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1. The aim of the present study was to examine the associations between micronutrients, inflammation and the prevalence of congestive heart failure (CHF) in the elderly aged  65 years, using the US National Health and Nutrition Examination Surveys. 2. After adjusting for age, gender, race/ethnicity and other covariates, subjects with decreased folate and vitamin B12 intake and with elevated serum levels of inflammatory biomarkers (C-reactive protein and total homocysteine) had significantly higher risk of CHF than their counterparts. 3. Elderly women had a significantly higher prevalence of hypovitaminosis D (serum 25-Hydroxyvitamin(OH)D < 20 ng/mL) than men (37 vs 23%, respectively; P < 0.01). Elderly African Americans had the lowest mean levels of serum 25(OH)D (20.9 ng/mL) compared with Mexican Americans (24.1 ng/mL) and Caucasians (28.2 ng/mL). 4. Subjects with decreased serum 25(OH)D levels had a significantly higher prevalence of CHF than those who had higher serum 25(OH)D, for both men and women. Multivariate logistic regression analyses indicated that a decrease of 10 ng/mL in the serum 25(OH)D level was associated with an increased relative risk (95% confidence interval) of 1.22 (1.08–1.36) for CHF. 5. Subjects with a micronutrient insufficient status and with coexisting metabolic syndrome had an even higher risk of CHF. [ABSTRACT FROM AUTHOR]

Background: Everolimus, a novel proliferation inhibitor and immunosuppressive agent, may suppress cardiac-allograft vasculopathy. We conducted a randomized, double-blind, clinical trial comparing everolimus with azathioprine in recipients of a first heart transplant. Methods: A total of 634 patients were randomly assigned to receive 1.5 mg of everolimus per day (209 patients), 3.0 mg of everolimus per day (211 patients), or 1.0 to 3.0 mg of azathioprine per kilogram of body weight per day (214 patients), in combination with cyclosporine, corticosteroids, and statins. The primary efficacy end point was a composite of death, graft loss or retransplantation, loss to follow-up, biopsy-proved acute rejection of grade 3A, or rejection with hemodynamic compromise. Results: At six months, the percentage of patients who had reached the primary efficacy end point was significantly smaller in the group given 3.0 mg of everolimus (27.0 percent, P<0.001) and the group given 1.5 mg of everolimus (36.4 percent, P=0.03) than in the azathioprine group (46.7 percent). Intravascular ultrasonography showed that the average increase in maximal intimal thickness 12 months after transplantation was significantly smaller in the two everolimus groups than in the azathioprine group. The incidence of vasculopathy was also significantly lower in the 1.5-mg group (35.7 percent, P=0.045) and the 3.0-mg group (30.4 percent, P=0.01) than in the azathioprine group (52.8 percent). The rates of cytomegalovirus infection were significantly lower in the 1.5-mg group (7.7 percent, P<0.001) and the 3.0-mg group (7.6 percent, P<0.001) than in the azathioprine group (21.5 percent). Rates of bacterial infection were significantly higher in the 3.0-mg group than in the azathioprine group. Serum creatinine levels were also significantly higher in the two everolimus groups than in the azathioprine group. Conclusions: Everolimus was more efficacious than azathioprine in reducing the severity and incidence of cardiac-allograft vasculopathy, suggesting that everolimus therapy may alleviate this serious problem. N Engl J Med 2003;349:847-58. [ABSTRACT FROM AUTHOR]

Since the restart of HTx, recipients have been expected to be disciplined, avoiding all behaviors that increase the risk of rejection, so that transplant medicine will never again be criticized. Vaccination is a mainstay of the global strategy to control the COVID-19 pandemic and rebuild vibrant daily lives and economies. How to preserve information equity for COVID-19 vaccination among severely immunocompromised populations: Challenges among heart transplant recipients in Japan. [Extracted from the article]

Despite some reports of cardiometabolic disorders associated with the risk of Alzheimer's disease (AD), limited studies have been conducted to examine the association between excessive sugar intake (a risk factor for cardiometabolic disorders) and AD risk. The purpose of our study was to evaluate if excessive sugar intake has a significant long-term effect on the risk of AD. A population sample of 37,689 participants, who enrolled in the United States (US) Women's Health Initiative – Dietary Modification Trial (WHI-DM) in 1993–2005 and its extended observational follow-up study through 1 March 2019, were analyzed. Dietary sugar intake was measured using food frequency questionnaires. AD was classified by reports using a standard questionnaire. A dietary pattern that explained the maxima variations in sugar intake was constructed using reduced rank regression (RRR) technique. Associations of RRR dietary pattern scores and sugar intake (g/day) by quartiles (Q1 through Q4) with AD risk were examined using Cox proportional hazards regression analysis with adjusting for key covariates. During a mean follow-up of 18.7 years, 4586 participants reported having incident AD. The total incidence rate (95% confidence interval [CI]) of AD was 6.5 (6.3–6.7) per 1000 person-years (PYs). The incidence rates (95% CI) of AD by total sugar intake were 6.2 (5.8–6.6), 6.4 (6.0–6.8), 6.6 (6.3–7.0), and 6.9 (6.5–7.3) per 1000 PYs among those in quartiles (Q) 1 to Q4 (toward higher sugar consumption) of total sugar intake, respectively (test for trend of AD incident rates, p < 0.001). Individuals in Q4 of total sugar intake had a 1.19 higher risk of incident AD than those in Q1 (hazard ratio [HR] = 1.19, 95% CI: 1.05–1.34, p = 0.01). An estimated increase of 10 g/day in total sugar intake (about 2.4 teaspoons) was associated with an increased AD risk by 1.3–1.4%. Of six subtypes of sugar intake, lactose was significantly associated with AD risk. Our study indicates that excessive total sugar intake was significantly associated with AD risk in women. Of six subtypes of sugar intake, lactose had a stronger impact on AD risk. [ABSTRACT FROM AUTHOR]

