A randomized, parallel group, double-blind study of ticagrelor compared with aspirin for prevention of vascular events in patients undergoing coronary artery bypass graft operation: Rationale and design of the Ticagrelor in CABG (TiCAB) trial: An Investigator-Initiated trial.

BACKGROUND: For patients with coronary artery disease undergoing coronary bypass surgery, acetylsalicylic acid (ASA) currently represents the gold standard of antiplatelet treatment. However, adverse cardiovascular event rates in the first year after coronary artery bypass grafting (CABG) still exceed 10%. Graft failure, which is predominantly mediated by platelet aggregation, has been identified as a major contributing factor in this context. Therefore, intensified platelet inhibition is likely to be beneficial. Ticagrelor, an oral, reversibly binding and direct-acting P2Y12 receptor antagonist, provides a rapid, competent, and consistent platelet inhibition and has shown beneficial results compared with clopidogrel in the subset of patients undergoing bypass surgery in a large previous trial. HYPOTHESIS: Ticagrelor is superior to ASA for the prevention of major cardiovascular events within 1 year after CABG. STUDY DESIGN: The TiCAB trial (NCT01755520) is a multicenter, phase III, double-blind, double-dummy, randomized trial comparing ticagrelor with ASA for the prevention of major cardiovascular events within 12 months after CABG. Patients undergoing CABG will be randomized in a 1:1 fashion to either ticagrelor 90 mg twice daily or ASA 100 mg once daily. The study medication will be started within 24 hours after surgery and maintained for 12 months. The primary end point is the composite of cardiovascular death, myocardial infarction, stroke, and repeat revascularization at 12 months after CABG. The sample size is based on an expected event rate of 13% of the primary end point within the first 12 months after randomization in the control group, a 2-sided α level of .0492 (to preserve the overall significance level of .05 after planned interim analysis), a power of 0.80%, 2-sided testing, and an expected relative risk of 0.775 in the active group compared with the control group and a dropout rate of 2%. According to power calculations based on a superiority design for ticagrelor, it is estimated that 3,850 patients should be enrolled. SUMMARY: There is clinical equipoise on the issue of optimal platelet inhibition after CABG. The TiCAB trial will provide a pivotal comparison of the efficacy and safety of ticagrelor compared with ASA after CABG.

Early detection of anomalous origin of left coronary artery from the right pulmonary artery after successful repair of critical coarctation of the aorta.

Left ventricular (LV) function is impaired by increased afterload in neonates with severe coarctation of the aorta, which may result in endocardial fibroelastosis. Repair of the coarctation usually solves the problem, with LV function normalizing after a few weeks. This report describes a patient who underwent successful repair of critical coarctation with normalization of LV function despite signs of endocardial fibroelastosis but with persisting elevation of cardiac troponin T. Cardiac catheterization showed the rare coincidence of anomalous origin of left coronary artery from the right pulmonary artery (ALCAPA) and coronary sinus orifice atresia with left superior vena cava.

Influence of inflow cannula length in axial-flow pumps on neurologic adverse event rate: results from a multi-center analysis.

BACKGROUND: The application of axial-flow pumps in patients with end-stage heart failure reveals a significantly reduced infectious complication rate as compared with rates observed with pulsatile devices. The remaining adverse event rate relates mainly to thromboembolic complications with neurologic consequences. We investigated the dependence of the neurologic adverse event rate on the length of the inflow cannula. METHODS: A total of 216 consecutive patients with an axial-flow pump (INCOR; Berlin Heart GmbH, Berlin, Germany) were included in a retrospective multi-center analysis. In 138 patients, a short inflow cannula (24-mm tip length into the left ventricle), and in 78 patients a long inflow cannula (tip length 34 mm) was applied. RESULTS: Patients with a long inflow cannula (LC) demonstrated a better survival rate than those with a short inflow cannula (SC) at the end of the observation period (LC, 63.4%; SC, 52.9%; p = 0.05). The thromboembolic adverse event rate was also significantly lower. Only 3 of the 78 patients (3.8%) with an LC had a thromboembolic adverse event (thromboembolic events per patient-year = 0.11) as compared with 32 (23.2%) of SC patients (thromboembolic events per patient-year = 0.50, p < 0.001). CONCLUSIONS: Patients with a long inflow cannula had a better survival rate and a lower incidence of cerebrovascular adverse events than patients with a short inflow cannula.

