Implementation of remote monitoring strategies to improve chronic heart failure management.

PURPOSE OF REVIEW: The goal of this review is to describe the current evidence available for remote monitoring devices available for patients with chronic heart failure, and also detail practical clinical recommendations for implementing these tools in daily clinical practice. RECENT FINDINGS: Several devices ranging from sophisticated multiparametric algorithms in defibrillators, implantable pulmonary artery pressure sensors, and wearable devices to measure thoracic impedance can be utilized as important adjunctive tools to reduce the risk of heart failure hospitalization in patients with chronic heart failure. Pulmonary artery pressure sensors provide the most granular data regarding hemodynamic status, while alerts from wearable devices for thoracic impedance and defibrillator-based algorithms increase the likelihood of worsening clinical status while also having high negative predictive value when values are within normal range. SUMMARY: Multiple device-based monitoring strategies are available to reduce longitudinal risk in patients with chronic heart failure. Further studies are needed to best understand a practical pathway to integrate multiple signals of data for early clinical decompensation risk predictionVideo abstract: http://links.lww.com/HCO/A95.

Development and Validation of a Risk Score Predicting Death Without Transplant in Adult Heart Transplant Candidates.

Importance: The US heart allocation system prioritizes medically urgent candidates with a high risk of dying without transplant. The current therapy-based 6-status system is susceptible to manipulation and has limited rank ordering ability. Objective: To develop and validate a candidate risk score that incorporates current clinical, laboratory, and hemodynamic data. Design, Setting, and Participants: A registry-based observational study of adult heart transplant candidates (aged ≥18 years) from the US heart allocation system listed between January 1, 2019, and December 31, 2022, split by center into training (70%) and test (30%) datasets. Adult candidates were listed between January 1, 2019, and December 31, 2022. Main Outcomes and Measures: A US candidate risk score (US-CRS) model was developed by adding a predefined set of predictors to the current French Candidate Risk Score (French-CRS) model. Sensitivity analyses were performed, which included intra-aortic balloon pumps (IABP) and percutaneous ventricular assist devices (VAD) in the definition of short-term mechanical circulatory support (MCS) for the US-CRS. Performance of the US-CRS model, French-CRS model, and 6-status model in the test dataset was evaluated by time-dependent area under the receiver operating characteristic curve (AUC) for death without transplant within 6 weeks and overall survival concordance (c-index) with integrated AUC. Results: A total of 16 905 adult heart transplant candidates were listed (mean [SD] age, 53 [13] years; 73% male; 58% White); 796 patients (4.7%) died without a transplant. The final US-CRS contained time-varying short-term MCS (ventricular assist-extracorporeal membrane oxygenation or temporary surgical VAD), the log of bilirubin, estimated glomerular filtration rate, the log of B-type natriuretic peptide, albumin, sodium, and durable left ventricular assist device. In the test dataset, the AUC for death within 6 weeks of listing for the US-CRS model was 0.79 (95% CI, 0.75-0.83), for the French-CRS model was 0.72 (95% CI, 0.67-0.76), and 6-status model was 0.68 (95% CI, 0.62-0.73). Overall c-index for the US-CRS model was 0.76 (95% CI, 0.73-0.80), for the French-CRS model was 0.69 (95% CI, 0.65-0.73), and 6-status model was 0.67 (95% CI, 0.63-0.71). Classifying IABP and percutaneous VAD as short-term MCS reduced the effect size by 54%. Conclusions and Relevance: In this registry-based study of US heart transplant candidates, a continuous multivariable allocation score outperformed the 6-status system in rank ordering heart transplant candidates by medical urgency and may be useful for the medical urgency component of heart allocation.

Post-transplant survival after normothermic regional perfusion versus direct procurement and perfusion in donation after circulatory determination of death in heart transplantation.