Abstract: The Mars Reconnaissance Orbiter (MRO) will be launched in August 2005 by an Atlas V 401 expendable launch vehicle from Cape Canaveral Air Force Station, USA. It will deliver to Mars orbit a payload to conduct remote sensing science observations, identify and characterize sites for future landers, and provide critical telecom/navigation relay capability for follow-on missions. The mission is designed to provide global, regional survey, and targeted observations from a low 255km by 320km Mars orbit with a 3:00 PM local mean solar time (ascending node). During the one Martian year (687 Earth days) primary science phase, the orbiter will acquire visual and near-infrared high-resolution images of the planet''s surface, monitor atmospheric weather and climate, and search the upper crust for evidence of water. After this science phase is completed, the orbiter will provide telecommunications support for spacecraft launched to Mars in the 2007 and 2009 opportunities. The primary mission ends on December 31, 2010, approximately 5.5 years after launch. [Copyright &y& Elsevier]

Abstract: Background: Although there is an increasing body of evidence for a deleterious effect of mismatched donor HLA antigens on the outcome of human cardiac transplantation, the role of anti-HLA lymphocytotoxic antibodies remains controversial. Thus, their appearance after cardiac transplantation has been associated with poor outcome by some groups; whereas others have reported them to be of no clinical significance. Furthermore, their presence prior to cardiac transplantation has also been the subject of similarly conflicting reports. The deleterious effect of such pre-existing antibodies has been predicted by a positive lymphocyte cross-match (LCM), which, for most patients awaiting renal transplantation and in many requiring a cardiac allograft, leads to cancellation of the operation. The reason for undertaking the current study was to test the hypothesis that the constraints which a positive LCM result impose in preventing renal transplantation may not apply to orthotopic heart transplantation (OHT). Patients and methods: Four sensitized patients underwent OHT across a positive prospective LCM. Three were females, and one of those females also underwent cadaveric renal transplantation at the time of OHT. All four patients received aggressive early post-transplant immunosuppressive therapy, which included plasmapheresis, intravenous immunoglobulin (IVIg), antiproliferative agents (cyclophosphamide, basiliximab) and cytokine down-regulators (calcineurin inhibitors, muromonab-CD3) and anticell antibodies (OKT3, ATG). They also received standard immunosuppressive therapy which included corticosteroids. Complement-dependent cytotoxicity (CDC) was used for the identification of anti-HLA lymphocytotoxic antibodies. Reactivity of the latter against more than 10% of a panel of well-characterized T cells was considered sensitization, and required LCM to be performed prospectively, which test was also performed using the CDC technique. Results: Three of the... [ABSTRACT FROM AUTHOR]

Among the estimated 6.2 million Americans living with heart failure (HF), ≈5%/y may progress to advanced, or stage D, disease. Advanced HF has a high morbidity and mortality, such that early recognition of this condition is important to optimize care. Delayed referral or lack of referral in patients who are likely to derive benefit from an advanced HF evaluation can have important adverse consequences for patients and their families. A 2-step process can be used by practitioners when considering referral of a patient with advanced HF for consideration of advanced therapies, focused on recognizing the clinical clues associated with stage D HF and assessing potential benefits of referral to an advanced HF center. Although patients are often referred to an advanced HF center to undergo evaluation for advanced therapies such as heart transplantation or implantation of a left ventricular assist device, there are other reasons to refer, including access to the infrastructure and multidisciplinary team of the advanced HF center that offers a broad range of expertise. The intent of this statement is to provide a framework for practitioners and health systems to help identify and refer patients with HF who are most likely to derive benefit from referral to an advanced HF center. [ABSTRACT FROM AUTHOR]

Transthyretin amyloid cardiomyopathy (ATTR-CM) results in a restrictive cardiomyopathy caused by extracellular deposition of transthyretin, normally involved in the transportation of the hormone thyroxine and retinol-binding protein, in the myocardium. Enthusiasm about ATTR-CM has grown as a result of 3 simultaneous areas of advancement: Imaging techniques allow accurate noninvasive diagnosis of ATTR-CM without the need for confirmatory endomyocardial biopsies; observational studies indicate that the diagnosis of ATTR-CM may be underrecognized in a significant proportion of patients with heart failure; and on the basis of elucidation of the mechanisms of amyloid formation, therapies are now approved for treatment of ATTR-CM. Because therapy for ATTR-CM may be most effective when administered before significant cardiac dysfunction, early identification of affected individuals with readily available noninvasive tests is essential. This scientific statement is intended to guide clinical practice and to facilitate management conformity by covering current diagnostic and treatment strategies, as well as unmet needs and areas of active investigation in ATTR-CM. [ABSTRACT FROM AUTHOR]

