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Prognostic significance of inverted T waves in patients with acute pulmonary embolism.

BACKGROUND: The significance of inverted T waves remains unclear in patients with acute pulmonary embolism (PE). METHODS AND RESULTS: The relationship of the number of leads with inverted T waves to the severity of PE in 40 patients with acute PE was studied. Patients were classified into 3 groups according to the number of leads with inverted T waves on the admission electrocardiogram (ECG): 15 patients, or=7 leads (group H). In groups L, M and H, the rates of right ventricular dysfunction on echocardiography were 47%, 92% and 100% (p<0.01), respectively, and the rates of in-hospital complicated events (including death or the need for catecholamine support, cardiopulmonary resuscitation or mechanical cardiovascular support because of hemodynamic instability) were 0%, 8% and 46% (p=0.004), respectively. On multivariate analysis, arterial hypotension at presentation (odds ratio (OR) 8.96, p=0.049) and inverted T waves in >or=7 leads on the admission ECG (OR 16.8, p=0.037) were the only independent predictors of in-hospital complicated events. CONCLUSIONS: The number of leads with inverted T waves may be a useful and simple marker of increased risk for early complications in patients with acute PE.

Acute Disease↗

Plasma exchange for hyperbilirubinemia following implantation of a left ventricle assist system: a case report.

A 49-year-old patient with end-stage dilated cardiomyopathy underwent implantation of a left ventricular assist system (LVAS). Although the systemic circulation seemed to be improved, the serum total bilirubin (Tbili) level increased sharply in the early postoperative period (preoperative Tbili, 5.7 mg/dl; postoperative day 3, 33.6 mg/dl). Plasma exchange (PE) was performed 7 times from postoperative day 4, and the Tbili level decreased to 16.3 mg/dl by postoperative day 11. Thereafter, serum Tbili normalized concomitant with improved circulatory condition. The cause of the hyperbilirubinemia was considered to be temporary right ventricular dysfunction or hepatic sinusoid endothelial dysfunction. The liver function was recoverable, so PE had been effective in this case. Unfortunately, the patient suffered a midbrain infarction and ultimately died. From this experience, PE is recommended if it is judged that liver function can be preserved and circulation is adequate, but its implementation should not be delayed. It is essential that LVAS is implanted before damage occurs to end-organ function and thus prevent hyperbilirubinemia.

Cardiomyopathy, Dilated↗

Predictors of nocturnal oxygen desaturation in pulmonary arterial hypertension.

BACKGROUND: Sleep may be associated with significant respiratory compromise in patients with lung disease and can result in hypoxia. In patients with pulmonary arterial hypertension (PAH), nocturnal desaturation may not be reflected in daytime evaluations of oxygenation and can lead to worsening pulmonary hemodynamics. The study was conducted to determine the prevalence and significance of nocturnal oxygen desaturation in patients with PAH. METHODS: A cross-sectional study conducted at the Cleveland Clinic. Patients were followed up at our institution except for the overnight oximetry study done at home. Data regarding degree of nocturnal desaturation, demographics, hemodynamics, pulmonary function, and functional capacity were collected. RESULTS: Forty-three patients (mean age, 47.9 +/- 13.5 years [+/- SD]; 36 women and 7 men) underwent nocturnal oximetry. The etiology of PAH included idiopathic PAH (88%) and PAH associated with connective tissue diseases (12%). The majority of patients were New York Heart Association functional class II (42%) or III (53%). Thirty patients (69.7%) spent > 10% of sleep time with oxygen saturation by pulse oximetry < 90%. Desaturators were older (p = 0.024) and had higher hemoglobin (p = 0.002). Sixteen of 27 patients (59%) without desaturation < 90% during a 6-min walk test were nocturnal desaturators. Nocturnal desaturators had higher brain natriuretic protein (p = 0.004), lower cardiac index (p = 0.03), and higher mean right atrial pressure (p = 0.09), mean pulmonary artery pressure, and pulmonary vascular resistance. On echocardiography, desaturators were more likely to have moderate or severe right ventricular dilation (p = 0.04) and pericardial effusion. Only one patient had significant sleep apnea. CONCLUSIONS: Nocturnal hypoxemia is common in PAH patients and correlates with advanced pulmonary hypertension and right ventricular dysfunction. Approximately 60% patients without exertional hypoxia had nocturnal desaturation. Overnight oximetry should be considered in the routine workup of PAH patients who do not demonstrate exertional desaturation.