BACKGROUND: Since 2019, the annual transplantation rate of hearts donated following circulatory death (DCD) has increased significantly in the United States. The 2 major heart procurement techniques following circulatory death are direct procurement and perfusion (DPP) and normothermic regional perfusion (NRP). Post-transplant survival for heart recipients has not been compared between these 2 techniques. METHODS: This observational study uses data on adult heart transplants from donors after circulatory death from January 1, 2019 to December 31, 2021 in the Scientific Registry of Transplant Recipients. We identified comparable transplant cases across procurement types using propensity-score matching and measured the association between procurement technique and 1-year post-transplant survival using Kaplan-Meier and Cox proportional hazards model stratefied by matching pairs. RESULTS: Among 318 DCD heart transplants, 216 (68%) were procured via DPP, and 102 (32%) via NRP. Among 22 transplant centers that accepted circulatory-death donors, 3 used NRP exclusively, and 5 used both procurement techniques. After propensity-score matching on recipient and donor factors, there was no significant difference in 1-year post-transplant survival (93.1% for NRP vs 91.1% for DPP, p = 0.79) between procurement techniques. CONCLUSIONS: NRP and DPP procurements are associated with similar 1-year post-transplant survival. If NRP is ethically permissible and improves outcomes for abdominal organs, it should be the preferred procurement technique for DCD hearts.

Financial Implication of Sodium Zirconium Cyclosilicate Therapy in Patients with Systolic Heart Failure and Hyperkalemia.

Sodium zirconium cyclosilicate (SZC), a newly-introduced potassium binder, can be used to manage hyperkalemia especially in patients with chronic kidney disease and in those on medical therapy which may raise serum potassium levels. The medication may incur additional costs but may in turn have a significant benefit in the effect of maintaining guideline-directed medical therapy for heart failure. We aimed to investigate the financial impact of SZC therapy in patients with systolic heart failure.Patients with systolic heart failure who received SZC for hyperkalemia between July 2020 and March 2023 were included. In-hospital medical costs were compared between the patients who discontinued SZC and those who continued SZC. For the continue group, the cost of SZC was added. All patients were followed for 2 years or until May 2023.A total of 36 patients (median age 81 years, 56% male, median left ventricular ejection fraction 43%) were included. Total medical costs were significantly lower in the continue group (n = 12) compared to the discontinue group (n = 24) (3.1 [3.1, 6.2] versus 12.1 [3.8, 48.6] × 104 JPY per month, P = 0.039). In the continue group, serum potassium levels were decreased, renin-angiotensin-aldosterone system inhibitor doses were up-titrated, and the left ventricular ejection fraction was increased, whereas these parameters remained unchanged or worsened in the discontinue group.SZC may have the potential to assist in the up-titration of potassium-sparing heart failure-specific medications, prevent readmissions, and minimize medical costs, by preventing recurrent hyperkalemia in patients with systolic heart failure.

Earlier First Publication Is Associated with More Future Publication.

Participation in clinical research has served clinicians to develop academic careers, as well as to deepen clinical insights, implement evidence-based medicine practices, and even inspire new clinical questions. Early engagement in academic pursuits may better prepare clinicians to maintain long-term research productivity, rather than starting later in their careers.We included medical doctors who graduated from a medical university and retrospectively followed them for 10 years after graduation. The impact of at least one publication within the first 5 years on the achievement of ≥ 5 publications within 10 years was evaluated.A total of 79 medical doctors, including 60 (76%) men, were included. During the first 5 years, 21 (27%) published at least one paper. Overall, 25 (32%) achieved the primary outcome. At least one publication during the first 5 years was an independent predictor of the primary outcome (odds ratio 30.4, 95% confidence interval 2.68-251, P = 0.002). Medical doctors with at least one publication within the first 5 years had significantly higher cumulative 10-year publications compared to no publications within the first 5 years (9 [5, 13] versus 0 [0, 3], P < 0.001).In this retrospective study, we demonstrated that an early involvement in research defined by academic output was associated with higher odds of multiple publications later in a career. Prospective studies to validate our findings by involving young medical doctors in academic pursuits are needed to understand the longitudinal effects of early career academic productivity.

Estimation of Small Dense LDL-Cholesterol Levels in Patients with Acute Coronary Syndrome.

