Impact of the New Heart Allocation System on the Medium-Term Outcomes in Patients With Hypertrophic Cardiomyopathy.

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.

Association of multiple metabolic and cardiovascular markers with the risk of cognitive decline and mortality in adults with Alzheimer's disease and AD-related dementia or cognitive decline: a prospective cohort study.

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.

Long-term post-transplantation outcomes in patients with hypertrophic cardiomyopathy: Single-center 35-year experience.

BACKGROUND: Heart transplantation (HT) is the only option for most patients with end-stage heart failure and hypertrophic cardiomyopathy (HCM) who fail medical therapy. Data on the long-term outcomes post-transplant in HCM individuals remain scarce. METHODS: We analyzed data of 319 adult patients who underwent HT between 1984 and 2019. Patients were followed for cardiac allograft rejection, cardiac allograft vasculopathy (CAV), death, or re-transplantation. RESULTS: Outcomes of 24 patients with HCM, 160 with ischemic, and 135 with dilated cardiomyopathy were compared. During a mean follow-up of 11.6 ± 7.2 (max 27.8), 16.7 ± 8.2 (max 32.7), and 16.1 ± 9.7 (max 34.6) years after HT in hypertrophic, ischemic, and dilated cardiomyopathy groups, respectively: 10-year survival rate was 67%, 62%, 69%, respectively (p = .04). Post-transplantation, HCM individuals more often than the other two studied groups required prolonged inotropic support (37%, 12%, 17%, respectively, p = .02), temporary mechanical circulatory support (45%, 13%, 14%, respectively, p < .01), and renal replacement therapy immediately post-HT (55%, 19%, 24%, respectively, p < .01). No significant inter-group differences were noted in the 10-year freedom from acute allograft rejection (38%, 46%, 43%, respectively, p = .38) or 10-year freedom from CAV (88%, 78%, 81%, respectively, p = .57). CONCLUSIONS: The long-term post-transplant prognosis of adult patients with hypertrophic cardiomyopathy is favorable despite more challenging immediate post-HT course.

HeartWare Left Ventricular Assist Device Exercise Hemodynamics With Speed Adjustment Based on Left Ventricular Filling Pressures.

Functional capacity remains limited in heart failure patients with left ventricular assist devices (LVADs) due to fixed pump speed and inability to offload the left ventricle adequately. We hypothesized that manually adjusting LVAD speed during exercise based on pulmonary capillary wedge pressures would increase total cardiac output and maximal oxygen consumption. Two participants with a HeartWare LVAD underwent an invasive ramp study at rest followed by an invasive cardiopulmonary stress test exercising in two randomized phases: fixed speed and adjusted speed. In the latter phase, speed was adjusted every 1 minute during exercise at ±20 rpm/1 mm Hg change from baseline pulmonary capillary wedge pressure. There was no difference in maximal oxygen consumption between the two phases, with a modest increase in total cardiac output during speed adjustment. Filling pressures were initially controlled during speed adjustment until speed was capped at 4,000 rpm, at which point filling pressures increased. Blood pressure was variable. The pressure across the head of the pump (ΔP) was higher with speed adjustment. Contrary to our hypothesis, LVAD speed adjustment during exercise did not improve total cardiac output and functional capacity. This variable response may be attributed to the native cardiac reserve and baroreceptor response; however, additional studies are needed.

Hematopoietic Stimulation During Impella 5.5 Support to Avoid Transfusions in a Jehovah's Witness.

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.

Autonomic Testing Optimizes Therapy for Heart Failure and Related Cardiovascular Disorders.

PURPOSE OF REVIEW: Cardiovascular autonomic control is an intricately balanced dynamic process. Autonomic dysfunction, regardless of origin, promotes and sustains the disease processes, including in patients with heart failure (HF). Autonomic control is mediated through the two autonomic branches: parasympathetic and sympathetic (P&S). HF is arguably the disease that stands to most benefit from P&S manipulation to reduce mortality risk. This review article briefly summarizes some of the more common types of autonomic dysfunction (AD) that are found in heart failure, suggests a mechanism by which AD may contribute to HF, reviews AD involvement in common HF co-morbidities (e.g., ventricular arrhythmias, AFib, hypertension, and Cardiovascular Autonomic Neuropathy), and summarizes possible therapy options for treating AD in HF. RECENT FINDINGS: Autonomic assessment is important in diagnosing and treating CHF, and its possible co-morbidities. Autonomic assessment may also have importance in predicting which patients may be susceptible to sudden cardiac death. This is important since most CHF patients with sudden cardiac death have preserved left ventricular ejection fraction and better discriminators are needed. Many life-threatening cardiovascular disorders will require invasive testing for precise diagnoses and therapy planning when modulating the ANS is important. In cases of non-life-threatening disorders, non-invasive ANS testing techniques, especially those that individually assess both ANS branches simultaneously and independently, are sufficient to diagnose and treat serially.