Temporary right heart support with percutaneous jugular access.

PURPOSE: Temporary right heart bypass has shown to improve hemodynamic stability and safety in beating heart revascularization. We sought to evaluate feasibility and safety of a right ventricular assist device percutaneously implanted in the right jugular vein. DESCRIPTION: The A-Med jugular coaxial cannula (A-Med Systems Inc, West Sacramento, CA) is designed for percutaneous implantation. Blood from the right heart is drained through the outer tube of this two-cannula device to a microcentrifugal pump and returned into the pulmonary artery through the inner tube. EVALUATION: In 10 patients scheduled for elective coronary bypass grafting without cardiopulmonary bypass, a total of 27 coronary anastomoses were performed with right heart support. Arterial pressure was significantly higher with right heart support when the heart was dislocated to access posterior and posterolateral anastomosis sites. Implantation through the right internal jugular vein was feasible without complications in all patients and facilitated the procedure. CONCLUSIONS: This initial study suggests safety and feasibility of temporary right heart support using percutaneous jugular access for posterior and posterolateral coronary bypass grafting.

Partial left ventriculectomy and mitral valve repair: favorable short-term results in carefully selected patients with advanced heart failure due to dilated cardiomyopathy.

BACKGROUND: Because of the scarcity of donor hearts, surgical alternatives to heart transplantation, such as partial left ventriculectomy (PLV), were introduced for treatment of advanced heart failure. Here, we report our experience with this procedure performed in combination with mitral valve repair. METHODS: Twelve patients with dilated cardiomyopathy (DCM), New York Heart Association (NYHA) class exceeding III on maximal medical therapy, cardiac index of 2.5 liter/min/m2 or less, VO2max of 14 ml/kg/min or less, left ventricular end-diastolic diameter (LVEDD) of 7.0 cm or more, and grade II or greater mitral incompetence, were selected for PLV and mitral valve reconstruction (MVR). Echocardiography, hemodynamics, spiroergometry, and clinical assessment were performed before and 1 year after the operation. RESULTS: One-year survival was 83.3%. All 10 surviving patients were free from failure of the procedure 1 year post-operatively. From pre-operatively to 1 year post-operatively, NYHA functional class improved from 3.3 +/- 0.3 to 1.9 +/- 0.2 (p < 0.001), cardiac index increased from 2.0 +/- 0.2 liter/min/m2 to 2.9 +/- 0.2 liter/min/m2 (p < 0.001), stroke volume index from 25.9 +/- 4.8 ml/m2 to 40.3 +/- 7.3 ml/m2 (p = 0.008), and VO2max from 10.9 +/- 2.4 ml/kg/min to 16.0 +/- 3.6 ml/kg/min (p = 0.016), whereas LVEDD decreased from 8.4 +/- 0.6 cm to 6.6 +/- 0.3 cm (p < 0.001), left ventricular end-systolic diameter from 6.8 +/- 0.8 cm to 5.3 +/- 0.5 cm (p < 0.001), and mitral incompetence from 2.4 +/- 0.6 to 0.9 +/- 0.6 (p < 0.001). Pulmonary pressures and fractional shortening did not change significantly (p > 0.05). Four patients received an implantable cardioverter/defibrillator as a result of their pathologic electrophysiologic examination. CONCLUSIONS: In carefully selected patients, PLV combined with MVR achieves short-term results comparable to that after heart transplantation. However, long-term results and multicenter evaluation will be needed to define its place in the treatment of advanced heart failure.

Long-term support of 9 patients with the DeBakey VAD for more than 200 days.