Background: Malignancy is a concern in cardiac transplant recipients, but the temporal trends of de novo malignancy development are unknown.Objectives: The goal of this study was to describe the temporal trends of the incidence, types, and predictors of de novo malignancy in cardiac transplant recipients.Methods: The authors analyzed the temporal trends of post-transplant incidence, types, and predictors of malignancy using 17,587 primary adult heart-only transplant recipients from the International Society for Heart and Lung Transplantation registry. The main study outcomes included the incidence of, types of, and time to de novo malignancy.Results: The risk of any de novo solid malignancy between years 1 and 5 after transplantation was 10.7%. The cumulative incidence by malignancy type was: skin cancer (7.0%), non-skin solid cancer (4.0%), and lymphoproliferative disorders (0.9%). There was no temporal difference in the time to development according to malignancy type. However, the cumulative incidence of de novo solid malignancy increased from 2000 to 2005 vs. 2006 to 2011 (10.0% vs. 12.4%; p < 0.0001). Survival in patients after de novo malignancy was markedly lower than in patients without malignancy (p < 0.0001). Older recipients and patients who underwent transplantation in the recent era had a higher risk of de novo malignancy.Conclusions: More than 10% of adult heart transplant recipients developed de novo malignancy between years 1 and 5 after transplantation, and this outcome was associated with increased mortality. The incidence of post-transplant de novo solid malignancy increased temporally, with the largest increase in skin cancer. Individualized immunosuppression strategies and enhanced cancer screening should be studied to determine whether they can reduce the adverse outcomes of post-transplantation malignancy. [ABSTRACT FROM AUTHOR]

We aimed to test two hypotheses that (1) there were significant variations in the prevalence of hypertension (HBP) across neighborhoods in the city of Philadelphia and (2) these variations were significantly explained by the variations in the neighborhood physical and socioeconomic environment (PSE). We used data from the Southeastern Pennsylvania Household Health Surveys in 2002-2004 (study period 1, n = 8,567), and in 2008-2010 (period 2, n = 8,747). An index of neighborhood PSE was constructed using multiple specific measures. The associations of HBP with PSE at the neighborhood level and other risk factors at the individual level were examined using multilevel regression analysis. The results show that age-adjusted prevalence of HBP increased from 30.33 to 33.04 % from study periods 1 to 2 (p < 0.001). An estimate of 44 and 53 % of the variations in the prevalence of HBP could be explained by the variations in neighborhood PSE in study periods 1 and 2, respectively. In conclusion, prevalence of HBP significantly increased from 2002-2004 to 2008-2010. Individuals living in neighborhoods with disadvantaged PSE have significantly higher risk of the prevalence of HBP. [ABSTRACT FROM AUTHOR]

We aimed to examine the trend in the prevalence of hospitalization attributable to hypertensive disease and its subtypes among United States adults aged ≥35 years from 1980 to 2007. Data (n = 4,598,488,000 hospitalized cases) from the National Hospital Discharge Surveys were used to examine the trends of hospitalized patients with first (the reason for admission) and patients with any second to seventh (a comorbid condition when admission) diagnosis of hypertensive disease (International Classification of Disease, 9th Revision, Clinical Modification: 401 to 405) by gender and geographic region. Age-adjusted rates of disease were calculated using the United States 2000 standard population. The results show that age-adjusted hospitalization rates due to first diagnosis of hypertensive disease increased from 1.74% to 2.06% in men (p <0.01), and from 2.0% to 2.09% in women (p = 0.06) from 1980 to 1981 to 2006 to 2007. Age-adjusted rates due to any second to seventh diagnosis of hypertensive disease significantly increased from 7.06% to 35.09% in men (p <0.001), and from 7.88% to 31.98% (p <0.001) in women from 1980 to 1981 to 2006 to 2007. Patients with second to seventh diagnosis of essential hypertension and hypertensive chronic kidney disease had the highest and the second highest annual percent increases. Subjects living in the Southern region of the United States had the highest prevalence of hospitalization due to any second to seventh diagnosis of hypertensive disease compared with all other regions in 2006 to 2007. In conclusion, the prevalence of hospitalization due to hypertensive disease significantly increased in the United States from 1980 to 2007. [ABSTRACT FROM AUTHOR]

We aimed to examine associations between serum 25-hydroxyvitamin D (25[OH]D) concentration and mortality from heart failure (HF) and cardiovascular disease (CVD) and premature death from all causes using data from the Third National Health and Nutrition Examination Survey, which included 13,131 participants (6,130 men, 7,001 women) ≥35 years old at baseline (1988 to 1994) and followed through December 2000. Premature death was defined all-cause death at <75 years of age. Results indicated that during an average 8-year follow-up, there were 3,266 deaths (24.9%) including 101 deaths from HF, 1,451 from CVD, and 1,066 premature all-cause deaths. Among HF deaths, 37% of decedents had serum 25(OH)D levels <20 ng/ml, whereas only 26% of those with non-HF deaths had such levels (p <0.001). Multivariate-adjusted Cox model indicated that subjects with serum 25(OH)D levels <20 ng/ml had 2.06 times higher risk (95% confidence interval 1.01 to 4.25) of HF death than those with serum 25(OH)D levels ≥30 ng/ml (p <0.001). In addition, hazard ratios (95% confidence intervals) for premature death from all causes were 1.40 (1.17 to 1.68) in subjects with serum 25(OH)D levels <20 ng/ml and 1.11 (0.93 to 1.33) in those with serum 25(OH)D levels of 20 to 29 ng/ml compared to those with serum 25(OH)D levels ≥30 ng/ml (p <0.001, test for trend). In conclusion, adults with inadequate serum 25(OH)D levels have significantly higher risk of death from HF and all CVDs and all-cause premature death. [ABSTRACT FROM AUTHOR]

