Stem-cell therapy for erectile dysfunction: a review of clinical outcomes.

The prevalence of erectile dysfunction (ED) has increased in recent decades. Although many treatments offer some benefits for patients with ED, unmet therapeutic needs remain, and promising new approaches are under investigation. One of these approaches is the use of stem-cell (SC) therapy for ED. We comprehensively reviewed the published literature and ongoing phase 1 and phase 2 trials and identified 27 trials by using SC therapy to treat ED. Of the 27 trials, three have been withdrawn, nine have published results, six are complete but without published results, and nine trials are ongoing or have an "unknown" status. Our analysis revealed that SC therapy represents a promising option to treat ED, although published data exist for less than 100 patients. Large placebo-controlled trials with longer follow-up are needed to confirm the long-term safety and efficacy of SC therapy for ED.

A systemic review on the antioxidant and anti-inflammatory effects of resveratrol, curcumin, and dietary nitric oxide supplementation on human cardiovascular health.

The potential benefits of supplemental nutrients and dietary interventions against cardiovascular morbidity and mortality have been extensively investigated throughout the years. Numerous supplements claim cardioprotection and reduction of cardiovascular risk factors, but the roles of many supplements have not been determined. In the vast number of supplements on the market asserting cardioprotective effects, only 3 have been thoroughly evaluated and consistently reported as effective by our clinic patients. They have used supplements such as fish oil, multivitamins, and calcium, but many had not known of the benefits of resveratrol, curcumin, and nitric oxide as supplements for improving cardiovascular health. The cardioprotective effects of these dietary supplements in both animal models and humans have been explored with proposed mechanisms of action mostly attributed to antioxidant and anti-inflammatory properties. Resveratrol is one of the most studied polyphenols with established cardiovascular benefits. Preclinical studies have demonstrated these effects exerted via improved inflammatory markers, atherogenic profile, glucose metabolism, and endothelial function and are further supported by clinical trials. Curcumin has a well-established anti-inflammatory role by regulating numerous transcription factors and cytokines linked to inflammation. Inflammation is an underlying pathology in cardiovascular diseases, rendering curcumin a potential therapeutic compound. Similarly, nitric oxide supplementation has demonstrated cardiovascular benefits by normalizing blood pressure; enhancing blood flow; and reducing inflammation, immune dysfunction, and oxidative stress. A comprehensive review was performed evaluating the cardioprotective effects of these 3 dietary supplements with hope to provide updated information, promote further awareness of these supplements, and inspire future studies on their effects on cardiovascular health.

Palliative care issues in heart transplant candidates.

PURPOSE OF REVIEW: Heart failure is a serious condition and equivalent to malignant disease in terms of symptoms burden and mortality. Presently, only a comparatively small number of heart failure patients receive specialized palliative care. A literature search was conducted with the terms, palliative care and heart failure, using the electronic databases of PubMed and MEDLINE. RECENT FINDINGS: Nine-hundred and five articles were reviewed and of those, 78 articles discussed clinical trials in palliative care and heart failure. A complex set of management tools and strategies were used and recommended, including but not limited to lifestyle modification, exercise programs, pain and sleep disorder management, and support in end-of-life care. Limited data are available of using palliative care in heart transplant candidates prior to transplant surgery. SUMMARY: Diminishing quality of life prevails throughout the course of chronic heart failure. Therefore, palliative care should be integrated into heart failure management. Heart transplant candidates may benefit from early palliative care involvement independent of the clinical course and outcome. Because of gaps in current scientific literature on palliative care, end-of-life care, and hospice care and the services rendered, further research is necessary to encourage healthcare professionals to introduce palliative care as an early resource in chronic disease progression.

Failing the failing heart: a review of palliative care in heart failure.

