Letter to the editor to update the article "Remote monitoring for heart failure using implantable devices: a systematic review, meta-analysis, and meta-regression of randomized controlled trials".

Our recently published systematic review and meta-analysis of heart failure (HF) remote monitoring using implantable devices (Hajduczok et al. in HF Reviews 1-20, 1) has been updated to reflected new data from the GUIDE-HF trial (Lindenfeld et al. in Lancet 398(10304):991-1001, 2). Data from randomized controlled trials (RCTs) was assessed to determine the effectiveness of implantable remote monitoring on the improvement of outcomes in HF patients. With the inclusion of the data from 1000 patients followed for 12 months in GUIDE-HF, our conclusions remain unchanged: Compared to standard of care, remote monitoring using implantable devices did not reduce mortality, CV, or HF hospitalizations. However, right ventricular/pulmonary pressure monitoring may reduce HF hospitalizations.

Remote monitoring for heart failure using implantable devices: a systematic review, meta-analysis, and meta-regression of randomized controlled trials.

In heart failure (HF) patients, remote monitoring using implantable devices may be used to predict and reduce HF exacerbations and mortality. Data from randomized controlled trials (RCTs) was assessed to determine the effectiveness of implantable remote monitoring on the improvement of outcomes in HF patients. A systematic review and meta-analysis of RCTs testing remote monitoring versus standard of care for management of HF patients was performed. Primary endpoints were all-cause mortality and a composite of cardiovascular (CV) and HF hospitalizations. Rate ratios (RRs) and 95% confidence intervals (CI) were calculated. A secondary analysis tested for heterogeneity of treatment effect (HTE) comparing right ventricular/pulmonary pressure monitoring versus impedance-based monitoring on hospitalization. A regression analysis was performed using the mean follow-up time as the moderator on each primary endpoint. Eleven RCTs (n = 6196) were identified with a mean follow-up of 21.9 months. The mean age and reported ejection fraction were 64.1 years and 27.7%, respectively. Remote monitoring did not reduce mortality (RR 0.89 [95% CI 0.77, 1.03]) or the composite of CV and HF hospitalizations (RR 0.98 [0.81, 1.19]). Subgroup analysis found significant HTE for hospitalizations between those studies that used right ventricular/pulmonary pressure monitoring versus impedance-based monitoring (I2 = 87.1%, chi2 = 7.75, p = 0.005). Regression analysis found no relationship between the log rate ratio of remote monitoring's effect on mortality, CV hospitalization or HF hospitalization, and mean follow-up time. Compared to standard of care, remote monitoring using implantable devices did not reduce mortality, CV, or HF hospitalizations. However, right ventricular/pulmonary pressure monitoring may reduce HF hospitalizations, which will need to be explored in future studies.

Remote Physiologic Monitoring for Heart Failure.

PURPOSE OF REVIEW: This review will describe the process of remote monitoring in the treatment of heart failure and the clinical trials for different modalities of data collection. RECENT FINDINGS: Small studies monitoring weights, sometimes with other parameters, suggested a significant outcome benefit in meta-analysis. However, this has not been seen in larger studies. Clinical trials of remote monitoring using hemodynamic parameters seems to lead to improved outcomes, with more studies underway. Recently, multi-parameter methods with wearable or implantable devices have shown promise in detecting heart failure. The impact on clinical outcomes is being assessed. When using parameters such as daily weights, remote monitoring for heart failure has not been demonstrated to be broadly beneficial, while remote monitoring of hemodynamic parameters to guide heart failure therapy has met with initial success. Methods of combining multiple physiologic measurements appear to accurately detect worsening heart failure, and clinical trials are underway to assess the impact.

Adhesion G protein-coupled receptors are activated by exposure of a cryptic tethered agonist.

The large class of adhesion G protein-coupled receptors (aGPCRs) bind extracellular matrix or neighboring cell-surface ligands to regulate organ and tissue development through an unknown activation mechanism. We examined aGPCR activation using two prototypical aGPCRs, GPR56 and GPR110. Active dissociation of the noncovalently bound GPR56 or GPR110 extracellular domains (ECDs) from the respective seven-transmembrane (7TM) domains relieved an inhibitory influence and permitted both receptors to activate defined G protein subtypes. After ECD displacement, the newly revealed short N-terminal stalk regions of the 7TM domains were found to be essential for G protein activation. Synthetic peptides comprising these stalks potently activated GPR56 or GPR110 in vitro or in cells, demonstrating that the stalks comprise a tethered agonist that was encrypted within the ECD. Establishment of an aGPCR activation mechanism provides a rational platform for the development of aGPCR synthetic modulators that could find clinical utility toward aGPCR-directed disease.

