Weight loss after laparoscopic adjustable gastric band and resolution of the metabolic syndrome and its components.

BACKGROUND: Substantial weight loss in the setting of obesity has considerable metabolic benefits. Yet some studies have shown improvements in obesity-related metabolic comorbidities with more modest weight loss. By closely monitoring patients undergoing bariatric surgery, we aimed to determine the effects of weight loss on the metabolic syndrome and its components and determine the weight loss required for their resolution. METHODS: We performed a prospective observational study of obese participants with metabolic syndrome (Adult Treatment Panel III criteria) who underwent laparoscopic adjustable gastric banding. Participants were assessed for all criteria of the metabolic syndrome monthly for the first 9 months, then 3-monthly until 24 months. RESULTS: There were 89 participants with adequate longitudinal data. Baseline body mass index was 42.4±6.2 kg m-2 with an average age was 48.2±10.7 years. There were 56 (63%) women. Resolution of the metabolic syndrome occurred in 60 of the 89 participants (67%) at 12 months and 60 of the 75 participants (80%) at 24 months. The mean weight loss when metabolic syndrome resolved was 10.9±7.7% total body weight loss (TBWL). The median weight loss at which prevalence of disease halved was 7.0% TBWL (17.5% excess weight loss (EWL)) for hypertriglyceridaemia; 11% TBWL (26.1-28% EWL) for high-density lipoprotein cholesterol and hyperglycaemia; 20% TBWL (59.5% EWL) for hypertension and 29% TBWL (73.3% EWL) for waist circumference. The odds ratio for resolution of the metabolic syndrome with 10-12.5% TBWL was 2.09 (P=0.025), with increasing probability of resolution with more substantial weight loss. CONCLUSIONS: In obese participants with metabolic syndrome, a weight loss target of 10-12.5% TBWL (25-30% EWL) is a reasonable initial goal associated with significant odds of having metabolic benefits. If minimal improvements are seen with this initial target, additional weight loss substantially increases the probability of resolution.

Unique presentation of cutis laxa with Leigh-like syndrome due to ECHS1 deficiency.

Clinical finding of cutis laxa, characterized by wrinkled, redundant, sagging, nonelastic skin, is of growing significance due to its occurrence in several different inborn errors of metabolism (IEM). Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade. Here, we further expand the list of inborn errors of metabolism associated with cutis laxa by describing the clinical presentation of a 17-month-old girl with Leigh-like syndrome due to enoyl coenzyme A hydratase, short chain, 1, mitochondria (ECHS1) deficiency, a mitochondrial matrix enzyme that catalyzes the second step of the beta-oxidation spiral of fatty acids and plays an important role in amino acid catabolism, particularly valine.

Does the "script" need a rewrite? Is medication advice in television medical dramas appropriate?

WHAT IS KNOWN AND OBJECTIVE: Television medical dramas depict the healthcare industry and draw considerable interest from the public, while pharmacists play an integral part in providing medication-related advice to the public and other health practitioners in real life. The main objective of this retrospective, observational study was to assess the appropriateness of medication advice given in televised medical dramas and how frequently pharmacists were involved in providing the medication advice. METHODS: Show selection was based on fictional series with a medical drama theme and having the highest viewership. Approximately 100 randomly selected hours of five medical television dramas (House, Grey's Anatomy, Nurse Jackie, Doc Martin and Royal Pains) were assessed for the appropriateness of advice given based on the medication indicated, number of safety checks performed, and the level of adherence to standard clinical guidelines. The appropriateness of medication advice was assessed as appropriate, mostly appropriate, partially appropriate and inappropriate using a piloted, 0-6 point scale. Other parameters recorded included patient demographics, health professionals involved, and the categories of medicines. RESULTS AND DISCUSSIONS: Medications were mentioned on 424 occasions (on average four times per hour), including 239 occasions where medication advice was given. A pharmacist was involved in giving medication advice only 16 times (7%). Using the assessment tool, overall, medication advice was deemed to be appropriate 24% of the time, mostly appropriate 34%, partially appropriate 13% and inappropriate 7%. Although the medication advice given was often for the correct indication and the advice somewhat followed clinical guidelines, it frequently omitted adequate safety checks. Doc Martin had the highest mean appropriateness score, whereas House and Grey's Anatomy had the lowest. WHAT IS NEW AND CONCLUSIONS: Medication was often used for the correct indication in television medical dramas; however, key safety checks were frequently omitted and other medication-related advice, including dose, was less reliable and accurate. Pharmacists were rarely involved in providing medication advice. Viewers should not base medication-related decisions solely on what they see in television medical dramas, and any medication-related advice should be interpreted with extreme caution.

