The Cost of Medications at a Student-Run Free Clinic in New Haven, Connecticut, 2021-2023.

Introduction: Haven is a student-run free clinic in New Haven, Connecticut, that serves more than 500 patients annually. Haven's pharmacy department helps patients obtain medications by providing discount coupons or medications from the clinic's in-house pharmacy, directly paying for medications at local pharmacies, and delivering medications to patients' homes. This study aimed to identify prescriptions that have the highest cost among Haven patients. Methods: Our sample consisted of all Haven patients who attended the clinic from March 2021 through March 2023. Patients were eligible to be seen at Haven if they were aged 18 to 65 years, lacked health insurance, and lived in New Haven. We determined the lowest cost of each medication prescribed to Haven patients by comparing prices among local pharmacies after applying a GoodRx discount. We defined expensive medication as more than $20 per prescription. We excluded medical supplies. Results: Of the 594 Haven patients in our sample, 64% (n = 378) required financial assistance and 22% (n = 129) were prescribed at least 1 expensive medication. Among 129 patients prescribed an expensive medication, the mean (SD) age was 45.0 (12.3) years; 65% were women, and 87% were Hispanic or Latino. Median (IQR) household annual income was $14,400 [$0-$24,000]. We identified 246 expensive medications; the median (IQR) price per prescription was $31.43 ($24.00-$52.02). The most frequently prescribed expensive medications were fluticasone propionate/salmeterol (accounting for 6% of all expensive medications), medroxyprogesterone acetate (6%), albuterol sulfate (5%), and rosuvastatin (5%). Conclusion: The average Haven patient has an income well below the federal poverty level, and many have chronic cardiovascular and respiratory conditions that require expensive medications. Future research should work toward making medications universally affordable.

Impact of New-Onset Conduction Disturbances following Transcatheter Aortic Valve Replacement on Outcomes: A Single-Center Study.

Background: Transcatheter aortic valve replacement (TAVR) is known to increase the incidence of conduction disturbances compared to surgical aortic valve replacement; however, there are limited data on the impact and duration of these conduction disturbances on longer term outcomes. Objective: To determine the differential impact of persistent versus nonpersistent new-onset conduction disturbances on TAVR-related complications and outcomes. Methods: This is a single-center retrospective analysis of 927 consecutive patients with aortic stenosis who underwent TAVR at Yale New Haven Hospital from July 2012 to August 2019. Patients with new-onset conduction disturbances within 7 days following TAVR were selected for this study. Persistent and nonpersistent disturbances were, respectively, defined as persisting or not persisting on all patient ECGs for up to 1.5 years after TAVR or until death. Results: Within 7 days after TAVR, conduction disturbances occurred in 42.3% (392/927) of the patients. Conduction disturbances persisted in 150 (38%) patients and did not persist in 187 (48%) patients, and 55 (14%) patients were excluded for having mixed (both persistent and nonpersistent) disturbances. Compared with nonpersistent disturbances, patients with persistent disturbances were more likely to receive a PPM within 7 days after the TAVR procedure (46.0% versus 4.3%, p < 0.001) and had a greater unadjusted 1-year cardiac-related and all-cause mortality risk (HR 2.54, p=0.044 and HR 1.90, p=0.046, respectively). Conclusion: Persistent conduction disturbances were associated with a greater cardiac and all-cause mortality rate at one year following TAVR. Future research should investigate periprocedural factors to reduce persistent conduction disturbances and outcomes beyond one year follow-up.

Effect of antecedent statin usage on conduction disturbances and arrhythmias after transcatheter aortic valve replacement.

BACKGROUND: Post-transcatheter aortic valve replacement (TAVR) conduction disturbances and atrial fibrillation (AF) are associated with markedly worse short- and long-term prognosis. Statins have multiple pleotropic effects that may be beneficial in mitigating the risk of these procedural complications as has been found for various other cardiac procedures and surgeries. METHODS: Data were retrospectively collected on consecutive patients in the Yale New Haven Health TAVR Registry who did not have a prior pacemaker, had at least 1 pre- and post-TAVR electrocardiogram, and did not have a change to their statin regimen during the index hospitalization. The primary endpoint was the composite of new pacemaker placement, new AF, and other new conduction disturbances evaluated at 7 days post-TAVR. RESULTS: Between, July 2012 and August 2019, 612 patients met inclusion criteria. Of these, 162 patients were not on antecedent statins, and 450 were (28 low-intensity, 225 moderate-intensity, and 197 high-intensity). After 1:1 propensity matching, 99 patients on moderate-/high-intensity statins were matched to 99 patients not on antecedent statins. At 7 days, there was no significant difference in the occurrence of the primary endpoint (57 % statin users vs 46 % non-statin users; p = 0.16). There was a trend toward increased conduction disturbances 7 days after TAVR in statin users (56 % vs 42 %; p = 0.07), but rates of AF (5 % vs 8 %; p = 0.39) and pacemaker placement (9 % vs 15 %; p = 0.20) were numerically lower in statin users. There was no significant difference in persistent conduction disturbances (21 % vs 18 %; p = 0.59). CONCLUSIONS: Statins do not appear to reduce the risk of post-TAVR AF or conduction abnormalities in this small retrospective study.