Heart Rate Variability Applications in Strength and Conditioning: A Narrative Review.

Heart rate variability (HRV) is defined as the fluctuation of time intervals between adjacent heartbeats and is commonly used as a surrogate measure of autonomic function. HRV has become an increasingly measured variable by wearable technology for use in fitness and sport applications. However, with its increased use, a gap has arisen between the research and the application of this technology in strength and conditioning. The goal of this narrative literature review is to discuss current evidence and propose preliminary guidelines regarding the application of HRV in strength and conditioning. A literature review was conducted searching for HRV and strength and conditioning, aiming to focus on studies with time-domain measurements. Studies suggest that HRV is a helpful metric to assess training status, adaptability, and recovery after a training program. Although reduced HRV may be a sign of overreaching and/or overtraining syndrome, it may not be a sensitive marker in aerobic-trained athletes and therefore has different utilities for different athletic populations. There is likely utility to HRV-guided programming compared to predefined programming in several types of training. Evidence-based preliminary guidelines for the application of HRV in strength and conditioning are discussed. This is an evolving area of research, and more data are needed to evaluate the best practices for applying HRV in strength and conditioning.

Relationship Between Obesity and Youth Athletes' Physical Activity and Exercise-Related Cardiac Symptoms.

Background: While studies have identified the negative cardiovascular effects of obesity, the effects of obesity on youth athletes are less studied. This study investigates the associations between obesity in youth athletes and exercise activity and exertional cardiac symptoms. Methods: The HeartBytes National Youth Database produced by Simon's Heart, a nonprofit that organizes adolescents' sports pre-participation examinations (PPEs), was used. This database contains demographic data, exercise-related symptoms, and electrocardiogram data obtained during PPEs. BMI was converted to percentiles, with obesity defined as BMI ≥95th percentile. Outcomes were evaluated using a chi-squared test with odds ratios (ORs) and 95% confidence intervals (CIs). Results: Of 7363 patients, there were 634 individuals with obesity. Youth athletes within normal weight ranges (5th-85th percentile) had higher exercise rates than those with underweight, overweight, or obesity (p < 0.001 for each). Athletes with obesity had higher odds of exertional symptoms overall (OR: 1.63 [CI: 1.36-1.96]; p < 0.001). However, for athletes who exercised >10 hours a week, there was no association between obesity and exertional symptoms. Athletes with obesity had higher odds of elevated blood pressure (OR: 5.35 [CI: 2.00-14.30]; p < 0.001) and hypercholesterolemia (OR: 3.84 [CI: 2.51-5.86]; p < 0.001). Conclusions: In this dataset, obesity in youth athletes is associated with decreased physical activity and increased exertional symptoms in general. Obesity is not associated with exertional symptoms in athletes who participated in higher weekly physical activity. Further studies are needed to elucidate the cause-effect relationship of these findings.

A multicenter evaluation of the HeartMate 3 risk score.

BACKGROUND: The Heartmate 3 (HM3) risk score (HM3RS) was derived and validated internally from within the Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy with HeartMate 3 (MOMENTUM 3) trial population and provides 1- and 2-year mortality risk prediction for patients in those before HM3 left ventricular assist device (LVAD) implantation. We aimed to evaluate the HM3RS in nontrial unselected patients, including those not meeting inclusion criteria for MOMENTUM 3 trial enrollment. METHODS: Patients who underwent HM3 LVAD implant at 1 of 7 US centers between 2017 and 2021, with at least 1-year follow-up, were included in this analysis. Patients were retrospectively assessed for their eligibility for the MOMENTUM 3 trial based on study inclusion and exclusion criteria. HM3RS risk discrimination was evaluated using time-dependent receiver operating characteristic curve analysis for 1-year mortality for all patients and further stratified by MOMENTUM 3 trial eligibility. Kaplan-Meier curves were constructed using the HM3RS-based risk categories. RESULTS: Of 521 patients included in the analysis, 266 (51.1%) would have met enrollment criteria for MOMENTUM 3. The 1- and 2-year survival for the total cohort was 85% and 81%, respectively. There was no statistically significant difference in survival between those who met and did not meet enrollment criteria at 1 (87% vs 83%; p = 0.21) and 2 years postimplant (80% vs 78%; p = 0.39). For the total cohort, HM3RS predicted 1-year survival with an area under the curve (AUC) of 0.63 (95% confidence interval [CI]: 0.57-0.69, p < 0.001). HM3RS performed better in the subset of patients meeting enrollment criteria: AUC 0.69 (95% CI:0.61-0.77, p < 0.001) compared to the subset that did not: AUC 0.58 (95% CI: 0.49-0.66, p = 0.078). CONCLUSIONS: In this real-world evidence, multicenter cohort, 1- and 2-year survival after commercial HM3 LVAD implant was excellent, regardless of trial eligibility. The HM3RS provided adequate risk discrimination in "trial-like" patients, but predictive value was reduced in patients who did not meet trial criteria.

