Nonvalvular Disease Research Articles

Comparative Expression of Proteins in Serum from Patients with Sinus Rhythm and Atrial Fibrillation

The aim of this study was to compare the 2D profiles of AF patients with the controls with sinus rhythm by serum proteomics technology. We believe that the 2-DE based serum proteome analysis can be useful in discovering new biomarkers that may aid in mechanism research and therapy of AF. Sera from 5 patients with AF and 5 controls with sinus rhythm were investigated using 2-DE and nanoliquid chromatography coupled to tandem mass spectrometry. 13 differentially expressed proteins were successfully identified, of which, transthyretin Val30Met Variant was expressed significantly and constantly only in AF patients. Haptoglobin Hp2 was down-regulated in AF group compared with the sinus rhythm group, and serum dermcidin preproprotein and transferrin were up-regulated in patients with RHD compared the patients with non-valvular diseases. Furthermore, increased expression levels of glutathione peroxidase 3, plasma glutathione peroxidase, plasma GSHPx, peroxiredoxin-2 isoform a, complement component C4A and complement C4B precursor were observed in RHD patients compared with non-valvular diseases. Conclusions: During atrial fibrillation, TTR or TTR variant may be involved in the maintenance of AF. The course of rheumatic heart disease is accompanied by the oxidative stress and activation of the complement system.

Managing thromboembolic risk in patients with atrial fibrillation: are we approaching a new frontier?

The risk of thromboembolic events, particu­ larly stroke, is increased in patients with atrial fibrillation. Therefore, it is vitally important to identify effective strategies for adequate antico­ agulation, especially for those at greatest risk. Determining which patient has a substantial risk and is most likely to derive benefit from anticoagulation without incurring excessive bleeding risk, however, is far from simple. The exact mechanisms and patient characteristics lending to this increased risk of thromboembo­ lism in atrial fibrillation are still being defined. Furthermore, current anticoagulation strategies are often cumbersome in clinical practice, replete with risks and restrictions, do not fully negate the risk of thrombo embolism and, as such, are unpalatable to patients and physicians alike. Several newer anticoagulants, including fac­ tor Xa antagonists and direct thrombin inhibi­ tors, appear promising despite the underlying complexities of atrial fibrillation. Recent data concerning dabigatran [1], a direct thrombin inhibitor, are compelling and give us pause to consider whether we are approaching a new fron­ tier in the management of thrombo embolic risk in atrial fibrillation patients. There are several described mechanisms responsible for the increased risk of thrombo­ embolic events in patients with atrial fibrilla­ tion [2]. One simple explanation is that inadequate atrial emptying, due to the rhythm itself, can cause stagnation of blood and a greater propen­ sity for thromboembolic events. Similarly, atrial remodeling as a result of fibrillation may increase the risk. Still, another consideration is that atrial fibrillation may lead to the activation of proco­ agulant pathways, perhaps based on an inflam­ matory response. Thromboemboli may also origi­ nate from noncardiac sources [3]. Despite these and other possible explanations, ongoing research seeks to better understand and characterize the responsible mechanisms so that treatment options may be developed to target these pathways. Comorbidities increase the risk of thrombo­ embolism in atrial fibrillation patients. Various scores that consider specific nonmodifiable clini­ cal characteristics have been developed to identify patients with nonvalvular disease at significant risk – the greater number of risk factors, the greater risk of stroke and need for anticoagulation. The CHADS 2 score, which assigns one point to the presence of congestive heart failure, hyper­ tension, age older than 75 years or diabetes, and two points to a history of stroke or transient ischemic attack, is commonly used to stratify the risk of thromboembolism in patients with nonvalvular atrial fibrillation. A score of 2 places a patient at an annual stroke risk of 4.0%; the annual risk of stroke is as high as 18.2% for those with a score of 6 [4–6]. While the annual risk of bleeding also varies by CHADS 2 score [7], ben­ efit in favor of warfarin anticoagulation increases when the score exceeds 1. The score, however, underestimates the substantial risk of thrombo­ embolism in some patients with atrial fibrillation. As a result, a more sophisticated and inclusive score, CHA 2 DS 2 ­VASc, incorporates female gen­ der, age of 65–74 years and presence of vascular disease as additional risk factors, each with its own impact [8]. Unfortunately, little attention is directed towards the paroxysmal and intermittent nature of atrial fibrillation in these risk stratification schemes. Patients may not be considered for anti­ coagulation after a documented return to sinus rhythm even though recurrent, but asymptom­ atic and occult atrial fibrillation puts patients at continued risk. In reality, any episode of atrial fibrillation has associated thrombo embolic risk, although the risk may be acceptably low. The use of an anticoagulant, like warfarin, involves evalu­ ating this risk and balancing it against the risk of bleeding [9], adverse effects and complexities of administration. The aforementioned risk stratification scores aid in determining which patients with atrial

