Cost-Effectiveness of Medical Therapy for Heart Failure With Mildly Reduced and Preserved Ejection Fraction.

BACKGROUND: Three medications are now guideline-recommended treatments for heart failure with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF), however, the cost-effectiveness of these agents in combination has yet to be established. OBJECTIVES: The purpose of this study was to determine the cost-effectiveness of mineralocorticoid receptor antagonists (MRA), angiotensin receptor-neprilysin inhibitors (ARNIs), and sodium glucose co-transporter 2 inhibitors (SGLT2is) in individuals with HFmrEF/HFpEF. METHODS: Using a 3-state Markov model, we performed a cost-effectiveness study using simulated cohorts of 1,000 patients with HFmrEF and HFpEF. Treatment with 1-, 2-, and 3-drug combinations was modeled. Based on a United States health care sector perspective, outcome data was used to calculate incremental cost-effectiveness ratios (ICERs) in 2023 United States dollars based on a 30-year time horizon. RESULTS: Treatment with MRA, MRA+SGLT2i, and MRA+SGLT2i+ARNI therapy resulted in an increase in life years of 1.04, 1.58, and 1.80 in the HFmrEF subgroup, respectively, and 0.99, 1.54, and 1.77 in the HFpEF subgroup, respectively, compared with placebo. At a yearly cost of $18, MRA therapy resulted in ICERs of $10,000 per quality-adjusted life year (QALY) in both subgroups. The ICER for the addition of SGLT2i therapy ($4,962 per year) was $113,000 per QALY in the HFmrEF subgroup and $141,000 in the HFpEF subgroup. The addition of ARNI therapy ($5,504 per year) resulted in ICERs >$250,000 per QALY in both subgroups. If SGLT2i and ARNI were available at generic pricing the ICERs become <$10,000 per QALY in both EF subgroups. Outcomes were highly sensitive to assumed benefit in cardiovascular death. CONCLUSIONS: For patients with heart failure, MRA was of high value, SGLT2i was of intermediate value, and ARNI was of low value in both HFmrEF and HFpEF subgroups. For patients with HFmrEF/HFpEF increased use of MRA and SGLT2i therapies should be encouraged and be accompanied with efforts to lower the cost of SGLT2i and ARNI therapies.

Economic Modeling Analysis of an Intensive GDMT Optimization Program in Hospitalized Heart Failure Patients.

BACKGROUND: The STRONG-HF trial (Safety, Tolerability and Efficacy of Up-Titration of Guideline-Directed Medical Therapies for Acute Heart Failure) demonstrated substantial reductions in the composite of mortality and morbidity over 6 months among hospitalized patients with heart failure (HF) who were randomized to intensive guideline-directed medical therapy (GDMT) optimization compared with usual care. Whether an intensive GDMT optimization program would be cost-effective for patients with HF with reduced ejection fraction is unknown. METHODS: Using a 2-state Markov model, we evaluated the effect of an intensive GDMT optimization program on hospitalized patients with HF with reduced ejection fraction. Two population models were created to simulate this intervention, a clinical trial model, based on the participants in the STRONG-HF trial, and a real-world model, based on the Get With The Guidelines-HF registry of patients admitted with worsening HF. We then modeled the effect of a 6-month intensive triple therapy GDMT optimization program comprised of cardiologists, clinical pharmacists, and registered nurses. Hazard ratios from the intervention arm of the STRONG-HF trial were applied to both population models to simulate clinical and financial outcomes of an intensive GDMT optimization program from a US health care sector perspective with a lifetime time horizon. Optimal quadruple GDMT use was also modeled. RESULTS: An intensive GDMT optimization program was extremely cost-effective with incremental cost-effectiveness ratios <$10 000 per quality-adjusted life-year in both models. Optimal quadruple GDMT implementation resulted in the most gains in life-years with incremental cost-effectiveness ratios of $60 000 and $54 000 in the clinical trial and real-world models, respectively. CONCLUSIONS: An intensive GDMT optimization program for patients hospitalized with HF with reduced ejection fraction would be cost-effective and result in substantial gains in clinical outcomes, especially with the use of optimal quadruple GDMT. Clinicians, payers, and policymakers should prioritize the creation of such programs.

