2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.

AIM: The "2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure" replaces the "2013 ACCF/AHA Guideline for the Management of Heart Failure" and the "2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure." The 2022 guideline is intended to provide patient-centric recommendations for clinicians to prevent, diagnose, and manage patients with heart failure. METHODS: A comprehensive literature search was conducted from May 2020 to December 2020, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from MEDLINE (PubMed), EMBASE, the Cochrane Collaboration, the Agency for Healthcare Research and Quality, and other relevant databases. Additional relevant clinical trials and research studies, published through September 2021, were also considered. This guideline was harmonized with other American Heart Association/American College of Cardiology guidelines published through December 2021. Structure: Heart failure remains a leading cause of morbidity and mortality globally. The 2022 heart failure guideline provides recommendations based on contemporary evidence for the treatment of these patients. The recommendations present an evidence-based approach to managing patients with heart failure, with the intent to improve quality of care and align with patients' interests. Many recommendations from the earlier heart failure guidelines have been updated with new evidence, and new recommendations have been created when supported by published data. Value statements are provided for certain treatments with high-quality published economic analyses.

2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: Executive Summary: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.

AIM: The "2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure" replaces the "2013 ACCF/AHA Guideline for the Management of Heart Failure" and the "2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure." The 2022 guideline is intended to provide patient-centric recommendations for clinicians to prevent, diagnose, and manage patients with heart failure. METHODS: A comprehensive literature search was conducted from May 2020 to December 2020, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from MEDLINE (PubMed), EMBASE, the Cochrane Collaboration, the Agency for Healthcare Research and Quality, and other relevant databases. Additional relevant clinical trials and research studies, published through September 2021, were also considered. This guideline was harmonized with other American Heart Association/American College of Cardiology guidelines published through December 2021. Structure: Heart failure remains a leading cause of morbidity and mortality globally. The 2022 heart failure guideline provides recommendations based on contemporary evidence for the treatment of these patients. The recommendations present an evidence-based approach to managing patients with heart failure, with the intent to improve quality of care and align with patients' interests. Many recommendations from the earlier heart failure guidelines have been updated with new evidence, and new recommendations have been created when supported by published data. Value statements are provided for certain treatments with high-quality published economic analyses.

The effect of tablet computer-based telemonitoring added to an established telephone disease management program on heart failure hospitalizations: The Specialized Primary and Networked Care in Heart Failure (SPAN-CHF) III Randomized Controlled Trial.

BACKGROUND: Mobile health applications are becoming increasingly common. Prior work has demonstrated reduced heart failure (HF) hospitalizations with HF disease management programs; however, few of these programs have used tablet computer-based technology. METHODS: Participants with a diagnosis of HF and at least 1 high risk feature for hospitalization were randomized to either an established telephone-based disease management program or the same disease management program with the addition of remote monitoring of weight, blood pressure, heart rate and symptoms via a tablet computer for 90 days. The primary endpoint was the number of days hospitalized for HF assessed at 90 days. RESULTS: From August 2014 to April 2019, 212 participants from 3 hospitals in Massachusetts were randomized 3:1 to telemonitoring-based HF disease management (n = 159) or telephone-based HF disease management (n = 53) with 98% of individuals in both study groups completing the 90 days of follow-up. There was no significant difference in the number of days hospitalized for HF between the telemonitoring disease management group (0.88 ± 3.28 days per patient-90 days) and the telephone-based disease management group (1.00 ± 2.97 days per patient-90 days); incidence rate ratio 0.82 (95% confidence interval, 0.43-1.58; P = .442). CONCLUSIONS: The addition of tablet-based telemonitoring to an established HF telephone-based disease management program did not reduce HF hospitalizations; however, study power was limited.

The Cardiac Amyloidosis Registry Study (CARS): Rationale, Design and Methodology.

BACKGROUND: CARS (Cardiac Amyloidosis Registry Study) is a multicenter registry established in 2019 that includes patients with transthyretin (ATTR, wild-type and variant) and light chain (AL) cardiac amyloidosis (CA) evaluated at major amyloidosis centers between 1997 and 2025. CARS aims to describe the natural history of CA with attention to clinical and diagnostic variables at the time of diagnosis, real-world treatment patterns, and associated outcomes of patients in a diverse cohort that is more representative of the at-risk population than that described in CA clinical trials. METHODS AND RESULTS: This article describes the design and methodology of CARS, including procedures for data collection and preliminary results. As of February 2023, 20 centers in the United States enrolled 1415 patients, including 1155 (82%) with ATTR and 260 (18%) with AL CA. Among those with ATTR, wild-type is the most common ATTR (71%), and most of the 305 patients with variant ATTR have the p.V142I mutation (68%). A quarter of the total population identifies as Black. More individuals with AL are female (39%) compared to those with ATTR (13%). CONCLUSIONS: CARS will answer crucial clinical questions about CA natural history and permit comparison of different therapeutics not possible through current clinical trials. Future international collaboration will further strengthen the validity of observations of this increasingly recognized condition.

