Call to action for drug interactions between tirzepatide and heart failure guideline-directed medical therapy.

BACKGROUND: No drug interaction between the guideline-directed medical therapy (GDMT) for heart failure (HF) with reduced ejection fraction (HFrEF) and glucose-dependent insulinotropic polypeptide (GIP)-glucagon-like peptide-1 (GLP-1) agonists is currently indexed in available drug interaction databases or package inserts for tirzepatide, the first dual GIP/GLP-1 agonist. The objective of our case series is to present 3 patients with HF who required modification in GDMT regimens for HFrEF or loop diuretic therapy after tirzepatide initiation. CASE SUMMARY: Three patients older than 60 years with HFrEF receiving GDMT agents (angiotensin receptor neprilysin inhibitors, beta blockers, mineralocorticoid receptor antagonists, and sodium-glucose cotransporter 2 inhibitors) were initiated on tirzepatide for weight loss management. After initiating tirzepatide therapy, all 3 patients developed symptomatic hypotension. Two cases had acute kidney injury owing to tirzepatide's direct vasodilation, natriuresis, reduction in extracellular volume, and weight loss. GDMT regimens and diuretic therapy were significantly modified to improve these adverse reactions. PRACTICE IMPLICATIONS: Clinicians must closely monitor vital signs and volume status after initiating tirzepatide for potential need to modify GDMT regimens. Authors request a call to action to index the drug interaction between GDMT agents and tirzepatide in major drug interaction databases for a potential hypotension or dehydration risk.

Outcomes of patients with active cancers and pre-existing cardiovascular diseases infected with SARS-CoV-2.

OBJECTIVE: To determine the impact of acute SARS-CoV-2 infection on patient with concomitant active cancer and CVD. METHODS: The researchers extracted and analyzed data from the National COVID Cohort Collaborative (N3C) database between January 1, 2020, and July 22, 2022. They included only patients with acute SARS-CoV-2 infection, defined as a positive test by PCR 21 days before and 5 days after the day of index hospitalization. Active cancers were defined as last cancer drug administered within 30 days of index admission. The "Cardioonc" group consisted of patients with CVD and active cancers. The cohort was divided into four groups: (1) CVD (-), (2) CVD ( +), (3) Cardioonc (-), and (4) Cardioonc ( +), where (-) or ( +) denotes acute SARS-CoV-2 infection status. The primary outcome of the study was major adverse cardiovascular events (MACE), including acute stroke, acute heart failure, myocardial infarction, or all-cause mortality. The researchers analyzed the outcomes by different phases of the pandemic and performed competing-risk analysis for other MACE components and death as a competing event. RESULTS: The study analyzed 418,306 patients, of which 74%, 10%, 15.7%, and 0.3% had CVD (-), CVD ( +), Cardioonc (-), and Cardioonc ( +), respectively. The Cardioonc ( +) group had the highest MACE events in all four phases of the pandemic. Compared to CVD (-), the Cardioonc ( +) group had an odds ratio of 1.66 for MACE. However, during the Omicron era, there was a statistically significant increased risk for MACE in the Cardioonc ( +) group compared to CVD (-). Competing risk analysis showed that all-cause mortality was significantly higher in the Cardioonc ( +) group and limited other MACE events from occurring. When the researchers identified specific cancer types, patients with colon cancer had higher MACE. CONCLUSION: In conclusion, the study found that patients with both CVD and active cancer suffered relatively worse outcomes when they had acute SARS-CoV-2 infection during early and alpha surges in the United States. These findings highlight the need for improved management strategies and further research to better understand the impact of the virus on vulnerable populations during the COVID-19 pandemic.

Outcomes of Patients with Active Cancers and Pre-Existing Cardiovascular Diseases Infected with SARS-CoV-2.

