Remission of recurrent gastrointestinal bleeding after septal reduction therapy in patients with hypertrophic obstructive cardiomyopathy-associated acquired von Willebrand syndrome.

BACKGROUND: Gastrointestinal hemorrhage is considered to be a severe complication of von Willebrand disease. The optimal therapy for acquired von Willebrand syndrome and severe gastrointestinal bleeding with hypertrophic cardiomyopathy is undefined. PATIENTS/METHODS: Seventy-seven patients (median age, 67 years; interquartile range [IQR], 56-75 years; 49% women) with hypertrophic cardiomyopathy underwent von Willebrand factor multimer testing and acquisition of bleeding history. Bleeding was detected in 27 (36%) (median age, 74 years; IQR 66-76 years; 74% women), 20 with gastrointestinal bleeding, including 11 women with transfusion dependence. In these 11 women, the median duration of transfusion dependency was 36 months (IQR 18-44 months), and the median number of transfusions required was 25 (IQR 20-38). Two patients had undergone bowel resection for bleeding, one of them twice. Seven patients showed angiodysplasia, and the remainder had no endoscopic lesion. Bleeding recurred after bowel surgery or endoscopic intervention and medical therapy for hypertrophic cardiomyopathy in 10 of 11 patients. Two patients had septal myectomy, and six patients underwent alcohol septal ablation. With the exception of one patient in whom a significant gradient persisted after septal ablation, after the periprocedural period, patients after septal reduction therapy remained free of recurrent bleeding and need for transfusions. CONCLUSION: Acquired von Willebrand syndrome is common in hypertrophic cardiomyopathy. Gastrointestinal bleeding often recurs after endoscopic therapy, but may be relieved by structural cardiac repair.

Shear stress-associated acquired von Willebrand syndrome in patients with mitral regurgitation.

BACKGROUND: Mitral valve regurgitation is associated with an acquired hemostatic defect. OBJECTIVE: We sought to assess the prevalence and severity of acquired von Willebrand syndrome in patients with native valve mitral regurgitation (MR). PATIENTS/METHODS: Fifty-three patients were prospectively observed with bleeding questionnaires and laboratory tests when undergoing an echocardiographic assessment of MR. In patients referred for mitral valve surgery, testing was repeated postoperatively. RESULTS: Echocardiography identified 13 patients with mild MR, 14 with moderate MR, and 26 with severe MR. Among patients with mild, moderate or severe MR, loss of the highest molecular weight von Willebrand factor (VWF) multimers occurred in 8%, 64%, and 85%, respectively, median platelet function analyzer collagen ADP closure times (PFA-CADPs) were 84 s (interquartile range [IQR] 73-96 s), 156 s (IQR 104-181 s), and 190 s (IQR 157-279 s), respectively, and the ratios of VWF latex activity to antigen were 0.92 (IQR 0.83-0.97), 0.85 (IQR 0.76-0.89), and 0.79 (IQR 0.75-0.82), respectively (all P < 0.001). Nine patients reported clinically significant bleeding, and seven had intestinal angiodysplasia and transfusion-dependent gastrointestinal bleeding (Heyde syndrome), with the median number of transfusions required being 20 (IQR 10-33; range 4-50). In patients who underwent mitral valve repair (n = 13) or replacement (n = 7), all measures of VWF function reported above improved significantly. CONCLUSION: The high-shear environment of moderate to severe MR is sufficient to produce prevalent perturbations in VWF activity. Acquired von Willebrand syndrome may occur in this setting, and appears to be reversible with mitral valve surgery.

Pathophysiologic correlates of thromboembolism in nonvalvular atrial fibrillation: II. Dense spontaneous echocardiographic contrast (The Stroke Prevention in Atrial Fibrillation [SPAF-III] study).

