Simultaneous subacute coronary drug-eluting stent thrombosis in two different vessels of a patient with factor V Leiden mutation

We review the case of a 46-year-old man who underwent elective percutaneous coronary intervention and stenting of the left anterior descending artery and right coronary artery with two sirolimus- and paclitaxel-eluting stents. Four days after angioplasty, he was readmitted with cardiogenic shock due to acute anterior and inferior myocardial infarction. Coronary angiography revealed subacute thrombosis of both stents, and balloon dilation was performed successfully thereafter. The follow-up investigations revealed that the patient was a carrier of factor V Leiden. We hereby discuss the importance of factor V Leiden as the most common cause of hypercoagulable state and its probable role in acute and subacute coronary stent thrombosis in drug-eluting stents.

Excellent outcome after surgical treatment of massive pulmonary embolism in critically ill patients

OBJECTIVE: Treatment of central and paracentral pulmonary embolism in patients with hemodynamic compromise remains a subject of debate, and no consensus exists regarding the best method: thrombolytic agents, catheter-based thrombus aspiration or fragmentation, or surgical embolectomy. We reviewed our experience with emergency surgical pulmonary embolectomy. METHODS: Between January of 2000 and March of 2007, 25 patients (17 male, mean age 60 years) underwent emergency open embolectomy for central and paracentral pulmonary embolism. Eighteen patients presented in cardiogenic shock, 8 of whom had cardiac arrest and required cardiopulmonary resuscitation. All patients underwent operation with mild hypothermic cardiopulmonary bypass. Concomitant procedures were performed in 8 patients (3 coronary artery bypass grafts, 2 patent foramen ovale closures, 4 ligations of the left atrial appendage, 3 removals of a right atrial thrombus). Follow-up is 96% complete with a median of 2 years (range, 2 months to 6 years). RESULTS: All patients survived the procedure, but 2 patients died in the hospital on postoperative days 1 (intracerebral bleeding) and 11 (multiorgan failure), accounting for a 30-day mortality of 8% (95% confidence interval: 0.98-0.26). Four patients died later because of their underlying disease. Pre- and postoperative echocardiographic pressure measurements demonstrated the reduction of the pulmonary hypertension to half of the systemic pressure values or less. CONCLUSION: Surgical pulmonary embolectomy is an excellent option for patients with major pulmonary embolism and can be performed with minimal mortality and morbidity. Even patients who present with cardiac arrest and require preoperative cardiopulmonary resuscitation show satisfying results. Immediate surgical desobstruction favorably influences the pulmonary pressure and the recovery of right ventricular function, and remains the treatment of choice for patients with massive central and paracentral embolism with hemodynamic and respiratory compromise.

Extracorporeal membrane oxygenation (ECMO): extended indications for artificial support of both heart and lungs

Extracorporeal membrane oxygenation (ECMO) was used to achieve temporary artificial support in cardiac and pulmonary function in 22 patients from 1987 to September 1990. Standard indications were postcardiotomy cardiogenic shock (n = 4), neonatal (n = 1) and adult respiratory distress syndrome (n = 4). ECMO was also used for extended indications, such as graft failure following heart (n = 11) or lung transplantation (n = 2). In six of these cases ECMO was instituted as a bridge device to subsequent retransplantation of either the heart (n = 4) or one lung (n = 2). One out of nine patients supported by ECMO for standard indications, and two out of 13 patients supported for extended indications are long-term survivors. This series illustrates the results with ECMO in emergency situations, in patients under immunosuppressive protocols, or in patients with advanced lung failure requiring almost complete artificial gas exchange. In such complex situations, ECMO does provide stabilization until additional therapeutic measures are in effect. ECMO cannot be recommended for postoperative cardiogenic shock but short-term ECMO support is an accepted method in most cases with graft failure or pulmonary failure or other origin.

Unprotected left main stenting in the real world: two-year outcomes of the French left main taxus registry

