Translating Pressure Into Practice: Operational Characteristics of Ambulatory Hemodynamic Monitoring Program in the United States.

BACKGROUND: Ambulatory hemodynamic monitoring (AHM) using an implantable pulmonary artery pressure sensor (CardioMEMS) is effective in improving outcomes for patients with heart failure. The operations of AHM programs are crucial to clinical efficacy of AHM yet have not been described. METHODS AND RESULTS: An anonymous, voluntary, web-based survey was developed and emailed to clinicians at AHM centers in the United States. Survey questions were related to program volume, staffing, monitoring practices, and patient selection criteria. Fifty-four respondents (40%) completed the survey. Respondents were 44% (n = 24) advanced HF cardiologists and 30% (n = 16) advanced nurse practitioners. Most respondents practice at a center that implants left ventricular assist devices (70%) or performs heart transplantation (54%). Advanced practice providers provide day-to-day monitoring and management in most programs (78%), and use of protocol-driven care is limited (28%). Perceived patient nonadherence and inadequate insurance coverage are cited as the primary barriers to AHM. CONCLUSIONS: Despite broad US Food and Drug Administration approval for patients with symptoms and at increased risk for worsening heart failure, the adoption of pulmonary artery pressure monitoring is concentrated at advanced heart failure centers, and modest numbers of patients are implanted at most centers. Understanding and addressing the barriers to referral of eligible patients and to broader adoption in community heart failure programs is needed to maximize the clinical benefits of AHM.

Autosomal-dominant biventricular arrhythmogenic cardiomyopathy in a large family with a novel in-frame DSP nonsense mutation.

A novel autosomal-dominant in-frame deletion resulting in a nonsense mutation in the desmoplakin (DSP) gene was identified in association with biventricular arrhythmogenic cardiomyopathy across three generations of a large Caucasian family. Mutations that disrupt the function and structure of desmosomal proteins, including desmoplakin, have been extensively linked to familial arrhythmogenic right ventricular cardiomyopathy (ARVC). Analysis of data from 51 individuals demonstrated the previously undescribed variant p.Cys81Stop (c.243_251delCTTGATGCG) in DSP segregates with a pathogenic phenotype exhibiting variable penetrance and expressivity. The mutation's pathogenicity was first established due to two sudden cardiac deaths (SCDs), each with a biventricular cardiomyopathy identified on autopsy. Of the individuals who underwent genetic screening, 27 of 51 were heterozygous for the DSP mutation (29 total with two obligate carriers). Six of these were subsequently diagnosed with arrhythmogenic cardiomyopathy. An additional nine family members have a conduction disorder and/or myocardial structural changes characteristic of an evolving condition. Previous reports from both human patients and mouse studies proposed DSP mutations with a premature stop codon impart mild to no clinical symptoms. Loss of expression from the abnormal allele via the nonsense-mediated mRNA decay pathway has been implicated to explain these findings. We identified an autosomal-dominant DSP nonsense mutation in a large family that led to SCD and phenotypic expression of arrhythmogenic cardiomyopathy involving both ventricles. This evidence demonstrates the pathogenic significance of this type of desmosomal mutation and provides insight into potential clinical manifestations.

Outcomes and predictors of recovery in acute-onset cardiomyopathy: A single-center experience of patients undergoing endomyocardial biopsy for new heart failure.

BACKGROUND: About one-third of patients with unexplained acute-onset heart failure (HF) recover left ventricular (LV) function; however, characterization of these patients in the setting of contemporary HF therapies is limited. We aim to describe baseline characteristics and predictors of recovery in patients with acute-onset cardiomyopathy. METHODS: We previously described 851 patients with unexplained HF undergoing endomyocardial biopsy. In this study, 235 patients with acute-onset HF were further retrospectively examined. RESULTS: Follow-up LV ejection fraction (LVEF) was available for 138 patients. At 1 year, 48 of 138 (33%) had LVEF recovery (follow-up LVEF ≥50%), and 90 of 138 (65%) had incomplete or lack of recovery. Higher cardiac index (P=.019), smaller LV diastolic diameter (P=.002), and lack of an intraventricular conduction delay (IVCD) (P=.002) were associated with LVEF recovery. IVCD (P=.001) and myocarditis (P=.016) were independent predictors of the composite end point of death, LV assist device placement, and/or transplant at 1 year. Those with an IVCD had a significantly lower 1-year survival than those without (P=.007). CONCLUSIONS: Patients with a smaller LV end-diastolic diameter, higher cardiac index, and lack of IVCD at presentation for acute-onset HF were more likely to have LVEF recovery. IVCD was a poor prognostic marker in all patients presenting with acute cardiomyopathy.

