State-of-the-Art: a Review of Cardiovascular Effects of Testosterone Replacement Therapy in Adult Males.

PURPOSE OF REVIEW: According to an Endocrine Society Clinical Practice Guideline published in June 2010, testosterone replacement therapy (TRT) should be administered only to men who are hypogonadal with documented low testosterone level on two morning measurements. This recommendation was based on previous studies that did not show an increased risk in cardiovascular events with TRT. In contrast, recent studies did show an increased risk which prompted the FDA to investigate further. RECENT FINDINGS: Multiple studies suggested an increased risk in cardiovascular events among groups of men prescribed TRT. There is recent evidence that TRT can be associated with higher cardiovascular risks, while these risks are still not well established, and more well-designed trials are needed. Physicians should always be cautious when prescribing TRT to their patients. Potential risks should be discussed with each patient, and TRT requires regular monitoring to help minimize side effects.

Case Illustration of the Natural History of Left Dominant Arrhythmogenic Cardiomyopathy.

Background: Arrhythmogenic left ventricular cardiomyopathy is an increasingly recognized cause of recurrent myocarditis, a mimicker of acute coronary syndrome, and an important cause of malignant ventricular arrythmias and heart failure. Desmoplakin is a protein that is critical to maintaining the structural integrity of the myocardium. Disruption of desmoplakin leads to fibrofatty infiltration of the myocardium which leads to congestive heart failure, cardiac arrhythmias, and sudden cardiac death. However, desmoplakin cardiomyopathy is often misdiagnosed, resulting in significant morbidity and mortality. We report 2 contrasting cases illustrating the natural history-hot and cold phases-of arrhythmogenic left ventricular cardiomyopathy. Case Series: The first case demonstrates a common phenotypic presentation of desmoplakin cardiomyopathy manifested as recurrent myocarditis and myocardial injury representing the hot phase. The second case is an undulating course of chronic systolic heart failure and ventricular arrhythmias representing the cold phase. Conclusion: Arrhythmogenic cardiomyopathy manifests as a spectrum of disease processes that involve the right, left, or both ventricles. Mutations in the desmoplakin gene are often associated with a left dominant ventricular cardiomyopathy. Diagnosis remains difficult as the condition has no signature clinical presentation, and imaging findings are variable.

Pathobiology and evolving therapies of coronary artery vasospasm.

Coronary artery vasospasm is a known cause of chest pain and requires a high level of clinical suspicion for diagnosis. It also remains in the differential diagnosis for patients presenting with type 2 myocardial infarction. There are few randomized controlled trials for guideline-based prevention and treatment for coronary artery vasospasm. In this article, we review updated concepts in coronary artery vasospasm. Specifically, our aim is to provide current evidence of pathophysiology, identify the risk factors, propose a diagnostic algorithm, review available evidence of evolving therapies, and identify patients who would benefit from automatic implantable cardioverter defibrillators.

Cost to Save a Life in Heart Failure: Health Disparity Costs Lives.

Objective The purpose of this paper is to assign a dollar value to life-saving medication, surgical procedures, and medical devices. The knowledge of the wide variation in the cost of drugs, surgery, and devices allows providers and patients to choose higher-valued therapies. Cost is a significant barrier to health. The current reimbursement system is complicated, representing a significant barrier to saving lives by promoting health disparity. Background The cost analysis of heart failure therapies is an important tool in the education of physicians, patients, and vendors of the intervention. The analysis demonstrates disparities between heart failure therapies. The cost to save a single life is calculated from annualized absolute mortality risk reduction, trial length, and estimated 10-year costs. The method allows comparisons of drugs, devices, and surgery. Methods The 10-year cost of drugs is 120 months times the cost of a drug/month as listed by the website GoodRX.com. The 10-year cost of surgery or device therapy was determined from a cost analysis found by a Google search of the literature. When wide ranges were reported, the mean value was selected. 1/absolute mortality risk reduction X 100 is the number needed to treat to save a life annualized for the mean length of the study. The cost to save a life can then be computed by the following formula: Cost/life saved = (10-year cost/annualized absolute mortality risk reduction) X (100) Results Beta-blockers and spironolactone had the lowest cost per life saved at $13,333 and $21,818, respectively. Defibrillators are the most expensive at $6,417,856. Valsartan/sacubitril has a cost of $1,127,733. Dapagliflozin, the newest class of heart failure drug, costs $4,853,200.  Conclusions Calculating the cost to save a life gives insight into the value of therapies and demonstrates disparities. It is a means of comparing drugs and devices. New drug therapies are costly, not affordable, and serve as a barrier to the successful treatment of heart failure.

Why We Fail at Heart Failure: Lymphatic Insufficiency Is Disregarded.

Is the definition of heart failure too narrow, not allowing research into compensatory mechanisms, comorbidities, right heart function, and lymphatic function? A review of the absolute mortality of heart failure drugs and devices suggests a modest improvement in outcomes. Absolute mortality from common comorbidities, including renal insufficiency, arrhythmia, conduction deficits, pulmonary hypertension, anemia, obstructive sleep apnea, infection, inflammation, edema, ischemic heart disease, and diabetes II, is significant. The lymphatic function is involved in short, intermediate, and long-term compensation for a failing heart and plays a role in most of the comorbidities. A better definition of heart failure is: Heart failure is a complex clinical syndrome that results from any structural or functional impairment of right or left ventricular filling or ejection of blood and failure of peripheral compensatory mechanisms. Lymphatic function from the anatomic, fluid management, immune modification standpoints requires study. New therapies from this analysis will improve patients with congestive heart failure.

Increased exhaled nitric oxide following autologous peripheral hematopoietic stem-cell transplantation: a potential marker of idiopathic pneumonia syndrome.

BACKGROUND: Increased production of nitric oxide (NO) and oxidative stress following bone marrow transplantation may play a role in the pathogenesis of idiopathic pneumonia syndrome (IPS). We hypothesize that patients who received high-dose chemotherapy followed by autologous peripheral hematopoietic stem-cell transplantation (APHSCT) have increased exhaled NO. METHOD: We measured exhaled lower respiratory tract NO concentration with a chemiluminescent NO analyzer during a slow vital capacity maneuver against a positive pressure of 16 cm H(2)O at an expiratory flow rate of 50 mL/s in 20 female patients who received high-dose chemotherapy (cyclophosphamide, carmustine, and cisplatin) followed by APHSCT for the treatment of stage III or IV breast carcinoma. Pulmonary function tests were performed, and exhaled NO measurements and clinical and laboratory data were obtained before transplantation and at every 6-week visit after transplantation for 24 weeks. RESULTS: All study patients had evidence of IPS with dyspnea and reduction in diffusion capacity of the lung for carbon monoxide (DLCO). Lower respiratory tract exhaled NO was significantly higher after APHSCT and during the 6 months of follow-up. Mean (+/- SD) exhaled NO increased from (mean +/- SD) 12.54 +/- 1.32 parts per billion (ppb) before APHSCT to 21.26 +/- 1.94 ppb at 6 weeks (p = 0.099), 21.26 +/- 1.94 ppb (p = 0.006) at 12 weeks, 24.62 +/- 2.55 ppb (p = 0.012) at 18 weeks, and 25.28 +/- 3.31 ppb (p = 0.013) at 24 weeks (all p values were compared to baseline). There was a strong negative correlation between DLCO and exhaled NO (regression coefficient - 0.60, p = 0.01). CONCLUSION: Lower respiratory tract concentration of exhaled NO is significantly increased following APHSCT and correlates with reduction in DLCO. Increase in lower respiratory tract concentration of NO is a potential marker of IPS.