Heart failure (HF) is the most common reason for hospital admission for patients older than 65 years. With an aging population and improving survival in heart failure patients, the number of people living with HF continues to grow. As this population increases, the importance of treating symptoms of fatigue, dyspnea, pain, and depression that diminish the quality of life in HF patients becomes increasingly important. Palliative care has been shown to help alleviate these symptoms and improve patients' satisfaction with the care they receive. Despite this growing body of evidence, palliative care consultation remains underutilized and is not standard practice in the management of HF. With an emphasis on communication, symptom management, and coordinated care, palliative care provides an integrated approach to support patients and families with chronic illnesses. Early communication with patients and families regarding the unpredictable nature of HF and the increased risk of sudden cardiac death enables discussions around advanced care directives, health care proxies, and deactivation of permanent pacemakers or implantable cardioverter defibrillators. Cardiologists and primary care physicians who are comfortable initiating these discussions are encouraged to do so; however, many fear destroying hope and are uncertain how to discuss end-of-life issues. Thus, in order to facilitate these discussions and establish an appropriate relationship, we recommend that patients and families be introduced to a palliative care team at the earliest appropriate time after diagnosis.

An evaluation of the prevalence and severity of pain and other symptoms in acute decompensated heart failure.

BACKGROUND: Heart failure is characterized by recurrent decompensations and persistent symptoms that decrease quality of life. Shortness of breath and fatigue are commonly identified symptoms but there is limited data on pain in heart failure patients. The Edmonton Symptom Assessment System (ESAS) was used to identify the prevalence and severity of pain and other symptoms experienced by patients with acute decompensated heart failure. METHODS: This is a cross-sectional study that evaluated patients with a history of chronic heart failure admitted to the hospital with acute decompensated heart failure. A standardized questionnaire (ESAS) was administered to patients within 24 hours of hospital admission. Exclusion criteria included patients <18 years of age, admission for a noncardiac reason, active malignancy, history of chronic pain, outpatient chronic pain medication use, and those actively followed by the palliative care service. RESULTS: One hundred patients, 67 males, with a mean age of 58 ± 17 years were recruited. The mean ejection fraction (EF) was 37%± 18%. Sixty patients (60%) reported pain of any degree. Patients with lower EF (≤ 40%, n=61) reported significantly higher pain scores (4.1 ± 3.6) compared to patients with higher EF (>40%, n=36, 2.7 ± 3.4, p<0.05). Tiredness, shortness of breath, and decreased well-being were the most severe symptoms with mean scores of 6.3 ± 2.8, 6.1 ± 3.1, and 5.7 ± 2.6, respectively. CONCLUSION: Pain is a common, underrecognized symptom in patients with chronic but acute decompensated heart failure. Decreased well-being, shortness of breath, and tiredness are the most common and severe symptoms in patients with chronic heart failure, regardless of ejection fraction.

Intrinsic cardiac origin of human cardiosphere-derived cells.

AIMS: Cardiosphere-derived cells (CDCs) are in clinical development as a regenerative cell product which can be expanded ex vivo from patient cardiac biopsies. Cardiosphere-derived cells are clonogenic, exhibit multilineage differentiation, and exert functional benefits in preclinical models of heart failure. The origin of CDCs remains unclear: are these cells endogenous to the heart, or do they arise from cells that populate the heart via blood-borne seeding? METHODS AND RESULTS: Right ventricular endomyocardial biopsies were obtained from cardiac transplant recipients (n = 10, age 57 ± 15 years), and CDCs expanded from each biopsy. Donor-recipient mismatches were used to probe the origin of CDCs in three complementary ways. First, DNA analysis of short-tandem nucleotide repeats (STRs) was performed on genomic DNA from donor and recipient, then compared with the STR pattern of CDCs. Second, in two cases where the donor was male and the recipient female, CDCs were examined for the presence of X and Y chromosomes by fluorescence in situ hybridization. Finally, in two cases, quantitative PCR (qPCR) was performed for individual-specific polymorphisms of a major histocompatability locus to quantify the contribution of recipient cells to CDCs. In no case was recipient DNA detectable in the CDCs by STR analysis. In the two cases in which a female patient had received a male heart, all CDCs examined had an X and Y chromosome, similarly indicating exclusively donor origin. Likewise, qPCR on CDCs did not detect any recipient DNA. CONCLUSION: Cardiosphere-derived cells are of endogenous cardiac origin, with no detectable contribution from extra-cardiac seeding.