Access to durable LVAD therapy for patients with limited social support: Surveying program-specific approaches.

Racial and ethnic disparities in provision of left ventricular assist device (LVAD) therapy have been identified. These disparities may be at least partially related to socioeconomic factors, including social support networks and financial constraints. This study aimed to identify specific barriers, and variations in institutional approaches, to the provision of equitable care to underserved populations. A survey was administered to 237 LVAD program personnel, including physicians, LVAD coordinators, and social workers, at more than 100 LVAD centers across 7 countries. Three fourths of respondents reported that their program required a support person to live with the LVAD patient for some period of time following implantation. In addition, 31% of respondents reported that patients with the inability to pay for medications are turned down at their program. The most significant barriers to successful LVAD implantation were lack of social support, lack of insurance, and lack of timely referral. The most consistently identified supports needed from the hospital system for success in underserved populations were the provision of a solution for patient transportation to and from hospital visits and the provision of financial support. This survey highlights the challenges facing LVAD programs that care for underserved patient populations and sets the stage for specific interventions aimed at reducing disparities in access to care.

Clinical Trial Inclusion and Impact on Early Adoption of Medical Innovation in Diverse Populations.

BACKGROUND: Inadequate inclusion in clinical trial enrollment may contribute to health inequities by evaluating interventions in cohorts that do not fully represent target populations. OBJECTIVES: The aim of this study was to determine if characteristics of patients with heart failure (HF) enrolled in a pivotal trial are associated with who receives an intervention after approval. METHODS: Demographics from 2,017,107 Medicare patients hospitalized for HF were compared with those of the first 10,631 Medicare beneficiaries who received implantable pulmonary artery pressure sensors. Characteristics of the population studied in the pivotal CHAMPION (CardioMEMS Heart Sensor Allows Monitoring of Pressure to Improve Outcomes in NYHA Class III Heart Failure Patients) clinical trial (n = 550) were compared with those of both groups. All demographic data were analyzed nationally and in 4 U.S. regions. RESULTS: The Medicare HF cohort included 80.9% White, 13.3% African American, 1.9% Hispanic, 1.3% Asian, and 51.5% female patients. Medicare patients <65 years of age were more likely to be African American (33%) and male (58%), whereas older patients were mostly White (84%) and female (53%). Forty-one percent of U.S. HF hospitalizations occurred in the South; demographic characteristics varied significantly across all U.S. regions. The CHAMPION trial adequately represented African Americans (23% overall, 35% <65 years of age), Hispanic Americans (2%), and Asian Americans (1%) but underrepresented women (27%). The trial's population characteristics were similar to those of the first patients who received pulmonary artery sensors (82% White, 13% African American, 1% Asian, 1% Hispanic, and 29% female). CONCLUSIONS: Demographics of Centers for Medicare and Medicaid Services beneficiaries hospitalized with HF vary regionally and by age, which should be considered when defining "adequate" representation in clinical studies. Enrollment diversity in clinical trials may affect who receives early application of recently approved innovations.

Impact of exercise on pulmonary artery pressure in patients with heart failure using an ambulatory pulmonary artery pressure monitor.

Background: In this multicenter prospective study, we explored the relationship between pulmonary artery pressure (PAP) at rest and in response to a 6-min walk test (6MWT) in ambulatory patients with heart failure (HF) with an implantable PAP sensor (CardioMEMS, Abbott). Methods: Between 5/2019 and 2/2021, HF patients with a CardioMEMS sensor were recruited from seven sites. PAP was recorded in the supine and seated position at rest and in the seated position immediately post-exercise. Results: In our cohort of 66 patients, mean age was 70 ± 12 years, 67% male, left ventricular ejection fraction (LVEF) < 50% in 53%, mean 6MWT distance was 277 ± 95 meters. Resting seated PAPs were 31 ± 15 mmHg (systolic), 13 ± 8 mmHg (diastolic), and 20 ± 11 mmHg (mean). The pressures were lower in the seated rather than the supine position. After 6MWT, the pressures increased to PAP systolic 37 ± 19 mmHg (p < 0.0001), diastolic 15 ± 10 mmHg (p = 0.006), and mean 24 ± 13 mmHg (p < 0.0001). Patients with elevated PAP diastolic at rest (>15 mmHg) demonstrated a greater increase in post-exercise PAP. Conclusion: The measurement of PAP with CardioMEMS is feasible immediately post-exercise. Despite being well-managed, patients had severely limited functional capacity. We observed a significant increase in PAP with ambulation which was greater in patients with higher baseline pressures.

