Aggregating platelets contract isolated canine pulmonary arteries by releasing 5-hydroxytryptamine.

To examine the effect of platelets and 5-hydroxytryptamine on pulmonary arterial smooth muscle, rings of canine pulmonary arteries, with and without endothelium, were studied under isometric conditions in physiological salt solution. 5-Hydroxytryptamine, but not the thromboxane-like endoperoxide analogue U-46619, produced concentration-dependent contractions of the rings with a maximum averaging 93% of that obtained with KC1. Autologous platelets in concentrations comparable to that in plasma caused contractions averaging 70% of the maximal responses to KC1. Solution withdrawn from baths containing platelet-contracted rings, but not the supernatant from nonaggregated platelets, also caused contraction. The serotonergic antagonists cyproheptadine, ketanserin, and methysergide caused concentration-dependent inhibition and eventually abolition of contractions evoked by platelets and 5-hydroxytryptamine. Phentolamine and prazosin produced significantly less inhibition of the contractile response to platelets. Pretreatment of the platelets with indomethacin or meclofenamate reduced thromboxane release but had no effect on platelet-induced contractions. Removal of the endothelium did not affect contractile responses to platelets or 5-hydroxy-tryptamine. These experiments demonstrate that in the canine pulmonary artery: (a) 5-hydroxytryptamine is the predominant mediator of the contractile response triggered by platelet aggregation; and (b) unlike in other blood vessels, the endothelium cannot curtail the contractile response to aggregating platelets.

The feasibility of utilizing the systolic pre-ejection interval as a determinant of pacing rate.

Rate-modulated pacing modes adjust the stimulus rate by responding to sensed alterations in physiologic indexes of metabolic demand. This study was designed to determine whether right ventricular pre-ejection interval, measured in patients by a prototype pacemaker system capable of tracking intraventricular volume, changes predictably with exercise and, if so, whether it can be used in an algorithm to vary heart rate appropriately. This system utilizes intraventricular electrical impedance measurements of injected microampere currents to determine intracavitary volume changes. Five pacemaker-dependent patients underwent temporary insertion of a tripolar electrode connected to an external device that sensed cardiac signals, generated an impedance wave form and produced stimuli at rates dependent on pre-ejection interval. Pre-ejection interval did not change as a result of variations in pacing rate itself (347 +/- 41 ms at 70 beats/min versus 321 +/- 19 ms at 130 beats/min), but consistently decreased during graded exercise (by 23% from baseline). During rate-modulated pacing based on pre-ejection interval, heart rate significantly increased during exercise compared with ventricular demand pacing (by 46 +/- 6 versus 7 +/- 6 beats/min, respectively), and increased appropriately during burst exercise. Thus, the pre-ejection interval appears to be a specific, reliable physiologic determinant of pacing rate during exertion, which may be applicable in implantable rate-modulated pacemakers.

Aortic and mitral valve incompetence: long-term follow-up (10 to 19 years) of patients treated with the Starr-Edwards prosthesis.

The long-term course (mean 15 years) of 336 patients with valvular incompetence who underwent Starr-Edwards ball valve implantation between 1962 and 1971 was reviewed. Eighteen patients (10%) with aortic valve replacement and 24 (16%) with mitral valve replacement died early postoperatively. Mortality remained high (31%) in the first 3 years after aortic valve replacement; it was highest (13%) in the first year after mitral valve replacement and then approached the normal rate. The most common mode of death was sudden death after aortic and cardiac failure after mitral valve replacement. At follow-up, 76% of survivors had improved symptomatically. Three instances of primary valve malfunction occurred. The probability of freedom from thromboembolism at 15 years postoperatively was 56% for aortic valve replacement and 52% for mitral valve replacement. The Starr-Edwards valve prosthesis is durable over prolonged follow-up period, but thromboembolism remains a persistent problem. Survival may be normal for patients surviving the early postoperative years.

Echocardiographic prediction of left ventricular function after correction of mitral regurgitation: results and clinical implications.

