Ernst R. Schwarz

Thrombolysis with recombinant unglycosylated single-chain urokinase-type plasminogen activator (saruplase) in acute myocardial infarction : influence of heparin on early patency rate (LIMITS study)

OBJECTIVESnThe Liquemin in Myocardial Infarction During Thrombolysis With Saruplase (LIMITS) study was instituted to evaluate and characterize the effect of a prethrombolytic heparin bolus (5,000 IU) on the efficacy and safety of saruplase in patients with acute myocardial infarction.nnnBACKGROUNDnHeparin has been used after thrombolytic therapy for acute myocardial infarction to prevent reocclusion of the infarct-related artery.nnnMETHODSnThe study was designed as a randomized, parallel-group, double-blind, multicenter trial. Patients were treated within 6 h of onset of symptoms with either a bolus of 5,000 IU of heparin (Liquemin) (n = 56, HSH group) or placebo (n = 62, PSH group) before thrombolytic treatment with saruplase given as a 20-mg bolus followed by an infusion of 60 mg over 60 min. Thirty minutes after completion of thrombolysis, an intravenous heparin infusion was administered for 5 days. Before coronary angiography was performed at 6 to 12 h after start of lysis, an additional bolus of 5,000 IU heparin was given to all patients. End points studied were patency of the infarct-related artery, changes in the hemostatic system and bleeding complications.nnnRESULTSnIn the HSH group (heparin-saruplase-heparin), 78.6% of patients had an open infarct-related vessel (Thrombolysis in Myocardial Infarction [TIMI] flow grade 2 or 3) compared with 56.5% in the PSH group (placebo-saruplase-heparin) (intention-to-treat analysis, p = 0.01). No significant difference was observed between the two groups with regard to changes in fibrinogen and fibrin/fibrinogen degradation products. A total of eight bleeding complications (14.3%) were observed in the HSH group and five (8.1%) in the PSH group; no cerebrovascular event occurred, and no allergic reaction was reported. A total of 12 patients died during the hospital stay, 3 in the HSH group (5.4%) and 9 in the PSH group (14.5%).nnnCONCLUSIONSnIn acute myocardial infarction, the administration of a heparin bolus before thrombolytic therapy with saruplase is associated with a significantly higher patency at angiography 6 to 12 h after the start of thrombolysis without any appreciable increase in risk of bleeding.

Induction Therapy With Thymoglobulin After Heart Transplantation : Impact of Therapy Duration on Lymphocyte Depletion and Recovery, Rejection, and Cytomegalovirus Infection Rates

BACKGROUNDnThis retrospective single-center study compared lymphocyte depletion in 144 heart transplant recipients using 2 different induction protocols with Thymoglobulin (Genzyme Transplant, Cambridge, MA).nnnMETHODSnThymoglobulin (1.5 mg/kg) was given to 105 patients for 7 days (Thymo7) and 39 patients for 5 days (Thymo5).nnnRESULTSnPatient clinical characteristics were similar except that the Thymo7 group had a higher prevalence of women (33% vs 15%, p = 0.04), gender mismatch (35% vs 19%, p = 0.07), donor African American race (19% vs 2%, p = 0.008), older donor age (35 +/- 13 vs 31 +/- 12, p = 0.08), and higher pre-transplant creatinine (1.43 +/- 0.67 vs 1.25 +/- 0.48 mg/dl, p = 0.095). Seventy-five percent of the Thymo7 group reached target (absolute lymphocyte count <or=200) and 42% at 21 days (p = 0.002). Thymo7 patients had significantly lower rejection rates (>or=1B) within the first year (7% vs 22%, p = 0.02). No humoral rejection occurred. At 1 year, freedom from rejection was 93% in the Thymo7 group vs 80% in the Thymo5 group (p = 0.007), and cytomegalovirus disease (9% and 5%, p = 0.5) and bacterial infection (26% vs 32%, p = 0.5) were similar. One-year actuarial survival was 92% +/- 3% in the Thymo7 and 100% in the Thymo5 group (p = 0.07), and at 3 years, 85 +/- 4% and 90 +/- 6%, respectively (p = 0.4).nnnCONCLUSIONSnBoth Thymoglobulin regimens were well tolerated. The 7-day treatment led to more efficient and prolonged lymphocyte depletion and significantly less rejection at 1 year, without an increase in cytomegalovirus infection rate.

