Association of multimorbidity with guideline-directed medical therapy intensification in heart failure: Findings from the EPIC-HF trial.

A potential contributor to the suboptimal rates of guideline directed medical therapy (GDMT) prescribing for heart failure with reduced ejection fraction (HFrEF) is the burden of multimorbidity in patients with HFrEF. We examined the effect of multimorbidity on GDMT prescription in the EPIC-HF trial, finding that multimorbidity was associated with decreased likelihood of GDMT intensification. Further study is needed to guide treatment in high-risk, multimorbid patients with HFrEF.

Pharmacotherapy in the heart transplant recipient: A primer for nurse clinicians and pharmacists.

Heart transplantation (HT) is the definitive treatment for eligible patients with end-stage heart disease. A major complication of HT is allograft rejection which can lead to graft dysfunction and death. The guiding principle of chronic immunosuppression therapy is to prevent rejection of the transplanted organ while avoiding oversuppression of the immune system, which can cause opportunistic infections and malignancy. The purpose of this review is to describe immunosuppressive management of the HT recipient-including agent-specific pharmacology and pharmacokinetics, outcomes data, adverse effects, clinical considerations, and recent guideline updates. We will also provide recommendations for medical prophylaxis of immunosuppressed patients based on the most recent clinical guidelines. Additionally, we highlight the importance of medical therapy adherence and the effect of social determinants of health on the long-term management of HT. HT recipients are a complex and high-risk population. The objective of this review is to describe basic pharmacotherapy in HT and implications for nurses and pharmacists.

Expanded use of sodium-glucose cotransporter 2 inhibitors: Evidence beyond heart failure with reduced ejection fraction.

Following the results observed in the DAPA-HF trial and subsequent FDA approval of dapagliflozin in patients living with heart failure with reduced ejection fraction (HFrEF), numerous trials quickly began to assess the effects of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in a wide range of cardiovascular (CV) conditions. Since the publication of those findings, multiple SGLT2i have demonstrated benefit in patients regardless of left ventricular ejection fraction (LVEF)-allowing the drug class to establish itself within the first line of guideline-directed medication therapy. Although the full mechanistic properties of SGLT2i in heart failure (HF) have yet to be fully understood, benefits in other disease states have continued to emerge over the past decade. This review summarizes the findings of 14 clinical trials investigating the use of SGLT2i in various CV disease states, with a special focus on HF with preserved ejection fraction (HFpEF) and acute decompensated HF (ADHF). Additionally, studies assessing the CV-related mechanisms, cost-effectiveness, and exploratory effects of dual SGLT1/2 blockade are described. A review of select ongoing trials has also been incorporated to further characterize the research landscape with this medication class. The aim of this review is to serve as a comprehensive tool for healthcare providers to better understand how this class of diabetes medications established its place in the treatment of HF.

Management of Acute Coronary Syndrome in the Older Adult Population: A Scientific Statement From the American Heart Association.

Diagnostic and therapeutic advances during the past decades have substantially improved health outcomes for patients with acute coronary syndrome. Both age-related physiological changes and accumulated cardiovascular risk factors increase the susceptibility to acute coronary syndrome over a lifetime. Compared with younger patients, outcomes for acute coronary syndrome in the large and growing demographic of older adults are relatively worse. Increased atherosclerotic plaque burden and complexity of anatomic disease, compounded by age-related cardiovascular and noncardiovascular comorbid conditions, contribute to the worse prognosis observed in older individuals. Geriatric syndromes, including frailty, multimorbidity, impaired cognitive and physical function, polypharmacy, and other complexities of care, can undermine the therapeutic efficacy of guidelines-based treatments and the resiliency of older adults to survive and recover, as well. In this American Heart Association scientific statement, we (1) review age-related physiological changes that predispose to acute coronary syndrome and management complexity; (2) describe the influence of commonly encountered geriatric syndromes on cardiovascular disease outcomes; and (3) recommend age-appropriate and guideline-concordant revascularization and acute coronary syndrome management strategies, including transitions of care, the use of cardiac rehabilitation, palliative care services, and holistic approaches. The primacy of individualized risk assessment and patient-centered care decision-making is highlighted throughout.

Safety and efficacy of IV theophylline for regadenoson-associated side effect reversal.