OBJECTIVES: This study attempted to determine the incidence, prognosis and predictability of postoperative left ventricular dysfunction in patients undergoing correction of mitral regurgitation. BACKGROUND: Left ventricular function in patients with mitral regurgitation is altered by loading conditions and is difficult to assess. Predictive value of preoperative variables on postoperative left ventricular function and the role of echocardiography are uncertain. METHODS: In 266 patients undergoing correction of mitral regurgitation between 1980 and 1989, left ventricular function was echocardiographically assessed preoperatively (within 6 months) and postoperatively (within 1 year). RESULTS: After correction of mitral regurgitation, left ventricular ejection fraction decreased significantly ([mean +/- SD] 50% +/- 14% vs. 58% +/- 13%, p < 0.0001). Postoperative left ventricular dysfunction (ejection fraction < 50%) was frequent (41% of patients) and carried a poor prognosis (at 8 years survival, 38% +/- 9% vs. 69% +/- 8%, p < 0.0001). Four preoperative echocardiographic variables showed good correlation with postoperative ejection fraction: preoperative ejection fraction (r = -0.70), systolic diameter (r = -0.63), diameter/thickness ratio (r = -0.64) and end-systolic wall stress (r = -0.62) (all p < 0.0001). With multivariate analysis, ejection fraction (p = 0.0001) and systolic diameter (p = 0.0005) were independent predictors of postoperative ejection fraction, and angiographic variables provided no incremental predictive power. In addition to echocardiographic variables, recent regurgitation, functional class and coronary artery disease were also independent predictors of postoperative ejection fraction. CONCLUSIONS: After surgical correction of mitral regurgitation, left ventricular dysfunction is frequent and carries a poor prognosis. Postoperative ejection fraction can be predicted by echocardiographic preoperative ejection fraction and systolic diameter. Recent onset of regurgitation, mild or no symptoms, and absence of coronary artery disease are independent and favorable predictors of postoperative ejection fraction. These results should lead to consideration of surgical correction at an earlier stage.

Lone atrial fibrillation in elderly persons: a marker for cardiovascular risk.

BACKGROUND: The risk of stroke in persons aged 60 years and younger with lone atrial fibrillation (LAF) is no greater than in the general population. The effect of older age on the risk of stroke in persons with LAF is less well established. PARTICIPANTS AND METHODS: The risk of stroke in persons with LAF and without substantial comorbidities was examined in a population-based study at a single institution in Olmsted County, Minnesota, and compared with that in an age- and sex-matched population. The mean age was 74 years (range, 61-97 years). The median duration of follow-up was 9.6 years until death or last follow-up. RESULTS: Of 55 patients, 26 had 31 cardiovascular events during follow-up, occurring a median of 5.1 years after diagnosis (range, 0.7-18 years). Of 11 cerebrovascular events, 6 were transient ischemic attacks and 5 were strokes. The event rates (percentage per person-year) were 0.9% for stroke, 1.1% for transient cerebral ischemia, and 2.6% for myocardial infarction, for a total cardiovascular event rate of 5.0% per person-year. The corresponding rates for the age- and sex-matched control group were 0.2%, 0%, and 1.1%, for a total of 1.3% per person-year. The incidence of total cardiovascular events was significantly greater (P< .01) in those with LAF, although there was no difference in survival. CONCLUSION: Lone atrial fibrillation occurring after age 60 years is a risk marker for a substantial increase in cardiovascular events that warrants consideration for antithrombotic therapy.

Long-term endocardial atrial pacing in children with postoperative bradycardia-tachycardia syndrome and limited ventricular access.

Permanent pacing in children, including those with postoperative bradycardia-tachycardia syndrome has been compromised by the availability of pulse generators, electrode leads and implantation techniques designed for the adult patient. Recent technologic improvements and simplified implantation techniques have reduced many of these barriers and have made endocardial as well as epicardial ventricular pacing more feasible. However, in some children, ventricular pacing may be impeded by anatomic abnormalities due to congenital anomalies or prior cardiac operations. In these instances, endocardial atrial pacing may provide an alternative therapeutic approach in selected patients. This report describes the use of endocardial atrial demand pacing in four children with postoperatively bradycardia-tachycardia syndrome and restricted ventricular access. This approach controls symptomatic bradycardia, helps prevent and convert paroxysmal intraatrial tachycardia and overcomes the problems of limited ventricular access.

Value of a Doppler-derived index combining systolic and diastolic time intervals in predicting outcome in primary pulmonary hypertension.

