ABSTRACT
The goals of evaluating pulmonary hypertension are detection, definition of severity and the nature of the hemodynamic lesion and its consequences, diagnosis of causal or associated conditions, and determination of optimal therapy. These objectives are reliably achieved by a disciplined approach employing multiple diagnostic tools. This chapter outlines the fundamental background and guidelines for assessing pulmonary hypertension, including consideration of several new and less frequently used methods to elucidate the physiologic mechanism. Since early detection and treatment may improve outcome, screening higher risk populations and a diagnostic approach to the milder spectrum of pulmonary hypertension is also addressed.
Subject(s)
Hypertension, Pulmonary/diagnosis , Algorithms , Cardiac Catheterization , Diagnosis, Differential , Echocardiography, Doppler , Echocardiography, Transesophageal , Humans , Hypertension, Pulmonary/diagnostic imaging , Hypertension, Pulmonary/physiopathology , Magnetic Resonance Imaging , Prognosis , Pulmonary Artery/physiopathology , Pulmonary Valve/physiopathology , Respiratory Function Tests , Vascular Resistance , Ventilation-Perfusion Ratio , Ventricular Function, RightABSTRACT
OBJECTIVE: To determine whether children with pallid breath-holding spells associated with bradycardia can be treated safely and successfully with permanent pacemaker implantation. METHODS: The records of pediatric patients who had apparent breath-holding spells and associated bradycardia and were treated with permanent pacemaker implantation were reviewed. RESULTS: Ten pediatric patients with apparent breath-holding spells associated with bradycardia were treated with a permanent ventricular demand pacemaker at the Mayo Clinic between 1985 and 1995. Patients had onset of symptoms between ages 6 days and 12 months and presented for evaluation between ages 12 months and 5 years. Duration of spells was 15 seconds to 10 minutes. Medications to prevent spells were unsuccessful. Electrocardiograms documented asystolic pauses of 1.7 to 24 seconds (mean: 11.9 seconds). Permanent ventricular demand pacemakers were implanted at 10 months to 5 years of age (median: 14.5 months): 9 endocardial and 1 epicardial. Three patients required pacemaker revision. At follow-up of 38 to 170 months (median: 65.5), 5 patients had complete resolution of spells, 2 had only mild color change without loss of consciousness or seizure activity, and 3 continued to have minor brief spells. CONCLUSIONS: Permanent pacemaker therapy for children with pallid breath-holding spells associated with severe bradycardia is safe, efficacious, and warranted.
Subject(s)
Apnea/complications , Bradycardia/etiology , Bradycardia/therapy , Pacemaker, Artificial , Bradycardia/diagnosis , Child , Child, Preschool , Cyanosis/complications , Electrocardiography , European Union , Female , Humans , Infant , Infant, Newborn , Male , Prostheses and Implants , Seizures/complications , Unconsciousness/complicationsABSTRACT
BACKGROUND: Pulmonary hypertension is a progressive and often fatal complication of the scleroderma spectrum of disease for which no treatment has been proven effective in a randomized trial. OBJECTIVE: To determine the effect of epoprostenol on pulmonary hypertension secondary to the scleroderma spectrum of disease. DESIGN: Randomized, open-label, controlled trial. SETTING: 17 pulmonary hypertension referral centers. PATIENTS: 111 patients with moderate to severe pulmonary hypertension. INTERVENTION: Epoprostenol plus conventional therapy or conventional therapy alone. MEASUREMENTS: The primary outcome measure was exercise capacity. Other measures were cardiopulmonary hemodynamics, signs and symptoms of pulmonary hypertension and scleroderma, and survival. RESULTS: Exercise capacity improved with epoprostenol (median distance walked in 6 minutes, 316 m at 12 weeks compared with 270 m at baseline) but decreased with conventional therapy (192 m at 12 weeks compared with 240 m at baseline). The difference between treatment groups in the median distance walked at week 12 was 108 m (95% CI, 55.2 m to 180.0 m) (P < 0.001). Hemodynamics improved at 12 weeks with epoprostenol. The changes in mean pulmonary artery pressure for the epoprostenol and conventional therapy groups were -5.0 and 0.9 mm Hg, respectively (difference, -6.0 mm Hg [CI, -9.0 to -3.0 mm Hg), and the mean changes in pulmonary vascular resistance were -4.6 and 0.9 mm Hg/L per minute, respectively (difference, -5.5 mm Hg/L per minute [CI, -7.3 to -3.7 mm Hg/L per minute). Twenty-one patients treated with epoprostenol and no patients receiving conventional therapy showed improved New York Heart Association functional class. Borg Dyspnea Scores and Dyspnea-Fatigue Ratings improved in the epoprostenol group. Trends toward greater improvement in severity of the Raynaud phenomenon and fewer new digital ulcers were seen in the epoprostenol group. Four patients in the epoprostenol group and five in the conventional therapy group died (P value not significant). Side effects of epoprostenol therapy included jaw pain, nausea, and anorexia. Adverse events related to the epoprostenol delivery system included sepsis, cellulitis, hemorrhage, and pneumothorax (4% incidence for each condition). CONCLUSIONS: Continuous epoprostenol therapy improves exercise capacity and cardiopulmonary hemodynamics in patients with pulmonary hypertension due to the scleroderma spectrum of disease.