Thrombus precursor protein for monitoring anticoagulation in patients with mechanical valve prosthesis

Objective To evaluate the plasma concentration of thrombus precursor protein (TPP) in patients after mechanical heart valve replacement, and to explore whether it can be used as a marker for monitoring anticoagulation. Methods Totally 60 patients who took warfarin after mitral valve replacement and 20 control patients with non-valvular heart diseases were subjected in this study. Their plasma TPP concentration and international normalized ratio (INR) were determined, and compared not only between the anticoagulant patients and the control patients, but also between the patients with atrial fibrillaiton (AF, n=37) and the patients with sinus rhythm (SR, n=23) after mechanical valve replacement. The relationship between plasma TPP concentration and INR in the 60 anticoagulant patients was analyzed with linear regression. Results It was found that the anticoagulant therapy effectively decreased plasma TPP concentration and elevated INR. In the anticoagulant group, the patients with AF had higher plasma TPP concentration than the others with sinus rhythm ( P<0.05), although there was no significant difference in INR level between these 2 groups of patients ( P>0.05). No significant correlation was found between plasma TPP concentration and INR in the anticoagulant patients ( P>0.05). INR did not accord with plasma TPP concentration in several patients. Conclusion INR can't reflect the coagulation status and guide the anticoagulation correctly sometimes; TPP may be a valuable assistant marker for monitoring anticoagulation in patients with mechanical heart valve prothesis; Patients with AF may require higher density of anticoagulation and TPP is strongly suggested to be monitored in these patients.

Optimal Noninvasive Assessment of Diastolic Heart Failure in Patients with Atrial Fibrillation: Comparison of Tissue Doppler Echocardiography, Left Atrium Size, and Brain Natriuretic Peptide

The aim of this study was to evaluate whether the ratio of early diastolic transmitral velocity to early diastolic mitral annular velocity (E/E') can be applied to identify diastolic heart failure (HF) noninvasively rather than using brain natriuretic peptide (BNP) or enlargement of left atrium (LA) in patients with atrial fibrillation (AF) by comparing the severity of HF symptoms. Moreover, we investigated the relationship between the changes in E/E' and the severity of HF or LA remodeling in the follow-up period. We examined 73 patients with nonvalvular AF disease and preserved left ventricular ejection fraction (>50%), ie, patients with diastolic HF accompanied with New York Heart Association (NYHA) functional class I to IV (n = 32, HF group) and those without HF (n = 41, non-HF group). No patients showed dyspnea caused by anemia, renal failure, lung disease, or other disease states except HF. We evaluated E, E', and E/E' by Doppler echocardiography, and the LA area (LAA) by 2-dimensional echocardiography. BNP levels were also examined. A follow-up study was performed in 18 of the 32 patients with HF. E/E', LAA, and BNP were higher in the HF group than in the non-HF group (E/E', 15 +/- 5 vs 9 +/- 2; LAA, 24 +/- 6 vs 20 +/- 6 cm(2); and BNP, 321 +/- 200 vs 140 +/- 76 pg/mL, each P < .01). Using the receiver operating characteristic curve for identification of symptomatic diastolic HF with NYHA functional class II to IV, the areas under the curves were: E/E', 0.96 (95% confidence interval 0.91-1.0); LAA, 0.77 (95% confidence interval 0.64-0.89); and BNP, 0.85 (95% confidence interval 0.75-0.95). In the HF group, 18 patients who were re-examined 17 +/- 9 weeks after were divided into two groups, depending on the improvement in NYHA functional class, ie, improved group (n = 10) and unchanged group (n = 8). In the follow-up period, E (112 +/- 20-94 +/- 21 cm/s), E/E' (17.1 +/- 5-13.1 +/- 3), and LAA (28 +/- 5-24 +/- 4) decreased in the improved group (each P < .05), but E' and BNP did not. E/E' could be useful in identifying symptomatic diastolic HF and evaluating the functional state in the process of HF in patients with AF. Moreover, E/E' is able to assess the improvement of diastolic HF in AF.

Cost analysis of a managed care decentralized outpatient pharmacy anticoagulation service.