2022 American College of Cardiology/American Heart Association/Heart Failure Society of America Guideline for the Management of Heart Failure: Executive Summary.

BACKGROUND: The 2022 American College of Cardiology/American Heart Association/Heart Failure Society of America (AHA/ACC/HFSA) Guideline for the Management of Heart Failure replaces the 2013 ACCF/AHA Guideline for the Management of Heart Failure and the 2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure. The 2022 guideline is intended to provide patient-centric recommendations for clinicians to prevent, diagnose and manage patients with heart failure. METHODS: A comprehensive literature search was conducted from May 2020 to December 2020, encompassing studies, reviews and other evidence conducted in human subjects that were published in English from MEDLINE (PubMed), EMBASE, the Cochrane Collaboration, the Agency for Healthcare Research and Quality, and other relevant databases. Additional relevant clinical trials and research studies published through September 2021 were also considered. This guideline was harmonized with other American Heart Association/American College of Cardiology guidelines published through December 2021. RESULTS AND CONCLUSIONS: Heart failure remains a leading cause of morbidity and mortality globally. The 2022 heart failure guideline provides recommendations based on contemporary evidence for the treatment of these patients. The recommendations present an evidence-based approach to managing patients with heart failure, with the intent to improve quality of care and align with patients' interests. Many recommendations from the earlier heart failure guidelines have been updated with new evidence, and new recommendations have been created when supported by published data. Value statements are provided for certain treatments that have high-quality published economic analyses.

Understanding Longitudinal Changes in Pulmonary Vascular Resistance After Left Ventricular Assist Device Implantation.

BACKGROUND: Elevated pulmonary vascular resistance (PVR) is common in patients with advanced heart failure. PVR generally improves after left ventricular assist device (LVAD) implantation, but the rate of decrease has not been quantified and the patient characteristics most strongly associated with this improvement are unknown. METHODS AND RESULTS: We analyzed 1581 patients from the Interagency Registry for Mechanically Assisted Circulatory Support registry who received a primary continuous-flow LVAD, had a baseline PVR of ≥3 Wood units (WU), and had PVR measured at least once postoperatively. Multivariable linear mixed effects modeling was used to evaluate independent associations between postoperative PVR and patient characteristics. PVR decreased by 1.53 WU (95% confidence interval [CI] 1.27-1.79 WU) per month in the first 3 months postoperatively, and by 0.066 WU (95% CI 0.060-0.070 WU) per month thereafter. Severe mitral regurgitation at any time during follow-up was associated with a 1.29 WU (95% CI 1.05-1.52 WU) higher PVR relative to absence of mitral regurgitation at that time. In a cross-sectional analysis, 15%-25% of patients had persistently elevated PVR of ≥3 WU at any given time within 36 months after LVAD implantation. CONCLUSION: The PVR tends to decrease rapidly early after implantation, and only more gradually thereafter. Residual mitral regurgitation may be an important contributor to elevated postoperative PVR. Future research is needed to understand the implications of elevated PVR after LVAD implantation and the optimal strategies for prevention and treatment.

Factors associated with neutropenia post heart transplantation.