Adult↗

Discontinuation of furosemide decreases PaCO(2) in patients with COPD.

STUDY OBJECTIVE: To evaluate whether the discontinuation of furosemide treatment resulted in a decrease in PaCO(2) and an increase in daytime and nocturnal oxygenation. BACKGROUND: Furosemide is widely prescribed in patients with COPD for the treatment of peripheral edema. It is known that furosemide causes a metabolic alkalosis. A diminished chemoreceptor stimulation may cause a decreased alveolar ventilation. DESIGN: Randomized, double-blind, placebo-controlled, crossover trial. SETTING: Department of Pulmonology, Rijnstate Hospital Arnhem, the Netherlands. PATIENTS: Twenty patients with stable COPD (10 men; median age, 70 years [range, 58 to 81 years]; FEV(1) 35% predicted [range, 19 to 70% predicted]). Subjects were included if they had received furosemide, 40 mg/d, for the treatment of peripheral edema for at least a month and if they had a mean nocturnal arterial oxygen saturation (SaO(2)) < 92%. Patients with cardiac left and/or right ventricular dysfunction, sleep apneas, and patients receiving other diuretics, angiotensin-converting enzyme inhibitors, potassium or chloride replacement therapy, or long-term oxygen treatment were excluded. INTERVENTION: Furosemide was discontinued for 1 week and replaced by placebo treatment in the first or the second week. MEASUREMENTS AND RESULTS: Ventilation, daytime arterial blood gas levels, and nocturnal SaO(2) were measured at baseline, after 1, and after 2 weeks. Sixteen subjects completed the study. Ventilation increased from 10.4 L/min (range, 6.7 to 15.4 L/min) at baseline to 11.6 L/min (range, 8.7 to 14.0 L/min) after discontinuation of furosemide (p < 0.05). PaCO(2) decreased from 45 mm Hg (range, 35 to 64 mm Hg) to 41 mm Hg (range, 32 to 61 mm Hg; p < 0.01). Daytime and nocturnal oxygenation did not improve. CONCLUSIONS: Although it does not improve oxygenation, the discontinuation of furosemide decreases PaCO(2) in patients with COPD.

Aged↗

Management of unsuccessful thrombolysis in acute massive pulmonary embolism.

BACKGROUND: The management of patients with acute massive pulmonary embolism (PE) who do not respond to fibrinolytic therapy remains unclear. We aimed to compare rescue surgical embolectomy and repeat thrombolysis in patients who did not respond to thrombolysis. METHODS: We conducted a prospective single-center registry of PE patients who underwent thrombolytic therapy. Lack of response to thrombolysis within the first 36 h was prospectively defined as both persistent clinical instability and residual echocardiographic right ventricular dysfunction. Patients underwent surgical embolectomy or repeat thrombolysis, at the discretion of the attending physician. The clinical end point was a combined end point including recurrent PE, bleeding complications, or PE-related death, which was defined as death from recurrent PE or cardiogenic shock. Long-term adverse outcomes included death, recurrent thromboembolic events, and congestive heart failure. RESULTS: From January 1995 to January 2005, 488 PE patients underwent thrombolysis, of whom 40 (8.2%) did not respond to thrombolysis. Fourteen patients were treated by rescue surgical embolectomy, and 26 were treated by repeat thrombolysis. There was no significant difference in baseline characteristics between the two groups. The in-hospital course was uneventful in 11 of the surgically treated patients (79%) and in 8 patients (31%) treated by repeat thrombolysis (p = 0.004). There was a trend for higher mortality in the medical group than in the surgical group (10 vs 1 deaths, respectively; p = 0.07). There were significantly more recurrent PEs (fatal and nonfatal) in the repeat-thrombolysis group (35% vs 0%, respectively; p = 0.015). While no significant difference was observed in number of major bleeding events, all bleeding events in the repeat-thrombolysis group were fatal. The rate of uneventful long-term evolution was the same in the two groups. CONCLUSION: Rescue surgical embolectomy led to a better in-hospital course when compared with repeat thrombolysis in patients with massive PE who have not responded to thrombolysis. The transfer of patients who have not responded to thrombolysis to tertiary cardiac surgery centers could be considered as an alternative option.