Subject(s)
Antihypertensive Agents/administration & dosage , Epoprostenol/administration & dosage , Hypertension, Pulmonary/drug therapy , Hypertension, Pulmonary/etiology , Scleroderma, Systemic/complications , Adult , Aged , Analysis of Variance , Antihypertensive Agents/adverse effects , Epoprostenol/adverse effects , Exercise Tolerance/drug effects , Female , Gastrointestinal Diseases/chemically induced , Hemodynamics/drug effects , Humans , Hypertension, Pulmonary/physiopathology , Infusion Pumps/adverse effects , Infusions, Intravenous/adverse effects , Jaw , Male , Middle Aged , Pain/chemically induced , Statistics, NonparametricABSTRACT
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.
Subject(s)
Appetite Depressants/adverse effects , Heart Valve Diseases/chemically induced , Hypertension, Pulmonary/chemically induced , Fenfluramine/adverse effects , Humans , Phentermine/adverse effectsABSTRACT
Pulmonary hypertension associated with increased pulmonary vascular resistance (PVR) and occurring in the setting of portal hypertension is referred to as "portopulmonary hypertension." Intravenous epoprostenol (prostacyclin) is a potent pulmonary and systemic vasodilator with antithrombotic properties. It can decrease PVR and pulmonary artery pressure in patients with primary (idiopathic) pulmonary hypertension. Using right-heart catheterization, we evaluated the acute pulmonary hemodynamic effects of intravenous epoprostenol in patients with moderate to severe pulmonary hypertension (mean pulmonary artery pressure [MPAP] >/=35 mm Hg) associated with clinical manifestations of portal hypertension. Effects of long-term infusion of epoprostenol were also evaluated. We studied 15 consecutive patients with portopulmonary hypertension; 14 underwent acute administration of epoprostenol, and no significant side effects were noted. Ten patients received continuous epoprostenol (range, 8 days-30 months). Acute changes in PVR (-34% +/- 18%), MPAP (-16% +/- 10%), and cardiac output (CO) (+21 +/- 18%), were statistically significant (P <.01). Long-term use of epoprostenol further lowered PVR (-47% +/- 12% from baseline and -31% +/- 22% from the acute change; P <.05) in the 6 patients restudied by right-heart catheterization. Death occurred in 6 of 10 (60%) of those receiving long-term epoprostenol. In moderate to severe portopulmonary hypertension, intravenous epoprostenol resulted in a significant improvement (both acute and long-term) in PVR, MPAP, and CO. Potential adverse effects on portal hypertension and implications for orthotopic liver transplantation (OLT), however, require further study.
Subject(s)
Epoprostenol/therapeutic use , Hypertension, Pulmonary/drug therapy , Lung/drug effects , Adult , Aged , Female , Hemodynamics/drug effects , Humans , Hypertension, Pulmonary/physiopathology , Liver Transplantation , Lung/physiopathology , Male , Middle Aged , Prospective StudiesABSTRACT
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.
Subject(s)
Atrial Fibrillation/complications , Cardiovascular Diseases/etiology , Aged , Aged, 80 and over , Atrial Fibrillation/drug therapy , Cardiovascular Diseases/prevention & control , Case-Control Studies , Cerebrovascular Disorders/etiology , Female , Fibrinolytic Agents/therapeutic use , Humans , Incidence , Middle Aged , MinnesotaABSTRACT
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.