OBJECTIVE: Pulsatile left ventricular assist devices serving as mechanical circulatory support for patients with end-stage heart failure are associated with complications, including bleeding, thromboembolism, and infection. Axial-flow pumps might overcome some of these shortcomings. Here we report our experience with long-term application of the DeBakey VAD (MicroMed Technology, Inc, Houston, Tex). METHODS: Nine male transplant candidates (37 +/- 14 years) with severe hemodynamic compromise (cardiac index, 1.6 +/- 0.5 L . min(-1) x m(-2); pulmonary capillary wedge pressure, 27 +/- 6 mm Hg) and beginning end-organ failure despite inotropic and intra-aortic balloon pump support received the DeBakey VAD. Clinical outcome was evaluated. RESULTS: Cumulative support was 7.8 years, and the mean duration of support was 314 +/- 75 days (range, 229-438 days). Eight patients were transplanted, and one died from intracerebral bleeding. Peripheral circulation and end-organ function recovered rapidly after implantation. Continuous flow was able to maintain adequate organ perfusion over the long term. Eight patients were discharged during support, with good quality of life. There were no early bleedings, but there were late bleedings in 3 patients caused by excessive anticoagulation and platelet inhibition. Neurologic events occurred in 4 patients. Three patients recovered completely from symptoms, and one had lethal intracerebral bleeding. Because of thrombus formation, the device was exchanged in 4 patients. With increasing experience, thrombolysis was performed in similar situations. All such patients underwent successful transplantation. Hemolysis occurred, with events indicating thrombus formation. Device-related infection was found in one patient. CONCLUSIONS: The DeBakey VAD demonstrated its potential for long-term bridge to transplantation. The risk for thrombus formation needs to be addressed by improvement of pump technology and new strategies for platelet inhibition.

Ischemic preconditioning by unstable angina reduces the release of CK-MB following CABG and stimulates left ventricular HSP-72 protein expression.

BACKGROUND AND AIM: Whether the CK-MB reducing effect of ischemic preconditioning (IP) by unstable angina within 24 to 48 hours before CABG is achieved by early or by delayed preconditioning of left ventricular myocardium in humans is unknown. We investigated whether IP is associated with phosphorylation of p38 MAPK (characteristic for early preconditioning) or with increased protein expression of HSP-72 (characteristic for delayed preconditioning) at the time of CABG in patients. METHODS: Nineteen patients were grouped according to the occurrence of ischemic episodes within 48 hours before CABG. The patients without angina were assigned to the control group (CON, n = 10) whereas patients who had experienced angina within 48 hours before CABG were assigned to the preconditioned group (IP, n = 9). The effect of IP on the CABG induced maximal release of creatine kinase (CK) and CK-MB was examined. Left ventricular biopsy specimens taken immediately before cross clamping from ischemic (ISCH) and from reference (REF) areas were processed to analyze p38 MAPK phosphorylation and HSP-72-protein expression. RESULTS: While IP significantly reduced CK-MB (18.7 +/- 1.3 vs. 13.8 +/- 1.5 U/L, mean +/- SEM, p < 0.05), it only tended to reduce CK (292.7 +/- 32.8 vs. 274.1+/-31.1 U/L, p = NS, mean +/- SEM). CK-MB release for any given cross-clamp time was significantly reduced by IP (regression lines: CON, y= 0.4x+ 2, r= 0.8; IP, y= 0.1x+ 10, r= 0.2; p < 0.01, ANCOVA). There was no effect of IP on left ventricular p38 MAPK phosphorylation. IP increased left ventricular HSP-72-protein expression in ischemic areas when compared to reference areas (1.78 +/- 0.35 vs. 2.58 +/- 0.65, REF vs. ISCH, PhosphorImager units x10(6), mean +/- SEM, p < 0.05, ANCOVA). CONCLUSIONS: Thus, in the human left ventricular myocardium there is a second window of protection lasting for at least 48 hours, while at that time the early phase of preconditioning has already gone.

Impact of a molecular approach to improve the microbiological diagnosis of infective heart valve endocarditis.