Trends and Predictors of Poor Outcomes in Patients With Right Heart Failure: Insights From the National Readmission Database.

Right heart failure (RHF) is a complex clinical syndrome that confers high risk of morbidity and mortality. We sought to study RHF using large national database. The study is a retrospective analysis of the National Readmission Database (NRD) of years 2017-2019. Admissions with a primary diagnosis of RHF were included. Study outcomes were temporal trends of RHF diagnosis and predictors of in-hospital mortality and 30-day readmission. Subgroup analysis according to co-presence of reduced or preserved left ventricular ejection fraction (LVEF). Multivariate logistic regression was utilized to detect predictors of poor outcome and difference between subgroups. A total of 127,503 admissions were identified from the database of which 4,717 primary RHF admissions were included in our cohort. There was a trend of increasing RHF diagnosis from 2017 4th Quarter to 2019 4th Quarter. Age, liver disease and reduced LVEF were amongst predictors of in-hospital mortality while iron deficiency anemia and a Charlson Comorbidity Score ≥ 3 were predictors of 30-day readmission. The study of real-world data contributes to a better understanding of RHF outcomes. Further studies are needed to investigate the association between RHF and different types of heart failure and its implications on clinical practice.

National Trends of Structural Heart Disease Interventions from 2016 to 2020 in the United States and the Associated Impact of COVID-19 Pandemic.

The Coronavirus Disease-2019 (COVID-19) pandemic placed an enormous strain on the healthcare system. Data on the impact of COVID-19 on the utilization and outcomes of structural heart disease interventions in the United States are scarce. The National Inpatient Sample from 2016 to 2020 was queried to identify adult admissions for transcatheter aortic valve replacement (TAVR), left atrial appendage occlusion (LAAO), and transcatheter end-to-end repair (TEER). The primary outcome was temporal trends of procedure utilization rate per 100,000 admissions over quarters from 2016 to 2020. The secondary outcomes were adjusted rates of in-hospital mortality, major complications, and length of stay (LOS). Among 434,630 weighted admissions (TAVR: 305,550; LAAO: 89,300; TEER: 40,160), 95,010 admissions (22%) were during the COVID-19 era. There was a decline during the second quarter of 2020 followed by an increase to the pre pandemic levels (TAVR: 220 to 253, LAAO: 57 to 109, and TEER: 31 to 36 per 100,000 admissions, Ptrend<0.001). There were no differences in the mortality or major complication rates. Median LOS has decreased in TAVR (4 days-1 day) and in TEER (3 days-1 day) but remained stable in LAAO (1 day). This nationwide analysis showed that structural heart disease interventions decreased during the early waves of COVID-19 pandemic. There was a significant reduction in hospital LOS without differences in in-hospital mortality or complication rates during the pandemic. These data suggest that hospitals adapted to the unprecedent challenges during the pandemic to provide advanced cardiac care to patients.

Adverse outcomes of atrial fibrillation ablation in heart failure patients with and without cardiac amyloidosis: a Nationwide Readmissions Database analysis (2015-2019).

Aims: Atrial fibrillation (AF) in patients with cardiac amyloidosis (CA) has been linked with a worse prognosis. The current study aimed to determine the outcomes of AF catheter ablation in patients with CA. Methods and results: The Nationwide Readmissions Database (2015-2019) was used to identify patients with AF and concomitant heart failure. Among these, patients who underwent catheter ablation were classified into two groups, patients with and without CA. The adjusted odds ratio (aOR) of index admission and 30-day readmission outcomes was calculated using a propensity score matching (PSM) analysis. A total of 148 134 patients with AF undergoing catheter ablation were identified on crude analysis. Using PSM analysis, 616 patients (293 CA-AF, 323 non-CA-AF) were selected based on a balanced distribution of baseline comorbidities. At index admission, AF ablation in patients with CA was associated with significantly higher adjusted odds of net adverse clinical events (NACE) [adjusted odds ratio (aOR) 4.21, 95% CI 1.7-5.20], in-hospital mortality (aOR 9.03, 95% CI 1.12-72.70), and pericardial effusion (aOR 3.30, 95% CI 1.57-6.93) compared with non-CA-AF. There was no significant difference in the odds of stroke, cardiac tamponade, and major bleeding between the two groups. At 30-day readmission, the incidence of NACE and mortality remained high in patients undergoing AF ablation in CA. Conclusion: Compared with non-CA, AF ablation in CA patients is associated with relatively higher in-hospital all-cause mortality and net adverse events both at index admission and up to 30-day follow-up.

