Risk stratification with exercise N(13)-ammonia PET in adults with anomalous right coronary arteries.

OBJECTIVE: In adults with an interarterial and intramural course of an anomalous right coronary artery from the left sinus (AAORCA), surgical unroofing is recommended in the setting of myocardial ischaemia. However, data regarding functional testing are limited, and the management of adults without ischaemia is unclear. To evaluate these patients, we employed an exercise N(13)-ammonia positron emission tomography (PET) protocol. We hypothesised that patients with typical angina and exertional dyspnoea would be more likely to have ischaemia and that patients without ischaemia could be managed conservatively. METHODS: Between July 2008 and December 2014, we retrospectively identified 27 consecutive patients >18 years old with an interarterial and intramural course of an AAORCA who had exercise N(13)-ammonia PET. RESULTS: The majority of patients had anatomic delineation with cardiac CT (25, 93%), and most patients had chest pain (24, 89%). Myocardial ischaemia with PET was common (13, 48%), and ischaemia was more likely in patients with typical angina and exertional dyspnoea (p<0.05). Surgery was performed in 12 patients including 11 patients with ischaemia. At a median follow-up of 245 days, there were no deaths in patients with surgery or in patients managed conservatively. CONCLUSIONS: In patients with an interarterial and intramural course of an AAORCA, typical angina and exertional dyspnoea are associated with ischaemia on exercise N(13)-ammonia PET. Referral for surgical unroofing in symptomatic patients with ischaemia on exercise N(13)-ammonia PET and initial conservative management in patients without ischaemia seems appropriate, though larger studies with long-term follow-up are needed.

Initial emergency department systolic blood pressure predicts left ventricular systolic function in acute decompensated heart failure.

Ejection fraction (EF) is often unknown in patients who present with acute decompensated heart failure (ADHF). The objective of this study was to determine whether a patient's systolic blood pressure is associated with their left ventricular EF. This study was a retrospective chart review of all patients admitted to an emergency department (ED) observation unit from January 2002 to December 2004. A low EF was defined as <40%. Among 475 patients, the median age was 72 years, 53% were men, 40% were white, 59% were black, and 59% had a low EF. Patients with low EFs were more likely male ( P<.0001), with prior congestive heart disease ( P<.0001), longer QRS duration ( P<.0001), left bundle branch block ( P<.0001), and higher B-type natriuretic peptide ( P<.0001). The low EF group was less likely to have diabetes ( P<.0001). Adjusted odds ratios for an EF >or=40% were significant at all systolic blood pressure readings >120 mm Hg. Having an ED systolic BP >120 mm Hg is associated with significantly higher rates of preserved left ventricular systolic function in patients with ADHF.

Endogenous B-type natriuretic peptide: a limb of the regulatory response to acutely decompensated heart failure.

Acutely decompensated heart failure (ADHF) represents an episodic failure of cardiorenal homeostasis that may resolve with upregulation of natriuretic peptides, bradykinin, and certain prostacyclins. B-type natriuretic peptide (BNP) has multiple favorable effects, including vasodilation, diuresis, natriuresis, and inhibition of vascular endothelial proliferation and cardiac fibrosis. By antagonizing the effects of activation of the renin-angiotensin-aldosterone system (RAAS) and the sympathetic nervous system in volume overload, the endogenous BNP response may help rescue patients from episodic ADHF. Although knowledge of BNP physiology is expanding, we still have limited understanding of the heterogeneity of proBNP-derived molecules, including active 32 amino acid BNP and less active junk BNP forms. Emerging evidence suggests that in ADHF, the endogenous BNP response is overwhelmed by neurohormonal activation. This relative BNP deficiency may also be accompanied by physiologic resistance to BNP. Additionally, abnormalities of BNP production may result in a lower proportion of active BNP relative to less active forms that may also be detected by point-of-care tests. Improved detection of the various BNP species may clarify these concepts and facilitate improved clinical management of ADHF.

The impact of hypogammaglobulinemia on infection outcome in patients undergoing ventricular assist device implantation.