Hyperphagia in male melanocortin 4 receptor deficient mice promotes growth independently of growth hormone.

KEY POINTS: Loss of function of the melanocortin 4 receptor (MC4R) results in hyperphagia, obesity and increased growth. Despite knowing that MC4Rs control food intake, we are yet to understand why defects in the function of the MC4R receptor contribute to rapid linear growth. We show that hyperphagia following germline loss of MC4R in male mice promotes growth while suppressing the growth hormone-insulin-like growth factor-1 (GH-IGF-1) axis. We propose that hyperinsulinaemia promotes growth while suppressing the GH-IGF-1 axis. It is argued that physiological responses essential to maintain energy flux override conventional mechanisms of pubertal growth to promote the storage of excess energy while ensuring growth. ABSTRACT: Defects in melanocortin-4-receptor (MC4R) signalling result in hyperphagia, obesity and increased growth. Clinical observations suggest that loss of MC4R function may enhance growth hormone (GH)-mediated growth, although this remains untested. Using male mice with germline loss of the MC4R, we assessed pulsatile GH release and insulin-like growth factor-1 (IGF-1) production and/or release relative to pubertal growth. We demonstrate early-onset suppression of GH release in rapidly growing MC4R deficient (MC4RKO) mice, confirming that increased linear growth in MC4RKO mice does not occur in response to enhanced activation of the GH-IGF-1 axis. The progressive suppression of GH release in MC4RKO mice occurred alongside increased adiposity and the progressive worsening of hyperphagia-associated hyperinsulinaemia. We next prevented hyperphagia in MC4RKO mice through restricting calorie intake in these mice to match that of wild-type (WT) littermates. Pair feeding of MC4RKO mice did not prevent increased adiposity, but attenuated hyperinsulinaemia, recovered GH release, and normalized linear growth rate to that seen in pair-fed WT littermate controls. We conclude that the suppression of GH release in MC4RKO mice occurs independently of increased adipose mass, and is a consequence of hyperphagia-associated hyperinsulinaemia. It is proposed that physiological responses essential to maintain energy flux (hyperinsulinaemia and the suppression of GH release) override conventional mechanisms of pubertal growth to promote the storage of excess energy while ensuring growth. Implications of these findings are likely to extend beyond individuals with defects in MC4R signalling, encompassing physiological changes central to mechanisms of growth and energy homeostasis universal to hyperphagia-associated childhood-onset obesity.

The role of pharmacotherapy in the prevention and treatment of paediatric metabolic syndrome--Implications for long-term health: part of a series on Pediatric Pharmacology, guest edited by Gianvincenzo Zuccotti, Emilio Clementi, and Massimo Molteni.

The metabolic syndrome (MetS) is defined as a clustering of risk factors predisposing to the future development of cardiovascular disease and Type 2 diabetes mellitus (T2DM). Its clinical relevance, above and beyond recognition and treatment of each of the component parts, is still hotly debated--especially within paediatric medicine. Prevention and treatment strategies for adult MetS focus on weight management, as obesity and insulin resistance are known to be at the central axis of the definition, alongside pharmacotherapy of integrally linked conditions such as hypertension and dyslipidaemia. In children and adolescents, however, opportunities for pharmacotherapy are currently limited and interventions aimed at weight management remain the sole treatment paradigm in the majority of cases. This is primarily due to a lack of long-term data relating to the degree of cardiovascular disease and T2DM risk from paediatric MetS, as well as concerns relating to safety and side effect profiles of currently available pharmacotherapies in those who are still growing and developing. Coupled with continuing concern about the recently recognised adverse effects of past and proposed anti-obesity drugs, this indicates that a new era of pharmacotherapy for paediatric MetS is unlikely to be imminent. In fact, the overall paucity of effective current interventions for paediatric MetS is concerning, especially given the fact that approximately 25-33% of all obese paediatric patients likely harbour the condition. It is therefore essential at the present time to concentrate efforts on properly testing the safety and efficacy of currently available products in well-constructed randomised controlled trials in obese adolescents. However, not all obese children and adolescents appear equally at-risk of long-term, weight-related morbidity and a change in emphasis is possibly warranted--one that moves away from simple weight reduction for all and more to a model of reducing long-term risk of cardiovascular disease and T2DM in those at greatest metabolic risk.