Accelerated Cardiac Allograft Vasculopathy in an Orthotopic Heart Transplant Recipient with Prior COVID-19.

BACKGROUND Cardiac allograft vasculopathy (CAV) is a post-orthotopic heart transplant (OHT) complication driven by intimal smooth muscle proliferation and immune hyperactivity to donor heart tissue. Accelerated CAV leads to allograft failure within 1 year after receiving a normal angiogram result. Viruses can contribute to CAV development, but CAV after SARS-CoV-2 infection has not been reported to date. CASE REPORT A 48-year-old man, 5 years after OHT for non-ischemic cardiomyopathy, was admitted to the Cardiac Care Unit with 3 days of abdominal pain, dyspnea, and palpitations. His medical history included hyperlipidemia and insulin-dependent diabetes. He was compliant with all medications. Two months prior, he had a mild COVID-19 case. An echocardiogram and coronary angiogram 6 and 9 months prior, respectively, were unremarkable. Right and left heart catheterization demonstrated increased filling pressures, a cardiac index of 1.7 L/ml/m², and diffuse vasculopathy most severe in the LAD artery. Flow could not be restored despite repeated ballooning and intra-catheter adenosine. Empiric ionotropic support, daily high-dose methylprednisolone, and plasmapheresis were started. A few days later, the patient had cardiac arrest requiring venoarterial extracorporeal membranous oxygenation. Given CAV's irreversibility, re-transplantation was considered, but the patient had an episode of large-volume hemoptysis and remained clinically unstable for transplant. The patient died while on palliative care. CONCLUSIONS Our patient developed accelerated CAV 2 months after having COVID-19. While CAV has known associations with certain viruses, its incidence after SARS-CoV-2 infection is unknown. Further research is needed to determine if prior SARS-CoV-2 infection is a risk factor for development of CAV in OHT recipients.

Cost-Effectiveness of Comprehensive Quadruple Therapy for Heart Failure With Reduced Ejection Fraction.

BACKGROUND: Heart failure with reduced ejection fraction (HFrEF) is one of the most costly and deadly chronic disease states. The cost effectiveness of a comprehensive quadruple therapy regimen for HFrEF has not been studied. OBJECTIVES: The authors sought to determine the cost-effectiveness of quadruple therapy comprised of beta-blockers, mineralocorticoid receptor antagonists, angiotensin receptor-neprilysin inhibitors, and sodium glucose cotransporter-2 inhibitors vs regimens composed of only beta-blockers, angiotensin-converting enzyme inhibitors, and mineralocorticoid receptor antagonists (triple therapy), and angiotensin-converting enzyme inhibitors and beta-blockers (double therapy). METHODS: Using a 2-state Markov model, the authors performed a cost-effectiveness study using simulated populations of 1,000 patients with HFrEF based on the participants in the PARADIGM-HF (Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure) trial and compared them by treatment strategy (quadruple therapy vs triple and double therapy) from a United States health care system perspective. The authors also performed 10,000 probabilistic simulations. RESULTS: Treatment with quadruple therapy resulted in an increase of 1.73 and 2.87 life-years compared with triple therapy and double therapy, respectively, and an increase in quality-adjusted life-years of 1.12 and 1.85 years, respectively. The incremental cost-effectiveness ratios of quadruple therapy vs triple therapy and double therapy were $81,000 and $51,081, respectively. In 91.7% and 99.9% of probabilistic simulations quadruple therapy had an incremental cost-effectiveness ratio of <$150,000 compared with triple therapy and double therapy, respectively. CONCLUSIONS: At current pricing, the use of quadruple therapy in patients with HFrEF was cost effective compared with triple therapy and double therapy. These findings highlight the need for improved access and optimal implementation of comprehensive quadruple therapy in eligible patients with HFrEF.

