BACKGROUND: Optimal timing of pulmonary valve replacement (PVR) in repaired tetralogy of Fallot (rTOF) remains challenging. We hypothesized that pre-PVR artificial intelligence-enabled electrocardiogram (AI-ECG) may info...BACKGROUND: Optimal timing of pulmonary valve replacement (PVR) in repaired tetralogy of Fallot (rTOF) remains challenging. We hypothesized that pre-PVR artificial intelligence-enabled electrocardiogram (AI-ECG) may inform optimal PVR timing in rTOF. METHODS: rTOF PVR patients at Boston Children's Hospital (BCH) and Toronto General Hospital (TGH) with analyzable ECGs ≤3 months pre-PVR were included. Patients undergoing PVR were propensity score-matched 1:1 to non-PVR patients. Patients were partitioned into risk tertiles based on pre-PVR AI-ECG probabilities of 5-year mortality: low-, intermediate-, and high-risk. RESULTS: The PVR cohort included 605 patients (504 at Boston Children's Hospital (BCH), 101 at Toronto General Hospital (TGH); median age 20.3 [IQR, 13.6-32.0] years; median follow-up 7.5 [IQR, 4.7-10.6] years; 3.6% mortality). Pre-PVR AI-ECG risk probability was predictive of post-PVR mortality (c-index 0.77), outperforming an established imaging-based model benchmark (c-index 0.70). AI-ECG remained an independent predictor when added to the benchmark model (P < .001) with a higher c-index of 0.84. Survival was similar between low- and intermediate-risk groups (97-98% 15-year survival; P = .6), with increased mortality for the high-risk group (83% 15-year survival; P = .009). The matched cohort demonstrated that PVR was associated with increased survival overall (HR 0.28 [95% CI, 0.13-0.60], P = .001). Exploratory analyses stratified by risk group tertiles showed survival benefit associated with PVR in the intermediate-risk (HR 0.10 [95% CI, 0.01-0.86]; P = .04) and high-risk (HR 0.3 [0.1-0.7]; P = .005) groups, but not in the low-risk group (P = .8). CONCLUSIONS: AI-ECG predicts post-PVR survival in rTOF patients with a PVR survival benefit in intermediate- and high-risk, but not low-risk, groups. AI-ECG may complement imaging biomarkers to determine rTOF PVR timing.
INTRODUCTION: Coronary microvascular dysfunction (CMD) is increasingly recognized as an important cause of anginal symptoms and poor outcomes. Angina with nonobstructive coronary arteries (ANOCA) is often related to CMD....INTRODUCTION: Coronary microvascular dysfunction (CMD) is increasingly recognized as an important cause of anginal symptoms and poor outcomes. Angina with nonobstructive coronary arteries (ANOCA) is often related to CMD. While physiological assessment of microcirculatory function by coronary bolus thermodilution is widely practiced, more precise and reproducible methodology as well as systematic assessment are necessary. Recently, absolute flow measurements by coronary continuous thermodilution and the concept of Microvascular Resistance Reserve (MRR) have been introduced. AIM: The European microCirculatory Resistance and Absolute Flow Team (EuroCRAFT) registry aims to compare major adverse cardiac and cerebrovascular events (MACCE)-rates in patients with and without CMD based on MRR at 1-year follow-up. METHODS: This prospective international, investigator-initiated, multicenter study is enrolling patients with stable chest pain suggestive of angina and nonobstructive epicardial coronary arteries on invasive coronary angiography, defined as fractional flow reserve >0.80. Patients will undergo coronary angiography and microvascular assessment using bolus and continuous thermodilution methods. The primary endpoint is to compare the rate of MACCE in patients with and without CMD assessed with MRR at 1 year. Based on the sample size estimation, 671 patients are initially planned for enrollment. We hypothesize that coronary continuous thermodilution-derived MRR has superior prognostic value for MACCE at 1 year compared to bolus thermodilution-derived microvascular metrics. RESULTS: Study recruitment started in September 2022 and has been completed in May 2025, resulting in a total of 678 patients enrolled.
Osude N, Granger CB, Young R
… +15 more, Al-Khalidil H, Ward K, Leyva M, Lambert C, Tillery M, Lin A, Mehta R, Satish M, Peigh G, Wright A, Epstein LM, Lundqvist CB, Piccini JP, Sohail MR, Pokorney SD
BACKGROUND: Cardiac implantable electronic device (CIED) infections are a growing concern due to their associated high morbidity, mortality, and healthcare costs. Current guidelines given complete device and lead removal...BACKGROUND: Cardiac implantable electronic device (CIED) infections are a growing concern due to their associated high morbidity, mortality, and healthcare costs. Current guidelines given complete device and lead removal for CIED infection a class I recommendation, yet adherence to these guidelines is low with delays in extraction associated with poor adverse clinical events. OBEJCTIVES: To determine the effect of implementation of quality improvement (QI) interventions on patients with CIED infections, including rates of extraction and time to extraction. METHODS: This is a prospective interventional study conducted across 3 U.S. health systems that employs QI interventions aimed at increasing early identification of CIED infections. The study will have a retrospective review of treatment of CIED infection patients, followed by a 6-month QI intervention period, and a 12-month prospective data collection period after the QI intervention. Eligible patients will have a CIED and a presumed CIED infection (pocket or systemic infection). The primary endpoints are the change in the number of extractions performed for CIED infections and the time to extraction during the study. CONCLUSIONS: The REview and improvement of Cardiac implanTable device InFection qualitY initiative (RECTIFY) is a multi-center demonstration project aimed to identify and address health system-wide barriers to timely diagnosis and guideline-driven management of CIED infections. TRIAL REGISTRATION: The trial was registered with the U.S. National Library of Medicine at the National Institutes of Health (NCT05471973).
