Post-transplantation lymphoproliferative disorder in heart and kidney transplant patients: a single-center experience.

BACKGROUND: Post-transplantation lymphoproliferative disorder (PTLD) after heart transplantation is a fatal complication, and standard treatment is either ineffective or too toxic. We have studied the incidence, clinical course, prognostic factors, and different treatment regimens pertaining to PTLD in 110 heart and 80 kidney transplant recipients. METHODS: Information was abstracted from chart review of 110 heart transplant recipients and 80 kidney transplant recipients between January 1989 and October 2002. We report 15 patients with PTLD, 6 patients received a heart transplant and 9 patients received a renal transplant. RESULTS: The overall incidence of PTLD was 8.9% (5.4% in heart and 13.7% in kidney transplant recipients). The average interval between transplantation and the diagnosis of PTLD in heart transplantation patients was 5.5 years, and their overall mean age was 44 years. The indications for transplantation were ischemic cardiomyopathy in 5 patients (1 patient received both heart and kidney transplants), glomerulonephritis in 6 patients, diabetes nephropathy in 2 patients, and polycystic disease in 2 patients. Six patients were diagnosed with early disease (<12 months), 7 with late onset (1 to 10 years), and 2 with very late onset (>10 years). Five patients had PTLD grade 2 (2 heart and 3 kidney transplants) and 10 patients had PTLD grade 3 (4 heart and 6 kidney transplants). Immunosuppressive treatment for PTLD patients consisted of cyclosporine, 73% (11/15); tacrolimus, 6.6% (1/15); prednisone, 100% (15/15); azathioprine, 80% (12/15); mycophenolate mofetil, 20% (3/15); murine monoclonal anti-human CD3 (OKT3), 7% (1/15); and anti-thymocyte globulin, 13% (2/15). PTLD developed in 11.5% of patients with primary Epstein-Barr virus infection and in 28.9% of patients with primary cytomegalovirus infection. Five patients received rituximab therapy, 5 had conventional chemotherapy, 3 had radiotherapy, 3 had reduction in immunosuppression, 2 had ganciclovir, 1 underwent surgery, and 1 patient died before receiving treatment. The mortality rate was 26.6%. The average interval between transplantation and the diagnosis of PTLD in heart transplant recipients was 5.5 years. The mortality rate was significantly higher in the control group than in the rituximab group. CONCLUSIONS: Caucasian race and male gender were independent risk factors for developing PTLD. Pretransplant cytomegalovirus seropositive status is a strong predictor of developing PTLD. Management of PTLD requires randomized controlled trials of various chemotherapeutic and antiviral drugs regimens. Treatment of PTLD with rituximab is a beneficial alternative with a favorable outcome. Patients in whom primary Epstein-Barr virus, cytomegalovirus, or hepatitis C infection develop after transplantation should be managed with heightened surveillance for the development of PTLD. Further randomized trials are needed to evaluate the efficacy of antiviral drugs, intravenous immunoglobulin, interferon, and prophylactic Epstein-Barr virus immunization strategies.

Adaptive-outward and maladaptive-inward arterial remodeling measured by intravascular ultrasound in hyperhomocysteinemia and diabetes.

BACKGROUND: Coronary artery remodeling implies structural changes in the vessel wall in response to various pathophysiologic conditions. However, the classification of remodeling is unclear. We hypothesized that the adaptive, positive-outward remodeling is a reactive and compensatory response to the stress. The maladaptive negative-inward constrictive remodeling is a passive atherosclerotic condition in which the vessel becomes stiffer. METHODS: Patients with atherosclerotic lesions underwent intravascular ultrasound (IVUS) scans. The size of the vessels distal to and proximal to plaques were analyzed by IVUS. Diabetes was created in mice by an intraperitoneal injection of alloxan (65 mg/kg). To reduce remodeling, mice received ciglitazone, an agonist of peroxisome proliferators activated receptor-gamma (PPARgamma) in drinking water. After 8 weeks, atherosclerotic vessels were analyzed for collagen and elastin. RESULTS: IVUS data suggest an adaptive coronary arterial remodeling was a positive compensatory response to various pathologic stimuli; for example, with the deposition of atherosclerotic plaque, coronary arterial segments enlarged to maintain luminal area. This phenomenon was commonly observed during the initial phases of the development of atherosclerosis. However, negative coronary artery remodeling, or a decrease in vessel area with the formation of atherosclerotic plaque, was maladaptive and was associated with smoking, hypertension, hyperhomocysteinemia, diabetes mellitus, and also after percutaneous coronary interventions (restenosis). In diabetic mice, there was increased collagen and decreased elastin contents; however, treatment with ciglitazone ameliorated the decrease in elastin contents. CONCLUSION: Global enlargement of the coronary vascular tree occurs during pressure and volume overload associated with ventricular hypertrophic states such as athletic conditioning, hypertensive heart disease, and dilated cardiomyopathy. On the other hand, maladaptive coronary arterial remodeling occurs in patients with severe deconditioning, diabetes mellitus, after coronary artery bypass surgery, and in some instances, postintervention.

Concurrent occurrence of Sweet's syndrome and erythema nodosum: an overlap in the spectrum of reactive dermatoses.