Primary pulmonary hypertension is characterized by elevated pulmonary arterial pressure and vascular resistance, frequently producing right heart failure and death. Therefore, the Doppler right ventricular (RV) index, which is a measure of global RV function, could be a useful predictor of outcome in primary pulmonary hypertension. The Doppler RV index, defined as the sum of isovolumic contraction time and isovolumic relaxation time divided by ejection time, was retrospectively measured in 53 patients (38 women, aged 45 +/- 14 years) with primary pulmonary hypertension. Ejection time was measured from the pulmonary outflow velocity signal. The sum of isovolumic contraction time and isovolumic relaxation time was obtained by subtracting ejection time from the duration of tricuspid regurgitation. The Doppler RV index tended to be elevated (median 0.83) compared with normal ranges. Normal Doppler RV index was 0.28 +/- 0.04. After a mean follow-up duration of 2.9 years, 4 patients underwent lung transplantation and 30 patients died; the cause was cardiac in 28, noncardiac in 1, and uncertain in 1. Univariately, the Doppler RV index (chi-square 20.7, p <0.0001), severity of tricuspid regurgitation (chi-square 8.2, p = 0.004), treatment with calcium blockers (chi-square 6.6, p = 0.01), heart rate (chi-square 5.1, p = 0.02), and symptom status (chi-square 4.9, p = 0.03) were associated with adverse outcome (cardiac deaths and lung transplantation). However, only the Doppler RV index and treatment with calcium blockers were independent predictors within the multivariate model. Our results indicate that the Doppler RV index is a useful predictor of adverse outcome in patients with primary pulmonary hypertension.

Safety and efficacy of epoprostenol in patients with severe congestive heart failure. Epoprostenol Multicenter Research Group.

Patients with advanced heart failure often remain severely symptomatic and have a high mortality rate despite currently available therapy. We studied the safety and efficacy of a new approach to the patient with refractory heart failure: continuous intravenous treatment via a portable infusion pump with epoprostenol (prostacyclin), a potent pulmonary and systemic vasodilator. A group of 33 patients with severe heart failure (64% New York Heart Association class IV and 36% class III) and profound ventricular dysfunction (median left ventricular ejection fraction, 0.15)--despite prior treatment with diuretics (100%), digitalis (91%), angiotensin-converting enzyme inhibitors (85%), and dobutamine (30%)--underwent a baseline 6-minute walk test prior to dose titration with epoprostenol during invasive hemodynamic monitoring. Subjects responding during the dose titration were randomized, on an open basis, to receive either continuous epoprostenol infusion via an indwelling central venous catheter plus conventional therapy or conventional therapy alone for 12 weeks. The initial dose-ranging study with epoprostenol produced a significant decline in systemic and pulmonary vascular resistance and a substantial increase in cardiac index despite a fall in pulmonary capillary wedge pressure. Symptoms related to vasodilation were noted within the first week after randomization to epoprostenol in 9 of 16 patients but resolved with adjustment of the infusion and concomitant medications in all but one subject. Dose adjustments during the chronic epoprostenol infusion were infrequent after the first week and complications related to the drug delivery system were rare. The change in distance walked from baseline to the last available 6-minute walk test was significantly greater in patients who received epoprostenol compared with patients assigned to standard therapy (72 +/- 40 vs -39 +/- 32 m, mean +/- SEM; p = 0.033). Our study suggests that long-term intravenous infusion of epoprostenol is feasible in patients with severe heart failure and our hemodynamic and functional results suggest clinical benefit as well. However, until recent results indicating an adverse effect of epoprostenol on survival are fully evaluated, the role of this drug in the treatment of advanced heart failure will remain uncertain.

Techniques of immunosuppression after cardiac transplantation.

Modulation of the normal immune response is the major challenge for successful organ transplantation. Cardiac allograft rejection is primarily the result of activation of T cells. Most currently used immunosuppressive agents mainly affect the T-cell-mediated limb of the immune system. Immunosuppressive strategies can be considered to have three goals: (1) prophylaxis against rejection early after cardiac transplantation, (2) long-term maintenance prophylaxis, and (3) treatment of acute rejection. The extent of immunosuppression needed varies with the time after transplantation and the rejection profile of the individual patient. The goal is to provide sufficient immunosuppression to retard rejection without causing undesirable side effects, including infection and neoplasms.

Vasodilator therapy for primary pulmonary hypertension.

