the ratio of days out of hospital (OOH)/days alive with device was calculated. RESULTS From 2006 to 2011, 71 adult patients implanted with a CF device were included. Indication for device implantation was bridge to transplant (n=19), potential bridge to transplant (n=25), or destination therapy (n=27). Length of support averaged 359 days. Total support time was 69.7 patient years. One hundred fifty-five readmissions accounted for a total of 1,659 hospital days. Fifty-six patients were readmitted during the study period. Median time to first readmission was 48 days (range 2 to 663 days). Median length of stay was 5 days. The single most common etiology for readmission was gastrointestinal bleeding accounting for 14% of readmissions. Readmissions were urgent (87%), elective (10%), or life-threatening (3%). Patients on the average enjoyed 92% of their time OOH. CONCLUSIONS Patients undergoing CF-LVAD support are often readmitted within 6 months of discharge. Readmissions tend to be of short duration and the most common reason is for gastrointestinal bleeding. Importantly, following discharge after implant procedure, 51 patients spent at least 90% of days OOH.

Anti-factor Xa assay is a superior correlate of heparin dose than activated partial thromboplastin time or activated clotting time in pediatric extracorporeal membrane oxygenation*.

Objective: To assess the utility of activated clotting time, activated partial thromboplastin time, and anti-Factor Xa assay for the monitoring and dosing of heparin in pediatric patients requiring support with extracorporeal membrane oxygenation. Design: Retrospective chart review. Setting: PICU in a single, tertiary care, academic children’s hospital. Patients: Seventeen patients (age 1 d to 13.9 yr, median 0.83 yr) managed on pulmonary and cardiac extracorporeal membrane oxygenation between March 2010 and August 2012 by a single surgeon. Interventions: None. Measurements and Main Results: Twice daily measurements of anti-Factor Xa assay, activated clotting time, and activated partial thromboplastin time were determined from the same blood specimen. Data were analyzed using SAS system v9.2. Fourteen patients (82.4%) were successfully weaned from extracorporeal membrane oxygenation and 12 (70.6%) were discharged from the hospital. Pearson correlations were used to compare heparin dose and activated clotting time, activated partial thromboplastin time, and anti-Factor Xa assay. Analysis showed negative Pearson correlations in 11 of 17 patients between the activated clotting time and heparin, as compared with seven of 17 for activated partial thromboplastin time and only one for heparin and anti-Factor Xa assay. Only four patients had moderate to strong positive correlations between activated clotting time and heparin as compared with a moderate to strong positive correlation in 10 patients for anti-Factor Xa assay and heparin. Conclusions: The anti-Factor Xa assay correlated better with heparin dosing than activated clotting time or activated partial thromboplastin time. Activated clotting time has a poor correlation to heparin doses commonly associated with extracorporeal membrane oxygenation. In pediatric extracorporeal membrane oxygenation, anti-Factor Xa assay may be a more valuable monitor of heparin administration.

A single dose of erythropoietin reduces perioperative transfusions in cardiac surgery: results of a prospective single-blind randomized controlled trial

We conducted a prospective single‐blind randomized study to assess whether a single 80,000 IU dose of human recombinant erythropoietin (HRE), given just 2 days before cardiac surgery, could be effective in reducing perioperative allogeneic red blood cell transfusion (aRBCt).

Progenitor Cells From the Explanted Heart Generate Immunocompatible Myocardium Within the Transplanted Donor Heart

Rationale: Chronic rejection, accelerated coronary atherosclerosis, myocardial infarction, and ischemic heart failure determine the unfavorable evolution of the transplanted heart in humans. Objective: Here we tested whether the pathological manifestations of the transplanted heart can be corrected partly by a strategy that implements the use of cardiac progenitor cells from the recipient to repopulate the donor heart with immunocompatible cardiomyocytes and coronary vessels. Methods and Results: A large number of cardiomyocytes and coronary vessels were created in a rather short period of time from the delivery, engraftment, and differentiation of cardiac progenitor cells from the recipient. A proportion of newly formed cardiomyocytes acquired adult characteristics and was integrated structurally and functionally within the transplant. Similarly, the regenerated arteries, arterioles, and capillaries were operative and contributed to the oxygenation of the chimeric myocardium. Attenuation in the extent of acute damage by repopulating cardiomyocytes and vessels decreased significantly the magnitude of myocardial scarring preserving partly the integrity of the donor heart. Conclusions: Our data suggest that tissue regeneration by differentiation of recipient cardiac progenitor cells restored a significant portion of the rejected donor myocardium. Ultimately, immunosuppressive therapy may be only partially required improving quality of life and lifespan of patients with cardiac transplantation.

