Panel-reactive screening and treatment practices following bridge to transplantation ventricular assist device placement.

The use of left ventricular assist devices (LVAD) as a bridge to transplantation is associated with the development of circulating antibodies. We conducted a survey of all adult cardiac transplantation programs in the United States in an attempt to define current practices with regard to LVAD implantation, monitoring panel-reactive antibody (PRA) levels, treatment options, and peritransplantation management. Pretransplantation sensitization with the use of LVAD is a concern to the majority of transplantation professionals and there is no consensus on the need or mode of treatment.

Oral anticoagulation in patients with cardiomyopathy or heart failure in sinus rhythm.

BACKGROUND: Despite many prospective randomized studies defining the benefits of anticoagulation in atrial fibrillation (AF), there have been no adequate studies in cardiomyopathy (CM) in sinus rhythm. METHODS: We review the current knowledge of the risk of stroke in CM, left ventricular systolic dysfunction and heart failure as well as the indications for antithrombotic agents and compare this with AF. RESULTS: The current knowledge of risk factors for stroke and indications for antithrombotic agents in CM is similar to that of AF prior to the treatment studies of the 1980s-1990s. CONCLUSION: Prospective randomized trial data are urgently needed to determine the role of antithrombotic drugs in CM.

Successful treatment of Nocardia nova bacteremia and multilobar pneumonia with clarithromycin in a heart transplant patient.

Nocardia is an opportunistic pathogen in solid organ transplantation for which long-term sulfonamide therapy is considered the treatment of choice. We report a patient 7 months status post-orthotopic heart transplantation with Nocardia nova bacteremia and pneumonia. Initial treatment consisted of intravenous trimethoprim-sulfamethoxazole, which cleared blood cultures, but the patient subsequently went into renal failure and required alternative therapy. This report describes the first case of N nova bacteremia after orthotopic heart transplantation successfully treated with clarithromycin. All therapy should be guided by antibiotic sensitivity, and combination therapy should be considered in acutely ill patients and cases where in vitro synergy has been documented. This case suggests that clarithromycin can be an alternative treatment in cases of sulfonamide resistance, intolerance, or allergy.

Optimal medical therapy is superior to transplantation for the treatment of class I, II, and III heart failure: a decision analytic approach.

BACKGROUND: The survival benefit of heart transplantation (HT) compared with optimal medical therapy (OMT) has never been tested. METHODS AND RESULTS: We created a decision analytic model that simulates a randomized clinical trial of OMT versus HT for each New York Heart Association (NYHA) class. The simulation calculates average life expectancy. The following assumptions were made for OMT annual mortality: class I no excess mortality from HF; class II and III based on MERIT-HF are 5.3% and 8.1%. Class IV is 12.8%, based on COPERNICUS. HT mortality rates were based on survival curves for HT 1982 to 2001. For classes I, II, and III, OMT demonstrated a life expectancy gain of 113 months (232+/-2.2 versus 119+/-2.1), 38 months (152+/-2.1 versus 114+/-2.1), and 6 months (117+/-1.8 versus 111+/-2.2), respectively, over HT. Class IV favored HT with a life expectancy gain of 26 months (107+/-2.1 versus 81+/-1.4) over OMT. Sensitivity analysis revealed if improvement in OMT decreased mortality by 38% for class IV patients, OMT and HT would have equivalent life expectancies. If improvement in HT resulted in a 7% increase in post-HT survival, OMT and HT would be equivalent for class III patients. If improvement in HT resulted in a 30% increase in post-HT survival, OMT and HT would be equivalent for class II patients. CONCLUSIONS: Our model predicts that currently, OMT is superior to HT for classes I, II, and III, but HT is superior for class IV. However, future advances in OMT or HT may change the relative benefits of these treatment modalities.

Cutaneous infection with rapidly-growing mycobacterial infection following heart transplant: a case report and review of the literature.