We analyzed transesophageal echocardiograms from 772 participants in the Stroke Prevention in Atrial Fibrillation (SPAF-III) study, characterizing spontaneous echocardiographic contrast (SEC) in the left atrium or appendage as faint or dense. The association of dense SEC with stroke risk factors and anatomic, hemodynamic, and hemostatic parameters related to specific thromboembolic mechanisms was evaluated by multivariate analysis. Spontaneous echocardiographic contrast was present in 55% of patients and was dense in 13%. Age (odds ratio [OR] 2.4/decade, P <.001), constant atrial fibrillation (OR 6.9, P <.001), history of hypertension (OR 3. 2, P <.001), and current tobacco smoking (OR 2.6, P =.04) were independent clinical predictors of dense SEC. Multivariate analysis of clinical, echocardiographic, and hemostatic parameters yielded age as the sole independent clinical predictor of dense SEC (OR 2. 4/decade, P <.001). Other independent predictors were measures of left atrial/appendage flow dynamics, left atrial size (OR 2.4/cm diameter, M-mode, P <.001), atherosclerotic aortic plaque (OR 2.8, P =.002), and plasma fibrinogen >350 mg/dL (P <.001). Results were similar when SEC of any density was analyzed. In conclusion, SEC occurred in more than half of these patients with prospectively defined nonvalvular atrial fibrillation but was usually faint. Dense SEC was strongly associated with previously reported clinical predictors of stroke, linking them to thromboembolism through atrial stasis. Diverse pathophysiologic factors including atrial stasis, fibrinogen level, and aortic plaque influence SEC.

Aortic plaque in atrial fibrillation: prevalence, predictors, and thromboembolic implications.

BACKGROUND AND PURPOSE: Thoracic aortic plaque identified by transesophageal echocardiography heightens the risk of stroke associated with atrial fibrillation (AF). We sought to identify the prevalence, predictors, and implications of aortic plaque in patients with nonvalvular AF. METHODS: Thoracic aortic plaque was prospectively sought in 770 persons with AF with the use of transesophageal echocardiography and classified as simple or complex on the basis of thickness >/=4 mm, ulceration, or mobility. Clinical and echocardiographic features of thromboembolism were correlated by multivariate analysis. RESULTS: Aortic plaque was detected in 57% of the cohort, and complex plaque was detected in 25%. Both were found more frequently in the descending than in the proximal aorta. Potentially etiologic patient characteristics independently associated with complex plaque included advanced age, history of hypertension, diabetes, and past or present tobacco use. Comorbidities associated with aortic plaque were prior thromboembolism, increased pulse pressure, ischemic heart disease, stenosis or sclerosis of the aortic valve, mitral annular calcification (>10%), elevated serum creatinine concentration, spontaneous echo contrast in the left atrium or appendage, and left atrial appendage thrombus. The prevalence of complex plaque in patients aged <70 years with <10% mitral annular calcification, without ischemic heart disease, or without pulse pressure >/=65 mm Hg was 4% (95% CI, 1% to 6%). CONCLUSIONS: Aortic plaque is prevalent in patients with AF and is associated with atherosclerosis risk factors and with left atrial stasis or thrombosis, which are themselves independent stroke risk factors. Since the predominant location of complex plaque was in the descending aorta, the role of aortic plaque as a source of embolism in AF is uncertain.

Angiosarcoma of the aorta: report of a case and review of the literature.

Primary malignant tumors of the thoracic and abdominal aortas are extremely rare. In most cases, a diagnosis is established either postmortem or after an emergency operation for embolic complications. We present the case of a thoracic aortic angiosarcoma in a 71-year-old man who initially was seen with peripheral embolization. The management of these tumors and the world literature are reviewed.

Valvular and coronary heart disease. When is it time for surgical referral?

Decisions about when to refer patients for cardiac surgery remain dynamic in the face of rapidly advancing technology. Coexisting health problems obviously play an important role, as do the natural history of the cardiovascular disorder, the indications for surgery, and the risks associated with the operative procedure. Nonetheless, many patients can be offered the possibility of improved cardiovascular function and survival through cardiac interventions.

Valve replacement in aortic stenosis with preoperative mean gradient < 50 mmHg: hemodynamic outcome.