BACKGROUND: Cardiac surgery is the reference treatment for patients with left main (LM) disease, although percutaneous coronary intervention with drug-eluting stents is emerging as a possible alternative. The objective of this registry was to evaluate the 2-year outcome of elective percutaneous coronary intervention for unprotected LM disease with paclitaxel-eluting stents. METHODS AND RESULTS: A total of 291 patients were prospectively included from 4 centers. Acute myocardial infarction and cardiogenic shock were the only exclusion criteria. Patients were 69+/-11 years old, 29% were diabetic, and 25% had 3-vessel disease. For distal LM lesions (78%), the provisional side-branch T-stenting approach was used in 92% of cases and final kissing balloon inflation in 97%. Angiographic success was obtained in 99.7% of cases. At 2-year follow-up, the total cardiac death rate was 5.4% (1 EuroSCORE point was associated with a 15% [95% confidence interval 2.9% to 28.2%, P=0.013] higher risk of cardiac death), target-lesion revascularization was 8.7%, and incidence of Q-wave or non-Q-wave myocardial infarction was 0.9% and 3.1%, respectively. The combined end point occurred in 15.8% of cases and stroke in 0.7%. The incidence of definite and probable LM stent thrombosis was 0.7%, whereas the incidence of any stent thrombosis was 3.8%, with a higher risk in patients with side-branch stenting in the presence of LM bifurcation lesions (hazard ratio 9.6, 95% confidence interval 1.2 to 77.7, P=0.035). CONCLUSIONS: Unprotected LM stenting with paclitaxel-eluting stents, with a strategy of provisional side-branch T-stenting for distal lesions, provides excellent acute angiographic results and good mid-term clinical outcomes, with a 15.8% rate of major adverse cardiac events at 2-year follow-up.

Comparison of two non-bronchoscopic methods for evaluating inflammation in patients with acute hypoxaemic respiratory failure

INTRODUCTION: The simple bedside method for sampling undiluted distal pulmonary edema fluid through a normal suction catheter (s-Cath) has been experimentally and clinically validated. However, there are no data comparing non-bronchoscopic bronchoalveolar lavage (mini-BAL) and s-Cath for assessing lung inflammation in acute hypoxaemic respiratory failure. We designed a prospective study in two groups of patients, those with acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) and those with acute cardiogenic lung edema (ACLE), designed to investigate the clinical feasibility of these techniques and to evaluate inflammation in both groups using undiluted sampling obtained by s-Cath. To test the interchangeability of the two methods in the same patient for studying the inflammation response, we further compared mini-BAL and s-Cath for agreement of protein concentration and percentage of polymorphonuclear cells (PMNs). METHODS: Mini-BAL and s-Cath sampling was assessed in 30 mechanically ventilated patients, 21 with ALI/ARDS and 9 with ACLE. To analyse agreement between the two sampling techniques, we considered only simultaneously collected mini-BAL and s-Cath paired samples. The protein concentration and polymorphonuclear cell (PMN) count comparisons were performed using undiluted sampling. Bland-Altman plots were used for assessing the mean bias and the limits of agreement between the two sampling techniques; comparison between groups was performed by using the non-parametric Mann-Whitney-U test; continuous variables were compared by using the Student t-test, Wilcoxon signed rank test, analysis of variance or Student-Newman-Keuls test; and categorical variables were compared by using chi-square analysis or Fisher exact test. RESULTS: Using protein content and PMN percentage as parameters, we identified substantial variations between the two sampling techniques. When the protein concentration in the lung was high, the s-Cath was a more sensitive method; by contrast, as inflammation increased, both methods provided similar estimates of neutrophil percentages in the lung. The patients with ACLE showed an increased PMN count, suggesting that hydrostatic lung edema can be associated with a concomitant inflammatory process. CONCLUSIONS: There are significant differences between the s-Cath and mini-BAL sampling techniques, indicating that these procedures cannot be used interchangeably for studying the lung inflammatory response in patients with acute hypoxaemic lung injury.

Cardiac c-kit+AT2+ cell population is increased in response to ischemic injury and supports cardiomyocyte performance

The expression pattern of angiotensin AT2 receptors with predominance during fetal life and upregulation under pathological conditions during tissue injury/repair process suggests that AT2 receptors may exert an important action in injury/repair adaptive mechanisms. Less is known about AT2 receptors in acute ischemia-induced cardiac injury. We aimed here to elucidate the role of AT2 receptors after acute myocardial infarction. Double immunofluorescence staining showed that cardiac AT2 receptors were mainly detected in clusters of small c-kit+ cells accumulating in peri-infarct zone and c-kit+AT2+ cells increased in response to acute cardiac injury. Further, we isolated cardiac c-kit+AT2+ cell population by modified magnetic activated cell sorting and fluorescence activated cell sorting. These cardiac c-kit+AT2+ cells, represented approximately 0.19% of total cardiac cells in infarcted heart, were characterized by upregulated transcription factors implicated in cardiogenic differentiation (Gata-4, Notch-2, Nkx-2.5) and genes required for self-renewal (Tbx-3, c-Myc, Akt). When adult cardiomyocytes and cardiac c-kit+AT2+ cells isolated from infarcted rat hearts were cocultured, AT2 receptor stimulation in vitro inhibited apoptosis of these cocultured cardiomyocytes. Moreover, in vivo AT2 receptor stimulation led to an increased c-kit+AT2+ cell population in the infarcted myocardium and reduced apoptosis of cardiomyocytes in rats with acute myocardial infarction. These data suggest that cardiac c-kit+AT2+ cell population exists and increases after acute ischemic injury. AT2 receptor activation supports performance of cardiomyocytes, thus contributing to cardioprotection via cardiac c-kit+AT2+ cell population.

