Journal of the American College of Cardiology

Published by Elsevier
Online ISSN: 0735-1097
Publications
Article
Aneurysm rupture is a potentially devastating complication of abdominal aortic aneurysms; however, the events leading to rupture remain unclear. It has been suggested that mural thrombus may play a role in this process (1). In this issue of the Journal, Shin et al. (2) examine the role of early growth response factor (Egr)-1 and tissue factor (TF) (a prothrom-botic factor) in thrombus formation. In human aneurysmal tissue, they observe (using quantitative polymerase chain reaction and immunohistochemistry) increased amounts of Egr-1 and TF in the thrombus-covered wall compared with the thrombus-free wall. They show that in tissue culture, overexpression of Egr-1 results in TF up-regulation. Lastly, they confirm that overexpression of Egr-1 promotes thrombus formation in a mouse vena cava ligation model. The authors conclude that Egr-1 is up-regulated in the human thrombus-covered aneurysm wall and that Egr-1 may play an early role in thrombus formation and, potentially, aneurysm rupture.
 
Article
To investigate the hemodynamic effects of the selective endothelin (ET)A receptor antagonist LU135252 in patients with congestive heart failure (CHF). Nonselective ET(A/B( receptor antagonists improve hemodynamics in patients with CHF. Since ET(B( receptors mediate the release of nitric oxide and the clearance of ET-1, selective ET(A) antagonists are of special interest. The hemodynamic effects of a single oral dose of the selective ET(A) receptor antagonist LU135252 (1, 10, 30, 100 or 300 mg) were investigated in a multicenter study involving 95 patients with CHF (New York Heart Association II-III) with an ejection fraction < or = 35%. Baseline ET-1 positively correlated with pulmonary vascular resistance, pulmonary capillary wedge pressure (PCWP), and mean pulmonary artery pressure (MPAP, r = 0.37-0.50, p < 0.0004) but were inversely related to cardiac index (CI; r = -0.36, p = 0.0004). LU135252 dose dependently increased CI and decreased mean arterial pressure and systemic vascular resistance (p < 0.03-0.0002), while heart rate remained constant or decreased slightly. Pulmonary capillary wedge pressure, MPAP, pulmonary vascular resistance and right atrial pressure also decreased significantly (p < 0.035- < 0.0001). Two hours after LU135252, plasma ET-1 did not significantly increase after 1 mg but did so by 23% (p = 0.003), 29% (p = 0.0018), 56% (p < 0.0001) and 101% (p < 0.0001) after 10, 30, 100 and 300 mg, respectively, while plasma catecholamines remained constant. In patients with CHF, a single oral dose of the selective ET(A) receptor antagonist LU135252 improves hemodynamics in a dose-dependent manner without activation of other neurohumoral systems and is well tolerated over a wide dose range.
 
Adverse Events r-Hirudin
Article
This study was performed to evaluate the efficacy of peri-interventional treatment with recombinant hirudin (r-hirudin [HBW 023]) compared with heparin in the prevention of troponin T release in patients with unstable angina. Percutaneous transluminal coronary angioplasty in patients with unstable angina is associated with a high risk of acute thrombotic complications. Serial troponin T measurements were performed in 61 patients with unstable angina during the 48-h observation period after coronary angioplasty of the ischemia-related lesion. Patients were randomly assigned to peri-interventional intravenous treatment with either r-hirudin (dosage group I: 0.3-mg/kg body weight bolus, 0.12 mg/kg per h for 24 h; dosage group II: 0.5-mg/kg bolus, 0.24 mg/kg per h for 24 h) or heparin (150-IU/kg bolus, 20 IU/kg per h for 24 h). All patients received acetylsalicylic acid before coronary angiography. After 24 h, patients received a constant low dose infusion of either hirudin (0.04 mg/kg per h) or heparin (7 IU/kg per h) for another 24 h. The power of the study to detect a decrease in abnormal troponin T levels from 60% (heparin group) to 20% (combined r-hirudin groups) was 88%. Serial troponin T measurements revealed two peaks within the 48 h after coronary angioplasty in the heparin but not the hirudin groups. An elevated serum troponin T concentration (> 0.2 ng/ml) within 48 h of coronary angioplasty was found in 9 (24%) of 38 patients in the hirudin groups (5 [25%] of 20 in dosage group I; 4 [22%] of 18 in dosage group II) compared with 11 (58%) of 19 in the heparin group (p = 0.01). We observed major cardiac events (death, myocardial infarction, abrupt vessel closure) in 1 (4.8%) of 21 patients in dosage group I, 1 (5.3%) of 19 in dosage group II and 3 (14.3%) of 21 in the heparin group (p = 0.33). In this pilot trial, hirudin appears to be superior to heparin in preventing troponin T release after coronary angioplasty.
 
Article
This analysis from the PROactive (PROspective pioglitAzone Clinical Trial In macroVascular Events) study assesses the effects of pioglitazone on mortality and macrovascular morbidity in patients with type 2 diabetes and a previous myocardial infarction (MI). People with type 2 diabetes have an increased incidence of MI compared with the general population. Those with diabetes and MI have a worse prognosis than nondiabetic patients with cardiovascular disease. The PROactive study was a prospective, multicenter, double-blind, placebo-controlled trial of 5,238 patients with type 2 diabetes and macrovascular disease. Patients were randomized to either pioglitazone or placebo in addition to their other glucose-lowering and cardiovascular medication. Treatment of diabetes, dyslipidemia, and hypertension was encouraged according to the International Diabetes Federation guidelines. Patients were followed for a mean of 2.85 years. The primary end point was the time to first occurrence of macrovascular events or death. Of the total cohort, the subgroup of patients who had a previous MI (n = 2,445 [46.7%]; n = 1,230 in the pioglitazone group and n = 1,215 in the placebo group) was evaluated using prespecified and post-hoc analyses. Pioglitazone had a statistically significant beneficial effect on the prespecified end point of fatal and nonfatal MI (28% risk reduction [RR]; p = 0.045) and acute coronary syndrome (ACS) (37% RR; p = 0.035). There was a 19% RR in the cardiac composite end point of nonfatal MI (excluding silent MI), coronary revascularization, ACS, and cardiac death (p = 0.033). The difference in the primary end point defined in the main PROactive study did not reach significance in the MI population (12% RR; p = 0.135). The rates of heart failure requiring hospitalization were 7.5% (92 of 1,230) with pioglitazone and 5.2% (63 of 1,215) with placebo. Fatal heart failure rates were similar (1.4% [17 of the 92] with pioglitazone versus 0.9% [11 of the 63] with placebo). In high-risk patients with type 2 diabetes and previous MI, pioglitazone significantly reduced the occurrence of fatal and nonfatal MI and ACS. (PROspective pioglitAzone Clinical Trial In macroVascular Events; http://www.clinicaltrials.gov/ct/show/NCT00174993?order = 1; ISRCTN NCT00174993).
 
Article
The thrombolytic and systemic effects of BM 06.022 were evaluated and compared with those of alteplase, anistreplase, streptokinase and urokinase in a canine model of coronary artery thrombosis. BM 06.022 consists of the kringle-2 and protease domains of human tissue plasminogen activator (t-PA) and is unglycosylated because of its expression in Escherichia coli cells. Thrombus formation in anesthetized open chest dogs was induced by electrical injury to the intimal surface of the left circumflex coronary artery at a high level site of obstruction. In heparinized dogs, none of six vehicle-treated animals exhibited reperfusion. Reperfusion was achieved in four of six dogs at 18.3 +/- 6 min after intravenous bolus injection of 140 kU/kg (0.24 mg/kg) of BM 06.022, whereas four of six dogs exhibited reperfusion later (p less than 0.05) at 76.5 +/- 16.1 min during infusion of 1.33 mg/kg of alteplase (0.13 mg/kg as initial bolus injection, followed by 0.66 mg/kg over 1 h and 0.53 mg/kg over 2 h). Significantly later (p less than 0.05) reperfusion than that achieved with BM 06.022 was achieved in five of six dogs at 57.8 +/- 12.1 min after intravenous injection of 0.4 U/kg of anistreplase. Streptokinase (21,000 IU/kg over 60 min) and urokinase (20,000 IU/kg as an intravenous bolus injection, followed by 20,000 IU/kg over 89 min) each induced reperfusion in three of six dogs but at 67 +/- 12 and 84.3 +/- 17.1 min (p less than 0.05 vs. BM 06.022), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
 