Subject(s)
Antihypertensive Agents/therapeutic use , Epoprostenol/therapeutic use , Hypertension, Pulmonary/physiopathology , Pulmonary Circulation/physiology , Antihypertensive Agents/administration & dosage , Contrast Media/administration & dosage , Echocardiography , Epoprostenol/administration & dosage , Hemangioma, Capillary/pathology , Humans , Hypertension, Pulmonary/drug therapy , Hypoxia/etiology , Infusions, Intravenous , Injections, Intravenous , Lung Neoplasms/pathology , Lung Transplantation , Male , Middle Aged , Pulmonary Circulation/drug effects , Pulmonary Fibrosis/pathology , Sodium Chloride/administration & dosageABSTRACT
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.
Subject(s)
Echocardiography, Doppler , Hypertension, Pulmonary/diagnostic imaging , Hypertension, Pulmonary/mortality , Myocardial Contraction , Adult , Cardiac Catheterization , Female , Humans , Male , Middle Aged , Multivariate Analysis , Predictive Value of Tests , Retrospective Studies , Survival AnalysisSubject(s)
Hypertension, Portal/physiopathology , Hypertension, Pulmonary/physiopathology , Blood Pressure , Cardiac Output , Humans , Liver Diseases/complications , Liver Diseases/physiopathology , Liver Diseases/surgery , Liver Transplantation/physiology , Prognosis , Pulmonary Artery , Pulmonary Wedge Pressure , Vascular Resistance , Ventricular Dysfunction, Right/physiopathologyABSTRACT
BACKGROUND: Fenfluramine and phentermine have been individually approved as anorectic agents by the Food and Drug Administration (FDA). When used in combination the drugs may be just as effective as either drug alone, with the added advantages of the need for lower doses of each agent and perhaps fewer side effects. Although the combination has not been approved by the FDA, in 1996 the total number of prescriptions in the United States for fenfluramine and phentermine exceeded 18 million. METHODS: We identified valvular heart disease in 24 women treated with fenfluramine-phentermine who had no history of cardiac disease. The women presented with cardiovascular symptoms or a heart murmur. As increasing numbers of these patients with similar clinical features were identified, there appeared to be an association between these features and fenfluramine-phentermine therapy. RESULTS: Twenty-four women (mean [+/-SD] age, 44+/-8 years) were evaluated 12.3+/-7.1 months after the initiation of fenfluramine-phentermine therapy. Echocardiography demonstrated unusual valvular morphology and regurgitation in all patients. Both right-sided and left-sided heart valves were involved. Eight women also had newly documented pulmonary hypertension. To date, cardiac surgical intervention has been required in five patients. The heart valves had a glistening white appearance. Histopathological findings included plaque-like encasement of the leaflets and chordal structures with intact valve architecture. The histopathological features were identical to those seen in carcinoid or ergotamine-induced valve disease. CONCLUSIONS: These cases arouse concern that fenfluramine-phentermine therapy may be associated with valvular heart disease. Candidates for fenfluramine-phentermine therapy should be informed about serious potential adverse effects, including pulmonary hypertension and valvular heart disease.