Nontuberculous mycobacteria are ubiquitous and infrequently cause disease in humans, most commonly in immunocompromised hosts. One type of nontuberculous mycobacteria is Mycobacterium abscessus. This rapidly growing mycobacterium is a soil or water saprophyte. It was previously classified as a subspecies of Mycobacterium chelonae; however, current taxonomy now designates it as a separate species. Rapidly growing mycobacteria are resistant to the usual antituberculous drugs. This emphasizes the need for tissue diagnosis and obtaining specimens for culture and drug susceptibility testing. M abscessus has been reported to cause infection in renal transplant patients, but is less well described in cardiac transplant recipients. We report the case of a 65-year-old man who presented 5 years after transplantation for heart failure, with a 2-day history of progressive right lower extremity swelling and redness. He recalled no antecedent trauma and denied any unusual epidemiologic exposure. Medical history included diabetes with peripheral neuropathy and renal insufficiency, hypertension, and right-sided heart failure felt to be due to obstructive sleep apnea. A punch biopsy of the area grew M abscessus sensitive only to clarithromycin (MIC not reported), amikacin (30 microg/mL), and kanamycin (30 microg/mL). On subsequent clinic visits, the patient had decreased leg swelling and resolution of the papular lesions. Ten weeks into antimycobacterial therapy, the patient had an increase in creatinine to 4.9 mg/dL from a baseline of 2.0 with fluid overload necessitating discontinuation of aminoglycoside therapy. He completed 6 months of treatment with oral clarithromycin. We describe these findings and review the literature in this report.

Thoracic organ transplantation in the United States, 1995-2004.

This article reviews trends in thoracic organ transplantation based on OPTN/SRTR data from 1995 to 2004. The number of active waiting list patients for heart transplants continues to decline, primarily because there are fewer patients with coronary artery disease listed for transplantation. Waiting times for heart transplantation have decreased, and waiting list deaths also have declined, from 259 per 1000 patient-years at risk in 1995 to 156 in 2004. Fewer heart transplants were performed in 2004 than in 1995, but adjusted patient survival increased to 88% at 1 year and 73% at 5 years. Emphysema, idiopathic pulmonary fibrosis and cystic fibrosis were the most common indications among lung transplant recipients in 2004. Waiting time for lung transplantation decreased between 1999 and 2004. Waiting list mortality decreased to 134 per 1000 patient-years at risk in 2004. One-year survival following transplantation has improved significantly in the past decade. The number of combined heart-lung transplants performed in the United States remains low, with only 39 performed in 2004. Overall unadjusted survival, at 58% at 1 year and 40% at 5 years, is lower among heart-lung recipients than among either heart or lung recipients alone.

Characteristics of patients referred for cardiac transplantation: implications for the donor organ shortage.

BACKGROUND: When the decision is made to proceed with cardiac transplantation, the risk/benefit ratio for continued medical therapy in that particular patient must be weighed against the risk/benefit ratio associated with cardiac transplantation. This can only be accomplished while the patient is on maximal medical therapy. METHODS: To better define the appropriateness of patients being referred for consideration of transplant, we examined the records of 100 consecutive adult patients referred to a cardiac transplant program. RESULTS: Two of five patients referred for transplantation had at least one contraindication for transplantation. Twenty percent of the patients were not treated with angiotensin-converting enzyme inhibitors and did not have any documented reason for undertreatment. Of those deemed too well for cardiac transplantation, 84% were alive and either class I or II (mean follow-up 21 months). CONCLUSIONS: We found the majority to be undertreated or with an absolute contraindication to transplantation. Of those deemed too well for transplantation after appropriate treatment, 84% were alive and well.

The effect of coenzyme Q10 in patients with congestive heart failure.

BACKGROUND: Coenzyme Q10 is commonly used to treat congestive heart failure on the basis of data from several unblinded, subjective studies. Few randomized, blinded, controlled studies have evaluated objective measures of cardiac performance. OBJECTIVE: To determine the effect of coenzyme Q10 on peak oxygen consumption, exercise duration, and ejection fraction. DESIGN: Randomized, double-blind, controlled trial. SETTING: University and Veterans Affairs hospitals. PATIENTS: 55 patients who had congestive heart failure with New York Heart Association class III and IV symptoms, ejection fraction less than 40%, and peak oxygen consumption less than 17.0 mL/kg per minute (or <50% of predicted) during standard therapy were randomly assigned. Forty-six patients completed the study. INTERVENTION: Coenzyme Q10, 200 mg/d, or placebo. MEASUREMENTS: Left ventricular ejection fraction (measured by radionuclide ventriculography) and peak oxygen consumption and exercise duration (measured by a graded exercise evaluation using the Naughton protocol) with continuous metabolic monitoring. RESULTS: Although the mean (+/-SD) serum concentration of coenzyme Q10 increased from 0.95+/-0.62 microg/mL to 2.2+/-1.2 microg/mL in patients who received active treatment, ejection fraction, peak oxygen consumption, and exercise duration remained unchanged in both the coenzyme Q10 and placebo groups. CONCLUSION: Coenzyme Q10 does not affect ejection fraction, peak oxygen consumption, or exercise duration in patients with congestive heart failure receiving standard medical therapy.