In the absence of a previous global comparison, we examined the variability in the prevalence of angina across 52 countries and its association with body weight and the poverty index using data from the World Health Organization-World Health Survey. The participants with angina were defined as those who had positive results using a Rose angina questionnaire and/or self-report of a physician diagnosis of angina. The body mass index (BMI) was determined as the weight in kilograms divided by the square of the height in meters. The poverty index (a standard score of socioeconomic status for a given country) was extracted from the United Nations'' statistics. The associations of angina with the BMI and poverty index were analyzed cross-sectionally using univariate and multivariate analyses. The results showed that the total participants (n = 210,787) had an average age of 40.64 years. The prevalence of angina ranged from 2.44% in Tunisia to 23.89% in Chad. Those participants with a BMI of <18.5 kg/m2 (underweight), 25 to 29 kg/m2 (overweight), or BMI ≥30 kg/m2 (obese) had a significantly greater risk of having angina compared to those with a normal BMI (≥18.5 but <25 k/m2). The odds ratios of overweight and obese for angina remained significant in the multilevel models, in which the influence of the country-level poverty status was considered. A tendency was seen for underweight status and a poverty index >14.65% to be associated with the risk of having angina, although these associations were not statistically significant in the multilevel models. In conclusion, significant variations were found in the anginal rates across 52 countries worldwide. An increased BMI was significantly associated with the odds of having angina. [Copyright &y& Elsevier]

Coronary artery vasculopathy (CAV) is one of the major factors that limit the long-term survival of heart transplant recipients. It is difficult to diagnose CAV, especially in the early stages. Traditional coronary angiography has been used for the diagnosis of CAV, but this method has limitations. Current literature suggests that intravascular ultrasound (IVUS) is a safe imaging technique that is beneficial for the early diagnosis of CAV; in comparison, IVUS with virtual histology (IVUS-VH) is an even more promising diagnostic utility. Despite its advantages, IVUS is currently not routinely utilized as the primary diagnostic modality for CAV in heart transplant recipients. In this review, we evaluate and summarize the clinical utility of IVUS in the early diagnosis of CAV, including its utility for assessing vessel remodeling, plaque composition, and prognostic value; morphometric analysis; and guiding therapy. After reviewing the relevant published literature, it is our recommendation that the use of IVUS be considered in all post-transplant CAV screening. (J Interven Cardiol 2011;24:9-14) [ABSTRACT FROM AUTHOR]

Background: Daclizumab, a humanized monoclonal antibody against the interleukin-2 receptor, reduced the risk of rejection without increasing the risk of infection among renal-transplant recipients and, in a single-center trial, among cardiac-transplant recipients. We conducted a multicenter, placebo-controlled, double-blind study to confirm these results in cardiac-transplant patients. Methods: We randomly assigned 434 recipients of a first cardiac transplant treated with standard immunosuppression (cyclosporine, mycophenolate mofetil, and corticosteroids) to receive five doses of daclizumab or placebo. The primary end point was a composite of moderate or severe cellular rejection, hemodynamically significant graft dysfunction, a second transplantation, or death or loss to follow-up within six months. Results: By six months, 104 of 218 patients in the placebo group had reached the primary end point, as compared with 77 of the 216 patients in the daclizumab group (47.7 percent vs. 35.6 percent, P=0.007), a 12.1 percent absolute risk reduction and a 25 percent relative reduction. The rate of rejection was lower in the daclizumab group than in the placebo group (41.3 percent vs. 25.5 percent). Among patients reaching the primary end point, the median time to the end point was almost three times as long in the daclizumab group as in the placebo group during the first 6 months (61 vs. 21 days) and at 1 year (96 vs. 26 days). More patients in the daclizumab group than in the placebo group died of infection (6 vs. 0) when they received concomitant cytolytic therapy. Conclusions: Daclizumab was efficacious as prophylaxis against acute cellular rejection after cardiac transplantation. Because of the excess risk of death, concurrent or anticipated use of cytolytic therapy with daclizumab should be avoided. N Engl J Med 2005;352:2705-13. [ABSTRACT FROM AUTHOR]

