Adaptive response to hypoxia and remote ischaemia pre-conditioning: a new hypoxia-inducible factors era in clinical medicine.

Transient ischaemia leads to tolerance to subsequent protracted ischaemia. This 'ischaemia pre-conditioning' results from the induction of numerous protective genes, involved in cell metabolism, proliferation and survival, in antioxidant capacity, angiogenesis, vascular tone and erythropoiesis. Hypoxia-inducible factors (HIF) play a pivotal role in this transcriptional adaptive response. HIF prolyl hydroxylases (PHDs), serving as oxygen sensors, control HIFα degradation. HIF-mediated ischaemic pre-conditioning can be achieved with the administration of PHD inhibitors, with the attenuation of organ injury under various hypoxic and toxic insults. Clinical trials are currently under way, evaluating PHD inhibitors as inducers of erythropoietin. Once their safety is established, their potential use might be further tested in clinical trials in various forms of acute ischaemic and toxic organ damage. Repeated transient limb ischaemia was also found to attenuate ischaemic injury in remote organs. This 'remote ischaemic pre-conditioning' phenomenon (RIP) has been extensively studied recently in small clinical trials, preceding, or in parallel with an abrupt insult, such as myocardial infarction, cardiac surgery or radiocontrast administration. Initial results are promising, suggesting organ protection. Large-scale multi-centre studies are currently under way, evaluating the protective potential of RIP in cardiac surgery, in the management of myocardial infarction and in organ transplantation. The mechanisms of organ protection provided by RIP are poorly understood, but HIF seemingly play a role as well. Thus, Inhibition of HIF degradation with PHD inhibitors, as well as RIP (in part through HIF), might develop into novel clinical interventions in organ protection in the near future.

The influence of clinical risk factors on pre-operative B-type natriuretic peptide risk stratification of vascular surgical patients.

The role of the revised cardiac risk index in risk stratification has recently been challenged by studies reporting on the superior predictive ability of pre-operative B-type natriuretic peptides. We found that in 850 vascular surgical patients initially risk stratified using B-type natriuretic peptides, reclassification with the number of revised cardiac risk index risk factors worsened risk stratification (p < 0.05 for > 0, > 2, > 3 and > 4 risk factors, and p = 0.23 for > 1 risk factor). When evaluated with pre-operative B-type natriuretic peptides, none of the revised cardiac risk index risk factors were independent predictors of major adverse cardiac events in vascular patients. The only independent predictor was B-type natriuretic peptide stratification (OR 5.1, 95% CI 1.8-15 for the intermediate class, and OR 25, 95% CI 8.7-70 for the high-risk class). The clinical risk factors in the revised cardiac risk index cannot improve a risk stratification model based on B-type natriuretic peptides.

Acute myocardial infarction after bone marrow transplantation: an unsuspected late complication.

Acute myocardial infarction is a common disease rarely seen as a complication of bone marrow transplantation in young patients. We report on a 25-year-old patient 3.5 years after bone marrow transplantation who suffered an acute anterior wall myocardial infarction complicated by cardiogenic shock. The patient was treated with thrombolysis and emergent coronary angioplasty but died a few hours following admission. We suggest that the combination of low-dose chest irradiation and prolonged immunosuppression with graft-versus-host disease contributed to the development of the coronary artery disease in this patient. Though rarely encountered, physicians caring for young patients after bone marrow transplantation should be aware of potential ischemic complications.

Left atrial appendage emptying velocity does not predict postoperative atrial fibrillation in patients undergoing cardiopulmonary bypass.

BACKGROUND: Atrial fibrillation is a common complication of cardio-pulmonary bypass and improved pre-operative risk assessment could help guide prophylactic therapy. This study examined whether reduced left atrial appendage flow velocities measured by transoesophageal echocardiography pre-operatively in patients in sinus rhythm predicted development of postoperative atrial fibrillation. METHODS AND RESULTS: All patients who underwent transoesophageal echocardiography for clinical indications with measurements of left atrial appendage velocities within twelve months prior to cardio-pulmonary bypass were retrospectively identified. Postoperative records were reviewed and the patients divided into two groups based on the presence or absence of clinically significant atrial fibrillation during hospitalization following cardio-pulmonary bypass. Thirty-six patients (mean age 61.1 +/- 14.8 years, 18M/18F) were included in the study. The overall incidence of atrial fibrillation in the cohort was 17/36 patients (47%). Mean left atrial appendage emptying velocity was 50.8 +/- 23.3 cm/s2 (range 26-119) in the patients with sinus rhythm only and 41.5 +/- 16.7 cm/s2 (range 16-76), in the patients with postoperative atrial fibrillation (P=ns). CONCLUSIONS: In our patient population there was no significant difference in left atrial appendage emptying velocity measured by transoesophageal echocardiography in patients with and without postoperative atrial fibrillation. Pre-operative measurement of left atrial appendage emptying velocity cannot be relied upon to risk stratify patients prior to cardio-pulmonary bypass.

