Depression Is Associated With Non-Home Discharge After Coronary Artery Bypass Graft.

INTRODUCTION: Depression is disproportionately high in patients with coronary artery disease and has been associated with adverse outcomes following coronary artery bypass graft (CABG). One quality metric, non-home discharge (NHD), can have substantial implications for patients and health care resource utilization. Depression increases the risk of NHD after many operations, but it has not been studied after CABG. We hypothesized that a history of depression would be associated with an increased risk of NHD following CABG. METHODS: CABG cases were identified from the 2018 National Inpatient Sample using ICD-10 codes. Depression, demographic data, comorbidities, length of stay (LOS), rate of NHD were analyzed using appropriate statistical tests where a P-value < 0.05 was defined as statistically significant. Adjusted multivariable logistic regression models were used to assess independent association between depression and NHD as well as LOS while controlling for confounders. RESULTS: There were 31,309 patients, of which 2743 (8.8%) had depression. Depressed patients were younger, females, in a lower income quartile, and more medically complex. They also demonstrated more frequent NHD and prolonged LOS. After adjusted multivariable analysis, depressed patients had a 70% increased odds of NHD (adjusted odds ratio: 1.70 [1.52-1.89] P < 0.001) and a 24% increased odds of prolonged LOS (AOR: 1.24 [1.12-1.38] P < 0.001). CONCLUSIONS: From a national sample, depressed patients were associated with more frequent NHD following CABG. To our knowledge, this is the first study to demonstrate this, and it highlights the need for improved preoperative identification in order to improve risk stratification and timely allocation of discharge services.

Patient-specific severity of von Willebrand factor degradation identifies patients with a left ventricular assist device at high risk for bleeding.

BACKGROUND: Continuous-flow left ventricular assist devices (LVADs) cause an acquired von Willebrand factor (VWF) deficiency and bleeding. Models to risk-stratify for bleeding are urgently needed. We developed a model of continuous-flow LVAD bleeding risk from patient-specific severity of VWF degradation. METHODS: In a prospective, longitudinal cohort study, paired blood samples were obtained from patients (n = 67) with a continuous-flow LVAD before and during support. After 640 ± 395 days, patients were categorized as all-cause bleeders, gastrointestinal (GI) bleeders, or nonbleeders. VWF multimers and VWF clotting function were evaluated to determine bleeding risk. RESULTS: Of 67 patients, 34 (51%) experienced bleeding, 26 (39%) experienced GI bleeding, and 33 (49%) did not bleed. In all patients, LVAD support significantly reduced high-molecular-weight VWF multimers (P < .001). Bleeders exhibited greater loss of high-molecular-weight VWF multimers (mean ± standard deviation, -10 ± 5% vs -7 ± 4%, P = .008) and reduced VWF clotting function versus nonbleeders (median [interquartile range], -12% [-31% to 4%] vs 0% [-9 to 26%], P = .01). A combined metric of VWF multimers and VWF function generated the All-Cause Bleeding Risk Score, which stratified bleeders versus nonbleeders (86 ± 56% vs 41 ± 48%, P < .001) with a positive predictive value of 86% (95% confidence interval, 66%-95%) and diagnostic odds ratio of 11 (95% confidence interval, 2.9-44). A separate GI Bleeding Risk Score stratified GI bleeders versus nonbleeders (202 ± 114 vs 120 ± 86, P = .003) with a positive predictive value of 88% (64%-97%) and diagnostic odds ratio of 18 (3.1-140). CONCLUSIONS: The severity of loss of VWF multimers and VWF clotting function generated Bleeding Risk Scores with high predictive value for LVAD-associated bleeding. This model may guide personalized antithrombotic therapy and patient surveillance.

COMPETENCE Trial: The EVAHEART 2 continuous flow left ventricular assist device.