Impact of sex on Transcatheter aortic valve replacement outcomes: Results of a single-center study.

BACKGROUND: Early studies on transcatheter aortic valve replacement (TAVR) outcomes showed that female sex was associated with better survival. With increased use of new-generation valves, the impact of sex on contemporary TAVR outcomes is less well known. METHODS: Retrospective analysis using institutional National Cardiovascular Data Registry STS/ACC TVT data was performed on all patients undergoing TAVR at Yale New Haven Hospital from July 2012 to August 2019. New-generation valves were Evolut PRO, Evolut R, and SAPIEN 3. Old-generation valves were CoreValve, SAPIEN, and SAPIEN XT. Log-rank test and Kaplan-Meier curves were used to compare sex differences in survival up to 1 year after TAVR. Cox modeling was used to adjust for baseline and procedural characteristic differences. RESULTS: 927 consecutive patients (41.4% women) underwent TAVR. Women were older (82.8 vs 80.6 years old; p < 0.001) with higher STS mortality scores compared with men (7.6% vs 6.4%; p < 0.001) despite lower prevalence of cardiovascular comorbidities including coronary artery disease, peripheral artery disease, and smoking. Most cases used transfemoral access (90.5%) and new-generation devices (72.3%). Women received smaller valves compared with men (20-26 mm: 78.0% vs 32.9%; 29-34 mm: 22.1% vs 67.1%; overall p < 0.0001). There were no statistically significant differences between sexes in both unadjusted and adjusted 1-year mortality. CONCLUSION: Our data show no significant difference in 1-year survival between sexes using primarily new generation valves. Further studies should reassess the impact of sex on TAVR outcomes and whether newer technologies like new valve design and sizes, and CT imaging may have eliminated sex-based disparities.

High- versus low-gradient aortic stenosis: Is our evaluation limited by aorto-mitral angle on cardiovascular CT?

BACKGROUND: Accurate assessment of aortic valve (AV) stenosis (AS) on transthoracic echocardiogram is crucial for appropriate clinical management. However, discordance between aortic valve area (AVA) and Doppler can complicate the diagnosis of severe AS in low-gradient (LG) AS phenotypes. METHODS: We reviewed 220 consecutive patients with suspected severe AS and AVA ≤1.0 cm2 on transthoracic echocardiogram who were evaluated for transcatheter AV replacement (TAVR) within a large health system from 2015 to 2019. We compared AV calcium score and aorto-mitral angle (AMA) on 3-chamber views from ECG-gated cardiovascular CT among patients with high-gradient (HG) AS (N = 19), paradoxical low-flow low-gradient (PLFLG) AS (N = 24) and normal-flow low-gradient (NFLG) AS (N = 14). RESULTS: All groups had comparable age, comorbidities, and AV calcium scores. Compared to patients with HG AS (mean AMA 120 ± 10°), those with PLFLG AS (104 ± 12°; p < 0.001) and NFLG AS (106 ± 13°; p = 0.008) had narrower mean AMA values on cardiovascular CT. CONCLUSION: LG AS patients have significantly narrower AMA than HG AS patients on cardiovascular CT. Due to difficulty obtaining parallel Doppler alignment, narrower AMA may contribute to AVA-Doppler discordance on echocardiogram. These findings emphasize the need for additional information in the setting of LG AS.

Cognitive impairment in pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is characterized by progressive pulmonary vascular remodeling with resultant abnormal increase in pulmonary artery pressure and right heart dysfunction. There is evidence that PAH includes cognitive impairment. However, the cognitive impairment syndrome has not been well described, and both the underlying mechanism and the relationship between cardiopulmonary and cognitive dysfunction in PAH are unknown. We performed cognitive evaluations and same day sub-maximum cardiopulmonary exercise testing on adult subjects with PAH. A frontal-subcortical syndrome suggestive of vascular cognitive impairment was found in 26% of subjects and was associated with noninvasive markers of pulmonary vascular remodeling.