Subject(s)
Appetite Depressants/adverse effects , Fenfluramine/adverse effects , Heart Valve Diseases/chemically induced , Phentermine/adverse effects , Adult , Aortic Valve Insufficiency/chemically induced , Aortic Valve Insufficiency/diagnostic imaging , Drug Combinations , Female , Heart Valve Diseases/complications , Heart Valve Diseases/diagnostic imaging , Heart Valve Diseases/pathology , Humans , Hypertension, Pulmonary/chemically induced , Hypertension, Pulmonary/complications , Middle Aged , Mitral Valve/pathology , Mitral Valve Insufficiency/chemically induced , Mitral Valve Insufficiency/diagnostic imaging , Mitral Valve Insufficiency/pathology , Tricuspid Valve Insufficiency/chemically induced , Tricuspid Valve Insufficiency/diagnostic imaging , UltrasonographyABSTRACT
BACKGROUND: Right heart failure is an important cause of morbidity and mortality in primary pulmonary hypertension. In a recent prospective, randomized study of severely symptomatic patients, treatment with prostacyclin (epoprostenol) produced improvements in hemodynamics, quality of life, and survival. This article describes the echocardiographic characteristics of participants in this trial; the relationship of echocardiographic variables to hemodynamic parameters, exercise capacity, and quality of life; and the echocardiographic changes associated with prostacyclin therapy. METHODS AND RESULTS: The 81 patients enrolled in this multicenter trial were randomized to treatment with a long-term infusion of prostacyclin in addition to conventional therapy (n = 41) or conventional therapy alone (n = 40) for 12 weeks. Echocardiograms and assessments of hemodynamics, exercise capacity, and quality of life were performed before and after the treatment phase. On baseline evaluation, patients had marked right ventricular dilatation and dysfunction, abnormal septal curvature, and significant tricuspid regurgitation with a high regurgitant velocity. Pericardial effusions were common. More pronounced abnormalities in right heart structure and function were associated with higher pulmonary arterial and mean right atrial pressures, lower cardiac index, and impaired exercise capacity but had no predictable relationship to quality-of-life indicators. The 12-week infusion of prostacyclin had beneficial effects on right ventricular size, curvature of the interventricular septum, and maximal tricuspid regurgitant jet velocity. CONCLUSIONS: The echocardiographic manifestations of severe primary pulmonary hypertension reflect abnormalities in hemodynamics and exercise capacity. Prostacyclin has beneficial effects on right heart structure and function that may contribute to the clinical improvement and prolonged survival observed with this drug.
Subject(s)
Antihypertensive Agents/therapeutic use , Echocardiography , Epoprostenol/therapeutic use , Hypertension, Pulmonary/drug therapy , Hypertension, Pulmonary/physiopathology , Ventricular Function, Right/drug effects , Adult , Blood Pressure , Female , Heart/drug effects , Hemodynamics , Humans , Male , Physical Fitness , Quality of Life , SystoleABSTRACT
Echocardiographic assessment of right ventricular function remains difficult and challenging. However, there is considerable clinical need for a simple, reproducible, and reliable parameter of right ventricular function in patients with right-sided heart disease. The purpose of this study was to assess the clinical value of a Doppler-derived index, combining systolic and diastolic intervals of the right cycle, in assessing global right ventricular function in patients with primary pulmonary hypertension. The study population comprised 26 consecutive patients with primary pulmonary hypertension and 37 age-matched normal subjects. The sum of right ventricular isovolumetric contraction time and isovolumetric relaxation time was obtained by subtracting right ventricular ejection time from the interval between cessation and onset of the tricuspid inflow velocities with pulsed-wave Doppler echocardiography. An index of combined right ventricular systolic and diastolic function was obtained by dividing the sum of both isovolumetric intervals by ejection time. The index was compared with available parameters of systolic or diastolic function, clinical symptoms, and survival. Right ventricular isovolumetric contraction time and isovolumetric relaxation time were prolonged significantly in patients with primary pulmonary hypertension (85 +/- 41 msec and 135 +/- 43 msec) compared with normal subjects (38 +/- 7 msec and 49 +/- 9 msec, respectively; p < 0.001). Ejection time was shortened significantly in patients with pulmonary hypertension (241 +/- 43 msec versus normal [322 +/- 21 msec]; p < 0.001). However, the index was the single most powerful variable to discriminate patients with primary pulmonary hypertension from normal subjects (0.93 +/- 0.34 versus 0.28 +/- 0.04; p < 0.001) and was the strongest predictor of clinical status and survival. The index was not significantly affected by heart rate, right ventricular pressure, right ventricular dilation, or tricuspid regurgitation. It is well known that right ventricular systolic and diastolic dysfunction coexist in patients with primary pulmonary hypertension. This article reports the use of an easily obtainable Doppler-derived index that combines elements of systolic and diastolic function. This index appears to be a useful noninvasive means that correlates with symptoms and survival in patients with primary pulmonary hypertension.
Subject(s)
Echocardiography, Doppler , Hypertension, Pulmonary/diagnostic imaging , Hypertension, Pulmonary/physiopathology , Myocardial Contraction , Ventricular Function, Right , Adult , Female , Heart Rate , Hemodynamics , Humans , Hypertension, Pulmonary/mortality , Male , Middle Aged , Survival Rate , Ventricular PressureABSTRACT
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.