BACKGROUND: Neutropenia is a serious complication following heart transplantation (OHT); however, risk factors for its development and its association with outcomes is not well described. We sought to study the prevalence of neutropenia, risk factors associated with its development, and its impact on infection, rejection, and survival. METHODS: A retrospective single-center analysis of adult OHT recipients from July 2004 to December 2017 was performed. Demographic, laboratory, medication, infection, rejection, and survival data were collected for 1 year post-OHT. Baseline laboratory measurements were collected within the 24 hours before OHT. Neutropenia was defined as absolute neutrophil count ≤1000 cells/mm3. Cox proportional hazards models explored associations with time to first neutropenia. Associations between neutropenia, analyzed as a time-dependent covariate, with secondary outcomes of time to infection, rejection, or death were also examined. RESULTS: Of 278 OHT recipients, 84 (30%) developed neutropenia at a median of 142 days (range 81-228) after transplant. Factors independently associated with increased risk of neutropenia included lower baseline WBC (HR 1.12; 95% CI 1.11-1.24), pre-OHT ventricular assist device (1.63; 1.00-2.66), high-risk CMV serostatus [donor positive, recipient negative] (1.86; 1.19-2.88), and having a previous CMV infection (4.07; 3.92-13.7). CONCLUSIONS: Neutropenia is a fairly common occurrence after adult OHT. CMV infection was associated with subsequent neutropenia, however, no statistically significant differences in outcomes were found between neutropenic and non-neutropenic patients in this small study. It remains to be determined in future studies if medication changes in response to neutropenia would impact patient outcomes.

Left thoracotomy vs full sternotomy for centrifugal durable LVAD implantation: 1-year outcome comparison post-LVAD and post-heart transplantation.

Left ventricular assist device (LVAD) implantations have traditionally been approached through a full median sternotomy (FS). Recently, a minimally invasive left thoracotomy (LT) approach has been popularized. This study sought to compare the outcomes of FS and LT patients post-primary LVAD implantation and post-subsequent heart transplant (HT). This was a single-center retrospective study. 83 patients who underwent primary centrifugal durable LVAD implantation from January 2014 to June 2018 were included (FS, n = 41; LT, n = 42). 41 patients had a subsequent HT (FS, n = 19; LT, n = 22). Pre-operative patient demographics, intraoperative variables, post-operative 1-year survival, length of hospital stay, complications, and outcomes for LVAD implantation and following HT were analyzed. Intraoperative data showed that the LT group had a 23.4% longer mean LVAD implant surgical time (p < 0.01). One-year post-LVAD survival was similar between the two groups (p = 0.05). Complication rates, with the exception of the rate of hemorrhagic stroke (p = 0.04) post-LVAD implant were similar. One-year survival post-HT was similar between groups (p = 0.35). Complication rates and mean length of hospital stay were also similar (p = 1.0) post-HT. Our study demonstrated that LT approach does not negatively affect post-LVAD implantation or post-HT outcomes. Further, larger studies may determine more detailed effects of LT approach.

In-hospital outcomes after bariatric surgery in patients with heart failure.

Based on the largest publicly available all-payer inpatient database in the United States, this study sought to evaluate real-world outcomes after bariatric surgery among patients with heart failure.

Outcomes of Severely Obese Patients Supported by a Centrifugal-Flow Left Ventricular Assist Device.

BACKGROUND: Ventricular assist devices provide improved outcomes for patients with advanced heart failure, but their benefit in the severely obese is not well documented. METHODS: Patients enrolled in the HeartWare ADVANCE trial (n=382) were divided into 2 body mass index (BMI) groups. Patients with severe obesity (>35 kg/m2) were compared with a control group with BMI ≤35 kg/m2. The association of BMI with survival was tested using Kaplan-Meier analysis and major adverse events were compared. RESULTS: At implantation, 48 (13%) of patients were severely obese. There was no difference in survival through 2 years of support between severely obese patients and the control group. Severely obese patients were at higher risk of driveline infection (P = .01) and acute renal dysfunction (P = .002). Both groups experienced similar improvements in quality of life. Functional capacity improved in both severely obese and control patients, although severely obese patients had smaller improvements than controls in their 6-minute walk scores. CONCLUSIONS: Despite an increased risk of adverse events, severe obesity was not associated with reduced survival or quality of life. A better understanding of the risks and benefits of left ventricular assist device therapy in obese patients will help in the shared decision-making of the patient selection process.

Timing and Trends of Right Atrial Pressure and Risk of Right Heart Failure After Left Ventricular Assist Device Implantation.