Role of echocardiography in the diagnosis and treatment of acute pulmonary thromboembolism.

The diagnosis and treatment of acute pulmonary thromboembolism (PE) remains a complex clinical challenge. Many studies have used both transthoracic and transesophageal echocardiography as a diagnostic and/or prognostic tool in this common disorder. In patients with central, hemodynamically significant PE, echocardiography can directly visualize thrombus or demonstrate the hemodynamic consequences of PE, whereas in the majority of patients, the sensitivity of echocardiography appears limited. Echocardiography may be useful in assessing the prognosis of patients with PE as well as their response to therapy. Further studies are needed in larger populations of patients to clarify the role of echocardiography in the assessment of patients with clinically suspected PE.

Four-year prospective study of pulmonary venous thrombosis after lung transplantation.

The objective of this study was to prospectively assess pulmonary venous anastomosis by transesophageal echocardiography after lung transplantation. Thrombus formation at the pulmonary venous anastomotic site after lung transplantation may have catastrophic consequences, including allograft failure and stroke. Eighty-seven consecutive adult lung transplant recipients underwent transesophageal echocardiography within 48 hours after surgery. Thrombosis of a pulmonary vein was diagnosed in 13 (15%) of 87 patients in the early postoperative period after lung transplantation. Mean thrombus width was 0.9 +/- 0.4 cm (range, 0.5 to 1.7 cm), with an average peak flow velocity at the site of obstruction of 127 +/- 23 cm/s (range, 90 to 150 cm/s). Five patients with pulmonary vein thrombosis died in the perioperative period, yielding a 90-day mortality rate of 38%. Larger thrombus size and greater acceleration of flow through a narrowed pulmonary vein correlated with poor clinical outcome. During each year of the study, the incidence of pulmonary vein thrombosis declined progressively. Pulmonary vein thrombosis is a potentially ominous complication in the early postoperative period after lung transplantation. Transesophageal echocardiography is a valuable tool for detecting abnormalities of the pulmonary venous anastomosis. Thrombus size and flow velocity at the anastomotic site may guide prognosis and clinical management. Complications of the pulmonary venous anastomosis are in part technical in nature.

Three-year follow-up of atrial sensing efficacy in children and adults with a single lead VDD pacing system.

The purpose of this study was to evaluate the efficacy of atrial sensing in children with a single pass lead VDD pacing system and to compare it with the efficacy of atrial sensing in adult patients with the same pacing system. Although the feasibility of single pass lead VDD pacing system implantation in children was recently demonstrated, the efficacy of atrial sensing remains unclear. In addition, the effect of accelerated growth of children on the systems' efficacy has not been addressed. Atrial sensing followed by ventricular sensing and atrial sensing followed by ventricular pacing was prospectively evaluated in 13 children (age 0.5-15 years) and 24 adult patients (age 19-74 years). All had the same endocardial pacing system using a single pass lead. The children and adults had effective atrial sensing at a success rate of 94.00 +/- 9.687% and 96.04 +/- 4.64%, respectively, during mean follow-up of 3.5 years. The atrial electrogram amplitude was similar in both groups, 1.8 +/- 1.5 mV in children and 1.8 +/- 1.1 mV in adults. The adult patients more frequently exhibited ventricular sensing following atrial sensing. The ventricular pacing threshold and impedance were stable in both groups. When necessary, in children, the atrial sensing was corrected by adjusting the pacemaker's lower rate programming. Highly effective atrial sensing was demonstrated in children and adult patients with a single pass lead VDD pacing system. During a mean follow-up of 3.5 years, not only was the atrial electrogram amplitude stable, but the clinically relevant atrial sensing was highly effective, justifying endocardial pacing with single pass lead VDD pacing in children and adults with preserved sinus node function.

Long-distance air travel soon after an acute coronary syndrome: a prospective evaluation of a triage protocol.