Simultaneous occurrence of Sweet's syndrome and erythema nodosum is very rare. We describe a case of a young male with a recent history of streptococcal infection who presented with concurrent Sweet's syndrome and erythema nodosum. Although the exact pathogenesis of these dermatoses is not yet clear, their similarities and simultaneous occurrence suggest a possible common underlying mechanism and may represent a continuum of reactive dermatoses. Evaluation of the role of cytokines in the etiopathogenesis of these conditions will be useful for further assessment and treatment of these conditions. Like the association of acanthosis nigricans and certain cancers and diabetes, Sweet's syndrome and erythema nodosum may be associated with certain malignancies, autoimmune disorders, or inflammatory bowel disease. Early recognition of these skin lesions can guide a search for underlying disorders. Patients with Sweet's syndrome should undergo an age-appropriate work-up for malignancy.

Cardiac resynchronization therapy for CHF. The rewards and risks of biventricular pacing.

Patients with advanced heart failure continue to experience high morbidity and mortality despite recent progress made with the use of such drugs as beta-blockers and angiotensin-aldosterone inhibitors. Cardiac transplantation has severe limitations due to the short supply of organs and the ineligibility of most CHF patients for this therapy. Approved heart-assist devices are cumbersome and costly. Therefore, these devices are currently used mainly in tertiary care centers in a limited number of patients. CRT has been rapidly evolving as a viable and beneficial therapy that is universally applicable by percutaneous method in patients with moderate or severe heart failure. Its relative ease of use and cost-effectiveness make it an attractive option for patients with symptomatic heart failure. Therefore, more physicians are becoming aware of the low threshold for its use.

Modern surgical and interventional options for the management of heart failure.

Current standard drug therapy provides only palliative and symptomatic relief for patients with severe heart failure, but there is now a wide array of device applications that holds great promise for reducing the mortality and disability that result from heart failure. Patients with severe chronic and refractory heart failure should be considered for heart transplantation or mechanical circulatory supportwith a ventricular assist device. Newer surgical and interventional treatments are in continuous evolution.

Pathology, prognosis, and prevention of heart failure.

Optimal management of patients with heart failure (HF) should be guided by thorough evaluation and use of functional classification and disease staging systems. Though the understanding of precise underlying pathophysiological mechanisms has increased dramatically in recent years, it is essential to continue the search for greater efficacy in preventing, controlling, and reversing this pathological state. Recent developments in the diagnosis and treatment of heart failure have improved prognosis in terms of both survival and morbidity due to re-hospitalization. The underutilization of medical and preventive therapies in patients with heart failure is a major public health issue, despite the recommendations of various evidence-based guide lines. Patient education and disease management programs have been shown to optimize HF-management by bridging the gap between evidence-based medicine and clinical practice, thereby, reducing hospitalization rate. This paper, the first in a series of three papers, will identify the pathology, prognosis and prevention of heart failure, while the paper to follow will discuss modern methods of interventional management.

Evidence-based drug treatment of heart failure.

Modern management strategies have revolutionized the treatment of patients with acute and chronic heart failure (HF). Physicians should identify the risks and benefits of each drug or interventional option being considered for the treatment of HF. Inhibition of the neurohormonal axis with angiotensin converting enzyme (ACE) inhibitors and beta-blockers has significantly improved morbidity and mortality of patients with chronic HF. An aggressive approach targeted at improving hemodynamics and end-organ function is warranted during acute exacerbations or decompensated heart failure. Immediate recognition and management of potentially reversible causes and simultaneous initiation of supportive therapy to augment the cardiac output are key elements to the successful treatment of acute heart failure.

Coronary vasospasm and myocardial infarction induced by oral sumatriptan.

Coronary vasospasm is well documented as a side effect of injectable subcutaneous forms of sumatriptan; only one such case has been reported so far with oral ingestion of sumatriptan in a patient with underlying coronary artery disease. This report describes a case of coronary vasospasm induced by oral sumatriptan even in normal coronary arteries. Physicians and patients should be aware of a small and unpredictable risk of the serious cardiac side effects of this drug.

Current perspectives of electrical remodeling and its therapeutic implications.

Electrical remodeling involves alterations in the electrophysiologic milieu of myocardium in various disease states, such as ventricular hypertrophy, heart failure, atrial tachyarrhythmias, myocardial ischemia, and infarction that are associated with cardiac arrhythmias. Although research in this area dates back to early part of the 19th century, we still lack the exact knowledge of ionic remodeling, the role of various genes and channel proteins, and their relevance for the newer antiarrhythmic therapies. Structural remodeling may also have an impact on the electrical remodeling process, although differences in both structural and electrical remodeling are associated with different disease states. Various electrophysiologic, cellular, and structural alterations, including anisotropic conduction, increased intracellular calcium levels, and gap junction remodeling predispose to increased dispersion of action potential duration and refractoriness. This constitutes a favorable substrate for early and late afterdepolarizations and reentrant arrhythmias. Studying the role of ionic remodeling in the initiation and propagation of cardiac arrhythmias has significant relevance for developing newer antiarrhythmic therapies, for identifying patients at risk of developing fatal arrhythmias, and for implementing effective preventive measures. Further research is required to understand the specific effects of individual ion channel remodeling, to understand the signal transduction mechanisms, and to address whether detrimental effects of electrical remodeling can be altered.