Patterns of Digoxin Prescribing for Medicare Beneficiaries in the United States 2013-2019.

Background: Studies show that digoxin use is declining but is still prevalent. Recent data on digoxin prescription and characteristics of digoxin prescribers are unknown, which can help understand its contemporary use. Methods: Using Medicare Part D data from 2013 to 2019, we studied the change in number and proportion of digoxin prescriptions and digoxin prescribers, overall and by specialty. Using logistic regression, we identified prescriber characteristics associated with digoxin prescription. Results: From 2013 to 2019, total digoxin prescriptions (4.6 to 1.8 million) and proportion of digoxin prescribers decreased (9.1% to 4.3% overall; 26.6% to 11.8% among General Medicine prescribers and 65.4% to 48.9% among Cardiology). Of digoxin prescribers from 2013 practicing in 2019 (91.2% remained active), 59.1% did not prescribe digoxin at all, 31.7% reduced, and 9.2% maintained or increased prescriptions. The proportion of all digoxin prescriptions that were prescribed by General Medicine prescribers declined from 59.7% to 48.2% and increased for Cardiology (29% to 38.5%). Among new prescribers in 2019 (N = 85,508), only 1.9% prescribed digoxin. Digoxin prescribers when compared to non-digoxin prescribers were more likely male, graduated from medical school earlier, were located in the Midwest or South, and belonged to Cardiology (all P < .001). Conclusions: Digoxin prescriptions continue to decline with over half of 2013 prescribers no longer prescribing digoxin in 2019. This may be a result of the increasing availability of newer heart failure therapies. The decline in digoxin prescription was greater among general medicine physicians than cardiologists, suggesting a change in digoxin use to a medication prescribed increasingly by specialists.

Characteristics of patients referred to a cardiovascular disease clinic for post-acute sequelae of SARS-CoV-2 infection.

Introduction: There is limited literature on cardiovascular manifestations of post-acute sequelae of SARS-CoV-2 infection (PASC). Methods: This observational study aimed to describe the characteristics, diagnostic evaluations, and new cardiac diagnoses in patients referred to a cardiovascular disease clinic designed for patients with PASC, and to identify factors associated with cardiovascular symptoms with no identifiable cardiac pathology. Results: Of 126 patients, average age was 46 years, and 34 % were male. Patients presented on average five months after COVID-19 diagnosis. The most common symptoms were dyspnea (52 %), chest pain/pressure (48 %), palpitations (44 %), and fatigue (42 %), commonly associated with exertion or exercise intolerance. New cardiovascular diseases were present in 23 % of cases. The remainder exhibited common symptoms which we termed "cardiovascular PASC syndrome." Discussion: We found that only one in four patients had a new cardiovascular diagnosis, but most displayed a pattern of symptoms associated with exercise intolerance.

Patient mutations linked to arrhythmogenic cardiomyopathy enhance calpain-mediated desmoplakin degradation.

Arrhythmogenic cardiomyopathy (ACM) is an inherited disorder with variable genetic etiologies. Here we focused on understanding the precise molecular pathology of a single clinical variant in DSP, the gene encoding desmoplakin. We initially identified a novel missense desmoplakin variant (p.R451G) in a patient diagnosed with biventricular ACM. An extensive single-family ACM cohort was assembled, revealing a pattern of coinheritance for R451G desmoplakin and the ACM phenotype. An in vitro model system using patient-derived induced pluripotent stem cell lines showed depressed levels of desmoplakin in the absence of abnormal electrical propagation. Molecular dynamics simulations of desmoplakin R451G revealed no overt structural changes, but a significant loss of intramolecular interactions surrounding a putative calpain target site was observed. Protein degradation assays of recombinant desmoplakin R451G confirmed increased calpain vulnerability. In silico screening identified a subset of 3 additional ACM-linked desmoplakin missense mutations with apparent enhanced calpain susceptibility, predictions that were confirmed experimentally. Like R451G, these mutations are found in families with biventricular ACM. We conclude that augmented calpain-mediated degradation of desmoplakin represents a shared pathological mechanism for select ACM-linked missense variants. This approach for identifying variants with shared molecular pathologies may represent a powerful new strategy for understanding and treating inherited cardiomyopathies.