Objective To determine the impact of acute SARS-CoV-2 infection on patient with concomitant active cancer and CVD. Methods The researchers extracted and analyzed data from the National COVID Cohort Collaborative (N3C) database between January 1, 2020, and July 22, 2022. They included only patients with acute SARS-CoV-2 infection, defined as a positive test by PCR 21 days before and 5 days after the day of index hospitalization. Active cancers were defined as last cancer drug administered within 30 days of index admission. The "Cardioonc" group consisted of patients with CVD and active cancers. The cohort was divided into four groups: (1) CVD (-), (2) CVD (+), (3) Cardioonc (-), and (4) Cardioonc (+), where (-) or (+) denotes acute SARS-CoV-2 infection status. The primary outcome of the study was major adverse cardiovascular events (MACE), including acute stroke, acute heart failure, myocardial infarction, or all-cause mortality. The researchers analyzed the outcomes by different phases of the pandemic and performed competing-risk analysis for other MACE components and death as a competing event. Results The study analyzed 418,306 patients, of which 74%, 10%, 15.7%, and 0.3% had CVD (-), CVD (+), Cardioonc (-), and Cardioonc (+), respectively. The Cardioonc (+) group had the highest MACE events in all four phases of the pandemic. Compared to CVD (-), the Cardioonc (+) group had an odds ratio of 1.66 for MACE. However, during the Omicron era, there was a statistically significant increased risk for MACE in the Cardioonc (+) group compared to CVD (-). Competing risk analysis showed that all-cause mortality was significantly higher in the Cardioonc (+) group and limited other MACE events from occurring. When the researchers identified specific cancer types, patients with colon cancer had higher MACE. Conclusion In conclusion, the study found that patients with both CVD and active cancer suffered relatively worse outcomes when they had acute SARS-CoV-2 infection during early and alpha surges in the United States. These findings highlight the need for improved management strategies and further research to better understand the impact of the virus on vulnerable populations during the COVID-19 pandemic.

Evaluation of a pharmacist-provider collaborative clinic for treatment of iron deficiency in patients with heart failure.

PURPOSE: Intravenous iron therapy is recommended to improve symptoms and exercise tolerance in patients with heart failure (HF) with -reduced ejection fraction and iron deficiency (ID), but there are limited published data on the implementation of intravenous iron therapy in practice. A pharmacist-provider collaborative ID treatment clinic was established within an advanced HF and pulmonary hypertension service to optimize IV iron therapy. The objective was to evaluate the clinical impacts of the pharmacist-provider collaborative ID treatment clinic. METHODS: A retrospective cohort study was performed to compare clinical outcomes among patients of the collaborative ID treatment clinic (the postimplementation group) and a cohort of patients who received usual care (the preimplementation group). The study included patients 18 years of age or older with diagnosed HF or pulmonary hypertension who met prespecified criteria for ID. The primary outcome was adherence to institutional intravenous iron therapy guidance. A key secondary outcome was ID treatment goal achievement. RESULTS: A total of 42 patients in the preimplementation group and 81 in the postimplementation group were included in the study. The rate of adherence to the institutional guidance was significantly improved in the postimplementation group (93%) compared to the preimplementation group (40%). There was no significant difference in the ID therapeutic target achievement rate between the pre- and postimplementation groups (38% vs 48%). CONCLUSION: Implementing a pharmacist-provider collaborative ID treatment clinic significantly increased the number of patients who adhered to intravenous iron therapy guidance compared to usual care.

Sacubitril/Valsartan Does Not Change the Use and Dose of Loop Diuretics in Patients With Heart Failure With Reduced Ejection Fraction.

BACKGROUND: There is no standard approach for managing the use or dose of loop diuretics after initiating sacubitril/valsartan. OBJECTIVE: To investigate longitudinal trends in loop diuretic therapy use and doses during the initial 6 months following sacubitril/valsartan initiation. METHODS: This retrospective cohort study included adult patients who were initiated on sacubitril/valsartan in cardiology clinics. Inclusion criteria were patients diagnosed with heart failure with reduced ejection fraction (ejection fraction ≤40%) and initiated on sacubitril/valsartan in an outpatient setting. We investigated longitudinal trends in the prevalence of loop diuretic use and furosemide equivalent dose at baseline, 2 weeks, 1 month, 3 month and 6 months following sacubitril/valsartan initiation. RESULTS: A total of 427 patients were included in the final cohort. Compared to the baseline loop diuretic use and dose, there were no significant longitudinal changes in the prevalence of loop diuretic use or the furosemide equivalent dose over the 6 months following sacubitril/valsartan initiation. The use of sacubitril/valsartan was not significantly associated with reductions in the use or dose of loop diuretics over a 6-month follow-up period. CONCLUSION: The use of sacubitril/valsartan did not significantly change the use or dose of loop diuretics over 6-month follow-up period. Initiation of sacubitril/valsartan may not need a pre-emptive loop diuretic dose reduction.