Background: We have previously demonstrated that a peripheral blood transcriptional profile using 11 distinct genes predicts onset of cardiac allograft rejection weeks to months prior to the actual event. Methods: In this analysis, we ascertained the performance of this transcriptional algorithm in a Bayesian representative population: 28 cardiac transplant recipients who progressed to moderate to severe rejection; 53 who progressed to mild rejection; and 46 who remained rejection-free. Furthermore, we characterized longitudinal alterations in the transcriptional gene expression profile before, during and after recovery from rejection. Results: In this patient cohort, we found that a gene expression score (range 0 to 40) of ≤20 represents very low risk of rejection in the subsequent 12 weeks: 0 progressed to treatable (ISHLT Grade ≥3A) rejection; 16 of 53 (30%) from the intermediate group (those who progressed to ISHLT Grade 1B or 2) and 13 of 46 (28%) controls (who remained Grade 0 or 1A) had scores ≤20. A gene score of ≥30 was associated with progression to moderate to severe rejection in 58% of cases. These two extreme scores (≤20 or ≥30) represented 44% of the cardiac transplant population within 6 months post-transplant. In addition, longitudinal gene expression analysis demonstrated that baseline scores were significantly higher for those who went on to reject, remained high during an episode of rejection, and dropped post-treatment for rejection (p < 0.01). Conclusions: The use of gene expression profiling early after transplantation allows for separation into low-, intermediate- or high-risk categories for future rejection, permitting development of discrete surveillance strategies. [Copyright &y& Elsevier]

Background: Profiling mRNA levels of 11 informative genes expressed by circulating immune effector cells identifies cardiac allograft recipients at low risk for current moderate–severe acute cellular rejection (ACR). Methods: We conducted a nested case–control study of 104 cardiac allograft recipients to investigate the association of transcriptional profiles of blood samples with either a future rejection episode within 12 weeks of a baseline clinical sample or persistent histologic quiescence for the same time period. Results: The transcription profile yielded a score (0 to 40 scale) of 27.4 ± 6.3 for future rejectors (n = 39) and 23.9 ± 7.1 for controls (n = 65) (p = 0.01). In patients who were ≤180 days post-transplant, the gene expression score was 28.4 ± 4.9 for rejectors (n = 28) and 22.4 ± 7.5 for controls (n = 48) (p < 0.001). In this period, no samples from patients who went on to reject within 12 weeks had gene expression scores of <20. Differential expression of the gene IL1R2 was significantly associated with future events. Of 33 additional genes profiled, 5 supported corticosteroid-sensitive constituents (IL1R2 and FLT3), whereas 6 supported T-cell activation (PDCD1). Conclusions: These data suggest that pathways regulating T-cell homeostasis and corticosteroid sensitivity are associated with future ACR in cardiac allografts and suggest that these signals are evident before histologically detectable rejection. [Copyright &y& Elsevier]

Background: Everolimus is an immunosuppressive agent that reduces cardiac allograft vasculopathy. This report presents the 24-month results of a multicenter trial of everolimus vs azathioprine in heart transplantation. Methods: A total of 634 patients were randomized to receive 1.5 mg everolimus, 3 mg everolimus or azathioprine, with cyclosporine and steroids. A 12-month, double-blind, double-dummy period was followed by a 12-month open-label period. Results: At 24 months, the percentage of patients reaching the composite efficacy end-points was significantly lower with everolimus (1.5 mg: 45.9%, p = 0.016; 3 mg: 36.0%, p < 0.001) than with azathioprine (57.5%). The change in maximal intimal thickness from baseline to 24 months was significantly smaller with everolimus 1.5 mg (0.07 mm, p = 0.014) and 3 mg (0.06 mm, p = 0.004) compared with azathioprine (0.15 mm). The 24-month incidence of vasculopathy was 33.3% with everolimus 1.5 mg, 45.5% with everolimus 3 mg and 58.3% with azathioprine (p = 0.017 vs everolimus 1.5 mg). Incidence of cytomegalovirus infection was 3-fold lower in patients receiving everolimus compared with azathioprine (7.2% and 7.1% in the 1.5-mg and 3-mg everolimus cohorts, respectively, and 21% in the azathioprine group; p < 0.0001). Median serum creatinine levels at 24 months were higher with everolimus than with azathioprine, but decreased when cyclosporine exposure was reduced (everolimus 1.5 mg: baseline 167 μmol, after 6 months 157.5 μmol; everolimus 3 mg: baseline 185.6 μmol, after 6 months 160 μmol; azathioprine: baseline 123.3 μmol, after 6 months 127 μmol). Conclusions: Everolimus significantly reduced acute rejection and limited the progression of allograft vasculopathy at 24 months compared with azathioprine. Although graft and patient survival was comparable at 24 months, everolimus therapy may improve longer-term outcomes after heart transplantation. [Copyright &y& Elsevier]

Background: Enteric-coated mycophenolate sodium (EC-MPS, myfortic) is an advanced formulation that delays the release of mycophenolic acid (MPA). Its efficacy and safety has been proven in several clinical trials in renal transplantation. Methods: In a single-blind, multicenter trial, a total of 154 de novo heart transplant patients were randomized to either EC-MPS 1,080 mg twice daily or mycophenolate mofetil (MMF) 1,500 mg twice daily. Eligible patients included men or women aged 18 to 65 years, undergoing primary heart transplantation, who were treated with cyclosporine microemulsion and corticosteroids as basic immunosuppression. The primary study objective was to investigate the incidence of biopsy-proven and treated acute rejection, graft loss or death (defined as treatment failure) for EC-MPS vs MMF during the first 6 months of treatment in de novo heart transplant recipients. Secondary objectives included assessment of the overall safety and tolerability of EC-MPS vs MMF in the study population. Results: The primary efficacy variable, treatment failure at 6 months, was similar for both treatments: 52.6% for EC-MPS and 57.9% for MMF (2-sided 95% confidence interval [CI]: −21.0% to 10.4%). At 12 months, treatment failure was 57.7% for EC-MPS and 60.5% for MMF (2-sided 95% CI: −18.4 to 12.7), and death and graft loss rate was 5.1% vs 9.2% for EC-MPS and MMF at 12 months, respectively (2-sided 95% CI: −12.2 to 4.1). The overall safety profile was similar for both groups. Significantly more patients on MMF had two or more study medication dose reductions during the treatment period. Conclusions: These 6- and 12-month results show that EC-MPS is therapeutically similar to MMF in de novo heart transplant recipients and has a comparable safety profile. [Copyright &y& Elsevier]