Right ventricular dysfunction following continuous flow left ventriccular assist device placement in 51 patients: predicators and outcomes

BackgroundRight ventricular (RV) dysfunction following implantation of a left ventricular assist device (LVAD) is a serious condition and is associated with increased mortality.MethodsThe aim of the study is to investigate the significance of pre-existing RV dysfunction, tricuspid valve (TV) insufficiency, and the severity of septal deviation following LVAD implantation on RV dysfunction, as well as the outcome and short-term complications in 51 patients from June 2006 to August 2010. Student t test was used to compare the data and estimate the p value.ResultsMean age was 55.1 ± 13, with a male to female ratio of 3.25. The 30-day mortality was 13.7% (7/51 patients), and the overall mortality was 23.5% (12/51 patients). Meanwhile, 21 patients (21/51; 41.2%) have undergone orthotopic heart transplantation. The mean time of support was 314.5±235 days with a median of 240 days at the time of closing this study. Echocardiographic evaluation of RV function pre- and post-implantation of an LVAD demonstrated septal deviation towards the left ventricle in immediate postoperative phase, which correlated with acute RV dysfunction (p = 0.002). Preoperative RV dysfunction was a significant predictor of postoperative right heart dysfunction following implantation of an LVAD (p = 0.001).ConclusionPreoperative RV dysfunction is a predictor of RV failure in LVAD patients. The adjustment of septal deviation through gradual increase of the LVAD flow can prevent the acute RV dysfunction following LVAD placement.

Outcomes of cardiac transplantation in septuagenarians

BACKGROUND Cardiac transplantation in many centers is programmatically limited to patients aged younger than 70 years. We investigated the trends and outcomes for cardiac transplantation in recipients aged 70 years and older in the United States. METHODS De-identified data were provided by United Network of Organ Sharing. Transplant recipients were grouped by age 60-69 years and 70 years and older. Univariate comparisons were performed using Students t-test or the Pearson chi-square test. Survival was estimated using the Kaplan-Meier technique and compared with the log-rank test. Cox regression was used to determine predictors of death after transplant. Statistical significance was assigned to p < 0.05. RESULTS Between January 1, 1998, and June 15, 2010, 5,807 sexagenarians and 332 septuagenarians received allografts. The septuagenarian cohort had more men, less diabetes, was less likely to have a ventricular assist device, and more likely to be status II. Donors for septuagenarians were older and died more frequently from intracranial hemorrhage. Median unadjusted survival was 9.8 years for sexagenarians vs 8.5 years for septuagenarians (p = 0.003). There was no difference in the incidence of cerebrovascular accident, length of stay, or pacemaker need between groups. Septuagenarians were less likely to be treated for rejection the first year (p = 0.001). Age was a multivariate predictor of death (hazard ratio, 1.289; 95% confidence interval, 1.039-1.6; p = 0.021). CONCLUSIONS Selected septuagenarians with advanced heart failure can derive great benefit from cardiac transplantation, although survival is inferior to that of an immediately younger sexagenarian cohort. Most of the mortality risk is seen in the first year after transplantation. A reduced incidence of rejection was observed and warrants further study.

Ratio of Left Atrial to Left Ventricular Size: An Anatomical Marker of the Diastolic Left Ventricular Pressure-Volume Relationship

Background: Classification of diastolic heart function is best defined by the degree of leftward and upward shift of the diastolic pressure‐volume relationship (DPVR). Direct measurement of DPVR, however, requires invasive techniques. Increased left atrial (LA) size is a marker of left ventricular (LV) diastolic hypertension, and so, the LA/LV diameter ratio has the potential to mark the degree of upward and leftward shift in the LV‐DPVR. We thus investigated the association of this novel marker with exposures known to induce diastolic dysfunction and with clinical evidence of diastolic dysfunction. Methods and Results: Reports from 7,803 patients undergoing maximal exercise stress echocardiography were reviewed. Increased LA/LV diameter ratio predicted diminished exercise capacity (P < 0.001) in a multivariate regression analysis. Increased LA and decreased LV diameters were each independently associated with exercise capacity (P < 0.001, both). Increased LA/LV diameter ratio was associated with hypertension (P = 0.001), diabetes (P = 0.03) and with increased severity of LV hypertrophy (P< 0.001). Those with LA/LV diameter ratio > 1.0 were more likely to use loop diuretics, odds ratio = 2.5 [95% CI, 1.4, 4.5], compared to those with lower ratio values. Conclusions: Increased LA/LV diameter ratio was observed in subjects with hypertension, diabetes and LV hypertrophy. Increased ratio predicted worse exercise capacity and was associated with more frequent loop diuretic use. These data are consistent with the hypothesis that this ratio is a noninvasive marker of the LV‐DPVR.