Owen Obel

Left atrial appendage: structure, function, and role in thromboembolism

The left atrial appendage (LAA) is derived from the left wall of the primary atrium, which forms during the fourth week of embryonic development. It has developmental, ultrastructural, and physiological characteristics distinct from the left atrium proper. The LAA lies within the confines of the pericardium in close relation to the free wall of the left ventricle and thus its emptying and filling may be significantly affected by left ventricular function. The physiological properties and anatomical relations of the LAA render it ideally suited to function as a decompression chamber during left ventricular systole and during other periods when left atrial pressure is high. These properties include the position of the LAA high in the body of the left atrium; the increased distensibility of the LAA compared with the left atrium proper; the high concentration of atrial natriuretic factor (ANF) granules contained within the LAA; and the neuronal configuration of the LAA. Thrombus has a predilection to form in the LAA in patients with atrial fibrillation, mitral valve disease, and other conditions. The pathogenesis has not been fully elucidated; however, relative stasis which occurs in the appendage owing to its shape and the trabeculations within it is thought to play a major role. Obliteration or amputation of the LAA may help to reduce the risk of thromboembolism, but this may result in undesirable physiological sequelae such as reduced atrial compliance and a reduced capacity for ANF secretion in response to pressure and volume overload.

A Randomized Controlled Trial of a Paclitaxel-Eluting Stent Versus a Similar Bare-Metal Stent in Saphenous Vein Graft Lesions: The SOS (Stenting Of Saphenous Vein Grafts) Trial

OBJECTIVES The aim of this study was to compare the frequency of angiographic restenosis and clinical events between a paclitaxel-eluting stent (PES) and a similar bare-metal stent (BMS) in saphenous vein graft (SVG) lesions. BACKGROUND There are conflicting and mostly retrospective data on outcomes after drug-eluting stent implantation in SVGs. METHODS Patients requiring SVG lesion stenting were randomized to BMS or PES. The primary study end point was binary in-segment restenosis at 12-month follow-up quantitative coronary angiography. Secondary end points included death, myocardial infarction, ischemia-driven target vessel and lesion revascularization, and target vessel failure. RESULTS Eighty patients with 112 lesions in 88 SVGs were randomized to a BMS (39 patients, 43 grafts, 55 lesions) or PES (41 patients, 45 grafts, 57 lesions). Binary angiographic restenosis occurred in 51% of the BMS-treated lesions versus 9% of the PES-treated lesions (relative risk: 0.18; 95% confidence interval [CI]: 0.07 to 0.48, p < 0.0001). During a median follow-up of 1.5 years the PES patients had less target lesion revascularization (28% vs. 5%, hazard ratio: 0.38; 95% CI: 0.15 to 0.74, p = 0.003) and target vessel failure (46% vs. 22%, hazard ratio: 0.65; 95% CI: 0.42 to 0.96, p = 0.03), a trend toward less target vessel revascularization (31% vs. 15%, hazard ratio: 0.66; 95% CI: 0.39 to 1.05, p = 0.08) and myocardial infarction (31% vs. 15%, hazard ratio: 0.67; 95% CI: 0.40 to 1.08, p = 0.10), and similar mortality (5% vs. 12%, hazard ratio: 1.56; 95% CI: 0.72 to 4.11, p = 0.27). CONCLUSIONS In SVG lesions, PES are associated with lower rates of angiographic restenosis and target vessel failure than BMS.