Temporal Trends and Sex Differences in Patients With Cardiac Amyloidosis and Heart Failure With Preserved Ejection Fraction: Retrospective Analysis of 22,015 Admissions From the National Inpatient Sample.

Cardiac amyloidosis (CA) often goes unrecognized as a cause of heart failure with preserved ejection fraction (HFpEF). There is paucity of contemporary data evaluating the trends of CA diagnosis and associated sex differences. Adult heart failure hospitalizations were identified from the National Inpatient Sample between 2016 and 2019. Hospitalizations with heart failure other than HFpEF were excluded. Hospitalizations with a diagnosis of CA were identified. A Linear regression was utilized to calculate the trend of CA diagnosis over time. A multivariate logistic regressions analysis was performed to analyze sex differences. There was an increasing trend of CA from 1.2 to 2.3 per 1000 HFpEF admission in the first quarter of 2016 to the fourth quarter of 2019 (Ptrend <0.001). In females, as compared to males, there was an increased risk of AIS (6% vs 3%, aOR: 1.68[1.24-2.27], P=0.001) and major bleeding events (10% vs 5%, aOR: 1.97[1.53-2.52], P<0.001). No difference was observed in the in-hospital mortality outcome (8% vs 7%, aOR: 1.2[0.95-1.53], P=0.12) between both groups. Our real-world contemporary analysis showed an increase in CA diagnosis from 2016 to 2019. Despite similar in-hospital mortality, females were associated with higher AIS and major bleeding events rates. Further prospective studies are needed to validate these results.

Late Right Heart Failure After Left Ventricular Assist Device Implantation: Contemporary Insights and Future Perspectives.

Late right heart failure (RHF) is increasingly recognized in patients with long-term left ventricular assist device (LVAD) support and is associated with decreased survival and increased incidence of adverse events such as gastrointestinal bleeding and stroke. Progression of right ventricular (RV) dysfunction to clinical syndrome of late RHF in patients supported with LVAD is dependent on the severity of pre-existing RV dysfunction, persistent or worsening left- or right-sided valvular heart disease, pulmonary hypertension, inadequate or excessive left ventricular unloading, and/or progression of the underlying cardiac disease. RHF likely represents a continuum of risk with early presentation and progression to late RHF. However, de novo RHF develops in a subset of patients leading to increased diuretic requirement, arrhythmias, renal and hepatic dysfunction, and heart failure hospitalizations. The distinction between isolated late RHF and RHF due to left-sided contributions is lacking in registry studies and should be the focus of future registry data collection. Potential management strategies include optimization of RV preload and afterload, neurohormonal blockade, LVAD speed optimization, and treatment of concomitant valvular disease. In this review, the authors discuss definition, pathophysiology, prevention, and management of late RHF.

Risk Factors for Sudden Death in Athletes, Is There a Role for Screening?

Purpose of Review: Sudden cardiac death (SCD) in a young athlete is an infrequent yet devastating event often associated with substantial media attention. Screening athletes for conditions associated with SCD is a controversial topic with debate surrounding virtually each component including the ideal subject, method, and performer/interpreter of such screens. In fact, major medical societies such as the American College of Cardiology/American Heart Association and the European Society of Cardiology have discrepant recommendations on the matter, and major sporting associations have enacted a wide range of screening policies, highlighting the confusion on this subject. This review seeks to summarize the literature in this area to address the complex and disputed subject of screening young athletes for SCD. Recent Findings: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can cause myocarditis, which is one acquired cardiac disease associated with SCD. The coronavirus 2019 (COVID-19) pandemic has therefore resulted in an increased incidence of an otherwise less common condition, providing an expanded dataset for further study of this condition. Recent findings indicate that cardiac complications of athletes with myocardial involvement of SARS-CoV-2 infection are rare. Other contemporary work in SCD screening has been focused on the implementation of various screening protocols and measuring their effectiveness. Summary: No universal consensus exists for athlete screening for conditions associated with SCD with varying guidelines and protocols across cardiology and sport-specific organizations. No screening program will prevent all SCD; however, small programs managed by physicians familiar with the examination of an athlete that carefully personalize screening to the individual may maximize detection of dangerous cardiac conditions while minimizing false positives.

Recurrent giant cell myocarditis after heart transplant: a case report.