BACKGROUND: Continuous flow left ventricular assist devices have improved outcomes in patients with end-stage heart failure that require mechanical circulatory support. Current devices have an adverse event profile that has hindered widespread application. The EVAHEART®2 left ventricular assist device (EVA2) has design features such as large blood gaps, lower pump speeds and an inflow cannula that does not protrude into the left ventricle that may mitigate the adverse events currently seen with other continuous flow devices. METHODS: A prospective, multi-center randomized non-inferiority study, COMPETENCE Trial, is underway to assess non-inferiority of the EVA2 to the HeartMate 3 LVAS when used for the treatment of refractory advanced heart failure. The primary end-point is a composite of the individual primary outcomes: Survival to cardiac transplant or device explant for recovery; Free from disabling stroke; Free from severe Right Heart Failure after implantation of original device. Randomization is in a 2:1 (EVA2:HM3) ratio. RESULTS: The first patient was enrolled into the COMPETENCE Trial in December of 2020, and 25 subjects (16 EVA2 and 9 HM3) are currently enrolled. Enrollment of a safety cohort is projected to be completed by third quarter of 2022 at which time an interim analysis will be performed. Short-term cohort (92 EVA2 subjects) and long-term cohort is expected to be completed by the end of 2023 and 2024, respectively. CONCLUSIONS: The design features of the EVA2 such as a novel inflow cannula and large blood gaps may improve clinical outcomes but require further study. The ongoing COMPETENCE trial is designed to determine if the EVA2 is non-inferior to the HM3.

Counterpulsation with symphony prevents retrograde carotid, aortic, and coronary flows observed with intra-aortic balloon pump support.

A counterpulsation device (Symphony) is being developed to provide long-term circulatory support for advanced heart failure (HF) patients. In acute animal experiments, flow waveform patterns in the aortic, carotid, and coronary arteries were compared during Symphony and intra-aortic balloon pump (IABP) support. Human data were examined for similarities. The 30-mL Symphony was compared to a 40-mL IABP in calves with cardiac dysfunction (80-100 kg, n = 8). Aortic pressures and aortic, carotid, and coronary artery flows were simultaneously recorded at baseline (devices off) and during 1:1 and 1:2 support. Forward, retrograde, and mean flows were calculated and compared for each test condition. Findings were also compared to aortic flow measurements recorded in HF patients (n = 21) supported by 40-mL IABP. IABP caused significant retrograde flows in the aorta, coronary (IABP: -24 ± 8 mL/min, Symphony: -6 ± 2 mL/min, baseline: -2 ± 1 mL/min, P < 0.05), and carotid arteries (IABP: -30 ± 5 mL/min, Symphony: -0 ± 0 mL/min, baseline: -0 ± 0 L/min, P < 0.05) during ventricular systole compared to the Symphony. IABP support produced higher diastolic pressure and flow augmentation compared to Symphony. Due to retrograde flows during IABP support, Symphony provided higher overall coronary, carotid, and aortic flows. Similar reduction in total aortic flows due to retrograde flow was observed in HF patients during IABP support. Counterpulsation with an IABP via aortic volume displacement produces retrograde flows during rapid balloon deflation that reduces total flow. Counterpulsation with Symphony via volume removal eliminates retrograde flow and improves total flow more than that achieved with IABP. The Symphony may provide long-term hemodynamic benefits in HF patients.

Intraaortic balloon pump timing discrepancies in adult patients.

The objective of this clinical study was to quantify the incidence and magnitude of intraaortic balloon pump (IABP) inflation and deflation landmark discrepancies associated with the IABP catheter arterial pressure waveform. Cardiac surgery patients with an IABP inserted prior to surgery were recruited. Following cardiac exposure, a high-fidelity pressure catheter was inserted into the aortic root for digital recording. The radial artery pressure signal was simultaneously recorded from the patient monitor along with the arterial pressure and electrocardiogram waveforms from the IABP console while operating at 1:1 and 1:2 synchronization. In selected patients, recordings were obtained with the IABP timed to the high-fidelity aortic root waveform. In all 11 patients, inflation and deflation landmark delays were observed when comparing the aortic root waveforms to the IABP arterial pressure waveforms (inflation delay = 74 ± 29 [23-117] ms; deflation delay = 71 ± 37 [24-141] ms, mean ± standard deviation [min-max]). Delays were greater when compared to the radial artery waveform (inflation delay = 175 ± 50 [100-233] ms; deflation delay = 168 ± 52 [100-274] ms). In all cases, the landmark delays were statistically different from zero (P < 0.001). Diastolic augmentation and afterload reduction varied with waveform source. Conflicting indications of afterload reduction occurred in four patients. Timing to the aortic root waveform resulted in greater diastolic pressure augmentation and afterload reduction but mixed changes in stroke volume. Delay and distortion of the arterial waveform was consistently found when measured through the IABP catheter lumen. These delays can alter IABP efficacy and may be eliminated by using high-fidelity sensing of aortic pressure.