Small dense LDL-cholesterol is an established risk factor for atherosclerosis, but it is not routinely measured in clinical practice, and its measurement has not yet been reimbursed. The Sampson equation that uses triglyceride and LDL-cholesterol levels has very recently been proposed to estimate small dense LDL-cholesterol levels. We validated its accuracy in patients with acute coronary syndrome.Serum samples were obtained on admission from hospitalized patients with acute coronary syndrome before heparinization. Small dense LDL-cholesterol levels were measured directly and were also estimated from triglyceride and LDL-cholesterol levels using the Sampson equation. The correlation between the Sampson's equation and direct measurement was investigated.A total of 55 patients were enrolled. The median age was 75 (65, 84) years old, and 35 (64%) were men. There was a moderate correlation between the two methods (r = 0.76, P < 0.001). A lower level of small dense LDL-cholesterol was independently associated with a greater overestimation of the Sampson equation.The Sampson equation is useful for estimating small dense LDL-cholesterol levels in patients with acute coronary syndrome. However, the estimated value may be overestimated in patients with low lipid profiles.

Negative Prognostic Impact of Mineralocorticoid Receptor Antagonist in Elderly Patients Receiving TAVR.

Background: Morbidity and mortality following trans-catheter aortic valve replacement (TAVR) remain high. Renin-angiotensin system inhibitors improve clinical outcomes in the cohort studied in this work. However, post-TAVR prognostic impact of mineralocorticoid receptor antagonist (MRA), another neuro-hormonal blocker, remains uncertain. Here, we hypothesized that MRA was associated with improved clinical outcomes in elderly patients with severe aortic stenosis receiving TAVR. METHODS: Consecutive patients who received TAVR at our institute between 2015 and 2022 were considered for inclusion. Propensity score matching analysis was performed to match pre-procedural baseline characteristics between those with and without MRA. The prognostic impact of MRA use on the composite primary endpoint consisting of all-cause death and heart failure during the 2-year observational period following index discharge was evaluated. RESULTS: Among 352 patients who received TAVR, 112 patients (median 86 years, 31 men) were included, consisting of baseline-matched 56 patients with MRA and 56 patients without MRA. Following TAVR, patients with MRA had more impaired renal function compared with no MRA group. Following index discharge, serum potassium tended to increase, and renal function tended to decline in patients with MRA. Patients with MRA had a higher cumulative incidence of the primary endpoints during a two-year observational period (30% versus 8%, p = 0.022). CONCLUSIONS: Routine prescription of MRA might not be recommended in elderly patients with severe aortic stenosis receiving TAVR, given its negative prognostic impact. Optimal patient selection for MRA administration in this cohort needs further study.

Association of remote dielectric sensing and six-minute walk distance among those with severe aortic stenosis.

BACKGROUND: Remote dielectric sensing (ReDS) is a novel non-invasive electromagnetic energy-incorporated technology to quantify lung fluid levels. The six-minute walk test is an established method to assess exercise capacity among those with a variety of chronic conditions related to heart and pulmonary diseases. We aimed to understand the association between ReDS value and six-minute walk distance (6MWD) in patients with severe aortic stenosis being evaluated for valve replacement. METHODS: Patients who were hospitalized to receive trans-catheter aortic valve replacement were prospectively included and simultaneous ReDS and 6MWD measurements were performed on admission. We attempted to correlate 6MWD with ReDS value. RESULTS: A total of 25 patients (median 85 years, 11 men) were included. Median 6MWD was 168 (133, 244) meters and median ReDS value was 26 % (23 %, 30 %). 6MWD displayed a moderate inverse correlation with ReDS value (r = -0.516, p = 0.008) and significantly distinguished ReDS value ≥30 %, representing mild or greater pulmonary congestion, at a cut-off of 170 m (sensitivity 0.67 and specificity 1.00). CONCLUSIONS: 6MWD had a moderate inverse correlation with ReDS values among candidates for trans-catheter aortic valve replacement, indicating that patients with shorter 6MWD had increased pulmonary congestion as assessed by ReDS system.

Association of high-priority exceptions with waitlist mortality among heart transplant candidates.