Iron deficiency anemia and cardiac mortality in patients with left ventricular systolic dysfunction undergoing coronary stenting.

AIM: The aim of this study was to assess cardiac mortality in patients with reduced ejection fraction (EF< or =45%) and anemia (Hb< or =12 g/dL) undergoing coronary stenting and to investigate whether iron-deficiency anemia influenced outcome when compared to non-anemic patients or patients with other types of anemia. METHODS: One hundred twenty consecutive patients undergoing percutaneous coronary intervention (PCI) between April 2003 and December 2005 were identified and followed for a median of 30 months. Patients were divided into 2 groups, anemic (Hb< or =12 g/dL) and non-anemic. Anemic patients were then divided into 3 sub-groups based on laboratory analysis and anemia work-up: iron-deficiency, malignancy-associated, and anemia of chronic disease (including chronic kidney disease). Mortality rates and cause of death were retrieved using both the Social Security database and the hospital records. RESULTS: Thirty-one percent of patients had iron deficiency, 24% had a malignancy-associated anemia and 45% had anemia of chronic disease. Overall mortality was 12% of which 29% was cardiac death. All-cause and cardiac mortality were significantly higher in anemic vs. non-anemic patients, (31% vs. 6%, P<0.001, and 10% vs. 1%, P=0.016, respectively). Iron-deficiency anemia strongly predicted cardiac mortality (33% vs. 1% in non-anemic patients, P<0.001), while malignancy-associated anemia was the strongest predictor of non-cardiac death (57% vs. 4% in non-anemic patients, P<0.001). Anemia of chronic disease neither predicted cardiac nor non-cardiac death. CONCLUSIONS: To the authors' knowledge, this is the first study to show that iron-deficiency anemia is a strong predictor of cardiac death when compared to patients with other types of anemia or to non-anemic patients.

Integration of NPY, AGRP, and melanocortin signals in the hypothalamic paraventricular nucleus: evidence of a cellular basis for the adipostat.

Energy stores are held relatively constant in many mammals. The circuitry necessary for maintaining energy homeostasis should (1) sense the amount of energy stored in adipose tissue, (2) sense and integrate the multiple opposing signals regarding nutritional state, and (3) provide output regulating energy intake and expenditure to maintain energy homeostasis. We demonstrate that individual neurons within the paraventricular nucleus of the hypothalamus (PVH) are capable of detection and integration of orexigenic (neuropeptide Y [NPY]) and anorexigenic (melanocortin) signals, that NPY and melanocortins are functional antagonists of each other within the PVH in the regulation of feeding behavior, and that melanocortin administration within the PVH regulates both feeding behavior and energy expenditure. These data provide a cellular basis for the adipostat within neurons in the PVH that appear to be jointly regulated by NPY- and melanocortin-responsive neurons.

Short-term high-fat diet increases the presence of astrocytes in the hypothalamus of C57BL6 mice without altering leptin sensitivity.

Diet-induced obesity is associated with hypothalamic inflammation and this phenomenon has been proposed to explain leptin resistance. In the present study, we used a short-term high-fat diet (HFD) paradigm for 10 days and analysed the cellular and physiological responses to leptin administration in C57BL6 mice. In parallel, we performed glial fibrillary acidic protein immunostaining to measure the presence of astrocytes in the arcuate nucleus of the hypothalamus (ARH) after 10 days and 20 weeks of HFD. Interestingly, the results obtained demonstrate that the presence of star-like astrocytes is significantly increased after 10 days of HFD, although this is not associated with the absence of cellular and physiological response to leptin administration in mice. Taken together, the results of the present study suggest that star-like astrocytes rapidly increase in numbers in the ARH in response to HFD, although this phenomenon cannot explain the development of leptin resistance by itself.