BACKGROUND: Aminophylline injection has been on an intermittent nation-wide shortage due to manufacturing delays leaving a need for an alternative reversal agent for regadenoson-associated side effects. Intravenous theophylline should be a logical acceptable pharmacological alternative; however, data regarding its safety and efficacy as a reversal agent are lacking. METHODS: Utilizing electronic medical records at the University of Colorado hospital, we identified patients ≥ 18 years of age who had a pharmacologic stress test using regadenoson during periods of aminophylline shortage (3/1/2013 to 5/31/2013 and 4/1/2018 to 8/30/2018) in which theophylline was used as an alternative antidote for side effect reversal. Intravenous theophylline was prepared by the inpatient pharmacy to a concentration of 0.8 mg/mL in a total volume of 100 mL D5W. Specific side effects and side effect resolution were evaluated. RESULTS: Of the 122 patients evaluated, theophylline was administered in doses ranging from 40 to 75 mg with the majority receiving 40 mg. Complete resolution of regadenoson side effects occurred in 98 patients with 12 experiencing partial resolution and 1 without resolution. No adverse effects or events were reported. CONCLUSION: Due to limited availability of aminophylline, theophylline may be a safe and effective alternative to reverse regadenoson-associated side effects.

Evaluation of an opioid pain teleconsultation service to address the opioid overdose epidemic in Colorado: A Health First Colorado demonstration project.

BACKGROUND: Since the mid-1990s, more than 500,000 deaths have been attributed to the opioid overdose epidemic, which has created a serious national crisis affecting public health and social and economic welfare. To mitigate these opioid-related overdoses and deaths, interventions targeted at both the patient and community level are needed. OBJECTIVE: This demonstration project sought to determine whether implementation of a provider-to-provider opioid pain teleconsultation service with a pain specialist was correlated with a reduction in inappropriate opioid use and improve health outcomes. METHODS: Individual-level claims data for Health First Colorado Medicaid members were collected between March 1, 2017, and September 30, 2021, for individuals who triggered a provider-to-provider pain management teleconsultation based on receipt of a prescription for an opioid where the member was receiving a high-dose opioid (n = 125) or was opioid-naive (n = 819). The primary outcome measures were a patient's opioid dose less than 200 morphine milligram equivalent (MME) by 6 months after the consult if consult was triggered for high-dose use or discontinuation of an opioid by 12 weeks after consult if the consult was triggered for opioid naivety. Secondary opioid-related health outcomes were also assessed. RESULTS: In the high-dose opioid cohort, 87% of the members had their monthly average MME reduced to less than 200 by 180 days after their consult. More than half of the opioid-naive group had discontinued their opioid by 90 days after their consult. CONCLUSION: Results indicate that provider-to-provider teleconsultation services with a pain specialist can be an effective intervention at reducing total inappropriate opioid use.

A Randomized Controlled Trial of Heart Failure Disease Management in Skilled Nursing Facilities.

OBJECTIVE: Patients discharged from the hospital to a skilled nursing facility (SNF) are not typically part of a heart failure disease management program (HF-DMP). The objective of this study is to determine if an HF-DMP in SNF improves outcomes for patients with HF. DESIGN: Cluster-randomized controlled trial. PARTICIPANTS: The trial was conducted in 47 SNFs, and 671 patients were enrolled (329 HF-DMP; 342 to usual care). METHODS: The HF-DMP included documentation of ejection fraction, symptoms, weights, diet, medication optimization, education, and 7-day visit post SNF discharge. The composite outcome was all-cause hospitalization, emergency department visits, or mortality at 60 days. Secondary outcomes included the composite endpoint at 30 days, change in the Kansas City Cardiomyopathy Questionnaire and the Self-care of HF Index at 60 days. Rehospitalization and mortality rates were calculated as an exploratory outcome. RESULTS: Mean age of the patients was 79 ± 10 years, 58% were women, and the mean ejection fraction was 51% ± 16%. At 30 and 60 days post SNF admission, the composite endpoint was not significant between DMP (29%) and usual care (32%) at 30 days and 60 days (43% vs 47%, respectively). The Kansas City Cardiomyopathy Questionnaire significantly improved in the HF-DMP vs usual care for the Physical Limitation (11.3 ± 2.9 vs 20.8 ± 3.6; P = .039) and Social Limitation subscales (6.0 ± 3.1 vs 17.9 ± 3.8; P = .016). Self-care of HF Index was not significant. The total number of events (composite endpoint) totaled 517 (231 in HF-DMP and 286 in usual care). Differences in the 60-day hospitalization rate [mean HF-DMP rate 0.43 (SE 0.03) vs usual care 0.54 (SE 0.05), P = .04] and mortality rate (HF-DMP 5.2% vs usual care 10.8%, P < .001) were significant. CONCLUSIONS AND IMPLICATIONS: The composite endpoint was high for patients with HF in SNF regardless of group. Rehospitalization and mortality rates were reduced by the HF-DMP. HF-DMPs in SNFs may be beneficial to the outcomes of patients with HF. SNFs should consider structured HF-DMPs for their patients.