Primary pulmonary hypertension is an uncommon but serious disease that often results in debilitating symptoms and early death. One approach to treatment has been to attempt reduction of pulmonary arterial pressure and right ventricular afterload by using vasodilator agents to decrease pulmonary arteriolar resistance. Use of a variety of vasodilators has yielded only limited and infrequent success. Although an occasional patient may respond to vasodilator therapy with improved pulmonary hemodynamics and symptomatic status, most patients do not. Reasons for lack of success include the presence of predominantly fixed vascular obstructive disease rather than active vasoconstriction, inexorable progression of disease, and adverse nonpulmonary vascular effects of vasodilators, such as systemic hypotension. Because of occasional beneficial responses, a trial of vasodilators is warranted in patients with primary pulmonary hypertension. Initiation of drug therapy should be undertaken during hemodynamic monitoring in order to allow assessment of response, identification of adverse effects, and comparison of different agents. No vasodilator is clearly superior in primary pulmonary hypertension.

Noninvasive conversion of a fixed-rate demand pacemaker to activity mode: a method for assessing the clinical effect of rate-responsiveness.

Some patients with fixed-rate demand pacemakers may benefit from conversion to a rate-responsive pacing system. In this report, we describe a technique by which the effect of rate-responsive pacing can be assessed before replacing the pacemaker system. An externally positioned activity-mode physiologic pulse generator was used to drive a previously implanted ventricular demand pacemaker programmed to the triggered mode. Comparison of exercise capacity under both conditions suggested a substantial benefit from rate-responsiveness.

Cardiac sarcoidosis: a potentially treatable form of myocarditis.

A 39-year-old woman had a 2-year history of heart block, which had necessitated pacemaker implantation, and a 6-month history of heart failure. Endomyocardial biopsy specimens initially revealed lymphocytic myocarditis but subsequently showed giant cell myocarditis. She died suddenly, and autopsy disclosed extensive cardiac sarcoidosis with minimal extracardiac involvement. Cardiac sarcoidosis may be difficult to diagnose clinically because the extent of cardiac and the extent of extracardiac involvement tend to be inversely related. Endomyocardial biopsy may be helpful in diagnosing such cases.

Selection of optimal drug therapy for the patient with angina pectoris.

The development of new drugs, especially beta-blocking and calcium entry-blocking agents, has greatly facilitated the medical treatment of angina pectoris. The specific needs of each patient should dictate the appropriate treatment of angina pectoris. Angina may occur in patients who have various concomitant disorders such as hypertension, diabetes mellitus, peripheral vascular disease, chronic obstructive pulmonary disease, or arrhythmias, and the physician must take these factors into account when a drug regimen is prescribed. Individual drugs should be chosen on the basis of specifically desired pharmacologic effects, and the dosages should be gradually adjusted according to the patient's response. Although a therapeutic regimen should be selected primarily on the basis of efficacy, the physician must also attempt to recommend a simple and cost-effective program.

Carotid sinus hypersensitivity and syncope.

The patient with a hypersensitive carotid sinus reflex and syncope may pose special challenges in evaluation and treatment. Specifically, although the finding of carotid sinus hypersensitivity may indeed indicate an exaggerated vagal tone that causes syncope, it may also be a chance association in a patient with syncope due to another cause. Careful clinical and electrophysiologic testing may be needed to distinguish these two possibilities. Furthermore, the need for drug therapy or cardiac pacing (or both) must be determined on an individual basis, depending on the relative contributions of cardioinhibitory and vasodepressor components to the patient's symptoms and also on the degree of patient limitation.

Chronic aortic regurgitation: indications for operation--1988.

Timing of operation in a patient with severe aortic regurgitation is a difficult and controversial decision, especially when the patient is asymptomatic or minimally symptomatic. A rational decision can be made when the pathophysiologic features of aortic regurgitation and the natural history of medically treated patients are understood and the benefits and risks associated with aortic valve replacement are known. Proper interpretation of the literature involving echocardiography and nuclear cardiology is essential, as is consideration of the constantly changing surgical techniques and results. Aortic valve replacement should be recommended for those patients with chronic aortic regurgitation who are severely symptomatic (New York Heart Association Functional Class III or IV), in order to ameliorate symptoms and increase longevity. In asymptomatic or minimally symptomatic patients, close continued serial follow-up is necessary in order to detect the onset of resting left ventricular dysfunction and to recommend the optimal timing for surgical intervention.

The clinical use of verapamil.