To determine the per-patient-per-month (PPPM) cost of a decentralized outpatient pharmacy anticoagulation service (OPAS) in patients with chronic atrial fibrillation (AF) who were maintained on warfarin sodium therapy in a managed care setting, to compare the annual costs versus the risk for stroke, and to assess the quality of the anticoagulant management. Data were collected retrospectively from clinical, research, and administrative claims databases. Patient demographic data were stratified to include age and risk factors for stroke. Inclusion criteria for the study were adult patients (>18 years) who were maintained on chronic warfarin therapy with a diagnosis of AF (diagnosis code 427.31) and continuously enrolled during calendar year 2000. The cost analysis included the personnel cost of clinical pharmacy specialists, direct and indirect cost of laboratory tests for international normalized ratios (INR), and anticoagulant (warfarin plus bridge therapy with a low molecular weight heparin) drug cost and dispensing fee. The percentage of INR values within or near target was used to evaluate the effectiveness of the service. A total of 97 patients on chronic warfarin therapy for AF were identified for cost analysis. The demographics for these patients included the following: 71% were male, with 32% of the patients over the age of 75 years, and 60% had 1 or more identifiable risk factors for stroke. Utilizing established criteria, 80.4% of the sample was considered to be at high risk for ischemic stroke. A majority of the patients (94.8%) had nonvalvular disease, with an INR goal in the range of 2 to 3 in 91.8% of the cases. The PPPM cost for the OPAS monitoring service was $51.25, distributed as $13.78 (27%) in personnel costs for monitoring pharmacists, $18.38 (36%) for lab tests, and $19.09 (37%) for anticoagulant drug costs. These costs did not significantly differ among patient groups with various risks for ischemic stroke. For nonvalvular AF patients, the percentage of INR values within each individual patient.s specific INR goal range was 60.4%; the percentage within or near goal was 74.6%. The average PPPM cost for pharmacist and laboratory monitoring as well as anticoagulant medication for CY 2000 was estimated to be $51.25. The annual costs were comparable among AF patients with different risks for ischemic stroke. The percentage of INR values within the individual patient.s stated target goal was 60.4%. Effective monitoring to maintain patients within their target INR goal is relatively inexpensive compared with the cost of complications such as ischemic stroke or intracranial bleeding.

Uso de anticoagulación al alta hospitalaria en pacientes con insuficiencia cardíaca y fibrilación auricular

To assess the degree of compliance with current guidelines for chronic anticoagulation in patients with heart failure and atrial fibrillation. From the INCARGAL Study database, we analyzed data from 195 consecutive patients (88 men; mean age 76 10 years) with both conditions, admitted to three Galician hospitals between January and March 1999. It was assumed that these patients should have received anticoagulant therapy at discharge, unless contraindicated. We studied the association of treatment at discharge (anticoagulation or not) with the presence or absence of contraindications. 152 patients (78%) had no contraindication for anticoagulation and 43 had at least one (absolute: 11, relative: 32). Only 50% of patients without contraindications received anticoagulation at the time of discharge. No patient with an absolute contraindication and 3 with a relative one received anticoagulation. Factors related with the less frequent prescription of anticoagulation therapy in patients without a formal contraindication were: age, a previous history of coronary heart disease, absence of valvular heart disease, prior myocardial infarction, treatment with beta-blocking agents, non performance of an echocardiogram, and admission to a department other than cardiology. On multivariate analysis, age, prior myocardial infarction, and non-valvular disease were found to be independent predictors of less use of anticoagulation. Anticoagulant therapy is used less often than recommended at discharge in patients with heart failure and atrial fibrillation for whom there were no contraindications. Advanced age reduces its use. The presence of other indications for antiplatelet or anticoagulation therapy appears to determine the choice of one or the other. Noncompliance with the guidelines due to overprescription was not found.

Underutilization of anticoagulation therapy in chronic atrial fibrillation.

Atrial fibrillation, the most common chronic arrhythmia, results in an increased risk of stroke. Anticoagulation therapy can reduce this risk, but appears to be underused. The objective of this study was to examine the use of warfarin and prevalence of stroke in patients with rheumatic, nonrheumatic valvular and nonvalvular atrial fibrillation. Between January 1993 and December 1998, 457 chronic atrial fibrillation patients with continuous follow-up in our hospital were identified as having rheumatic heart disease (n = 114): nonrheumatic valvular disease (n = 65); or nonvalvular disease (n = 278). Warfarin was used less often in patients with nonrheumatic valvular (16.7%) and nonvalvular diseases (20.1%) than in those with rheumatic heart disease (81.6%, p < 0.001). In contrast, the prevalence of stroke among patients with nonvalvular disease was 40.3% which was similar to the 33.3% found in patients with rheumatic heart disease but significantly higher than the 24.6% found in patients with nonrheumatic valvular disease (p < 0.05). A history of stroke did not alter the trend of use of warfarin among the three groups of patients. Only 20.6% of patients on warfarin received monthly monitoring of prothrombin time. In conclusion, the anticoagulation therapy in our patients with chronic atrial fibrillation, regardless of their associated valvular diseases, is significantly underutilized. This underuse could account for a high prevalence of stroke. This risk of stroke, however, is less in patients with nonrheumatic valvular discase than in those with nonvalvular atrial fibrillation.

