Safety Window for Effective Lesion Crossing in Patients With Chronic Thromboembolic Pulmonary Hypertension.

Background: Balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension (CTEPH) is limited by a lack of safe and effective tools for crossing these lesions. We aim to identify a safety window for an intraluminal crossing device in this vascular bed by studying the piercing properties of pulmonary arterial vessel walls and intraluminal CTEPH lesion specimens. As a secondary objective, we also describe the histopathologic features of CTEPH lesions. Methods: Specimens were procured from 9 patients undergoing pulmonary endarterectomy. The specimens were subsampled and identified grossly as arterial wall or intraluminal CTEPH lesions. The force needed for tissue penetration was measured using a 0.38-mm (0.015-in) diameter probe in an ex vivo experimental model developed in our lab. Concurrent histology was also performed. Results: The mean force needed to penetrate the arterial wall and intraluminal CTEPH lesions was 1.75 ± 0.10 N (n = 121) and 0.30 ± 0.04 N (n = 56), respectively (P < .001). Histology confirmed the presence of intimal hyperplasia with calcium and hemosiderin deposition in the arterial wall as well as an old, organized thrombus in the lumen. Conclusions: The pulmonary arterial wall is friable and prone to perforation during instrumentation with workhorse coronary guide wires. However, the results of this study demonstrate that a much lower force is needed for the 0.38-mm (0.015-in) probe to penetrate an intraluminal CTEPH lesion compared to pulmonary arterial intima. This finding suggests the existence of a safety window for lesion-crossing devices, enabling effective balloon pulmonary angioplasty.

Clinical trial design, end-points, and emerging therapies in pulmonary arterial hypertension.

Clinical trials in pulmonary arterial hypertension (PAH) have led to the approval of several effective treatments that improve symptoms, exercise capacity and clinical outcomes. In phase 3 clinical trials, primary end-points must reflect how a patient "feels, functions or survives". In a rare disease like PAH, with an ever-growing number of treatment options and numerous candidate therapies being studied, future clinical trials are now faced with challenges related to sample size requirements, efficiency and demonstration of incremental benefit on traditional end-points in patients receiving background therapy with multiple drugs. Novel clinical trial end-points, innovative trial designs and statistical approaches and new technologies may be potential solutions to tackle the challenges facing future PAH trials, but these must be acceptable to patients and regulatory bodies while preserving methodological rigour. In this World Symposium on Pulmonary Hypertension task force article, we address emerging trial end-points and designs, biomarkers and surrogate end-point validation, the concept of disease modification, challenges and opportunities to address diversity and representativeness, and the use of new technologies such as artificial intelligence in PAH clinical trials.

Optimizing Triage of Ambulatory Patients With Advanced Heart Failure: 2-Year Outcomes From REVIVAL.

BACKGROUND: Left ventricular assist device (LVAD) use remains uncommon in advanced heart failure (HF) patients not dependent on inotropes. OBJECTIVES: Before considering a randomized trial comparing a strategy of earlier use of LVAD to continued medical therapy, a better understanding is needed of the clinical trajectory of ambulatory patients with advanced systolic HF on optimal guideline-directed medical therapy (GDMT). METHODS: REVIVAL enrolled 400 patients with advanced ambulatory systolic HF, ≥1 HF mortality risk marker (≥2 HF hospitalizations past year; or HF hospitalization and high natriuretic peptide; or no HF hospitalizations but low peak oxygen consumption, 6-minute walk, serum sodium, HF survival score or Seattle HF model predicted survival), and no LVAD contraindication at 21 LVAD centers from July 2015 to June 2016. Patients were followed for 2 years or until a primary outcome (death, durable ventricular assist device, or urgent transplant). Clinical outcomes and health-related quality of life were evaluated. RESULTS: Mean baseline left ventricular ejection fraction was 21%, median 6-minute walk was 341 m, and 92% were Interagency Registry for Mechanically Assisted Circulatory Support profiles 5 to 7. Adherence to GDMT and electrical device therapies was robust. Composite primary outcome occurred in 22% and 37% at 1 and 2 years, with death alone in 8% and 16%, respectively. Patients surviving for 2 years maintained GDMT intensity and had no decline in health-related quality of life. CONCLUSION: Structured, serial follow-up at programs with expertise in caring for advanced ambulatory systolic HF patients facilitates triage for advanced therapies. Better strategies are still needed to avoid deaths in a small but significant group of patients who die without advanced therapies. REVIVAL patients not selected for VAD or transplant have robust survival and patient-reported outcomes, which challenges advocacy for earlier VAD implantation. (Registry Evaluation of Vital Information for VADs in Ambulatory Life [REVIVAL]; NCT01369407).