SerpinB2 regulates stromal remodelling and local invasion in pancreatic cancer.

Pancreatic cancer has a devastating prognosis, with an overall 5-year survival rate of ~8%, restricted treatment options and characteristic molecular heterogeneity. SerpinB2 expression, particularly in the stromal compartment, is associated with reduced metastasis and prolonged survival in pancreatic ductal adenocarcinoma (PDAC) and our genomic analysis revealed that SERPINB2 is frequently deleted in PDAC. We show that SerpinB2 is required by stromal cells for normal collagen remodelling in vitro, regulating fibroblast interaction and engagement with collagen in the contracting matrix. In a pancreatic cancer allograft model, co-injection of PDAC cancer cells and SerpinB2-/- mouse embryonic fibroblasts (MEFs) resulted in increased tumour growth, aberrant remodelling of the extracellular matrix (ECM) and increased local invasion from the primary tumour. These tumours also displayed elevated proteolytic activity of the primary biochemical target of SerpinB2-urokinase plasminogen activator (uPA). In a large cohort of patients with resected PDAC, we show that increasing uPA mRNA expression was significantly associated with poorer survival following pancreatectomy. This study establishes a novel role for SerpinB2 in the stromal compartment in PDAC invasion through regulation of stromal remodelling and highlights the SerpinB2/uPA axis for further investigation as a potential therapeutic target in pancreatic cancer.

JRK is a positive regulator of ß-catenin transcriptional activity commonly overexpressed in colon, breast and ovarian cancer.

The loss of ß-catenin inhibitory components is a well-established mechanism of carcinogenesis but ß-catenin hyperactivity can also be enhanced through its coactivators. Here we first interrogated a highly validated genomic screen and the largest repository of cancer genomics data and identified JRK as a potential new oncogene and therapeutic target of the ß-catenin pathway. We proceeded to validate the oncogenic role of JRK in colon cancer cells and primary tumors. Consistent with a ß-catenin activator function, depletion of JRK in several cancer cell lines repressed ß-catenin transcriptional activity and reduced cell proliferation. Importantly, JRK expression was aberrantly elevated in 21% of colorectal cancers, 15% of breast and ovarian cancers and was associated with increased expression of ß-catenin target genes and increased cell proliferation. This study shows that JRK is required for ß-catenin hyperactivity regardless of the adenomatous polyposis coli/ß-catenin mutation status and targeting JRK presents new opportunities for therapeutic intervention in cancer.

Percutaneous coronary intervention in the current era compared with 1985-1986: the National Heart, Lung, and Blood Institute Registries.

BACKGROUND: Although refinements have occurred in coronary angioplasty over the past decade, little is known about whether these changes have affected outcomes. METHODS AND RESULTS: Baseline features and in-hospital and 1-year outcomes of 1559 consecutive patients in the 1997-1998 Dynamic Registry who were having first coronary intervention were compared with 2431 patients in the 1985-1986 National Heart, Lung, and Blood Institute Registry. Compared with patients in the 1985-1986 Registry, Dynamic Registry patients were older (mean age, 62 versus 58 years; P:<0.001) and more often female (32.1% versus 25.5%; P:<0.001). In the Dynamic Registry, procedures were more often performed for acute myocardial infarction (22.9% versus 9.9%; P:<0.001) and treated lesions were more severe (84.5% versus 82.5% diameter reduction; P:<0.001), thrombotic (22.1% versus 11.3%; P:<0.001) or calcified (29.5% versus 10.8%; P:<0.001). Stents were used in 70.5% of Dynamic Registry patients, whereas 1985-1986 patients received balloon angioplasty alone. Procedural success was higher in the Dynamic Registry (92.0% versus 81.8%; P:<0.001) and the rate of in-hospital death, myocardial infarction, and emergency coronary bypass surgery combined was lower (4.9% versus 7.9%; P:=0.001) than in the 1985-1986 Registry. The 1-year rate for CABG was lower in the Dynamic Registry (6.9% versus 12.6%; P:<0.001). CONCLUSIONS: Although Dynamic Registry patients had more unstable and complex coronary disease than those in the 1985-1986 Registry, their rate of procedural success was higher whereas rates of complications and subsequent CABG were lower. Results of percutaneous coronary intervention have improved substantially over the past decade.