Guidelines for Stroke Prevention in Patients with Atrial Fibrillation

Atrial fibrillation (AF) is a major independent risk factor for stroke. AF is most commonly associated with nonvalvular cardiovascular disease and is especially frequent among the elderly. The annual risk for stroke in patients with AF is approximately 5% with a wide range depending on the presence of additional risk factors. For patients who cannot successfully be converted and maintained in normal sinus rhythm (NSR), antithrombotic therapy is an effective method for preventing stroke. The 2 drugs which are indicated for stroke prophylaxis in patients with AF are warfarin and aspirin. For primary prevention, warfarin reduces the risk of stroke approximately 68%. Aspirin therapy is less effective, resulting in a 20 to 30% risk reduction. Combination therapy with aspirin and low intensity warfarin adjusted to an International Normalised Ratio (INR) of 1.2 to 1.5 has not been shown to be superior to standard intensity warfarin with a target INR of 2.0 to 3.0. In patients with AF and a prior history of stroke or transient ischaemic attack (TIA), the absolute risk reduction with warfarin is even greater because of the high risk of stroke in this population. In contrast, aspirin has not been shown to significantly reduce the risk of stroke in patients with AF when used for secondary prevention. When appropriately managed, warfarin is associated with a low risk of major bleeding. In controlled trials of highly selected patients, the annual rate of intracranial haemorrhage (ICH) with warfarin was approximately 0.3%. Studies have shown that specialty anticoagulation clinics can achieve similar low rates of major bleeding. However, these results cannot be extrapolated to the general population. Factors which have been identified as predictors of bleeding include advanced age, number of medications and most importantly, the intensity of anticoagulation. INR values above 4.0 have been associated with an increased risk of major bleeding while values below 2.0 have been associated with thrombosis. Slow careful dosage titration, regular laboratory monitoring and patient education can substantially reduce the risk of complications. In patients with AF, antithrombotic therapy has been shown to be cost effective. For high risk patients, warfarin is the most cost-effective therapy, provided the risks for bleeding are minimised. In contrast, aspirin is the most cost-effective agent for low risk patients. Current practice guidelines for stroke prophylaxis recommend warfarin (target INR 2.5: range 2.0 to 3.0) for AF patients at high risk for stroke including those over 75 years of age or younger patients with additional risk factors. Aspirin should be reserved for low risk patients or those unable to take warfarin. Although these recommendations are strongly supported by the clinical trial evidence, studies show that many patients are not receiving appropriate antithrombotic therapy. In particular, warfarin is underutilised in high risk elderly patients. Additional studies are needed to identify barriers that prevent implementation of the clinical trial findings into clinical practice.

Mid-term results of heart transplantation for end-stage valvular disease.

The results of heart transplantation in a consecutive series of 19 end-stage valvular disease patients (15 male, aged 48 +/- 8 years) were analysed retrospectively. The indication for heart transplantation was heart failure due to left and/or right ventricular dysfunction; 16 patients had undergone previous valve surgery, but prosthetic dysfunction was present in only one patient. All patients were in NYHA class IV, 15 were on oral anticoagulants and 5 on i.v. catecholamine support. There were four in-hospital deaths (21%) and one late death (5%), resulting in a 1-year mortality rate slightly, but not significantly, higher than that of patients transplanted for other indications (16%). Mean follow-up of the survivors was 48 +/- 33 months (range 9-95); 5-year actuarial survival was similar to that observed among the other heart transplantation patients (74 +/- 10% vs 77 +/- 3%, P = NS). The incidence of acute rejection and infection was also similar in valvular disease and non-valvular disease patients. Kidney and liver function at 1 year post-heart transplantation was preserved in all cases; cardiac catheterization revealed normal graft function in all patients and the absence of coronary lesions in all but two. In conclusion, in our limited experience morbidity and mortality in patients transplanted for end-stage valvular disease seem to be similar to those of patients undergoing heart transplantation for other etiologies.

Correlation between systolic time intervals and roentgen findings in normal subjects and cardiopathic patients.