BACKGROUND: Elevated right atrial pressure (RAP) is associated with poor outcomes after left ventricular assist device (LVAD) implantation. However, the optimal time for RAP measurement and the importance of resolution of right heart congestion prior to LVAD implantation remain unclear. METHODS AND RESULTS: We performed a retrospective cohort study of 134 consecutive LVAD recipients from our institution. Congestion was defined as RAP ≥ 14 mmHg and was assessed at hospital admission and implant. The primary outcome was death or right ventricular assist device (RVAD) implantation. When stratified by congestion status at admission, congested and non-congested patients had similar event-free survival rates (hazard ratio [HR]: 1.2, 95% confidence interval [CI]: 0.6-2.6). However, when stratified at implant, congested patients had a higher rate death or RVAD implantation (HR: 2.5, 95% CI: 1.1-5.6). Patients were then divided into 4 groups based on their trajectory of congestion status: no congestion, resolved congestion, new congestion, or persistent congestion. Patients with no congestion and resolved congestion had similar outcomes, whereas patients with persistent congestion had a markedly increased rate of death or RVAD implantation (HR: 3.1, 95% CI: 1.3-7.6). CONCLUSION: RAP at LVAD implantation is more strongly associated with postoperative outcomes than admission RAP. Patients not responsive to decongestive therapies, with persistently elevated RAP, represent a high-risk cohort for adverse outcomes following LVAD implantation.

A case series: the outcomes, support duration, and graft function recovery after VA-ECMO use in primary graft dysfunction after heart transplantation.

Primary graft dysfunction (PGD) is a rare complication associated with high mortality after heart transplantation, which may require veno-arterial extra-corporeal membrane oxygenation (VA-ECMO) support. A standardized definition for PGD was developed by the International Society of Heart and Lung Transplantation in 2014. Due to limited reports using this definition, the detailed outcomes after VA-ECMO support remain unclear. Therefore, we retrospectively analyzed our single-center outcomes of PGD following VA-ECMO support. Between September 2014 and August 2018, 160 patients underwent heart transplantation in our single center. Nine PGD patients required VA-ECMO support, with an incidence of 5.6%. Pre-operative recipient/donor demographics, intra-operative variables, timing of VA-ECMO initiation and support duration, graft function recovery during 30 days after heart transplant, VA-ECMO complications, and survival were analyzed. The indication for VA-ECMO support was biventricular failure for all nine patients. Six patients had severe PGD requiring intra-operative VA-ECMO, while two patients had moderate PGD and one patient had mild PGD requiring post-operative VA-ECMO. All cohorts were successfully decannulated in a median of 10 days. Survival to discharge rate was 88.9%. One-year survival rate was 85.7%. Left ventricular ejection fraction recovered to normal within 30 days in all PGD patients. Our study showed VA-ECMO support led to high survival and timely graft function recovery in all cohorts. Further larger research can clarify the detailed effects of VA-ECMO support which may lead to standardized indication of VA-ECMO support for PGD patients.

The Neutrophil-Lymphocyte Ratio and Survival During Left Ventricular Assist Device Support.

BACKGROUND: Systolic heart failure (HF) is a low-grade systemic inflammatory state. Neutrophil-lymphocyte ratio (NLR) is a nonspecific inflammatory marker with prognostic value in HF. We aimed to determine the relationship between NLR and mortality during left ventricular assist device (LVAD) support. METHODS AND RESULTS: We retrospectively reviewed LVAD recipients implanted in the years 2010-2018. NLR was recorded before LVAD implantation and at intervals during LVAD support; pre-LVAD and 90-day LVAD NLRs were compared. Cox proportional hazard models were constructed to study the impact of NLR, both before LVAD implantation and at 90 days with LVAD, on mortality during subsequent LVAD support. Among 301 subjects, the median pre-LVAD NLR was 4.7 (interquartile range 3.0-8.0). Higher pre-LVAD NLR was independently associated with increased mortality during a median 324 days of LVAD support (adjusted hazard ratio [HR] 1.03, 95% confidence interval [CI] 1.01-1.06; P = .012, adjusted for pre-LVAD age, HF etiology, white blood count, hemoglobin, blood urea nitrogen, and sodium). After LVAD implantation, the NLR rose initially and then plateaued lower by day 90. Despite the mean decrease, higher 90-day LVAD NLR remained independently associated with increased mortality (adjusted HR 1.06, 95% CI 1.01-1.13; P = .033, stratified by early infection events). CONCLUSIONS: Higher pre-LVAD NLR is independently associated with mortality during LVAD support. NLR improves during LVAD support, but even accounting for early infections, a higher NLR at day 90 remains associated with subsequent mortality.

Nutrition, Obesity, and Cachexia in Patients With Heart Failure: A Consensus Statement from the Heart Failure Society of America Scientific Statements Committee.