BACKGROUND: Even today, infective endocarditis (IE) remains a severe and potentially fatal disease demanding sophisticated diagnostic strategies for detection of the causative microorganisms. Despite the use of appropriate laboratory techniques, classic microbiological diagnostics are characterized by a high rate of negative results. METHODS AND RESULTS: Broad-range polymerase chain reaction (PCR) targeting bacterial and fungal rDNA followed by direct sequencing was applied to excised heart valves (n=52) collected from 51 patients with suspected infectious endocarditis and from 16 patients without any signs of IE during an 18-month period. The sensitivity, specificity, and the positive and negative predictive values for the bacterial broad-range PCR were 41.2%, 100.0%, 100.0%, and 34.8%, respectively, compared with 7.8%, 93.7%, 80.0%, and 24.2% for culture and 11.8%, 100.0%, 100.0%, and 26.2% for Gram staining. Without exception, database analyses allowed identification up to the (sub)species level comprising streptococcal (n=13), staphylococcal (n=4), enterococcal (n=2), and other signature sequences such as Bartonella quintana and Nocardia paucivorans. Fungal ribosomal sequences were not amplified. All valve tissues of the reference group were negative for both PCR and conventional methods, except one sample that was contaminated by molds. CONCLUSIONS: Culture-independent molecular methods substantially improve the diagnostic outcome of microbiological examination of excised heart valves. Importantly, this was true not only for fastidious, slow-growing, and/or nonculturable microorganisms but also for easy-to-culture pathogens such as streptococci and staphylococci. Both patient management and empiric antibiotic therapy of IE are likely to benefit from improved knowledge of the spectrum of pathogens now causing IE.

Left ventricular pressure and volume unloading during pulsatile versus nonpulsatile left ventricular assist device support.

BACKGROUND: Nonpulsatile axial or centrifugal pumps are the latest generation of left ventricular assist devices (LVAD). Whether left ventricular (LV) unloading and outcome in these devices is similar to pulsatile LVADs during long-term support has not been investigated. We compared LV unloading and mortality between different types of LVAD support (pulsatile versus nonpulsatile). METHODS: In 31 patients undergoing long-term LVAD implantation (nonpulsatile = 10, pulsatile = 21) preoperative and postoperative echocardiographic and hemodynamic assessment with right heart catheterization had been obtained. RESULTS: All patients had similar echocardiographic, hemodynamic, and clinical heart failure characteristics at baseline. The degree of LV pressure unloading was the same in both device types, caused by similar reduction of mean pulmonary pressure (18.6 +/- 5.1 versus 18.3 +/- 7.5 mm Hg) and pulmonary capillary wedge pressure (8.9 +/- 4.4 versus 8.0 +/- 7.0 mm Hg). Left ventricular volume unloading was pronounced with a pulsatile device owing to a statistically significant higher pump output (5.1 +/- 1.0 L/min) in comparison with nonpulsatile LVADs (3.6 +/- 0.9 L/min, p < 0.001). Echocardiographic-determined end-systolic indicators confirm this augmentation in pulsatile LVADs. Etiology or the time interval of hemodynamic reassessment had no impact in left ventricular pressure unloading, but LV volume unloading decreased between day 60 and 120 in patients with nonpulsatile LVADs. The preoperative and postoperative transplant mortality was comparable in both groups. CONCLUSIONS: Left ventricular pressure unloading is similar in patients with nonpulsatile as compared with pulsatile implantable long-term assist devices. Left ventricular volume unloading is pronounced in pulsatile LVADs.

Reversible pulmonary hypertension in heart transplant candidates--pretransplant evaluation and outcome after orthotopic heart transplantation.

BACKGROUND: Heart transplantation is the most effective treatment for well-selected patients with endstage heart failure. Unfortunately, transplant candidates with pulmonary hypertension (PHT) are often not considered for heart transplantation. This study was performed to assess the value of prostaglandin E(1) (PG-E(1)) for reduction of PHT and to predict the postoperative outcome, compared to patients without PHT. PATIENTS AND METHODS: We studied a group of 151 consecutive heart transplant candidates using right heart catheterization. In patients with PHT (pulmonary vascular resistance, PVR> or =2.5 Wood-Units (WU) and/or transpulmonary gradient (TPG)> or =12 mmHg) a short-term treatment protocol with PG-E(1) was performed, to achieve PVR<2.5 WU and TPG<12 mmHg. RESULTS: 61 patients (40%) had PHT according to our criteria. Reduction of PHT was successful in 71% of patients (n=43), of these, 18 patients underwent cardiac transplantation and the 1-year mortality rate was 22% (n=4). The 1-year mortality rate in transplanted patients without PHT was 14% (n=3). There was no statistical difference in survival between the PHT and the non-PHT group. Outcome in patients without heart transplantation was similar in both groups, except for patients with non-reducible PHT (1-year mortality 50%). CONCLUSIONS: Our study demonstrates the efficacy and safety of PG-E(1) in lowering PHT in heart transplant candidates, as well as the need for aggressive evaluation and treatment in these patients. Patients with reversible PHT have comparable post-transplant outcomes and no tendency to higher acute right ventricular failure.