Acute Disease↗

Right ventricular stroke-work. An index of distribution of pulmonary perfusion in acute respiratory failure.

To evaluate the possibility that an elevated right ventricular stroke-work index observed in acute respiratory failure correlates with less dead space ventilation, 20 patients requiring mechanical ventilation were studied. Ratio of physiologic dead space to tidal volume was used as an index of distribution of pulmonary perfusion. An inverse linear relationship was found between right ventricular stroke-work index and dead space ratio (r = -0.74, p less than 0.001). No correlation was present between cardiac index and dead space ratio. To evaluate the effects of other hemodynamic data on the distribution of pulmonary perfusion, the patients were divided into two groups based on a dead space ratio. Comparison of the two groups revealed right ventricular stroke-work index was significantly higher in the low dead space ratio group (p less than 0.001). There were no differences in cardiac index, pulmonary-artery pressure, or right atrial pressures. These data suggest that elevated right ventricular stroke-work index in acute respiratory failure is associated with more even distribution of pulmonary perfusion, and that patients with a high dead space ratio were characterized by right ventricular dysfunction when compared to patients with a low dead space ratio.

Acute Disease↗

Pulmonary hypertensive diseases.

Pulmonary hypertension may occur as a primary disorder of the pulmonary vasculature or secondary to a variety of cardiac or pulmonary diseases. The reversibility of pulmonary hypertension is dependent on the relative contribution of reversible vasoconstriction and irreversible structural changes in the pulmonary vessels. Despite recent advances in the understanding of pulmonary vascular physiology, knowledge of the pathogenesis and natural history of pulmonary hypertension has been limited by an inability to measure pulmonary arterial pressure noninvasively. Thus, when patients have symptoms or signs of pulmonary hypertension, the disease is usually at an advanced stage. It is possible that early in the course of hypoxic pulmonary disease, pulmonary hypertension may be protective in optimizing matching of ventilation and perfusion. It is not known at what point pulmonary hypertension per se becomes harmful. Certainly, treatment directed at underlying cardiac or pulmonary disease is indicated. It also seems reasonable to treat severe degrees of pulmonary hypertension complicated by right ventricular dysfunction. With the advent of orally effective pulmonary vasodilators, direct treatment of primary and secondary pulmonary hypertension may now be possible. Hopefully, with careful clinical evaluation of the response to vasodilator therapy, we will learn whether these drugs prolong life and reduce morbidity in primary and secondary pulmonary hypertension. In the meantime, much more information is needed regarding the mechanisms of acute pulmonary vasoconstriction and sustained pulmonary hypertension. In addition, a means of early identification of patients with mild hypertension is needed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The cardiopulmonary and renal hemodynamic effects of norepinephrine in canine pulmonary embolism.

Autologous blood clot was injected into six dogs to produce a graduated decrease in cardiac output (CO). The effects of an infusion of norepinephrine, titrated to specific end points, were recorded before embolization and at two levels of pulmonary hypertension. Simultaneous measurements of systemic and renal hemodynamics were made. Sequential blood clot injection increased (p less than .01) pulmonary vascular resistance (PVR) from 1.3 to 13 to 33 mm Hg.L-1.min and reduced CO 45 percent and 75 percent (p less than .01). Norepinephrine increased both stroke volume and CO (p less than .01) in each condition and did not increase PVR. Since the biventricular filling pressures remained constant or fell slightly with norepinephrine, the increase in CO is best explained by an improvement in pump performance. There was no deterioration in renal blood flow or creatinine clearance with norepinephrine. The data suggested that in this model of right ventricular dysfunction, norepinephrine consistently improved myocardial performance without provoking further vasoconstriction in either the pulmonary or renal circulations.