BACKGROUND: Infection is a major comorbidity after ventricular assist device (VAD) placement. Defects in cellular immunity have been reported after VAD placement. However, to our knowledge, quantitative immunoglobulin G (IgG) level determination and the impact of hypogammaglobulinemia (HGG) on infections after VAD implantation have not been evaluated before. METHODS: A total of 76 patients (mean age, 53 years) underwent VAD implantation as a bridge to transplantation and had IgG levels determined as a baseline before transplantation. Patients were divided into 2 groups according to IgG level: Control Group (n = 56, IgG > or = 700 mg/dl) and HGG Group (n = 20, IgG < 700 mg/dl). Infection outcome during the VAD course and after transplantation was analyzed in relation to the IgG level. RESULTS: Baseline characteristics were similar in both groups. The incidence of bacteremia (14/20 [70%] vs 18/56 [32%], p = 0.0032) and major infection (19/20 [95%] vs 31/56 [56%], p = 0.0009) were significantly increased in the HGG Group compared with the Control Group. After transplantation, the episodes of rejection were similar in both groups and survival was similar. The HGG Group experienced more cytomegalovirus infections compared with the Control Group (9/20 [45%] vs 9/56 [16%], p = 0.009). CONCLUSIONS: VAD patients with HGG are at increased risk of infections. After transplantation, these patients also experience increased cytomegalovirus infections. A randomized preemptive IgG replacement trial may be warranted in the future to determine if this intervention will alleviate the risk of infection.

Vasopressin receptor antagonists in heart failure.

Vasopressin receptor antagonists are a new class of drugs that address the problems of fluid retention, hyponatremia, and renal dysfunction in heart failure. Elevated vasopressin levels in heart failure cause myocardial fibrosis, hypertrophy and vasoconstriction by activating the V1a receptors, as well as water retention and hyponatremia by activating V2 receptors. Antagonism of V1a receptors alone is of little benefit. In contrast, antagonism of V2 receptors results in increased free water excretion and increased sodium concentration. Vasopressin receptor antagonists may be viewed as the first new class of agents with predominantly aquaretic effects, in contrast to the natriuretic effects of loop diuretics. The predominant action of vasopressin receptor antagonists is water excretion, without depletion of other electrolytes, and less neurohormonal stimulation compared with loop diuretics. Classified as neurohormonal antagonists, vasopressin receptor antagonists acutely may improve congestion and hyponatremia, while chronically preventing progression of left ventricular dysfunction. Several compounds have been evaluated in late-stage clinical trial programs, and at least one may be used as an adjunct to standard medical therapy, combining aquaresis for congestion with neurohormonal antagonism for morbidity and mortality. We reviewed recent patents dealing with heart failure, hyponatremia, anti-diuretic hormone, and vasopressin antagonists.

Intravascular ultrasound evidence of angiographically silent progression in coronary atherosclerosis predicts long-term morbidity and mortality after cardiac transplantation.

OBJECTIVES: The aim of this study was to determine whether angiographically silent early coronary intimal thickening could predict long-term morbidity and mortality. BACKGROUND: Although intravascular ultrasound (IVUS) is widely used to detect early transplant coronary disease, its prognostic significance has not been well defined. METHODS: The study cohort consisted of 143 patients who underwent early multivessel (2.1 +/- 0.7 arteries/patient) IVUS examination 1.0 +/- 0.5 month and 12.0 +/- 1.0 month after transplantation. The change in intimal thickness was evaluated using paired analysis of 1,069 matched sites. Rapidly progressive vasculopathy was defined as the change in intimal thickness >/=0.5 mm. Patients were followed for a primary end point of all-cause mortality and a secondary composite end point of mortality and nonfatal myocardial infarction (MI). Angiographic disease, defined as any >/=50% diameter stenosis, was assessed in 126 patients. RESULTS: Intravascular ultrasound at one year demonstrated rapid progression in 54 (37%) of 143 patients and new lesions in 67 (47%) of 143 of patients. At a mean clinical follow-up of 5.9 years, more patients with rapidly progressive vasculopathy died, as compared with those without (26% vs. 11%, p = 0.03). Death and MI also occurred more frequently among those with rapid progression than in those without it (51% vs. 16%, p < 0.0001). There was no significant difference in outcome in patients with and without donor-transmitted lesions. Angiographic disease was found in 11 (22%) of 50 patients with and in 2 (2.1%) of 76 patients without (p = 0.003) rapidly progressive vasculopathy. The IVUS-defined rapid progression correlated highly with future development of angiographic disease (p = 0.0005). CONCLUSIONS: Rapidly progressive vasculopathy by IVUS, defined as an increase of >/=0.5 mm in intimal thickness within the first year after transplantation, is a powerful predictor of all-cause mortality, MI, and angiographic abnormalities. Accordingly, such patients may be candidates for more aggressive anti-atherosclerotic and/or immunosuppressive therapy.

