Kenneth L. Baughman

Thresholds of Physical Activity and Life Expectancy for Patients Considering Destination Ventricular Assist Devices

BACKGROUNDnCurrent implantable left ventricular assist devices (LVAD) improve survival and function for patients with very late stage heart failure (HF) but may also offer benefit before inotrope dependence. Debate continues about selection of HF patients for LVAD therapy. We sought to determine what level of personal risk and disability HF patients thought would warrant LVAD therapy.nnnMETHODSnThe study included 105 patients with symptomatic HF and an LV ejection fraction (EF) < 35% who were given a written paragraph about LVADs and asked about circumstances under which they would consider such a device. New York Heart Association (NYHA) functional class, time trade-off utility, and patient-assessed functional score were determined.nnnRESULTSnParticipants (mean age, 58 years) had an LVEF of 21%. The median duration of HF was 5 years, and 65% had a primary prevention implantable cardioverter defibrillator. Presented with a scenario of bed-ridden HF, 81% stated they would definitely or probably want an LVAD; 50% would consider LVAD to prolong survival if HF survival were predicted to be < 1 year and 75% if < 6 months. Meanwhile, 44% would consider LVAD if they could only walk < 1 block and 64% if they could not dress without stopping. Anticipated thresholds did not differ by NYHA class, time trade-off, or functional score.nnnCONCLUSIONSnPatient thresholds for LVAD insertion parallel objective survival and functional data. HF patients would be receptive to referral for discussion of LVAD by the time expected mortality is within 6 to 12 months and activity remains limited to less than 1 block.

Myocardial Parvovirus B19 Persistence: Lack of Association with Clinicopathologic Phenotype in Adults with Heart Failure

Background—Multiple viruses have been isolated from the heart, but their significance remains controversial. We sought to determine the prevalence of cardiotropic viruses in endomyocardial biopsy (EMB) samples from adult patients with heart failure (HF) and to define the clinicopathologic profile of patients exhibiting viral positivity. Methods and Results—EMB from 100 patients (median ejection fraction, 30%; interquartile range [IQR], 20% to 45%) presenting for cardiomyopathy evaluation (median symptom duration, 5 months; IQR, 1 to 13 months) were analyzed by polymerase chain reaction for adenovirus, cytomegalovirus, enteroviruses, Epstein-Barr virus, and parvovirus B19. Each isolate was sequenced, and viral load was determined. Parvovirus B19 was the only virus detected in EMB samples (12% of subjects). No patient had antiparvovirus IgM antibodies, but all had IgG antibodies, suggesting viral persistence. The clinical presentation of parvovirus-positive patients was markedly heterogeneous with both acute and chronic HF, variable ventricular function, and ischemic cardiomyopathy. No patient met Dallas histopathologic criteria for active or borderline myocarditis. Two patients with a positive cardiac MRI and presumed “parvomyocarditis” had similar viral loads to autopsy controls without heart disease. The oldest parvovirus-positive patients were positive for genotype 2, suggesting lifelong persistence in the myocardium. Conclusions—Parvovirus B19 was the only virus isolated from EMB samples in this series of adult patients with HF from the United States. Positivity was associated with a wide array of clinical presentations and HF phenotypes. Our studies do not support a causative role for parvovirus B19 persistence in HF and, therefore, advocate against the use of antiviral therapy for these patients.Background— Multiple viruses have been isolated from the heart, but their significance remains controversial. We sought to determine the prevalence of cardiotropic viruses in endomyocardial biopsy (EMB) samples from adult patients with heart failure (HF) and to define the clinicopathologic profile of patients exhibiting viral positivity.nnMethods and Results— EMB from 100 patients (median ejection fraction, 30%; interquartile range [IQR], 20% to 45%) presenting for cardiomyopathy evaluation (median symptom duration, 5 months; IQR, 1 to 13 months) were analyzed by polymerase chain reaction for adenovirus, cytomegalovirus, enteroviruses, Epstein-Barr virus, and parvovirus B19. Each isolate was sequenced, and viral load was determined. Parvovirus B19 was the only virus detected in EMB samples (12% of subjects). No patient had antiparvovirus IgM antibodies, but all had IgG antibodies, suggesting viral persistence. The clinical presentation of parvovirus-positive patients was markedly heterogeneous with both acute and chronic HF, variable ventricular function, and ischemic cardiomyopathy. No patient met Dallas histopathologic criteria for active or borderline myocarditis. Two patients with a positive cardiac MRI and presumed “parvomyocarditis” had similar viral loads to autopsy controls without heart disease. The oldest parvovirus-positive patients were positive for genotype 2, suggesting lifelong persistence in the myocardium.nnConclusions— Parvovirus B19 was the only virus isolated from EMB samples in this series of adult patients with HF from the United States. Positivity was associated with a wide array of clinical presentations and HF phenotypes. Our studies do not support a causative role for parvovirus B19 persistence in HF and, therefore, advocate against the use of antiviral therapy for these patients.

Hawthorn extract: Is it time to turn over a new leaf?