Multicenter registry and test bed for extended outpatient hemodynamic monitoring: the hemodynamic frontiers in heart failure (HF2) initiative.

Background: Hemodynamic Frontiers in Heart Failure (HF2) is a multicenter academic research consortium comprised of 14 US institutions with mature remote monitoring programs for ambulatory patients with heart failure (HF). The consortium developed a retrospective and prospective registry of patients implanted with a wireless pulmonary artery pressure (PAP) sensor. Goals/aims: HF2 registry collects demographic, clinical, laboratory, echocardiographic (ECHO), and hemodynamic data from patients with PAP sensors. The aims of HF2 are to advance understanding of HF and to accelerate development of novel diagnostic and therapeutic innovations. Methods: HF2 includes adult patients implanted with a PAP sensor as per FDA indications (New York Heart Association (NYHA) Class III HF functional class with a prior hospitalization, or patients with NYHA Class II or brain natriuretic peptide (BNP) elevation without hospitalization) at a HF2 member site between 1/1/19 to present. HF2 registry is maintained at University of Kansas Medical Center (KUMC). The registry was approved by the institutional review board (IRB) at all participating institutions with required data use agreements. Institutions report data into the electronic registry database using REDCap, housed at KUMC. Results: This initial data set includes 254 patients implanted from the start of 2019 until May 2023. At time of device implant, the cohort average age is 73 years old, 59.8% are male, 72% have NYHA Class III HF, 40% have left ventricular ejection fraction (LVEF) < 40%, 35% have LVEF > 50%, mean BNP is 560 pg/ml, mean N-Terminal pro-BNP (NTproBNP) is 5,490 pg/ml, mean creatinine is 1.65 mg/dl. Average baseline hemodynamics at device implant are right atrial pressure (RAP) of 11 mmHg, pulmonary artery systolic pressure (PASP) of 47 mmHg, pulmonary artery diastolic pressure (PADP) 21 mmHg, mean pulmonary artery pressure (mPAP) of 20 mmHg, pulmonary capillary wedge pressure (PCWP) of 19 mmHg, cardiac output (CO) of 5.3 L/min, and cardiac index (CI) of 2.5 L/min/m2. Conclusion: A real-world registry of patients implanted with a PAP sensor enables long-term evaluation of hemodynamic and clinic outcomes in highly-phenotyped ambulatory HF patients, and creates a unique opportunity to validate and test novel diagnostic and therapeutic approaches to HF.

Survivors of veno-arterial membrane oxygenation have good long-term quality of life.

Veno-arterial extracorporeal membrane oxygenation (VA ECMO) is used for the management of acute cardiogenic shock with improving short term survival. However, the long-term quality of life (QOL) of this patient population is not well characterized. We prospectively evaluated the QOL of adult patients who survived VA ECMO support for cardiogenic shock at our institution between October 2011 and January 2018 with the Minnesota Living with Heart Failure Questionnaire (MLWHFQ). We surveyed survivors at 3, 6, and 9 months after discharge, and annually for up to 5 years thereafter. A total of 64 patients were evaluated: mean age 54 ± 13 years, 73% male. There were 178 total surveys completed. MLWHFQ total scores significantly improved over time and this pattern was sustained (51.7 ± 25.3 at 3 months, vs 37.7 ± 23.6 at 6 months, vs 25.4 ± 21.3 at ⩾9 months (p < 0.01, p-trend < 0.01)). Most patients supported with VA ECMO for cardiogenic shock who survive to discharge demonstrate excellent quality of life, 6 months since index hospitalization, which is maintained over subsequent years.

Odor-evoked gene regulation and visualization in olfactory receptor neurons.

Odorant-evoked activity contributes to olfactory epithelium organization and axon targeting. We examined the consequences on gene expression of a genetic disruption of the channel responsible for olfactory transduction. Genes encoding calcium-binding EF-hand motifs, were among the most highly regulated transcripts consistent with the central role of Ca(2+) influx in neuronal depolarization. Several genes encoding integral membrane proteins are also highly regulated. One gene, Lrrc3b, was regulated more than 10-fold by odorant activity. Changes in expression occur within thirty minutes and are maintained for several hours. In genetic disruptions of Lrrc3b, a Lrrc3b-promoter-driven reporter adopts the activity-regulated expression of the endogenous gene. Individual olfactory glomeruli have a wide spectrum of activity levels that can be modulated by altering odor exposure. The Lrrc3b reporter mouse permits direct assessment of activity in identified glomeruli. In stable odorant environments, activity-regulated proteins provide a characteristic signature that is correlated with the olfactory receptor they express.