Subject(s)
Electrodes , Pacemaker, Artificial , Aged , Humans , Retrospective StudiesABSTRACT
Coronary endothelial dysfunction has been demonstrated in patients with symptomatic heart failure. Furthermore the endothelium has been implicated in the pathogensis of cardiomyopathy in patients with normal coronary angiograms and no other known causes of heart failure. Herein we describe an asymptomatic patient with an early cardiomyopathy and abnormal coronary endothelial function. There was no evidence for coronary disease by both angiography and intravascular ultrasound. Epicardial coronary artery vasoconstriction and a decrease in coronary blood flow was noted during the intracoronary infusion of graded concentrations of acetylcholine. This case demonstrates that endothelial dysfunction occurs in the setting of asymptomatic left ventricular dysfunction and highlights the potential importance of the endothelium in the early development of heart failure.
Subject(s)
Coronary Circulation/physiology , Endothelium, Vascular/physiopathology , Ventricular Dysfunction, Left/physiopathology , Acetylcholine , Cardiomyopathy, Dilated/diagnosis , Cardiomyopathy, Dilated/physiopathology , Coronary Angiography , Female , Heart Failure/diagnosis , Heart Failure/physiopathology , Humans , Middle Aged , Ultrasonography, Interventional , Vascular Resistance/drug effects , Vascular Resistance/physiology , Ventricular Dysfunction, Left/diagnosis , Ventricular Function, Left/drug effects , Ventricular Function, Left/physiologyABSTRACT
BACKGROUND: Primary pulmonary hypertension is a progressive disease for which no treatment has been shown in a prospective, randomized trial to improve survival. METHODS: We conducted a 12-week prospective, randomized, multicenter open trial comparing the effects of the continuous intravenous infusion of epoprostenol (formerly called prostacyclin) plus conventional therapy with those of conventional therapy alone in 81 patients with severe primary pulmonary hypertension (New York Heart Association functional class III or IV). RESULTS: Exercise capacity was improved in the 41 patients treated with epoprostenol (median distance walked in six minutes, 362 m at 12 weeks vs. 315 m at base line), but it decreased in the 40 patients treated with conventional therapy alone (204 m at 12 weeks vs. 270 m at base line; P < 0.002 for the comparison of the treatment groups). Indexes of the quality of life were improved only in the epoprostenol group (P < 0.01). Hemodynamics improved at 12 weeks in the epoprostenol-treated patients. The changes in mean pulmonary-artery pressure for the epoprostenol and control groups were -8 percent and +3 percent, respectively (difference in mean change, -6.7 mm Hg; 95 percent confidence interval, -10.7 to -2.6 mm Hg; P < 0.002), and the mean changes in pulmonary vascular resistance for the epoprostenol and control groups were -21 percent and +9 percent, respectively (difference in mean change, -4.9 mm Hg/liter/min; 95 percent confidence interval, -7.6 to -2.3 mm Hg/liter/min; P < 0.001). Eight patients died during the study, all of whom had been randomly assigned to conventional therapy (P = 0.003). Serious complications included four episodes of catheter-related sepsis and one thrombotic event. CONCLUSIONS: As compared with conventional therapy, the continuous intravenous infusion of epoprostenol produced symptomatic and hemodynamic improvement, as well as improved survival in patients with severe primary pulmonary hypertension.
Subject(s)
Epoprostenol/administration & dosage , Hypertension, Pulmonary/drug therapy , Platelet Aggregation Inhibitors/administration & dosage , Adult , Anticoagulants/therapeutic use , Drug Administration Schedule , Epoprostenol/adverse effects , Exercise Tolerance/drug effects , Female , Hemodynamics/drug effects , Humans , Hypertension, Pulmonary/mortality , Hypertension, Pulmonary/therapy , Infusions, Intravenous , Male , Platelet Aggregation Inhibitors/adverse effects , Prospective Studies , Survival Analysis , Treatment Outcome , Vasodilator Agents/therapeutic useABSTRACT
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.
Subject(s)
Epoprostenol/therapeutic use , Heart Failure/drug therapy , Aged , Dose-Response Relationship, Drug , Epoprostenol/administration & dosage , Epoprostenol/adverse effects , Female , Hemodynamics/drug effects , Humans , Infusions, Intravenous , Male , Middle Aged , Pilot ProjectsABSTRACT
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.