BACKGROUND: An increasing number of patients have an acute coronary syndrome while abroad. Such an event may entail significant emotional and financial stress, and patients are usually anxious to return home as soon as possible. The safety of long-distance air travel soon after an acute coronary syndrome is, however, uncertain, and few data exist regarding the evaluation of such patients, the proper timing and conditions of the flight, and short-term complications. METHODS AND RESULTS: We prospectively evaluated 21 tourists who had an acute coronary syndrome in Jerusalem. Patients at high risk were offered angiography; others underwent stress testing. Telephone interviews were conducted a few weeks after the patients returned home, and follow-up information was obtained. Patients flew home 18.2 +/- 11 days (mean +/- SD) after the acute event. Flight duration was substantial (12.5 +/- 3 hours). No patient had cardiac symptoms en route. At follow-up (21.3 +/- 13 days), all but 2 patients were alive and free of cardiac symptoms. CONCLUSIONS: A long-distance flight within 2 to 3 weeks after an acute coronary syndrome is reasonably safe, provided significant ischemia is excluded or treated.

Transvenous pacemaker leads do not worsen tricuspid regurgitation: a prospective echocardiographic study.

Limited prospective data are available regarding the influence of pacemaker leads on tricuspid valve function. To examine the true incidence of these complications, 35 patients were prospectively examined by two-dimensional and Doppler echocardiography before and after implantation of either a permanent pacemaker or an automatic implantable cardioverter-defibrillator. Of the 35 patients imaged preoperatively, the amount of tricuspid regurgitation (TR) was judged as normal or trivial in 15 (43%), mild in 10 (29%), moderate in 8 (23%), and severe in 2 (6%). Following electrode implantation, TR was noted to be normal or trivial in 13 (38%), mild in 15 (48%), moderate in 6 (17%) and severe in 1 (3%). We conclude that implantation of permanent right ventricular electrodes is not usually associated with an acute worsening of tricuspid regurgitation in most patients.

Fertility drug therapies: past, present, and future.

Throughout the last 30 years there has been an evolution of drug therapies aimed at the treatment of infertility. These agents primarily address the induction of ovulation or enhancing ovulation by allowing more oocytes to mature simultaneously. As this evolution has progressed, drugs have moved away from human products to the advent of the recombinant or genetically engineered technology. The drugs have not cured infertility, but they have affected positively the quest of families confronted by infertility.

Artifacts recorded through failing bipolar polyurethane insulated permanent pacing leads.

Pacing failure in bipolar systems using polyurethane insulated leads may be frequent depending on the type of polyurethane and can cause oversensing and or failure to capture. The reason for this failure is often breakage in the inner insulation. The aim of this study was to evaluate the signals created by such a short circuit. Thirty-seven patients were included in the study, 13 with failing leads with polyurethane 80A insulation, 14 with old but normally functioning leads and 10 patients with new leads. Artifacts in the form of spikes were recorded, during surgical revision, from 11 patients with failing leads (84.6%). In patients with normally functioning leads and newly implanted leads no artifacts were recorded. A significant decrease in impedance of 373.4 Ohms (99% confidence intervals 286.4-460.4, P<0.05) was noted in the failing leads compared with a decrease of only 113.0 Ohms (99%, confidence intervals 6.5-219.6, P<0.01) in the control leads. The difference between the groups was highly significant. In 10 newly implanted and five normally functioning bipolar ventricular leads similar artifacts could be created by making intermittent contact between the proximal lead connections. Thus, artifacts could be recorded from failing leads and from intact leads with artificial intermittent connection at the proximal end. Our results suggest that the failure is caused by a short circuit in the lead. This finding may have important clinical applications in the follow-up of bipolar pacing and defibrillation leads.

Takayasu's arteritis identified by computerized tomography: revealing the submerged portion of the iceberg?