Article
We sought to evaluate whether anticoagulation by an intravenous heparin infusion prevents deterioration of coronary blood flow restored by the novel recombinant plasminogen activator BM 06.022, and to compare the effects of profound fibrinogenolysis with those of an intravenous bolus injection of heparin. Recent clinical studies indicate that heparin appears to be effective in reducing reocclusion when combined with recombinant tissue-type plasminogen activator (rt-PA), but that heparin is associated with an increased bleeding incidence. Therefore, the need for heparin has to be critically evaluated in the development of BM 06.022. BM 06.022 is an unglycosylated variant of human tissue-type plasminogen activator. Thrombus formation in anesthetized open chest dogs was induced by electrical injury. Left circumflex coronary artery blood flow was monitored for 4 h using an electromagnetic flow probe. Twenty dogs were randomized to receive intravenous heparin (100 IU/kg bolus plus 100 IU/kg per h) in group B or saline solution in group A before an intravenous bolus injection of 200 kU/kg (= 0.34 mg/kg) BM 06.022 1 h after thrombus formation. Another 14 dogs were randomized to receive a single intravenous bolus injection of 200 IU/kg heparin plus 200 kU/kg BM 06.022 in group D or saline solution plus 1,000 kU/kg BM 06.022 in group C. In the absence of a systemic lytic state, heparin infusion prolonged (p < 0.05) the cumulative patency time (sum of time intervals during which the coronary artery was patent) to 204.3 +/- 7.4 min (group B) compared with 34.6 +/- 10.8 min with saline solution (group A), and increased (p < 0.05) the area under the curve for coronary blood flow versus time (AUCFlow) to 34.0 +/- 3.4 ml.h.min-1 compared with 7.7 +/- 4.6 ml.h.min-1. Profound fibrinogenolysis after administration of 1,000 kU/kg BM 06.022 (group C) and a single intravenous heparin injection (group D) did not differ in their effects on the cumulative patency time (182 +/- 30.3 vs. 177.5 +/- 25.4 min) and AUCFlow (36.0 +/- 10.3 vs. 30.5 +/- 4.8 ml.h.min-1), but these values were improved (p < 0.05) compared with those obtained after administration of saline solution plus 200 kU/kg BM 06.022 (group A). In the absence of a systemic lytic state, intravenous heparin is required as an adjunct to BM 06.022 to maintain coronary blood flow in dogs.
 
Article
The aim of this study was to determine the appropriate dose of a novel recombinant tissue-type plasminogen activator (BM 06.022) for thrombolysis in patients with acute myocardial infarction. BM 06.022 is a mutant of tissue-type plasminogen activator expressed in Escherichia coli that can be given as a single bolus because of a prolonged half-life, which might obviate the need for complicated regimens. BM 06.022 given as a single bolus was investigated in 142 patients in a multicenter sequential dose-finding study. Efficacy of the drug was assessed from infarct-related artery patency by coronary angiography. With the first dose of 10 MU of BM 06.022, the predefined minimal 90-min patency of 70% was not achieved, as indicated by the sequential probability ratio test after treatment of 42 patients (group A). The second dose of 15 MU of BM 06.022 was given subsequently in the preset maximum of 100 patients (group B). Angiography 30, 60 and 90 min after the bolus injection of BM 06.022 revealed a patent infarct-related artery (Thrombolysis in Myocardial Infarction trial [TIMI] grade 2 or 3) in 65% and 66%, 73% and 74% and 66% and 75% of patients in groups A and B, respectively. Very early reocclusion up to the 90-min angiogram occurred in 17% and 13%, late reocclusion until predischarge angiography occurred in 7% and 5%, and rescue percutaneous transluminal coronary angioplasty after the 90-min angiogram was performed in 6 and 14 patients in groups A and B, respectively. Plasma fibrinogen decreased from 2.79 g/liter (range 0.94 to 4.75) to 1.69 g/liter (range 0.0 to 3.95) in group A and from 2.54 g/liter (range 0.0 to 5.02) to 0.92 g/liter (range 0.0 to 2.68) in group B. Two bleeding complications requiring transfusion or surgical intervention and one nonfatal intracranial hemorrhage were encountered. Eight patients had a reinfarction, and five patients died, all of cardiac causes. With BM 06.022 given as a single bolus, a high early patency rate of the infarct-related coronary artery can be achieved. The speed of thrombolysis seems to be superior to standard thrombolytic drugs. The compound warrants further evaluation with respect to safety and efficacy by clinical end points.
 
Article
Cholesterol embolization syndrome is a systemic disease caused by distal showering of cholesterol crystals after angiography, major vessel surgery, or thrombolysis. We prospectively evaluated a total of 1,786 consecutive patients 40 years of age and older, who underwent left-heart catheterization at 11 participating hospitals. The diagnosis of CES was made when patients had peripheral cutaneous involvement (livedo reticularis, blue toe syndrome, and digital gangrene) or renal dysfunction. Twenty-five patients (1.4%) were diagnosed as having CES. Twelve patients (48%) had cutaneous signs, and 16 patients (64%) had renal insufficiency. Eosinophil counts were significantly higher in CES patients than in non-CES patients before and after cardiac catheterization. The in-hospital mortality rate was 16.0% (4 patients), which was significantly higher than that without CES (0.5%, p < 0.01). All four patients with CES who died after cardiac catheterization had progressive renal dysfunction. The incidence of CES increased in patients with atherosclerotic disease, hypertension, a history of smoking, and the elevation of baseline plasma C-reactive protein (CRP) by univariate analysis. The femoral approach did not increase the incidence, suggesting a possibility that the ascending aorta may be a potential embolic source. As an independent predictor of CES, multivariate regression analysis identified only the elevation of pre-procedural CRP levels (odds ratio 4.6, P = 0.01). Cholesterol embolization syndrome is a relatively rare but serious complication after cardiac catheterization. Elevated plasma levels of pre-procedural CRP are associated with subsequent CES in patients who undergo vascular procedures.
 
Article
![Figure][1] Many of us attend the Annual Scientific Session and i2 Summit every year to see the late breaking clinical trials (LBCTs), present an abstract, and often attend 1 or more ancillary meetings. In the past 2 years, we have asked several Fellows why they have not attended regularly
 
Article
This study was designed to determine the incidence and to quantitate aortic debris retrieved during placement of guiding catheters in patients undergoing percutaneous interventions. Studies have shown that atherosclerotic aortic debris predisposes patients to spontaneous or procedurally related ischemic events. In 1,000 consecutive percutaneous interventions, the amount of visible atheromatous material from large-lumen-guiding catheters was recorded. Clinical characteristics and in-hospital complications were prospectively collected and associated with debris production. Visible aortic debris (1+ to 3+) occurred more frequently with the Judkins left (JL) catheter, followed by the multipurpose (Multi) catheter compared to any other type of guiding catheter (65%, p = 0.001 and 60%, p = 0.01, respectively). Large debris (2+ and 3+) was observed most frequently with the Multi (odds ratio 3.79, C.I. = 2.32 to 6.21, p = 0.001), JL (odds ratio 2.83, C.I. = 1.98 to 4.05, p = 0.001) and voda left (VL) (odds ratio 2.73, C.I. = 1.51 to 4.95, p = 0.001) catheters. The Judkins right (JR) catheter type was least likely to produce any debris (24%, p = 0.001). A history of unstable angina (p = 0.05) or myocardial infarction (p = 0.003) was associated with a decreased incidence of debris production. The presence of debris was not found to be associated with in-hospital ischemic complications. Studies have shown that atherosclerosis of the aorta is a potential source of systemic embolism in patients undergoing cardiac catheterization. Our study shows that in more than 50% of percutaneous revascularization procedures, guiding catheter placement is associated with scraping debris from the aorta. Design characteristics of the JL, Multi and VL guiding catheters make them most likely to produce such debris. Meticulous attention to allow the debris to exit the back of the catheter is essential to prevent injecting atheromatous debris into the vascular bed.
 