Kenneth L. Baughman, MD, David J. Bradley, MD, PhD Hawthorn (Crataegus oxyacantha), also known as haw, maybush, or whitehorn, is a fruit-bearing shrub with thorny branches, deciduous leaves, and white flowers that contain flavonoids, amines, triterpene, saponins, and oligomeric procyanidins (1). These compounds have inotropic, vasodilating, lipid-lowering, antioxidant, and anti-inflammatory properties, which may protect against reperfusion-related myocardial damage and arrhythmias (2,3). This herbal remedy has limited apparent adverse effects, including rash, sweating, palpitations, dizziness, agitation, sleepiness, and gastrointestinal symptoms. Although hawthorn extract has been used for various medical complaints for more than 700 years, it has only been recently evaluated systematically for heart disease, particularly chronic heart failure. In this issue of The American Journal of Medicine, Pittler et al. (4) present a meta-analysis of randomized clinical trials of hawthorn extract in patients with chronic heart failure (New York Heart Association class I to III). They found that use of hawthorn extract was associated with a modest improvement in maximal exercise workload. By performing a thorough search of eligible studies and by restricting their analysis to double-blind, randomized, controlled trials, the authors minimized bias and enhanced the validity of their analysis. Should we, however, exchange digitalis leaf for hawthorn extract? Despite the positive results of the metaanalysis, there are lingering concerns. First, use of angiotensin-converting enzyme inhibitors was either not allowed or not reported in four trials included in the metaanalysis. There has been only one trial comparing hawthorn extract with an established agent in the treatment of heart failure (5). Whether hawthorn extract provides clinical benefits beyond those of proven heart failure drugs remains uncertain. Second, the observed improvement in maximal exercise workload was derived from a total of 310 randomized patients with only 3 to 16 weeks of follow-up. There has been no long-term randomized trial of this agent, and many inotropic predecessors have improved symptoms and exercise capacity in the short term at the expense of increased mortality with continued use (6). Studies involving larger samples and a longer follow-up will be required to assess the effects of hawthorn extract on mortality as well as on quality of life and hospitalization. To that end, the Survival and Prognosis: Investigation of Crataegus Extract—WS1442 (SPICE) trial will enroll approximately 2300 patients from 120 international centers and evaluate the longterm effects (24 months) of a standard preparation of hawthorn extract, as compared with placebo, on hospitalizations and mortality in patients with modest heart failure and an established standard medical regimen (7). Results of this trial, which are expected to be available during 2003–2004, should help determine if hawthorn extract is appropriate as therapy for heart failure. Herbal therapy is currently estimated to be used by 12.1% to 14% of the U.S. population, an increase from 2.5% in 1990 (8,9). Approximately 16% to 18.4% of patients taking prescription medication also take herbal remedies. Unfortunately, less than 40% of these patients inform their physicians that they are taking herbal treatments (8,9). Hence, it is important that physicians inquire about their patients’ use of alternative therapies and become knowledgeable about the effects and potential adverse effects of commonly used agents. In addition, despite the limited profit motive for rigorous investigation of these agents because of less easily obtained patent protection to those companies studying or manufacturing herbal compounds (10), we must evaluate herbal agents as carefully as we do newly synthesized drugs. Finally, we cannot allow herbal treatments to be unregulated, exposing patients to false claims and increased medical risk based on nonstandard preparations and contaminants in these products.

Cardiac Sarcoidosis Presenting as Heart Block

A 47-year-old man without prior cardiac disease presented with lightheadedness, nausea, and fatigue while golfing. The initial 12-lead ECG demonstrated a first-degree atrioventricular delay, a transthoracic echocardiogram revealed normal myocardial thickness and left ventricular function, and stress nuclear imaging studies showed no ischemia; however, atrioventricular block was noted during the stress test. Within 2 months, complete heart block with junctional escape rhythm (Figure 1) developed. Laboratory testing that included thyroid studies and Lyme titers was unrevealing. Magnetic resonance imaging demonstrated 2 focal regions of late gadolinium enhancement (Figure 2) in a pattern suggestive …

Management of a case of peripartum cardiomyopathy.

Background A 49-year-old woman presented at hospital, 8 days after giving birth to twins, with signs and symptoms of congestive heart failure. She had no history of heart disease, exposure to cardiotoxic agents or family history of heart muscle disease.Investigations Physical examination and laboratory blood tests, electrocardiography, transthoracic echocardiography.Diagnosis Peripartum cardiomyopathy.Management Standard heart failure therapy including β-blockers, angiotensin-converting-enzyme inhibitors, diuretics and systemic anticoagulation.

Clinical management of acute myocarditis and cardiomyopathy

Several forms of acute myocarditis may present as new onset cardiomyopathy and congestive heart failure. These include myocarditis characterized as fulminant, giant cell, chronic acute, eosinophilic (particularly necrotizing eosinophilic myocarditis), peripartum, Lyme, small pox vaccine related, HIV-related, and acute myocardial infarction caused by myocarditis with coronary arteritis. Treatment of each of these disorders is dependent upon considering the diagnosis, performing endomyocardial biopsy for histologic confirmation, and use of immune modulating or immunosuppressive therapy in appropriate candidates. Some forms of acute myocarditis may resolve spontaneously without any treatment including fulminant myocarditis, peripartum, and small pox vaccine related myocarditis. Others require immune modulating therapy including giant cell myocarditis, and eosinophilic myocarditis; while others require specific treatment for the infectious or autoimmune pathogen responsible including eosinophilic myocarditis, Lyme myocarditis, and HIV-related. We currently have the technology which may allow us to determine if the 50% of patients with “idiopathic” cardiomyopathy in fact have a viral or post viral autoimmune related compromise of cardiac function.