Time in Therapeutic Range Significantly Impacts Survival and Adverse Events in Destination Therapy Patients.

The study aim was to examine the impact time in therapeutic range (TTR, International Normalized Ratio [INR] 2.0-3.0) has on survival and adverse events in patients receiving the HeartWare HVAD System in the ENDURANCE and ENDURANCE Supplemental Trials. Evaluable subjects (n = 495) had >1 INR value recorded 1-24 months postimplant and were categorized as: low TTR (10-39%), moderate TTR (40-69%), and high TTR (≥70%). Baseline characteristics, adverse events, and survival were analyzed. Low TTR patients experienced higher rates of major bleeding (1.69 vs. 0.54 events per patient year [EPPY]; p < 0.001), GI bleeding (1.22 vs. 0.38 EPPY; p < 0.001), stroke (0.47 vs. 0.17 EPPY; p < 0.001), thrombus requiring exchange (0.05 vs. 0.01 EPPY; p = 0.02), infection (1.44 vs. 0.69 EPPY; p < 0.001), and renal dysfunction (0.23 vs. 0.05 EPPY; p < 0.001) compared with high TTR. Moderate TTR had higher rates of major bleeding (0.75 vs. 0.54 EPPY; p < 0.001), thrombus requiring exchange (0.05 vs. 0.01 EPPY; p = 0.007), cardiac arrhythmia (0.32 vs. 0.24 EPPY; p = 0.04), and infection (0.90 vs. 0.69 EPPY; p = 0.001) compared with high TTR. Two year survival was greater among moderate and high versus low cohorts (Log-rank p = 0.001). The significant reduction in morbidity and mortality in destination therapy (DT) HVAD patients with well-controlled TTR (≥70%) emphasizes the importance of vigilant anticoagulation management.

Two-Year Follow Up of the LATERAL Clinical Trial: A Focus on Adverse Events.

BACKGROUND: The LATERAL trial validated the safety and efficacy of the thoracotomy approach for implantation of the HeartWare HVAD System, leading to Food and Drug Administration approval. We sought to analyze 24-month adverse event (AE) rates, including a temporal analysis of the risk profile, associated with the thoracotomy approach for the HVAD system. METHODS: AEs from the LATERAL trial were evaluated over 2 years postimplant. Data was obtained from the Interagency Registry for Mechanically Assisted Circulatory Support database for 144 enrolled United States and Canadian patients. Temporal AE profiles were expressed as events per patient year. RESULTS: During 162.5 patient years of support, there were 25 driveline infections (0.15 events per patient year), 50 gastrointestinal bleeds (0.31 events per patient year), and 21 strokes (0.13 events per patient year). Longitudinal AE analysis at follow-up intervals of <30 and 30 to 180 days, and 6 to 12 and 12 to 24 months revealed the highest AE rate at <30 days, with a decrease in total AEs within the first 6 months. After 6 months, most AE rates either stabilized or decreased through 2 years, including a 95% overall freedom from disabling stroke. CONCLUSIONS: Two-year follow-up of the LATERAL trial revealed a favorable morbidity profile in patients supported with the HVAD system, as AE rates were more likely to occur in the first 30 days postimplant, and overall AE rates were significantly reduced after 6 months. Importantly, 2-year freedom from disabling stroke was 95%. These data further support the improving AE profile of patients on long-term HVAD support. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02268942.

Giant right coronary artery aneurysm presenting as cardiac tamponade.

Giant coronary artery aneurysms are rare and have variable presentations, which range from an incidental finding to sudden death. We report a case of a female presenting with chest pain and signs of cardiac tamponade who underwent a computed tomography (CT) pulmonary embolus protocol and was found to have haemopericardium with accumulation of contrast adjacent to the aorta. She underwent emergent sternotomy and was found to have a ruptured giant right coronary artery aneurysm, which was ligated and bypassed. This report highlights the difficulty of diagnosing a ruptured giant coronary artery aneurysm via CT and provides valuable information on an atypical presentation.

Low-level-laser irradiation induces photorelaxation in coronary arteries and overcomes vasospasm of internal thoracic arteries.