BACKGROUND: The US heart allocation system ranks candidates using six categorical status levels. Transplant programs can request exceptions to increase a candidate's status level if they believe their candidate has the same medical urgency as candidates who meet the standard criteria for that level. We aimed to determine if exception candidates have the same medical urgency as standard candidates. METHODS: Using the Scientific Registry of Transplant Recipients, we constructed a longitudinal waitlist history dataset of adult heart-only transplant candidates listed between October 18, 2018 and December 1, 2021. We estimated the association between exceptions and waitlist mortality with a mixed-effects Cox proportional hazards model that treated status and exceptions as time-dependent covariates. RESULTS: Out of 12,458 candidates listed during the study period, 2273 (18.2%) received an exception at listing and 1957 (15.7%) received an exception after listing. After controlling for status, exception candidates had approximately half the risk of waitlist mortality as standard candidates (hazard ratio [HR] 0.55, 95% confidence interval [CI] [0.41, 0.73], p < .001). Exceptions were associated with a 51% lower risk of waitlist mortality among Status 1 candidates (HR 0.49, 95% CI [0.27, 0.91], p = .023) and a 61% lower risk among Status 2 candidates (HR 0.39, 95% CI [0.24, 0.62], p < .001). CONCLUSIONS: Under the new heart allocation policy, exception candidates had significantly lower waitlist mortality than standard candidates, including exceptions for the highest priority statuses. These results suggest that candidates with exceptions, on average, have a lower level of medical urgency than candidates who meet standard criteria.

Prognostic Impact of Baseline Six-Minute Walk Distance following Trans-Catheter Aortic Valve Replacement.

BACKGROUND: The six-minute walk test is a practical tool for assessing functional capacity in patients with a variety of etiologies including pulmonary disease and heart failure. Six-minute walk distance (6MWD) is associated with mortality and morbidity in patients with a variety of comorbidities. We aimed to assess the prognostic impact of baseline 6MWD in patients with severe aortic stenosis undergoing trans-catheter aortic valve replacement (TAVR). METHODS: Patients with severe aortic stenosis who underwent a six-minute walk test after index admission and underwent TAVR between 2015 and 2022 were included in this retrospective study. Patients were followed up for two years or until November 2022 following TAVR. The impact of baseline 6MWD on the primary composite outcome, defined as all-cause death and all-cause readmission during the 2-year observation period following index discharge, was assessed. RESULTS: A total of 299 patients (median age 86 years old, 85 men) were included. They received a 6-min walk test prior to TAVR, underwent successful TAVR procedures, and were discharged alive. The median baseline 6MWD was 204 (143, 282) meters. Shorter baseline 6MWD was associated with higher cumulative incidence of the primary outcome with an adjusted hazard ratio of 0.76 (95% confidence interval 0.58-1.01, p = 0.055) with a cutoff 6MWD of 178 m during the 2-year observation period after index discharge. CONCLUSIONS: Overall, functional capacity was impaired in the elderly patients with severe aortic stenosis prior to TAVR. Patients with severe aortic stenosis having shorter baseline 6MWD tended to have higher rates of morbidity and mortality after successful TAVR. The clinical implication of aggressive cardiac rehabilitation to improve patients' functional capacity and 6MWD-guided optimal patient selection remain the future concerns.

Prognostic Impact of Polypharmacy following Trans-Catheter Aortic Valve Replacement.

BACKGROUND: Polypharmacy in elderly patients with various comorbidities is associated with mortality and morbidity. However, the prognostic impact of polypharmacy in patients with severe aortic stenosis receiving trans-catheter aortic valve replacement remains unknown. METHODS: Patients with severe aortic stenosis who received trans-catheter aortic valve replacement between 2015 and 2022 and were followed up at our institute following index discharge were included in this retrospective study. The impact of polypharmacy, which was defined as medication numbers ≥10 at index discharge, upon 2-year all-cause death was investigated. RESULTS: A total of 345 patients (median age 85 [83, 89] years old, 99 (29%) men) were included. Median medication number was 9 (7, 10) at the index discharge and 88 (26%) were classified as receiving polypharmacy. Frailty index, including mini-mental state examination and CSHA score, were not significantly different between those with and without polypharmacy (p > 0.05 for both). Polypharmacy was associated with higher 2-year cumulative mortality with an adjusted hazard ratio of 21.4 (95% confidence interval, 6.06-74.8, p < 0.001). As a sub-analysis, the number of cardiovascular medications was not associated with 2-year mortality (hazard ratio 1.12, 95% confidence interval 0.86-1.48, p = 0.46), whereas a higher number of non-cardiovascular medications was associated with an incremental increase in 2-year mortality with a hazard ratio of 1.39 (95% confidence interval, 1.15-1.63, p < 0.001). CONCLUSIONS: In elderly patients with severe aortic stenosis, polypharmacy was associated with worse short-term survival following trans-catheter aortic valve replacement. Prognostic implication of aggressive intervention to decrease the amount of medication among those receiving TAVR requires further prospective studies.