Ultrafiltration for the Management of Acute Decompensated Heart Failure

Heart failure is a major public health problem and is increasing in incidence throughout the industrialized world. Despite recent advances in pharmacotherapy, the overall mortality remains high and largely unchanged. Ultrafiltration has received increased attention in the treatment of acute decompensated congestive heart failure, and recent clinical trials suggest its usefulness in removing volume while preserving renal function. This review will focus on the background of ultrafiltration in the treatment of acute decompensated heart failure as well as the current evidence regarding its efficacy and safety.

The Potential Effects of IGF-1 and GH on Patients With Chronic Heart Failure:

Heart failure (HF) is an important health concern with almost a quarter million deaths each year despite advances in medical therapy. Improvement of cardiac function has been shown to reduce morbidity and mortality in patients with HF. There has been recent interest in the growth hormone (GH) / insulin-like growth factor (IGF) pathway as a potential therapeutic target for patients with HF. Insulin-like growth factor 1 has been shown to augment cardiac function ex vivo and in animals. It was hypothesized that IGF-1/IGF-binding protein 3 levels might be able to provide prognostic benefits in patients with heart disease. Initial observational studies have shown significant benefits from GH supplementation including improved ejection fraction, increased exercise tolerance, and decreased New York Heart Association functional class. These results, however, were not replicated in randomized, controlled trials. Patients with advanced stages of HF might develop cachexia associated with a state of significant GH resistance. The lack of response to GH supplementation may be secondary to a deficiency in IGF-1, the effector hormone. Hypothetically, this group of patients could benefit from direct IGF-1 supplementation. Combined therapy with GH and IGF-1 is appealing; however, future trials in patients with advanced HF are warranted to prove this concept.

Left ventricular assist device placement in a patient with end-stage heart failure and human immunodeficiency virus

Left ventricular assist device (LVAD) insertion has been used more frequently within the recent years either as a bridge to transplant or as destination therapy in patients with advanced heart failure who fail medical therapy. We present a report of a 60-year-old male patient with end-stage heart failure and cardiomyopathy with a history of human immunodeficiency virus (HIV) infection who underwent LVAD placement as destination therapy. To our knowledge, LVAD placement in this fashion has not been reported previously. Following LVAD implantation, the patient recovered during the course of five weeks and was discharged home from the hospital in good condition. The patient was alive and free of any activity limitations sixteen months postoperatively. We conclude that LVAD placement for end-stage heart failure may be a feasible option as destination therapy in patients with HIV.

Case of fulminant giant-cell myocarditis associated with polymyositis, treated with a biventricular assist device and subsequent heart transplantation

Giant-cell myocarditis is an autoimmune myocarditis that rapidly progresses to heart failure, and is often associated ventricular tachycardia. We describe an otherwise healthy patient who was acutely ill with decompensated heart failure and ventricular tachycardia associated with rash and polymyositis, who then developed cardiogenic shock and multiorgan failure due to giant-cell myocarditis.

Sexual dysfunction in cardiac rehabilitation patients is much more than simply an epiphenomenon and needs more study.

