Interindividual heterogeneity in the hypoxic regulation of VEGF: significance for the development of the coronary artery collateral circulation.

BACKGROUND: The coronary artery collateral circulation may be beneficial in protecting against myocardial ischemia and necrosis. However, there is a tremendous interindividual variability in the degree of new collateral formation in patients with coronary artery disease. The basis for this interindividual heterogeneity is not understood. In this study we test the hypothesis that failure to generate collateral vessels is associated with a failure to appropriately induce with hypoxia or ischemia the angiogenic factor, vascular endothelial growth factor (VEGF). METHODS AND RESULTS: We correlated the VEGF response to hypoxia in the monocytes harvested from patients with coronary artery disease with the presence of collaterals visualized during routine angiography. We found that there was a highly significant difference in the hypoxic induction of VEGF in patients with no collaterals compared with patients with some collaterals (mean fold induction 1.9+/-0.2 versus 3.2+/-0.3, P<0.0001). After subjecting the data to ANCOVA, using as covariates a number of factors that might influence the amount of collateral formation (ie, age, sex, diabetes, smoking, hypercholesterolemia), patients with no collaterals still have a significantly lower hypoxic induction of VEGF than patients with collaterals. CONCLUSIONS: This study provides evidence in support of the hypothesis that the ability to respond to progressive coronary artery stenosis is strongly associated with the ability to induce VEGF in response to hypoxia. The observed interindividual heterogeneity in this response may be due to environmental, epigenetic, or genetic causes. This interindividual heterogeneity may also help to explain the variable angiogenic responses seen in other conditions such as diabetic retinopathy and solid tumors.

Acute and 30-day results of the serpentine balloon expandable stent implantation in simple and complex coronary arterial narrowings.

We report the acute and 30-day results with a new serpentine-design, tubular, stainless steel, balloon-expandable stent (beStent) in the first 100 patients. One hundred forty-eight stents were used to treat 103 narrowings in the left anterior descending (n = 46), left circumflex (n = 20), and right coronary (n = 37) arteries. There were 85 de novo and 18 restenotic lesions (lesion length: < 10 mm [31], 10 to 20 mm [43] > 20 mm [29]; lesion type: A [10] B1 [29], B2 [20], C [44]; total occlusions, 23. More than 1 stent was used in 31 patients for treatment of long lesions that could not be covered by 1 stent. The stents used were 15-mm (n = 106), 25-mm (n = 38), or 35-mm (n = 4) long. Stent implantation strategy involved predilatation, deployment, and high-pressure dilatation, using the same balloon if possible. Clinical in-hospital success was 97% (2 patients had stent thrombosis that was recanalyzed, with myocardial infarction developing in 1, and 1 patient died on day 14 from retroperitoneal bleeding treated with surgery and complicated by sepsis). One-month event-free survival was 96%, with 1 death on day 21 due to hypertensive crisis. There were no other major adverse cardiac events in this first complex cohort of patients. In conclusion, the initial experience with this stent demonstrates its safety and efficiency for treating simple and complex coronary disease, with a relatively low rate of complications. Long-term clinical follow-up awaits further investigation.

Haptoglobin phenotype as a predictor of restenosis after percutaneous transluminal coronary angioplasty.

We have demonstrated that a genetic polymorphism in the antioxidant protein haptoglobin is important in determining which patients develop restenosis after percutaneous transluminal coronary angioplasty. Knowledge of the haptoglobin phenotype may be useful in the assessment and utilization of new therapies to reduce restenosis, particularly in patients who are homozygous for the haptoglobin 2 allele.

Long-term prognosis of acute pulmonary oedema--an ominous outcome.

BACKGROUND: Acute pulmonary oedema (APOE) is a major health problem, leading to poor hospital and long-term outcomes. There is a relative paucity of studies describing prognosis of consecutive unsolicited patients diagnosed with APOE and hospitalized in internal medicine departments. AIMS: To describe the clinical profile and outcome (in hospital and 1-year prognosis) of successive unselected patients with APOE, in a prospective observational study. METHODS AND RESULTS: The study population included 150 consecutive unsolicited patients (90 men, 60 women; median age 75 years) with APOE all hospitalized in an internal medicine department, in a 900-bed care centre. Ischaemic heart disease (IHD), hypertension and diabetes were present in 85%, 70% and 52% of patients, respectively. The most common precipitating factors for APOE included high blood pressure (29%), rapid atrial fibrillation (29%), unstable angina pectoris (25%), infection (18%) and acute myocardial infarction (MI; 15%). Eighteen patients (12%) died in hospital, with 82% of these deaths attributed to cardiac pump failure. Predictors for an increased in-hospital mortality included: diabetes (P<0.05), orthopnoea (P<0. 05), echocardiographic finding of depressed global left ventricular systolic function (P<0.001), acute MI during hospital stay (P<0.001), hypotension/shock (P<0.05), and the need for mechanical ventilation (P<0.001). After a median hospital stay of 10 days, 132 patients were discharged home. The 1-year mortality was 40%. Only the presence of pleural effusion was found as a predictor for 1-year mortality. CONCLUSION: Most patients with APOE in this study are elderly, and have IHD, hypertension, diabetes and a previous history of APOE. The overall mortality is high (in-hospital, 12%: 1-year, 40%). Left ventricular dysfunction was associated with high in-hospital mortality, but not with long-term prognosis.