Animals↗

Inhaled diazeniumdiolates (NONOates) as selective pulmonary vasodilators.

Selective pulmonary vasodilators cause vasodilatation limited to the pulmonary vasculature, within well-ventilated lung regions. Selective pulmonary vasodilators ideally cause only a minimal effect on the systemic circulation and improve ventilation/perfusion matching. NONOates are a novel group of chemical compounds that spontaneously and continuously release nitric oxide under physiological conditions, over periods of up to 24 h. Inhaled NONOates retain the benefits of gaseous nitric oxide without many of its therapeutic disadvantages. This review focuses on the therapeutic potential of inhaled NONOates in pulmonary hypertension, other lung conditions associated with right ventricular dysfunction and in asthma. The potential toxicity of NONOates is also discussed.

Acute Disease↗

Pharmacotherapy of pulmonary embolism.

Pulmonary embolism (PE) and deep vein thrombosis are common causes of illness and death. The pharmacological approach to pulmonary embolism includes the use of anticoagulants, unfractionated heparin for the acute phase, and oral anticoagulants for prophylaxis. In massive PE, the use of thrombolytic agents is suggested to reduce systemic hypotension and right ventricular failure and increase cardiac output. Thrombolytic agents act on pulmonary vascular obstruction. In clinical practice, thrombolytic therapy is recommended in case of massive embolism with haemodynamic failure. Recent studies suggest the use of thrombolytic drugs in patients with normal systemic blood pressure who show right ventricular dysfunction at echocardiographic examination. A large randomised trial on lytic agents in submassive PE is therefore needed. Anticoagulants were primarily indicated for prevention of recurrences. Due to the development of low molecular weight heparin, the role of anticoagulants needs to be re-evaluated.

Anticoagulants↗

Current understanding of the role of bosentan in inoperable chronic thromboembolic pulmonary hypertension.

Chronic thromboembolic pulmonary hypertension may occur in the context of incomplete lysis of acute pulmonary emboli, resulting in the obstruction of pulmonary blood flow, as well as progressive right ventricular dysfunction and failure. The treatment of choice for this condition is surgical removal of the obstructing material. However, in many patients, surgery is not possible due to either an unfavourable distribution of the disease, the development of a concurrent small vessel pulmonary arteriopathy, or the presence of significant comorbid conditions. There is increasing evidence that the medical therapies that are used in other forms of pulmonary hypertension may also be effective in inoperable chronic thromboembolic pulmonary hypertension. This article examines the rationale for the use of the oral dual endothelin receptor antagonist bosentan in this life-threatening condition.

Antihypertensive Agents↗

Evaluation of right ventricular function in patients with idiopathic dilated and ischemic cardiomyopathy by equilibrium radionuclide ventriculography.

We performed equilibrium radionuclide ventriculography in 12 patients with idiopathic dilated cardiomyopathy, 11 patients with ischemic cardiomyopathy and 11 normal subjects to determine whether measurements of right ventricular function could be used to distinguish dilated cardiomyopathy from ischemic cardiomyopathy. The left ventricular ejection fraction in patients with dilated cardiomyopathy (26 +/- 8%, mean +/- SD) or ischemic cardiomyopathy (32 +/- 5%) was significantly lower than in normals (69 +/- 6%, p less than 0.001). The right ventricular ejection fraction (RVEF) in normals was 57 +/- 7%. RVEF was decreased in 11 of 12 patients with dilated cardiomyopathy and the mean value (32 +/- 10%) was significantly lower than that in patients with ischemic cardiomyopathy (56 +/- 7%, p less than 0.001), none of whom had decreased RVEF. Our data show that right ventricular dysfunction commonly exists in patients with dilated cardiomyopathy but not in patients with ischemic cardiomyopathy. This finding may be useful in the differentiation between dilated and ischemic cardiomyopathy.

Adult↗

Technical report: diagnosis and management of childhood obstructive sleep apnea syndrome.

