Citations

Background —Dual-chamber pacing (DDD) has been proposed as a treatment alternative to surgery for severely symptomatic patients with obstructive hypertrophic cardiomyopathy (HCM), based largely on uncontrolled studies. Methods and Results —This prospective, multicenter trial assessed pacing in 48 symptomatic HCM patients with ≥50 mm Hg basal gradient, refractory to drug therapy. Patients were randomized to 3 months each of DDD pacing and pacing backup (AAI-30) in a double-blind, crossover study design, followed by an uncontrolled and unblinded 6-month pacing trial. With randomization, no significant differences were evident between pacing and no pacing for subjective or objective measures of symptoms or exercise capacity, including NYHA functional class, quality of life score, treadmill exercise time or peak oxygen consumption. After 6 additional months of unblinded pacing, functional class and quality of life score were improved compared with baseline ( P <0.01), but peak oxygen consumption was unchanged. Outflow gradient decreased 40%, 82±32 mm Hg to 48±32 mm Hg ( P <0.001), and was reduced in 57% of patients but showed no change or an increase in 43%. At 12 months, 6 individual patients (12%) showed improved functional capacity; each was 65 to 75 years of age. Left ventricular wall thicknesses in the overall study group showed no remodeling between baseline (22±5 mm) and 12 months (21±5 mm; P= NS). Conclusions —(1) Pacing cannot be regarded as a primary treatment for obstructive HCM; (2) with randomization, perceived symptomatic improvement was most consistent with a substantial placebo effect; (3) longer, uncontrolled pacing periods were associated with some subjective benefit but unaccompanied by objective improvement in cardiovascular performance and should be interpreted cautiously; (4) modest reduction in outflow gradient was achieved in most patients; and (5) a small subset (12%) ≥ 65 years of age showed a clinical response, suggesting that DDD pacing could be a therapeutic option for some elderly patients.

Background —The outcome of aortic regurgitation conservatively followed in clinical practice is poorly defined. Methods and Results —Long-term outcome of 246 patients with severe or moderately severe aortic regurgitation diagnosed by color Doppler echocardiography was analyzed. With conservative management, mortality rate was higher than expected (at 10 years, 34±5%, P <0.001) and morbidity was high (10-year rates of 47±6% for heart failure and 62±4% for aortic valve surgery). At 10 years, 75±3% of patients had died or had surgery and 83±3% had had cardiovascular events. In multivariate analysis, predictors of survival were age ( P <0.001), functional class ( P <0.001), comorbidity index ( P =0.033), atrial fibrillation ( P =0.002), and left ventricular end-systolic diameter corrected for body surface area ( P =0.025). Ejection fraction was also an independent predictor of overall survival, including postoperative follow-up of surgically treated patients ( P <0.001). High risk during conservative treatment, with mortality rate in excess of that expected, was noted among patients with severe, even transient, symptoms (24.6% yearly, P <0.001) but also in those with mild (class II) symptoms (6.3% yearly, P =0.02) and in asymptomatic patients with left ventricular ejection fraction <55% (5.8% yearly, P =0.03) or with end-systolic diameter normalized to body surface area ≥25 mm/m 2 (7.8% yearly, P =0.004). Surgery performed during follow-up was independently associated with reduced cardiovascular mortality (adjusted hazard ratio, 0.54; P =0.048). Conclusions —Patients diagnosed with severe aortic regurgitation in clinical practice incur excess mortality and high morbidity, underscoring the serious prognosis of the disease. Surgery, which reduces cardiac mortality rates, should be considered promptly in high-risk patients.