Abnormalities in the Von Willebrand-Angiopoietin Axis Contribute to Dysregulated Angiogenesis and Angiodysplasia in Children With a Glenn Circulation.

Children with a bidirectional superior cavopulmonary (Glenn) circulation develop angiodysplasia and pulmonary arteriovenous malformations (AVMs). The von Willebrand factor (vWF)-angiopoietin axis plays a major role in AVM formation in multiple diseases. We observed derangements in global angiogenic signaling, vWF metabolism, angiopoietins, and in vitro angiogenesis in children with a Glenn circulation versus controls and within Glenn pulmonary versus systemic circulations. These findings support the novel hypothesis that abnormalities in the vWF-angiopoietin axis may dysregulate angiogenesis and contribute to Glenn pulmonary AVMs. The vWF-angiopoietin axis may be a target to correct angiogenic imbalance in Glenn patients, for whom no targeted therapy exists.

Continuous-Flow Left Ventricular Assist Device Support Improves Myocardial Supply:Demand in Chronic Heart Failure.

Continuous-flow left ventricular assist devices (CF LVADs) are rotary blood pumps that improve mean blood flow, but with potential limitations of non-physiological ventricular volume unloading and diminished vascular pulsatility. In this study, we tested the hypothesis that left ventricular unloading with increasing CF LVAD flow increases myocardial flow normalized to left ventricular work. Healthy (n = 8) and chronic ischemic heart failure (IHF, n = 7) calves were implanted with CF LVADs. Acute hemodynamics and regional myocardial blood flow were measured during baseline (LVAD off, clamped), partial (2-4 L/min) and full (>4 L/min) LVAD support. IHF calves demonstrated greater reduction of cardiac energy demand with increasing LVAD support compared to healthy calves, as calculated by rate-pressure product. Coronary artery flows (p < 0.05) and myocardial blood flow (left ventricle (LV) epicardium and myocardium, p < 0.05) decreased with increasing LVAD support in normal calves. In the IHF model, blood flow to the septum, LV, LV epicardium, and LV myocardium increased significantly with increasing LVAD support when normalized to cardiac energy demand (p < 0.05). In conclusion, myocardial blood flow relative to cardiac demand significantly increased in IHF calves, thereby demonstrating that CF LVAD unloading effectively improves cardiac supply and demand ratio in the setting of ischemic heart failure.

Development and early testing of a simple subcutaneous counterpulsation device.

The intra-aortic balloon pump has been widely and successfully used as a treatment for cardiac dysfunction, but it only has short-term applications. To overcome this limitation, a superficial counterpulsation device (CPD) is being developed to provide extended counterpulsation support to promote myocardial recovery. The CPD is a valveless, monoport, pneumatically driven, 40-ml sac that is intended to be implanted in a pacemaker-type pocket in the subclavian fossa. The sac is designed to fill in systole and empty during diastole through an outflow graft anastomosed to the subclavian artery. A feasibility study was conducted to investigate acute hemodynamic responses to the CPD in eight calves with diminished cardiac function. The CPD augmented aortic diastolic pressure, reduced left ventricular peak systolic and aortic ejection pressures by up to 18%, and increased diastolic coronary flow by up to 21% and stroke volume by up to 12%. A cadaver fit study demonstrated that the human subclavian artery is a reasonable anastomosis site to consider and that the 40-ml CPD needs to be reduced in size to provide a better anatomical fit. The clinical attractiveness of this approach is that it may provide extended support through a subcutaneous surgical procedure.

Initial clinical experience with the Symphony heart assist system.