Doppler microembolic load predicts risk of thromboembolic complications in Novacor patients.

OBJECTIVE: Left ventricular assist devices have become an established method to bridge patients with end-stage cardiac failure to heart transplantation. Besides infection and bleeding, thromboembolism represents one of the most serious complications. We evaluated the value of microembolic signals in predicting thromboembolic events for individual patients and distinctive left ventricular assist device periods. METHODS: Twenty patients (14 male) aged 23-57 years supported with the Novacor N100 left ventricular assist device were enrolled in this study. All patients were on effective anticoagulation, 12 patients additionally received antiplatelet therapy. Unilateral detection of microembolic signals was performed once weekly by insonation of the middle cerebral artery using transcranial Doppler sonography for 30 minutes duration. Evidence of clinically manifest thromboembolic events was based on regular questionnaires, clinical examinations, and results of diagnostic procedures. RESULTS: During a cumulative follow-up of 3876 left ventricular assist device days, 44 thromboembolic complications occurred (incidence, 1.1%) in 15 out of 20 patients. A total of 360 transcranial Doppler sonography monitorings (range, 5-34 per patient) were performed with an overall microembolic signals prevalence of 35.3% and a microembolic signal mean of 2.3 +/- 9.2 per examination. There was a highly significant correlation between the individual microembolic signal activity and the respective incidence of clinical thromboembolism (r = 0.61-0.9; P <.01). Patients with additional antiplatelet treatment had significantly less thromboembolic complications (0.7%) and lower microembolic signal prevalence (18.3%) than those without (2.8% and 65.4%, respectively). Individual patients and left ventricular assist device months with clinical thromboembolization could be identified using the microembolic signal activity with moderate positive (0.37-0.7) and high negative predictive values (0.82-1.0). CONCLUSIONS: The amount of microembolic signals, serially detected in patients with the Novacor left ventricular assist device, is significantly associated with their incidence of embolic complications. The high negative predictive value of microembolic signals enables to identify those patients and left ventricular assist device periods with particularly low risk of clinical thromboembolization.

Partial left ventriculectomy in modified adriamycin-induced cardiomyopathy in the dog.

BACKGROUND: The purpose of this study was to evaluate modified adriamycin-induced cardiomyopathy in the dog for research on partial left ventriculectomy (PLV). METHODS: An intracoronary catheter was introduced into the left main stem via the first marginal branch in a retrograde fashion in 12 adult foxhound dogs. The catheter was connected to a percutaneous access port that was used for weekly adriamycin administration (10 mg over a 1-hour period on 5 occasions). Follow-up examinations (transthoracic echocardiography, hemodynamic parameters, cardiopulmonary status, neurohormones) were done before, 1 week after the last adriamycin administration, and then 6 weeks later. This protocol was performed in 6 dogs (control group: Group 1). The other 6 dogs underwent PLV 1 week after the last adriamycin administration (Group 2). After the last measurements, all dogs were killed with saturated potassium chloride under general anesthesia and the hearts were excised for histologic examination. All data were calculated as mean and standard error of the mean. Differences were calculated by the Wilcoxon signed-rank test for paired and unpaired data. p < 0.05 was considered statistically significant. RESULTS: One dog from each group died suddenly during adriamycin administration (probably due to ventricular arrhythmia). In addition, 1 dog from Group 2 suffered from a severe systemic inflammatory response syndrome after PLV and died 36 hours after surgery. Thus, 5 dogs from Group 1 and 4 from Group 2 underwent the entire study protocol. Adriamycin administration resulted in a severe dilated cardiomyopathy that was comparable in both groups (significant increase of central venous pressure, mean pulmonary artery pressure, pulmonary wedge pressure, left ventricular end-systolic and end-diastolic diameters, oxygen extraction, troponin I and anti-diuretic hormone, whereas cardiac output, ejection fraction and venous oxygen saturation decreased significantly). Deterioration of cardiac function continued after termination of adriamycin administration in Group 1 dogs, albeit not as progressively as during adriamycin administration. In contrast, cardiac function improved in Group 2 dogs after PLV, but did not reach baseline values. Cardiac index increased and oxygen extraction (p = 0.03) decreased, resulting in an enhanced venous oxygen saturation (p = 0.02). In particular, the distance of the papillary muscles at end diastole (p = 0.02) and at end systole (p = 0.02) at the mid-papillary level decreased significantly after PLV, resulting in reduced left ventricular diameter and volume (statistically significant for left ventricular end-systolic diameter and volume). All hearts had severe histologic alterations characteristic of adriamycin-induced toxicity, including cytoplasmic vacuolation, myocyte degeneration and increased fibrosis. CONCLUSION: Modified adriamycin-induced cardiomyopathy in the dog may be suitable for research on PLV.