Pilot study of palliative care consultation in patients with advanced heart failure referred for cardiac transplantation.

BACKGROUND: Heart failure (HF) in its chronic form is an irreversible and progressive disease. Palliative care (PC) interventions have traditionally been focused on patients with advanced cancer. We performed a pilot study to assess the feasibility of implementing the American College of Cardiology/American Heart Association (ACC/AHA) guidelines for early PC intervention in patients with advanced HF who were seeking or received potentially curative therapies. METHODS: Twenty consecutive patients with advanced HF referred to PC from the heart transplant service with stage D, New York Heart Association (NYHA) class III-IV symptoms were analyzed retrospectively in a tertiary care setting. Data were reviewed to assess the clinical impact of PC intervention. Feedback was obtained to assess satisfaction of the patients, their families, and the health care professionals. An independent assessment of the impact of the PC service in the care of each patient was performed by a cardiologist and PC physician by use of a scoring system. RESULTS: Twenty consecutive patients with HF were analyzed. PC consult was obtained for a variety of reasons. All patients complained of a high symptom burden. PC consultation resulted in a decrease in the use of opioids and increased patient satisfaction. Patients and their family members generally reported improved holistic care, continuity of care, more focused goals of care, and improved planning of treatment courses. The nonstandardized scoring system used to determine the impact of the PC service showed an average of moderate to significant impact when assessed by both a cardiologist and a PC physician. CONCLUSION: PC consultation appears to be beneficial in the treatment and quality of life of advanced HF patients, independent of their prognosis. This pilot study demonstrated feasibility and sufficient evidence of clinical benefit to warrant a larger randomized clinical trial assessing the benefit of standard involvement by PC in patients with advanced HF, independent of the patient's prognosis or treatment goals.

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.

The effects of spirituality and religion on outcomes in patients with chronic heart failure.

Heart failure (HF) is a chronic progressive disease with marked morbidity and mortality. Patients enduring this condition suffer from fluctuations in symptom burden such as fatigue, shortness of breath, chest pain, sexual dysfunction, dramatic changes in body image and depression. As physicians, we often ask patients to trust in our ability to ameliorate their symptoms, but oftentimes we do not hold all of the answers, and our best efforts are only modestly effective. The suffering endured by these individuals and their families may even call into question one's faith in a higher power and portends to significant spiritual struggle. In the face of incurable and chronic physical conditions, it seems logical that patients would seek alternative or ancillary methods, notably spiritual ones, to improve their ability to deal with their condition. Although difficult to study, spirituality has been evaluated and deemed to have a beneficial effect on multiple measures including global quality of life, depression and medical compliance in the treatment of patients with HF. The model of HF treatment incorporates a multidisciplinary approach. This should involve coordination between primary care, cardiology, palliative care, nursing, patients and, importantly, individuals providing psychosocial as well as spiritual support. This review intends to outline the current understanding and necessity of spirituality's influence on those suffering from HF.

Update on the safety of testosterone therapy in cardiac disease.

INTRODUCTION: Testosterone has been used for decades in the treatment of men with hypogonadism and women with low libido. More recently, it has been used in patient populations with cardiac disease and, in particular, in those patients with heart failure. The benefits of testosterone supplementation have been demonstrated in the literature, but there is also concern that testosterone supplementation may not be benign, especially when administered to achieve supraphysiological levels, e.g., to improve athletic performance. AREAS COVERED: This review seeks to address the link between testosterone levels and cardiac disease while discussing the safety concerns of testosterone supplementation in clinical practice. Randomized controlled trials, systematic reviews and meta-analyses that were obtained through a literature search of the Medline database are discussed in this paper. EXPERT OPINION: Ultimately, the definitive role of testosterone in cardiovascular disease remains contentious, but testosterone may have niche roles in certain conditions, such as advanced heart failure and cardiac cachexia. Testosterone has been used safely, and we believe may continue to be used safely, in men with cardiac disease when achieving physiological levels, with adequate monitoring of prostate specific antigen and hematocrit levels during the course of treatment per established clinical guidelines. Testosterone might exert beneficial effects on physical capacity and functioning as well as overall outcomes in patients with chronic heart failure.