Background: Listing status for heart transplantation (Tx) patients was changed in 1999 from Status 1 and 2 to Status 1A, 1B and 2. Because the selection process was modified in favor of seriously ill patients, it was not clear whether this change would affect survival or other aspects of transplant management. Methods: We examined outcomes in 551 patients transplanted at our institution between 1986 and 2002 (pre-1999: n = 419; post-1999: n = 132) to determine the effects of change in listing protocol on transplant outcome. Results: Using Cox proportional hazard analysis, survival was not different between pre-1999 (pre) and post-1999 (post). Overall waiting-list times were longer post-1999 (pre: 134 ± 10.5 days, post: 172 ± 15.6 days; p = 0.044), and were longer post-1999 for blood groups A (177 vs 123 days), B (96 vs 84 days) and O (229 vs 172 days), but were shorter post for blood group AB (42 vs 68 days). Survival was not affected by age (pre: 53.7 ± 0.52 years, post: 53.1 ± 1.04 years; hazard ratio [HR] 1.00; 95% confidence interval [CI] 0.996 to 1.023; p = 0.181), male gender (HR 1.132; 95% CI 0.822 to 1.56; p = 0.447) or waiting-list time. Serum creatinine was similar between the 2 groups (pre: 1.25 ± 0.02, post: 1.26 ± 0.04; p = 0.794), whereas pulmonary artery (PA) diastolic pressure was increased post-1999 (pre: 24.9 ± 0.46, post: 27.0 ± 0.74; p = 0.023). Survival was not affected by PA pressure (HR 1.00; 95% CI 0.986 to 1.014; p = 0.976), but an elevated pre-transplant creatinine reduced survival (HR 1.484; 95% CI 1.139 to 1.933; p = 0.003). Conclusions: The change in listing status implemented in 1999 caused an increase in wait times for patients with blood types A, B and O, and shortened wait time for type AB; however, no differences occurred in overall post-transplant survival after the change in listing protocol. Age, gender and PA pressure had no effect on survival in either time period, whereas pre-transplant serum creatinine decreased survival in both patient groups. [Copyright &y& Elsevier]

Although small, randomized trials have shown that statin use is associated with decreased risks of mortality and severe rejection, no study has examined statin therapy as used in actual practice in large numbers of heart transplant recipients. We analyzed data from the Heart Transplant Lipid Registry (n = 12 centers). Patients were included if they underwent transplantation between 1995 and 1999, survived ≥30 days after transplantation, and had ≥30 days of Registry follow-up. Multivariable Cox regression models, with propensity scoring performed to adjust for nonrandom allocation of statin therapy, were performed to determine the association of statin therapy with death and fatal rejection. The study included 1,186 patients, with a mean follow-up of 580 ± 469 days; 937 patients (79%) received statin therapy. Overall, 71 patients (6%) died and 40 (3.4%) had fatal rejection. The statin group had a lower frequency of death (4% vs 13.7%, p &#60;0.0001) and fatal rejection (2.4% vs 7.2%, p = 0.0001). Using multivariable Cox regression, with propensity scoring included to adjust for likelihood of receiving statin therapy, statin use was the only factor associated with lower risk of death (hazard ratio 0.29, 95% confidence interval 0.13 to 0.67) and fatal rejection (hazard ratio 0.27, 95% confidence interval 0.09 to 0.78). This study represents the largest population of heart transplant recipients analyzed for the relation between statin therapy and clinical outcomes in actual practice. Statin therapy was significantly associated with lower risk of death and fatal rejection, benefits that were independent of lipid values. [Copyright &y& Elsevier]

Background: We evaluated a new marker of heart transplant rejection, the breath methylated alkane contour (BMAC). Rejection is accompanied by oxidative stress that degrades membrane polyunsaturated fatty acids, evolving alkanes and methylalkanes, which are excreted in the breath as volatile organic compounds (VOCs).Methods: Breath VOC samples (n = 1,061) were collected from 539 heart transplant recipients before scheduled endomyocardial biopsy. Breath VOCs were analyzed by gas chromatography and mass spectroscopy, and BMAC was derived from the abundance of C4–C20 alkanes and monomethylalkanes. The “gold standard” of rejection was the concordant set of International Society for Heart and Lung Transplantation (ISHLT) grades in biopsies read by 2 reviewers.Results: Concordant biopsies were: Grade 0, 645 of 1,061 (60.8%); 1A, 197 (18.6%); 1B, 84 (7.9%); 2, 93 (8.8%); and 3A, 42 (4.0%). A combination of 9 VOCs in the BMAC identified Grade 3 rejection (sensitivity 78.6%, specificity 62.4%, cross-validated sensitivity 59.5%, cross-validated specificity 58.8%, positive predictive value 5.6%, negative predictive value 97.2%). Site pathologists identified the same cases with sensitivity of 42.4%, specificity 97.0%, positive predictive value 45.2% and negative predictive value 96.7%.Conclusions: A breath test for markers of oxidative stress was more sensitive and less specific for Grade 3 heart transplant rejection than a biopsy reading by a site pathologist, but the negative predictive values of the 2 tests were similar. A screening breath test could potentially identify transplant recipients at low risk of Grade 3 rejection and reduce the number of endomyocardial biopsies. [Copyright &y& Elsevier]

