Expanding the Paradigm for Cardiovascular Palliative Care.

Cardiovascular disease (CVD) is the leading cause of death worldwide. Despite medical advances, patients with CVD experience high morbidity and mortality rates, affecting their quality of life and death. Among CVD conditions, palliative care has been studied mostly in patients with heart failure, where palliative care interventions have been associated with improvements in patient-centered outcomes, including quality of life, end-of-life care, and health care use. Although palliative care is now incorporated into the American Heart Association/American College of Cardiology/Heart Failure Society of America guidelines for heart failure, the role of palliative care for non-heart failure CVD remains uncertain. Across all causes of CVD, palliative care can play an important role in all domains of CVD care from initial diagnosis to terminal care. In addition to general cardiovascular palliative care practices applicable to all areas, disease-specific palliative care needs may warrant individualized palliative care models. In this review, we discuss the role of cardiovascular palliative care for ischemic heart disease, valvular disease, arrhythmias, peripheral artery disease, and adult congenital heart disease. Although there are multiple barriers to cardiovascular palliative care, we recommend a framework for studying and developing cardiovascular palliative care models to improve patient-centered goal-concordant care for this underserved patient population.

Incidence, Treatment, and Outcomes of Symptomatic Device Lead-Related Venous Obstruction.

BACKGROUND: The incidence and clinical impact of lead-related venous obstruction (LRVO) among patients with cardiovascular implantable electronic devices (CIEDs) is poorly defined. OBJECTIVES: The objectives of this study were to determine the incidence of symptomatic LRVO after CIED implant; describe patterns in CIED extraction and revascularization; and quantify LRVO-related health care utilization based on each type of intervention. METHODS: LRVO status was defined among Medicare beneficiaries after CIED implant from October 1, 2015, to December 31, 2020. Cumulative incidence functions of LRVO were estimated by Fine-Gray methods. LRVO predictors were identified using Cox regression. Incidence rates for LRVO-related health care visits were calculated with Poisson models. RESULTS: Among 649,524 patients who underwent CIED implant, 28,214 developed LRVO, with 5.0% cumulative incidence at maximum follow-up of 5.2 years. Independent predictors of LRVO included CIEDs with >1 lead (HR: 1.09; 95% CI: 1.07-1.15), chronic kidney disease (HR: 1.17; 95% CI: 1.14-1.20), and malignancies (HR: 1.23; 95% CI: 1.20-1.27). Most patients with LRVO (85.2%) were managed conservatively. Among 4,186 (14.8%) patients undergoing intervention, 74.0% underwent CIED extraction and 26.0% percutaneous revascularization. Notably, 90% of the patients did not receive another CIED after extraction, with low use (2.2%) of leadless pacemakers. In adjusted models, extraction was associated with significant reductions in LRVO-related health care utilization (adjusted rate ratio: 0.58; 95% CI: 0.52-0.66) compared with conservative management. CONCLUSIONS: In a large nationwide sample, the incidence of LRVO was substantial, affecting 1 of every 20 patients with CIEDs. Device extraction was the most common intervention and was associated with long-term reduction in recurrent health care utilization.

Underperformance of Contemporary Phase III Oncology Trials and Strategies for Improvement.

BACKGROUND: Statistical testing in phase III clinical trials is subject to chance errors, which can lead to false conclusions with substantial clinical and economic consequences for patients and society. METHODS: We collected summary data for the primary endpoints of overall survival (OS) and progression-related survival (PRS) (eg, time to other type of event) for industry-sponsored, randomized, phase III superiority oncology trials from 2008 through 2017. Using an empirical Bayes methodology, we estimated the number of false-positive and false-negative errors in these trials and the errors under alternative P value thresholds and/or sample sizes. RESULTS: We analyzed 187 OS and 216 PRS endpoints from 362 trials. Among 56 OS endpoints that achieved statistical significance, the true efficacy of experimental therapies failed to reach the projected effect size in 33 cases (58.4% false-positives). Among 131 OS endpoints that did not achieve statistical significance, the true efficacy of experimental therapies reached the projected effect size in 1 case (0.9% false-negatives). For PRS endpoints, there were 34 (24.5%) false-positives and 3 (4.2%) false-negatives. Applying an alternative P value threshold and/or sample size could reduce false-positive errors and slightly increase false-negative errors. CONCLUSIONS: Current statistical approaches detect almost all truly effective oncologic therapies studied in phase III trials, but they generate many false-positives. Adjusting testing procedures in phase III trials is numerically favorable but practically infeasible. The root of the problem is the large number of ineffective therapies being studied in phase III trials. Innovative strategies are needed to efficiently identify which new therapies merit phase III testing.