BACKGROUND AND OBJECTIVE: As low-level laser irradiation (LLLI) seems to induce vasodilation besides many other known biological effects, LLLI has been increasingly used in therapy of medical conditions with various irradiation parameters. The aim of this study was to investigate the effect of LLLI on photorelaxation of human coronary and internal thoracic arteries (ITA). MATERIALS AND METHODS: Thirty vessel segments of ITA used for routine coronary artery bypass grafting as well as left anterior descending coronary arteries (LAD) of patients undergoing cardiac transplantation were cut into 4-mm rings stored in a modified Krebs-Henseleit solution and evaluated in a myograph. Both types of vessel segments were irradiated by a semiconductor non-thermal GaAs diode laser operating at a wavelength of 680 nm. After precontraction with thromboxane agonist U44619, respective relaxation responses were evaluated and compared to pharmacological dilatation induced by substance P. RESULTS: Mean pharmacological vasodilation by substance P was 22.6 ± 3.3%, 12.8 ± 1.4%, and 20.4 ± 3.2% in macroscopic healthy LAD, LAD with atheromatous plaque, and ITA, respectively. Average photorelaxation induced by LLLI was 16.5 ± 2.0%, 1.9 ± 1.7%, and 6.8 ± 4.7%, accordingly. Vasodilatatory responses induced either by substance P or administration of LLLI were significantly decreased in LAD with atheromatous plaque (P < 0.0001). Vasospasms of ITA segments occurring during experiments could be abandoned when LLLI was administered. CONCLUSION: Macroscopic healthy LAD exposed to LLLI revealed significant photorelaxation. With the administration of LLLI, 73% of the maximal obtainable effect by an endothelium-dependent vasodilator could be reached. Furthermore, LLLI has the potential to overcome vasospasms of ITA.

Initial clinical experience with a novel left ventricular assist device with a magnetically levitated rotor in a multi-institutional trial.

BACKGROUND: Third-generation rotary blood pumps have magnetically levitated rotors that eliminate mechanical wear over the years. Together with their potential for miniaturization, these pumps seem suitable for long-term support of patients with a wide range of body surface areas (BSA). Recently, the novel HVAD pump (HeartWare Inc, Framingham, MA), a miniaturized centrifugal pump with a hydrodynamic, magnetically levitated rotor, became ready for clinical application. METHODS: In a multi-institutional trial in Europe and Australia, 23 patients (mean age, 47.9 ± 12 years) in end-stage heart failure were enrolled in 5 centers. The primary end point of the bridge-to-transplant study was survival to heart transplant or survival to 180 days on the device, whichever occurred first. Follow-up data at 1 year are presented. The small size of the device allows for intrapericardial placement of the pump. RESULTS: Implant procedures were generally fast and uneventful. Mean duration of support was 167 ± 143 days (range, 13-425 days), and mean blood flow provided by the pump was 6.1 ± 1.1 liters/min. At the 180-day end point, 2 patients had undergone successful transplant at 157 and 175 days, 2 patients died while on the device, and 19 patients continued pump support for more than 180 days. Actuarial survival after 6 months was 91% and was 86% at the 1-year follow-up. CONCLUSIONS: The design of the HVAD pump enables a quick and less invasive implantation. The results to date demonstrate satisfactory long-term survival with excellent quality of life in this cohort of 23 patients of the initial multi-institutional Conformité Européene (CE) mark trial.

Age and outcome after continuous-flow left ventricular assist device implantation as bridge to transplantation.

OBJECTIVE: The effect of age on outcomes after continuous-flow left ventricular assist device (LVAD) implantation as a bridge to transplantation (BTT) was determined. METHODS: From November 1998 to July 2007, 86 patients with advanced heart failure underwent continuous-flow LVAD implantation as BTT and were retrospectively analyzed. Patients were categorized into 2 groups by age at LVAD implantation: 56 patients (65.1%) younger than 60, Group 1; and 30 (34.9%) aged 60 years or older, Group 2. RESULTS: Group 2 patients had a higher incidence of heart failure caused by ischemic heart disease (63.3% vs 32.1%, p = 0.005) and more severely impaired renal function by Modification of Diet in Renal Disease-derived glomerular filtration rates (51.9 +/- 15.9 vs. 68.0 +/- 20.5 ml/min/1.73 m(2), p < 0.001) than Group 1. Age was the only independent predictor of post-LVAD death (hazard ratio, 1.4 p = 0.003). The BTT rate was lower (33.3% vs 62.5%, p = 0.010), and incidence of post-LVAD renal failure was higher (53.3% vs 30.4%, p = 0.037) in Group 2 vs Group 1. Post-LVAD survival at 1, 3, and 6 months was 92.9%, 79.9%, and 74.0% for Group 1 and 90.0%, 62.0%, and 37.0% for Group 2 (p = 0.007). Post-transplant survival at 1, 3, and 5 years was 87.8%, 82.3%, and 76.0% for Group 1 and 90.0%, 67.5%, 67.5% for Group 2 (p = 0.517). CONCLUSIONS: Patients aged 60 years and older have inferior post-LVAD survival; however, post-transplant survival is excellent. We advocate LVAD placement as bridge-to-transplant therapy only in carefully selected older patients most well suited for transplantation.