Verapamil was the first of a class of agents known as calcium entry blockers to be released for clinical use in the United States. Although only recently approved by the Food and Drug Administration (August 1981), verapamil has been used clinically in countries other than the United States for more than 15 years and has been extensively studied experimentally. Because it is now available, it is necessary for physicians to have a working understanding of its pharmacologic effects and clinical applications. Accordingly, we are reviewing reported experience with verapamil and results of its use at the Mayo Clinic.

Extraction of the Telectronics Accufix 330-801 atrial lead: the Mayo Clinic experience.

OBJECTIVE: To document a cumulative experience with removal of the Telectronics 330-801 Accufix atrial lead after it was withdrawn from the market. DESIGN: We reviewed our results with 96 attempted lead extraction procedures through Dec. 1, 1995. MATERIAL AND METHODS: All patients underwent preoperative assessment, including fluoroscopic screening of the lead. Patients had blood typing and screening done before the extraction procedure, and extractions were performed with cardiac surgical intervention available. Pacing dependence was assessed to determine the need for temporary pacing. RESULTS: The mean patient age was 65.7 +/- 1.6 years and the mean duration of lead implantation was 31.0 +/- 1.4 months. Of the 96 lead extractions attempted, 94 were successful. Of the 96 cases, the retention wires were normal in 29, fractured without protrusion in 34, and fractured with protrusion in 33. Fifty-three leads were removed with use of simple traction only, and seven leads were removed by using a locking stylet and telescoping sheaths. The Cook workstation was used in the removal of 32 leads through the femoral vein; in 1 of these 32 patients, the retention wire was removed before lead extraction. The retention wire was removed but the lead was left intact in one patient. One lead was removed during an opertive maze procedure. Associated complications were minimal. CONCLUSION: Although lead extraction is a potentially fatal procedure, the Telectronics 330-801 Accufix atrial lead can be extracted safely with minimal morbidity when performed by experienced personnel.

Obesity drugs and the heart.

Appetite suppressant-related pulmonary hypertension and valvular heart disease are established disorders. Currently, the mechanism of these disorders is not certain. An estimated 6 million Americans and 70 million persons worldwide have been exposed to fenfluramine and dexfenfluramine. The clinical significance and long-term prognosis of cardiovascular effects and, thus, the potential public health effect of these disorders are not known. Longitudinal studies are required to further evaluate these disease processes. In addition, although isolated cases of regression of pulmonary hypertension and valve disease have been reported after the cessation of appetite suppressant therapy, the natural history remains uncertain.

Permanent cardiac pacing after the Fontan procedure.

Permanent cardiac pacing after a Fontan procedure is complicated by complex cardiovascular anatomy. Of 332 patients undergoing the Fontan procedure at the Mayo Clinic, we evaluated 15 who postoperatively required permanent pacing (mean age 16.5 years, range 4 to 31 years). Underlying congenital cardiac defects included univentricular heart in nine patients, double-outlet right ventricle in three, and tricuspid atresia in three. The indication for pacing was postoperative heart block in seven patients, congenital heart block in five, postoperative sick sinus syndrome in two, and heart block because of previous operation in one. Pacemakers were implanted immediately postoperatively in 11 patients and 12 to 57 months later in four patients. VVI systems were used in nine patients, DDD in four, AAI in one, and a Medtronic Activitrax VVI in one. All ventricular leads were epicardial. Four atrial leads were transvenous endocardial and one was epicardial. Three patients died 4, 9, and 69 months later of causes unrelated to pacing. Among the 12 survivors, mean follow-up was 34 months (range 1 to 107 months). Two patients had a total of three episodes of loss of ventricular capture because of increased chronic thresholds. Our current approach to pacing after a Fontan procedure includes (1) intraoperative placement of temporary atrial and ventricular electrodes, (2) intraoperative attachment of a permanent ventricular epicardial lead for congenital or surgically induced high-grade atrioventricular block, (3) postoperative insertion of transvenous atrial leads if dual-chamber pacing is indicated, and (4) use of programmable pulse generators with high output capability.

Intrapulmonary shunting in primary pulmonary hypertension: an observation in two patients treated with epoprostenol sodium.

Continuous intravenous infusion of epoprostenol sodium in selected patients with primary pulmonary hypertension improves symptoms and survival. This report describes two patients with primary pulmonary hypertension treated with epoprostenol in whom intrapulmonary shunting and severe hypoxemia occurred. Intrapulmonary shunting was confirmed by contrast echocardiography showing delayed appearance of bubbles in the left cardiac chambers after peripheral venous injection of agitated saline solution.