Is There Such a Thing as Theological Medicine?

The idea that science must be understood in existential contradiction to religion and even theology is more of a conviction than a philosophical or experiential necessity. Indeed, we may now propose "Theological Medicine" as a new terminology for a perennial reality: that most physicians, health care providers, patients, and their caretakers experience the reality of illness within a theological framework, at least for those who have some degree of spiritual or religious belief. Developing a curriculum in Theological Medicine could develop a mechanism to offer appropriate training to healthcare providers. Such a course would have to be created and delivered by experienced physicians and nursing staff, spiritual advisors, clergy representatives such as pastors or priests from different churches or faith communities, bioethicists, psychologists, social workers, psychotherapists, patient support group members, members of institutional review boards, researchers, and even legal advisors, if available. Continuing professional education requirements also create an opportunity to introduce and evaluate competency in theological medicine, an emerging discipline that could add significant value to the lived experience of medical practice which remains based on the uniquely rich relationship between physician and patient.

Safety and outcomes analysis: transcatheter implantation of autologous angiogenic cell precursors for the treatment of cardiomyopathy.

BACKGROUND: Stem cell transplantation is an emerging therapy for severe cardiomyopathy, proffering stem cell recruitment, anti-apoptosis, and proangiogenic capabilities. Angiogenic cell precursors (ACP-01) are autologous, lineage-specific, cells derived from a multipotent progenitor cell population, with strong potential to effectively engraft, form blood vessels, and support tissue survival and regeneration. METHODS: This IRB approved outcome analysis reports upon 74 consecutive patients who failed medical management for severe cardiomyopathy, and were selected to undergo transcatheter intramyocardial or intracoronary implantation of ACP-01. Serious adverse events (SAEs) were reported. Cell analysis was conducted for each treatment. The left ventricular ejection fraction (LVEF) was measured by multi-gated acquisition scan (MUGA) or echocardiogram at 4 months ± 1.9 months and 12 months ± 5.5 months. Patients reported quality of life statements at 6 months (± 5.6 months). RESULTS: Fifty-four of 74 patients met requirements for inclusion (48 males and five females; age 68.1 ± 11.3 years). The mean treatment cell number of 57 × 106 ACP-01 included 7.7 × 106 CD34 + and 21 × 106 CD31 + cells with 97.6% viability. SAEs included one death (previously unrecognized silent MI), ventricular tachycardia (n = 2) requiring cardioversion, and respiratory infection (n = 2). LVEF in the ischemic subgroup (n = 41) improved by 4.7% ± 9.7 from pre-procedure to the first follow-up (4 months ± 1.9 months) (p < 0.004) and by 7.2% ± 10.9 at final follow-up (n = 25) at average 12 months (p < 0.004). The non-ischemic dilated cardiomyopathy subgroup (n = 8) improved by 7.5% ± 6.0 at the first follow-up (p < 0.017) and by 12.2% ± 6.4 at final follow-up (p < 0.003, n = 6). Overall improvement in LVEF from pre-procedure to post-procedure was significant (Fisher's exact test p < 0.004). LVEF improvement was most marked in the patients with the most severe cardiomyopathy (LVEF < 20%) improving from a mean 14.6% ± 3.4% pre-procedurally to 28.4% ± 8% at final follow-up. Quality of life statements reflected improvement in 33/50 (66%), no change in 14/50 (28%), and worse in 3/50 (6%). CONCLUSION: Transcatheter implantation of ACP-01 for cardiomyopathy is safe and improves LVEF in the setting of ischemic and non-ischemic cardiomyopathy. The results warrant further investigation in a prospective, blinded, and controlled clinical study. TRIAL REGISTRATION: IRB from Genetic Alliance #APC01-001, approval date July 25, 2022. Cardiomyopathy is common and associated with high mortality. Stem cell transplantation is an emerging therapy. Angiogenic cell precursors (ACP-01) are lineage-specific endothelial progenitors, with strong potential for migration, engraftment, angiogenesis, and support of tissue survival and regeneration. A retrospective outcomes analysis of 53 patients with ischemic and non-ischemic dilated cardiomyopathy undergoing transcatheter implantation of ACP-01 demonstrated improvements in the left ventricular ejection fraction of 7.2% ± 10.9 (p < 0.004) and 12.2% ± 6.4, respectively, at 12 months (± 5) follow-up. Quality of life statements reflected improvement in 33/50 (66%) patients.

Dietary nitrate biochemistry and physiology. An update on clinical benefits and mechanisms of action.