It appears interesting that 2 of the world’s most intellectual and scientifically productive minds commented often about the relevance of sexual function and its potential problems. Johann Wolfgang Von Goethe (1749-1832) was not only a writer and scientist who independently discovered the human intermaxillary bone in 1784 and the first who formulated a theory of plant metamorphosis, but many of Goethe’s artistic works such as Faust or the Venetian Epigrams do contain a relatively heavy sexual content, since he saw sexuality in general as a topic that merited poetic and artistic depiction. A few hundred years earlier than that, Leonardo da Vinci (1452-1519), the epitome of the Italian Renaissance stated: “The penis does not obey the order of its master, who tries to erect or shrink it at will, whereas instead the penis erects freely while its master is asleep. The penis must be said to have its own mind, by any stretch of the imagination.” Since then, researchers have determined the penis isn’t quite as independently minded as da Vinci observed hundreds of years ago, but is largely under the control of the central nervous system and its function as a sexual organ is highly dependent on vascular properties. In spite of the appreciation of sexuality as essential in human life and the attempts to understand the pathophysiology of dysfunction by these and several other extraordinary minds, the acceptance of sexual problems, in men as well as in women up to this day and therefore, the intuitive search for scientific answers continues to be blurred by an overwhelming lack of comprehension. Sexual Dysfunction in Cardiac Rehabilitation Patients Is Much More Than Simply an Epiphenomenon and Needs More Study Ernst R. Schwarza and Biing-Jiun Shenb

Intermittent outpatient nesiritide infusion reduces hospital admissions in patients with advanced heart failure

Recombinant B-type natriuretic peptide (BNP) is a therapeutic modality in patients with decompensated congestive heart failure. Retrospectively tested are the effects of intermittent outpatient nesiritide infusion on symptoms, hospital readmission rates, endogenous BNP, and renal function in patients with advanced heart failure. Twenty-four patients in heart failure in New York Heart Association (NYHA) classes III-IV received a 6- to 8-hour intermittent nesiritide outpatient infusion (0.01 mcg/kg/min continuously intravenously) once weekly for a total duration of 3 months in addition to standard medical therapy. Data were analyzed retrospectively to compare hospital readmission rates, endogenous BNP levels, blood urea nitrogen, and creatinine levels 1 year before and up to 12 months after starting treatment. All patients tolerated nesiritide infusions well with no significant adverse events. At the end of the observation period, NYHA classes had improved 1 class in 16 patients and 2 classes in 4 patients and remained unchanged in 4 patients. There was a significant reduction in hospital readmissions within 1 year with nesiritide treatment compared with the year before (0.94 ± 0.8 vs 3.6 ± 2.2, P < .005). No significant changes were seen regarding endogenous BNP levels (1002 ± 870 vs 1092 ± 978 pg/mL, P = .95), blood urea nitrogen levels (45 ± 28 vs 45 ± 26 mg/dL, P = .96), and a tendency of slightly elevated creatinine levels that did not differ significantly compared with prior levels (1.76 ± 0.85 vs 1.1 ± 0.56 mg/dL, P = .5). Intermittent outpatient nesiritide treatment resulted in improved symptoms and reduced hospital readmission rates without a significant decline in renal function in patients with advanced heart failure but did not alter endogenous BNP levels.

Topical Testosterone Gel for the Treatment of Male Hypogonadism

Objective: This review describes the current knowledge of biological external testosterone (T) application using dermal products for the treatment of late-onset male hypogonadism (LOH). n nMethods: An English language search of medical literature using Pubmed was conducted between January of 1984 and March of 2012 using the search term testosterone gel. Special emphasis was given to clinical controlled trials and large case studies. n nResults: We describe the current knowledge on testosterone replacement therapy using gel applications. A reference search revealed 1567 publications; 44 were clinical studies in human patients with male hypogonadism, 80 were reviews, 27 were case reports, and 9 were retrospective studies. Data from the literature and from 20 clinical studies involving human patients were analyzed since they met the inclusion criteria of testosterone gel administration in hypogonadal males. For the purpose of this review, a total number of 2,378 human patients were studied. Overall, biological T administration resulted in improvement of sexual dysfunction and symptoms of metabolic syndrome and represented an effective and safe treatment option for hypogonadal men. n nConclusions: Administration of biological T gel appears to represent a valid alternative treatment option for male hypogonadism with a favorite efficacy and safety profile.