Article
The complications of clinical cardiac electrophysiologic studies were prospectively evaluated in 1,000 consecutive patients studied in one laboratory with an unaltered protocol to better assess the risks of this procedure. There were 728 men and the mean age of the entire group was 58 years (range 16 to 84). Coronary artery disease was the most common type of heart disease (56%) and 200 patients had no identifiable organic heart disease. The indication for study was a ventricular tachyarrhythmia or cardiac arrest in 582 patients. Each patient underwent an initial (baseline) study and 444 patients underwent serial drug studies (2.7/patient). There was one death during these studies. Other major complications included arterial injury (0.4%), thrombophlebitis (0.6%), systemic arterial embolism (0.1%), pulmonary embolism (0.3%) and cardiac perforation (0.2%). Significant arrhythmic complications included catheter-induced permanent complete atrioventricular (AV) block in 1 patient, nonclinical atrial fibrillation that required therapy in 10 patients and severe proarrhythmic events in 12 (3%) of 397 patients undergoing drug studies for ventricular tachyarrhythmias. Cardioversion was required for termination of ventricular tachyarrhythmias in 179 baseline studies (53% of patients with inducible arrhythmia), and in an additional 35 patients, cardioversion was required at least once during follow-up studies. Although clinical cardiac electrophysiologic studies are associated with complications, the risks are small and acceptable.
 
Article
The purpose of this study was to investigate the incidence, morphology, and clinical course of thrombus formation after catheter closure of intra-atrial shunts. Post-procedure detailed information about thrombotic material on different devices for transcatheter closure is missing. A total of 1,000 consecutive patients were investigated after patent foramen ovale (PFO) (n = 593) or atrial septal defect (ASD) (n = 407) closure. Transesophageal echocardiography (TEE) was scheduled after four weeks and six months. Additional TEEs were performed as clinically indicated. Thrombus formation in the left atrium (n = 11), right atrium (n = 6), or both (n = 3) was found in 5 of the 407 (1.2%) ASD patients and in 15 of the 593 (2.5%) PFO patients (p = NS). The thrombus was diagnosed in 14 of 20 patients after four weeks and in 6 of 20 patients later on. The incidence was: 7.1% in the CardioSEAL device (NMT Medical, Boston, Massachusetts); 5.7% in the StarFLEX device (NMT Medical); 6.6% in the PFO-Star device (Applied Biometrics Inc., Burnsville, Minnesota); 3.6% in the ASDOS device (Dr. Ing, Osypka Corp., Grenzach-Wyhlen, Germany); 0.8% in the Helex device (W.L. Gore and Associates, Flagstaff, Arizona); and 0% in the Amplatzer device (AGA Medical Corp., Golden Valley, Minnesota). The difference between the Amplatzer device on one hand and the CardioSEAL device, the StarFLEX device, and the PFO-Star device on the other hand was significant (p < 0.05). A pre-thrombotic disorder as a possible cause of the thrombus was found in two PFO patients. Post-procedure atrial fibrillation (n = 4) and persistent atrial septal aneurysm (n = 4) had been found as significant predictors for thrombus formation (p < 0.05). In 17 of the 20 patients, the thrombus resolved under anticoagulation therapy with heparin or warfarin. In three patients, the thrombus was removed surgically. The incidence of thrombus formation on closure devices is low. The thrombus usually resolves under anticoagulation therapy.
 
Article
This report describes our experience with fetal congenital heart disease since 1980. Knowledge and expertise in the diagnosis, management and natural history of fetal congenital heart disease is increasingly demanded by both obstetricians and parents. The analysis of a large series should help the pediatric cardiologist to provide this service. The notes of 1,006 patients, where a prospective diagnosis of fetal congenital heart disease was made, were reviewed. The reason for referral, the diagnosis made, the accuracy of diagnosis, the fetal karyotype and the outcome of the pregnancy were noted. The cases were grouped into malformation categories, and the spectrum of disease seen was compared with that found in infants. Most fetal cardiac anomalies are now suspected by the ultrasonographer during obstetric scanning. A different incidence of abnormalities is seen compared with that expected in infants. Chromosomal anomalies were more frequent in the fetus than in live births. The accuracy of diagnosis was good. The survival rate after diagnosis was poor because of frequent parental choice to interrupt pregnancy and the complexity of disease. A large experience with fetal congenital heart disease allows the spectrum of disease to be described with accuracy and compared with that in infancy. Knowledge of the natural history of heart malformations when they present in the fetus allows accurate counseling to be offered to the parents. If the trend in parental decisions found in this series continues, a smaller number of infants and children with complex cardiac lesions will present in postnatal life.
 
Kaplan-Meier curves relating treatment location to (A) survival and to (B) freedom from recurrent myocardial infarction (MI) or target vessel revascularization (TVR) for matched patients undergoing elective percutaneous coronary intervention. ISJ Immanuel St. Joseph's Hospital–Mayo Health System; SMH St. Mary's Hospital.  
Article
We sought to compare clinical outcomes of elective percutaneous coronary intervention (PCI) and primary PCI for ST-segment elevation myocardial infarction (STEMI) at a community hospital without onsite cardiac surgery to those at a tertiary center with onsite cardiac surgery. Disagreement exists about whether hospitals with cardiac catheterization laboratories, but without onsite cardiac surgery, should develop PCI programs. Primary PCI for STEMI at hospitals without onsite cardiac surgery have achieved satisfactory outcomes; however, elective PCI outcomes are not well defined. A total of 1,007 elective PCI and primary PCI procedures performed from March 1999 to August 2005 at the Immanuel St. Joseph's Hospital-Mayo Health System (ISJ) in Mankato, Minnesota, were matched one-to-one with those performed at St. Mary's Hospital (SMH) in Rochester, Minnesota. Strict protocols were followed for case selection and PCI program requirements. Clinical outcomes (in-hospital procedural success, death, any myocardial infarction, Q-wave myocardial infarction, and emergency coronary artery bypass surgery) and follow-up survival were compared between groups. Among 722 elective PCIs, procedural success was 97% at ISJ compared with 95% at SMH (p = 0.046). Among 285 primary PCIs for STEMI, procedural success was 93% at ISJ and 96% at SMH (p = 0.085). No patients at ISJ undergoing PCI required emergent transfer for cardiac surgery. Survival at two years' follow-up by treatment location was similar for patients with elective PCI and primary PCI. Similar clinical outcomes for elective PCI and primary PCI were achieved at a community hospital without onsite cardiac surgery compared with those at a tertiary center with onsite cardiac surgery using a prospective, rigorous protocol for case selection and PCI program requirements.
 
Article
The electrocardiogram in 1,029 obese subjects was correlated with the severity of obesity and with age, sex and blood pressure. The heart rate, PR interval, QRS duration, QTc interval and voltage (R + S or Q wave in leads I, II and III) increased, and the QRS vector shifted to the left with increasing obesity. These changes were independent of age, sex and blood pressure. Bradycardia was present in 19% of the patients, but tachycardia in only 0.5%. ST and T wave abnormalities were present in 11%, correlating better with increasing age and blood pressure than with severity of obesity. Conduction abnormalities were infrequent. Low voltage was present in only 3.9% of the patients and QTc prolongation was present in 28.3%. The heart rate and QRS voltage increase with increasing obesity. Conduction is slowed, and the QRS vector shifts toward the left as percent overweight increases. These changes must be considered when evaluating both baseline electrocardiographic studies in obese patients and the changes seen during weight reduction.
 
Article
We prospectively investigated the prevalence of curable forms of primary aldosteronism (PA) in newly diagnosed hypertensive patients. The prevalence of curable forms of PA is currently unknown, although retrospective data suggest that it is not as low as commonly perceived. Consecutive hypertensive patients referred to 14 hypertension centers underwent a diagnostic protocol composed of measurement of Na+ and K+ in serum and 24-h urine, sitting plasma renin activity, and aldosterone at baseline and after 50 mg captopril. The patients with an aldosterone/renin ratio >40 at baseline, and/or >30 after captopril, and/or a probability of PA (by a logistic discriminant function) > or =50% underwent imaging tests and adrenal vein sampling (AVS) or adrenocortical scintigraphy to identify the underlying adrenal pathology. An aldosterone-producing adenoma (APA) was diagnosed in patients who in addition to excess autonomous aldosterone secretion showed: 1) lateralized aldosterone secretion at AVS or adrenocortical scintigraphy, 2) adenoma at surgery and pathology, and 3) a blood pressure decrease after adrenalectomy. Evidence of excess autonomous aldosterone secretion without such criteria led to a diagnosis of idiopathic hyperaldosteronism (IHA). A total of 1,180 patients (age 46 +/- 12 years) were enrolled; a conclusive diagnosis was attained in 1,125 (95.3%). Of these, 54 (4.8%) had an APA and 72 (6.4%) had an IHA. There were more APA (62.5%) and fewer IHA cases (37.5%) at centers where AVS was available (p = 0.002); the opposite occurred where AVS was unavailable. In newly diagnosed hypertensive patients referred to hypertension centers, the prevalence of APA is high (4.8%). The availability of AVS is essential for an accurate identification of the adrenocortical pathologies underlying PA.
 
