Holmes, David R.

BACKGROUND Virtually all natural history studies of Wolff-Parkinson-White (WPW) syndrome have been case series and, as such, have been constrained by referral biases, skewed age and sex distributions, or brief follow-up periods. The purpose of our study was to examine the natural history, the development of arrhythmias, and the incidence of sudden death in an entire cohort of pediatric and adult WPW patients from a community-based local population. METHODS AND RESULTS We identified 113 residents of Olmsted County, Minnesota, during the period 1953-1989 using the centralized records-linkage system provided by the Mayo Clinic and the Rochester Epidemiology Program Project. Medical records and ECGs were reviewed to confirm the diagnosis and to establish pathway location by ECG criteria. Follow-up, via record review and telephone interview, was complete in 95% of subjects through 1990. The incidence of newly diagnosed cases was approximately four per 100,000 per year. Preexcitation was not present on the initial ECG of 22% of the cohort. Approximately 50% of the population was asymptomatic at diagnosis, with 30% subsequently having symptoms related to arrhythmia at follow-up. Two sudden cardiac deaths (SCD) occurred over 1,338 patient-years of follow-up, yielding an overall SCD rate of 0.0015 (95% confidence interval, 0.0002-0.0054) per patient-year. No SCD occurred in patients asymptomatic at diagnosis. CONCLUSIONS The incidence of sudden death in a local community-based population is low and suggests that electrophysiological testing should not be performed routinely in asymptomatic patients with WPW syndrome. Nevertheless, young, asymptomatic patients, particularly those < 40 years old, should return for medical follow-up should symptoms develop.

Aims: Percutaneous coronary intervention (PCI) is frequently accompanied by myocardial injury. The present study was performed to determine whether remote ischemic preconditioning (IP) induces cardioprotection during PCI. Methods: We enrolled 95 patients requiring nonemergency PCI for stable disease or unstable angina into this prospective clinical trial. Patients were randomized to either remote IP (induced by three 3‐min cycles of blood pressure cuff inflations to 200 mm Hg around the upper arm, followed by 3‐min of reperfusion n = 47) or sham control ( n = 48) immediately preceding PCI. The primary outcome measure was the frequency of post‐PCI myonecrosis, defined as a peak postprocedural cTnT T ≥0.03 ng/dL. Secondary outcome measures were the change in plasma high‐sensitivity C‐reactive protein (hsCRP) levels following PCI and in endothelial progenitor cells (EPC) counts following IP. Results: There was no difference in the primary endpoint of the frequency of PCI related myonecrosis which occurred in 22 (47%) and 19 (40%) patients in the remote IP and control groups, respectively, P = 0.42. There was significant increase in hsCRP post‐PCI in both groups ( P < 0.001), but there was no difference between the groups (median %change in hsCRP 46% vs. 54%, P = 0.73). There was no significant change in circulating early (CD34 −/CD133+/KDR+), intermediate (CD34+/CD133+/KDR+), or late (CD34+/CD133−/KDR+) EPC in the two groups immediately following IP. The composite rate of death, myocardial infarction, and target lesion revascularization at 1 year was 14.1% versus 13.7% ( P = 0.90). Conclusions: Our study indicates that remote IP immediately before PCI does not induce cardioprotection in low to moderate risk patients. © 2012 Wiley Periodicals, Inc.