Dietary guidance for patients with heart failure (HF) has traditionally focused on sodium and fluid intake restriction, but dietary quality is frequently poor in patients with HF and may contribute to morbidity and mortality. Restrictive diets can lead to inadequate intake of macronutrients and micronutrients by patients with HF, with the potential for deficiencies of calcium, magnesium, zinc, iron, thiamine, vitamins D, E, and K, and folate. Although inadequate intake and low plasma levels of micronutrients have been associated with adverse clinical outcomes, evidence supporting therapeutic repletion is limited. Intravenous iron, thiamine, and coenzyme Q10 have the most clinical trial data for supplementation. There is also limited evidence supporting protein intake goals. Obesity is a risk factor for incident HF, and weight loss is an established approach for preventing HF, with a role for bariatric surgery in patients with severe obesity. However weight loss for patients with existing HF and obesity is a more controversial topic owing to an obesity survival paradox. Dietary interventions and pharmacologic weight loss therapies are understudied in HF populations. There are also limited data for optimal strategies to identify and address cachexia and sarcopenia in patients with HF, with at least 10%-20% of patients with ambulatory systolic HF developing clinically significant wasting. Gaps in our knowledge about nutrition status in patients with HF are outlined in this Statement, and strategies to address the most clinically relevant questions are proposed.

Left Ventricular Assist Devices, Kidney Disease, and Dialysis.

Left ventricular assist devices (LVADs) improve survival in patients with advanced heart failure. As LVAD use increases, so do the number of patients with LVADs who also have kidney disease. However, there are only sparse data on how best to care for these patients. This review provides an overview of LVAD principles and indications, including blood pressure assessment and criteria for receipt of both destination and bridge to transplantation LVADs. Following LVAD implantation, kidney function may improve in the short term, particularly if cardiorenal physiology was present; in the longer term, data remain limited. Individuals with glomerular filtration rates chronically < 30mL/min/1.73m2, including those treated with maintenance dialysis, are generally ineligible for destination LVADs. However, select patients with advanced chronic kidney disease can be considered for LVADs as a bridge to heart or heart-kidney transplantation. Patients who develop acute kidney injury and require dialysis following LVAD implantation have high mortality rates. Although thrice-weekly hemodialysis is the most common modality for patients with LVADs, peritoneal dialysis and home hemodialysis are additional options. Peritoneal dialysis in particular may be associated with lower risk for bloodstream infection and fewer hemodynamic shifts. For those treated with hemodialysis, arteriovenous fistulas can successfully be used for vascular access. Many questions remain, including optimal anemia management and refinement of hemodialysis protocols for patients with an LVAD, and further research is needed in this field.

Remote Monitoring of Patients With Heart Failure: A White Paper From the Heart Failure Society of America Scientific Statements Committee.

BACKGROUND: After several neutral telehealth trials, the positive findings and subsequent Food and Drug Administration approval of an implantable pulmonary arterial pressure monitor (PAPM) led to renewed interest in remote patient monitoring (RPM). Here we seek to provide contemporary guidance on the appropriate use of RPM technology. RESULTS: Although early trials of external RPM devices suggested benefit, subsequent multicenter trials failed to demonstrate improved outcomes. Monitoring features of cardiac implantable electronic devices (CIEDs) also did not deliver improved HF outcomes, newer, multisensor algorithms may be better. Earlier technologies using direct pressure measurement via implanted devices failed to show benefit owing to complications or failure. Recently, 1 PAPM showed benefit in a randomized controlled trial. Although not showing cost reduction, cost-benefit analysis of that device suggests that it may meet acceptable standards. Additional research is warranted and is in progress. Consumer-owned electronic devices are becoming more pervasive and hold hope for future benefit in HF management. Practical aspects around RPM technology include targeting of risk populations, having mechanisms to ensure patient adherence to monitoring, and health care team structures that act on the data. CONCLUSIONS: Based on available evidence, routine use of external RPM devices is not recommended. Implanted devices that monitor pulmonary arterial pressure and/or other parameters may be beneficial in selected patients or when used in structured programs, but the value of these devices in routine care requires further study. Future research is also warranted to better understand the cost-effectiveness of these devices.

Disseminated mucormycosis masquerading as rejection early after orthotopic heart transplantation.

Mucorales organisms are an uncommon cause of invasive fungal infections after solid organ transplantation but are associated with great morbidity and mortality. We report a fatal case of disseminated Cunninghamella infection early after heart transplantation. The patient developed graft dysfunction and elevated markers of myocyte injury and autopsy revealed fulminant fungal myocarditis. This case highlights the need for a high index of suspicion in immunocompromised patients who are not improving with standard antimicrobial therapy.