It is now more than 35 years since endothelium derived relaxing factor was identified as nitric oxide (NO). The last few decades have seen an explosion around nitric oxide biochemistry, physiology and clinical translation. The science reveals that all chronic disease is associated with decreased blood flow to the affected organ which results in increased inflammation, oxidative stress and immune dysfunction. This is true for cardiovascular disease, neurological disease, kidney, lung, liver disorders and every other major disorder. Since nitric oxide controls and regulates blood flow, oxygen and nutrient delivery to every cell, tissue and organ in the body and also mitigates inflammation, oxidative stress and immune dysfunction, a focus on restoring nitric oxide production is an obvious therapeutic strategy for a number of poorly managed chronic diseases. Since dietary nitrate is a major contributor to endogenous nitric oxide production, it should be considered as a means of therapy and restoration of nitric oxide. This review will update on the current state of the science and effects of inorganic nitrate administered through the diet on several chronic conditions and reveal how much is needed. It is clear now that antiseptic mouthwash and use of antacids disrupt nitrate metabolism to nitric oxide leading to clinical symptoms of nitric oxide deficiency. Based on the science, nitrate should be considered an indispensable nutrient that should be accounted for in dietary guidelines.

Improved Physical Function After Cardiac Contractility Modulation Therapy in 10 Patients With Chronic Heart Failure.

BACKGROUND: A new generation of therapeutic devices has expanded the options for managing advanced heart failure. We examined the outcomes of cardiac contractility therapy in a series of 10 patients with chronic heart failure. METHODS: Ten patients with chronic heart failure were nonrandomly selected to receive cardiac contractility modulation therapy. Hemodynamics, left ventricular ejection fraction, functional capacity, and clinical outcomes were evaluated at baseline and after 6 months of therapy. RESULTS: Eight male and 2 female patients (mean [SD] age, 63.4 [9.4] years) received cardiac contractility modulation therapy. Between baseline and 6-month follow-up, mean (SD) left ventricular ejection fraction improved from 27.1% (4.18%) to 35.1% (9.89%), New York Heart Association class declined from 3.9 (0.32) to 2.44 (0.52), and 6-minute walk test distance increased from 159.2 (93.79) m to 212.4 (87.24) m. Furthermore, the mean (SD) number of hospital admissions within the 6 months before cardiac contractility modulation therapy was 2.4 (2.27) compared with 1 (1.52) during the 6 months after therapy. CONCLUSION: Cardiac contractility modulation therapy improved physical functioning and reduced hospital admissions in these patients.

Quo Vadis, Dottore? Religious, Philosophical and Medical Perspectives on the Quest for Immortality.

In the daily practice of medicine, health care providers oftentimes confront the dilemma of offering 'maximum care' based on available technologies and advances versus ethical concerns about futility. Regardless of cultural backgrounds and differences, most human beings aspire to an illness-free life, or better yet, a life lived with utmost quality and longevity. On account on ongoing advances in science and technology, the possibility of achieving "immortality" (a term used as a metaphor for an extremely long and disease-free life) is increasingly perceived as a realistic goal, which is aggressively pursued by some of the world's wealthiest individuals and corporations. However, this quest is not taking place in a philosophical or religious vacuum, which is why we attempt to evaluate the current state of knowledge on religious beliefs revolving around immortality and their alignments with today's medical advancements. The literature searches were performed using relevant databases including JSTOR and PubMed, as well as primary religious sources. Most religions present longevity as a blessing and believe in some sort of immortality, afterlife or reincarnation for the immortal soul. The quest for immortality beyond life in a "body of death" remains consistent with access to medical care and the legitimate possibility of achieving longevity-as long as certain ethical and religious parameters are preserved.

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.

Effects of an oral nitric oxide supplement on functional capacity and blood pressure in adults with prehypertension.

Nitric oxide (NO) is an integral molecule especially important in the regulation of the cardiovascular system. Literature indicates that the number of studies continues to grow with regard to the effects of NO on cardiovascular disease and hypertension. "Prehypertension" is the clinical stage leading to hypertension. Diet and lifestyle modifications are the only treatment options for prehypertension. The objective of this study was to determine the effects of oral NO supplementation on blood pressure in patients with clinical prehypertension. This pilot phase study evaluated the effect of an orally disintegrating lozenge that generates NO in the oral cavity on blood pressure, functional capacity, and quality of life. Thirty patients with clinical prehypertension were recruited and enrolled in either the NO treatment or the placebo group over a 30-day period in an outpatient setting. Nitric oxide supplementation resulted in a significant decrease in resting blood pressure (138 ± 12 mm Hg in systole and 84 ± 5 mm Hg in diastole at baseline vs 126 ± 12 mm Hg in systole and 78 ± 4 mm Hg in diastole at follow-up, P < .001, vs baseline) and a significant increase in the achieved walking distance in the standard 6-minute walk test (596 ± 214 meters at baseline vs 650 ± 197 meters at follow-up, P < .005 vs baseline). Using a standardized questionnaire to assess quality of life, patients receiving NO supplementation showed improvement in the Physical Component Summary Score (PCS) and Mental Component Summary Score (MCS). Nitric oxide supplementation appears to lower blood pressure in patients with prehypertension and might be beneficial as a routine supplementation for cardiovascular protection.