Renal function and outcome after continuous flow left ventricular assist device implantation.

BACKGROUND: Renal dysfunction as a risk factor with the use of left ventricular assist devices (LVAD) is controversial. We determined the effect of renal function on outcomes after continuous flow LVAD implantation. METHODS: Eighty-six patients with advanced heart failure undergoing continuous flow LVAD implantation as bridge to transplantation from November 1998 to July 2007 were retrospectively analyzed. Renal function was assessed using the Modification of Diet in Renal Disease study-derived glomerular filtration rates (GFR [mL x min(-1) x 1.73 m(-2)]). Patients were categorized into two groups based on pre-LVAD GFR: those with normal renal function (GFR > 60, n = 46), and those with renal dysfunction (GFR < 60, n = 40). RESULTS: Post-LVAD survival at 1, 3, and 6 months for GFR greater than 60 was 91.3%, 79.9%, 72.6%, respectively, and for GFR less than 60, it was 92.5%, 66.5%, 47.9%, respectively (p = 0.038). Bridge-to-transplant rate was lower for GFR less than 60 than for GFR greater than 60 (40.0% versus 63.0%, p = 0.033). For GFR less than 60, GFR improved on LVAD support: implant to month 6, 41.7 +/- 11.5 to 62.7 +/- 25.0 (p = 0.021). Post-LVAD survival was improved in GFR less than 60 patients who after LVAD implantation recovered renal function to GFR greater than 60 (p < 0.001). Patients with post-LVAD renal failure had significantly lower post-LVAD survival regardless of pre-LVAD renal function (p < 0.001). CONCLUSIONS: Patients with renal dysfunction have poorer outcomes after continuous flow LVAD implantation. However, renal function improves after LVAD implantation and is associated with improved survival. Our data underscore the importance of end-organ function in patient selection for LVAD therapy.

Low molecular weight heparin as an alternative to unfractionated heparin in the immediate postoperative period after left ventricular assist device implantation.

We present a regimen for anticoagulation in the immediate postoperative period after left ventricular assist device (LVAD) implantation using low molecular weight heparin (LMWH) as an alternative to unfractionated heparin. Between May and September 2007, eight consecutive patients undergoing LVAD implantation for advanced heart failure received the LMWH nadroparin. Nadroparin was given twice daily to achieve anti-Factor Xa activity target peak levels of 0.4 +/- 0.1 U/mL. The antiplatelet therapy consisted of aspirin (100 mg/day) and dipyridamole (3 x 75 mg/day). One patient underwent heart transplantation, three patients died, and four patients continued to receive device support. The median duration of support was 78 days (range, 46 to 174). No major bleeding was observed; minor bleeding occurred in three patients. In two patients, pump thrombosis was suspected. There were two ischemic and no hemorrhagic strokes. The use of LMWH may provide a new anticoagulation treatment option in the immediate postoperative period after LVAD implantation.

Renal function after implantation of continuous versus pulsatile flow left ventricular assist devices.

