Burden with No Benefit: Prior Authorization in Congenital Cardiology.

Prior authorization is a process that health insurance companies use to determine if a patient's health insurance will cover certain medical treatments, procedures, or medications. Prior authorization requests are common in adult congenital and pediatric cardiology (ACPC) due to need for advanced diagnostics, complex procedures, disease-specific medications, and the heterogeneity of the ACPC population. Prior authorizations in ACPC are rarely denied, but nonetheless, they are often accompanied by significant administrative burden on clinical care teams and delays in patient care. Prior authorizations have been implicated in worsening care inequities. The prior authorization process is insurer specific with differences between commercial and public insurers. Prior authorization rejections were previously found to be more common for women, racial minorities, those with low education, and in low-income groups. Prior authorization unduly burdens routine diagnostics, routine interventional and surgical procedures, and routine cardiac specific medication use in the ACPC population. This manuscript highlights the burdens of prior authorization and advocates for the elimination of prior authorization for ACPC patients.

Experiences and Attitudes Toward Telemedicine in an Adult Congenital Heart Disease Clinic: Lessons Learned from the COVID-19 Pandemic.

The coronavirus disease 2019 (COVID-19) pandemic has driven a broader adoption of telemedicine (TM). We aim to describe adult congenital heart disease (ACHD) patient experiences with TM and explore factors associated with positive attitude toward future TM visits. This is a cross-sectional, single-center study in an outpatient ACHD clinic from February to June, 2022. Between-group comparisons were made using Wilcoxon-Rank Sum, Chi-Square, or Fisher-Exact tests. Univariate logistic regression was performed for variables that could correlate with a "positive" attitude toward future TM visits. Significance was determined using an alpha level of 0.05. Of 262 patients (median age 33 years, 55% female, 81% White), 115 (44%) had a prior TM visit and 110 (96%) reported a positive experience. There were 64 (24%) with a positive attitude toward future TM visits. Concerns include lack of cardiac testing and limited quality of visit. Patients with visits every 3-6 months (Odds Ratio [OR] 2.44; p < 0.01) and prior TM visit (OR 1.89; p = 0.03) had higher odds of a positive attitude toward future TM, whereas males had lower odds (OR 0.53; p = 0.04). Age, annual income, disease complexity, distance from clinic, and employment status were not associated. There is high rate of satisfaction with TM among ACHD patients but only one-quarter indicated interest in using TM in the future. Factors associated with interest in TM visits are identified, and together with patient feedback, can be used to understand potential role of TM for the ACHD population in the post-pandemic era.

Novel Therapeutic Strategies in Heart Failure in Adult Congenital Heart Disease: of Medicines and Devices.

PURPOSE OF REVIEW: This paper reviews the latest literature on the growing field of heart failure in the adult congenital heart disease population. RECENT FINDINGS: After highlighting the increasing prevalence and a few of the unique potential causes, including the concept of early senescence, this review begins with novel medical management strategies such as the angiotensin II receptor blocker and neprilysin inhibitors and sodium glucose cotransporter-2 inhibitors. Then, it addresses the latest applications of percutaneous techniques like implantable hemodynamic monitoring, transcatheter pulmonary and aortic valve replacement, and mitral clips. Cardiac resynchronization therapy and novel lymphatic system imaging and intervention are then described. Finally, the use of mechanical support devices, temporary and durable, is discussed as well as heart and combined heart and liver transplantation. There have been recent exciting advances in the strategies used to manage adult congenital heart disease patients with heart failure. As this population continues to grow, it is likely we will see further rapid evolution in this field.

The Association of Cardiac Biomarkers, the Intensity of Tc99 Pyrophosphate Uptake, and Survival in Patients Evaluated for Transthyretin Cardiac Amyloidosis in the Early Therapeutics Era.