Background —Patients with obstructive sleep apnea (OSA) experience repetitive episodic hypoxemia with consequent sympathetic activation and marked blood pressure surges, each of which may impair endothelial function. We tested the hypothesis that patients with OSA have impaired endothelium-dependent vasodilation, even in the absence of overt cardiovascular disease. Methods and Results —We studied 8 patients with OSA (age 44±4 years) and 9 obese control subjects (age 48±3 years). Patients with OSA were newly diagnosed, never treated for OSA, on no medications, and free of any other known diseases. All obese control subjects underwent complete overnight polysomnographic studies to exclude occult OSA. Resistance-vessel function was tested by use of forearm blood flow responses to intra-arterial infusions of acetylcholine (a vasodilator that stimulates endothelial release of nitric oxide), sodium nitroprusside (an exogenous nitric oxide donor), and verapamil (a calcium channel blocker). Conduit-vessel function was also evaluated by ultrasonography. Brachial artery diameter was measured under baseline conditions, during reactive hyperemia (with flow increase causing endothelium-dependent dilatation), and after sublingual administration of nitroglycerin (an endothelium-independent vasodilator). Patients with OSA had a blunted vasodilation in response to acetylcholine ( P <0.007), but responses to sodium nitroprusside and verapamil were not significantly different from those of control subjects. No significant difference in conduit-vessel dilation was evident between OSA patients and obese control subjects. Conclusions —Patients with OSA have an impairment of resistance-vessel endothelium-dependent vasodilation. This may be implicated in the pathogenesis of hypertension and heart failure in this condition.

Background —Coronary endothelial dysfunction is characterized by vasoconstrictive response to the endothelium-dependent vasodilator acetylcholine. Although endothelial dysfunction is considered an early phase of coronary atherosclerosis, there is a paucity of information regarding the outcome of these patients. Thus, this study was designed to evaluate the outcome of patients with mild coronary artery disease on the basis of their endothelial function. Methods and Results —Follow-up was obtained in 157 patients with mildly diseased coronary arteries who had undergone coronary vascular reactivity evaluation by graded administration of intracoronary acetylcholine, adenosine, and nitroglycerin and intracoronary ultrasound at the time of diagnostic study. Patients were divided on the basis of their response to acetylcholine into 3 groups: group 1 (n=83), patients with normal endothelial function; group 2 (n=32), patients with mild endothelial dysfunction; and group 3 (n=42), patients with severe endothelial dysfunction. Over an average 28-month follow-up (range, 11 to 52 months), none of the patients from group 1 or 2 had cardiac events. However, 6 (14%) with severe endothelial dysfunction had 10 cardiac events ( P <0.05 versus groups 1 and 2). Cardiac events included myocardial infarction, percutaneous or surgical coronary revascularization, and/or cardiac death. Conclusions —Severe endothelial dysfunction in the absence of obstructive coronary artery disease is associated with increased cardiac events. This study supports the concept that coronary endothelial dysfunction may play a role in the progression of coronary atherosclerosis.

Background —Our goal was to test sympathetic and cardiovagal baroreflex sensitivity and the transduction of sympathetic traffic into vascular resistance during the early follicular (EF) and midluteal (ML) phases of the menstrual cycle. Methods and Results —Sympathetic baroreflex sensitivity was assessed by lowering and raising blood pressure with intravenous bolus doses of sodium nitroprusside and phenylephrine. It was defined as the slope relating muscle sympathetic nerve activity (MSNA; determined by microneurography) and diastolic blood pressure. Cardiovagal baroreflex sensitivity was defined as the slope relating R-R interval and systolic blood pressure. Vascular transduction was evaluated during ischemic handgrip exercise and postexercise ischemia, and it was defined as the slope relating MSNA and calf vascular resistance (determined by plethysmography). Resting MSNA (EF, 1170±151 U/min; ML, 2252±251 U/min; P <0.001) and plasma norepinephrine levels (EF, 240±21 pg/mL; ML, 294±25 pg/mL; P =0.025) were significantly higher in the ML than in the EF phase. Furthermore, sympathetic baroreflex sensitivity was greater during the ML than the EF phase in every subject (MSNA/diastolic blood pressure slopes: EF, −4.15; FL, −5.42; P =0.005). No significant differences in cardiovagal baroreflex sensitivity or vascular transduction were observed. Conclusions —The present study suggests that the hormonal fluctuations that occur during the normal menstrual cycle may alter sympathetic outflow but not the transduction of sympathetic activity into vascular resistance.