Background— Clinical outcomes after stent placement in patients with a history of metal allergy remain incompletely understood. We performed a single-center retrospective study to evaluate such outcomes. Methods and Results— Twenty-nine allergic patients who underwent coronary stent implantation were compared with a nonallergic group (n=250) matched for demographics and a propensity score for allergy to metal. Hypersensitivity to nickel was reported in 26 of 29 and chromium in 9 of 29. Patch testing performed in 11 of 29 patients was positive in all. Comparing allergy versus control subjects, there were no differences in number of segments treated (1.4±0.7 versus 1.5±0.7), stents placed (1.7±1.1 versus 1.6±0.9), and frequency of drug-eluting stent usage (52% versus 60%). In-hospital death (0% versus 0%), myocardial infarction (MI, 4% versus 3%, P =0.27), and 30-day death (3% versus 0%, P =0.53) and MI (3% versus 4%, P =0.71) were statistically similar. There were no differences in 4-year death (12% versus 13%), target lesion revascularization (TLR, 13 versus 17%, P =0.54), or death/MI/TLR (24% versus 34%, P =0.20). Clinically driven repeat angiography in 12 of 29 allergy patients revealed binary restenosis rates of 27% in bare metal stents and 0% in drug-eluting stents, with mean diameter in-stent restenosis of 36% and 8%, respectively. There was no change in circulating eosinophil and lymphocyte counts after stenting in the allergy group (0.19–0.20, P =0.67, and 1.90–1.79, P =0.59, respectively). Conclusions— A history of metal allergy was not associated with adverse early or late outcomes in this single-center study.

The optimal regimen of the anticoagulant and antiplatelet therapies in patients with atrial fibrillation who have had a coronary stent is unclear. It is well recognized that “triple therapy” with aspirin, clopidogrel, and warfarin is associated with an increased risk of bleeding. National guidelines have not made specific recommendations, given the lack of adequate data. In choosing the best antithrombotic options for a patient, consideration needs to be given to the risks of stroke, stent thrombosis, and major bleeding. This executive summary describes these risks, provides specific recommendations concerning vascular access, stent choice, concomitant use of proton pump inhibitors, and the use and duration of triple therapy after stent placement, based on the risk assessment.

Background— The impact of incomplete revascularization (IR) on adverse outcomes after percutaneous coronary intervention remains inconclusive, and few studies have examined mortality during follow-ups longer than 5 years. The objective of this study is to test the hypothesis that IR is associated with higher risk of long-term (8-year) mortality after stenting for multivessel coronary disease. Methods and Results— A total of 13 016 patients with multivessel disease who had undergone stenting procedures with bare metal stents in 1999 to 2000 were identified in the New York State's Percutaneous Coronary Intervention Reporting System. A logistic regression model was fit to predict the probability of achieving complete revascularization (CR) in these patients using baseline risk factors; then, the CR patients were matched to the IR patients with similar likelihoods of achieving CR. Each patient's vital status was followed through 2007 using the National Death Index, and the difference in long-term mortality between IR and CR was compared. It was found that CR was achieved in 29.2% (3803) of the patients. For the 3803 pair-matched patients, the respective 8-year survival rates were 80.8% and 78.5% for CR and IR ( P =0.04), respectively. The risk of death was marginally significantly higher for IR (hazard ratio=1.12; 95% confidence interval, 1.01–1.26, P =0.04). The 95% bootstrap confidence interval for the hazard ratio was 0.98 to 1.32. Conclusions— IR may be associated with higher risk of long-term mortality after stenting with BMS in patients with multivessel disease. More prospective studies are needed to further test this association.

A model of proliferative human restenosis was developed in domestic pigs by using deep injury to the coronary arterial media. Metal wire coils were delivered percutaneously to the coronary arteries of 11 pigs with an oversized, high-pressure (14 atm) balloon and were left in place for times ranging from 28 to 70 days. During placement, the balloon expanded the coils and delivered them securely within the arterial lumen. Light microscopic examination of the vessels confirmed fracture of the internal elastic lamina by the coil. An extensive proliferative response occurred in 10 of the 11 pigs and was associated with a luminal area narrowing of at least 50% in all but one pig. The histopathologic features of the proliferative response were identical to those observed in human cases of restenosis after angioplasty. Immunohistochemical studies confirmed the prominence of smooth muscle cells in the proliferative tissue. A similar response was obtained in two of five porcine coronary arteries in which balloon inflation only was performed, without coil implant. This model is practical and inexpensive and closely mimics the proliferative portion of human restenosis both grossly and microscopically. Thus, it may be useful for understanding human restenosis and for testing therapies aimed at preventing restenosis after balloon angioplasty or other coronary interventional procedures.