Embolic complications of direct current cardioversion of atrial arrhythmias: Association with low intensity of anticoagulation at the time of cardioversion

OBJECTIVES The goal of this study was to identify the factors responsible for embolic complications of direct current (DC) cardioversion of atrial arrhythmias. BACKGROUND Direct current cardioversion of atrial fibrillation (AF) carries a risk of thromboembolism, which is reduced, but not eliminated, by anticoagulation. The risk of embolism after conversion of atrial flutter is believed to be lower. No series to date has included enough patients receiving anticoagulants or enough patients with atrial flutter to estimate the risk in these groups. METHODS We reviewed the case records of 1,950 patients who underwent 2,639 attempts at DC cardioversion. RESULTS Cardioversion was performed within two days of the apparent onset of the arrhythmia in 443 episodes, 352 without subsequent prolonged anticoagulation with one embolic complication. Cardioversion was preceded by warfarin therapy for > or = 3 weeks in 1,932 instances. No embolic complication occurred in 779 attempts performed with an international normalized ratio (INR) of > or = 2.5 (95% confidence limits 0% to 0.48%). Of 756 cases in which the INR was <2.5 or was not measured before conversion, nine were complicated by thromboembolism. Embolism was significantly more common at an INR of 1.5 to 2.4 than at an INR > or = 2.5 (0.93% vs. 0%, p = 0.012). The incidence of embolism after conversion of atrial flutter or tachycardia was similar to that after cardioversion of AF (0.72% vs. 0.46%, p = NS). CONCLUSIONS The INR should be > or = 2.5 at the time of cardioversion if the duration of AF is uncertain or >2 days. Cardioversion of atrial flutter presents similar risks and requires similar anticoagulation.

Continued Benefit From Paclitaxel-Eluting Compared With Bare-Metal Stent Implantation in Saphenous Vein Graft Lesions During Long-Term Follow-Up of the SOS (Stenting of Saphenous Vein Grafts) Trial

OBJECTIVES This study sought to report the long-term outcomes after drug-eluting stent (DES) implantation in saphenous vein graft (SVG) lesions in the SOS (Stenting of Saphenous Vein Grafts) trial. BACKGROUND The long-term outcomes after DES implantation in SVGs are poorly studied. Apart from the SOS trial, the only other randomized trial comparing DES with bare-metal stents (BMS) in SVGs reported higher mortality in the DES group at 32 months. METHODS In the SOS trial, 80 patients with 112 lesions in 88 SVGs were randomized to a BMS or paclitaxel-eluting stent (PES) and demonstrated improved short-term angiographic and clinical outcomes with PES. Extended clinical follow-up was subsequently obtained. RESULTS Mean age was 67 ± 9 years, and all patients were men. The indications for stenting included acute coronary syndrome in 60% and stable angina in 31% of patients. The mean SVG age was 12 ± 6 years. The baseline characteristics of the patients in the 2 study groups were similar. Procedural success was achieved in 77 patients (96%). During a median follow-up of 35 months, compared with patients randomized to BMS, those receiving PES had a lower incidence of myocardial infarction (hazard ratio [HR]: 0.32, p = 0.01), target lesion revascularization (HR: 0.20, p = 0.004), target vessel revascularization (HR: 0.41, p = 0.03), and target vessel failure (HR: 0.34, p = 0.001) as well as a trend toward less definite or probable stent thrombosis (HR: 0.15, p = 0.08). All-cause mortality (HR: 2.04, p = 0.19) and cardiac mortality (HR: 0.62, p = 0.51) did not differ between groups. CONCLUSIONS During long-term follow-up, use of PES was associated with significantly better clinical outcomes than BMS in SVG lesions. (Stenting of Saphenous Vein Grafts Trial [SOS]; NCT00247208).

A randomized controlled trial evaluating the safety and efficacy of cardiac contractility modulation in advanced heart failure.