Hemodynamic comparison of twice daily metoprolol tartrate with once daily metoprolol succinate in congestive heart failure.

OBJECTIVES: To compare the hemodynamic effects of twice daily metoprolol tartrate (MT) and once daily metoprolol succinate (MS) in congestive heart failure patients. BACKGROUND: Adverse hemodynamic effects with MT demonstrated during initiation persist with drug readministration during chronic therapy. METHODS: Patients were randomly assigned to 6.25 mg MT or 25 mg MS orally and the dose was gradually increased to a target of 50 mg twice a day or 100 mg once a day, respectively. Hemodynamic measurements were obtained at baseline and after three months of therapy--both before and after drug readministration. RESULTS: Long term metoprolol therapy produced significant functional, exercise and hemodynamic benefits with no difference in response between either metoprolol preparation in the 27 patients (MT [14], MS [13]). When full dose metoprolol was readministered during chronic therapy, there were parallel adverse hemodynamic effects in both drug groups. Cardiac index decreased by 0.6 liters/min/m2 (p < 0.0001) with MT and by 0.5 liters/min/m2 (p < 0.0001) with MS. Systematic vascular resistance increased by 253 dyne-sec-cm(-5) (p < 0.001) with MT and by 267 dyne-sec-cm(-5) (p < 0.0005) with MS. Stroke volume index decreased by 7.0 ml/m2 (p < 0.0005) with MT and by 6.5 ml/m2 (p < 0.0001) with MS, while SWI decreased by 6.2 g-m/m2 (p < 0.0005) with MT and by 6.0 g-m/m2 (p < 0.001) with MS. CONCLUSION: Metoprolol tartrate and MS produce similar hemodynamic and clinical effects acutely and chronically despite the fourfold greater starting dose of MS used in this study. A more rapid initiation with readily available starting doses of MS may offer distinct advantages compared with MT in treating chronic heart failure patients with beta-adrenergic blocking agents.

Effects of BG9719 (CVT-124), an A1-adenosine receptor antagonist, and furosemide on glomerular filtration rate and natriuresis in patients with congestive heart failure.

OBJECTIVES: To determine the effects of furosemide and the selective A1 adenosine receptor BG9719 on renal function in patients with congestive heart failure (CHF). BACKGROUND: Studies suggest that adenosine may affect renal function by various mechanisms, but the effects of blockade of this system in humans is unknown. In addition, the effects of a therapeutic dose of furosemide on glomerular filtration rate (GFR) and renal plasma flow (RPF) in heart failure patients are controversial. METHODS: On different days, 12 patients received placebo, BG9719 and furosemide. Glomerular filtration rate, RPF and sodium and water excretion were assessed immediately following drug administration. RESULTS: Glomerular filtration rate was 84 +/- 23 ml/min/1.73m2 after receiving placebo, 82 +/- 24 following BG9719 administration and a decreased (p < 0.005) 63 +/- 18 following furosemide. Renal plasma flow was unchanged at 293 +/- 124 ml/min/1.73m2 on placebo, 334 +/- 155 after receiving BG9719 and 374 +/- 231 after receiving furosemide. Sodium excretion increased from 8 +/- 8 mEq following placebo administration to 37 +/- 26 mEq following BG9719 administration. In the six patients in whom it was measured, sodium excretion was 104 +/- 78 mEq following furosemide administration. CONCLUSIONS: Natriuresis is effectively induced by both furosemide and the adenosine A1 antagonist BG9719 in patients with CHF. Doses of the two drugs used in this study did not cause equivalent sodium and water excretion but only furosemide decreased GFR. These data suggest that adenosine is an important determinant of renal function in patients with heart failure.