Current and future uses of nesiritide.

Nesiritide, recombinant human B-type natriuretic peptide, is an intravenous vasodilator that is used to treat acutely decompensated heart failure. In addition to its modest diuretic and natriuretic properties, nesiritide reduces intracardiac filling pressures, increases cardiac index and improves symptoms. Long-term safety data are accruing, and a number of ongoing clinical trials will explore the potential benefit of nesiritide in a variety of clinical situations: peri-operative cardiac surgery, serial out-patient infusions, continuous out-patient or pretransplant infusions, and infusions in patients with pulmonary hypertension, bronchospasm, renal insufficiency, and acute coronary syndromes. Alternative delivery methods also are under development.

Management of decompensated heart failure.

Hospitalizations for heart failure have increased threefold during the past 3 decades, and this trend is expected to continue for the next 25 years. Heart failure now is the largest single expense for Medicare, and hospitalizations account for more than half of these costs. Most hospitals sustain financial losses with heart failure management because expenses exceed reimbursement. The hospital emergency department often is the initial encounter site for patients with new-onset heart failure, but most heart failure emergency department visits are for recurrent decompensation. The majority of these patients will be admitted to the hospital. Although accurate diagnosis and effective treatment are important for improving outcomes and lowering costs, there are no published guidelines for managing acutely decompensated heart failure. This review describes new diagnostic and management strategies, utilizing the emergency department observational unit as a triage area, that may decrease hospital length of stay, reduce hospital costs, and prevent readmissions.

Guidelines for the diagnosis and management of heart failure.

Heart failure has reached epidemic proportions. Five million Americans have been diagnosed with heart failure, and this number is expected to double within the next 30 years. One million patients are hospitalized annually with decompensated heart failure, and half will be readmitted for recurrent symptoms within 6 months. Heart failure primarily affects the elderly and is the most common reason for hospitalization in this age group. The prognosis for heart failure is poor, worse than most malignancies. Heart failure accounts for 280,000 deaths annually, and the 5-year survival rate is less than 50% despite multiple therapeutic advances. Poor survival may be attributed in part to poor application of evidence-based heart failure therapies and patient noncompliance. This review describes current guidelines for diagnosing and managing patients with heart failure.

Nesiritide in perspective: evolving approaches to the management of acute decompensated heart failure.

Nesiritide is currently indicated for the management of acute decompensated heart failure defined by the presence of volume overload and dyspnea at rest or with minimal activities. Hypotension and cardiogenic shock are the major contraindications to nesiritide use. The recommended dosing schedule is a 2 micro g/kg bolus followed by a 0.01 micro g/kg/min infusion. Some clinicians, however, opt to begin the infusion at the recommended dose without a loading bolus in nonemergency situations. The average duration of infusion in the Vasodilation in the Management of Acute Congestive Heart Failure (VMAC) trial was approximately 28 hours. Clinical efficacy endpoints included resolution of dyspnea and reduction of volume overload. Appropriate oral drug therapy for heart failure management should be initiated during the nesiritide infusion. The 15-year transition of B-type natriuretic peptide from a newly discovered physiologic entity to clinical use in the diagnosis and treatment of heart failure provides a remarkable example of rapid technological improvement and enhanced clinical understanding. As with most advances, the process of rolling back the frontiers of knowledge has posed even more questions. However, we must not overlook the progress to date, simply because all of the answers are not yet available.

Early constriction or expansion of the external elastic membrane area determines the late remodeling response and cumulative lumen loss in transplant vasculopathy: an intravascular ultrasound study with 4-year follow-up.

BACKGROUND: Early constriction of the external elastic membrane (EEM) area has been observed after cardiac transplantation. The aim of this study was to compare the late disease process of transplant vasculopathy between coronary segments with early constrictive and expansive remodeling. METHODS: Serial intravascular ultrasound data obtained annually for 4 years after transplantation in 38 transplant recipients was available. In 135 matched segments from 59 coronary arteries ultrasound images were digitized at 1-mm intervals. Mean values of the external elastic membrane (EEM), lumen and intimal areas were calculated. On the basis of a decrease or increase in EEM area within the first year after transplantation, we defined segments with early constrictive remodeling (CR, n = 71) or early expansive remodeling (ER, n = 64). RESULTS: Annual changes in intimal area were similar between segments with early CR and ER throughout the follow-up period. However, during the second and third year, annual increases in EEM area were greater in segments with early CR than in segments with early ER (second year: 1.5 +/- 2.7 vs 0.6 +/- 2.8 mm(2), p = 0.052; third year: 1.3 +/- 2.5 vs -0.03 +/- 2.6 mm(2), p = 0.003). Despite this late expansion, segments with early CR showed a cumulative decrease in the EEM area and a greater lumen loss than segments with early ER (-2.5 +/- 3.4 vs -0.6 +/- 2.6 mm(2), p < 0.001). CONCLUSIONS: In transplant vasculopathy, the late remodeling response was different between segments with early constrictive and expansive remodeling, despite similar intimal thickening. Early constriction caused an overall decrease in EEM area and greater loss of lumen during follow-up.