Renin Angiotensin Aldosterone System Antagonism in 2019 Novel Coronavirus Acute Lung Injury.

It has been established that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses angiotensin-converting enzyme 2 (ACE2), a membrane-bound regulatory peptide, for host cell entry. Renin-angiotensin-aldosterone system (RAAS) inhibitors have been reported to increase ACE2 in type 2 pneumocyte pulmonary tissue. Controversy exists for the continuation of ACE inhibitors, angiotensin II receptor blockers, and mineralocorticoid receptor antagonists in the current pandemic. ACE2 serves as a regulatory enzyme in maintaining homeostasis between proinflammatory angiotensin II and anti-inflammatory angiotensin 1,7 peptides. Derangements in these peptides are associated with cardiovascular disease and are implicated in the progression of acute respiratory distress syndrome. Augmentation of the ACE2/Ang 1,7 axis represents a critical target in the supportive management of coronavirus disease 2019-associated lung disease. Observational data describing the use of RAAS inhibitors in the setting of SARS-CoV-2 have not borne signals of harm to date. However, equipoise persists, requiring an analysis of novel agents including recombinant human-ACE2 and existing RAAS inhibitors while balancing ongoing controversies associated with increased coronavirus infectivity and virulence.

A systematic review and meta-analysis of randomized controlled trials of cardiovascular toxicity of medical cannabinoids.

BACKGROUND: Several systematic reviews (SRs) have summarized the potential effectiveness of medical cannabinoids, but it is unclear to what extent safety-related outcomes were incorporated. OBJECTIVE: The objective of this study was to evaluate the cardiovascular toxicity associated with medical use of cannabinoids. METHODS: A 2-stage systematic review (SR) approach was undertaken to assess the current evidence on cannabinoid-associated cardiovascular events reported among randomized controlled trials (RCTs). First, we searched for SRs in multiple sources until June 2019. Second, RCTs identified from the SRs were included if they assessed medical cannabis and reported cardiovascular events. The outcomes of interest were all types of cardiovascular events. Data were extracted by 2 independent reviewers. Study quality was assessed using the Cochrane risk of bias. A statistical test of heterogeneity was performed. The summary risk ratios (RRs) and 95% CIs were calculated using a random-effects model. RESULTS: A total of 47 studies involving 2800 patients were included. The median duration of cannabinoid use was 15.8 days (range 1 to 322), and 45% of the studies excluded patients with underlying cardiovascular diseases. Cannabinoid use was significantly associated with increased risks of orthostatic hypotension (RR 3.16 [95% CI 2.27-4.40], I2 = 2.3%) and hypotension (3.55 [1.45-8.71], I2 = 31.8%), with a trend of increased risk of tachycardia (1.94 [0.81-4.64], I2 = 48.6%). No study reported serious cardiovascular events. CONCLUSIONS: Cannabinoid use was associated with tachycardia, hypotension, and orthostatic hypotension. There is a paucity of data for other cardiovascular events among medical cannabis users. More data, especially regarding long-term effects among patients with existing cardiovascular diseases, are needed.

Association Between Variants in Calcineurin Inhibitor Pharmacokinetic and Pharmacodynamic Genes and Renal Dysfunction in Adult Heart Transplant Recipients.