The Accuracy of Initial U.S. Heart Transplant Candidate Rankings.

BACKGROUND: The U.S. heart allocation system ranks candidates with only 6 treatment-based categorical "statuses" and ignores many objective patient characteristics. OBJECTIVES: This study sought to determine the effectiveness of the standard 6-status ranking system and several novel prediction models in identifying the most urgent heart transplant candidates. METHODS: The primary outcome was death before receipt of a heart transplant. The accuracy of the 6-status system was evaluated using Harrell's C-index and log-rank tests of Kaplan-Meier estimated survival by status for candidates listed postpolicy (November 2018 to March 2020) in the Scientific Registry of Transplant Recipients data set. The authors then developed Cox proportional hazards models and random survival forest models using prepolicy data (2010-2017). The predictor variables included age, diagnosis, laboratory measurements, hemodynamics, and supportive treatment at the time of listing. The performance of these models was compared with the candidate's 6-status ranking in the postpolicy data. RESULTS: Since policy implementation, the 6-status ranking at listing has had moderate ability to rank-order candidates (C-index: 0.67). Statuses 4 and 6 had no significant difference in survival (P = 0.80), and status 5 had lower survival than status 4 (P < 0.001). Novel multivariable prediction models derived with prepolicy data ranked candidates correctly more often than the 6-status rankings (Cox proportional hazards model C-index: 0.76; random survival forest model C-index: 0.74). Objective physiologic measurements, such as glomerular filtration rate, had high variable importance. CONCLUSIONS: The treatment-based 6-status heart allocation system has only moderate ability to rank-order candidates by medical urgency. Predictive models that incorporate physiologic measurements can more effectively rank-order heart transplant candidates by urgency.

Association between Remote Dielectric Sensing and Estimated Plasma Volume to Assess Body Fluid Distribution.

Background: Pulmonary congestion is quantified by a remote dielectric sensing (ReDSTM) system, while systemic congestion is estimated by calculated plasma volume. The type of clinical patient profile as defined by the ReDS system and calculated plasma volume remains uncertain. Methods: Hospitalized patients with or without heart failure were included in this prospective study. On admission, ReDS values were measured and plasma volume status (PVS) was estimated using their body weight at the same time. Cutoffs of ReDS value and PVS were defined at 34% and −2.7%, respectively. The association between the two parameters was assessed. Results: A total of 482 patients (median 76 years, 288 men) were included. The median ReDS value was 28% (25%, 32%) and median PVS was −16.4% (−26.3%, −5.9%). Of the patients, 64 had high ReDS value (and low PVS) and 80 had high PVS (and low ReDS value). The high ReDS group had a higher prevalence of clinical heart failure with a more elevated echocardiographic E/e' ratio, whereas the high PVS group had a higher prevalence of chronic kidney disease (p < 0.05 for all). Four out of a total of six patients with high ReDS value and high PVS had both heart failure and chronic kidney disease profiles. Conclusion: The combination of ReDS value and PVS was able to clinically stratify the types of body fluid distribution and patient profiles. Utilizing these tools may assist the clinician in constructing a therapeutic strategy for the at-risk hospitalized patient.

Prognostic Implication of Small Dense LDL-Cholesterol Levels following Acute Coronary Syndrome.