BACKGROUND: Transthyretin amyloid cardiomyopathy (ATTR-CM) is an increasingly recognized cause of heart failure. Given the expansion of noninvasive diagnosis with 99mTc-pyrophosphate (99mTc-PYP) scanning, and clinical use of the transthyretin stabilizer, tafamidis, we sought to examine the interplay of planar imaging heart-to-contralateral lung (H/CL) ratio, cardiac biomarkers, and survival probability in a contemporary cohort of patients referred for noninvasive evaluation of ATTR-CM. METHODS: This single-center retrospective cohort study included 351 consecutive patients who underwent a standardized imaging protocol with 99mTc-PYP scanning for the evaluation of ATTR-CM from January 1, 2018, to January 1, 2020. After the exclusion of light chain amyloidosis, patients were characterized as scan consistent with ATTR (+ATTR-CM) or scan not consistent with ATTR (-ATTR-CM) using current guidelines. Linear regression was used to examine the relationship between biomarkers and H/CL and univariate Cox proportional hazards models were used to assess the probability of transplant-free survival. RESULTS: We included 318 patients in the analysis (n = 86 patients +ATTR-CM; n = 232 patients -ATTR-CM). The median follow-up time was 20.1 months. During the study period, 67% of +ATTR-CM patients received tafamidis (median treatment duration, 17 months). The median H/CL ratio was 1.58 (interquartile range, 1.40-1.75). An H/CL ratio of more than 1.6 or less than 1.6 did not seem to have an impact on survival probability in +ATTR-CM patients (P = .30; hazard ratio, 0.65; 95% confidence interval, 0.31-1.41). Cardiac biomarkers were poorly correlated with H/CL (troponin T, R2 = 0.024; N-terminal pro-B-type natriuretic peptide, R2 =0.023). The Gillmore staging system predicted survival probability in +ATTR-CM as well as in the entire cohort referred for scanning. There was a trend toward longer survival among those who were -ATTR-CM compared with +ATTR-CM (P = .051; hazard ratio, 0.64; 95% confidence interval, 0.40-1.00). CONCLUSIONS: At a large referral center, the intensity of 99mTc-PYP uptake (H/CL ratio) has neither correlation with cardiac biomarker concentrations nor prognostic usefulness in an analysis of intermediate term outcomes in the early therapeutics era. The H/CL ratio has diagnostic value, but offers little prognostic value in patients with ATTR-CM. Established staging schema were predictive of survival in this contemporary cohort, re-emphasizing the importance of cardiac biomarkers and renal function in assessing disease severity and prognosis.

Race, Genotype, and Prognosis in Black Patients With Transthyretin Cardiac Amyloidosis.

Previous studies suggest worse outcomes in patients with variant transthyretin cardiac amyloidosis (ATTR-CA) because of valine-to-isoleucine substitution at Position 122 (V122I) (ATTRv-CA) compared with patients with wild-type (WT) disease (ATTRwt-CA). Given V122I is almost exclusively found in Black patients, it is unclear if this is attributable to the biology of genotype or racial differences. Patients with ATTR-CA diagnosed between January 2001 and August 2021 were characterized into 3 categories: (1) White with ATTRwt-CA (White-WT); (2) Black with V122I ATTRv-CA (Black-V122I), and (3) Black with ATTRwt-CA (Black-WT). Event-free survival (composite of death, left ventricular assist device, or cardiac transplant) was evaluated using univariable and multivariable analyses over a median follow-up of 1.6 (0.7 to 2.90) years. Of 694 ATTR-CA patients, 502 (72%) were White-WT, 139 Black-V122I (20%), and 53 Black-WT (8%). Notably, 28% of Black patients with ATTR-CA had WT disease and not the V122I variant. Using multivariable modeling to adjust for several prognostic features, Black-V122I had higher risk of the composite adverse outcome compared with a grouped cohort of patients with WT disease (White-WT and Black-WT) (hazard ratio [HR] 1.82, confidence interval [CI] 1.30-2.56, p < 0.001). Furthermore, the Black cohort as a whole (Black-V122I and Black-WT) demonstrated greater risk of adverse outcomes compared with White-WT (HR 1.63, CI 1.19-2.24, p = 0.002). Black-V122I had greater risk of the primary end point compared with White-WT (HR 1.80, CI 1.27-2.56, p = 0.001). Black patients with ATTR-CA have worse event-free survival than White-WT despite risk adjustment. However, it remains unclear whether this is driven by differences in race or genotype given the smaller number of Black-WT patients. Approximately one-quarter of Black patients had WT, of which a greater proportion were female compared with White-WT.