Direct epicardial mapping can differentiate hibernating from scarred myocardium: a validation study with 18F-FDG-PET.

AIM: This study investigated the value of epicardial mapping immediately before CABG in the differentiation of hibernating from scarred myocardium in correlation to the noninvasive gold standard (18)F-FDG PET. METHODS AND RESULTS: In 35 patients with CAD, myocardial perfusion ((99m)Tc-Tetrofosmin-SPECT), viability ((18)F-FDG-PET), and function (LVangiography) were assessed before CABG. 102 bipolar epicardial electrograms per patient (n = 3570 electrograms) were recorded simultaneously with a ventricular jacket array. Based on the scintigraphic and LV angiographic data at the site of each electrode with good myocardial contact (n = 1963), segments (n = 492, 14.1 +/- 5.6 per patient; mean +/- SD) were classified into three groups: hibernating (n = 139), scarred (n = 104), and control (n = 249). Regional mean bipolar voltage values were calculated for Receiver Operating Characteristic (ROC) analysis. Mean bipolar voltage was significantly lower in scarred when compared to hibernating myocardium. ROC curve analysis (area under the curve of 0.92 +/- 0.47, mean +/- SE) for mean bipolar voltage to discriminate between hibernating and scarred myocardium revealed a sensitivity of 94% with a specificity of 83% at a cut-off value of 8.75 mV. CONCLUSION: Hibernating myocardium can be differentiated correctly from scarred myocardium by direct epicardial mapping. In the future, hibernating myocardium may be detectable by body surface mapping techniques using inverse solutions.

Biochemical mechanisms of hibernation and stunning in the human heart.

BACKGROUND: Myocardial hibernation and stunning are characterized by depressed cardiac function in the presence of reduced or normal coronary blood flow. The underlying biochemical mechanisms are widely unknown and only limited data are available in human hearts. METHODS AND RESULTS: Left ventricular transmural myocardial biopsies were obtained from normal and dysfunctional segments of patients undergoing coronary bypass surgery. Segments were classified as hibernating (n=10) or stunned (n=9) using contrast ventriculography and echocardiography, single photon emission computed tomography (SPECT), and positron emission tomography (PET). In each patient, biopsies from normal myocardial segments were used as controls (n=19). Compared to control myocardium, levels of cAMP (3'-5'cyclic adenosine monophosphate, in fmol/mg wet weight, means+/-S.E.M.) were higher in hibernating (673+/-76 versus 518+/-47, P<0.05) but unchanged in stunned myocardium (513+/-73 versus 466+/-97, P>0.05). Protein expression of phospholamban, sarcoendoplasmic Ca(2+)-ATPase 2a, calsequestrin, the inhibitory subunit of troponin, as well as the activation of p38 MAP kinase were not different when compared to controls. However, heat shock protein 72 (Hsp72) was increased 55% in stunned (2.89+/-0.58 versus 1.86+/-0.32, P<0.05) but not in hibernating myocardium (1.68+/-0.34 versus 1.67+/-0.29, P>0.05). CONCLUSIONS: The data from the present study suggest different pathophysiological mechanisms for myocardial hibernation and stunning. Alterations in the homeostasis of cAMP might be a compensatory mechanism in myocardial hibernation, whereas expression of Hsp72 appears to be cardioprotective in human myocardial stunning. Future studies should further elucidate these mechanisms and their potential impact on future therapeutic interventions.