Angiographic morphology of coronary artery stenoses in prolonged rest angina: evidence of intracoronary thrombosis.

Previous clinical and angiographic/histopathologic correlative studies have demonstrated that angiographic findings of occlusive thrombus, intraluminal filling defects and complex lesion morphology indicate the presence of intracoronary thrombosis. The purpose of this study was to determine whether the presence of these descriptors of intracoronary thrombosis is associated with the syndrome of prolonged rest angina. The coronary angiograms of 50 patients with prolonged rest angina without myocardial infarction (group I) and 42 concurrent patients with stable angina (group II) were reviewed without knowledge of the clinical syndrome. Patients with prior myocardial infarction, coronary angioplasty or coronary artery bypass graft surgery were excluded, as were patients with important aortic stenosis. Each coronary artery stenosis in a major epicardial vessel was evaluated for the presence or absence of intracoronary thrombus (defined using standard criteria), complex lesion morphology (defined as the presence of haziness, a smudged appearance or irregular lesion margins) and eccentricity, and the frequency of each of these findings in groups I and II was compared. Intracoronary thrombus was present significantly more often in group I patients (42%) than in group II patients (17%) (chi 2 5.77; p less than 0.02). Complex lesion morphology was also present significantly more often in group I (44%) than in group II (14%) patients (chi 2 8.17; p less than 0.01). Either standard criterion for intracoronary thrombus or complex morphology was present in 70% of group I but only 21% of group II patients (chi 2 19.7; p less than 0.001). These results support a strong association of the angiographic descriptors of intraluminal thrombosis with the clinical syndrome of prolonged rest angina.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute changes in global and regional rest left ventricular function after successful coronary angioplasty: comparative results in stable and unstable angina.

The immediate effects of successful percutaneous transluminal coronary angioplasty on global and regional left ventricular function were assessed by comparing 30 degrees right anterior oblique left ventricular angiograms performed immediately before and after angioplasty on 39 patients undergoing 42 successful procedures. Mean (+/- SD) lesion stenosis decreased from 88 +/- 10% to 35 +/- 11% (p less than or equal to 0.001), whereas left ventricular ejection fraction increased from 57 +/- 11% to 64 +/- 10% (p less than or equal to 0.001) for the entire group. Left ventricular functional changes were further subgrouped according to stability of angina. Eighteen procedures were performed on 17 patients with stable angina: 24 procedures were performed on 22 patients with unstable angina defined as angina at rest or on minimal activity or recently accelerated angina. There were no significant subgroup differences in mean age, gender ratio, vessel anatomy, drug therapy or extent of coronary stenosis before or after angioplasty. Global ejection fraction increased significantly for the unstable group (from 54 +/- 11% to 66 +/- 9%, p less than or equal to 0.001) but was unchanged for the stable group (from 61 +/- 9% to 61 +/- 11%, p = NS). In unstable angina, regional ejection fraction (segmental area method) increased for both jeopardized (from 37 +/- 11% to 52 +/- 9%, p less than or equal to 0.001) and nonjeopardized myocardial segments (from 43 +/- 13% to 51 +/- 13%, p less than or equal to 0.001), but improvement was significantly (p less than or equal to 0.02) greater in jeopardized segments.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiographic diagnosis of posterior mitral valve leaflet prolapse.