BACKGROUND AND AIMS OF THE STUDY: No prior studies have defined pre- versus postoperative hemodynamics of large numbers of patients with low mean transvalvular gradients. This was our objective. METHODS: Retrospective analysis was undertaken of preoperative and postoperative echo/Doppler data in 294 patients who underwent aortic valve replacement (AVR) for aortic stenosis (AS). Some 136 patients had a preoperative mean gradient of < 50 mmHg. The relationship of preoperative to pre- minus postoperative (delta) mean gradient (GRAD), peak valvular velocity (V2), left ventricular outflow tract velocity (V1), V1/V2 ratio, V2-V1, and aortic valve area (AVA) were plotted and analyzed such that a 'zero-benefit threshold' from surgery could be estimated. RESULTS: Strong relationships (r > 0.80) were noted for GRAD to delta GRAD, V2 to delta V2, and (V2-V1) to delta (V2-V1) with zero-benefit thresholds of 16 mmHg for GRAD, 2.6 m/s for V2 and 1.7 m/s for V2-V1. These thresholds were lower in patients who received homografts (11 mmHg, 2.2 m/s, and 1.1 m/s respectively), p < 0.02. The relationship of pre operative V1/V2 to delta V1/V2 and AVA-delta AVA were weaker (r = 0.52 and 0.33 respectively) with zero-benefit thresholds of 0.41 and 2.0 cm2. Among patients with depressed preoperative fractional shortening, improvement was confined to those without coexistent coronary artery disease. CONCLUSION: This analysis of thresholds of mean gradient benefit suggests that most patients with low gradient AS improve hemodynamically from AVR. The hemodynamic 'break-even' point averages a mean gradient of 16 mmHg.

Thoracoscopic obliteration of the left atrial appendage: potential for stroke reduction?

BACKGROUND: In a review of all relevant articles describing the site of left atrial thrombus in patients with atrial fibrillation, the thrombus was localized to the left atrial appendage in 43% of patients with rheumatic heart disease and in 91% of patients with nonrheumatic atrial fibrillation. This study was designed to test the feasibility of thoracoscopic obliteration of the left atrial appendage as a means of reducing thromboembolic stroke. METHODS: Thoracoscopic obliteration of the left atrial appendage was undertaken in 10 dogs, 5 with staples and 5 with an endoloop. Obliteration also was attempted in 8 fresh human cadavers. RESULTS: In all dogs, the appendage was rapidly obliterated (21.3 +/- 7.6 minutes) and confirmed at euthanasia at 11 weeks. In 3 cadavers, anatomic and disease factors prevented visualization of the left atrial appendage; in 1 the appendage tore, and in the remainder the appendage was obliterated. CONCLUSIONS: Obliteration of the left atrial appendage is feasible and may be considered as an additional surgical procedure to reduce stroke. The group of patients in whom it offers the greatest potential are those with atrial fibrillation deemed ineligible for warfarin, those without atrial thrombus and with a free pericardial and pleural space.

Appendage obliteration to reduce stroke in cardiac surgical patients with atrial fibrillation.

BACKGROUND: Left atrial appendage obliteration was historically ineffective for the prevention of postoperative stroke in patients with rheumatic atrial fibrillation who underwent operative mitral valvotomy. It is, however, a routine part of modern "curative" operations for nonrheumatic atrial fibrillation, such as the maze and corridor procedures. METHODS: To assess the potential of left atrial appendage obliteration to prevent stroke in nonrheumatic atrial fibrillation patients, we reviewed previous reports that identified the etiology of atrial fibrillation and evaluated the presence and location of left atrial thrombus by transesophageal echocardiography, autopsy, or operation. RESULTS: Twenty-three separate studies were reviewed, and 446 of 3,504 (13%) rheumatic atrial fibrillation patients, and 222 of 1,288 (17%) nonrheumatic atrial fibrillation patients had a documented left atrial thrombus. Anticoagulation status was variable and not controlled for. Thrombi were localized to, or were present in the left atrial appendage and extended into the left atrial cavity in 254 of 446 (57%) of patients with rheumatic atrial fibrillation. In contrast, 201 of 222 (91%) of nonrheumatic atrial fibrillation-related left atrial thrombi were isolated to, or originated in the left atrial appendage (p < 0.0001). CONCLUSIONS: These data suggest that left atrial appendage obliteration is a strategy of potential value for stroke prophylaxis in nonrheumatic atrial fibrillation.

Nocturnal dyspnea and atrial fibrillation predict Cheyne-Stokes respirations in patients with congestive heart failure.