Background —Epidemiological studies have demonstrated that hyperfibrinogenemia is an independent risk factor for cerebrovascular atherosclerosis. However, the underlying mechanisms are poorly understood. We studied whether hyperfibrinogenemia could modify the histological composition of atherosclerotic plaque and precipitate carotid thrombosis resulting from rupture of the plaque. Methods and Results —We studied the histological composition of 71 carotid atherosclerotic plaques from patients who had undergone surgical endarterectomy after a first episode of transient ischemic attack. Patients were divided into 3 groups corresponding to the tertiles of plasma fibrinogen values. Hypercholesterolemia, hypertriglyceridemia, hypertension, diabetes, and smoking habit were also assessed. At the histological analysis, plaques of patients in the highest tertile of fibrinogen (>407 mg/dL) were characterized by a high incidence of thrombosis (66.7% of cases) compared with plaques of subjects in the lower (21.7%) ( P =0.002) and middle (29.2%) ( P =0.009) tertiles. Plaque rupture was significantly associated with high fibrinogen levels (54.2%, P =0.003). Multivariate logistic regression indicated that hyperfibrinogenemia was an independent risk factor for a decrease in cap thickness ( P =0.0005), macrophage foam cell infiltration of the cap ( P =0.003), and thrombosis ( P =0.003). When the presence of other risk factors was accounted for, hyperfibrinogenemia remained an independent predictor of carotid thrombosis with an odds ratio of 5.83, compared with other risk factors. Conclusions —The results of the present study add to the evidence that hyperfibrinogenemia, independently of other risk factors, is associated with a specific histological composition of carotid atherosclerotic plaques that predisposes them to rupture and thrombosis.

Background —Idiopathic restrictive cardiomyopathy is a poorly recognized entity of unknown cause characterized by nondilated, nonhypertrophied ventricles with diastolic dysfunction resulting in dilated atria and variable systolic function. Methods and Results —Between 1979 and 1996, 94 patients (61% women) 10 to 90 years old (mean, 64 years) met strict morphological echocardiographic criteria for idiopathic restrictive cardiomyopathy, mainly dilated atria with nonhypertrophied, nondilated ventricles. None had known infiltrative disease, hypertension of >5 years’ duration, or cardiac or systemic conditions associated with restrictive filling. Nineteen percent were in NYHA class I, 53% in class II, and 28% in class III or IV. Atrial fibrillation was noted in 74% of patients and systolic dysfunction in 16%. Follow-up (mean, 68 months) was complete for 93 patients (99%). At follow-up, 47 patients (50%) had died, 32 (68%) of cardiovascular causes. Four had heart transplantation. The death rate compared with actuarial statistics was significantly higher than expected ( P <0.0001). Kaplan-Meier 5-year survival was 64%, compared with expected survival of 85%. Multivariate analysis using proportional hazards showed that the risk of death approximately doubles with male sex (hazard ratio [HR] =2.1), left atrial dimension >60 mm (HR=2.3), age >70 years (HR=2.0), and each increment of NYHA class (HR=2.0). Conclusions —Idiopathic restrictive cardiomyopathy or nondilated, nonhypertrophic ventricles with marked biatrial dilatation, as defined morphologically by echocardiography, affects predominantly elderly patients but can occur in any age group. Patients present with systemic and pulmonary venous congestion and atrial fibrillation and have a poor prognosis, particularly men >70 years old with higher NYHA class and left atrial dimension >60 mm.