PURPOSE: Current cardiac assist devices provide full support, require a major operation, and function asynchronously to the native heart. In contrast, we developed a novel circulatory support device that provides synchronous partial support and can be placed with a minor operation. We report the first clinical implantation with the Symphony device (Abiomed, Danvers, MA). DESCRIPTION: Patients with advanced heart failure despite optimal therapy who had exhausted all options were evaluated. A 64-year-old man with ischemic cardiomyopathy underwent implantation of the Symphony device in the right infraclavicular fossa. EVALUATION: After initiating device support, the cardiac index increased from 1.7 to 2.5 L/min/m(2), pulmonary capillary wedge pressure decreased from 26 to 13 mm Hg, right atrial pressure decreased from 12 to 7 mm Hg, creatinine level decreased from 2.3 to 1.5 mg/dL, and New York Heart Association (NYHA) class improved from IIIB to II. CONCLUSIONS: Placement of the Symphony device resulted in improvements in hemodynamics and functional status. Further clinical data will help define the role for this approach of partial synchronous support through a less invasive operation in patients with advanced heart failure.

Initial experience with the AbioCor implantable replacement heart system.

OBJECTIVE: We sought to evaluate the safety and efficacy of the first available totally implantable replacement heart (AbioCor Implantable Replacement Heart System) in the treatment of severe, irreversible biventricular heart failure in human patients. METHODS: Seven male adult patients with severe, irreversible biventricular failure (>70% thirty-day predicted mortality) who were not candidates for transplantation met all institutional review board study criteria and had placement of the AbioCor Implantable Replacement Heart. All were in cardiogenic shock despite maximal medical therapy, including inotropes and intra-aortic balloon pumps. Mean age was 66.7 +/- 10.4 years (range, 51-79 years). Four of 7 patients had prior operations. Six had ischemic and one had idiopathic cardiomyopathy. All had 3-dimensional computer-simulated implantation of the thoracic unit that predicted adequate fit. At the time of the operation, the internal transcutaneous energy transfer coil, battery, and controller were placed. Biventriculectomy was then performed, and the thoracic unit was placed in an orthotopic position and attached to the atrial cuffs and outflow conduits with quick-connects. The flow was adjusted to 4 to 8 L/min. Central venous and left atrial pressures were maintained at 5 to 15 mm Hg. The device is powered through transcutaneous energy transfer. An atrial flow-balancing chamber is used to adjust left/right balance. The balance chamber and transcutaneous energy transfer eliminate the need for percutaneous lines. RESULTS: There was one intraoperative death caused by coagulopathic bleeding and one early death caused by an aprotinin reaction. There have been multiple morbidities primarily related to preexisting illness severity: 5 patients had prolonged intubation, 2 had hepatic failure (resolved in 1), 4 had renal failure (resolved in 3), and 1 each had recurrent gastrointestinal bleeding, acute cholecystitis requiring laparotomy, respiratory failure that resolved after 3 days of extracorporeal membrane oxygenation, and malignant hyperthermia (resolved). There were 3 late deaths: one caused by multiple systems organ failure (postoperative day 56), one caused by a cerebrovascular accident (postoperative day 142), and one caused by retroperitoneal bleeding and resultant multiple systems organ failure (postoperative day 151). This latter patient was not able to tolerate anticoagulation (no anticoagulation or antiplatelet therapy alone for 80% of the first 60 days) and had a transient ischemic attack on postoperative day 61 and a cerebrovascular accident on postoperative day 130. At autopsy, blood pumps were clean. The 2 patients who had large cerebrovascular accidents had thrombus on the atrial cage struts. These struts have been removed for future implants. There has been no significant hemolysis or device-related infections. The balance chamber has allowed for left/right balance in all patients (left atrial pressure within 5 mm Hg of right atrial pressure). Three patients have taken multiple (>50) trips out of the hospital, and 2 have been discharged from the hospital. Total days on support with the AbioCor are 759. CONCLUSION: The initial clinical experience suggests that the AbioCor might be effective therapy in patients with advanced biventricular failure. There have been no significant device malfunctions. Two of these patients have been discharged from the hospital.

Creation of a diaphragm patch to facilitate placement of the AbioCor implantable replacement heart.

One of the concerns when placing a total artificial heart is whether the device will fit in the thoracic cavity without impinging on vital structures. We report the creation of a patch in a recipient of the AbioCor Implantable Replacement Heart that allowed for an appropriate fit of the device without adversely affecting pulmonary and hemodynamic functions.

The AbioCor implantable replacement heart.