Sudden Unexpected Death Due to Myocarditis in Young People, Including Athletes.

Sudden deaths in young active people and athletes are distinctly uncommon and frequently related to highly visible cardiovascular conditions including hypertrophic cardiomyopathy and congenital coronary anomalies. Myocarditis is also a cause of sudden death in the young, but frequently under-recognized clinically, and therefore deserving of the present analysis. Two large registries were interrogated for cases of myocarditis, and clinical, demographic, and pathologic findings were assessed. Of 97 cases of myocarditis identified, ages were 19.3 ± 6.2 years, 76% male, and 58 were physically active at or near the time of death. Almost one-half of the 97 cases (47%) had a viral prodrome or symptoms (i.e., syncope, malaise, chest pain or palpitations). Nine were evaluated by cardiologists, but in none was a diagnosis of myocarditis established before death. The inflammatory cellular infiltrate was predominantly lymphocytic (67%), was most frequently multifocal (59%) and involved the conduction system (including atrioventricular node), 38%. In conclusion, myocarditis is an important but under-recognized cause of sudden death in young people including competitive athletes. Clinical diagnosis is difficult because symptoms are nonspecific and often ignored, requiring high index of suspicion for diagnosis. Our data support the ACC/AHA consensus guidelines recommending removal of individuals with myocarditis from competitive sports during recovery. Selective examination of conduction systems showed a number of cases with involvement of myocarditis, suggesting a novel mechanism for sudden death.

Pulmonary Artery Pressure Monitoring Effectively Guides Management to Reduce Heart Failure Hospitalizations in Obesity.

OBJECTIVES: This study sought to determine the impact of therapy guided by pulmonary artery (PA) pressure monitoring in patients with heart failure (HF) and obesity. BACKGROUND: Obesity is prevalent in HF and associated with volume retention, but it complicates clinical assessment of congestion. METHODS: The CardioMEMS Post Approval Study was a prospective, multicenter, open-label trial in 1,200 patients with New York Heart Association functional class III HF and prior HF hospitalization (HFH) within 12 months. Patients with a body mass index (BMI) >35 kg/m2 were required to have a chest circumference <65 inches. Therapy was guided by PA pressure monitoring at sites, and HFHs were adjudicated 1 year before implantation and throughout follow-up. This analysis stratified patients according to ejection fraction (EF) <40% or ≥40% and by BMI <35 kg/m2 or ≥35 kg/m2. RESULTS: Baseline PA diastolic pressure was higher in patients with BMI ≥35 kg/m2 regardless of EF, but all PA pressures were reduced at 12 months in each cohort (P < 0.0001). HFH rate was reduced by >50% in both cohorts for EF <40% (BMI <35 kg/m2 [HR: 0.48; 95% CI: 0.41-0.55] and ≥35 kg/m2 [HR: 0.40; 95% CI: 0.31-0.53]) and EF ≥40% (BMI <35 kg/m2 [HR: 0.42; 95% CI: 0.35-0.52] and ≥35 kg/m2 [HR: 0.34; 95% CI: 0.25-0.45]; P < 0.0001). There was a nonsignificant trend toward greater reduction with more obesity. The all-cause hospitalization rate was also significantly reduced during monitoring (P < 0.01). CONCLUSIONS: Management guided by PA pressure monitoring effectively reduced pressures, HFH, and all-cause hospitalization in patients with obesity regardless of EF. (CardioMEMS HF System Post Approval Study; NCT02279888).

Acute Myocardial Infarction-Like Events in Related Patients With a Desmoplakin-Associated Arrhythmogenic Cardiomyopathy.

Patients with familial arrhythmogenic cardiomyopathy typically present with ventricular arrhythmias or progressive heart failure. This paper characterizes a rare presentation of an underlying genetic cardiomyopathy with clinical manifestations mimicking an acute myocardial infarction in 2 siblings, each with the same mutation in the desmoplakin (DSP) gene. (Level of Difficulty: Advanced.).

Silence sets on a sensory map.

Recent efforts to understand the contribution of neuronal activity in the creation of the olfactory sensory map have focused on odor-evoked events. In this issue of Neuron, Yu et al. discover a new role for neuronal activity in the organization and maintenance of the olfactory system. Their results highlight the role of spontaneous activity and synaptic transmission in axon outgrowth and olfactory neuron survival.

Home monitoring of heart failure patients at risk for hospital readmission using a novel under-the-mattress piezoelectric sensor: A preliminary single centre experience.