Study objectives: The mechanism(s) by which nasal continuous positive airway pressure (CPAP) is effective in the treatment of Cheyne-Stokes respiration (CSR) in patients with congestive heart failure (CHF) remains uncertain, and may involve an increase in total oxygen body stores (dampening), changes in central and peripheral controller gain, and/or improvement in cardiac function. The purpose of this study was to evaluate the effects of nasal CPAP on total oxygen stores, as measured by the rate of fall of arterial oxyhemoglobin saturation (dSao[sub 2]/dt), to determine if dampening may play a role in the attenuation of CSR in patients with CHF. Design: Prospective controlled trial. Setting: University hospital. Patients: Nine male patients (mean ± SD age, 59 ± 8 years) with CHF and a mean left ventricular ejection fraction (LVEF) of 16 ± 4%. Interventions and measurements: All patients had known CSR, as identified on a baseline polysomnographic study. Patients then underwent repeat polysomnography while receiving nasal CPAP (9 ± 0.3 cm H[sub 2]O). The polysomnography consisted of recording of breathing pattern, pulse oximetry, and EEG. dSao[sub 2]/dt was measured as the slope of a line drawn adjacent to the falling linear portion of the arterial oxygen saturation (Sao[sub 2]) curve associated with a central apnea. All patients underwent echocardiography and right-heart catheterization within 1 month of the study to measure LVEF and cardiac hemodynamics, respectively. Results: There was a significant decrease in the apnea-hypopnea index (AHI) with nasal CPAP, from 44 ± 27 events per hour at baseline to 15 ± 24 events per hour with nasal CPAP (p = 0.004). When compared to baseline, dSao[sub 2]/dt significantly decreased with nasal CPAP from 0.42 ± 0.15% to 0.20 ± 0.07%/s (p < 0.001). The postapneic Sao[sub 2], when compared to baseline, significantly increased with nasal CPAP, from 87 ± 5% to 91... [ABSTRACT FROM AUTHOR]

Background: Photopheresis is an immunoregulatory technique in which lymphocytes are reinfused after exposure to a photoactive compound (methoxsalen) and ultraviolet A light. We performed a preliminary study to assess the safety and efficacy of photopheresis in the prevention of acute rejection of cardiac allografts. Methods: A total of 60 consecutive eligible recipients of primary cardiac transplants were randomly assigned to standard triple-drug immunosuppressive therapy (cyclosporine, azathioprine, and prednisone) alone or in conjunction with photopheresis. The photopheresis group received a total of 24 photopheresis treatments, each pair of treatments given on two consecutive days, during the first six months after transplantation. The regimen for maintenance immunosuppression, the definition and treatment of rejection episodes, the use of prophylactic antibiotics, and the schedule for cardiac biopsies were standardized among all 12 study centers. All the cardiac-biopsy samples were graded in a blinded manner at a central pathology laboratory. Plasma from the subgroup of 34 patients (57 percent) who were enrolled at the nine U.S. centers was analyzed by polymerase-chain-reaction amplification for cytomegalovirus DNA. Results: After six months of follow-up, the mean (±SD) number of episodes of acute rejection per patient was 1.44±1.0 in the standard-therapy group, as compared with 0.91±1.0 in the photopheresis group (P=0.04). Significantly more patients in the photopheresis group had one rejection episode or none (27 of 33) than in the standard-therapy group (14 of 27), and significantly fewer patients in the photopheresis group had two or more rejection episodes (6 of 33) than in the standard-therapy group (13 of 27, P=0.02). There was no significant difference in the time to a first episode of rejection, the incidence of rejection associated with hemodynamic compromise, or survival at 6 and 12 months. Although there were no significant differences in the rates or types of infection, cytomegalovirus DNA was detected significantly less frequently in the photopheresis group than in the standard-therapy group (P=0.04). Conclusions: In this pilot study, the addition of photopheresis to triple-drug immunosuppressive therapy significantly decreased the risk of cardiac rejection without increasing the incidence of infection. (N Engl J Med 1998;339:1744-51.) [ABSTRACT FROM AUTHOR]

Mechanical circulatory support has emerged as a vital therapeutic modality for patients awaiting heart transplantation (HT). However, it is unknown how it affected the characteristics and post-HT outcomes of patients with hypertrophic cardiomyopathy (HCM). This retrospective cohort study analyzed adult HT recipients from the International Society for Heart and Lung Transplantation registry (1998-2017). Two equal-duration eras were defined: era 1 1998-2007 and era 2 2008-2017. Patients with HCM were compared across the two eras (n1 = 742 and n2 = 1,211) and within each era, they were contrasted with individuals with nonischemic (NICM) (n1 = 15,964 and n2 = 20,394) and ischemic cardiomyopathy (ICM) (n1 = 14,140 and n2 = 12,986). Across eras, the number of HTs among patients with HCM increased by 63%. The rate of recipients with HCM in the intensive care unit (ICU) supported with intra-aortic balloon pump (IABP) increased, yet their pre-HT functional status improved, and 5 year post-HT survival remained unchanged and favorable. In era 2, at the time of HT, patients with HCM were more frequently than their NICM and ICM counterparts in the ICU and supported with inotropes. In the same era, 1 and 5 year survival were more favorable in HCM compared to ICM and comparable to NICM., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © ASAIO 2024.)