The left ventricular cineangiograms of 22 asymptomatic, apparently healthy male aviators without noninvasive (echocardiographic or auscultatory) evidence of mitral valve prolapse were reviewed and compared with those of 12 men with noninvasive evidence of mild mitral valve prolapse. The maximal protrusion of the posterior mitral valve leaflet superior and posterior to a line perpendicular to the long axis of the left ventricle at end-systole was measured from the right anterior oblique left ventricular cineangiogram by repeated observation of left ventricular inflow. The values were 7.5 +/- 1.6 mm in patients without mitral valve prolapse and 11.2 +/- 3.4 mm in patients with mitral valve prolapse (mean +/- 1 standard deviation). This measurement did not exceed 11 mm in any patient without prolapse. It is concluded that: 1) with meticulous attention to angiographic landmarks of the left ventricular inflow area, the limits of normal systolic posterior mitral leaflet motion can be defined; and 2) systolic motion outside these limits constitutes a quantitative criterion for the angiographic diagnosis of mitral valve prolapse.

Triple vessel coronary angioplasty: acute outcome and long-term results.

Triple vessel coronary angioplasty, defined as angioplasty of one or more lesions in each of the three major coronary arteries (left anterior descending, left circumflex, right coronary artery) was performed in 50 (11%) of 469 patients who had angioplasty of multiple vessels. There were 32 men and 18 women with a mean age of 56 years. All 50 patients had severe three vessel coronary disease and represent approximately 5% of patients with three vessel disease who had revascularization in this institution; 8 (16%) had previous coronary bypass surgery, and 23 (46%) had previous myocardial infarction. Unstable angina was present in 33 patients (66%) and 96% had Canadian Heart Association class III or IV angina; mean left ventricular ejection fraction was 57 +/- 11%. Angioplasty was performed in 176 vessels (3.5 vessels per patient, range 3 to 6) and in 250 lesions (5 lesions per patient, range 3 to 9); angiographic success was achieved in 240 lesions (96%) and 166 vessels (94%). Success in all vessels attempted was achieved in 40 (80%) of the 50 patients. Clinical success (angiographic success associated with clinical improvement) was obtained in all 50 patients in whom triple vessel angioplasty was performed; none of them required urgent bypass surgery and 5 patients (10%) had a non-Q wave myocardial infarction. In four other patients triple vessel angioplasty was planned but not performed because of failure to dilate the primary vessel; urgent bypass surgery was required in one of these, who developed a Q wave infarction. Thus, overall clinical success in 54 patients was 93%; the incidence rate of myocardial infarction was 11%, and that of urgent surgery 1.8%.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary angioplasty in patients with severe left ventricular dysfunction.

The applications for coronary angioplasty have greatly expanded and the procedure is now increasingly used in complex and potentially high risk conditions. This report describes the short- and long-term effects of coronary angioplasty in 61 patients with severely depressed left ventricular function (ejection fraction less than or equal to 35%) with unstable or refractory anginal symptoms, or both, in whom revascularization was necessary despite increased risk. In a retrospective analysis of 1,260 patients undergoing angioplasty between January 1985 through December 1987, 61 had an ejection fraction less than or equal to 35%. The common clinical presentation was unstable angina (70%) with or without recent myocardial infarction. Mean left ventricular ejection fraction was 27 +/- 6%. Forty-five patients (74%) had multivessel disease. Clinical success after angioplasty was achieved in 55 patients (90%). Major complications (death, infarction and emergency bypass surgery) occurred in five patients (8.2%), with death in two (3.2%). During long-term (mean 21 +/- 11 months) follow-up study of the 55 patients with successful angioplasty, 13 (23%) died, including 3 of noncardiac causes, and 11 (20%) had clinically symptomatic recurrence. Continued clinical success was present in 39 patients (71%), of whom 28 (51%) were event-free patients and 11 (20%) had clinical recurrence; a successful second angioplasty procedure was performed in 9 because of restenosis. Thus, in patients with depressed left ventricular function, coronary angioplasty can be performed with a short-term success rate comparable to that of routine angioplasty or surgical procedures. However, acute complications are more frequent and the late mortality rate is higher than in patients with less depressed function.

Multivessel coronary angioplasty early after acute myocardial infarction.