OBJECTIVE: This technical report describes the procedures involved in developing the recommendations of the Subcommittee on Obstructive Sleep Apnea Syndrome in children. The group of primary interest for this report was otherwise healthy children older than 1 year who might have adenotonsillar hypertrophy or obesity as underlying risk factors of obstructive sleep apnea syndrome (OSAS). The goals of the committee were to enhance the primary care clinician's ability to recognize OSAS, identify the most appropriate procedure for diagnosis of OSAS, identify risks associated with pediatric OSAS, and evaluate management options for OSAS. METHODS: A literature search was initially conducted for the years 1966-1999 and then updated to include 2000. The search was limited to English language literature concerning children older than 2 and younger than 18 years. Titles and abstracts were reviewed for relevance, and committee members reviewed in detail any possibly appropriate articles to determine eligibility for inclusion. Additional articles were obtained by a review of literature and committee members' files. Committee members compiled evidence tables and met to review and discuss the literature that was collected. RESULTS: A total of 2115 titles were reviewed, of which 113 provided relevant original data for analysis. These articles were mainly case series and cross-sectional studies; overall, very few methodologically strong cohort studies or randomized, controlled trials concerning OSAS have been published. In addition, a minority of studies satisfactorily differentiated primary snoring from true OSAS. Reports of the prevalence of habitual snoring in children ranged from 3.2% to 12.1%, and estimates of OSAS ranged from 0.7% to 10.3%; these studies were too heterogeneous for data pooling. Children with sleep-disordered breathing are at increased risk for hyperactivity and learning problems. The combined odds ratio for neurobehavioral abnormalities in snoring children compared with controls is 2.93 (95% confidence interval: 2.23-3.83). A number of case series have documented decreased somatic growth in children with OSAS; right ventricular dysfunction and systemic hypertension also have been reported in children with OSAS. However, the risk growth and cardiovascular problems cannot be quantified from the published literature. Overnight polysomnography (PSG) is recognized as the gold standard for diagnosis of OSAS, and there are currently no satisfactory alternatives. The diagnostic accuracy of symptom questionnaires and other purely clinical approaches is low. Pulse oximetry appears to be specific but insensitive. Other methods, including audiotaping or videotaping and nap or home overnight PSG, remain investigational. Adenotonsillectomy is curative in 75% to 100% of children with OSAS, including those who are obese. Up to 27% of children undergoing adenotonsillectomy for OSAS have postoperative respiratory complications, but estimates are varied. Risk factors for persistent OSAS after adenotonsillectomy include continued snoring and a high apnea-hypopnea index on the preoperative PSG. CONCLUSIONS: OSAS is common in children and is associated with significant sequelae. Overnight PSG is currently the only reliable diagnostic modality that can differentiate OSAS from primary snoring. However, the PSG criteria for OSAS have not been definitively validated, and it is not clear that primary snoring without PSG-defined OSAS is benign. Adenotonsillectomy is the first-line treatment for OSAS but requires careful postoperative monitoring because of the high risk of respiratory complications. Adenotonsillectomy is usually curative, but children with persistent snoring (and perhaps with severely abnormal preoperative PSG results) should have PSG repeated postoperatively.

Adenoidectomy↗

Corrected transposition of the great arteries with several associated anomalies in a 68-year-old patient.

Few patients with corrected transposition of the great arteries survive past 50 years of age because of the association with congenital defects, development of total atrioventricular block, and right ventricular dysfunction. We report the case of a male patient with dextrocardia in situs solitus and corrected transposition of the great arteries associated with a wide atrial septal defect and severe pulmonary valvar and subvalvar stenoses. The patient also developed a large aneurysm on the pulmonary artery, total atrioventricular block diagnosed 8 years earlier, symptoms of dysfunction of the systemic ventricle in the previous 2 years, insufficiency of the left atrioventricular valve, and aortic regurgitation. Despite all these associated anomalies, the patient developed class III cardiac decompensation only at the age of 68 years, which makes this case a rarity. The patient was clinically treated, and was discharged from the hospital in good condition.

Age Factors↗

[Respiratory changes in the blood flow pattern of the superior vena cava in patients with chronic obstructive pulmonary diseases].