Prognosis Communication in Heart Failure: Experiences and Preferences of End-Stage Heart Failure Patients and Care Partners.

BACKGROUND: Patients with heart failure (HF) overestimate survival compared with model-predicted estimates, but the reasons for this discrepancy are poorly understood. We characterized how patients with end-stage HF and their care partners understand prognosis and elicited their preferences around prognosis communication. METHODS: We conducted in-depth, semistructured interviews with patients with end-stage HF and their care partners between 2021 and 2022 at a tertiary care center in Michigan. Participants were asked to describe barriers they faced to understanding prognosis. All interviews were coded and analyzed using an iterative content analysis approach. RESULTS: Fifteen patients with end-stage HF and 15 care partners participated, including 7 dyads. The median patient age was 66.5 years (range, 31-80) and included 9 of 15 (60%) White participants and 9 of 15 (60%) were males. Care partners included 10 of 15 (67%) White participants and 6 of 15 (40%) were males. Care partners were partners (n=7, 47%), siblings (n=4, 27%), parents (n=2, 13%), and children (n=2, 13%). Most patients demonstrated a poor understanding of their prognosis. In contrast, care partners commonly identified the patient's rapidly declining trajectory. Patients and care partners described ineffective prognosis communication with clinicians, common barriers to understanding prognosis, and similar suggestions on improving prognosis communication. Barriers to understanding prognosis included (1) conversation avoidance by physicians, (2) information inconsistency across different physicians, (3) distractions during prognosis communication due to emphasis on other conditions, and (4) confusion related to the use of medical jargon. Most patients and care partners wanted discussions around prognosis to begin early in the course of the disease, repeated routinely using layperson's terms, incorporating both quality of life and survival assessments, and involving care partners. Both patients and care partners did not expect precise survival estimates. CONCLUSIONS: Patients with end-stage HF demonstrate a poor understanding of their prognosis compared with their care partners. Patients and care partners are open to discussing prognosis early, using direct and patient-centered language.

Cardiac Rehabilitation Use After Heart Failure Hospitalization Associated With Advanced Heart Failure Center Status.

PURPOSE: Cardiac rehabilitation (CR) is an evidence-based, guideline-endorsed therapy for patients with heart failure with reduced ejection fraction (HFrEF) but is broadly underutilized. Identifying structural factors contributing to increased CR use may inform quality improvement efforts. The objective here was to associate hospitalization at a center providing advanced heart failure (HF) therapies and subsequent CR participation among patients with HFrEF. METHODS: A retrospective analysis was performed on a 20% sample of Medicare beneficiaries primarily hospitalized with an HFrEF diagnosis between January 2008 and December 2018. Outpatient claims were used to identify CR use (no/yes), days to first session, number of attended sessions, and completion of 36 sessions. The association between advanced HF status (hospitals performing heart transplantation or ventricular assist device implantations) and CR participation was evaluated with logistic regression, accounting for patient, hospital, and regional factors. RESULTS: Among 143 392 Medicare beneficiaries, 29 487 (20.6%) were admitted to advanced HF centers (HFCs) and 5317 (3.7%) attended a single CR session within 1 yr of discharge. In multivariable analysis, advanced HFC status was associated with significantly greater relative odds of participating in CR (OR = 2.20: 95% CI, 2.08-2.33; P < .001) and earlier initiation of CR participation (-8.5 d; 95% CI, -12.6 to 4.4; P < .001). Advanced HFC status had little to no association with the intensity of CR participation (number of visits or 36 visit completion). CONCLUSIONS: Medicare beneficiaries hospitalized for HF were more likely to attend CR after discharge if admitted to an advanced HFC than a nonadvanced HFC.

Gastrointestinal bleeding following Heartmate 3 left ventricular assist device implantation: The Michigan Bleeding Risk Model.