Coronary angioplasty has been applied in patients with recent myocardial infarction, but results of angioplasty of multiple vessels early after myocardial infarction in patients with severe multivessel disease have not been reported. Coronary angioplasty of multiple vessels was performed in 105 patients 0 to 15 days (mean 5 +/- 4) after recent myocardial infarction. There were 77 men (73%) and 28 women (27%), with a mean age of 57 years. All patients had severe multivessel disease, 68% with two vessel and 32% with three vessel disease. Twenty-eight patients (27%) had successful thrombolysis before angioplasty and 70 (67%) had postinfarction angina. Mean left ventricular ejection fraction was 58 +/- 10% and was less than 45% in 13 patients (12%). Angioplasty was attempted in 319 lesions (mean 3 lesions per patient, range 2 to 9) and 252 vessels (mean 2.4 vessels per patient, range 2 to 4), with success in 302 lesions (95%) and 237 vessels (94%); angioplasty was done in two stages in 59 patients (56%). Clinical success was achieved in 102 patients (97%). Complications included myocardial infarction in six patients (5.7%) (one Q wave, five non-Q wave), urgent bypass surgery in two (1.9%) and death in one (0.9%); overall, seven patients (7%) had a major complication. All patients had a follow-up duration greater than 1 year (mean 31 months, range 12 to 73). Clinical recurrence developed in 24 patients (23%), of whom 21 had repeat angioplasty, 1 had bypass surgery and 2 were managed medically. Ten patients (9.8%) had a late infarction and 5 (4.9%) died of cardiac death during the follow-up period.(ABSTRACT TRUNCATED AT 250 WORDS)

Prospective case-control comparison of percutaneous transluminal coronary revascularization in patients with multivessel disease treated in 1986-1987 versus 1991: improved in-hospital and 12-month results. Multivessel Angioplasty Prognosis Study (MAPS) Group.

OBJECTIVES: This study sought to ascertain whether early and 12-month clinical outcomes after percutaneous coronary revascularization have improved between 1986-1987 and 1991. BACKGROUND: Since the mid-1980s, when the results of percutaneous revascularization were considered to be somewhat static, justifying large-scale clinical trials of percutaneous transluminal coronary angioplasty versus other modes of therapy, balloon technology has improved, and several new percutaneous revascularization techniques have become available. The clinical results of the current integrated approach to revascularization compared with those for coronary angioplasty alone in the late 1980s are not known. METHODS: In this prospective case-control study, 200 consecutively treated patients with multivessel disease in 1991 were studied prospectively and compared with 400 consecutive patients from the same centers during 1986-1987. Patients from 1991 were matched with earlier patients on the basis of four previously described prognostic determinants (left ventricular ejection fraction, presence of unstable angina, diabetes and target lesion morphology score) and the treating institution and were assessed for treatment outcome (completeness of revascularization, procedural success and event-free survival [freedom from death, myocardial infarction and further revascularization]). RESULTS: The 1991 cohort of patients was older (mean [+/- SD] age 62 +/- 11 vs. 58 +/- 11 years, p < 0.001) and tended to have slightly worse left ventricular function (ejection fraction 56 +/- 10% vs. 58 +/- 11%, p = 0.009) than the 1986-1987 cohort. Overall lesion morphology risk scores were similar. New devices (other than coronary angioplasty) were used in 26% of patients. The 1991 patient cohort had more frequent total revascularization (35% vs. 21%, p = 0.003), fewer emergency bypass operations (1.0% vs. 5.5%, p = 0.006) and an improved overall procedural success rate (90% vs. 84%, p = 0.04). In addition, at 12 months the event-free survival rate was superior in the 1991 cohort (73.3% vs. 63.6%, p = 0.02), although there was no difference in infarct-free survival rate (94.6% vs. 93.2%, p = NS). CONCLUSIONS: Improved results with percutaneous revascularization in 1991 have important implications for patient care and interpretation of ongoing randomized trials enrolling patients in the late 1980s and intending to compare standard coronary angioplasty with other forms of therapy.

Is traditionally defined complete revascularization needed for patients with multivessel disease treated by elective coronary angioplasty? Multivessel Angioplasty Prognosis Study (MAPS) Group.