BACKGROUND: Takayasu's arteritis is a rare, probably underdiagnosed disorder in Israel. OBJECTIVE: To evaluate the contribution of computerized tomography to the diagnosis of Takayasu's arteritis. METHODS: A retrospective analysis of the diagnostic process was recently conducted in three consecutive patients diagnosed over the last 3 years. RESULTS: Three females of Arab origin with Takayasu's arteritis were recently identified by CT. In two of the three patients the imaging procedure was performed for different working hypotheses, and the radiological findings (wall thickening, perivascular edema, and segmental intraluminal obliteration of the aorta and its major branches) were unexpected. In these two patients, repeated physical examination following the imaging procedure disclosed initially missed findings that could have led to an earlier consideration of Takayasu's arteritis (bruits above the epigastrium, subclavian and carotid arteries, and absent brachial pulses). Retrospective analysis of the patients' symptoms following CT revealed the true nature of the patients misinterpreted complaints (e.g., typical abdominal angina replaced a faulty obtained history compatible with renal colic or dyspepsia). In the third patient CT was performed for the evaluation of an epigastric bruit associated with constitutional complaints. The diagnosis of aortitis, based upon the presence of diffuse aortic wall thickening and edema of the surrounding fat, without intraluminal narrowing, could have been missed by angiography, the traditional "gold standard" diagnostic procedure. All three patients complained of ill-defined epigastric abdominal pain and had epigastric tenderness during examination. CONCLUSIONS: CT has the potential for detecting Takayasu's disease and may be superior to angiography, particularly at the early non-obliterative stage. Since the diagnosis of Takayasu's disease is rarely considered, the expanding use of CT and MRI technologies may reveal missed cases that are evaluated for other plausible diagnoses. The true incidence of Takayasu's arteritis in Israel may be much higher than reported, particularly in the Arab population. Our findings suggest that epigastric tenderness, originating from active inflammatory reaction in the abdominal aortic wall, should be considered as a diagnostic criterion of Takayasu's aortitis.

Two-year follow-up in pediatric and adult patients with single-pass lead VDD pacing system.

VDD pacing follow-up is similar in pediatric and adult patients. Atrial and ventricular pacing parameters are stable during 2-year follow-up in children, and single-pass lead VDD pacing is recommended when the sinus node function is normal.

Association between right ventricular function and perfusion abnormalities in hemodynamically stable patients with acute pulmonary embolism.

BACKGROUND/OBJECTIVES: Patients presenting with acute pulmonary embolism associated with hemodynamic compromise exhibit right ventricular enlargement and dysfunction on transthoracic echocardiogram. However, the degree of echocardiographic abnormalities among hemodynamically stable patients without preexisting cardiopulmonary disease during the acute stage of pulmonary embolism, and following treatment, is unknown. Therefore, this study was designed to assess the extent of right ventricular abnormalities detected on transthoracic echocardiogram in patients following acute pulmonary embolism and during treatment with anticoagulation or vena caval interruption. The extent of pulmonary vascular obstruction and complication rate on follow-up were also assessed. DESIGN/INTERVENTIONS: Sixty-four consecutive hemodynamically stable patients without preexisting known cardiopulmonary disorder presenting with acute pulmonary embolism and undergoing treatment with anticoagulation or inferior vena caval interruption were studied. All subjects underwent a two-dimensional transthoracic echocardiogram within 24 h of diagnosis. The degree of perfusion abnormality on lung scan was quantified. Twenty-six patients underwent follow-up echocardiogram and lung scan at 6 weeks. The echocardiographic findings were compared with those obtained from a group of normal control subjects matched for gender and age. RESULTS: Although the mean right ventricular end-diastolic areas did not differ (21.9+/-5.2 cm2 vs 20.1+/-2.9 cm2 for control subjects; p=not significant), the right ventricular end-systolic area was larger in comparison to our series of control subjects (14.6+/-5.1 cm2 vs 11.7+/-2.0 cm2; p=0.025). Fractional right ventricular area change was reduced in the patient group compared with the control subjects (34.3+/-9.0% vs 41.3+/-7.0%; p=0.003). The extent of right ventricular end-systolic area enlargement and decrease in fractional area change did not correlate with the degree of pulmonary vascular obstruction. Patients who were restudied at 6 weeks showed minimal improvement in echocardiographic findings, despite almost complete resolution of perfusion defects on lung scan. CONCLUSIONS: The extent of right ventricular dysfunction in hemodynamically stable, previously normal patients with acute pulmonary embolism does not reflect the extent of the perfusion abnormalities. Further, right ventricular enlargement and systolic dysfunction are present and persistent despite treatment with heparin and warfarin therapy or vena caval interruption.

Relation between patent foramen ovale and perfusion abnormalities in acute pulmonary embolism.

The frequency of right-to-left shunt through a patent foramen ovale is increased in hemodynamically stable patients without preexisting cardiopulmonary disease with acute pulmonary embolism. This is associated with a greater degree of perfusion abnormalities as quantified by perfusion scan and the presence of tricuspid regurgitation.