BACKGROUND: Gastrointestinal bleeding (GIB) results in frequent hospitalizations and impairs quality of life in durable left ventricular assist device (LVAD) recipients. Anticipation of these events before implantation could have important implications for patient selection and management. METHODS: The study population included all adult HeartMate 3 (HM3) primary LVAD recipients enrolled in the STS Intermacs registry from January 2017 to December 2020. Using multivariable modeling methodologies, we investigated the relationships between preimplantation characteristics and postimplant bleeding, bleeding and death, and additional bleeding episodes on subsequent bleeding episodes and created a risk score to predict the likelihood of post-LVAD GIB based solely on preimplantation factors. RESULTS: Of 6,425 patients who received an HM3 LVAD, 1,010 (15.7%) patients experienced GIB. Thirteen preimplantation factors were independent predictors of post-LVAD GIB. A risk score was created from these factors and calculated for each patient. By 3 years postimplant, GIB occurred in 11%, 26%, and 43% of low-, medium- and high-risk patients, respectively. Experiencing 1 post-LVAD GIB event was associated with an increased risk for further GIB events, with 33.9% of patients experiencing at least 1 recurrence. While post-LVAD GIB was associated with mortality, there was no relationship between number of GIB events and death. CONCLUSIONS: The Michigan Bleeding Risk Model is a simple tool, which facilitates the prediction of post-LVAD GIB in HM3 recipients using 13 preimplant variables. The implementation of this tool may help in the risk stratification process and may have therapeutic and clinical implications in HM3 LVAD recipients.

Pulmonary Rehabilitation for Adults with Chronic Respiratory Disease: An Official American Thoracic Society Clinical Practice Guideline.

Background: Despite the known benefits of pulmonary rehabilitation (PR) for patients with chronic respiratory disease, this treatment is underused. Evidence-based guidelines should lead to greater knowledge of the proven benefits of PR, highlight the role of PR in evidence-based health care, and in turn foster referrals to and more effective delivery of PR for people with chronic respiratory disease. Methods: The multidisciplinary panel formulated six research questions addressing PR for specific patient groups (chronic obstructive pulmonary disease [COPD], interstitial lung disease, and pulmonary hypertension) and models for PR delivery (telerehabilitation, maintenance PR). Treatment effects were quantified using systematic reviews. The Grading of Recommendations, Assessment, Development and Evaluation approach was used to formulate clinical recommendations. Recommendations: The panel made the following judgments: strong recommendations for PR for adults with stable COPD (moderate-quality evidence) and after hospitalization for COPD exacerbation (moderate-quality evidence), strong recommendation for PR for adults with interstitial lung disease (moderate-quality evidence), conditional recommendation for PR for adults with pulmonary hypertension (low-quality evidence), strong recommendation for offering the choice of center-based PR or telerehabilitation for patients with chronic respiratory disease (moderate-quality evidence), and conditional recommendation for offering either supervised maintenance PR or usual care after initial PR for adults with COPD (low-quality evidence). Conclusions: These guidelines provide the basis for evidence-based delivery of PR for people with chronic respiratory disease.

Periprocedural Complications With Balloon Pulmonary Angioplasty: Analysis of Global Studies.

BACKGROUND: Balloon pulmonary angioplasty (BPA) was introduced as a treatment modality for patients with inoperable, medically refractory chronic thromboembolic pulmonary hypertension decades ago; however, reports of high rates of pulmonary vascular injury have led to considerable refinement in procedural technique. OBJECTIVES: The authors sought to better understand the evolution of BPA procedure-related complications over time. METHODS: The authors conducted a systematic review of original articles published by pulmonary hypertension centers globally and performed a pooled cohort analysis of procedure-related outcomes with BPA. RESULTS: This systematic review identified 26 published articles from 18 countries worldwide from 2013 to 2022. A total of 1,714 patients underwent 7,561 total BPA procedures with an average follow up of 7.3 months. From the first period (2013-2017) to the second period (2018-2022), the cumulative incidence of hemoptysis/vascular injury decreased from 14.1% (474/3,351) to 7.7% (233/3,029) (P < 0.01); lung injury/reperfusion edema decreased from 11.3% (377/3,351) to 1.4% (57/3,943) (P < 0.01); invasive mechanical ventilation decreased from 0.7% (23/3,195) to 0.1% (4/3,062) (P < 0.01); and mortality decreased from 2.0% (13/636) to 0.8% (8/1,071) (P < 0.01). CONCLUSIONS: Procedure-related complications with BPA, including hemoptysis/vascular injury, lung injury/reperfusion edema, mechanical ventilation, and death, were less common in the second period (2018-2022), compared with first period (2013-2017), likely from refinement in patient and lesion selection and procedural technique over time.