This study was designed to evaluate the usefulness of non-invasive parameters in the follow-up of cardiopathic patients without valvular cardiac diseases. In 49 patients suffering from heart disease we have studied the changes of radiologic cardiac measurements and systolic time intervals (STI) in the 4 functional classes of the NYHA classification, investigating also the existence of any relationship between these different parameters. Only the patients in the 3rd and the 4th functional classes showed significant changes in STI and radiologic measurements, as compared with the control group. Moreover, significant negative correlations have been observed between relative heart volume and LVET (r = 0.69, P less than 0.001) and LVETc (r = 0.82, P less than 0.001) and positive correlations between relative heart volume and PEP (r = 0.59, P less than 0.01) and PEP/LVET ratio (r = 0.75, P less than 0.001). These results, while confirming the close correlation between STI and cardiac performance, seem to demonstrate that relative heart volumetry is a fairly accurate index of the cardiac conditions in non-valvular heart diseases.

Pulmonary Blood Volume in Congestive Heart Failure

By utilizing indicator-dilution techniques, determinations of the pulmonary blood volume (PBV) and central blood volume (CBV) were made in 25 patients during simultaneous right and transseptal left heart catheterization. Of these, 12 patients had normal hemodynamics, six had heart failure associated with mitral stenosis, and seven had heart failure secondary to nonvalvular myocardial disease. In the normal patients the PBV averaged 271 ml/m2 (se, ±10.0) and the CBV 596 ml/m2 (se, ±25.7). The mean value for PBV and CBV in the patients with heart failure associated with mitral stenosis was 238 ml/m2 (se, ±26.3) and 600 ml/m2 (se, ±40.9), respectively. Among the patients with nonvalvular heart failure the PBV averaged 292 ml/m2 (se, ±21.4) while the CBV averaged 679 ml/m2 (se, ±45.8). In 12 of the 13 patients with heart failure, the individual values for PBV and CBV did not differ significantly from normal. However, in each of the 13 patients pulmonary artery, left atrial, and mean pulmonary distending press...

The technique of estimating the instantaneous aortic blood velocity in man from the pressure gradient

mhe time relationships between pres1 sure and blood velocity in the asdending aorta can be used to define the mechanical function of the heart. To the extent that the mechanical function is altered early in disease, evaluation of these pressure-velocity relationships has important clinical as well as biophysical implications. It is possible to estimate both the aortic pressure and the instantaneous blood velocity by the use of a catheter method.’ This method requires accurate measurement of the instantaneous lateral pressures at two relatively close points along the axis of the aorta. The difference between these pressures is an approximate measure of the instantaneous pressure gradient from which the blood velocity may be computed by means of simple analog computer methods. The computation of the aortic blood velocity from the spatial pressure gradient requires extremely accurate measurement of the pressure and meticulous attention to a number of experimental details. A number of problems are raised by these requirements in the application of this technique to studies in human subjects. It is the purpose of this report to present certain approaches to many of these problems and to make available the details necessary to apply this method successfully in the clinical physiology laboratory. Examples are also given which illustrate the pressure-velocity relationships as measured in patients with nonvalvular myocardial disease and after the administration of certain pharmacologic agents. The discussion of the application of the computed pressure gradient technique may be divided into five general areas: catheter, gauges, electrical circuits and amplifiers, calibration, and evaluation of the total system response. Catheter. The catheter, as diagrammatically illustrated in Fig. 1, is of a special double-lumen design,? with two lateral pressure taps at the end of each lumen. The entry to each lumen is separated by a distance of 5 cm. The No. 69; French catheter will pass through a short beveled modification of a No. 12 gauge Robb needle. The stopcocks connecting the catheter to the gauges must be made to fine tolerance.1

DRUG TREATMENT OF CARDIAC DECOMPENSATION

This is one of a series of articles written by eminent clinicians for the purpose of extending information concerning the official medicines. The twenty-four articles in this series have been planned and developed through the cooperation of the U. S. Pharmacopeial Committee of Revision and The Journal of the American Medical Association.—Ed. By cardiac decompensation is meant a combination of symptoms and signs that indicate that the heart by reason of its abnormal condition no longer is able to maintain an efficient circulation. In cardiac decompensation is not included the circulatory failure of acute infectious diseases. Various forms of heart disease may lead to the condition spoken of as cardiac decompensation, such as chronic valvular heart disease, chronic nonvalvular or myocardial heart disease, chronic pericarditis or congenital cardiac lesions. As factors in the production of these forms of heart disease, rheumatic fever and hypertension play very important

Some Non-Valvular Diseases of the Heart

Some Non-Valvular Diseases of the Heart