Article
We investigated the diagnostic accuracy of 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) scintigraphy for differentiation of monoclonal immunoglobulin light-chain (AL) and transthyretin (TTR)-related cardiac amyloidosis. Differential diagnosis between TTR-related and AL amyloidosis is often complex and time-consuming. Patients under routine observation with TTR-related/AL systemic amyloidosis and echocardiographic evidence of cardiac involvement were studied with 99mTc-DPD scintigraphy. Patients with cardiac involvement of TTR-related (group A; n = 15) and AL (group B; n = 10) etiology were comparable for left ventricular mass and renal function. Heart and heart/whole-body tracer retention were significantly higher (p < 0.05) in group A as compared with group B and with 10 unaffected controls. At visual scoring, cardiac 99mTc-DPD uptake was present in all group A patients and absent in all group B patients; thus, using genotyping/immunohistochemistry as the reference technique, the accuracy of 99mTc-DPD scintigraphy for distinction of TTR-related and AL etiology was 100%. Cardiac 99mTc-DPD uptake was also absent among unaffected controls. Using echocardiography as the reference standard for recognition of cardiac involvement, sensitivity and specificity of scintigraphy were both 100% for group A patients; in group B, sensitivity was 0% and specificity was 100% (accuracy, 50%). Eleven patients with myocardial 99mTc-DPD uptake underwent 99mTc-methylene diphosphonate (99mTc-MDP) scintigraphy; all patients showed a 99mTc-MDP myocardial visual score of 0. Etiology is a third major cause--in addition to type of organ-involved (soft-tissue/heart) and tracer type--of scintigraphic variability in cardiac amyloidosis. This is a highly relevant consideration for future studies. We conclude that 99mTc-DPD scintigraphy is a useful step in the workup of the differential diagnosis of TTR versus AL etiology in patients with documented cardiac amyloidosis.
 
Article
Simultaneous lactate production and extraction have been previously demonstrated in the myocardium in patients with coronary artery disease. To quantitate this lactate production and determine its source, dual carbon-labeled isotope experiments were performed. L-[1,2,3-13C3] lactate and D-[6-14C] glucose were infused in 10 patients with significant coronary artery disease. Metabolic samples were obtained at rest and during atrial pacing. Despite net chemical myocardial lactate extraction in the 10 patients at rest and no evidence of clinical ischemia, the L-[1,2,3-13C3] lactate analysis demonstrated that lactate was being released by the myocardium. During atrial pacing, seven patients did not develop clinical symptoms of ischemia, and the chemical lactate analysis showed net lactate extraction. However, tracer analysis demonstrated that there was a significant increase in the lactate released during atrial pacing (from 6.9 +/- 2.3 to 16.2 +/- 10.1 mumol/min) (p less than 0.05). In these seven patients, circulating glucose was the source of 23 +/- 15% of the lactate released at rest, and there was no significant change during pacing. The remaining three patients had mild chest pain and net chemical lactate production during pacing. Lactate release detected by the tracer increased from 5.7 +/- 3.0 mumol/min at rest to 50.9 +/- 16.8 mumol/min during pacing (p less than 0.01). In these patients, the contribution of glucose to lactate production increased significantly during pacing-induced clinical ischemia from 25 +/- 22 to 67 +/- 14% (p less than 0.005). Thus, dual carbon-labeled isotopic experiments are powerful tools for investigating myocardial metabolic pathways.(ABSTRACT TRUNCATED AT 250 WORDS)
 
Article
This single-center registry presents the results of proximal endovascular occlusion (PEO) use in an unselected patient population. In published multicenter registries, the use of PEO for carotid artery stenting (CAS) has been demonstrated to be safe and efficient in patient populations selected for anatomical and/or clinical conditions. From July 2004 to May 2009, 1,300 patients underwent CAS using PEO. Patients received an independent neurological assessment before the procedure and 1 h, 24 h, and 30 days after the procedure. Procedural success was achieved in 99.7% of patients. In hospital, major adverse cardiac or cerebrovascular events included 5 deaths (0.38%), 6 major strokes (0.46%), 5 minor strokes (0.38%), and no acute myocardial infarction. At 30 days of follow-up, 2 additional patients died (0.15%), and 1 patient had a minor stroke (0.07%). The 30-day stroke and death incidence was 1.38% (n = 19). Symptomatic patients presented a higher 30-day stroke and death incidence when compared with asymptomatic patients (3.04% vs. 0.82%; p < 0.05). No significant difference in 30-day stroke and death rate was observed between patients at high (1.88%; n = 12) and average surgical risk (1.07; n = 7) (p = NS). Operator experience, symptomatic status, and hypertension were found to be independent predictors of adverse events. The use of PEO for CAS is safe and effective in an unselected patient population. Anatomical and/or clinical conditions of high surgical risk were not associated with an increased rate of adverse events.
 
Article
This study sought to examine the outcome of a large group of patients after normal exercise echocardiography and to identify potential predictors of subsequent cardiac events. Earlier studies suggested that prognosis after normal exercise echocardiography is favorable, with a low subsequent cardiac event rate. These studies involved a small number of patients and did not have sufficient statistical power to stratify risk. The outcomes of 1,325 patients who had normal exercise echocardiograms were examined. End points were overall and cardiac event-free survival. Cardiac events were defined as cardiac death, nonfatal myocardial infarction and coronary revascularization. Patient characteristics were analyzed in relation to time to first cardiac event in a univariate and multivariate manner to determine which, if any, were associated with an increased hazard of subsequent cardiac events. Overall survival of the study group was significantly better than that of an age- and gender-matched group obtained from life tables (p < 0.0001). The cardiac event-free survival rates at 1, 2 and 3 years were 99.2%, 97.8% and 97.4%, respectively. The cardiac event rate per person-year of follow-up was 0.9%. Subgroups with an intermediate or high pretest probability of having coronary artery disease also had low cardiac event rates. Multivariate predictors of subsequent cardiac events were angina during treadmill exercise testing (risk ratio [RR] 4.1, 95% confidence interval [CI] 1.5 to 11.0), low work load (defined as < 7 metabolic equivalents [METs] for men and < 5 METs for women; RR 3.2, 95% CI 1.4 to 7.6), echocardiographic left ventricular hypertrophy (RR 2.6, 95% CI 1.1 to 6.3) and advancing age (RR 1.04/year, 95% CI 1.0 to 1.1). The outcome after normal exercise echocardiography is excellent. Subgroups with an intermediate or high pretest probability of having coronary artery disease also have a favorable prognosis after a normal exercise echocardiogram. Characteristics predictive of subsequent cardiac events (i.e., patient age, work load, angina during exercise testing and echocardiographic left ventricular hypertrophy) should be considered in the clinical interpretation of a normal exercise echocardiogram.
 