Greater geographic sharing and heart transplantation waitlist outcomes following the 2018 heart allocation policy.

BACKGROUND: In 2018, a new heart allocation policy was introduced to reduce variability in access to and outcomes after transplantation, in part, through attempts at broader geographic sharing of donor hearts. We evaluated how this policy affected geographic sharing and waitlist outcomes by donation service area (DSA). METHODS: This retrospective study of the Scientific Registry of Transplant Recipients database included adult patients waitlisted between October 2016 and October 2020, stratified by policy period. Our primary outcomes were mean proportion of imported and exported hearts aggregated by DSA as well as time to transplant. RESULTS: Following the policy change, there was substantial evidence of sharing across DSAs. The mean proportion of imported hearts transplanted by a DSA increased from 32% (95% CI: 27%-36%) to 74% (95% CI: 71%-78%; p < 0.001), and the mean proportion of exported hearts increased from 37% (95% CI: 33%-42%) to 75% (95% CI: 71%-79%; p < 0.001). The mean sharing ratio, defined as the log-transformed ratio of imported to exported hearts per DSA, shifted from 1.15 (95% CI: 0.88-1.42) to 1.02 (95% CI: 0.96-1.07), with a 76% decline in the variance across DSAs. As sharing increased, time to transplant per DSA declined from 153.9 days (95% CI, 143.4-164.4 days) pre-policy to 89.6 days (95% CI, 83.1-96.1 days) post-policy (p < 0.001). A larger decrease in waitlist time was associated with a higher proportion of exported hearts. CONCLUSIONS: The 2018 heart allocation policy was associated with more uniform access to heart transplantation and improved waitlist outcomes.

Failure to rescue: A candidate quality metric for durable left ventricular assist device implantation.

OBJECTIVE: Failure to rescue (FTR), defined as death after a complication, is recognized as a principal driver of variation in mortality among hospitals. We evaluated FTR as a quality metric in patients who received durable left ventricular assist devices (LVADs) using the Society of Thoracic Surgeons Interagency Registry for Mechanically Assisted Circulatory Support. METHODS: Data on 13,617 patients who received primary durable LVADs from April 2012 to October 2017 at 131 hospitals that performed at least 20 implants were analyzed from the Society of Thoracic Surgeons Interagency Registry for Mechanically Assisted Circulatory Support. Rates of major complications and FTR were compared across risk-adjusted in-hospital mortality terciles (low, medium, high) and hospital volume. Logistic regression was used to estimate expected FTR rates on the basis of patient factors for each major complication. RESULTS: The overall unadjusted in-hospital mortality rate was 6.96%. Risk-adjusted in-hospital mortality rates varied 3.1-fold across terciles (low, 3.3%; high, 10.3%; P trend <.001). Rates of major complications varied 1.1-fold (low, 34.0%; high, 38.8%; P < .0001). Among patients with a major complication, 854 died in-hospital for an FTR rate of 17.7%, with 2.8-fold variation across mortality terciles (low, 8.5%; high, 23.9%; P < .0001). FTR rates were highest for renal dysfunction requiring dialysis (45.3%) and stroke (36.5%). Higher average annual LVAD volume was associated with higher rates of major complications (<10 per year, 26.7%; 10-20 per year, 34.0%; 20-30 per year, 34.0%; >30 per year, 40.1%; P trend <.0001) whereas hospitals implanting <10 per year had the highest FTR rate (<10 per year, 23.5%; 10-20 per year, 16.5%; 20-30 per year, 17.0%; >30 per year, 17.9%; P = .03). CONCLUSIONS: FTR might serve as an important quality metric for durable LVAD implant procedures, and identifying strategies for successful rescue after complications might reduce hospital variations in mortality.

Readability and Non-English Language Resources of Heart Transplant Center Websites in the United States.