Background —The outcome of aortic valve replacement in patients with severe aortic stenosis, low transvalvular gradient, and severe left ventricular dysfunction is not well known. Methods and Results —Between 1985 and 1995, 52 patients with left ventricular ejection fraction (EF) ≤35% and aortic stenosis with transvalvular mean gradient <30 mm Hg underwent aortic valve replacement. The mean (±SD) preoperative characteristics included EF, 26±8%; aortic valve mean gradient, 23±4 mm Hg; aortic valve area, 0.7±0.2 cm 2 ; and cardiac output, 3.7±1.2 L/min. Simultaneous coronary artery bypass graft surgery was performed in 32 patients (62%). Perioperative (30-day) mortality was 21% (11 of 52 patients). Ten additional patients died during follow-up. Advanced age ( P =0.048) and small aortic prosthesis size ( P =0.03) were significant predictors of hospital mortality by univariate analysis. By multivariate analysis, the only predictor of surgical mortality was smaller prosthesis size. The only predictor of postoperative survival was improvement in postoperative functional class ( P =0.04). Postoperative functional improvement occurred in most patients. Postoperative EF was assessed in 93% of survivors; 74% demonstrated improvement. Positive change in EF was related to smaller preoperative aortic valve area and female sex. Conclusions —Despite severe left ventricular dysfunction, low transvalvular mean gradient, and increased operative mortality, aortic valve replacement was associated with improved functional status. Postoperative survival was related to younger patient age and larger aortic prosthesis size, and medium-term survival was related to improved postoperative functional class.

Background —Previous studies of atrial flutter have found linear block at the crista terminalis; this was thought to predispose the patient to the arrhythmia. More recent observations, however, have demonstrated crista conduction. We sought to characterize the posterior boundary of atrial flutter. Methods and Results —Patients with counterclockwise flutter (n=20), clockwise flutter (n=3), or both (n=5) were studied using two 20-pole catheters. Biplane fluoroscopy determined catheter positions. During counterclockwise flutter, craniocaudal activation occurred along the entire lateral and posterior right atrial walls. Septal activation proceeded caudocranially. In all patients, a line of block was seen in the posteromedial (sinus venosa) right atrium; this was manifested by the presence of double potentials where the upward and downward activations collided. Anatomic location was confirmed by intracardiac echocardiography in 9 patients. In patients with clockwise flutter, the line of block and double potentials were seen in the same location during counterclockwise flutter, but the activation sequence around the line of block was reversed. Pacing near the site of double potentials during sinus rhythm excluded a fixed line of block, and premature atrial complexes demonstrated functional block with manifest double potentials. In 2 patients, posterior ectopy organized to subsequently initiate isthmus-dependent atrial flutter. Conclusions —(1) A functional line of block is seen at the posteromedial (sinus venosa region) right atrium during counterclockwise and clockwise atrial flutter. (2) All lateral wall right atrial activation can be uniform during flutter, without linear block or double potentials in the region of the crista terminalis. (3) Activation at the site of posteromedial right atrial functional block can organize to subsequently initiate isthmus-dependent atrial flutter.

Background —In a previous randomized trial, the 12F laser sheath removed pacing leads via the implant vein more successfully than traditional mechanical tools alone. Two larger sizes of laser sheath, the 14F and 16F models, were developed to extract defibrillator leads and large-diameter pacing leads implanted for the chronic. These devices use pulsed ultraviolet laser light to core though fibrotic tissue grown over the lead body to free the lead from the vasculature. A mandatory prospective registry studied the safety and effectiveness profiles of the larger laser sheaths vis-à-vis the 12F laser sheath. Methods and Results —In this study, 863 patients underwent extraction of 1285 leads at 52 sites. Patients treated with the 14F device tended to have older leads than the 12F population; the 16F population, which comprised mostly defibrillator patients, were younger, had younger leads, and were more often male than the 12F population. Clinical success (extracting the entire lead or the lead body minus the distal electrode) was observed in 91% to 92% of cases for all device sizes. The overall complication rate was 3.6%, with 0.8% perioperative mortality. Incidence of complications was independent of laser sheath size. Conclusions —The 14F and 16F laser sheaths offer an extraction option for larger long-term transvenous pacemaker and defibrillator leads that is as safe and effective as the 12F laser sheath.