The role of nitric oxide and vasopressin in refractory right heart failure.

The standard treatment for right heart failure includes aggressive fluid resuscitation, inotropic agents, and avoiding drugs, such as diuretics or nitrates, or maneuvers that decrease pre-load. Even an increase in vagal tone caused by the insertion of a bladder catheter can acutely decrease preload and lead to cardiogenic shock. Other modalities include early reperfusion therapy and pacemaker implantation for complete heart block or loss of atrioventricular synchrony. Acute right heart failure carries a very high mortality because of the limited options available for its management. Among newer treatments, inhaled nitric oxide and intravenous vasopressin have shown promise for acute right ventricular failure.

Echocardiography predicts adverse cardiac remodelling in heart failure.

Congestive heart failure remains a primary cause of cardiovascular-related events. Heart failure patients face two health care challenges. First, they are uncertain about their prognosis and second, they have an unpredictable clinical course with recurrent exacerbations of heart failure. The echocardiogram is an easily accessible bedside test without any associated procedural complications. Additionally, it provides a wealth of information about chamber size and function, valve integrity and the pericardial sac. In the present review, the most common echocardiographic predictors of impending cardiac events in congestive heart failure are described.

Aortic valve sclerosis: is it a cardiovascular risk factor or a cardiac disease marker?

BACKGROUND: Aortic valve sclerosis, without stenosis, has been associated with an increased cardiovascular mortality and morbidity due to myocardial infarction. However, it is unclear whether it is a cardiovascular risk factor or a cardiac disease marker. The goal of our study is to evaluate the difference in the prevalence of cardiovascular disease and risk factors among patients with or without aortic sclerosis. METHODS: This observational study compared a group of 142 consecutive subjects with aortic valve sclerosis, assigned as group S, with a group of 101 subjects without aortic sclerosis, assigned as group C. Patients with bicuspid aortic valves and those with antegrade Doppler velocity across aortic valve leaflets exceeding 2.0 m/sec were excluded. RESULTS: Mean ages of groups S and C were 71 +/- 8, and 68.8 +/- 6 years, respectively (P value = not significant). The prevalence of smoking, diabetes, hypercholesterolemia, hypertension, pulse pressure, left ventricular diastolic dysfunction, atrial fibrillation, and stroke was not significantly different between the two groups. However, there was a significantly higher prevalence of left ventricular hypertrophy (P = 0.05), ventricular arrhythmias (P = 0.02), myocardial infarction (P = 0.04), and systolic heart failure (P = 0.04) in aortic sclerosis group. CONCLUSIONS: Aortic sclerosis is associated with a higher prevalence of left ventricular hypertrophy, ventricular arrhythmias, myocardial infarction, and systolic heart failure, while the prevalence of cardiovascular risk factors is not different between aortic sclerosis patients and controls. Hence, aortic sclerosis represents a cardiac disease marker useful for early identification of high-risk patients beyond cardiovascular risk factors rate.

Determining functional significance of subclavian artery stenosis using exercise thallium-201 stress imaging.

Subclavian artery stenosis (SAS) is a rare lesion accounting for nearly 2.5% of all extracranial arterial occlusions. Symptoms from SAS usually relate to subclavian steal, and include syncope, vertigo, ataxia, and, rarely, upper limb paralysis or hemipareses. Upper extremity ischemia may result in intermittent or constant arm pain. The majority of patients with SAS are asymptomatic. Upper extremity ischemia is particularly unusual. More commonly, patients with significant SAS have symptoms of cerebral ischemia, which are usually triggered by vigorous motion of the arm on the side of the severe proximal subclavian obstruction. Stress exercise radionuclide imaging appears to be a valuable modality in determining the functional significance of SAS. We describe a case in which radionuclide imaging with thallium-201 after stress of the upper extremities was used for risk stratification of subclavian stenosis, and to help decide treatment options.

Single coronary artery with the absence of a left anterior descending artery.

Anomalous origin of coronary arteries is discovered incidentally during coronary arteriography or at autopsy, and awareness among angiographers is required. We describe a case with a rare combination of a single coronary artery originating from the right sinus of Valsalva associated with an absent left anterior descending artery and a secundum-type atrial septal defect.

Role of transesophageal echocardiography in detecting implantable cardioverter defibrillator lead infection.

Implantable cardioverter defibrillator (ICD) lead infection is a rare condition with reported incidence of 0.2% to 16%. It usually presents with persistent bacteremia or fever of unknown origin and requires high clinical suspicion for diagnosis. Whenever ICD lead infection is suspected, transesophageal echocardiography is the diagnostic technique of choice for detection and characterization of the lesions. Lead infections are extremely difficult to manage conservatively and surgical removal of the entire defibrillator system is recommended along with antimicrobial therapy. We describe a case of recurrent staphylococci bacteremia due to an ICD lead infection in a patient with arrhythmogenic right ventricular dysplasia.