OBJECTIVES: The purpose of this study was to determine the effect of incomplete revascularization by percutaneous transluminal coronary angioplasty in patients with multivessel disease on adverse long-term cardiac events (death, coronary artery bypass surgery or myocardial infarction) and to develop an optimal definition of adequate revascularization based on clinical outcome. BACKGROUND: The effect of incomplete coronary revascularization by coronary angioplasty on long-term adverse clinical events remains controversial. METHODS: Three hundred seventy well characterized patients were followed-up for 27 +/- 16 months after angioplasty. Mean patient age was 58 +/- 11 years; 72% were male; 70% had two-vessel disease (> or = 50% diameter stenosis by caliper measurement); and the mean left ventricular ejection fraction was 58 +/- 11% (range 20% to 85%). Angioplasty was successfully accomplished in 339 patients (91.6%), but complete revascularization by the standard definition (no residual > or = 50% stenosis in a coronary artery > or = 1.5 mm in diameter) was achieved in only 91 patients (25%). RESULTS: Three-year event-free survival (i.e., freedom from death, myocardial infarction, coronary artery bypass surgery) in the entire cohort was 76.5%. By the standard definition, complete revascularization was strongly and negatively associated (p = 0.003) with long-term cardiac events, even after correction for the effects of other independent correlates of events, using Cox proportional hazard regression analysis. Seventeen other definitions, evaluating the severity and extent of residual stenoses and whether they were associated with contractile myocardium, were tested to find that which best stratified late event-free survival and had an outcome with complete revascularization no worse than that associated with the standard definition. The best definition for the entire cohort, having more predictive value than the standard definition, allowed < 10% of estimated left ventricular mass to be served by vessels with mild stenoses (< 60%) without being considered "incomplete." CONCLUSIONS: Mild stenoses in coronary arteries > or = 1.5 mm in diameter serving modest amounts of myocardium do not appear to need to be revascularized to achieve good long-term outcome with coronary angioplasty. Hence, angioplasty in such lesions may not be justified except when they are documented to cause life-style-limiting angina, and the standard definition of complete revascularization by angioplasty appears to be suboptimal. The importance of optimally defined adequate revascularization should be considered in the interpretation of the results of randomized trials assessing the clinical efficacy of coronary angioplasty compared with that of other modalities of therapy.

Restenosis after coronary angioplasty: a multivariate statistical model to relate lesion and procedure variables to restenosis. The M-HEART Investigators.

The Multi-Hospital Eastern Atlantic Restenosis Trial group obtained follow-up angiography in 510 patients with 598 successfully dilated coronary lesions who were enrolled in a controlled trial of the effects of a single dose of 1 g of methylprednisolone on restenosis after coronary angioplasty. The overall restenosis rate was 39.6%. The strongest univariate relations to the restenosis rate were found for lesion location (saphenous vein graft, 68%; left anterior descending artery, 45%; left circumflex artery and right coronary artery, 32%; p = 0.002); lesion length (less than or equal to 4.6 mm, 33%; greater than 4.6 mm, 45%; p = 0.001); percent stenosis before angioplasty (less than or equal to 73%, 25%; greater than 73%, 43%; p = 0.005), percent stenosis after angioplasty (less than or equal to 21%, 33%; greater than 21%, 46%; p = 0.017) and arterial diameter (less than 2.9 mm, 44%; greater than or equal to 2.9 mm, 34%; p = 0.036). Two multivariate models to predict restenosis probability were developed with use of stepwise logistic regression. The preprocedural model, which included only variables whose values were known before angioplasty, entered lesion length, vein graft location, left anterior descending artery location, percent stenosis before angioplasty, eccentric lesion and arterial diameter. The postprocedural model, which also included variables whose values were known after angioplasty was performed, was similar to the preangioplasty model except that it also entered postangioplasty percent stenosis and "optimal" balloon sizing but did not enter eccentric lesion. These data indicate that the probability of restenosis after angioplasty is determined predominantly by the characteristics of the lesion being dilated. They are consistent with the known intimal proliferative mechanism of restenosis, offer a means of identifying lesions at unusually high or low risk of restenosis, and of predicting the likelihood that a particular lesion will restenose after angioplasty and provide a rationale for stratification by restenosis probability in the design of future studies of restenosis.