Background: Giant cell myocarditis (GCM) is a rare but well-known cause of fulminant myocarditis. Despite optimal medical therapy, many patients progress to orthotopic heart transplant (OHT). We present a case of recurrent GCM following OHT, including complex considerations in patient management and infectious sequelae. Case summary: A 33-year-old previously healthy male presented with 2 months of worsening shortness of breath. Transthoracic echocardiogram (TTE) demonstrated a left ventricular ejection fraction of 30-35%. After ruling out an ischaemic aetiology, he was discharged on guideline-directed medical therapy and later presented with productive cough, worsening dyspnoea on exertion, and diarrhoea. He was found to have elevated troponins and N-terminal pro-brain natriuretic peptide, lactic acidosis, progression of severe bi-ventricular dysfunction on TTE and right heart catheterization, and low cardiac index (1.0 L/min/m2) requiring inotropes. He then required left ventricular assist device as a bridge to OHT. Pathology of the apical core diagnosed GCM as the cause of his fulminant heart failure. He eventually underwent heart transplantation, which was complicated by recurrent GCM. Treatment required intensification of his immunosuppressive regimen, which led to multiple infectious sequelae including norovirus, Shiga-like toxin producing Escherichia coli, and disseminated nocardia of the lung and brain. As of the most recent follow-up, the patient is currently clinically stable. Discussion: Although recurrent GCM after OHT has been reported in the literature, the prognosis is not well understood and there are no clear guidelines regarding management. This case summarizes clinical considerations, treatment strategies, and adverse effects of recurrent GCM treatment.

Catheter-Based Management of Heart Failure: Pathophysiology and Contemporary Data.

Device therapy for severe heart failure (HF) has shown efficacy both in acute and chronic settings. Recent percutaneous device innovations have pioneered a field known as interventional HF, providing clinicians with a variety of options for acute decompensated HF that are centered on nonsurgical mechanical circulatory support. Other structural-based therapies are aimed at the pathophysiology of chronic HF and target the underlying etiologies such as functional mitral regurgitation, ischemic cardiomyopathy, and increased neurohumoral activity. Remote hemodynamic monitoring devices have also been shown to be efficacious for the ambulatory management of HF. We review the current data on devices and investigational therapies for HF management whereby pharmacotherapy falls short.

Physiologic Response to the Pfizer-BioNTech COVID-19 Vaccine Measured Using Wearable Devices: Prospective Observational Study.

BACKGROUND: The Pfizer-BioNTech COVID-19 vaccine uses a novel messenger RNA technology to elicit a protective immune response. Short-term physiologic responses to the vaccine have not been studied using wearable devices. OBJECTIVE: We aim to characterize physiologic changes in response to COVID-19 vaccination in a small cohort of participants using a wearable device (WHOOP Strap 3.0). This is a proof of concept for using consumer-grade wearable devices to monitor response to COVID-19 vaccines. METHODS: In this prospective observational study, physiologic data from 19 internal medicine residents at a single institution that received both doses of the Pfizer-BioNTech COVID-19 vaccine was collected using the WHOOP Strap 3.0. The primary outcomes were percent change from baseline in heart rate variability (HRV), resting heart rate (RHR), and respiratory rate (RR). Secondary outcomes were percent change from baseline in total, rapid eye movement, and deep sleep. Exploratory outcomes included local and systemic reactogenicity following each dose and prophylactic analgesic use. RESULTS: In 19 individuals (mean age 28.8, SD 2.2 years; n=10, 53% female), HRV was decreased on day 1 following administration of the first vaccine dose (mean -13.44%, SD 13.62%) and second vaccine dose (mean -9.25%, SD 22.6%). RHR and RR showed no change from baseline after either vaccine dose. Sleep duration was increased up to 4 days post vaccination, after an initial decrease on day 1. Increased sleep duration prior to vaccination was associated with a greater change in HRV. Local and systemic reactogenicity was more severe after dose two. CONCLUSIONS: This is the first observational study of the physiologic response to any of the novel COVID-19 vaccines as measured using wearable devices. Using this relatively small healthy cohort, we provide evidence that HRV decreases in response to both vaccine doses, with no significant changes in RHR or RR. Sleep duration initially decreased following each dose with a subsequent increase thereafter. Future studies with a larger sample size and comparison to other inflammatory and immune biomarkers such as antibody response will be needed to determine the true utility of this type of continuous wearable monitoring in regards to vaccine responses. Our data raises the possibility that increased sleep prior to vaccination may impact physiologic responses and may be a modifiable way to increase vaccine response. These results may inform future studies using wearables for monitoring vaccine responses. TRIAL REGISTRATION: ClinicalTrials.gov NCT04304703; https://www.clinicaltrials.gov/ct2/show/NCT04304703.