Predictive Modeling to Assess Pretest Probability of Transthyretin Gene Variants Based on Demographic Information.

BACKGROUND: Transthyretin amyloid cardiomyopathy (ATTR-CM) is a morbid condition, though recent advances in diagnosis and therapy stand to change its natural history. Patients' TTR genotype may guide family screening as more treatments and preventive strategies become available. An efficient, intuitive means of determining pretest genetic risk may better inform patients/clinicians when pursuing genetic testing. METHODS: This is a cohort study of 767 consecutive patients diagnosed with ATTR-CM who underwent genetic testing. Classification and regression trees (CART) analysis created a decision tree assessing likelihood of carrying a pathologic TTR gene variant. Age, sex, and race were used as independent variables. Logistic regression was also performed to model probability of pathologic TTR genotype. The primary outcome was the decision tree's accuracy in 2 separate institutions' ATTR-CM registry. RESULTS: In our study cohort, 208 patients (27.1%) had ATTRv. Race has served most efficiently as the root node followed by age and sex in a CART algorithm, and showed 88.2% accuracy (75.3% sensitivity, 93.9% specificity) in the validation cohort. The odds of having a TTR gene variant were greater in Black patients compared with non-Black patients (OR, 34.6 [95% CI, 20.5-58.3]; P<0.001). Non-Black patients with ATTR-CM aged 69 years and older had <4% risk of having a predisposing mutation. CONCLUSIONS: This CART algorithm incorporating age, sex, and race was able to determine which patients with ATTR-CM have pathogenic TTR mutations with high specificity. Non-Black patients diagnosed at age 69 years or older with ATTR-CM have a low likelihood to have ATTRv.

Changes in Left Ventricular Ejection Fraction and Clinical Trajectories of Transthyretin Cardiac Amyloidosis with Systolic Dysfunction.

BACKGROUND: Transthyretin cardiac amyloidosis (ATTR-CM) is classically thought of as a progressive disease with preserved systolic function. The longitudinal clinical trajectories of ATTR-CM with impaired left ventricular ejection fraction (LVEF) remain unclear. METHODS: This is a single-center retrospective cohort study of consecutive patients with ATTR-CM who underwent two or more echocardiograms with baseline LVEF < 50%. Patients were stratified according to the presence of ≥5% change in LVEF. A Cox proportional hazard model examined hazard of a composite outcome of death, transplant, or LVAD insertion over the two years following diagnosis. RESULTS: In our study cohort of 179 patients, 62 patients (34.6%) experienced an increase in LVEF while 33 (18.4%) experienced a decrease in LVEF. After adjusting for covariates, patients with a decrease in EF experienced increased hazard of death (HR 2.15, 95% CI 1.05-4.40, p = 0.038) compared to those with stable or an increase in LVEF. Changes in LVEF corresponded with significant differences in NT proBNP trajectories, but initial biomarker levels or clinical staging were not predictive of LVEF trajectory. CONCLUSIONS: in ATTR-CM patients with impaired LVEF, over a third demonstrated improved LVEF over time, while those with a decrease in LVEF had worse long-term outcomes.

Durable Mechanical Circulatory Support in Adult Congenital Heart Disease: Reviewing Clinical Considerations and Experience.

Adults with congenital heart disease (ACHD) patients are one of the fastest growing populations in cardiology, and heart failure (HF) is the most common cause of morbidity and mortality amongst them. The need for advanced HF therapies in ACHD patients stands to grow substantially. The anatomic considerations for placing durable mechanical circulatory support (MCS) devices in ACHD patients often require specialized approaches. Despite this, increasing evidence suggests that durable MCS can be implanted safely with favorable outcomes in ACHD patients. Expansion of MCS use in ACHD patients is imperative to improve their clinical outcomes. Knowledge of ACHD-specific anatomic and physiologic considerations is crucial to HF programs' success as they work to provide care to this growing population.