Multidisciplinary Care in Heart Failure Services.

The American College of Cardiology/American Heart Association/Heart Failure Society of American 2022 guidelines for heart failure (HF) recommend a multidisciplinary team approach for patients with HF. The multidisciplinary HF team-based approach decreases the hospitalization rate for HF and health care costs and improves adherence to self-care and the use of guideline-directed medical therapy. This article proposes the optimal multidisciplinary team structure and each team member's delineated role to achieve institutional goals and metrics for HF care. The proposed HF-specific multidisciplinary team comprises cardiologists, surgeons, advanced practice providers, clinical pharmacists, specialty nurses, dieticians, physical therapists, psychologists, social workers, immunologists, and palliative care clinicians. A standardized multidisciplinary HF team-based approach should be incorporated to optimize the structure, minimize the redundancy of clinical responsibilities among team members, and improve clinical outcomes and patient satisfaction in their HF care.

Donor heart selection: Evidence-based guidelines for providers.

The proposed donor heart selection guidelines provide evidence-based and expert-consensus recommendations for the selection of donor hearts following brain death. These recommendations were compiled by an international panel of experts based on an extensive literature review.

Evaluating Guideline Directed Medical Therapy in Patients With Heart Failure With Reduced Ejection Fraction Post-coronary Artery Bypass Grafting.

Background: Limited evidence regarding the use of guideline directed medical therapy (GDMT) in patients with heart failure with reduced ejection fraction (HFrEF) undergoing coronary artery bypass grafting (CABG) is available. Objective: The purpose of this study was to characterize prescription of HFrEF GDMT use before and after CABG. Methods: A retrospective analysis of adult patients with an ejection fraction ≤40% undergoing CABG was performed. The primary objective was to evaluate patients receiving HFrEF GDMT, defined as a heart failure beta-blocker (HFBB) and a renin-angiotensin inhibitor preoperatively and postoperatively. Secondary outcomes included dosing, percent of patients on each individual therapy, mineralocorticoid receptor antagonist (MRA) use, and the combination thereof. The follow up period was 1 year. Results: Thirty-eight patients met criteria for inclusion. Prior to CABG, 52.6% of patients were receiving HFrEF GDMT. The prescribing rate of HFrEF GDMT was not significantly higher at any point within 1 year postoperatively (P = .299). The rate of renin-angiotensin inhibitors, HFBB, and aldosterone antagonists use significantly increased from 13.2% preoperatively to 36.8% at 1 year after CABG (P = .022). Doses of individual therapies were not significantly different across all time points preoperatively and postoperatively. Conclusion: HFrEF GDMT use and doses of individual therapies after CABG were not maximized. Collaborative efforts between cardiac surgeons, heart failure cardiologists, and pharmacists could be used to optimize HFrEF GDMT use and dose titration.

Economic Impact of Ambulatory Clinical Pharmacists in an Advanced Heart Failure Clinic.

BACKGROUND: Clinical pharmacists play pivotal roles in multidisciplinary heart failure (HF) teams through the management of HF pharmacotherapy, but no study has examined the economic impact of HF ambulatory clinical pharmacists in an advanced HF clinic. OBJECTIVE: The objective of the study was to evaluate the economic impact of HF ambulatory clinical pharmacist interventions in an advanced HF clinic using a cost-benefit analysis. METHODS: This prospective observational study detailed HF ambulatory clinical pharmacist interventions over 6 months in an advanced HF clinic in a single-center tertiary teaching hospital. The economic impact of the interventions was estimated based on the indirect cost savings with pharmacist interventions and direct cost savings recommendations. A cost-benefit analysis was performed to assess the cost of delivering the interventions compared with the benefits generated by clinical pharmacists. Results were reported as a benefit-cost ratio and net benefits. RESULTS: HF ambulatory clinical pharmacists made a total of 2,361 provider-accepted interventions over 6 months. Overall, the 3 most common intervention types were medication reconciliation (28.7%), dose change (20.8%), and addition of medication (12.3%). Anticoagulation (21.2%) was the most common intervened class of medication, followed by sodium-glucose cotransporter-2 inhibitor (12.3%) and angiotensin receptor neprilysin inhibitor (9.2%). The total net benefits were $55,553.24 over 6 months and the benefit-cost ratio was 1.55. CONCLUSION AND RELEVANCE: The addition of cardiology clinical pharmacists to an advanced HF clinic may be financially justified and cost-beneficial.