Vitamin d deficiency and metabolic syndrome: The joint effect on cardiovascular and all-cause mortality in the United States adults.

BACKGROUND: The long-term impact of vitamin D deficiency and metabolic syndrome (MetS) on cardiovascular disease (CVD) and all-cause mortality are still a matter of debate. AIM: To test the hypotheses that lower serum 25 hydroxyvitamin D [25(OH)D] concentrations (a marker of vitamin D level) and MetS have a long-term impact on the risk of CVD and all-cause mortality, and individuals with vitamin D deficiency can be identified by multiple factors. METHODS: A sample of 9094 adults, 20 to 90 years of age, who participated in the Third National Health and Nutrition Examination Survey (NHANES III, 1988 to 1994) were followed through December 2015 was analyzed. The associations of serum 25(OH)D concentrations and MetS with CVD and all-cause mortality were analyzed longitudinally using Cox regression models. Classification and regression tree (CART) for machine learning was applied to classify individuals with vitamin D deficiency. RESULTS: Of 9094 participants, 30% had serum 25(OH)D concentrations < 20 ng/mL (defined as vitamin D deficiency), 39% had serum 25(OH)D concentrations between 20 to 29 ng/mL (insufficiency), and 31% had serum 25(OH)D concentrations ≥30 ng/mL (sufficiency). Prevalence of MetS was 28.4%. During a mean of 18 years follow-up, vitamin D deficiency and MetS were significantly associated with increased risk of CVD and all-cause mortality. Subjects with both vitamin D deficiency and MetS had the highest risk of CVD mortality (HR = 1.77, 95%CI: 1.22-2.58) and all-cause mortality (HR = 1.62, 95%CI: 1.26-2.09), followed by those with both vitamin D insufficiency and MetS for CVD mortality (HR = 1.59, 95%CI: 1.12-2.24), and all-cause mortality (HR = 1.41, 95%CI: 1.08-1.85). Meanwhile, vitamin D sufficiency significantly decreased the risk of CVD and all-cause mortality for those who even had MetS. Among the total study sample, CART analysis suggests that being non-Hispanic Black, having lower serum folate level, and being female were the first three predictors for those with serum 25(OH)D deficiency. CONCLUSION: Vitamin D deficiency and MetS were significantly associated with increased risk of CVD and all-cause mortality. There was a significant joint effect of vitamin D deficiency and MetS on the risk of mortality. Findings of the CART analysis may be useful to identify individuals positioned to benefit from interventions to reduce the risk of CVD and all-cause mortality.

Management of Hypertension in Patients With Ventricular Assist Devices: A Scientific Statement From the American Heart Association.

Mechanical circulatory support with durable continuous-flow ventricular assist devices has become an important therapeutic management strategy for patients with advanced heart failure. As more patients have received these devices and the duration of support per patient has increased, the postimplantation complications have become more apparent, and the need for approaches to manage these complications has become more compelling. Continuous-flow ventricular assist devices, including axial-flow and centrifugal-flow pumps, are the most commonly used mechanical circulatory support devices. Continuous-flow ventricular assist devices and the native heart have a constant physiological interplay dependent on pump speed that affects pressure-flow relationships and patient hemodynamics. A major postimplantation complication is cerebrovascular vascular accidents. The causes of cerebrovascular vascular accidents in ventricular assist device recipients may be related to hypertension, thromboembolic events, bleeding from anticoagulation, or some combination of these. The most readily identifiable and preventable cause is hypertension. Hypertension management in these patients has been hampered by the fact that it is difficult to accurately measure blood pressure because these ventricular assist devices have continuous flow and are often not pulsatile. Mean arterial pressures have to be identified by Doppler or oscillometric cuff and treated. Although guidelines for hypertension management after ventricular assist device implantation are based largely on expert consensus and conventional wisdom, the mainstay of treatment for hypertension includes guideline-directed medical therapy for heart failure with reduced ejection fraction because this may reduce adverse effects associated with hypertension and increase the likelihood of favorable ventricular remodeling. The use of systemic anticoagulation in ventricular assist device recipients may at a given blood pressure increase the risk of stroke.