BACKGROUND: This study was designed to determine the effect of continuous vs pulsatile flow devices on renal function after left ventricular assist device (LVAD) implantation. METHODS: Ninety-two patients undergoing LVAD implantation as bridge-to-transplant therapy were retrospectively analyzed. Patients receiving continuous flow devices (n = 63, 68.5%) were compared with patients receiving pulsatile flow devices (n = 29, 31.5%). Renal function was assessed by 2 calculated glomerular filtration rates (GFR) using the Modification of Diet in Renal Disease (MDRD)-derived GFR (ml/min/1.73 m(2)) and the Cockcroft-Gault-derived creatinine clearance (CrCl, ml/min). RESULTS: Mean GFR/CrCl was comparable between the groups at LVAD implantation, in the post-implantation period, and at transplantation. Both groups had a significant increase in mean GFR at Week 1 post-implantation (continuous, 59.4 +/- 22.8 to 76.4 +/- 38.6, p = 0.001; pulsatile, 52.5 +/- 21.1 to 69.2 +/- 34.7; p = 0.007), Week 4 (continuous, 59.9 +/- 23.0 to 84.3 +/- 32.9; p < 0.001; pulsatile, 50.3 +/- 21.1 to 79.9 +/- 38.7, p = 0.007), and Week 12 (continuous, 60.3 +/- 23.1 to 75.3 +/- 30.2, p = 0.004; pulsatile, 55.5 +/- 23.1 to 74.2 +/- 27.2, p = 0.037) that was also seen with the Cockcroft-Gault-calculated CrCl. No significant increase occurred in mean GFR/CrCl to transplantation. Incidence of post-implantation renal failure was comparable between the groups (continuous, 38.1%; pulsatile, 31.0%; p = 0.512). CONCLUSIONS: After LVAD implantation, patients with continuous flow devices and patients with pulsatile flow devices have comparable renal function.

Endocrine function is not impaired in patients with a continuous MicroMed-DeBakey axial flow pump.

OBJECTIVES: Pulsatile blood flow has been regarded to be of importance for the regulation of endocrine organs. A new generation of continuous flow mechanical blood pumps is now available for clinical application. Patients with implanted MicroMed-DeBakey axial pumps show nonphysiologic low-pulsatile blood flow profiles, and therefore it appeared to be of interest to evaluate their possible effect on the endocrine system. METHODS: Eight male patients and 1 female patients (mean age, 51 +/- 10 years) with end-stage left-sided heart failure were implanted with a MicroMed-DeBakey axial pump. After a mean period of 67 +/- 19 days, basal pituitary hormone concentrations and their responses to a bolus injection of hypothalamic releasing hormones were tested. In addition, thyroid hormones, testosterone, and plasma and urinary catecholamine levels were measured at baseline. RESULTS: Administration of the hypothalamic releasing hormones revealed normal responses of all pituitary hormones (adrenocorticotropic hormone, thyroid-stimulating hormone, luteinizing hormone, and prolactin), except for growth hormone, the response of which was slightly impaired (10.2 +/- 6.8 vs 19.9 +/- 6.5 ng/L, P < .05). Also, the cortisol response to the corticotropin-releasing hormone-stimulated adrenocorticotropic hormone release was normal, as were basal concentrations of thyroid hormones (triiodothyronine, thyroxine, free triiodothyronine, and free thyroxine), testosterone, and urinary catecholamines. CONCLUSIONS: Implantation of a continuous flow axial pump with low-pulsatile blood flow profile appears to have no major effect on the hypothalamic-pituitary-endorgan system and sympathoadrenal functions. This finding is reassuring for the growing number of patients treated with this convenient new pump and could contribute considerably to their prognosis and quality of life.

The DuraHeart VAD, a magnetically levitated centrifugal pump: the University of Vienna bridge-to-transplant experience.

BACKGROUND: The clinical application of the DuraHeart (Terumo Heart Inc, USA) has begun in Europe as a clinical trial of a third-generation implantable centrifugal blood pump. Four successful clinical implants are presented. METHODS AND RESULTS: Four male patients had end-stage left heart failure and received a DuraHeart VAD as a left ventricular assist device for bridge-to-transplantation. The pump showed good performance with flow rates of 4.9+/-0.5 L/min after gradual weaning of extracorporeal circulation. The pump flow was then maintained at 6.1+/-0.5, 5.5+/-0.3, 5.5+/-0.1, 5.7+/-0.1, 5.5, 6.4 and 6.5 L/min at the 1st, 4th, 8th, 12th, 16th, 20th and 24th postoperative week, respectively. No significant elevation of mean plasma-free hemoglobin was detected. The patients were discharged on the 18th, 42nd, 41st and 31st postoperative day, respectively, and all were successfully transplanted on the 202nd, 84th, 128th and 96th postoperative day, respectively. At the time of transplant surfaces of the removed pumps were free from thrombus formation, although intraventricular pannus growth was observed around the inflow cannulae in all patients. CONCLUSION: The DuraHeart VAD showed stable and sufficient circulatory support for the bridge-to-transplant procedure in this cohort of 4 patients.