Association Between Breast Arterial Calcification on Mammography and Coronary Artery Disease: A Systematic Review and Meta-Analysis.

Background: Breast arterial calcification (BAC), which may be detected during screening mammography, is hypothesized to be a noninvasive imaging marker that may enhance cardiovascular risk assessment. Materials and Methods: In this systematic review and meta-analysis, we sought to assess the association between BAC and coronary artery disease (CAD) by conducting a meta-analysis. We conducted a literature search of PubMed, Scopus, Cochrane library, ClinicalTrials.gov, and conference proceedings, from inception through December 24, 2019. The outcome of interest was the presence of CAD in patients with BAC. This was reported as crude and adjusted odds ratio (OR). Results: A total of 18 studies comprising 33,494 women (mean age of 60.8 ± 3.7 years, 25% with diabetes, 57% with hypertension, and 21% with history of tobacco smoking) were included in the current meta-analysis. The prevalence of BAC among study participants was 10%. There was a statistically significant association between BAC and CAD (unadjusted OR 2.14; 95% confidence interval [CI] 1.63-2.81, p < 0.001, I2 = 76.5%). Moreover, adjusted estimates were available from 10 studies and BAC was an independent predictor of CAD (OR 2.39; 95% CI 1.68-3.41, p < 0.001, I2 = 61.7%). In the meta-regression analysis, covariates included year of publication, age, hypertension, diabetes mellitus, and history of tobacco smoking. None of these study covariates explained the heterogeneity across studies. Conclusions: BAC detected as part of screening mammography is a promising noninvasive imaging marker that may enhance CAD risk prediction in women. The clinical value of BAC for cardiovascular risk stratification merits further evaluation in large prospective studies.

Clinical and demographic factors associated with stimulant use disorder in a rural heart failure population.

BACKGROUND: Heart failure is becoming increasingly common among patients under 50 years of age, particularly in African Americans and patients with stimulant use disorder. Yet the sources of these disparities remain poorly understood. This study identified key demographic and clinical factors associated with stimulant use disorder in a largely rural heart failure patient registry. METHODS: Patient records reporting a diagnosis of heart failure between January 2008 and March 2020 were requested from West Virginia University Hospital Systems (n=37,872). Odds of stimulant use disorder were estimated by demographic group (age, race, sex), insurance carrier, and clinical comorbidities using logistic regression. RESULTS: Multivariable regression analysis identified higher odds of stimulant use disorder among Black/African Americans (1.95 [1.32, 2.77]) and patients who report drinking one or more alcoholic drinks per week (2.23 [1.72, 2.88]). Lower odds of stimulant use disorder were identified among patients with hypertension (0.59 [0.47, 0.73]), or diabetes (0.65 [0.52, 0.81]).. Likewise, lower odds of stimulant use disorder were noted among females, patients older than 30 years of age and those not enrolled in Medicaid. CONCLUSION: These results highlight the alarming extent to which Medicaid enrollees, Black/African Americans, people aged 18-24 and 25-44, or persons with a past alcohol use disorder diagnosis are associated with stimulant use disorder among heart failure populations living in largely rural areas. Additionally, they emphasize the need to develop policies and refine clinical care that affects this vulnerable population's prognoses.

Invasive Hemodynamic Monitoring in Cardiogenic Shock Is Associated With Lower In-Hospital Mortality.