Gender-related mortality trends among diabetic patients with ST-segment elevation myocardial infarction: insights from a nationwide registry 1997-2010

BACKGROUND Data on temporal trends in outcomes, gender differences, and adherence to evidence-based therapy (EBT) of diabetic patients with ST-segment elevation myocardial infarction (STEMI) are sparse. METHODS We performed a retrospective analysis of prospectively acquired data on 3565 diabetic (2412 males and 1153 females) STEMI patients enrolled in the Swiss AMIS Plus registry between 1997 and 2010 and compared in-hospital outcomes and adherence to EBT with the nondiabetic population (n=15,531). RESULTS In-hospital mortality dramatically decreased in diabetic patients, from 19.9% in 1997 to 9.0% in 2010 (p trend<0.001) with an age-adjusted decrease of 6% per year of admission. Similar trends were observed for age-adjusted reinfarction (OR 0.86, p<0.001), cardiogenic shock (OR 0.88, p<0.001), as well as death, reinfarction, or stroke (OR 0.92, p<0.001). However, the mortality benefit over time was observed in diabetic males (p trend=0.006) but not females (p trend=0.082). In addition, mortality remained twice as high in diabetic patients compared with nondiabetic ones (12.1 vs. 6.1%, p<0.001) and diabetes was identified as independent predictor of mortality (OR 1.23, p=0.022). Within the diabetic cohort, females had higher mortality than males (16.1 vs. 10.2%, p<0.001) and female gender independently predicted in-hospital mortality (OR 1.45, p=0.015). Adherence to EBT significantly improved over time in diabetic patients (p trend<0.001) but remained inferior - especially in women - to the one of nondiabetic individuals. CONCLUSIONS In-hospital mortality and morbidity of diabetic STEMI patients in Switzerland improved dramatically over time but, compared with nondiabetic counterparts, gaps in outcomes as well as EBT use persisted, especially in women.

Death by patent foramen ovale in a soccer player

A 34-year-old male patient was referred for primary percutaneous coronary intervention for ST-segment elevation myocardial infarction with cardiogenic shock and was found to have embolic left coronary artery occlusion and subsegmental pulmonary artery emboli as a consequence of venous thrombosis to trauma to the thigh in the presence of a patent foramen ovale.

Fixed low-dose ultrasound-assisted catheter-directed thrombolysis for intermediate- and high-risk pulmonary embolism

AIMS No standardized local thrombolysis regimen exists for the treatment of pulmonary embolism (PE). We retrospectively investigated efficacy and safety of fixed low-dose ultrasound-assisted catheter-directed thrombolysis (USAT) for intermediate- and high-risk PE. METHODS AND RESULTS Fifty-two patients (65 ± 14 years) of whom 14 had high-risk PE (troponin positive in all) and 38 intermediate-risk PE (troponin positive in 91%) were treated with intravenous unfractionated heparin and USAT using 10 mg of recombinant tissue plasminogen activator per device over the course of 15 h. Bilateral USAT was performed in 83% of patients. During 3-month follow-up, two [3.8%; 95% confidence interval (CI) 0.5-13%] patients died (one from cardiogenic shock and one from recurrent PE). Major non-fatal bleeding occurred in two (3.8%; 95% CI, 0.5-13%) patients: one intrathoracic bleeding after cardiopulmonary resuscitation requiring transfusion, one intrapulmonary bleeding requiring lobectomy. Mean pulmonary artery pressure decreased from 37 ± 9 mmHg at baseline to 25 ± 8 mmHg at 15 h (P < 0.001) and cardiac index increased from 2.0 ± 0.7 to 2.7 ± 0.9 L/min/m(2) (P < 0.001). Echocardiographic right-to-left ventricular end-diastolic dimension ratio decreased from 1.42 ± 0.21 at baseline to 1.06 ± 0.23 at 24 h (n = 21; P < 0.001). The greatest haemodynamic benefit from USAT was found in patients with high-risk PE and in those with symptom duration < 14 days. CONCLUSION A standardized catheter intervention approach using fixed low-dose USAT for the treatment of intermediate- and high-risk PE was associated with rapid improvement in haemodynamic parameters and low rates of bleeding complications and mortality.