Article
We sought to examine, angiographically, the longterm fate of a large number of mainly venous coronary bypass grafts and to correlate graft patency and disease with patient survival and reoperation. Much is known about bypass graft patency and disease, but the precise relation between graft fate and patient outcome has not been substantiated and documented. A total of 1,388 patients underwent a first coronary artery bypass graft procedure at a mean age of 48.9 years, 234 had a second bypass procedure at a mean age of 53.3 years, and 15 had a third bypass procedure at a mean age of 58.2 years during the 25-year period from 1969 to 1994. Most were male military personnel or veterans; 12% were < or = 39 years old. Of 5,284 grafts placed, 91% were venous and 9% arterial. Angiograms were performed on 5,065 (98% of surviving) grafts early, on 3,993 grafts at 1 year and on 1,978 grafts at 5 years after operation; other examinations were also performed up to 22.5 years after operation, and 353 grafts were examined after > or = 15 years. Grafts were graded for patency and disease. The status of all patients was known at the study's end. The perioperative mortality rate was 1.4% for an isolated first coronary bypass procedure, 6.6% for reoperation. Vein graft patency was 88% early, 81% at 1 year, 75% at 5 years and 50% at > or = 15 years; when suboptimal grafts, graded B, were excluded from calculation, the proportion of excellent grafts, graded A, decreased to 40% after > or = 12.5 years. After the early study, the vein graft occlusion rate was 2.1%/year. Internal mammary artery graft patency was significantly better but decreased with time. Vein graft disease appeared by 1 year and the rate accelerated by > or = 2.5 years, involving 48% of grafts at 5 years and 81% at > or = 15 years; 44% of the latter grafts were narrowed > 50%. Survival of all patients was 93.6% at 5 years. 81.1% at 10 years, 62.1% at 15 years, 46.7% (150 patients) at 20 years and 38.4% (25 patients) at 23 years after operation. Survival decreased as age increased, but curves approximated "normal" life expectancy for older patients. Survival curves at all ages showed a steeper decline after 7 years. The rate of reoperation increased between 5 years and 10 to 14 years, then decreased to stable levels. Coronary atheroembolism from vein grafts was the major cause of morbidity and mortality associated with reoperation. Vein graft patency and disease were temporally and closely related to reoperation and survival. Coronary bypass graft disease and occlusion are common after coronary artery bypass grafting and increase with time. They are major determinants of clinical prognosis, specifically measured by reoperation rate and survival. Intraoperative graft atheroembolism was a major reoperation hazard. Reoperation is definitely worthwhile but entails identifiable risks that must be dealt with.
 
Article
This study sought to assess gender-based differences in long-term outcome after very early aggressive revascularization for non-ST-elevation acute coronary syndromes (NSTACS). The Fragmin and fast Revascularization during InStability in Coronary artery disease (FRISC) II study suggested that women have less to gain from an early invasive strategy. We conducted a prospective cohort study in 1,450 consecutive patients with NSTACS undergoing coronary angiography and subsequent coronary stenting of the culprit lesion as the primary revascularization strategy within 24 h of admission. The combined primary end point was defined as death or nonfatal myocardial infarction (MI) and recorded for a mean of 20 months. Percutaneous coronary intervention was performed in more than 50% of patients in women and men and accompanied with stenting in 80%. The percutaneous coronary intervention:coronary artery bypass grafting ratio was 4:1 in men and 5:1 in women. The primary end point occurred in 29 (7.0%) women as compared with 108 (10.5%) men (hazard ratio for women, 0.65; 95% confidence interval [CI] 0.42 to 0.99; p = 0.045). Backward-stepwise multivariate Cox regression analysis identified female gender as an independent predictor of death or MI (hazard ratio for female gender, 0.51; 95% CI, 0.28 to 0.92; p = 0.024). Kaplan-Meier analysis showed that women had consistently lower event rates during the entire follow-up period (p = 0.037 by log-rank for death or MI). Women treated with very early aggressive revascularization with coronary stenting of the culprit lesion as the primary revascularization strategy have a better long-term outcome as compared with men.
 
Article
This study sought to determine the prognostic value of wall motion and perfusion assessment during high-dose dobutamine stress (DS) cardiac magnetic resonance imaging (MRI) in a large patient cohort. DS-MRI offers the possibility to integrate myocardial perfusion and wall motion analysis in a single examination for the detection of coronary artery disease (CAD). A total of 1,493 consecutive patients with suspected or known CAD underwent DS-MRI, using a standard protocol in a 1.5-T magnetic resonance scanner. Wall motion and perfusion were assessed at baseline and during stress, and outcome data including cardiac death, nonfatal myocardial infarction ("hard events"), and "late" revascularization performed >90 days after the MR scans were collected during a 2 ± 1 year follow-up period. Fifty-three hard events, including 14 cardiac deaths and 39 nonfatal infarctions, occurred during the follow-up period, whereas 85 patients underwent "late" revascularization. Using multivariable regression analysis, an abnormal result for wall motion or perfusion during stress yielded the strongest independent prognostic value for both hard events and late revascularization, clearly surpassing that of clinical and baseline magnetic resonance parameters (for wall motion: adjusted hazard ratio [HR] of 5.9 [95% confidence interval (CI): 2.5 to 13.6] for hard events and of 3.1 [95% CI: 1.7 to 5.6] for late revascularization, and for perfusion: adjusted HR of 5.4 [95% CI: 2.3 to 12.9] for hard events and of 6.2 [95% CI: 3.3 to 11.3] for late revascularization, p < 0.001 for all). DS-MRI can accurately identify patients who are at increased risk for cardiac death and myocardial infarction, separating them from those with normal findings, who have very low risk for future cardiac events. (Prognostic Value of High Dose Dobutamine Stress Magnetic Resonance Imaging; NCT00837005).
 
Article
This study correlated the electron beam computed tomographic (EBCT) calcium scores with the results of coronary angiography in symptomatic patients in order to assess its value to predict or exclude significant coronary artery disease (CAD). Electron beam computed tomography is a sensitive method to detect coronary calcium. However, it is unclear whether it may play a role as a filter before invasive procedures in symptomatic patients. A total of 1,764 patients (1,225 men and 539 women) with suspected CAD from a single center were included in our study. All patients underwent calcium screening with EBCT (C150XP Imatron) and conventional coronary angiography. Fifty-six percent of men and 47% of women revealed significant coronary stenoses (> or =50%). Total exclusion of coronary calcium (14% of the study group) was associated with an extremely low probability of stenosis (<1%). With calcium scores > or =20th, > or =100th or > or =75th percentile of age groups, the sensitivity to detect stenoses decreased to 97%, 93% and 81%, respectively, in men and to 98%, 82% and 76%, respectively, in women. At the same time, the specificity increased up to 77% in men and women. There was a significant difference in coronary calcium between men and women in all age groups; however, receiver-operating characteristic curves indicated that the test can be performed with equal accuracy in all of these subgroups. Calcium screening with EBCT is a highly sensitive and moderately specific test to predict stenotic disease. Exclusion of coronary calcium defines a substantial subgroup of patients, albeit symptomatic, with a very low probability of significant stenoses.
 
Article
This study was designed to assess the prognostic value of thallium-201 single-photon emission computed tomographic (thallium SPECT) perfusion imaging in patients evaluated for stable angina pectoris and to examine the relation, if any, between the presence and extent of myocardial defect and future fatal or nonfatal cardiovascular events (revascularization, secondary myocardial infarction). Compared with planar scintigraphy, thallium SPECT enables better evaluation of the extent of myocardial perfusion defect. However, its prognostic value has not yet been studied in a large population of patients. Between 1987 and 1989 we studied 3,193 patients. After exclusion of patients with unstable angina, myocardial infarction during the previous month or earlier revascularization, 1,926 patients were followed up for 33 +/- 10 (mean +/- SD) months after stress thallium SPECT imaging (performed after exercise in 1,121 patients or during dipyridamole infusion in 805 patients). Thallium SPECT imaging of the left ventricle was divided into six segments. After normal thallium SPECT imaging (715 patients), the annual total and cardiovascular mortality rates were, respectively, 0.42%/year and 0.10%/year and were significantly higher after abnormal thallium SPECT imaging (respectively, 2.1%, relative risk 5, p = 0.012; 1.5%, relative risk 15, p < 0.0001 [log-rank test]). There was a significant relation between the number of abnormal segments and cardiovascular mortality during follow-up (p < 0.02) or the occurrence of nonfatal events (p < 0.001). The extent of defect on the initial scan provided the best SPECT variable for long-term prognosis. Thallium SPECT imaging provided additive prognostic information compared with other clinical variables (gender, previous myocardial infarction) and exercise electrocardiogram. In patients with stable angina, normal thallium SPECT imaging indicates a low risk patient, and the extent of myocardial defect is an important prognostic predictive factor.
 