The outlook for patients with double-outlet right ventricle has improved since the development of corrective operations. Late arrhythmic deaths after successful procedures have been reported; however, the magnitude remains unknown. This study was undertaken to identify the magnitude of late sudden death and the significant factors associated with it. From 1965 through 1985, 118 patients underwent corrective operation for double-outlet right ventricle; of these, 23 died in the hospital and six were lost to follow-up. The 89 remaining patients (52 male and 37 female) made up the study population. Their mean age (+/- SD) was 10.3 +/- 7.8 years at the time of repair. The mean duration of follow-up was 82 months. Of the 22 late deaths, 16 (73%) were sudden. Eight (50%) of the sudden deaths occurred within 1 year of operation. Cox proportional hazards multivariate analysis revealed the following significant risk factors for late sudden death: older age at the time of operation, perioperative or postoperative ventricular tachyarrhythmias, and third-degree atrioventricular block. Factors not associated with late sudden death included year of operation, sex, type and number of associated cardiac anomalies, preoperative functional class, previous palliative procedures, surgical technique, perioperative or postoperative single premature ventricular contractions, and postoperative left or right bundle branch block with or without fascicular block. We conclude that the incidence of late sudden death after successful surgical repair of double-outlet right ventricle is very high. Complete corrective operation at an early age and aggressive diagnosis and treatment of arrhythmias and conduction defects after operation are warranted.

To evaluate the short-term results of percutaneous aortic balloon valvuloplasty, 55 consecutive elderly patients with symptomatic, severe aortic stenosis who were at high risk for surgical intervention underwent the procedure, with follow-up by clinical evaluation and Doppler echocardiography. Over a mean follow-up of 6.2 months, there were three early deaths (less than 30 days) and eight late deaths. Nine patients underwent subsequent aortic valve surgery, and four had repeat balloon valvuloplasty. Doppler echocardiography revealed a reduction in aortic valve mean gradient from 48 +/- 18 to 33 +/- 12 mm Hg after the procedure (p less than 0.0001) but a return to 46 +/- 16 mm Hg at follow-up (p less than 0.05). The aortic valve area increased from 0.54 +/- 0.15 to 0.85 +/- 0.23 cm2 after the procedure (p less than 0.0001), but there was a significant decrease to 0.67 +/- 0.19 cm2 at follow-up (p less than 0.05). Of patients free of aortic valve operation or death after 30 days after the procedure, 76% were severely symptomatic before the procedure as compared with 38% at follow-up. In patients undergoing percutaneous aortic balloon valvuloplasty, there is a continued high short-term mortality and a significant incidence of restenosis over short-term follow-up. Nonetheless, a subset of patients do experience sustained clinical improvement from this procedure.

Acute occlusion after a successful angioplasty is a severe complication that has been reported in 2-12% of patients. Therefore, to determine whether there was a relation between the dosage of heparin and the presence of mural thrombosis, we studied in a pig model the relation between the dosage of heparin and acute platelet-thrombus deposition on the site of arterial injury. We retrospectively analyzed the effect of three heparin regimens on platelet deposition in 32 normal pigs (mean weight, 32.7 kg) that underwent bilateral carotid angioplasty and were sacrificed 90 +/- 26 minutes later. Pigs in protocol 1 (n = 7) received an intravenous bolus injection of 4,000 units heparin 10 minutes before angioplasty. Pigs in protocol 2 (n = 11) received two bolus injections of 4,000 units heparin 40 minutes apart; the angioplasty was performed immediately after the second bolus. Pigs in protocol 3 (n = 14) had an initial 4,000-unit bolus injection of heparin followed immediately by an infusion of 4,000 units/hr; angioplasty was performed 20 minutes after starting the infusion. 111In-labeled platelet deposition on deeply injured (torn into the media) arterial segments were 86.3 +/- 68, 56.2 +/- 56.9, and 37.7 +/- 37.7 X 10(6)/cm2 for protocols 1, 2, and 3, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)