The AbioCor implantable replacement heart (IRH) is the first available totally implantable artificial heart. We recently initiated a multicenter trial of this device in patients with severe, irreversible biventricular failure. Patients who were not candidates for other therapies, including transplantation, were evaluated. All candidates were adults with inotrope-dependent biventricular failure, whose 30-day predicted mortality was higher than 70%. A three-dimensional computerized fit study predicted fit of the AbioCor thoracic unit in all recipients. At operation, the internal battery controller and transcutaneous energy transfer unit were placed. The AbioCor thoracic unit was placed in an orthotopic position after incision of the ventricals. There were 2 intraoperative deaths (due to intraoperative bleeding or aprotinin reaction). Four late deaths were recorded, 1 from multisystem organ failure and 3 cerebrovascular accidents. Autopsy revealed thrombus on the atrial struts of the 3 patients with cerebrovascular accident. Blood pumps and valves were clean on all patients. Significant morbidity was observed, primarily related to preexisting severity of illness. However, 3 patients recovered to the point of being able to take multiple trips outside of the hospital. Two patients were discharged from the hospital, with 1 patient being discharged home for more than 7 months. No significant device malfunctions or multi-system organ failure device-related infections were noted. The AbioCor IRH may be effective therapy for patients with end-stage heart failure. Many milestones have been achieved in the initial trial in humans, including the successful discharge of a patient to home and no significant device malfunctions. The occurrence of stroke is likely related to the presence of thrombus on the atrial struts and may be decreased as these atrial struts have been removed for future clinical implants.

Transmyocardial revascularization: 5-year follow-up of a prospective, randomized multicenter trial.

BACKGROUND: In prospective randomized trials at 1 year, transmyocardial revascularization (TMR) provided superior relief of angina, decreased rehospitalizations, and improved exercise times. We evaluated 5-year mortality and angina class in "no-option" patients with diffuse coronary artery disease randomized to TMR or continued medical management. METHODS: Two hundred twelve patients with refractory class IV angina who were not candidates for conventional therapy were randomized to receive holmium:yttrium-aluminum-garnet TMR (n = 100) or continued medical management (n = 112) at nine centers. Follow-up included all-cause mortality along with angina class assessment by blinded evaluators. Mean follow-up was 5.7 +/- 0.8 years. RESULTS: Mean angina scores for TMR patients were 4.0 +/- 0.0 at baseline, 1.5 +/- 1.4 at 1 year, and 1.2 +/- 1.1 at a mean of 5 years (p < 0.001). After an average of 5 years, a significantly greater proportion of TMR than medical management patients experienced two or more class improvement in angina (88% versus 44%; p < 0.001). Kaplan-Meier intention-to-treat survival at 5 years was 65% versus 52% (TMR versus medical management; p = 0.05). Cumulative hazard curves demonstrated a significantly reduced risk of late death for TMR patients; average annual mortality beyond 1 year was 8% versus 13% (TMR versus medical management; p = 0.03). CONCLUSIONS: Five-year follow-up of prospectively randomized, no-option class IV angina patients demonstrated significantly increased Kaplan-Meier survival in patients randomized to TMR. The significant angina relief observed 12 months after sole therapy TMR was sustained long term and continued to be superior to that observed for patients maintained on continued medical management alone.

Treadmill exercise in calves implanted with the AbioCor replacement heart.

The aim of this study was to evaluate the function of the AbioCor artificial heart implanted in calves that underwent treadmill exercise testing and to investigate the cardiovascular and metabolic responses during exercise. Six calves were implanted with the AbioCor. One week after surgery, exercise training was undertaken and animals were put on a treadmill at a speed of 0.5-1.0 mph, with the AbioCor operating at the maximum heart rate of 150 beats per minute. During exercise, the left and right atrial pressures were significantly increased (p < 0.05). Oxygen consumption was significantly elevated (p < 0.05). Lactate levels did not significantly increase (p > 0.05). The index of metabolic adequacy remained higher than 2.0, indicating that there was no substantial transition to anaerobic metabolism during exercise. There was an increased extraction of oxygen during exercise to meet the increased energy demands. Our study demonstrated that animals implanted with the AbioCor heart were able to maintain aerobic metabolism during low levels of exercise testing.