Article
To examine patient-level discordance between population percentiles of non-HDL cholesterol (non-HDL-C) and LDL cholesterol (LDL-C). Non-HDL-C is an alternative to LDL-C for risk stratification and lipid-lowering therapy. The justification for the present guideline-based non-HDL-C cutpoints of 30 mg/dL higher than LDL-C cutpoints remains largely untested. We assigned population percentiles to non-HDL-C and Friedewald-estimated LDL-C values of 1,310,440 U.S. adults with triglycerides < 400 mg/dL who underwent lipid testing by vertical spin density gradient ultracentrifugation (Atherotech, Birmingham, Alabama) from 2009 to 2011. LDL-C cutpoints of 70, 100, 130, 160, and 190 mg/dL were in the same population percentiles as non-HDL-C values of 93, 125, 157, 190, and 223 mg/dL, respectively. Non-HDL-C reclassified a significant proportion of patients within a higher treatment category compared with Friedewald LDL-C, especially at LDL-C levels in the treatment range of high-risk patients and at triglyceride levels ≥ 150 mg/dL. Of patients with LDL-C < 70 mg/dL, 15% had a non-HDL-C ≥ 100 mg/dL (guideline-based cutpoint) and 25% had a non-HDL-C ≥ 93 mg/dL (percentile-based cutpoint); 22% and 50% respectively if triglycerides concurrently 150-199 mg/dL. There is significant patient-level discordance between non-HDL-C and LDL-C percentiles at lower LDL-C and higher triglycerides; a finding with implications for treatment of high-risk patients. Current non-HDL-C cutpoints for high-risk patients may need to be lowered to match percentiles of LDL-C cutpoints. Relatively small absolute reductions in non-HDL-C cutpoints result in substantial reclassification of patients to higher treatment categories with potential implications for risk assessment and treatment. VLDL-2; NCT01698489.
 
Article
Our aim was to establish and evaluate a strategy for safe performance of magnetic resonance imaging (MRI) at 1.5-T in patients with implantable cardioverter-defibrillators (ICDs). Expanding indications for ICD placement and MRI becoming the imaging modality of choice for many indications has created a growing demand for MRI in ICD patients, which is still considered an absolute contraindication. Non-pacemaker-dependent ICD patients with a clinical need for MRI were included in the study. To minimize radiofrequency-related lead heating, the specific absorption rate was limited to 2 W/kg. ICDs were reprogrammed pre-MRI to avoid competitive pacing and potential pro-arrhythmia: 1) the lower rate limit was programmed as low as reasonably achievable; and 2) arrhythmia detection was programmed on, but therapy delivery was programmed off. Patients were monitored using electrocardiography and pulse oximetry. All ICDs were interrogated before and after the MRI examination and after 3 months, including measurement of pacing capture threshold, lead impedance, battery voltage, and serum troponin I. Eighteen ICD patients underwent a total of 18 MRI examinations at 1.5-T; all examinations were completed safely. All ICDs could be interrogated and reprogrammed normally post-MRI. No significant changes of pacing capture threshold, lead impedance, and serum troponin I were observed. Battery voltage decreased significantly from pre- to post-MRI. In 2 MRI examinations, oversensing of radiofrequency noise as ventricular fibrillation occurred. However, no attempt at therapy delivery was made. MRI of non-pacemaker-dependent ICD patients can be performed with an acceptable risk/benefit ratio under controlled conditions by taking both MRI- and pacemaker-related precautions. (Implantable Cardioverter Defibrillators and Magnetic Resonance Imaging of the Heart at 1.5-Tesla; NCT00356239).
 
Article
We sought to determine trends in the treatment of myocardial infarction from 1990 through 1999 in the U.S. and to relate these trends to current guidelines. Limited data are available to show how recent clinical trials and clinical guidelines have impacted treatment of myocardial infarction. Temporal trends in myocardial infarction treatment and outcome were assessed by using data from 1,514,292 patients in the National Registry of Myocardial Infarction (NRMI) 1, 2 and 3 from 1990 through 1999. During this interval, the use of intravenous thrombolytic therapy declined from 34.3% to 20.8%, but the use of primary angioplasty increased from 2.4% to 7.3% (both p = 0.0001). The median "door-to-drug" time among thrombolytic therapy recipients fell from 61.8 to 37.8 min (p = 0.0001), primarily owing to shorter "door-to-data" and "data-to-decision" times. The prevalence of non-Q wave infarctions increased from 45% in 1994 to 63% in 1999 (p = 0.0001). From 1994 through 1999, there was increased usage of beta-blockers, aspirin and angiotensin-converting inhibitors, both during the first 24 h after admission and on hospital discharge (all p = 0.0001). Between 1990 and 1999, the median duration of hospital stay fell from 8.3 to 4.3 days, and hospital mortality declined from 11.2% to 9.4% (both p = 0.0001). The NRMI data from 1990 through 1999 demonstrate that the recommendations of recent clinical trials and published guidelines are being implemented, resulting in more rapid administration of intravenous thrombolytic therapy, increasing use of primary angioplasty and more frequent use of adjunctive therapies known to reduce mortality, and may be contributing to the higher prevalence of non-Q wave infarctions, shorter hospital stays and lower hospital mortality.
 
Article
Patients with a permanent pacemaker are currently restricted from diagnostic nuclear magnetic resonance (NMR) imaging because of potential adverse effects on the pacemaker by the magnet. Previous work has shown that NMR imaging will result in asynchronous pacing of the pulse generator within a given distance of the magnet. The radiofrequency signal generated by the system may also result in rapid cardiac pacing, which may have deleterious effects. This study utilized a 1.5 tesla unit in an in vivo laboratory animal to evaluate the unit's effects on eight different pulse generators from two manufacturers. All pacemakers functioned in an asynchronous mode when placed within a certain distance of the magnet. In addition, transient reed switch inhibition was observed. Seven of the eight pulse generators paced rapidly when exposed to the radiofrequency signal and there was a dramatic decrease in arterial blood pressure. Whether effective rapid cardiac pacing would occur could not be predicted before exposure to the magnetic resonance unit. Nuclear magnetic resonance imaging with high magnetic fields in patients with a pacemaker should continue to be avoided until the mechanism of the rapid cardiac pacing can be further delineated and either predicted or prevented.
 
Article
This study was designed to establish the diagnostic accuracy of cardiovascular magnetic resonance (CMR) perfusion imaging at 3-Tesla (T) in suspected coronary artery disease (CAD). Myocardial perfusion imaging is considered one of the most compelling applications for CMR at 3-T. The 3-T systems provide increased signal-to-noise ratio and contrast enhancement (compared with 1.5-T), which can potentially improve spatial resolution and image quality. Sixty-one patients (age 64 +/- 8 years) referred for elective diagnostic coronary angiography (CA) for investigation of exertional chest pain were studied (before angiogram) with first-pass perfusion CMR at both 1.5- and 3-T and at stress (140 microg/kg/min intravenous adenosine, Adenoscan, Sanofi-Synthelabo, Guildford, United Kingdom) and rest. Four short-axis images were acquired during every heartbeat using a saturation recovery fast-gradient echo sequence and 0.04 mmol/kg Gd-DTPA bolus injection. Quantitative CA served as the reference standard. Perfusion deficits were interpreted visually by 2 blinded observers. We defined CAD angiographically as the presence of > or =1 stenosis of > or =50% diameter in any of the main epicardial coronary arteries or their branches with a diameter of > or =2 mm. The prevalence of CAD was 66%. All perfusion images were found to be visually interpretable for diagnosis. We found that 3-T CMR perfusion imaging provided a higher diagnostic accuracy (90% vs. 82%), sensitivity (98% vs. 90%), specificity (76% vs. 67%), positive predictive value (89% vs. 84%), and negative predictive value (94% vs. 78%) for detection of significant coronary stenoses compared with 1.5-T. The diagnostic performance of 3-T perfusion imaging was significantly greater than that of 1.5-T in identifying both single-vessel disease (area under receiver-operator characteristic [ROC] curve: 0.89 +/- 0.05 vs. 0.70 +/- 0.08; p < 0.05) and multivessel disease (area under ROC curve: 0.95 +/- 0.03 vs. 0.82 +/- 0.06; p < 0.05). There was no difference between field strengths for the overall detection of coronary disease (area under ROC curve: 0.87 +/- 0.05 vs. 0.78 +/- 0.06; p = 0.23). Our study showed that 3-T CMR perfusion imaging is superior to 1.5-T for prediction of significant single- and multi-vessel coronary disease, and 3-T may become the preferred CMR field strength for myocardial perfusion assessment in clinical practice.
 