Novel Immunosuppression in Solid Organ Transplantation.

Solid organ transplantation and survival has improved tremendously in the last few decades, much of the success has been attributed to the advancements in immunosuppression. While steroids are being replaced and much of the immunosuppressive strategies focus on steroid free regimens, novel agents have introduced in the induction, maintenance, and treatment of acute rejection phase. MTOR inhibitors have helped with the renal sparing side effect from the calcineurin inhibitors, newer agents such as rituximab have decreased the incidence of donor-specific antibodies which led to decreased incidence of acute rejection reactions. In this chapter we discuss the newer therapies directed specifically for solid organ transplantation.

Mechanistic Target of Rapamycin (mTOR) Inhibitors.

Mechanistic target of rapamycin (mTOR) inhibitors are macrocyclic lactone antibiotics derived from Streptomyces hygroscopicus that prevent T lymphocyte activation and B cell differentiation. Unlike calcineurin inhibitors (CNIs) that inhibit cytokine production, mTOR inhibitors block the cytokine signal transduction to arrest cells in the G1 to S phase. This class of drugs is commonly used for post-transplantation and cancer management because of its immunosuppressive and antiproliferative properties, respectively. The potential uses of mTOR inhibitors are heavily explored because of their impact on cell growth and proliferation. However, mTOR inhibitors have a broad range of effects that can result in adverse reactions, but side effects can occur with other immunosuppressive agents as well. Thus, the performance of mTOR inhibitors is compared to the outcomes and adverse effects of other immunosuppressive drugs or the combination of other immunosuppressants and mTOR inhibitors. Because mTOR regulates many downstream pathways, mTOR inhibitors can affect these pathways to manage various diseases. Sirolimus (rapamycin) is approved by the Food and Drug Administration (FDA) to treat post-renal transplantation and lymphangioleiomyomatosis (LAM). Everolimus is approved by the FDA to treat postmenopausal advanced hormone receptor-positive, HER2-negative breast cancer in women, progressive neuroendocrine tumors of pancreatic origin (PNET), advanced renal cell carcinoma (RCC), renal angiomyolipoma (AML) and tuberous sclerosis complex (TSC), and subependymal giant cell astrocytoma (SEGA) associated with TSC as well as renal and liver transplantation. Temsirolimus is approved by the FDA to treat advanced RCC. Opportunities to use mTOR inhibitors as therapy for other transplantation, metabolic disease, and cancer management are being researched. mTOR inhibitors are often called proliferation signal inhibitors (PSIs) because of their effects on proliferation pathways.

Antiproliferatives and Transplantation.

Antiproliferative agents include Mycophenolic acid and Azathioprine (which is less commonly used unless in certain conditions). They were initially identified for use in autoimmune and cancer research due to their role in disruption of cellular replication. They have now become the cornerstone of antirejection maintenance therapy in solid organ transplant. In this chapter we will describe the major times that lead to discovery, mechanisms of action, side effects, use during pregnancy and the major clinical trials.

Dietary sugar intake and risk of Alzheimer's disease in older women.

BACKGROUND: 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. AIM: The purpose of our study was to evaluate if excessive sugar intake has a significant long-term effect on the risk of AD. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Proceedings from the metrics forum in heart transplantation for performance monitoring.

Regulatory oversight for heart transplant programs is currently under review by the United Network for Organ Sharing (UNOS). There is concern whether 1-year patient and graft survival truly represent heart transplant center performance. Thus, a forum was organized by the Thoracic and Critical Care Community of Practice (TCC COP) of the American Society of Transplantation (AST) for the heart transplant community to voice their opinions on matters involving program performance monitoring by UNOS. A TCC COP work group was formed to review outcome metrics for adult heart transplantation and culminated in a virtual community forum (72 participants representing 61 heart transplant programs) on November 12-13, 2020. One-year posttransplant survival is still considered an appropriate and important measure to assess program performance. Waitlist mortality and offer acceptance rate as pretransplant metrics could also be useful measures of program performance, recognizing that outside factors may influence these metrics. In depth discussion of these metrics and other issues including auditing thresholds, innovations to reduce risk-averse behavior and personally designed program scorecards are included in this meeting proceedings.

Guidance for Timely and Appropriate Referral of Patients With Advanced Heart Failure: A Scientific Statement From the American Heart Association.

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.