Philosophical implications of the systemic and patient-oriented management of chronic heart failure.

Chronic heart failure is a lifelong disease that involves a large variety of symptoms and, ultimately, the entire organism relatively early in the disease process. At least in part, this is in contrast to other chronic conditions such as diabetes, renal failure or cancer. Modern treatment of patients with chronic heart failure goes beyond the mere prescription of vasodilators or inotropes. The multitude of multi-organ involvements and associated symptoms unrelated to pure cardiac contractile failure, as well as the psychosocial burden for patients and their direct environment, calls for a re-engagement with the philosophical aspects of medical care. Such a process may well challenge the approach commonly taken by health care providers. We further suggest a broader and more holistic view of medical care--in this case in regard to heart failure--and one that is based on patients' and physicians' understanding of health and disease, autonomy, suffering, existential values and expectations that might positively affect treatment strategies and outcomes.

Heart failure therapy: beyond the guidelines.

Heart failure is a chronic and debilitating disease responsible for high cardiac morbidity and mortality in the world and is associated with over 290 000 deaths in the United States each year. This article reviews palliative care and self-care, which are critical components of heart failure management that are inadequately defined in the current American College of Cardiology/American Heart Association Guidelines for the Diagnosis and Management of Heart Failure. Palliative care describes a multidisciplinary approach to the treatment of heart failure therapy that addresses both the symptomatic and psychosocial aspects of the disease. Self-care aims to maintain disease stability and prevent clinical decline through a variety of patient-based behavioral and lifestyle modifications.

The new concept of ''interventional heart failure therapy'': part 2--inotropes, valvular disease, pumps, and transplantation.

Recent advances in heart failure therapy include a variety of mechanical and device-based technologies that target structural aspects of heart failure that cannot be treated with drug therapy alone; these newer therapies can collectively be described as interventional heart failure therapy. This article is the second in a 2-part series reviewing interventional heart failure therapy. Interventions included in this discussion include those indicated for the treatment of end-stage refractory heart failure, including interventional medical therapy, interventional treatment of valvular disease, mechanical assist devices, and heart transplantation. Also included is a review of the currently available catheter-based pumps, which are intended to provide temporary support in patients with acute hemodynamic compromise. The use of cellular or stem cell therapy for the treatment of heart failure is an emerging interventional therapy and data supporting its use for the treatment heart failure will also be presented, as will a discussion of the role of palliative care and self-care in heart failure therapy.

Review article: the new concept of interventional heart failure therapy--part 1: electrical therapy, treatment of CAD, fluid removal, and ventricular support.

Congestive heart failure is a chronic and debilitating disease responsible for high cardiac morbidity and mortality in the world and is associated with more than 290 000 deaths in the United States each year. Recent advances in heart failure therapy target many of the mechanical and structural aspects of heart failure that are not addressed by drug-based therapies; these include abnormalities in electrical conduction, coronary artery or valvular architecture, and in ventricular size and shape. To target these abnormalities, newer therapies have largely been mechanical and device-based in nature and can be collectively described as interventional therapy. Interventional therapy includes the use of interventional medical therapy, electrical-based devices to augment ventricular function, catheterization-based devices for the treatment of underlying coronary artery disease and valvular disease, machines for the removal of excess fluid, mechanical pumps to assist the ventricles, surgical techniques aimed at reshaping the ventricles, the use of tissue therapies such as stem cell transplantation or complete heart transplant, palliative care, and self-care. This article is the first in a 2-part series that will review interventional heart failure therapy and present the most recent data supporting its use.

Persistent sexual dysfunction impairs quality of life after cardiac transplantation.