Background: The goal of the study was to assess the relationship between single nucleotide variants (SNVs) in calcineurin inhibitor (CNI) pharmacokinetic and pharmacodynamic genes and renal dysfunction in adult heart transplant (HTx) recipients. Methods: This retrospective analysis included N = 192 patients receiving a CNI at 1-year post-HTx. Using a candidate gene approach, 93 SNVs in eight pharmacokinetic and 35 pharmacodynamic genes were chosen for investigation. The primary outcome was renal dysfunction 1-year after HTx, defined as an estimated glomerular filtration rate (eGFR) <45 ml/min/1.73m2. Results: Renal dysfunction was present in 28.6% of patients 1-year after HTx. Two SNVs [transforming growth factor beta 1 (TGFB1) rs4803455 C > A and phospholipase C beta 1 (PLCB1) rs170549 G > A] were significantly associated with renal dysfunction after accounting for a false discovery rate (FDR) of 20%. In a multiple-SNV adjusted model, variant A allele carriers of TGFB1 rs4803455 had lower odds of renal dysfunction compared to C/C homozygotes [odds ratio (OR) 0.28, 95% CI 0.12-0.62; p = 0.002], whereas PLCB1 rs170549 variant A allele carriers had higher odds of the primary outcome vs. patients with the G/G genotype (OR 2.66, 95% CI 1.21-5.84, p = 0.015). Conclusion: Our data suggest that genetic variation in TGFB1 and PLCB1 may contribute to the occurrence of renal dysfunction in HTx recipients receiving CNIs. Pharmacogenetic markers, such as TGFB1 rs4803455 and PLCB1 rs170549, could help identify patients at increased risk of CNI-associated renal dysfunction following HTx, potentially allowing clinicians to provide more precise and personalized care to this population.

Comparative effectiveness of direct oral anticoagulants and warfarin for the treatment of left ventricular thrombus.

Left ventricular (LV) thrombus is a complication of acute endomyocardial injury and chronic ventricular wall hypokinesis, resulting in increased risk of thromboembolic complications. Observational studies support the general safety and efficacy of warfarin for this indication. Limited data exists regarding the use of direct oral anticoagulants (DOACs) for LV thrombus. This retrospective cohort study sought to compare the incidence of thromboembolic events, bleeding rates, and blood product administration in patients receiving a DOAC versus warfarin. A total of 949 patients met inclusion, 180 (19%) received a DOAC and 769 (81%) warfarin. For the primary endpoint of new onset thromboembolic stroke, no difference existed between treatments (DOAC: 7.8% vs warfarin: 11.7%, p = 0.13). When compared to warfarin, no difference existed in the composite of thromboembolic events (33% vs 30.6%, p = 0.53, respectively) or in GUSTO bleeding (10.9% vs 7.8%, p = 0.40, respectively). More patients on warfarin received blood products compared to those taking a DOAC (25.8% vs 13.9%, p < 0.001).DOACs may be an alternative to warfarin for the treatment of LV thrombus based on a retrospective assessment of thromboembolic events and GUSTO bleeding events within 90 days of diagnosis of LV thrombus. However, further prospective studies are warranted.

Impairments in Blood Pressure Regulation and Cardiac Baroreceptor Sensitivity Among Patients With Heart Failure Supported With Continuous-Flow Left Ventricular Assist Devices.

BACKGROUND: Continuous-flow (CF) left ventricular assist devices (LVADs) improve outcomes for patients with advanced heart failure (HF). However, the lack of a physiological pulse predisposes to side-effects including uncontrolled blood pressure (BP), and there are little data regarding the impact of CF-LVADs on BP regulation. METHODS: Twelve patients (10 males, 60±11 years) with advanced heart failure completed hemodynamic assessment 2.7±4.1 months before, and 4.3±1.3 months following CF-LVAD implantation. Heart rate and systolic BP via arterial catheterization were monitored during Valsalva maneuver, spontaneous breathing, and a 0.05 Hz repetitive squat-stand maneuver to characterize cardiac baroreceptor sensitivity. Plasma norepinephrine levels were assessed during head-up tilt at supine, 30o and 60o. Heart rate and BP were monitored during cardiopulmonary exercise testing. RESULTS: Cardiac baroreceptor sensitivity, determined by Valsalva as well as Fourier transformation and transfer function gain of Heart rate and systolic BP during spontaneous breathing and squat-stand maneuver, was impaired before and following LVAD implantation. Norepinephrine levels were markedly elevated pre-LVAD and improved-but remained elevated post-LVAD (supine norepinephrine pre-LVAD versus post-LVAD: 654±437 versus 323±164 pg/mL). BP increased during cardiopulmonary exercise testing post-LVAD, but the magnitude of change was modest and comparable to the changes observed during the pre-LVAD cardiopulmonary exercise testing. CONCLUSIONS: Among patients with advanced heart failure with reduced ejection fraction, CF-LVAD implantation is associated with modest improvements in autonomic tone, but persistent reductions in cardiac baroreceptor sensitivity. Exercise-induced increases in BP are blunted. These findings shed new light on mechanisms for adverse events such as stroke, and persistent reductions in functional capacity, among patients supported by CF-LVADs. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03078972.