Transient loss of consciousness and syncope

Syncope describes a sudden and brief transient loss of consciousness (TLOC) with postural failure due to cerebral global hypoperfusion. The term TLOC is used when the cause is either unrelated to cerebral hypoperfusion or is unknown. The most common causes of syncopal TLOC include: (1) cardiogenic syncope (cardiac arrhythmias, structural cardiac diseases, others); (2) orthostatic hypotension (due to drugs, hypovolemia, primary or secondary autonomic failure, others); (3) neurally mediated syncope (cardioinhibitory, vasodepressor, and mixed forms). Rarely neurologic disorders (such as epilepsy, transient ischemic attacks, and the subclavian steal syndrome) can lead to cerebal hypoperfusion and syncope. Nonsyncopal TLOC may be due to neurologic (epilepsy, sleep attacks, and other states with fluctuating vigilance), medical (hypoglycemia, drugs), psychiatric, or post-traumatic disorders. Basic diagnostic workup of TLOC includes a thorough history and physical examination, and a 12-lead electrocardiogram (ECG). Blood testing, electroencephalogram (EEG), magnetic resonance imaging (MRI) of the brain, echocardiography, head-up tilt test, carotid sinus massage, Holter monitoring, and loop recorders should be obtained only in specific contexts. Management strategies involve pharmacologic and nonpharmacologic interventions, and cardiac pacing.

Different Contribution of Splanchnic Organs to Hyperlactatemia in Fecal Peritonitis and Cardiac Tamponade

Background. Changes in hepatosplanchnic lactate exchange are likely to contribute to hyperlactatemia in sepsis. We hypothesized that septic and cardiogenic shock have different effects on hepatosplanchnic lactate exchange and its contribution to hyperlactatemia. Materials and Methods. 24 anesthetized pigs were randomized to fecal peritonitis (P), cardiac tamponade (CT), and to controls ( per group). Oxygen transport and lactate exchange were calculated during 24 hours. Results. While hepatic lactate influx increased in P and in CT, hepatic lactate uptake remained unchanged in P and decreased in CT. Hepatic lactate efflux contributed 20% (P) and 33% (CT), respectively, to whole body venous efflux. Despite maintained hepatic arterial blood flow, hepatic oxygen extraction did not increase in CT. Conclusions. Whole body venous lactate efflux is of similar magnitude in hyperdynamic sepsis and in cardiogenic shock. Although jejunal mucosal pCO2 gradients are increased, enhanced lactate production from other tissues is more relevant to the increased arterial lactate. Nevertheless, the liver fails to increase hepatic lactate extraction in response to rising hepatic lactate influx, despite maintained hepatic oxygen consumption. In cardiac tamponade, regional, extrasplanchnic lactate production is accompanied by hepatic failure to increase oxygen extraction and net hepatic lactate output, despite maintained hepatic arterial perfusion.

Management of ST-elevation myocardial infarction according to European and American guidelines.

AIMS To highlight differences between the most recent guidelines of the European Society of Cardiology (ESC) and the American College of Cardiology Foundation/American Heart Association (ACCF/AHA) on the management of ST-elevation myocardial infarction (STEMI). METHODS AND RESULTS ESC 2012 and ACCF/AHA 2013 guidelines on the management of STEMI were systematically reviewed for consistency. Recommendations were matched, directly compared in terms of class of recommendation and level of evidence, and classified as "identical", "overlapping", or "different". Out of 32 recommendations compared, 26 recommendations (81%) were classified as identical or overlapping, and six recommendations (19%) were classified as different. Most diverging recommendations were related to minor differences in class of recommendation between the two documents. This applies to recommendations for reperfusion therapy >12 hours after symptom onset, immediate transfer of all patients after fibrinolytic therapy, rescue PCI for patients with failed fibrinolysis, and intra-aortic balloon pump use in patients with cardiogenic shock. More substantial differences were observed with respect to the type of P2Y12 inhibitor and duration of dual antiplatelet therapy. CONCLUSIONS The majority of recommendations for the management of STEMI according to ESC and ACCF/AHA guidelines were identical or overlapping. Differences were explained by gaps in available evidence, in which case expert consensus differed between European and American guidelines due to divergence in interpretation, perception, and culture of medical practice. Systematic comparisons of European and American guidelines are valuable and indicate that interpretation of available evidence leads to agreement in the vast majority of topics. The latter is indirect support for the process of review and guideline preparation on both sides of the Atlantic.