Article
The study was done to determine whether patients with pacemakers could safely undergo magnetic resonance imaging (MRI) at 1.5-Tesla (T). Because of theoretical risks, it is an absolute contraindication for a patient with a pacemaker to undergo MRI. However, there are times when an MRI is needed to provide valuable clinical information. Fifty-four patients underwent a total of 62 MRI examinations at 1.5-T. The type of MRI examination was not limited and included cardiac, vascular, and general MRI studies using various whole-body averaged specific absorption rate (SAR) of radiofrequency power. Restrictions were not placed on the type of pacemaker present in the patient. All pacemakers were interrogated immediately before and after MRI scanning, and patients were continuously monitored. Before and after MRI, interrogation was done, and pacing and sensing thresholds, as well as lead impedances, were all measured. A total of 107 leads and 61 pulse generators were evaluated. No adverse events occurred. Forty (37%) of the leads underwent changes, whereas 10 (9.4%) leads underwent a significant change. Only 2 of the 107 (1.9%) leads required a change in programmed output. Threshold changes were unrelated to cardiac chamber, anatomical location, peak SAR, and time from lead implant to the MRI examination. Electrocardiographic changes and patient symptoms were minor and did not require cessation of MRI. Safety was demonstrated in this series of patients with pacemakers at 1.5-T.
 
Article
Objectives: This study sought to identify the risk of sudden cardiac death (SCD) associated with obstructive sleep apnea (OSA). Background: Risk stratification for SCD, a major cause of mortality, is difficult. OSA is linked to cardiovascular disease and arrhythmias and has been shown to increase the risk of nocturnal SCD. It is unknown if OSA independently increases the risk of SCD. Methods: We included 10,701 consecutive adults undergoing their first diagnostic polysomnogram between July 1987 and July 2003. During follow-up up to 15 years, we assessed incident resuscitated or fatal SCD in relation to the presence of OSA, physiological data including the apnea-hypopnea index (AHI), and nocturnal oxygen saturation (O2sat) parameters, and relevant comorbidities. Results: During an average follow-up of 5.3 years, 142 patients had resuscitated or fatal SCD (annual rate 0.27%). In multivariate analysis, independent risk factors for SCD were age, hypertension, coronary artery disease, cardiomyopathy or heart failure, ventricular ectopy or nonsustained ventricular tachycardia, and lowest nocturnal O2sat (per 10% decrease, hazard ratio [HR]: 1.14; p = 0.029). SCD was best predicted by age >60 years (HR: 5.53), apnea-hypopnea index >20 (HR: 1.60), mean nocturnal O2sat <93% (HR: 2.93), and lowest nocturnal O2sat <78% (HR: 2.60; all p < 0.0001). Conclusions: In a population of 10,701 adults referred for polysomnography, OSA predicted incident SCD, and the magnitude of risk was predicted by multiple parameters characterizing OSA severity. Nocturnal hypoxemia, an important pathophysiological feature of OSA, strongly predicted SCD independently of well-established risk factors. These findings implicate OSA, a prevalent condition, as a novel risk factor for SCD.
 
Article
The goal of this study was to determine if a "hybrid" approach to the treatment of complex combined coronary and valve disease is superior to the results predicted by a Society of Thoracic Surgeons' (STS) algorithm with conventional coronary artery bypass graft (CABG)/valve surgery in high-risk patients. With advancements in percutaneous coronary interventions (PCIs), some patients requiring coronary revascularization and valve surgery may benefit from a hybrid approach involving initial planned PCI followed by valve surgery, rather than conventional CABG/valve surgery. We retrospectively analyzed 26 consecutive patients with coronary artery and valve disease who underwent planned initial PCI followed by valve surgery during the same hospital stay between September 1997 and August 2003. We calculated the predicted mortality at the time of PCI and compared it with the observed mortality. There were 12 male and 14 female patients with a median age of 72 years (range 53 to 91 years). Balloon angioplasty was performed in all patients, followed by stenting in 22 (85%) patients. Within a median of 5 days (range 0 to 14 days), 15 patients (58%) underwent primary and 11 patients (42%) underwent re-operative valve surgery. Operative mortality was 1 of 26 patients (3.8%), dramatically lower than the STS-predicted mortality of 22%. Median blood loss was 900 ml, and 22 patients (85%) required blood transfusions. Survival at 1, 3, and 5 years was 78%, 56%, and 44%, respectively. Hybrid initial PCI followed by staged valve surgery represents an excellent alternative to conventional CABG/valve surgery in some high-risk patients, particularly those who present in shock after myocardial infarction. Lower mortality rates come at the cost of more bleeding and transfusion requirements.
 
Article
This study was conducted to identify the determinants of successful nonthoracotomy cardioverter-defibrillator implantation. Until recently, either median sternotomy or thoracotomy was necessary to implant the electrodes used for internal cardioverter-defibrillator systems. A number of manufacturers have developed nonthoracotomy lead systems comprising two transvenous coil electrodes and a subcutaneous patch electrode. At present, the factors associated with the success or failure of a nonthoracotomy approach are unknown. A total of 101 consecutive patients requiring a cardioverter-defibrillator underwent an initial nonthoracotomy approach. Factors associated with successful nonthoracotomy implantation were prospectively determined. A nonthoracotomy system was implanted in 72 (71%) of 101 patients. Twenty-nine patients (29%) required thoracotomy. Univariate predictors of successful nonthoracotomy implantation included smaller cardiac size (p < 0.0001), smaller cardiothoracic ratio (p < 0.0002), QRS duration < 120 ms (p = 0.003), female gender (p = 0.006), ventricular fibrillation as the presenting arrhythmia (p = 0.03) and smaller echocardiographic left ventricular size (p = 0.04). Multivariate predictors included smaller cardiac size (p < 0.002) and female gender (p < 0.007). Total actuarial survival over a mean (+/- SD) follow-up interval of 12 +/- 7 months was 91 +/- 0.03% and was not different in the thoracotomy and nonthoracotomy groups. A nonthoracotomy cardioverter-defibrillator system can be implanted in a majority of patients. Smaller cardiac size and female gender are associated with a high probability of successful implantation.
 
Article
Serial gated blood pool scintigraphic monitoring of cardiac function with both a nonimaging scintillation probe and a conventional gamma camera-computer imaging system was performed in 101 patients receiving doxorubicin hydrochloride (Adriamycin) chemotherapy. Comparison of probe- and camera-derived ejection fractions (n = 287) correlated significantly (r = 0.70, p less than 0.005) as did the interstudy (n = 183) change in ejection fraction (r = 0.76, p greater than 0.005). Significant discordance in probe- and camera-derived ejection fraction change occurred in 3 (1.6%) of 183 interstudy intervals. Average intrastudy variability of absolute probe-derived ejection fraction was 2.9%. This variability was unrelated to the level of cardiac function. Thirteen patients (13%) developed clinical cardiotoxicity, including four at cumulative Adriamycin levels less than 450 mg/m2. Mean absolute camera ejection fraction decline for these patients was 21% from baseline evaluation, and mean absolute probe ejection fraction decline was 22%. The minimal absolute ejection fraction decline was 11% for patients with clinical congestive heart failure. Eight asymptomatic patients had therapy terminated before the development of clinical cardiotoxicity after a mean decline in absolute camera ejection fraction of 19 +/- 4% (SD) and in probe ejection fraction of 19 +/- 9% into abnormal ranges (a decline in magnitude equivalent to that in patients developing congestive failure). None of these five asymptomatic patients available for clinical follow-up at 6 months after termination of Adriamycin therapy subsequently developed signs of ventricular dysfunction. The majority of patients (83%) studied at 450 mg/m2 cumulative dose levels did not have a 15% or greater decline from baseline into the abnormal range.(ABSTRACT TRUNCATED AT 250 WORDS)
 
Article
Cardiac resynchronization therapy (CRT) is an effective treatment for heart failure (HF) for patients who still have significant symptoms despite optimal medical therapy. Many patients with HF have interventricular and intraventricular conduction delays that cause delayed activation of the lateral
 
Article
Objectives: This study sought to investigate the technical feasibility and safety of the transaortic (TAO) transcatheter aortic valve replacement (TAVR) approach in patients not eligible for transfemoral (TF) access by using a device commercially available in the United States. Background: A large proportion of candidates for TAVR have inadequate iliofemoral vessels for TF access. The transapical route (TAP) is the current alternative but is associated with less favorable outcomes. Other access options need to be explored. Methods: Forty-four consecutive patients with inoperable, severe aortic stenosis underwent TAO TAVR in our institution. Procedural and 30-day clinical outcomes data were compared with data from 76 consecutive patients who underwent TAP TAVR at our site. Technical learning curves were assessed by comparing outcomes of the first 20 cases with the subsequent patients who underwent each procedure. Results: The TAO and TAP TAVR groups were similar in terms of device success according to Valve Academic Research Consortium criteria (89% vs. 84%; p = 0.59) and rates of the 30-day combined safety endpoint of all-cause mortality, myocardial infarction, major stroke, disabling bleeding, severe acute kidney injury, and valve reintervention (20% vs. 33%; p = 0.21). The TAO approach, compared with TAP TAVR, was associated with lower combined bleeding and vascular event rate (27% vs. 46%; p = 0.05), shorter median intensive care unit length of stay (3 vs. 6 days; p = 0.01), and a favorable learning curve. Conclusions: TAVR via the TAO approach is technically feasible, seems to be associated with favorable outcomes, and expands the current alternative options for access sites in patients with inoperable aortic stenosis who are ineligible for TF TAVR.
 