Valvular heart disease in congenital heart disease: a narrative review.

Patients with congenital heart disease (CHD) are one of the fastest growing populations in cardiology, and valvular pathology is at the center of many congenital lesions. Derangements in valvular embryology lead to several anomalies prone to dysfunction, each with hemodynamic effects that require appropriate surveillance and management. Surgical innovation has provided new treatments that have improved survival in this population, though has also contributed to esotericism in patients who already have unique anatomic and physiologic considerations. Conduit and prosthesis durability are often monitored collaboratively with general and specialized congenital-focused cardiologists. As such, general cardiologists must become familiar with valvular disease with CHD for appropriate care and referral practices. In this review, we summarize the embryology of the semilunar and atrioventricular (AV) valves as a foundation for understanding the origins of valvular CHD and describe the mechanisms that account for heterogeneity in disease. We then highlight the categories of pathology from the simple (e.g., bicuspid aortic valve, isolated pulmonic stenosis) to the more complex (e.g., Ebstein's anomaly, AV valvular disease in single ventricle circulations) with details on natural history, diagnosis, and contemporary therapeutic approaches. Care for CHD patients requires collaborative effort between providers, both CHD-specialized and not, to achieve optimal patient outcomes.

Early Experience with High-density Electroanatomical Mapping Using the Rhythmia™ Mapping System in Congenital and Pediatric Heart Disease.

The Rhythmia™ system (Boston Scientific, Natick, MA, USA) facilitates the rapid acquisition of high-resolution electroanatomical and activation maps. However, there are limited data on its efficacy and safety in pediatric and adult congenital heart disease (CHD) patients. In a retrospective, observational cohort study, adult CHD and pediatric patients followed by pediatric cardiology underwent electrophysiologic study using the Rhythmia™ electroanatomic mapping system. Variables examined included the number of electroanatomical maps required, acquisition time, procedure time, fluoroscopy time, radiation dosage, and rate of recurrent arrhythmia. Twelve consecutive patients, including six male patients (50%), were included with an average age of 27.7 years (range: 11-64 years). Seven (58%) of these patients had a diagnosis of CHD [moderate complexity in two (17%) and great complexity in five patients (42%)] and 10 (83%) patients underwent ablation. A total of 37 high-density maps were created in 12 procedures, with a median of 8,140 mapping points, taking a median of 631 seconds. The median procedure time was 189.5 minutes. The median fluoroscopy time was 0.9 minutes, with eight (67%) patients receiving no fluoroscopy at all. Recurrence occurred in one patient (8%) over a median follow-up duration of 16 months (interquartile range: 12.8-17.3 months). No adverse periprocedural events were recorded. This study suggests the use of high-density electroanatomic mapping in adult CHD patients showed potential for rapid acquisition of highly detailed maps with minimal fluoroscopy time or risk of periprocedural events in the studied population.

SARS-CoV-2 and ACE2: The biology and clinical data settling the ARB and ACEI controversy.

BACKGROUND: SARS-CoV-2 enters cells by binding of its spike protein to angiotensin-converting enzyme 2 (ACE2). Angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) have been reported to increase ACE2 expression in animal models, and worse outcomes are reported in patients with co-morbidities commonly treated with these agents, leading to controversy during the COVID-19 pandemic over whether these drugs might be helpful or harmful. METHODS: Animal, in vitro and clinical data relevant to the biology of the renin-angiotensin system (RAS), its interaction with the kallikrein-kinin system (KKS) and SARS-CoV-2, and clinical studies were reviewed. FINDINGS AND INTERPRETATION: SARS-CoV-2 hijacks ACE2to invade and damage cells, downregulating ACE2, reducing its protective effects and exacerbating injurious Ang II effects. However, retrospective observational studies do not show higher risk of infection with ACEI or ARB use. Nevertheless, study of the RAS and KKS in the setting of coronaviral infection may yield therapeutic targets.

Cardiac Denial and Expectations Associated With Depression in Adults With Congenital Heart Disease.