Nonphysiologic blood flow triggers endothelial and arterial remodeling in vivo: implications for novel left ventricular assist devices with a peripheral anastomosis.

OBJECTIVES: Less invasive circulatory support devices have been developed that require anastomosis to a peripheral artery. The Symphony Heart Assist System (Abiomed, Inc, Danvers, Mass) is a volume-displacement pump sewn to the subclavian artery to provide partial circulatory support. The surgical configuration produces nonphysiologic blood pressure and bidirectional flow in the subclavian artery. Our objective was to identify effects of altered hemodynamics on arterial structure and function. METHODS: In calves (n = 23; 80-100 kg), the Symphony pump was sewn end-to-side to the carotid artery. Acutely, carotid blood pressure and flow were recorded to evaluate hemodynamic changes. After medium-term support (1-4 weeks), carotid artery was studied. Histologic and molecular assays evaluated architectural changes. Quantitative real-time polymerase chain reaction evaluated gene expression of matrix metalloproteinase (MMP)-2, MMP-9, and connective tissue growth factor. In vitro carotid arterial-ring studies evaluated physiologic responses. RESULTS: During Symphony support, carotid arterial pressure was 200/15 mm Hg. Antegrade flow increased significantly (P < .05) from 1.40 ± 0.32 to 4.29 ± 0.33 L/min. Flow during native cardiac diastole reversed completely from 0.25 ± 0.05 to -4.15 ± 0.38 L/min in carotid artery proximal to the anastomosis. After medium-term support, the carotid artery was significantly dilated with significantly thinner tunica media and thicker tunica adventitia than in control carotid arteries. MMP-9 gene expression decreased significantly, connective tissue growth factor gene expression increased significantly, and collagen, elastin, and total extracellular matrix increased significantly. Endothelial cells were significantly hypertrophied and produced significantly more von Willebrand factor. Endothelial apoptosis increased significantly. Platelet-endothelial interactions decreased significantly. Endothelial-independent contraction decreased significantly, whereas endothelial-dependent relaxation increased modestly. CONCLUSIONS: Assisted circulation with a left ventricular assist device triggered arterial remodeling that allowed a peripheral artery to accommodate the altered hemodynamics of a novel partial-support pump. Further delineation of remodeling pathways may be of significance for the emerging field of partial circulatory support.

Insights into the mechanism(s) of von Willebrand factor degradation during mechanical circulatory support.

OBJECTIVE: Left ventricular assist device support produces a bleeding diathesis. Evidence suggests a major role for von Willebrand factor (vWF). We examined vWF metabolism in a preclinical model of short-term mechanical circulatory support. METHODS: In 25 calves (weight, 80-110 kg), the inflow/outflow graft of the Symphony Heart Assist System was sewn end-to-side to the carotid artery. Support was initiated (acute, n = 4; 1 week, n = 16; 2 weeks, n = 5). Acutely, carotid artery pressure and flow were measured to evaluate the hemodynamic changes near the anastomosis. At baseline and after ≤2 weeks of support, platelet aggregometry with adenosine 5'-diphosphate, collagen, and ristocetin was performed. Gel electrophoresis and wet immunoblotting qualitatively evaluated vWF multimers and quantified plasma ADAMTS-13, the vWF-cleaving protease. Carotid arterial rings near the anastomosis were studied with immunohistochemical staining for ADAMTS-13 and were cultured to quantify endothelial ADAMTS-13 production. Fluorescent resonance energy transfer was used to evaluate the enzymatic activity of ADAMTS-13 in the plasma and in supernatant from cultured carotid arterial rings. Plasma interleukin-6, which inhibits ADAMTS-13 activity, was measured using an enzyme-linked immunosorbent assay. RESULTS: During support, statistically significant (P < .05) changes in the carotid endothelium arterial hemodynamics were observed. The highest molecular weight vWF multimers were absent, and the vWF-ristocetin platelet aggregation pathway was significantly impaired. A modest but significant increase in plasma ADAMTS-13 protein and activity was observed. ADAMTS-13 decreased significantly in the carotid near the anastomosis but increased significantly in supernatant from cultured carotid arterial rings. The plasma interleukin-6 levels did not change significantly. CONCLUSIONS: Hemodynamic activation of vWF and increased plasma ADAMTS-13 activity may have reduced high-molecular-weight vWF multimers and thereby impaired the vWF-platelet aggregation pathway. Additional delineation of these pathways may improve management of left ventricular assist device-associated bleeding.