Functional Characterization and Comparison of Intercellular Communication in Stem Cell-Derived Cardiomyocytes

One novel treatment strategy for the diseased heart focuses on the use of pluripotent stem cell-derived cardiomyocytes (SC-CMs) to overcome the heart's innate deficiency for self-repair. However, targeted application of SC-CMs requires in-depth characterization of their true cardiogenic potential in terms of excitability and intercellular coupling at cellular level and in multicellular preparations. In this study, we elucidated the electrical characteristics of single SC-CMs and intercellular coupling quality of cell pairs, and concomitantly compared them with well-characterized murine native neonatal and immortalized HL-1 cardiomyocytes. Firstly, we investigated the electrical properties and Ca2+ signaling mechanisms specific to cardiac contraction in single SC-CMs. Despite heterogeneity of the new cardiac cell population, their electrophysiological activity and Ca2+ handling were similar to native cells. Secondly, we investigated the capability of paired SC-CMs to form an adequate subunit of a functional syncytium and analyzed gap junctions and signal transmission by dye transfer in cell pairs. We discovered significantly diminished coupling in SC-CMs compared with native cells, which could not be enhanced by a coculture approach combining SC-CMs and primary CMs. Moreover, quantitative and structural analysis of gap junctions presented significantly reduced connexin expression levels compared with native CMs. Strong dependence of intercellular coupling on gap junction density was further confirmed by computational simulations. These novel findings demonstrate that despite the cardiogenic electrophysiological profile, SC-CMs present significant limitations in intercellular communication. Inadequate coupling may severely impair functional integration and signal transmission, which needs to be carefully considered for the prospective use of SC-CMs in cardiac repair.

Effects of dialysis modality on blood loss, bleeding complications and transfusion requirements in critically ill patients with dialysis-dependent acute renal failure.

Blood loss and bleeding complications may often be observed in critically ill patients on renal replacement therapies (RRT). Here we investigate procedural (i.e. RRT-related) and non-procedural blood loss as well as transfusion requirements in regard to the chosen mode of dialysis (i.e. intermittent haemodialysis [IHD] versus continuous veno-venous haemofiltration [CVVH]). Two hundred and fifty-two patients (122 CVVH, 159 male; aged 61.5±13.9 years) with dialysis-dependent acute renal failure were analysed in a sub-analysis of the prospective randomised controlled clinical trial-CONVINT-comparing IHD and CVVH. Bleeding complications including severity of bleeding and RRT-related blood loss were assessed. We observed that 3.6% of patients died related to severe bleeding episodes (between group P=0.94). Major all-cause bleeding complications were observed in 23% IHD versus 26% of CVVH group patients (P=0.95). Under CVVH, the rate of RRT-related blood loss events (57.4% versus 30.4%, P=0.01) and mean total blood volume lost was increased (222.3±291.9 versus 112.5±222.7 ml per patient, P <0.001). Overall, transfusion rates did not differ between the study groups. In patients with sepsis, transfusion rates of all blood products were significantly higher when compared to cardiogenic shock (all P <0.01) or other conditions. In conclusion, procedural and non-procedural blood loss may often be observed in critically ill patients on RRT. In CVVH-treated patients, procedural blood loss was increased but overall transfusion rates remained unchanged. Our data show that IHD and CVVH may be regarded as equivalent approaches in critically ill patients with dialysis-dependent acute renal failure in this regard.

Identification and characterization of new genes involved in Drosophila heart development

Heart development is a crucial and conserved process that is related to the major type of human birth defects. Dorsal vessel, the Drosophila heart, has been regarded as an insightful system to identify new genes and study gene functions involved in heart development. Using heart-specific GFP transgenes, I did a genetic screen for cardiogenic genes on Drosophila chromosome II. Drosophila mutants that carry chromosome II deficiencies were tested for their phenotypes of heart development. Based on the screen results, chromosome regions containing genes required for heart development were identified. Fly strains with single gene mutations located within the defined deficiency regions were tested further. Seven genes have been identified to be involved in heart development. ^ The LIM homeodomain transcription factor gene tailup (tup) was further studied for its function in heart development. Based on this study, tup is expressed in cardioblasts and pericardial cells of the heart tube, as well as in associated lymph glands and alary muscles. In depth analysis of tup mutant phenotypes demonstrated tup is required for normal development of both heart and lymph glands. Tup was shown to bind to two DNA recognition sequences in the dorsal vessel enhancer of the Hand bHLH transcription factor gene, with one site proven essential for the expression of Hand in lymph glands, pericardial cells, and Svp/Doc cardioblasts. Together, these studies demonstrate that Tup is a critical new transcription factor in dorsal vessel morphogenesis and lymph gland formation, and strongly suggest Tup is a direct regulator of the expression of Hand in these developmental processes. ^