Switching from nitrate therapy to ranolazine in patients with coronary artery disease receiving phosphodiesterase type-5 inhibitors for erectile dysfunction.

Coronary artery disease (CAD) and erectile dysfunction (ED) frequently coexist. The introduction of phosphodiesterase type-5 (PDE-5) inhibitors has revolutionized medical management of organic ED; however, in patients with angina pectoris, a common symptom of CAD, coadministration of PDE-5 inhibitors and nitrates has been implicated in CAD-related deaths following sexual activity. The mechanism of action of PDE-5 inhibitors results in a potential cumulative drop in blood pressure (BP); thus, these agents are contraindicated in patients receiving nitrates. Beta-blockers and calcium channel antagonists are considered the mainstays of antianginal therapy, but may not be tolerated by all patients. Ranolazine is an antianginal agent that produces minimal reductions in heart rate and BP. Here we report three cases of men with CAD, chronic angina, and concomitant ED. We describe our treatment approach in these patients, using ranolazine as a potential substitute to nitrate therapy.

The beneficial role of spiritual counseling in heart failure patients.

To ascertain the beneficial role of spiritual counseling in patients with chronic heart failure. This is a pilot study evaluating the effects of adjunct spiritual counseling on quality of life (QoL) outcomes in patients with heart failure. Patients were assigned to "religious" or "non-religious" counseling services based strictly on their personal preferences and subsequently administered standardized QoL questionnaires. A member of the chaplaincy or in-house volunteer organization visited the patient either daily or once every 2 days throughout the duration of their hospitalization. All patients completed questionnaires at baseline, at 2 weeks, and at 3 months. Each of the questionnaires was totaled, with higher scores representing positive response, except for one survey measure where lower scores represent improvement (QIDS-SR16). Twenty-three patients (n = 23, age 57 ± 11, 11 (48 %) male, 12 (52 %) female, mean duration of hospital stay 20 ± 15 days) completed the study. Total mean scores were assessed on admission, at 2 weeks and at 3 months. For all patients in the study, the mean QIDS-SR16 scores were 8.5 (n = 23, SD = 3.3) versus 6.3 (n = 18, SD = 3.5) versus 7.3 (n = 7, SD = 2.6). Mean FACIT-Sp-Ex (version 4) scores were 71.1 (n = 23, SD = 15.1) versus 74.7 (n = 18, SD = 20.9) versus 81.4 (n = 7, SD = 8.8). The mean MSAS scores were 2.0 (n = 21, SD = 0.6) versus 1.8 (n = 15, SD = 0.7) versus 2.5 (n = 4, SD = 0.7). Mean QoL Enjoyment and Satisfaction scores were 47.2 % (n = 23, SD = 15.0 %) versus 53.6 % (n = 18, SD = 16.4 %) versus 72.42 % (n = 7, SD = 22 %). The addition of spiritual counseling to standard medical management for patients with chronic heart failure patients appears to have a positive impact on QoL.

Left ventricular noncompaction cardiomyopathy: updated review.

The first case of noncompaction was described in 1932 after an autopsy performed on a newborn infant with aortic atresia/coronary-ventricular fistula. Isolated noncompaction cardiomyopathy was first described in 1984. A review on selected/relevant medical literature was conducted using Pubmed from 1984 to 2013 and the pathogenesis, clinical features, and management are discussed. Left ventricular noncompaction (LVNC) is a relatively rare congenital condition that results from arrest of the normal compaction process of the myocardium during fetal development. LVNC shows variability in its genetic pattern, pathophysiologic findings, and clinical presentations. The genetic heterogeneity, phenotypical overlap, and variety in clinical presentation raised the suspicion that LVNC might just be a morphological variant of other cardiomyopathies, but the American Heart Association classifies LVNC as a primary genetic cardiomyopathy. The familiar type is common and follows a X-linked, autosomal-dominant, or mitochondrial-inheritance pattern (in children). LVNC can occur in isolation or coexist with other cardiac and/or systemic anomalies. The clinical presentations are variable ranging from asymptomatic patients to patients who develop ventricular arrhythmias, thromboembolism, heart failure, and sudden cardiac death. Increased awareness over the last 25 years and improvements in technology have increased the identification of this illness and improved the clinical outcome and prognosis. LVNC is commonly diagnosed by echocardiography. Other useful diagnostic techniques for LVNC include cardiac magnetic resonance imaging, computerized tomography, and left ventriculography. Management is symptom based and patients with symptoms have a poorer prognosis. LVNC is a genetically heterogeneous disorder which can be associated with other anomalies. Making the correct diagnosis is important because of the possible associations and the need for long-term management and screening of living relatives.

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.