Potential Unintended Consequences Of Recent Shared Decision Making Policy Initiatives.

Shared decision making (SDM)-when clinicians and patients make medical decisions together-is moving swiftly from an ethical ideal toward widespread clinical implementation affecting millions of patients through recent policy initiatives. We argue that policy initiatives to promote SDM implementation in clinical practice carry the risk of several unintended negative consequences if limitations in defining and measuring SDM are not addressed. We urge policy makers to include prespecified definitions of desired outcomes, offer guidance on the tools used to measure SDM in the multitude of contexts in which it occurs, evaluate the impact of SDM policy initiatives over time, review that impact at regular intervals, and revise SDM measurement tools as needed.

Clinical and regulatory considerations for novel electrophysiology mapping systems: Lessons from FIRM.

Atrial fibrillation (AF) presents a growing clinical and public health burden for which better rhythm control therapies are needed. Focal impulse and rotor mapping (FIRM), currently marketed as a part of the Topera Rotor Mapping system (Abbott Laboratories, Austin, TX, USA), represents a potentially transformational approach to guide the invasive treatment of AF. However, many years after its initial marketing clearance, the clinical utility of this technology remains uncertain. In this article, we review the scientific rationale for this novel approach to AF ablation, evaluate the current clinical evidence for FIRM-guided ablation, and characterize its premarket regulatory assessment. Lessons for clinicians considering adoption of newly marketed mapping systems are presented.

An unusual cause of abnormal intrathoracic impedance in a patient with arrhythmogenic right ventricular cardiomyopathy.

A device interrogation for a 32-year-old woman with arrhythmogenic right ventricular cardiomyopathy and an implantable cardioverter-defibrillator capable of monitoring intrathoracic impedance demonstrated a dramatic increase in her OptiVol Fluid index levels in the absence of clinical heart failure. The timing of her intrathoracic impedance changes correlated with plasma volume changes during an uneventful pregnancy without cardiovascular complications. The strengths and limitations of intrathoracic impedance are described in the context of the physiology of pregnancy.

Premarket clinical evaluation of novel cardiovascular devices: quality analysis of premarket clinical studies submitted to the Food and Drug Administration 2000-2007.

The quality of clinical data submitted by manufacturers to support Food and Drug Administration cardiovascular device premarket approval (PMA) applications varies widely and formal quality assessment has not been previously performed. This study evaluated all original cardiovascular device PMAs with Food and Drug Administration decisions between January 1, 2000, and December 31, 2007, to assess the quality of clinical investigations submitted by manufacturers. Effectiveness and safety end points were judged high quality if they were clearly defined and associated with a specific time point for analysis. Subject accounting was high quality if 90% or greater of the original cohort was accounted for at study conclusion. In total, 88 cardiovascular device PMAs (77.3% permanent implants), 132 clinical studies, 37,328 study subjects (age 61.0 +/- 14.5 years, 33.9% women, 86.3% white), and 29,408 device recipients were analyzed. All PMAs contained clinical data. Primary effectiveness end points, primary safety end points, and subject accounting were deemed high quality in 81.8%, 60.2%, and 77.3% of pivotal studies, respectively. Key cardiovascular comorbidities (coronary artery disease 51.1%, diabetes 36.6%, hypertension 35.2%, heart failure 37.5%, tobacco use 31.8%) and race (14.8%) were infrequently reported, and studies rarely included patients younger than 18 years of age (10.2% of studies). Poorly defined safety and effectiveness end points, poor patient accounting, and incomplete collection of important patient comorbidities make device safety and effectiveness assessments more challenging. Women, pediatric, and nonwhite populations are underrepresented in premarket cardiovascular clinical trials. Manufacturers, regulators, and the clinical community should collaborate to address these study shortcomings to ensure that patients are treated with reliable, safe, and clinically useful medical devices.