The introduction of the new heart allocation system in the United States in 2018 resulted in an increase in the number of heart transplants (HT) performed among patients with hypertrophic cardiomyopathy (HCM). However, whether that affected medium-term post-HT outcomes in this group of patients remains unknown. We conducted an analysis of the United Network for Organ Sharing Transplant Database, including adults with HCM who underwent heart transplantation between 2015 and 2021. Patients were divided into two equal-duration eras: Era 1 (October 17, 2015, to October 17, 2018) and Era 2 (October 18, 2018, to October 18, 2021). In the studied period, 444 patients with HCM underwent HT: 204 in Era 1 and 240 in Era 2. In Era 2, the waitlist time was shorter, transplant rates were higher, patients were less frequently supported with inotropes but more often with an IABP, ischemic time was longer, and donor-to-recipient distance larger. Pre- and post-transplant functional status was comparable across the two eras, while the pre-HT employment rate was higher in the new system. The 3 year survival was unchanged across eras. In the new allocation system, despite more frequent mechanical circulatory support (MCS) use and increased ischemic time, the medium-term outcomes of patients with HCM remained favorable., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © ASAIO 2024.)

Background and Objectives: There is a scarcity of data stemming from large-scale epidemiological longitudinal studies focusing on potentially preventable and controllable risk factors for Alzheimer's disease (AD) and AD-related dementia (ADRD). This study aimed to examine the effect of multiple metabolic factors and cardiovascular disorders on the risk of cognitive decline and AD/ADRD., Methods: We analyzed a cohort of 6,440 participants aged 45-84 years at baseline. Multiple metabolic and cardiovascular disorder factors included the five components of the metabolic syndrome [waist circumference, high blood pressure (HBP), elevated glucose and triglyceride (TG) concentrations, and reduced high-density lipoprotein cholesterol (HDL-C) concentrations], C-reactive protein (CRP), fibrinogen, interleukin-6 (IL-6), factor VIII, D-dimer, and homocysteine concentrations, carotid intimal-medial thickness (CIMT), and urine albumin-to-creatinine ratio (ACR). Cognitive decline was defined using the Cognitive Abilities Screening Instrument (CASI) score, and AD/ADRD cases were classified using clinical diagnoses., Results: Over an average follow-up period of 13 years, HBP and elevated glucose, CRP, homocysteine, IL-6, and ACR concentrations were significantly associated with the risk of mortality in the individuals with incident AD/ADRD or cognitive decline. Elevated D-dimer and homocysteine concentrations, as well as elevated ACR were significantly associated with incident AD/ADRD. Elevated homocysteine and ACR were significantly associated with cognitive decline. A dose-response association was observed, indicating that an increased number of exposures to multiple risk factors corresponded to a higher risk of mortality in individuals with cognitive decline or with AD/ADRD., Conclusion: Findings from our study reaffirm the significance of preventable and controllable factors, including HBP, hyperglycemia, elevated CRP, D-dimer, and homocysteine concentrations, as well as, ACR, as potential risk factors for cognitive decline and AD/ADRD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Liu, Gracely, Zhao, Gliebus, May, Volpe, Shi, DiMaria-Ghalili and Eisen.)

The population presenting with cardiogenic shock is heterogenous. Anemia is common in advanced heart failure and associated with poor outcomes. Microaxial flow pumps may cause ongoing blood trauma and worsen anemia. Treatment with recombinant erythropoietin, iron, vitamin B, and folate is recommended before cardiac surgery to reduce perioperative transfusion requirements but no data exist on the feasibility and safety during support with microaxial flow pumps. This novel strategy was born out of necessity to support a Jehovah's Witness who opposes blood transfusion but required mechanical circulatory support. We present its efficacy over the duration of 19 days of Impella 5.5 support where hemoglobin level remained stable, and platelet count significantly improved despite a brief episode of gastrointestinal bleeding. No thromboembolic complications occurred. We anticipate this strategy could help not only Jehovah's Witnesses, but also patients awaiting cardiac transplantation since transfusions stimulate development of antibodies which may preclude or postpone finding a suitable donor organ. Furthermore, it may minimize or prevent perioperative needs for transfusions for patients being bridged to durable left ventricular assist devices., Competing Interests: Disclosure: R.D. has received travel funding from Abiomed. R.D. has received speaker honoraria from Abiomed, Penn State HVI is supported by Abiomed with a research grant unrelated to this topic. The other authors have no conflicts of interest to report., (Copyright © ASAIO 2023.)

Competing Interests: The author declares no conflicts of interest.