Introduction A piezoelectric sensor (PS) converts mechanical deformations into electrical signals. We used a contactless under-the-mattress PS to monitor physiological vibrations resulting from breathing, pumping of the heart, and body movements, among individuals at home following hospitalization for heart failure (HF). Our objectives were to assess acceptability of the device in the home, to assess physiological patterns, and to determine if altered patterns correlate with readmission. Methods We conducted a prospective observational study of 30 patients discharged home following HF hospitalization. PS data included a continuous nightly assessment of heart rate, respiration rate, movement rate, rapid and shallow respiration duration, and a behaviour score. We utilized random forest classification to classify average nightly data by readmission status. Results We collected 640 nights of PS data from 29 patients. There were nine readmissions, of which four were for HF. PS monitoring was tolerated by all but one of the participants. We inspected continuous nightly physiological profiles and noted differences between patients who were and were not readmitted. Patients readmitted for HF had higher average heart and respiration rates, and more respiration variability. Average nightly respiratory rate was most predictive of readmission. Discussion We are the first to study nocturnal physiological patterns of HF patients at home using a contactless under-the-mattress monitoring system. We noted patterns that may be unique to patients at risk for readmission due to HF. Respiratory rate was the most important risk-adjusted associate of readmission for HF. Further studies should investigate the efficacy of home PS monitoring in HF populations.

Time in Therapeutic Range for Left Ventricular Assist Device Patients Anticoagulated With Warfarin: A Correlation to Clinical Outcomes.

Left ventricular assist devices (LVADs) require anticoagulation therapy with vitamin K antagonists to reduce the risk of thrombotic events. The quality of anticoagulation may be assessed by the time in therapeutic range (TTR). We analyzed a retrospective cohort of LVAD patients at a single institution from January 2012 to September 2014. Primary outcomes included TTR during the study time period and TTR 30 days preceding a bleeding or thrombotic event. Fifty-one patients (mean age 57.0 ± 14.6 years; 78% male) had an overall TTR of 52%. Median international normalized ratio (INR) preceding a bleeding and thrombotic event was 2.7 and 2.2, respectively (p = 0.049). In the 30 days before an event, patients with a bleeding event were more likely to be on low-dose aspirin (37% vs. 12%; p = 0.018) and spend a higher proportion of time above therapeutic range (41% vs. 17%; p = 0.007) compared with those with thrombotic events. The association between a greater percentage of time above therapeutic range in the 30 days before a bleeding event demonstrates the importance of avoiding a supratherapeutic INR in the LVAD patient population and the usefulness of TTR as a measure of the overall quality of anticoagulation and monitoring in an LVAD cohort.

Percutaneous Venoarterial Extracorporeal Membrane Oxygenation for Refractory Cardiogenic Shock Is Associated with Improved Short- and Long-Term Survival.

Mortality due to refractory cardiogenic shock (RCS) exceeds 50%. Venoarterial extracorporeal membrane oxygenation (VA-ECMO) has become an accepted therapy for RCS. The aim of our study was to evaluate outcomes of patients with RCS treated with percutaneous VA-ECMO (pVA-ECMO). Retrospective review of patients supported with VA-ECMO at our institution in 2012-2013. Clinical characteristics, bleeding, vascular complications, and outcomes including survival were assessed. A total of 37 patients were supported with VA-ECMO for RCS. The majority of VA-ECMO (76%) was placed in the catheterization laboratory. Nearly half (49%) of the patients presented with acute myocardial infarction. Seven patients (19%) underwent insertion of pVA-ECMO in the setting of cardiopulmonary resuscitation with mechanical chest compression device. Median duration of support was 5 days. Index hospitalization, 30-day, and 1-year survival were 65%, 65%, and 57%, respectively. Survival rate for discharged patients was 87.5% with a median follow-up of 450 days. Refractory cardiogenic shock supported with pVA-ECMO is associated with an improved survival in patients with a traditionally poor prognosis.

Blood pressure management in mechanical circulatory support.

Durable mechanical support has become widely available for end stage heart failure as destination therapy and as bridge to transplantation. The accurate measurement of blood pressure (BP) as well as the recognition and management of hypertension in patients with continuous flow left ventricular assist devices (CF-VADs) is an essential component of optimal clinical care. Strategies for the control of BP in CF-VAD patients are increasingly important as there is an evolving understanding of the connection between hypertension, pump output, and adverse outcomes. As clinical experience grows, optimal BP targets, as well as methods to measure BP in CF-VAD patients have been further defined.