Article
The purpose of this study was to determine, in a large referral population, the rate of echocardiographic change in mitral valve area (MVA) without interim intervention, to determine which factors influence progression of narrowing and to examine associated changes in the right side of the heart. Little information is currently available on the echocardiographic progression of mitral stenosis, particularly on progressive changes in the right side of the heart and the ability of a previously proposed algorithm to predict progression. We studied 103 patients (mean age 61 years; 74% female) with serial two-dimensional and Doppler echocardiography. The average interval between entry and most recent follow-up study was 3.3 +/- 2 years (range 1 to 11). During the follow-up period, MVA decreased at a mean rate of 0.09 cm2/year. In 28 patients there was no decrease, in 40 there was only relatively little change (< 0.1 cm2/year) and in 35 the rate of progression of mitral valve narrowing was more rapid (> or = 0.1 cm2/year). The rate of progression was significantly greater among patients with a larger initial MVA and milder mitral stenosis (0.12 vs. 0.06 vs. 0.03 cm2/year for mild, moderate and severe stenosis, p < 0.01). Although the rate of mitral valve narrowing was a weak function of initial MVA and echocardiographic score by multivariate analysis, no set of individual values or cutoff points of these variables or pressure gradients could predict this rate in individual patients. There was a significant increase in right ventricular diastolic area (17 to 18.7 cm2) and tricuspid regurgitation grade (2 + to 3 +; p < 0.0001 between entry and follow-up studies). Progression in right heart disease occurred even in patients with minimal or no change in MVA. Patients with associated aortic regurgitation had a higher rate of decrease in MVA than did those with trace or no aortic regurgitation (0.19 vs. 0.086 cm2/year, p < 0.05). The rate of mitral valve narrowing in individual patients is variable and cannot be predicted by initial MVA, mitral valve score or transmitral gradient, alone or in combination. Right heart disease can progress independent of mitral valve narrowing.
 
Article
The purpose of this prospective study was to examine the role of echocardiography in patients with Staphylococcus aureus bacteremia (SAB). The reported incidence of infective endocarditis (IE) among patients with SAB varies widely. Distinguishing patients with uncomplicated bacteremia from those with IE is therapeutically and prognostically important, but often difficult. One hundred-three consecutive patients undergoing both transthoracic (TTE) echocardiography and transesophageal (TEE) echocardiography were prospectively evaluated. All patients presented with fever and > or = 1 positive blood culture and were followed up for 12 weeks. Although predisposing heart disease was present in 42 patients (41%), clinical evidence of infective endocarditis (IE) was rare (7%). TTE revealed anatomic abnormalities in 33 patients, but vegetations in only 7 (7%), and was considered indeterminate in 19 (18%). TEE identified vegetations in 22 patients (aortic valve in 5, mitral valve in 9, tricuspid valve in 4, catheter in 2 and pacemaker in 2, abscesses in 2, valve perforation in 1 and new severe regurgitation in 1; 26 total [25%]). Using Duke criteria for the diagnosis of IE, definite IE was present in 26 patients (25%). Clinical findings and predisposing heart disease did not distinguish between patients with and without IE. The sensitivity of TTE for detecting IE was 32%, and the specificity was 100%. The addition of TEE increased the sensitivity to 100%, but resulted in one false positive result (specificity 99%). TEE detected evidence of IE in 19% of patients with a negative TTE and 21% of patients with an indeterminate TTE. At follow-up, cure of staphylococcal infection occurred in a similar percentage of patients with and without IE (77% and 75%, respectively). However, death due to sepsis was significantly more likely among patients with IE (4 of 26 [15%]) than among those without IE (2 of 77 [3%]) (p = 0.03). Our results suggest that IE is common among patients admitted to the hospital with SAB and is associated with an increased risk of death due to sepsis. TEE is essential to establish the diagnosis and to detect associated complications. Therefore, the test should be considered part of the early evaluation of patients with SAB.
 
Article
The goal of this study was to determine the relative prognostic importance of noninvasive measures of endothelial function and atheroma burden in patients with coronary artery disease (CAD). Direct measurement of atherosclerosis by carotid ultrasound and endothelial function assessment by brachial artery flow-mediated dilation (FMD) have both been shown to predict vascular events. The combined prognostic utility of carotid ultrasound and FMD relative to traditional risk markers and cardiovascular fitness has not been evaluated. A total of 152 patients with CAD underwent metabolic testing, exercise stress tests, carotid ultrasound, and endothelial function measurements. Patients were followed for 34 +/- 10 months during which 22 vascular events occurred. Peak FMD (p = 0.012) and FMD/nitroglycerin-mediated dilation (NMD) ratio (p = 0.008) were lower in subjects with events. Univariate analysis with Cox proportional hazards modeling identified plaque area (p = 0.0047), total area (p = 0.0085), peak FMD (p = 0.01), FMD/NMD ratio (p = 0.008), stress test workload (p = 0.027), long-acting nitroglycerin (NTG) (p = 0.0071), and calcium blockers (p = 0.0057) as predictors of adverse events. Multivariate analysis showed that FMD/NMD ratio (p < 0.0001), carotid plaque area (p = 0.06), and NTG (p = 0.005) were independent predictors. Based on median values, subjects were divided into high and low "plaque burden" groups and into high and low FMD/NMD subgroups. Patients with high FMD/NMD had low event rates irrespective of the degree of carotid atheroma. Patients with low FMD/NMD and high "plaque burden" had the highest event rate (p < 0.05). The structural and functional status of the vasculature are independent predictors of coronary events as shown by noninvasive measurement of endothelial function and carotid atheroma burden in patients with CAD. Preserved endothelial function attenuates the risk of future events associated with a high plaque burden.
 
Article
During a 14 month period autopsies were performed on 107 patients with coronary heart disease and the results were evaluated prospectively with special reference to right ventricular infarction. A total of 214 regional infarcts were found, 107 (50%) of which involved the right ventricle. Right ventricular infarction was found in 90 hearts (84%), but only three isolated right ventricular infarcts were seen. Right ventricular involvement was found with equal frequency in anterior and posterior infarction (64 versus 66%), but posterior right ventricular infarcts were much larger (15% of the right ventricle was infarcted versus 1%). Proximal right coronary artery occlusion caused larger right ventricular infarction than did distal occlusion (15 versus 5 g). Right ventricular infarct size was not influenced by coronary artery disease (evaluated angiographically) in noninfarct-related vessels. Anterior right ventricular infarcts were predominantly located near the apex of the heart (to the left of the sternum), whereas posterior right ventricular infarcts were located near the atrioventricular groove (along the right sternal border). Infarct size was equal in patients who died from a first acute anterior or posterior infarct. However, posterior infarcts had more right ventricular involvement (28% of total infarct size versus 7% in anterior infarcts) leaving more of the left ventricular myocardium intact (79 versus 64%). These differences in infarct topography may explain why right ventricular involvement seldom is diagnosed clinically in patients with anterior infarction, and why left ventricular function and prognosis usually are better after posterior compared with anterior infarcts of enzymatically equal size.
 
Article
To the Editor: Chronic heart failure (HF) is a significant problem in the United States, affecting 5.7 million Americans. Studies have consistently demonstrated substantial racial and ethnic disparities in the use of guideline-recommended device therapies related to HF care. For example, although
 
Top-cited authors
Sidney Smith
  • University of North Carolina at Chapel Hill
Elliott M Antman
  • Partners HealthCare
Joseph S Alpert
  • The University of Arizona
David P Faxon
  • Brigham and Women's Hospital
Patrick W Serruys
  • National University of Ireland, Galway / Imperial College London