Clinical predictors and implications of cardiac inflammation detected on positron emission tomography (PET) in patients referred for premature ventricular complex (PVC) ablation.

BACKGROUND: Positron emission tomography computed tomography (PET-CT) is not routinely used for premature ventricular complexes (PVCs). Whether specific clinical factors are associated with abnormal PET-CT results is not clear. METHODS: The treatment courses and baseline characteristics of consecutive patients in a single center between 2012 and 2021, age > 18 years old, and who received 18F-fluorodeoxyglucose (FDG) PET-CT imaging for evaluation of PVCs were retrospectively analyzed. RESULTS: A total of 102 patients was included. Of these, 27 patients (26.4%) had abnormal PET-CT and 61 (59.8%) had normal imaging. Abnormal PET-CT findings were associated with non-sustained ventricular tachycardia (NSVT) (95.2% vs. 52.6%, p = 0.001), higher number of PVC morphologies (2.29 ± 0.7 vs. 1.31 ± 0.6, p < 0.001), greater PVC coupling interval dispersion (72.47 ± 66.4 ms vs. 13.42 ± 17.9 ms, p < 0.001), and greater likelihood of fast heart rate dependent PVCs (78.5% vs. 38.2%, p = 0.017). Fourteen (51.8%) patients had an abnormal PET-CT and abnormal late gadolinium enhancement (LGE). Patients with abnormal PET-CT were more frequently treated with immunosuppression (81.4% vs. 3.2%, p < .0001) than with catheter ablation (11.1% vs. 45.9%, p = 0.002) compared to the normal PET-CT group. Over a median follow-up of 862 days (IQR 134, 1407), PVC burden decreased in both groups [from 23 ± 16% to 9 ± 10% (p < 0.001) in abnormal PET-CT group and from 21 ± 15% to 7 ± 10% (p < 0.001) in normal PET-CT group]. CONCLUSIONS: Abnormal PET-CT findings were more commonly associated with NSVT, multiform PVCs, greater PVC coupling interval dispersion, and fast heart rate dependent PVCs. LGE was not sensitive for detecting inflammation. Immunosuppression was effective in managing PVCs with abnormal PET-CT.

SGLT2 Inhibitors in Heart Failure: Early Initiation to Achieve Rapid Clinical Benefits.

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are a recent addition to the pillars of medical therapy for heart failure (HF) with reduced ejection fraction, all of which improve quality of life, morbidity, and mortality. These benefits are evident within the first 30 days of initiation. This review discusses the rationale for SGLT2i initiation in simultaneous or in rapid sequence with other guideline-directed medical therapy (GDMT). We also discuss SGLT2i use and early benefits in HF patients with an ejection fraction greater than 40%.

Cancer therapy's impact on lipid metabolism: Mechanisms and future avenues.

Atherosclerotic cardiovascular disease is a growing threat among cancer patients. Not surprisingly, cancer-targeting therapies have been linked to metabolic dysregulation including changes in local and systemic lipid metabolism. Thus, tumor development and cancer therapeutics are intimately linked to cholesterol metabolism and may be a driver of increased cardiovascular morbidity and mortality in this population. Chemotherapeutic agents affect lipid metabolism through diverse mechanisms. In this review, we highlight the mechanistic and clinical evidence linking commonly used cytotoxic therapies with cholesterol metabolism and potential opportunities to limit atherosclerotic risk in this patient population. Better understanding of the link between atherosclerosis, cancer therapy, and cholesterol metabolism may inform optimal lipid therapy for cancer patients and mitigate cardiovascular disease burden.

Integration of clinical pharmacists into a heart failure clinic within a safety-net hospital.