One-year clinical follow-up with the serpentine balloon expandable stent: report of the first 100 patients.

BACKGROUND: We recently reported a high technical and 30-day clinical success rate among the first 100 patients treated with the tubular, serpentine design, stainless steel, balloon-expandable stent (beStent) in Israel. The present study examined the clinical results in these patients after the first year. METHODS: Seventy-eight men and 22 women were included in the study. Previous myocardial infarction, bypass surgery and percutaneous transluminal coronary angioplasty had occurred in 52%, 12% and 26% of the patients, respectively. Diabetes mellitus was present in 30 patients and hypertension in 34 patients. One hundred and forty-eight stents of 15, 25, and 35 mm lengths were used. The indications for stenting were suboptimal results (n = 85), bailout conditions (n = 10) or for the prevention of restenosis (n = 8), and lesion types were A (n = 10), B1 (n = 29), B2 (n = 20), and C (n = 44). All patients were clinically monitored with regular visits at 1, 3, 6, 9 and 12 months. RESULTS: Overall, the 12-month event-free survival rate was 82%. Subacute thrombosis occurred in two patients. There were two non-cardiac deaths, one O-wave myocardial infarction, six elective bypass surgeries and 12 target lesion revascularizations. Event-free survival was significantly higher for those with lesions shorter than 15 mm than for those with lesions longer than 15 mm (90% versus 67%, P = 0.003), and for women compared with men (96% versus 78%, P = 0.02). CONCLUSIONS: The initial experience with the beStent shows favorable long-term results with an overall event rate of 18% for this subset of relatively complex lesions; higher event rates were observed for longer lesions.

A fatal case of Behçet's disease associated with multiple cardiovascular lesions.

Behçet's disease is recognised as a chronic multisystem disorder with vasculitis as its underlying pathological process. Cardiac involvement is rare and often associated with poor prognosis. A large right atrial thrombus, pulmonary aneurysms and aortic pseudoaneurysm that developed 17 years after surgery for bilateral renal artery stenosis is presented in a 26-year-old Behçet's disease patient. He was admitted to the hospital with fever of unknown origin associated with chest pain, dyspnea, cough, haemoptysis and pulmonary opacity in chest X-ray. Initial pulmonary CT demonstrated small subpleural infiltrates bilaterally, one of which was round and suspected as being metastatic. Examination of open lung biopsy demonstrated haemorrhagic infarct surrounded by some occluded pulmonary arteries. Subsequent CT showed pulmonary aneurysms compatible with Behçet's disease. Echocardiography demonstrated a large pedunculated mass in the right atrium. Injection of urographin showed a right atrial mass and a large right pulmonary artery aneurysm. The atrial mass was completely excised during open heart surgery and was identified as being an organising thrombus. Eight weeks later while taking prednisone, he was readmitted because of an infected mid sternal wound. CT showed slight separation of the stemum, retrosternal fluid, pulmonary arteries aneurysm and ascending aorta aneurysm. The next day, the patient died from massive bleeding from his ruptured ascending aortic pseudoaneurysm. Bizarre presentation of arterial and venous thromboses or arterial aneurysm formation, particularly in young patients, should suggest Behçet's disease.

Superior vena cava syndrome as a primary manifestation of Behçet's disease. A case report.

Superficial thrombophlebitis is a common finding in Behçet's disease. However, the potential life-threatening complication of superior vena cava (SVC) syndrome due to thrombotic occlusion is a rare manifestation and usually occurs several years after the onset of the diagnosis. The authors describe a twenty-nine-year-old Arab man who had an acute thrombosis of the SVC as the presenting manifestation of his Behçet's disease. The patient was successfully treated with thrombolytic and anticoagulant therapy, and during follow-up no relapse was observed. Behçet's disease should be suspected in young patients presenting with thrombosis of the SVC and without evidence of a hypercoagulable state.

Interventional cardiology--promises and challenges.