Depression is common and precludes accurate assessment of functional status in elderly patients with congestive heart failure.

BACKGROUND: Congestive heart failure (CHF) and depression are independently known to result in physical decline and diminished functional capacity in the general population. The prevalence and relationship of depressive symptoms in CHF to physical limitations has not been objectively examined. METHODS AND RESULTS: The Center for Epidemiological Studies Depression Scale (CES-D) was used to ascertain depressive symptoms in 33 elderly ambulatory individuals with CHF. Self-report assessment of functional status, cardiopulmonary exercise testing (CPX), and measurement of energy expenditure by doubly labeled water and Caltrac Accelerometer (Muscle Dynamics, Torrance, CA) were performed. Depressed and nondepressed groups were compared. Forty-two percent of the patients scored in the depressed range (CES-D score of 16 or greater). There were no differences in demographic variables or severity of illness between the depressed and nondepressed patients. Energy expenditure was comparable across groups. Although obtaining similar maximal heart rate and maximal oxygen consumption (VO2max) on CPX, the depressed group showed less exertion on exercise testing with a significantly lower respiratory quotient (P = .017). CONCLUSION: Depressive symptoms were common and unrelated to the severity of CHF. Although depressed individuals tended to report worse physical functioning than nondepressed individuals, objective assessment of energy expenditure was comparable. Depressed patients appear to underestimate their functional ability. Subsequently, inaccurate assessment of functional status may occur.

Antithrombotic effect of FK506 vs cyclosporine in cardiac transplant recipients: potential implications in transplant arteriopathy.

BACKGROUND: An activated coagulation system has been implicated as a potential initiating or inciting factor in the development and progression of cardiac allograft vasculopathy (CAV). METHODS: By performing ex vivo perfusion studies of blood thrombogenicity under constant rheologic conditions and with a constant substrate, we sought to determine the relative effects on the coagulation system of FK506 vs cyclosporine in patients who have undergone cardiac transplantation. RESULTS-CONCLUSIONS: Compared with cyclosporine, FK506 significantly decreased the propensity to form thrombus; this suggests that FK506 may have a favorable impact on the development of CAV.

Effects of exercise training on peak performance and quality of life in congestive heart failure patients.

BACKGROUND: Exercise programs for patients with heart failure have often enrolled and evaluated relatively healthy, young patients. They also have not measured the impact of exercise performance on daily activities and quality of life. METHODS AND RESULTS: We investigated the impact of a 6-month supervised and graded exercise program in 33 elderly patients with moderate to severe heart failure randomized to usual care or an exercise program. Six of 17 patients did not tolerate the exercise program. Of those who did, peak oxygen consumption increased by 2.4 +/- 2.8 mL/kg/min (P < .05) and 6-minute walk increased by 194 ft (P < .05). However, outpatient energy expenditure did not increase, as measured by either the doubly labeled water technique or Caltrac accelerometer. Perceived quality of life also did not improve, as measured by the Medical Outcomes Study, Functional Status Assessment, or Minnesota Living With Heart Failure questionnaires. CONCLUSION: Elderly patients with severe heart failure can safely exercise, with an improvement in peak exercise tolerance. However, not all patients will benefit, and daily energy expenditure and quality of life do not improve to the same extent as peak exercise.

Short-term and long-term hemodynamic and clinical effects of metoprolol alone and combined with amlodipine in patients with chronic heart failure.