Blood flow patterns in the superior vena cava (SVC) obtained from 20 elderly cases of COPD (aged 60-81) were compared with those from 24 elderly normal subjects (aged 61-80). The peak flow velocity and duration of two major antegrade flows during systole and diastole (S & D wave) were both qualitatively and quantitatively assessed with pulsed Doppler echocardiography. While peak flow velocity and duration of the S and D waves increased during inspiration and decreased during expiration in normal subjects, respiratory variations of these antegrade waves were extremely greater in patients with COPD with augmented and/or fused antegrade waves during inspiration, and there decrease was associated with an upward shift above the zero level during expiration. The duration of the D wave was significantly longer in COPD patients than in normal subjects and also revealed a significantly positive correlation with FEV1.0%. These findings suggest that SVC flow pattern is useful for the assessment of early right ventricular dysfunction in patients with COPD, but further clinical studies are required to confirm this thesis.

Aged↗

Venous thromboembolism: diagnosis and management of pulmonary embolism.

Pulmonary embolism (PE) affects 0.5-1 per 1000 people in the general population each year, and is one of the most common preventable causes of death among hospitalised patients. The clinical diagnosis of PE is unreliable and must be confirmed objectively with ventilation perfusion scanning or computed tomography pulmonary angiography. The diagnosis of PE can be reliably excluded, without the need for diagnostic imaging, if the clinical pretest probability for PE is low and the D-dimer assay result is negative. The initial treatment of PE is low-molecular-weight heparin or unfractionated heparin for at least 5 days, followed by warfarin (target international normalised ratio [INR], 2.0-3.0) for at least 3-6 months. Patients with a high clinical pretest probability of PE should commence treatment immediately while awaiting the results of the diagnostic work-up. Thrombolysis is indicated for patients with objectively confirmed PE who are haemodynamically unstable. Percutaneous transcatheter or surgical embolectomy may be life-saving in patients ineligible for, or unresponsive to, thrombolytic therapy. Unresolved issues in the management of venous thromboembolism include the roles of thrombophilia testing, thrombolysis for the treatment of stable PE patients who present with right ventricular dysfunction, and new anticoagulants; and the duration of anticoagulation for first unprovoked venous thromboembolism.

Angiography↗

Outcome of congestive heart failure in elderly persons: influence of left ventricular systolic function. The Cardiovascular Health Study.

BACKGROUND: Most persons with congestive heart failure are elderly, and many elderly persons with congestive heart failure have normal left ventricular systolic function. OBJECTIVE: To evaluate the relationship between left ventricular systolic function and outcome of congestive heart failure in elderly persons. DESIGN: Population-based longitudinal study of coronary heart disease and stroke. SETTING: Four U.S. sites: Forsyth County, North Carolina; Sacramento County, California; Allegheny County, Pennsylvania; and Washington County, Maryland. PARTICIPANTS: 5888 persons who were at least 65 years of age and were recruited from the community. MEASUREMENTS: Total mortality and cardiovascular morbidity and mortality. RESULTS: Of 5532 participants, 269 (4.9%) had congestive heart failure. Among these, left ventricular function was normal in 63%, borderline decreased in 15%, and overtly impaired in 22%. The mortality rate was 25 deaths per 1000 person-years in the reference group (no congestive heart failure and normal left ventricular function at baseline); 154 deaths per 1000 person-years in participants with congestive heart failure and impaired left ventricular systolic function; 87 and 115 deaths per 1000 person-years in participants with congestive heart failure and normal or borderline systolic function, respectively; and 89 deaths per 1000 person-years in persons with impaired left ventricular function but no congestive heart failure. Although the risk for death from congestive heart failure was lower in persons with normal systolic function than in those with impaired function, more deaths were associated with normal systolic function because more persons with heart failure fall into this category. CONCLUSIONS: Community-dwelling elderly persons, especially those with impaired left ventricular function, have a substantial risk for death from congestive heart failure. However, more deaths occur from heart failure in persons with normal systolic function because left ventricular function is more often normal than impaired in elderly persons with heart failure.

Aged↗