BACKGROUND: Cheyne-Stokes respirations have frequently been noted in highly selected groups of patients with congestive heart failure, but their prevalence in an unselected population with congestive heart failure is undefined. METHODS: One hundred consecutive unselected outpatients or stable inpatients with clinical congestive heart failure encountered by three clinical cardiologists during a 6-month period were screened for Cheyne-Stokes respirations with overnight oximetry. RESULTS: The mean age (+/- SD) of the patients was 70 +/- 8.6 years. Of the 100 patients, 33% had had previous coronary bypass surgery, 77% were men, 57% had hypertension, and 32% had atrial fibrillation. The mean ejection fraction (+/- SD) was 34% +/- 13%. Periodic breathing was assessed qualitatively as Cheyne-Stokes respirations in 27% of patients, nonspecific sleep-disordered breathing (apneas and/or hypopneas) in 43%, and normal in 30%. For patients with Cheyne-Stokes respirations, patients with nonspecific sleep-disordered breathing, and normal subjects, the mean numbers of oxyhemoglobin desaturation events per hour were 24, 10, and 2, and the total numbers of desaturations of 4% or more that lasted less than 3 minutes were 172, 74, and 13. Independent predictors of Cheyne-Stokes respirations vs non-Cheyne-Stokes respirations included a history of nocturnal dyspnea (odds ratio, 4.00; 95% confidence interval, 1.33 to 12.04; P = .01) and atrial fibrillation (odds ratio, 3.24; 95% confidence interval, 1.21 to 8.48; P = .02). CONCLUSIONS: Cheyne-Stokes respirations and nonspecific sleep-disordered breathing are common in unselected patients with congestive heart failure, and Cheyne-Stokes respirations are predicted by a history of nocturnal dyspnea and the presence of atrial fibrillation. Techniques designed to modify the nocturnal breathing pattern of patients with congestive heart failure may be applicable to a large portion of the congestive heart failure population.

Effects of oral potassium supplements on upper gastrointestinal mucosa: multicenter clinical comparison of three formulations and placebo.

In a carefully controlled multicenter investigation of the effects of oral potassium chloride (KCl) supplements on the gastrointestinal mucosa, 120 healthy men with no endoscopically apparent gastrointestinal lesions were confined to a research ward for 18 days. By random assignment, they were given 60 mEq/day (20 mEq TID) of KCl as either a microencapsulated gelatin capsule, a wax/polymer matrix tablet, or a powder-in-liquid formulation or a placebo capsule for two weeks. All subjects were given glycopyrrolate concomitantly to delay gastric emptying. After treatment was completed, endoscopic examinations of the esophagus, stomach, and duodenum were performed and evaluated by specialists blinded to the particular treatment given. Mild to moderate gastrointestinal irritation, characterized by erythema and edema, was found with similar frequency in all four treatment groups. Two of 30 subjects given the microencapsulated KCl had a single erosion each. Single or multiple erosions were also observed in 14/30 men given the wax/polymer matrix tablet, in 7/30 given the powder, and in 1/30 given placebo. One subject given the wax/polymer matrix tablet had a gastric ulcer. The incidence of gastrointestinal injury with the microencapsulated form was significantly less (P less than 0.01) than that with the wax/polymer matrix tablet and was not significantly different from that seen with either the powder or placebo.

Comparison of the response of the renal blood supply to acetylcholine and to a calcium channel blocking agent, diltiazem, in the dog.

Several vasodilators, including acetylcholine, are capable of inducing maximal renal vasodilatation when infused into the renal artery. Despite substantial interest in the renal vascular response to calcium channel blocking agents, there has been no systematic comparison of any of these agents to an index vasodilator, such as acetylcholine. We compared the renal vascular angiographic response to acetylcholine and diltiazem, infused into the renal artery in graded dosage, in 14 dogs. In eight of the dogs renal blood flow was measured with an electromagnetic flowmeter. At peak, the acetylcholine-induced increase in renal blood flow (155 +/- 25 to 309 +/- 55 ml/min) slightly exceeded that induced by diltiazem (143 +/- 13 to 257 +/- 58 ml/min). A close correlation was found between the maximal blood flow increase induced by acetylcholine and by diltiazem (R = .95). Dilatation of the intrarenal arterial tree evident on the renal arteriogram was substantially less striking with diltiazem than with acetylcholine in these eight dogs. To ascertain the possible contributing role of the surgery required for blood flow measurement, the two agents were assessed in six additional dogs without blood flow measurement. In these six dogs diltiazem and acetylcholine induced essentially identical degrees of renal arterial vasodilatation. It is concluded that diltiazem, the calcium channel blocking agent, produces near maximal renal vasodilatation at the arteriolar level and that responses of more proximal elements of the renal arterial tree, visible during renal arteriography, are sensitive to the conditions of the experiment.