Repeated intravascular ultrasound imaging in cardiac transplant recipients does not accelerate transplant coronary artery disease.

OBJECTIVES: This study was designed to examine the impact of repeated intravascular ultrasound (IVUS) examinations on transplant coronary artery disease (CAD). BACKGROUND: Serial IVUS is the most accurate method for early detection and surveillance of transplant CAD. However, the long-term safety of serial IVUS exams is not well described. Accordingly, we examined the impact of repeated IVUS examinations on transplant CAD. METHODS: We examined 226 transplant recipients who underwent one or more IVUS examinations and coronary angiography at least one year after the last IVUS exam. The coronary angiograms were analyzed using quantitative coronary angiography. Vessel diameters, frequency, and severity of stenoses in IVUS-imaged and nonimaged coronary arteries were compared. In a subgroup analysis of 31 patients, angiographic lumen diameters were measured at baseline (within eight weeks of transplantation) and during follow-up (after two, three, or four IVUS studies). RESULTS: In the 226 patients, 548 coronary arteries were previously imaged by IVUS and 130 arteries were not imaged by IVUS. On subsequent angiograms, stenoses were observed in 16.2% (21/130) of nonimaged arteries and 19.5% (107/548) of imaged arteries (p = 0.38). The arterial diameters of nonimaged and imaged arteries were not significantly different (p = 0.07), regardless of the number of IVUS exams and duration of follow-up. Subgroup analysis revealed a significant decrease in vessel lumen diameter over time in nonimaged as well as imaged arteries. The magnitude of the diameter decrease was not significantly different between the two groups. CONCLUSIONS: Repeated IVUS examinations following heart transplantation do not result in angiographically evident acceleration of transplant CAD. Therefore, serial IVUS imaging is a safe method for the detection and surveillance of transplant CAD.

Using BNP to diagnose, manage, and treat heart failure.

A rapid assay for B-type natriuretic peptide (BNP) not only can be used to diagnose heart failure, it can help the clinician evaluate effectiveness of therapy, determine when discharge from the hospital is appropriate, and estimate prognosis. A synthetic formulation of BNP (nesiritide) is used to treat decompensated heart failure, resulting in improved hemodynamics and symptoms.

"BNP" for heart failure: role of nesiritide in cardiovascular therapeutics.

B-type natriuretic peptide, or nesiritide, recently gained US Food and Drug Administration approval as the first new parenteral agent approved for heart failure therapy in more than a decade. Nesiritide refers to a peptide identical to endogenous B-type natriuretic peptide, currently manufactured by recombinant DNA technology. Nesiritide has been evaluated in clinical trials involving more than 700 subjects. The drug produces a prompt fall in systemic vascular resistance and pulmonary capillary wedge pressure, associated with rapid clinical improvement in decompensated heart failure. Nesiritide represents an attractive choice for first-line therapy of acutely decompensated heart failure patients. In this review, the authors summarize the currently available data regarding the use of nesiritide, and offer recommendations for its use based on our experience with the compound in clinical trials.

How to use nesiritide in treating decompensated heart failure.

Nesiritide (Natrecor), a synthetic formulation of B-type natriuretic peptide (BNP), is the first new parenteral agent to be approved for treating heart failure in more than a decade. In patients hospitalized with decompensated congestive heart failure, nesiritide promptly reduces pulmonary capillary wedge pressure, pulmonary arterial pressure, right atrial pressure, and systemic vascular resistance, resulting in clinical improvement.

Congestive heart failure.

Preview Patients with congestive heart failure generally have a poor prognosis, and sudden death is common. Concepts of management have changed drastically through the years, in hopes that predisposing factors can be modified. In this article, Drs Hobbs and Czerska give an overview of the problem and examine the status of pharmacologic therapy and various surgical techniques.