Self-efficacy mediates the associations of social support and depression with treatment adherence in heart failure patients.

BACKGROUND: Nonadherence to treatment recommendations is a leading preventable cause of rehospitalization and premature mortality in chronic heart failure (HF) patients. PURPOSE: This study examined whether self-efficacy mediates the contributions of social support and depression to treatment adherence. METHODS: A sample of 252 HF outpatients with a mean age of 54 years completed self-report questionnaires assessing depression, perceived social support, self-efficacy, and treatment adherence. RESULTS: Self-efficacy mediated the associations of social support and depression with treatment adherence after adjusting for demographic (age, gender, marital status, education, and ethnicity) and medical (New York Heart Association Classification and comorbidity) covariates. CONCLUSION: Self-efficacy explains the influence of social support and depression on treatment adherence and may be a key target for interventions to improve disease management and self-care behaviors in HF patients.

Syncope in adults: systematic review and proposal of a diagnostic and therapeutic algorithm.

This review aims to provide a practical and up-to-date description on the relevance and classification of syncope in adults as well as a guidance on the optimal evaluation, management and treatment of this very common clinical and socioeconomic medical problem. We have summarized recent active research and emphasized the value for physicians to adhere current guidelines. A modern management of syncope should take into account 1) use of risk stratification algorithms and implementation of syncope management units to increase the diagnostic yield and reduce costs; 2) early implantable loop recorders rather than late in the evaluation of unexplained syncope; and 3) isometric physical counter-pressure maneuvers as first-line treatment for patients with neurally-mediated reflex syncope and prodromal symptoms.

Periprocedural adverse events in cell therapy trials in myocardial infarction and cardiomyopathy: a systematic review.

BACKGROUND: Cell therapy (CTh) is a promising novel therapy for myocardial infarction (MI) and ischemic cardiomyopathy (iCMP). Recognizing adverse events (AE) is important for safety evaluation, harm prevention and may aid in the design of future trials. OBJECTIVE: To define the prevalence of periprocedural AE in CTh trials in MI and iCMP. METHODS: A literature search was conducted using the MEDLINE database from January 1990 to October 2010. Controlled clinical trials that compared CTh with standard treatment in the setting of MI and/or iCMP were selected. AE related to CTh were analyzed. RESULTS: A total of 2,472 patients from 35 trials were included. There were 26 trials including 1,796 patients that used CTh in MI and 9 trials including 676 patients that used CTh in iCMP. Periprocedural arrhythmia monitoring protocols were heterogeneous and follow-up was short in most of the trials. In MI trials, the incidence of periprocedural adverse events (AE) related to intracoronary cell transplantation was 7.5 % (95 % CI 6.04-8.96 %). AE related to granulocyte colony-stimulating factor (GCS-F) used for cell mobilization for peripheral apheresis was 16 % (95 % CI 9.44-22.56 %). During intracoronary transplantation in iCMP, the incidence of periprocedural AE incidence was 2.6 % (95 % CI 0.53-4.67 %). There were no AE reported during transepicardial transplantation and AE were rare during transendocardial transplantation. CONCLUSIONS: The majority of periprocedural AE in CTh trials in MI occurred during intracoronary transplantation and GCS-F administration. In iCMP, periprocedural AE were uncommon. Avoiding intracoronary route for CTh implantation may decrease the burden of periprocedural AE. Standardization of AE definition in CTh trials is needed.

Tadalafil as monotherapy and in combination regimens for the treatment of pulmonary arterial hypertension.

The purpose of this review is to evaluate the use of tadalafil as monotherapy and in combination regimens for the treatment of pulmonary arterial hypertension (PAH). A systematic English language search of the medical literature using PubMed was conducted between January 1960 and May 2012 using the search terms 'tadalafil', 'therapy', 'pulmonary (arterial) hypertension' and 'combination therapy'. Special emphasis was given to controlled clinical trials and case studies relevant for the use of tadalafil in PAH. The search revealed 113 relevant publications, 31 of which were clinical trials, 52 were reviews and 12 were case reports. Of these, 12 were clinical studies in human patients with PAH who were treated with tadalafil alone, and seven were clinical studies in human patients with PAH who were treated with tadalafil in combination with other agents. Only clinical studies in human patients were included. Exclusion criteria were monotherapy other than using tadalafil and any combination therapy that excluded tadalafil as part of the treatment regimen. Overall, 1353 human subjects were studied; 896 were treated with tadalafil alone while 457 subjects were treated with tadalafil in coadministration. Tadalafil appears to be an effective and a safe treatment option for patients with PAH. It improves clinical status, exercise capacity, hemodynamic parameters, compliance issues and quality of life and reduces the occurrence of clinical worsening. Tadalafil in combination therapy seems to be additive and synergistic in relaxing pulmonary vascular muscle cells but more clinical trials on human subjects are warranted.

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.