Extensive coagulation monitoring in patients after implantation of the MicroMed Debakey continuous flow axial pump.

Ventricular assist device (VAD) implantation is associated with impaired primary hemostasis and thromboembolic complications. Recently, a new generation of implantable continuous flow axial pumps was introduced into clinical application. To study the potential thrombogenic properties of this type of pump, we applied extensive platelet monitoring was applied. In our institution, 13 patients received the MicroMed DeBakey VAD as a bridge to transplantation. Routine coagulation tests (platelet count, activated partial thromboplastin time, prothrombin time, antithrombin III activity) and platelet function tests (whole blood aggregometry, thrombelastography, flow cytometry) were performed. No clinically relevant thromboembolic events were detected. No correlation was found between global function tests, platelet aggregation, and thrombelastography. No correlation was detected between platelet activation and hemolysis parameters. Platelet aggregation and coagulation index were significantly suppressed early after operation. A subsequent phase of hyper-aggregability, starting around day 6, suggested the initiation of antiaggregation therapy. Platelet activation markers were upregulated in the postoperative period but were returned to preoperative levels after initiation of aspirin. In contrast to routine coagulation monitoring, platelet function tests reflect in detail the coagulation status of blood pump recipients and the efficiency of antiaggregation therapy. Aspirin and dipyridamole therapy in addition to oral anticoagulation using phenprocoumon may contribute to platelet function and clot mechanics restoration and is, therefore, recommended for patients after VAD implantation.

Special considerations on the implantation technique for the MicroMed-DeBakey ventricular assist device axial pump.

Implantable continuous flow axial pumps were introduced to clinical settings in November 1998 with the MicroMed-DeBakey ventricular assist device. Axial pumps continuously unload the failing left ventricle and accurate positioning of the inflow cannula prevents substantial reductions in pump flow. Considerations on the implantation technique are made to minimize surgical trauma, to prevent ventricular collapse, to optimize inflow conditions (flow increased from 4.3 +/- 0.6 to 6.7 +/- 0.3 L/min), and to facilitate the subsequent transplantation.

Cognitive deficit after aortic valve replacement.

BACKGROUND: Impairment of cognitive brain function after coronary artery bypass grafting (CABG) is well known. In contrast the potential neurocognitive damage related to aortic valve replacement (AVR) is uncertain. METHODS: In this contemporary case-matched control study we followed 30 patients (mean age 70 years) receiving isolated AVR with a biological prosthesis. A cohort of sex-and age-matched patients (n = 30, mean age 70 years) receiving CABG with cardiopulmonary bypass served as controls. Cognitive brain function was measured by means of auditory evoked P300 potentials (peak latencies, ms) before the operation and 7 days and 4 months after the operation. Additionally, two standard psychometric tests (Mini-Mental State Examination and the Trailmaking Test A) were performed. RESULTS: In preoperative measures there was no difference between patients undergoing AVR and patients undergoing CABG (AVR 378 +/- 37 ms, CABG 374 +/- 32 ms, p = 0.629). One week after surgery P300 peak latencies were prolonged (impaired) in both groups compared with preoperative values (AVR 405 +/- 43 ms, p = 0.001; CABG 398 +/- 44 ms, p = 0.004). At this point of follow-up there was no difference between the groups (p = 0.607). Finally, 4 months after surgery P300 auditory evoked potentials returned to normal in the CABG group (380 +/- 24 ms, p = 0.940) while in contrast in the valve group they continued to become prolonged (worsened) compared with preoperative values (410 +/- 47 ms, p = 0.005). At this time of follow-up P300 peak latencies were prolonged in AVR patients as compared with CABG patients (p = 0.032). The Trailmaking Test A and Mini-Mental State Examination failed to discriminate any difference. CONCLUSIONS: Four-month impairment of cognitive brain function is more pronounced in patients undergoing biological AVR as compared with age-matched control patients undergoing CABG. Further studies are needed to clarify the potential pathologic mechanisms causing an ongoing cognitive impairment in patients with biological aortic valve prostheses.