BACKGROUND: Initiation of beta-blocker therapy is often limited by worsening congestive heart failure, which may manifest as worsening hemodynamics. Deleterious hemodynamic effects might be mitigated with the vasodilation of combined calcium channel/beta-blocker therapy. METHODS AND RESULTS: This prospective, randomized study assessed the safety and efficacy of metoprolol alone or combined with amlodipine on hemodynamic parameters at baseline, 2 hours after the first dose of study medication, and after 12 weeks of therapy in patients receiving background triple therapy for mild to severe heart failure. Functional, exercise, and hormonal status were assessed at baseline and end of study. Twenty-nine patients (mean age 50 +/- 12.1 years) were enrolled; 21 completed 12 weeks of treatment. Mean ejection fraction at baseline was 13.4% +/- 5.7%; 79% of patients had heart failure classified as New York Heart Association class III, and 66% had heart failure of idiopathic origin. Heart rate and blood pressure did not change with short-term therapy in either group. The first dose of both regimens produced significant increases in systemic vascular resistance and significant decreases in cardiac output and index and stroke volume and stroke work indexes; combination therapy acutely yielded small but statistically significant increases in pulmonary artery, pulmonary capillary wedge, and right atrial pressures. Long-term therapy with both regimens produced significant decreases in heart rate, systemic vascular resistance, and pulmonary capillary wedge pressure and significant increases in cardiac output and index and stroke volume and stroke work indexes. Combination therapy produced significant long-term decreases in blood pressure. CONCLUSIONS: There was no further measurable benefit with the addition of amlodipine to metoprolol compared with the effects of metoprolol alone. Therapy with metoprolol alone and the combination of metoprolol and amlodipine was well tolerated in patients with mild to severe heart failure, as evidenced by a lack of adverse effects on hemodynamic parameters over the short term and clinical and hemodynamic improvement with long-term treatment.

Intravenous amiodarone suppression of electrical storm refractory to chronic oral amiodarone.

We report the case of an electrical storm in a cardiac arrest survivor with an ICD, in whom chronic oral amiodarone failed to suppress ventricular arrhythmias, and in whom intravenous amiodarone resulted in stability for 6 weeks prior to successful cardiac transplantation. Intravenous amiodarone can be successful in suppressing life-threatening ventricular arrhythmias, even when chronic oral amiodarone is unsuccessful.

A four-part regimen for clinical heart failure.

Combination therapy with a diuretic, digoxin, ACE inhibitor, and beta-blocker can help patients with heart failure caused by severe systolic dysfunction feel better and live longer. Especially with ACE inhibitors and beta-blockers, the key to success is starting at low doses and titrating carefully to proven target doses. The demanding complexity of the four-drug regimen is well worth the results.

Effect of race in the response to metoprolol in patients with congestive heart failure secondary to idiopathic dilated or ischemic cardiomyopathy.

We sought to determine the effect of race in response to metoprolol in patients with dilated cardiomyopathy. We found no difference in exercise, hemodynamic, and neurohormonal responses to metoprolol based on race in patients with cardiomyopathy.

Therapeutic options in advanced heart failure.

Treatment of advanced heart failure is usually a challenge. The successful use of beta-blockers to alleviate mild to moderate symptoms of cardiac dysfunction suggests that even severe cases of heart failure may be reversible. Transplantation remains the only sure way to obtain a fully functional heart, but new medications, mechanical devices, and surgical procedures could eventually prove to be alternatives.

Combined alpha-beta blockade (doxazosin plus metoprolol) compared with beta blockade alone in chronic congestive heart failure.

There has been growing evidence for the benefits of beta blockers, but alpha blockers have not shown sustained benefits in chronic congestive heart failure (CHF). Thirty patients with moderate to severe CHF (New York Heart Association class II to IV) were sequentially assigned to receive metoprolol 6.25 mg with the alpha-1 antagonist doxazosin 4 mg/day or metoprolol alone. The dose of metoprolol was gradually increased to a target dose of 50 mg orally twice daily. Hemodynamic measurements were obtained before drug therapy, 2 hours after the first dose of combined alpha-beta therapy or metoprolol alone, and after 3 months of continuous treatment. Nuclear ejection fraction, plasma norepinephrine, and submaximal and maximal exercise capacity were also measured before and after chronic therapy. With initial combined drug administration, mean arterial pressure, left ventricular filling pressure, and systemic vascular resistance decreased significantly compared with results after metoprolol alone. However, after 3 months of continuous therapy, both treatment groups showed similar and significant reductions in systemic vascular resistance and heart rate, with significant increases in cardiac index, stroke volume index, stroke work index, ejection fraction, and exercise capacity. Furthermore, the next dose of chronic combined medication no longer showed vasodilating effects. Chronic therapy with fixed-dose doxazosin and increasing doses of metoprolol produced identical effects as those seen in patients receiving metoprolol alone.