Depression in adults with congenital heart disease is highly prevalent and strongly associated with adverse prognosis. Better management of risk factors for depression may improve clinical outcomes in this population. We conducted a single-site, cross-sectional study of 78 adults with congenital heart disease followed at Washington University School of Medicine. Data considered in the analyses included retrospectively obtained clinical information and patients' self-assessed psychosocial functioning and health status. To identify the clinical and psychosocial variables associated with depression, we built a stepwise multivariate model to measure the relative contribution of these variables to depression status. The prevalence of depression in our sample was 26%. Our model accounted for approximately 67% of the variability in depression scores. The final model consisted of the Cardiac Denial of Impact Scale, expectations domain of Barriers to Care, and the energy and social domains of the Rand 36-Item Short Form Health Survey. Clinical variables did not predict variability in depression scores. In conclusion, greater cardiac denial and negative expectations of the healthcare team were associated with increased depression symptoms in ACHD.

Contributors to disease-specific health knowledge in adults with congenital heart disease: A correlational study.

OBJECTIVE: Growth in the adults with congenital heart disease (ACHD) population represents a challenge to the health care infrastructure. As patients with chronic disease are increasingly held accountable for their own care, contributors to disease-specific health knowledge, which are known to correlate with patients' participation in care, merit investigation to design patient-focused interventions. DESIGN: We conducted a single-site, cross-sectional study of ACHD patients. Investigators retrospectively gathered clinical data as well as psychometric and health status assessments completed at the time of enrollment. OUTCOME MEASURES: We investigated the impact of clinical and psychological variables on Leuven Knowledge Questionnaire for Congenital Heart Diseases health knowledge composite scores (HKCS). Variables with significant associations were considered in a stepwise multivariable regression model to determine which combination of variables jointly explained variability in HKCS. RESULTS: Overall HKCS was associated with the number of prior cardiac surgeries (r = 0.273; 95% CI: 0.050-0.467; P = .016), perceived stress (r = 0.260; 95% CI: 0.033-0.458; P = .024), SF-36 emotional well-being (r = -0.251; 95% CI: -0.451, -0.024; P = .030), history of noncardiac surgery (P = .037), cirrhosis (P = .048), and presence of implantable cardioverter-defibrillator (P = .028). On multivariable modeling, only the number of cardiac surgeries was found to correlate with HKCS. CONCLUSIONS: While univariate correlations were found between HCKS and several other clinical and psychological variables, only number of prior cardiac surgeries independently correlated with disease-specific health knowledge in ACHD patients. These results suggest that clinical and psychological variables are not impediments to disease-specific health knowledge.

Effect of Ambrisentan on Exercise Capacity in Adult Patients After the Fontan Procedure.

The Fontan operation is a common end point for children born with a single functional ventricle. Fontan patients typically experience physiological deterioration leading to transplant or death in their third or fourth decades of life. This deterioration is partially attributable to progressive increases in pulmonary vascular resistance (PVR) and as such endothelin receptor antagonists, which are known to decrease pulmonary vascular resistance, have been proposed as potentially beneficial in this population. We conducted a single-center, randomized, double-blind, placebo-controlled, crossover study of 12 weeks of ambrisentan therapy (10 mg per day) versus placebo to test the hypothesis that endothelin receptor antagonism will improve cardiopulmonary exercise test parameters and 36-item short form (SF-36) assessed quality of life in adult Fontan patients. Twenty-eight patients entered the trial, 19 patients completed the protocol. Ambrisentan therapy improved peak oxygen consumption by 1.7 ml/kg/min in patients who achieved a respiratory exchange ratio of >0.95 (p = 0.05) and decreased the slope of the ventilatory equivalent ratio for oxygen (-2.8, p = 0.019) in all completers. It did not change SF-36 physical function score compared with placebo (p = 0.28). Ambrisentan therapy resulted in a decrease in (-1.4 g/dl, p <0.001) with no change in liver or renal function. Therapy was generally well tolerated, with no greater rate of side effects than placebo. In conclusion, ambrisentan is well tolerated and improves exercise capacity in adult Fontan patients.