Treatment of thrombus formation associated with the MicroMed DeBakey VAD using recombinant tissue plasminogen activator.

BACKGROUND: The latest generation of left ventricular assist devices consists of nonpulsatile impeller pumps. In these small pumps, thrombus formation inside the device does not lead to thromboembolic end-organ dysfunction but may dramatically impair pump flow. We report on our experience with thrombus-related pump dysfunctions of the MicroMed DeBakey left ventricular assist device and its treatment. METHODS: Eight of 22 patients with a MicroMed DeBakey VAD presented with a critically reduced pump flow. In 7 cases, an increased power demand indicative of progressive thrombus formation associated with the device was evident, whereas 1 case presented with thrombus formation within the inflow conduit associated with a very low power demand. Brief spontaneously resolving pump stops had been noted in 6 patients. All 8 patients were treated with 100 mg of recombinant tissue plasminogen activator (rt-PA), administered via an IV line. RESULTS: Rt-PA lysis led to an increase of pump flow along with a reduction of power demand within a short time in all patients. No severe bleeding complications occurred. However, 4 patients experienced transient epistaxis. All patients could be discharged from intensive care immediately after discontinuation of thrombolytic therapy. CONCLUSION: Rt-PA lysis is a very effective tool for thrombus-related pump dysfunction in patients with impeller pumps, which renders emergency surgical exchange unnecessary in most cases.

Crossing atrial thrombus in a patient with recurrent pulmonary embolism.

OBJECTIVES: To report the detection of a thrombus entrapped in a patent foramen ovale by echocardiography in a patient with recurrent pulmonary embolism. DESIGN: Case report. SETTING: Intensive care unit of a university hospital. PATIENT: A 62-yr-old man with initial deep venous thrombosis and recurrent minor pulmonary embolism followed by a severe embolic event with transitory hemiparesis 10 days after prostatectomy. INTERVENTION: Systemic anticoagulation, surgical removal of a crossing atrial thrombus, closure of a patent foramen ovale, and venous thrombectomy. MEASUREMENTS AND MAIN RESULTS: Transesophageal echocardiography revealed a large thrombus entrapped in a patent foramen ovale with portions in all four heart chambers. Intraoperatively, a 19-cm-long thrombus, shaped like the pelvic veins, was found. The patient was successfully weaned from cardiopulmonary bypass, requiring temporary positive inotropic support because of right ventricular dysfunction. Within 24 hrs of the operation, the patient was discharged to the intermediate care unit. CONCLUSIONS: Recurrent pulmonary embolism can potentially result in paradoxic embolism in patients with a patent foramen ovale. In such patients, it may be crucial to monitor right ventricular function and exclude right-to-left shunts by transesophageal echocardiography, regardless of clinical symptoms. The patent foramen ovale should be closed. This case emphasizes an important indication for transesophageal echocardiography in critically ill patients.

Adriamycin-induced cardiomyopathy in the dog--an appropriate model for research on partial left ventriculectomy?