The current explosion in coronary stent use for the treatment of coronary artery disease has helped to better define who really benefits from coronary stenting. It is clear that plain old balloon angioplasty can be at least as efficacious as stenting in certain patient groups. Patients with reference vessel diameter of < 2.5 mm, a small post-stent minimal lumen diameter, lesion length > 30 mm, diabetes mellitus and end-stage renal failure--all associated with a high incidence of diffuse in-stent restenosis--should not be stented routinely. The judicious use of stents in percutaneous revascularization will improve patient outcomes and decrease cost. The progress that has been achieved in coronary stent designs has led to many new questions, such as which patients benefit the most from stenting and whether adjunctive therapies or stent coatings will effectively prevent restenosis. Despite the advances in stent/balloon technology, antiplatelet agents, and interventional operator skill, the problems of in-stent restenosis remain. Novel therapeutic strategies for the management of severe coronary artery disease are evolving rapidly. Radiation therapy shows promise on this front. This therapy may reduce rates of restenosis by inhibiting smooth muscle proliferation and migration. However, important issues regarding the type of radiation and the matter of edge-restenosis are yet to be resolved, and the results of ongoing prospective randomized trials should provide valuable information on the efficacy of this modality. Patients with severe, non-revascularizable coronary artery disease and debilitating symptoms represent another frustrating clinical problem. PMR performed in the cardiac catheterization laboratory may improve symptoms of angina in patients with end-stage coronary artery disease. The early results are propitious. Among patients who have undergone this procedure 80-90% have improved from class IV (the most severe chest pain) to class I or II, enabling them to live relatively normal lives. Most investigators believe that PMR may be used only for those who are unsuitable candidates for percutaneous or surgical revascularization. Finally, gene therapy, by stimulating angiogenesis and improving coronary collateral development, may prove to be the most optimal treatment. Each of these strategies is currently under active investigation to confirm the results of the pilot studies, identify patient subgroups likely to respond to therapy, and determine long-term safety. Together with its challenges, the future of interventional cardiology is indeed bright.

[Pacing mode influence on morbidity and mortality].

It is widely believed that physiologic pacing (defined as atrial or atrioventricular synchronous pacing) reduces cardiac morbidity and mortality and is associated with improved quality of life compared to ventricular pacing. In this review we present data from three large prospective trials (PASE, CTOPP, MOST) comparing physiologic pacing to ventricular pacing. The prospective trials report that physiologic pacing is associated with a reduced risk of developing chronic atrial fibrillation over time and improved quality of life in patients with sinus node disease compared to ventricular pacing. However, these trials failed to demonstrate that physiologic pacing reduces heart failure, thromboembolism, or cardiac death compared to ventricular pacing. Based on the available clinical trials, physiologic pacing is not indicated in patients with a short life expectancy. Physiologic pacing should be considered for younger patients (age < 75 years), patients likely to be pacemaker dependent, and patients for whom maintenance of sinus rhythm is desirable, i.e., patients with ventricular hypertrophy and diastolic dysfunction who are most likely to be severely symptomatic if AV synchrony is lost.

[Brucella orchitis].

Brucellosis is a multi-organ infectious disease which affects the genito-urinary system in 2-10% of cases, mainly as orchitis. There have been very few reports in Israel of genito-urinary system involvement in patients with brucellosis, possible due to a low index of suspicion. Identification of brucella orchitis would result in proper medical treatment, thus preventing unnecessary surgery. We present a case of brucella orchitis, highlighting the place of brucellosis in the differential diagnosis of orchitis.

[Malignant solid tumors in the first year of life].

The records of all children in Northern Israel under the age of 1 year in whom a malignant solid tumor was diagnosed were analyzed. Between 1973-1990 such tumors were found in 39 boys and 25 girls. The overall annual incidence was 137.1 per million, and the incidence was higher in boys (1.9/1.0), in Jews compared to non-Jews (1.3/1.0), and in Ashkenazic Jews compared to Sephardic Jews (1.2/1.0). Neuroblastoma was the most common (52% of all malignancies), followed by Wilms' tumor (13%), CNS neoplasm (11%), retinoblastoma (8%), soft tissue sarcoma (6%), lymphoma (5%) and all others (6%). The retinoblastomas were all in non-Jews, but Jews had a higher incidence of neuroblastomas. No differences in incidence were observed in other neoplasms.

[Ifosfamide in pediatric malignancy--experiences in the Northern Israel Oncology Center].

The records of 46 children treated with ifosfamide between 1987-1994 were analyzed. 24 received the drug as first-line chemotherapy in combination with vincristine and etoposide or with adriamycin, vincristine and cyclophosphamide. Complete remission was achieved in 8/10 children with soft tissue sarcoma, 7/8 with Ewing's sarcoma, 2/2 with ovarian carcinoma and 2/2 with clear cell sarcoma of the kidney. 22 children in whom first-line chemotherapy failed were then treated with ifosfamide and etoposide. Complete remission was achieved in 7/10 children with osteosarcoma, 1/2 with Wilms' tumor and 1/3 with neuroblastoma.

[Malignant mesothelioma in families of asbestos workers].

Malignant mesothelioma is primarily an occupational disease of asbestos workers. While there is usually a latent period of 20-40 years between exposure and appearance of the tumor, the duration of exposure may be as short as a single month. Rarely, it may appear in family members and others living with asbestos workers who might be exposed to asbestos from work clothes during laundering, or from fibers on the skin or hair of the asbestos worker. Attention should therefore be paid to those with nonoccupational contact with asbestos. We report 2 cases of pleural mesothelioma in families of asbestos workers. In both cases the laundering of work clothes was done at home. The first was a 33-year-old man; during his childhood his father worked with asbestos boards for 5 years. The second was a 76-year-old woman whose husband worked in an asbestos factory for 32 years, up to 18 years before diagnosis.