BACKGROUND Cardiac contractility modulation (CCM) delivers nonexcitatory electrical signals to the heart during the absolute refractory period intended to improve contraction. METHODS We tested CCM in 428 New York Heart Association class III or IV, narrow QRS heart failure patients with ejection fraction (EF) ≤ 35% randomized to optimal medical therapy (OMT) plus CCM (n = 215) versus OMT alone (n = 213). Efficacy was assessed by ventilatory anaerobic threshold (VAT), primary end point, peak Vo₂ (pVo₂), and Minnesota Living with Heart Failure Questionnaire (MLWFQ) at 6 months. The primary safety end point was a test of noninferiority between groups at 12 months for the composite of all-cause mortality and hospitalizations (12.5% allowable delta). RESULTS The groups were comparable for age (58 ± 13 vs 59 ± 12 years), EF (26% ± 7% vs 26% ± 7%), pVo₂ (14.7 ± 2.9 vs 14.8 ± 3.2 mL kg⁻¹ min⁻¹), and other characteristics. While VAT did not improve at 6 months, CCM significantly improved pVo₂ and MLWHFQ (by 0.65 mL kg⁻¹ min⁻¹ [P = .024] and -9.7 points [P < .0001], respectively) over OMT. Forty-eight percent of OMT and 52% of CCM patients experienced a safety end point, which satisfied the noniferiority criterion (P = .03). Post hoc, hypothesis-generating analysis identified a subgroup (characterized by baseline EF ≥ 25% and New York Heart Association class III symptoms) in which all parameters were improved by CCM. CONCLUSIONS In the overall target population, CCM did not improve VAT (the primary end point) but did improve pVo₂ and MLWHFQ. Cardiac contractility modulation did not have an adverse affect on hospitalizations or mortality within the prespecified boundaries. Further study is required to clarify the role of CCM as a treatment for medically refractory heart failure.

Comparison of thyroid function in pregnant and non-pregnant Asian and western Caucasian women.

BACKGROUND Gestational thyrotoxicosis may be more prevalent in Asian women. METHODS We have measured thyroid function, ferritin and bone specific alkaline phosphatase (BALP) as peripheral markers of thyroid function and hCG in Asian and western Caucasian women in non-pregnant and early pregnancy. RESULTS TSH was lower in Asian women in non-pregnancy but not during normal pregnancy and this may reflect increased sensitivity of the thyroid gland to thyroid stimulation in the Asian population. No ethnic difference was found in FT3, FT4 or hCG but ferritin was lower and BALP higher in Asian women whether pregnant or not and this may be a reflection of iron balance and vitamin D status. CONCLUSIONS We found during normal pregnancy that dynamic patterns of change for thyroid hormones and hCG are not different in Asian and western Caucasian women. We have developed gestation related reference intervals, which are a pre-requisite to the study of ethnic differences in gestation thyrotoxicosis in pregnancy.

Clinical Presentation and Angiographic Characteristics of Saphenous Vein Graft Failure After Stenting: Insights From the SOS (Stenting Of Saphenous Vein Grafts) Trial

OBJECTIVES We sought to compare the clinical presentation and angiographic patterns of saphenous vein graft (SVG) failure after stenting with a paclitaxel-eluting stent (PES) versus a similar bare-metal stent (BMS). BACKGROUND The mode of SVG failure after stenting has been poorly characterized. METHODS The SOS (Stenting Of Saphenous Vein Grafts) trial enrolled 80 patients with 112 lesions in 88 SVGs who were randomized to a BMS or PES. Angiographic follow-up at 12 months was available in 83% of the patients. RESULTS Binary angiographic restenosis occurred in 51% (24 of 47) of BMS-treated lesions versus 9% (4 of 43) of PES-treated lesions (p < 0.0001). Graft occlusion occurred in 9 of the 21 SVGs (43%) that failed in the BMS group and in 2 of 4 SVGs (50%) that failed in the PES group. SVG failure after stenting presented as an acute coronary syndrome in 10 of the 24 patients (42%) (7 of those 10 patients presented with non-ST-segment elevation acute myocardial infarction), stable angina in 9 (37%) patients, and without symptoms in 5 (21%) patients. Of the 19 patients (with 20 grafts) who developed symptomatic graft failure, repeat SVG revascularization was successfully performed in all 13 (100%) subtotally obstructed SVGs but was attempted (and successful) in only 1 of 7 (14%) occluded SVGs. Revascularization of a native coronary artery was performed in an additional 4 of 7 (57%) symptomatic patients with an occluded SVG. CONCLUSIONS SVG failure after stenting often presents as acute myocardial infarction and with SVG occlusion. Compared with BMS, PES reduce SVG failure.