Background There is increasing utilization of cardiogenic shock treatment algorithms. The cornerstone of these algorithms is the use of invasive hemodynamic monitoring (IHM). We sought to compare the in-hospital outcomes in patients who received IHM versus no IHM in a real-world contemporary database. Methods and Results Patients with cardiogenic shock admitted during October 1, 2015 to December 31, 2018, were identified from the National Inpatient Sample. Among this group, we compared the outcomes among patients who received IHM versus no IHM. The primary end point was in-hospital mortality. Secondary end points included vascular complications, major bleeding, need for renal replacement therapy, length of stay, cost of hospitalization, and rate of utilization of left ventricular assist devices and heart transplantation. Propensity score matching was used for covariate adjustment. A total of 394 635 (IHM=62 565; no IHM=332 070) patients were included. After propensity score matching, 2 well-matched groups were compared (IHM=62 220; no IHM=62 220). The IHM group had lower in-hospital mortality (24.1% versus 30.6%, P<0.01), higher percentages of left ventricular assist devices (4.4% versus 1.3%, P<0.01) and heart transplantation (1.3% versus 0.7%, P<0.01) utilization, longer length of hospitalization and higher costs. There was no difference between the 2 groups in terms of vascular complications, major bleeding, and the need for renal replacement therapy. Conclusions Among patients with cardiogenic shock, the use of IHM is associated with a reduction in in-hospital mortality and increased utilization of advanced heart failure therapies. Due to the observational nature of the current study, the results should be considered hypothesis-generating, and future prospective studies confirming these findings are needed.

Hereditary Apolipoprotein A-I-Associated Cardiac Amyloidosis: Importance of Endomyocardial Biopsy When Suspicion Remains High.

Cardiac amyloidosis has recently garnered substantial attention. Although the advent of noninvasive diagnostic algorithms revolutionized diagnosis, endomyocardial biopsy may still be considered in select cases to determine the amyloidosis subtype definitively. We report a case of a patients with a known mutation causing hereditary apolipoprotein A-I-associated cardiac amyloidosis. (Level of Difficulty: Advanced.).

Association of Body Mass Index With Clinical Outcomes in Patients With Heart Failure With Reduced Ejection Fraction Treated With Sacubitril/Valsartan.

BACKGROUND: Only limited data are available that address the association between body mass index (BMI) and clinical outcomes in patients with heart failure with reduced ejection fraction who are receiving sacubitril/valsartan. METHODS: We performed a retrospective multi-center cohort study in which we compared 3 body mass index groups (normal, overweight and obese groups) in patients with heart failure with reduced ejection fraction receiving sacubitril/valsartan. The follow-up period was at least 1 year. Propensity score weighting was performed. The primary outcomes were hospitalization for heart failure and all-cause mortality. RESULTS: Of the 721 patients in the original cohort, propensity score weighting generated a cohort of 540 patients in 3 groups: normal weight (n = 78), overweight (n = 181), and obese (n = 281). All baseline characteristics were well-balanced between 3 groups after propensity score weighting. Among our results, we found no significant differences in hospitalization for heart failure (normal weight versus overweight: average hazard ratio [AHR] 1.29, 95% confidence interval [CI] = 0.76-2.20, P = 0.35; normal weight versus obese: AHR 1.04, 95% CI = 0.63-1.70, P = 0.88; overweight versus obese groups: AHR 0.81, 95% CI = 0.54-1.20, P = 0.29) or all-cause mortality (normal weight versus overweight: AHR 0.99, 95% CI = 0.59-1.67, P = 0.97; normal weight versus obese: AHR 0.87, 95% CI = 0.53-1.42, P = 0.57; overweight versus obese: AHR 0.87, 95% CI = 0.58-1.32, P = 0.52). CONCLUSION: We identified no significant associations between BMI and clinical outcomes in patients diagnosed with heart failure with a reduced ejection fraction who were treated with sacubitril/valsartan. A large-scale study should be performed to verify these results.

Evaluating Sacubitril/Valsartan Dose Dependence on Clinical Outcomes in Patients With Heart Failure With Reduced Ejection Fraction.