BACKGROUND: Management of heart failure with reduced ejection fraction (HFrEF) requires timely initiation and up-titration of guideline-directed medical therapy (GDMT). In safety-net hospitals (SNHs), limited health care staff and resources make achievement of optimal medical therapy challenging. Recent studies have shown that medication titration performed by clinical pharmacists can improve outcomes in ambulatory management of HFrEF; however, the impact of these services within an SNH remains unknown. OBJECTIVE: Determine the impact of integrating clinical pharmacists into a heart failure (HF) clinic on initiation and titration of GDMT within an SNH. METHODS: We performed a single-center retrospective cohort study of patients with HFrEF treated in an ambulatory HF medication titration clinic within an SNH before and after clinical pharmacist integration. Primary outcomes included dose optimization rates of GDMT, time between clinic visits, and time to optimization of GDMT. Exploratory secondary outcomes were all-cause, HF, and cardiovascular acute care service utilization and all-cause, HF, and cardiovascular mortality before and after clinical pharmacist integration up to 6 months after initial clinic visit. RESULTS: A total of 153 patients with HFrEF were treated. Baseline characteristics in the pre- and postintervention groups were comparable. After clinical pharmacist integration, there was a statistically significant improvement in optimization of renin-angiotensin-aldosterone system inhibitor or hydralazine-nitrate equivalent (82% vs. 94%, P = 0.02). Dose optimization rates of beta-blockers (90% vs. 83%, P = 0.22) and mineralocorticoid receptor antagonists (57% vs. 57%, P > 0.99) were unchanged. There was a statistically significant reduction in mean time between clinic visits (26 vs. 14 days, P < 0.001) and in mean time to optimization of GDMT (88 vs. 45 days, P = 0.002). All-cause mortality was reduced (13% vs. 2%, P = 0.01). CONCLUSION: In SNHs, where limited health care staff and resources present as barriers to timely initiation and titration of GDMT, integration of clinical pharmacists into HF clinics can serve as a practical solution.

COVID 19 in-hospital mortality, body mass index and obesity related conditions.

OBJECTIVE: Obese patients with respiratory failure need more intensive care and invasive mechanical ventilation than their non-obese counterparts. We aimed to evaluate the impact of body mass index and obesity related conditions on fatal outcome during a hospitalization for COVID-19. METHODS: From March 1 to April 30, 2020, 425 consecutive patients with severe acute respiratory syndrome coronavirus 2 were hospitalized at University Medical Center, in New Orleans. Clinical variables, comorbidities, and hospital course were extracted from electronic medical records. Special attention was given to obesity related conditions like hypertension, type 2 diabetes, and dyslipidemia. Severe obesity was defined as a body mass index ≥35-<40 kg/m2 and morbid obesity as body mass index ≥40 kg/m2. Risk of mortality was determined by applying multivariate binary logistic regression modeling to risk factor variables (age, sex, race, and Charlson comorbid score). RESULTS: Patients were mostly African American (77.9%) and 51.0% were women. Age and Charlson comorbidity index scores averaged 60 (50-71 years) and 3.0 (1.25-5), respectively. In-hospital mortality was greater in morbidly obese than non-morbidly obese patients. Of the 64 severely obese patients, 16 had no obesity related conditions, and 48 had at least one obesity related condition: hypertension (60%), type 2 diabetes mellitus (28%), and dyslipidemia (20%). In-hospital mortality was greater in severely obese patients with than without at least one obesity related condition. CONCLUSION: During a hospitalization for COVID-19, severely obese patients with at least one obesity related condition and morbidly obese patients have a high mortality.

Post-Acute COVID-19 Syndrome and the cardiovascular system: What is known?