TACHYCARDIA-INDUCED ATRIAL MYOPATHY : AN IMPORTANT MECHANISM IN THE PATHOPHYSIOLOGY OF ATRIAL FIBRILLATION?

Tachycardia‐Induced Atrial Myopathy. The atrial myocardium of patients with chronic atrial fibrillation (AF) is often abnormal in its histologic features and in its electrophysiologic properties. These abnormalities have been interpreted in some cases as the cause of AF and in others as a consequence of AF. We believe that both are the case. We will review the features of this atrial myopathy and discuss the likely mechanisms and consequences of the process.

Contemporary use of embolic protection devices in saphenous vein graft interventions: Insights from the stenting of saphenous vein grafts trial

Background: We sought to evaluate the contemporary use of embolic protection devices (EPDs) in saphenous vein graft (SVG) interventions. Methods: We examined EPD use in the stenting of saphenous vein grafts (SOS) trial, in which 80 patients with 112 lesions in 88 SVGs were randomized to a bare metal stent (39 patients, 43 grafts, and 55 lesions) or paclitaxel‐eluting stent (41 patients, 45 grafts, and 57 lesions). Results: An EPD was used in 60 of 112 lesions (54%). A Filterwire (Boston Scientific) was used in 70% of EPD‐treated lesions, Spider (ev3, Plymouth, Minnesota) in 12%, Proxis (St. Jude, Minneapolis, Minnesota) in 12%, and Guardwire (Medtronic, Santa Rosa, California) in 7%. Of the remaining 52 lesions, an EPD was not utilized in 13 lesions (25%) because the lesion was near the distal anastomosis, in 14 lesions (27%) because of an ostial location, in one lesion (2%) because of small SVG size, in two in‐stent restenosis lesions (4%) because of low distal embolization risk, and in 22 lesions (42%) because of operators preference even though use of an EPD was feasible. Procedural success was achieved in 77 patients (96%); in one patient a Filterwire was entrapped requiring emergency coronary bypass graft surgery and two patients had acute stent thrombosis. Conclusion: In spite of their proven efficacy, EPDs were utilized in approximately half of SVG interventions in the SOS trial. Availability of a proximal protection device could allow protection of ∼25% of unprotected lesions, yet operator discretion appears to be the major determinant of EPD use.

Prevalence and outcomes of intermediate saphenous vein graft lesions: Findings from the stenting of saphenous vein grafts randomized-controlled trial

BACKGROUND We sought to examine the prevalence and progression rate of intermediate saphenous vein graft (SVG) lesions in the Stenting Of Saphenous vein grafts (SOS) trial. METHODS The baseline and follow-up angiograms of 80 patients participating in the SOS trial were analyzed to determine the prevalence of intermediate (30-60% angiographic diameter stenosis) SVG lesions and their progression rate. RESULTS At least one intermediate SVG lesion was present in 31 of 143 (22%) SVGs in 27 of 80 (34%) patients. Most intermediate lesions were present in the SOS stented SVGs (20 grafts in 19 patients). During a median follow-up of 35 months, angiographic follow-up was available for 28 grafts in 25 patients. Progression (defined as percent diameter stenosis ≥ 70% but <100% at follow-up angiography) was seen in 11 of 28 SVGs (39%) in 11 of 25 patients (44%). Progression rate at 12, 24 and 36 months was 28% and 47% and 84%, respectively. Seven of 11 patients (64%) with intermediate SVG lesion progression presented with an acute coronary syndrome and 8 (73%) underwent PCI. Four of the 28 grafts with intermediate lesions at baseline were 100% occluded at follow-up; all of those SVGs had received a stent in another location in the SVG as part of the SOS trial. CONCLUSIONS Intermediate SVG lesions are common in patients undergoing SVG stenting, have high rates of progression and frequently present with an acute coronary syndrome. Further study of pharmacologic and mechanical treatments to prevent progression of these lesions is needed.