Background and Objectives: Small dense LDL cholesterol is a strong risk factor for atherosclerosis. However, few studies have investigated the impacts of this specific lipid profile on the incident risk of adverse cardiovascular events in patients with acute coronary syndrome. Materials and Methods: Patients with acute coronary syndrome, who underwent revascularization, were included and followed for 2 years. The levels of small dense LDL cholesterol were measured at index discharge (day 0) in the setting of newly administered therapies for secondary prevention, including aspirin and statins, during the index hospitalization. The prognostic impact of small dense LDL-cholesterol levels on the risk of a primary composite endpoint, including cardiac death, non-fatal myocardial infarction, unstable angina pectoris, stroke, and heart failure, was investigated. Results: In total, 46 patients (median 75 (59, 83) years old, 63% men) were included. Median small dense LDL cholesterol was 19.4 (13.5, 23.8) mg/dL at index discharge. All patients initiated statin treatment before the index discharge, with a median LDL-cholesterol level of 77 (64, 109) mg/dL. Small dense LDL-cholesterol level was independently associated with an incremental risk for the primary endpoint (p < 0.05 by adjusting for several potential risk factors, including LDL cholesterol) with a cutoff of 32.6 mg/dL. Conclusions: Small dense LDL-cholesterol level was a significant risk factor for cardiovascular events following presentations of acute coronary syndrome.

Changes in lung fluid levels with variations in the respiratory cycle.

The association between respirophasic variation and lung fluid levels is unknown. Remote dielectric sensing (ReDS™) is a novel non-invasive technology to quantify lung fluid levels. We investigated the change in ReDS values over the course of the respiratory cycle. Patients with clinically stable chronic heart failure at outpatient clinics were prospectively included. ReDS values were measured at three respiratory statuses and compared: (1) at rest with normal breathing, (2) at inspiration, and (3) at expiration. A total of 11 patients were included. Median age was 73 (58, 78) years and 9 were men. ReDS value was 28% (25%, 32%) at rest and decreased significantly with inspiration down to 26% (24%, 30%) (p = 0.004). ReDS value were significantly higher on expiration as 30% (27%, 34%) as compared with rest (p = 0.003). Lung fluid levels in chronic heart failure patients can vary with changes in the respiratory cycle-attention should be paid to what point in the respiratory cycle measurements are taken when interpreting results in each modality, such as chest X-ray (measured at inspiratory status) and right heart catheterization (measured at expiratory status). ReDS system might be a physiologically ideal modality to assess lung fluid amount under natural breathing.

Clinical implications of remote dielectric sensing system to estimate lung fluid levels.

The reduction of pulmonary congestion is an essential clinical target in the management of chronic heart failure. This proves to be challenging given the lack of a gold standard method to quantify the degree of pulmonary congestion both quickly and non-invasively. Remote dielectric sensing (ReDS) is a non-invasive electromagnetic energy-based technology to quantify lung fluid levels as a percentage within minutes. This technique, due to its high negative predictive value, may be a useful tool particularly to rule out primarily cardiac causes of dyspnea in ambulatory patients when the values are normal. Further studies are warranted to establish ReDS-guided management of congestive heart failure patients.

Risk Factors for Rapid Recurrence of Hyperkalemia following Cessation of Sodium Zirconium Cyclosilicate.

Background: Sodium zircon`ium cyclosilicate (SZC), a recently introduced potassium binder, is indicated to treat hyperkalemia. SZC is often terminated soon after the normalization of hyperkalemia in real-world clinical practice. We aimed to investigate the risk factors for the rapid recurrence of hyperkalemia following cessation of SZC. Methods: Patients in whom SZC was discontinued following an improvement in hyperkalemia were followed up for three months. The baseline characteristics that were associated with the rapid recurrence of hyperkalemia (>5.0 mEq/L of serum potassium levels within 3 months) were investigated. Results: A total of 44 patients terminated SZC following the normalization of hyperkalemia. The median age was 81 (69, 87) years old, and 59% were men. When evaluating baseline characteristics, a higher dose of renin-angiotensin system inhibitors was significantly associated with the recurrence of hyperkalemia (adjusted hazard ratio of 1.26, 95% confidence interval 1.02−1.69, p = 0.045) at a designated cutoff of 2.5 mg/day of equivalent enalapril dose. Conclusions: SZC should be considered for ongoing continuation after normalization of hyperkalemia, particularly in patients receiving a relatively higher dose of renin-angiotensin system inhibitors.