Mechanism of myocardial ischemia with an anomalous left coronary artery from the right sinus of Valsalva.

OBJECTIVE: An ectopic coronary artery that courses between the aortic root and the pulmonary trunk may lead to sudden cardiac death, especially in athletes. It has been speculated that during exercise, compression of the coronary artery between the great vessels may impair coronary blood flow and produce myocardial ischemia and fatal arrhythmia. However, this hypothesis cannot be tested in humans, and little experimental data exist to explain this phenomenon. To this end, in a calf with an anomalous left coronary artery that coursed from the right sinus of Valsalva between the great vessels, we assessed for myocardial ischemia during pharmacologically induced tachycardia and hypertension. METHODS: We identified a juvenile male calf (103 kg) with an anomalous left coronary artery from the right sinus of Valsalva that coursed between the great vessels. Via thoracotomy, the animal was instrumented for hemodynamic measurements. Intravenous dobutamine increased heart rate and myocardial metabolic demands. Intravenous phenylephrine produced arterial hypertension and increased myocardial metabolic demands. Fluorescent-labeled microspheres were used to map regional myocardial blood flow, and hemodynamics were recorded during each condition. Masson's trichrome staining for fibrosis, wheat-germ agglutinin staining for myocyte size, terminal deoxynucleotidyl transferase dUTP nick end-label staining for apoptosis, and isolectin-B4 staining for capillary density were performed. RESULTS: For the first time, empiric data documented that an ectopic coronary artery produced myocardial ischemia during elevated myocardial metabolic demands. Left coronary artery resistance increased in a cardiac cycle-dependent pattern that was consistent with systolic compression between the great vessels. Increased cardiac fibrosis, myocyte hypertrophy, cardiac apoptosis, and capillary density indicated that regional ischemic, inflammatory-mediated myocardial remodeling was present. CONCLUSIONS: These findings confirm the proposed mechanism of sudden death and support early surgical repair of coronary arteries that course between the aortic root and the pulmonary trunk.

Antigens of persistent Chlamydia pneumoniae within coronary atheroma from patients undergoing heart transplantation.

AIMS: In order for Chlamydia pneumoniae to play a causative role in chronic human disease, it would need to persist within infected tissue for extended periods of time. Current theory suggests that C pneumoniae may persist at the site of infection via an alternative replicative form, known as an aberrant body. METHODS: A panel of C pneumoniae-specific antibodies upregulated by the aberrant body was used to probe tissue specimens from the coronary atheroma from 13 explanted hearts to identify patterns of reactivity in these tissues, as well as to determine the presence and prevalence of C pneumoniae aberrant bodies. RESULTS: Six of 13 patients had an ischaemic cardiomyopathy secondary to coronary atherosclerosis, while another six patients had an idiopathic, dilated cardiomyopathy. One additional patient, a young (24 years) woman with cardiomyopathy, had no history of atherosclerotic disease. Eleven patients were positive by immunohistochemistry with at least one antibody. Coronary arteries of the two other patients were negative by immunohistochemistry with all antibodies. One of these patients was the 24-year-old woman with grade I disease and no risk factors for coronary artery disease. CONCLUSIONS: The protein antigens of persistent C pneumoniae infection found in the atheromatous lesions from patients in this study could potentially be used as markers to detect such infections and some may be virulence factors or immunogens specific to C pneumoniae, thus serving as target molecules for diagnostic use or therapeutic intervention.

The future of adult cardiac assist devices: novel systems and mechanical circulatory support strategies.

The recent, widespread success of mechanical circulatory support has prompted the development of numerous implantable devices to treat advanced heart failure. It is important to raise awareness of novel device systems, the mechanisms by which they function, and implications for patient management. This article discusses devices that are being developed or are in clinical trials. Devices are categorized as standard full support, less-invasive full support, partial support: rotary pumps, partial support: counterpulsation devices, right ventricular assist device, and total artificial heart. Implantation strategy, mechanism of action, durability, efficacy, hemocompatibility, and human factors are considered. The feasibility of novel strategies for unloading the failing heart is examined.