The Clinical Conundrum of Cannabis: Current Practices and Recommendations for Transplant Clinicians: An Opinion of the Immunology/Transplantation PRN of the American College of Clinical Pharmacy.

Cannabis, or marijuana, comprises many compounds with varying effects. It has become a treatment option for chronic diseases and debilitating symptoms, and evidence suggests that it has immunomodulatory and antiinflammatory properties. Transplant centers are more frequently facing issues about cannabis, as indications and legalization expand. As of February 2020, 33 states and the District of Columbia have legalized medical cannabis, and 14 have legalized recreational cannabis. Moreover, 8 states have passed legislation prohibiting the denial of transplant listing solely based on cannabis use. Studies demonstrate the potential for significant pharmacokinetic and pharmacodynamic interactions between cannabis and immunosuppression. Additionally, safety concerns include increased risk of myocardial infarction, ischemic stroke, tachyarrhythmias, malignancy, neurocognitive deficits, psychosis, other neuropsychiatric disorders, cannabis use disorder, respiratory symptoms, and infection. A recent retrospective database study found a negative association between documented cannabis use disorder and graft survival, but little additional evidence exists evaluating this relationship. In the absence of robust clinical data, transplant centers need a clear, reasoned, and systematic approach to cannabis. The results of our national survey, unfortunately, found little consensus among institutions. As both recreational and medicinal cannabis become more ubiquitous nationwide, transplant centers will need to develop comprehensive policies to address its use.

An Electronically Delivered Patient-Activation Tool for Intensification of Medications for Chronic Heart Failure With Reduced Ejection Fraction: The EPIC-HF Trial.

BACKGROUND: Major gaps exist in the routine initiation and dose up-titration of guideline-directed medical therapies (GDMT) for patients with heart failure with reduced ejection fraction. Without novel approaches to improve prescribing, the cumulative benefits of heart failure with reduced ejection fraction treatment will be largely unrealized. Direct-to-consumer marketing and shared decision making reflect a culture where patients are increasingly involved in treatment choices, creating opportunities for prescribing interventions that engage patients. METHODS: The EPIC-HF (Electronically Delivered, Patient-Activation Tool for Intensification of Medications for Chronic Heart Failure with Reduced Ejection Fraction) trial randomized patients with heart failure with reduced ejection fraction from a diverse health system to usual care versus patient activation tools-a 3-minute video and 1-page checklist-delivered electronically 1 week before, 3 days before, and 24 hours before a cardiology clinic visit. The tools encouraged patients to work collaboratively with their clinicians to "make one positive change" in heart failure with reduced ejection fraction prescribing. The primary endpoint was the percentage of patients with GDMT medication initiations and dose intensifications from immediately preceding the cardiology clinic visit to 30 days after, compared with usual care during the same period. RESULTS: EPIC-HF enrolled 306 patients, 290 of whom attended a clinic visit during the study period: 145 were sent the patient activation tools and 145 were controls. The median age of patients was 65 years; 29% were female, 11% were Black, 7% were Hispanic, and the median ejection fraction was 32%. Preclinic data revealed significant GDMT opportunities, with no patients on target doses of ß-blocker, sacubitril/valsartan, and mineralocorticoid receptor antagonists. From immediately preceding the cardiology clinic visit to 30 days after, 49.0% in the intervention and 29.7% in the control experienced an initiation or intensification of their GDMT (P=0.001). The majority of these changes were made at the clinician encounter itself and involved dose uptitrations. There were no deaths and no significant differences in hospitalization or emergency department visits at 30 days between groups. CONCLUSIONS: A patient activation tool delivered electronically before a cardiology clinic visit improved clinician intensification of GDMT. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03334188.

Report from the 2018 consensus conference on immunomodulating agents in thoracic transplantation: Access, formulations, generics, therapeutic drug monitoring, and special populations.

In 2009, the International Society for Heart and Lung Transplantation recognized the importance and challenges surrounding generic drug immunosuppression. As experience with generics has expanded and comfort has increased, substantial issues have arisen since that time with other aspects of immunomodulation that have not been addressed, such as access to medicines, alternative immunosuppression formulations, additional generics, implications on therapeutic drug monitoring, and implications for special populations such as pediatrics and older adults. The aim of this consensus document is to address critically each of these concerns, expand on the challenges and barriers, and provide therapeutic considerations for practitioners who manage patients who need to undergo or have undergone cardiothoracic transplantation.