OBJECTIVE: To evaluate the adriamycin-induced cardiomyopathy in the dog for research on partial left ventriculectomy (PLV). METHODS: An intracoronary catheter was introduced into the left main stem via the first diagonal branch in a retrograde fashion in 6 adult FBI (Foxhound Boehringer Ingelheim) dogs weighing 30 to 35 kg. The catheter was connected to a percutaneous access port that was used for weekly adriamycin administration (10 mg over a 1-hour period for 5 times). Follow-up examinations (transthoracic echocardiography, hemodynamic parameters, cardiopulmonary status, and neurohormones) were done before, 1 week after the last adriamycin administration, and 6 weeks later. After the last measurements, all dogs were euthanized with saturated potassium chloride under general anesthesia and the hearts were excised for histologic examinations. All data were calculated as mean values and standard error of the mean. Differences were calculated by the Wilcoxon signed rank test for paired and unpaired data. p values less than 0.05 were considered significant. RESULTS: Central venous pressure (2.2 +/- 0.8 vs 5.2 +/- 0.4 mm Hg, p = 0.03), mean pulmonary artery pressure (8.6 +/- 1.1 vs 12.4 +/- 0.5 mm Hg, p = 0.03), pulmonary wedge pressure (2.6 +/- 0.9 vs 7.0 +/- 0 mm Hg, p = 0.03), left ventricular endsystolic diameter (2.5 +/- 0.2 vs 3.1 +/- 0.4 cm, p = 0.03), and enddiastolic (4.5 +/- 0.2 vs 4.9 +/- 0.2 cm, p = 0.03) diameter increased significantly after adriamycin administration, whereas cardiac output (4.0 +/- 0.3 vs 3.3 +/- 0.1 liter/min, p = 0.03), stroke volume index (66.0 +/- 7.4 vs 54.0 +/- 3.9 ml/beat/m(2), p = 0.03), and ejection fraction (61.1 +/- 5.1 vs 37.7 +/- 5.7%, p = 0.03) decreased markedly. These changes were accompanied by a significant decline of oxygen delivery (1130 +/- 170 vs 790 +/- 65 ml/min, p = 0.03), which led to an enhanced oxygen extraction (0.12 +/- 0.01 vs 0.24 +/- 0.01, p = 0.03). Consequently, venous oxygen saturation (82.7 +/- 4.1 vs 71.3 +/- 2.5%, p = 0.03) decreased. Troponin I (0.02 +/- 0.025 vs 1.7 +/- 0.6 ng/ml, p = 0.03) and the anti-diuretic hormone (1.9 +/- 0.9 vs 20.0 +/- 1.9 pg/ml, p = 0.03) increased significantly after adriamycin administration. Deterioration of cardiac function continued after termination of adriamycin administration, albeit slower than during adriamycin administration. All hearts had severe histologic alterations, which were characteristic of adriamycin-induced toxicity: cytoplasmic vacuolation, myocyte degeneration, and increased fibrosis. CONCLUSIONS: The adriamycin-induced cardiomyopathy in the dog is similar to the dilated cardiomyopathy in humans and may be an appropriate model for PLV.

Successful cardiac transplantation after 4 cases of DeBakey left ventricular assist device failure.

Left ventricular assist devices (LVADs) are an established surgical therapy for patients with end-stage heart failure as a bridge to cardiac transplantation. Major disadvantages of these devices are thromboembolic events, bleeding complications, infections, and malfunctions. We report on our experiences with DeBakey LVAD malfunctions requiring LVAD exchange in 4 patients. All patients underwent subsequent cardiac transplantation and are doing well now.

Effect of ventricular fibrillation duration on the defibrillation threshold in humans.

Early during ventricular fibrillation, the defibrillation threshold may be low, as ventricular fibrillation most probably arises from a localized area with only a few wavefronts and the effects of global ischemia, ventricular dilatation, and sympathetic discharge have not yet fully developed. The purpose of this study was to explore the effect of the timing of shock delivery in humans. During implantation of an ICD in 26 patients (24 men, 60 +/- 11 years, 19 coronary artery disease, NYHA 2.2 +/- 0.4, left ventricular ejection fraction 0.42 +/- 0.16), the defibrillation threshold was determined after approximately 10 and 2 seconds of ventricular fibrillation. Ventricular fibrillation was induced by T wave shocks. Mean defibrillation threshold was 9.9 +/- 3.6 J after 10.3 +/- 1.0 seconds. Within 2 seconds, 20 of 26 patients could be successfully defibrillated with < or = 8 J. In these patients, the mean defibrillation threshold was 4.0 +/- 2.1 J after 1.4 +/- 0.3 seconds compared to 9.5 +/- 3.1 J after 10.2 +/- 1.1 seconds (P < 0.001). There were no clinical differences between patients who could be successfully defibrillated within 2 seconds and those patients without successful defibrillation within 2 seconds. In the majority of patients, the defibrillation threshold was significantly lower within the first few cycles of ventricular fibrillation than after 10 seconds of ventricular fibrillation. These results should lead to exploration of earlier shock delivery in implantable devices. This could possibly reduce the incidence of syncope in patients with rapid ventricular tachyarrhythmias and ICDs.