INTRODUCTION: The impact of sexual dysfunction (SD) on mental and physical health after heart transplantation (HTx) has not been established. AIM: We investigated the relationship of SD on quality of life (QoL), physical and mental health, and depressive symptoms after HTx. MAIN OUTCOME MEASURES: We evaluated SD according to the International Index of Erectile Dysfunction and the Female Sexual Function Index. QoL, physical and mental health were assessed using: 1) Short Form 12 Health Survey Questionnaire, 2) Quality of Life Enjoyment and Satisfaction Questionnaire--Short Form, and two depressive symptoms questionnaires: 1) Beck Depression Inventory-II and 2) Quick Inventory Depressive Symptomatology-Self Report. METHODS: We enrolled patients who were greater than 6 months post HTx. Patients unable to read English, had pelvic surgery or trauma, urogenital abnormalities, or sexually inactive were excluded. RESULTS: Out of 79 subjects that were screened, 33 men and 6 women participated (mean age 61.4 + 1.4). Response rates were at least 82% for all questionnaires. Overall prevalence of SD was 61%, with 78% of men being affected and 50% of women. There was no significant difference in measures between genders. HTx recipients with SD reported significantly worse QoL on measures of physical health when compared to those without SD. After HTx, patients suffering from SD had significantly worse general health (P = 0.02) and physical health (P = 0.02), including physical functioning (P = 0.01) and physical role limitation (P = 0.01). In contrast, mental health and depressive symptoms after HTx were not significantly different between those with and without SD. CONCLUSIONS: After HTx a high prevalence of SD remains among both men and women. Patients with SD had worse general and physical health but not depressive symptoms when compared to those without SD. The contributing factors may be more related to physical rather than psychological causes.

Acute cellular transplant rejection following laparoscopic adjustable gastric banding in a morbidly obese patient post heart transplantation.

BACKGROUND: Obesity is a worldwide health problem that is often worsened after organ transplantation. As obesity is associated with increased incidence of metabolic syndrome, cardiovascular events and death, it is essential to control weight and avoid weight gain in patients especially following cardiac transplantation. Of the various strategies that are available for weight reduction, bariatric surgery seems to be the most effective in achieving weight loss and in maintaining the reduced body weight. However, this has not been frequently performed in organ-transplant recipients. CASE REPORT: We are reporting a unique case of a bariatric surgery procedure performed in a patient after cardiac transplantation. A 30-year-old African-American man with a history of end-stage heart failure due to idiopathic dilated cardiomyopathy underwent orthotopic cardiac transplantation. Three years after transplantation, the patient underwent laparoscopic adjustable gastric banding surgery for morbid obesity. Two months later, the patient presented with severe heart failure and was diagnosed with acute cellular rejection as evidenced by endomyocardial biopsy results despite continued combined immunosuppressive therapy that had not been changed but with significantly reduced blood levels of calcineurin inhibitors. CONCLUSION: We hypothesize that the altered gastro-intestinal motility and delayed gastric emptying due to laparoscopic adjustable gastric banding may have caused incomplete absorption of the administered immunosuppressant drugs in this particular case, as evidenced by the low tacrolimus level, resulting in acute cellular rejection of the transplanted heart, which has never been described before.

Heart transplantation using bivalirudin as anticoagulant.

We present the case of a man with heparin-induced thrombocytopenia (HIT) and acute idiopathic decompensated cardiomyopathy who underwent successful heart transplantation with the use of bivalirudin as anticoagulant.

Impact of obesity in patients with congestive heart failure.

Obesity is a known risk factor for developing cardiovascular disease, including heart failure. However, the impact of obesity on patients with heart failure is unclear. Weight reduction is a recommended method of prevention of cardiovascular disease. However, the phenomenon of the "obesity paradox" (or "reverse epidemiology") revealed that overweight and mild to moderate obesity are associated with better outcomes in patients with heart failure compared with patients at normal or ideal weight. Even more, increases of weight in cachectic heart failure patients might improve survival, although patients with heart failure who are overweight or mildly to moderately obese have better outcomes than patients with heart failure who are at ideal or normal weight. In heart failure patients, weight reduction through diet regulation, moderate exercise, and bariatric surgery can improve quality of life and New York Heart Association functional class, but it is yet unclear if these measures will improve survival.