OBJECTIVE: Health literacy is associated with heart failure (HF) care and outcomes. Online resources offer important educational materials for patients seeking access to heart transplantation but tend to be complex and potentially ineffective for non-English speakers and those with low reading levels. The purpose of this study was to evaluate both the readability of patient-level information posted on United States heart transplant center websites and the availability of non-English resources. METHODS AND RESULTS: We performed a review of patient-facing information on websites of U.S. heart transplant centers identified through the United Network for Organ Sharing in August 2022. Written English text was extracted and assessed for readability by using the Fry Graph Readability score. Websites were additionally evaluated for non-English language text and translator tools. Standard ANOVA analysis was used to compare readability levels across transplant regions. The median Fry readability level to understand a piece of text for all regions was 15, which is equivalent to a college-junior reading level (range: 7-17, 7th grade to postgraduate level). There was no statistical difference in median Fry readability levels among regions (P = 0.16). Of the 139 eligible heart transplant center websites, only 56.1% (78/139) had non-English resources available for patients. Regions 5 (75% [15/20]) and 6 (75% [3/4]) had the highest percentage of non-English resources, and region 2 had the lowest (38% [6/16]). CONCLUSIONS: Heart transplant center online resources are inadequate, and many do not provide translations of the English language. Additional work is needed to standardize heart-transplant patient information for a diverse U.S.

Racial Inequities in Access to Ventricular Assist Device and Transplant Persist After Consideration for Preferences for Care: A Report From the REVIVAL Study.

BACKGROUND: Racial disparities in access to advanced therapies for heart failure (HF) patients are well documented, although the reasons remain uncertain. We sought to determine the association of race on utilization of ventricular assist device (VAD) and transplant among patients with access to care at VAD centers and if patient preferences impact the effect. METHODS: We performed an observational cohort study of ambulatory chronic systolic HF patients with high-risk features and no contraindication to VAD enrolled at 21 VAD centers and followed for 2 years in the REVIVAL study (Registry Evaluation of Vital Information for VADs in Ambulatory Life). We used competing events cause-specific proportional hazard methodology with multiple imputation for missing data. The primary outcomes were (1) VAD/transplant and (2) death. The exposures of interest included race (Black or White), additional demographics, captured social determinants of health, clinician-assessed HF severity, patient-reported quality of life, preference for VAD, and desire for therapies. RESULTS: The study included 377 participants, of whom 100 (26.5%) identified as Black. VAD or transplant was performed in 11 (11%) Black and 62 (22%) White participants, although death occurred in 18 (18%) Black and 36 (13%) White participants. Black race was associated with reduced utilization of VAD and transplant (adjusted hazard ratio, 0.45 [95% CI, 0.23-0.85]) without an increase in death. Preferences for VAD or life-sustaining therapies were similar by race and did not explain racial disparities. CONCLUSIONS: Among patients receiving care by advanced HF cardiologists at VAD centers, there is less utilization of VAD and transplant for Black patients even after adjusting for HF severity, quality of life, and social determinants of health, despite similar care preferences. This residual inequity may be a consequence of structural racism and discrimination or provider bias impacting decision-making. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01369407.

Safe and Effective Balloon Pulmonary Angioplasty in the Outpatient Setting: The Michigan Medicine Experience.

Background: Balloon pulmonary angioplasty (BPA) is currently performed at select centers worldwide, with the current standard of practice being postprocedural inpatient monitoring for 24 to 72 hours. We sought to evaluate the safety and efficacy of BPA in a cohort of patients with chronic thrombo-embolic pulmonary disease (CTEPD) and chronic thromboembolic pulmonary hypertension (CTEPH) and outline a protocol for implementation in the outpatient setting. Methods: All patients with distal, inoperable CTEPH, residual symptoms after pulmonary endarterectomy, or symptomatic CTEPD from July 1, 2020, to June 30, 2022, were evaluated by a multidisciplinary chronic thromboembolic pulmonary hypertension team for consideration of BPA. Patients undergoing each BPA session adhered to a regimented protocol developed and implemented at our institution. Safety and efficacy were retrospectively evaluated with a mean follow-up time of 8.5 months. Results: Eighteen patients underwent a total of 78 BPA sessions. Overall, there was a significant improvement in World Health Organization functional class and mean improvement in 6-minute walking distance of +67 m. Hemodynamic parameters significantly improved with a mean decrease in mean pulmonary artery pressure and pulmonary vascular resistance of 7.3 ± 5.8 mm Hg and 1.7 ± 1.5 Wood units, respectively (P <.05). Complication rates were low with 3 (3.9%) of 78 patients developing scant hemoptysis and 1 (1.3%) of 78 experiencing vascular injury requiring inpatient hospitalization. Conclusions: BPA is both safe and effective when implemented in the outpatient setting using a regimented protocol provided there are necessary contingencies in place.