Post-Acute COVID-19 Syndrome (PACS) is defined by persistent symptoms >3-4 weeks after onset of COVID-19. The mechanism of these persistent symptoms is distinct from acute COVID-19 although not completely understood despite the high incidence of PACS. Cardiovascular symptoms such as chest pain and palpitations commonly occur in PACS, but the underlying cause of symptoms is infrequently known. While autopsy studies have shown that the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) rarely causes direct myocardial injury, several syndromes such as myocarditis, pericarditis, and Postural Orthostatic Tachycardia Syndrome have been implicated in PACS. Additionally, patients hospitalized with acute COVID-19 who display biomarker evidence of myocardial injury may have underlying coronary artery disease revealed by the physiological stress of SARS-CoV-2 infection and may benefit from medical optimization. We review what is known about PACS and the cardiovascular system and propose a framework for evaluation and management of related symptoms.

Use of the 1,3-ß-D-Glucan Assay for the Early Detection of Fungal Endocarditis in a 45-Year-Old Man.

BACKGROUND The management of fungal endocarditis is difficult due to high mortality and incidence of embolization. Fungal blood cultures are the criterion standard for diagnosis but show slow growth or remain negative in more than 50% of cases. We present a case in which the 1,3-ß-D-glucan (BG) assay was used to initiate antifungal treatment prior to growth in blood culture. CASE REPORT A 45-year-old man with known intravenous drug use presented to the Emergency Department in acute hypoxemic respiratory failure with a prominent aortic regurgitation murmur. Imaging findings were suggestive of endocarditis. In the Intensive Care Unit, investigations confirmed aortic valve infective endocarditis with abscess. Evidence of widespread embolization, including a shin abscess positive for Candida albicans combined with a positive BG assay prompted treatment with antifungal medication prior to positive fungal cultures. The patient underwent valve replacement and during recovery was incidentally found to have subclinical cerebral infarctions caused by a septic thrombus positive for C. albicans in the right carotid artery despite weeks of antifungal treatment. Carotid endarterectomy successfully removed the thrombus, but the patient developed a right-sided stroke. Four months later, the patient has no evidence of aortic insufficiency on echocardiogram and has made a nearly full recovery from the stroke. CONCLUSIONS We report a case of left-sided fungal endocarditis in which the BG assay was used for timely medical and surgical management leading to a successful cardiac outcome. Stroke from septic emboli is a potential complication even after weeks of antifungal therapy and valvular replacement.

Sudden Cardiac Arrest in a Patient With Myxedema Coma and COVID-19.

SARS-CoV-2 infection is associated with significant lung and cardiac morbidity but there is a limited understanding of the endocrine manifestations of coronavirus disease 2019 (COVID-19). Although thyrotoxicosis due to subacute thyroiditis has been reported in COVID-19, it is unknown whether SARS-CoV-2 infection can also lead to decompensated hypothyroidism. We present the first case of myxedema coma (MC) in COVID-19 and we discuss how SARS-CoV-2 may have precipitated multiorgan damage and sudden cardiac arrest in our patient. A 69-year-old woman with a history of small cell lung cancer presented with hypothermia, hypotension, decreased respiratory rate, and a Glasgow Coma Scale score of 5. The patient was intubated and administered vasopressors. Laboratory investigation showed elevated thyrotropin, very low free thyroxine, elevated thyroid peroxidase antibody, and markedly elevated inflammatory markers. SARS-CoV-2 test was positive. Computed tomography showed pulmonary embolism and peripheral ground-glass opacities in the lungs. The patient was diagnosed with myxedema coma with concomitant COVID-19. While treatment with intravenous hydrocortisone and levothyroxine were begun the patient developed a junctional escape rhythm. Eight minutes later, the patient became pulseless and was eventually resuscitated. Echocardiogram following the arrest showed evidence of right heart dysfunction. She died 2 days later of multiorgan failure. This is the first report of SARS-CoV-2 infection with MC. Sudden cardiac arrest likely resulted from the presence of viral pneumonia, cardiac arrhythmia, pulmonary emboli, and MC-all of which were associated with the patient's SARS-CoV-2 infection.