BACKGROUND: Limited evidence is available regarding low (24/26 mg) and middle (49/51 mg) doses of sacubitril/valsartan. OBJECTIVES: The purpose of this study was to investigate the effect of sacubitril/valsartan dose on heart failure (HF) hospitalization and mortality in patients with HF with reduced ejection fraction (HFrEF). METHODS: A retrospective multicenter cohort study compared 3 doses of sacubitril/valsartan in patients with HFrEF. The coprimary outcomes were all-cause mortality and rehospitalization for HF. Propensity matching analysis was performed. RESULTS: Of 721 eligible patients, propensity matching created a cohort with an effective sample size of 652 (24/26-mg group [n = 326], 49/51-mg group [n = 147], 97/103-mg group [n = 179]). The HF hospitalization rates were 29.14% in the 24/26-mg group, 19.51% in the 49/51-mg group, and 16.10% in the 97/103-mg group (24/26 vs 49/51 mg: HR = 1.56, 95% CI = 1.04-2.34; 24/26 vs 97/103 mg: HR = 1.79, 95% CI = 1.18-2.73; 49/51 vs 97/103 mg: HR = 1.15, 95% CI = 0.70-1.89). All-cause mortality rates were 29.63% in the 24/26-mg group, 17.58% in the 49/51-mg group, and 9.27% in the 97/103-mg group (24/26 vs 49/51 mg: HR = 1.67, 95% CI = 1.07-2.59; 24/26 vs 97/103 mg: HR = 2.56, 95% CI = 1.54-4.24; 49/51 vs 97/103 mg: HR = 1.54, 95% CI = 0.84-2.82). CONCLUSION AND RELEVANCE: Sacubitril/valsartan 97/103- or 49/51-mg dose is associated with a lower mortality or hospitalization rate for HF in patients receiving sacubitril/valsartan compared with the 24/26-mg dose group.

Non-invasive prediction of tissue Doppler-derived E/e' ratio using lung Doppler signals.

AIMS: Lung Doppler signals (LDS) represent the radial movement of small pulmonary blood vessel walls, caused by pulse waves of cardiac origin. We sought to investigate the accuracy and prognostic value of LDS as a predictor of mitral valve early diastolic flow to annular velocity ratio (E/e'), in patients with acute decompensated heart failure (ADHF). METHODS AND RESULTS: We prospectively enrolled patients with ADHF (n = 99, mean age 65 ± 15 years, 61% males) who underwent echocardiographic and simultaneous LDS evaluation at hospital admission. Patients with hospital stay over 72 h underwent a repeat echocardiogram and LDS assessment before discharge. Patients were followed for the occurrence of short-term all-cause mortality and heart failure (HF) hospitalization. Predicted E/e' from LDS correlated with echocardiographic E/e' at admission and discharge (r = 0.67 and 0.83; P < 0.001 for both), respectively. Patients were dichotomized into two groups by the median predicted-E/e'. A high predicted-E/e' was associated with age, hypertension, anaemia, history of HF with preserved ejection fraction (EF), and chronic kidney disease. Over a median follow-up period of 7 months, 22 (22.2%) patients died and 23 (23.2%) patients were rehospitalized for HF. Kaplan-Meier analysis revealed a significantly lower event-free survival in high predicted-E/e' group HF patients with reduced EF (P = 0.0247). No significant differences were observed in HF rehospitalization rates between the two groups. CONCLUSION: In this single-centre prospective study of patients with ADHF, LDS predicted echocardiographic E/e' measurements and showed prognostic value in predicting all-cause mortality in HF patients with a reduced EF.

Understanding the early mortality benefit observed in the PARADIGM-HF trial: considerations for the management of heart failure with sacubitril/valsartan.

This review aims to elucidate the optimal dosing of angiotensin receptor-neprilysin inhibitor (ARNI) therapy in the heart failure (HF) treatment paradigm through examination of the trial population characteristics and the mortality benefit observed in the Prospective Comparison of ARNI with angiotensin-converting enzyme inhibitor (ACEI) to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF; NCT01035255) trial. Considerations regarding the initiation and titration of sacubitril/valsartan, a first-in-class ARNI, will also be addressed. The approval of sacubitril/valsartan heralded the first novel pharmacological class in over a decade for the treatment of heart failure with reduced ejection fraction (HFrEF). The PARADIGM-HF trial showed that treatment with valsartan/valsartan reduced the risk of first occurrence of either cardiovascular death or HF-related hospitalization (composite primary endpoint) by 20% compared with enalapril in patients with HFrEF. The incremental benefits of treatment with valsartan/valsartan over enalapril demonstrated in the PARADIGM-HF trial led to strong recommendations for its use over ACEIs or angiotensin receptor blockers to further reduce morbidity and mortality in the 2016 and 2017 American College of Cardiology/American Heart Association/Heart Failure Society of America updates to the guidelines for the management of HF. Although the optimal timing for the initiation of valsartan/valsartan has yet to be determined, its early use is likely to have a positive impact on patient outcomes.