AIM: Shockable rhythm on initial electrocardiogram is a predictor of favorable neurological outcomes of out-of-hospital cardiac arrest in patients undergoing extracorporeal cardiopulmonary resuscitation (ECPR). The prese...AIM: Shockable rhythm on initial electrocardiogram is a predictor of favorable neurological outcomes of out-of-hospital cardiac arrest in patients undergoing extracorporeal cardiopulmonary resuscitation (ECPR). The present study evaluated the impact of conversion from shockable rhythm to pulseless electrical activity (PEA) before ECPR on patient outcomes. METHODS: In this secondary analysis of the data from SAVE-J II, a retrospective multicenter registry including 36 participating institutions in Japan, patients with initial shockable rhythm were categorized into those with conversion to PEA and sustained shockable rhythm. The primary outcome was favorable neurological outcome, defined as a cerebral performance category of 1-2 at hospital discharge. RESULTS: The final cohort included 718 patients. The rate of favorable neurological outcomes was lower in patients who were converted to PEA than in those with sustained shockable rhythm (12.9 % vs 26.4 %, P < .01). By multivariable analysis, conversion to PEA was significantly associated with a lower rate of favorable neurological outcomes (odds ratio 0.42, 95% confidence interval 0.27-0.66; P < .01). The rates of favorable neurologic outcomes were 9.8%, 18.0%, and 21.4% (P = .06) in patients who converted to PEA, during emergency medical services transport, at hospital arrival, and before ECMO initiation, respectively. However, outcomes did not significantly differ between the patients who converted to PEA after hospital arrival and those with sustained shockable rhythm (19.6% vs 26.4%, P = .19). CONCLUSIONS: Patients with conversion to PEA before ECPR were associated with a lower rate of favorable neurological outcomes in those with an initial shockable rhythm. Especially, early conversion to PEA, ie, during EMS transport, may be a factor for lower favorable neurological outcomes compared to those with sustained shockable rhythm.
BACKGROUND: Left atrial (LA) stiffness is linked to pulmonary congestion and exercise intolerance in patients with acquired form of heart failure but has not been studied in adults with coarctation of aorta (COA). We hyp...BACKGROUND: Left atrial (LA) stiffness is linked to pulmonary congestion and exercise intolerance in patients with acquired form of heart failure but has not been studied in adults with coarctation of aorta (COA). We hypothesized that adults with COA had increased LA stiffness, and in turn, worse cardiac reserve, pulmonary congestion, and impaired aerobic capacity compared to controls, and that LA stiffness index was associated with the presence of these abnormalities in the COA group. METHOD: In this prospective study, 46 adults with repaired COA and 46 controls underwent exercise echocardiogram with expired gas analysis. LA stiffness was assessed at rest as the quotient for lateral E/e' and LA reservoir strain (E/e'/LARS). Cardiac reserve was assessed by exercise-induced change in LA reservoir strain, right ventricular free wall strain/right ventricular systolic pressure (RV-PA coupling), and cardiac output (CO). Pulmonary congestion was assessed by lung ultrasound. RESULTS: The COA group had higher LA stiffness index (0.47 ± 0.12 vs 0.14 ± 0.09, P < .001), and in turn, worse cardiac reserve, pulmonary congestion, and aerobic capacity compared to controls. Within the COA group, those with high LA stiffness index (>0.42) had worse cardiac reserve, pulmonary congestion, and aerobic capacity. The correlates of LA stiffness index were high pulsatile left ventricular (LV) afterload, LV hypertrophy, and atrial fibrillation. CONCLUSIONS: These data suggest a mechanistic link between LA stiffness, pulmonary congestion, and exercise intolerance among patients with COA, and the correlates of LA stiffness index may provide viable targets for therapeutic interventions to improve outcomes in this population.
BACKGROUND AND AIMS: Heart transplantation is the preferred treatment for selected patients with end stage heart failure. Kidney function often declines after heart transplantation. Sodium-glucose cotransporter 2 inhibit...BACKGROUND AND AIMS: Heart transplantation is the preferred treatment for selected patients with end stage heart failure. Kidney function often declines after heart transplantation. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) slow the decline in eGFR in different populations. However, the effect of SGLT2i on kidney function in heart transplant recipients is unknown. METHODS: The Dapagliflozin for Renal protection in Heart Transplant recipients (DAPARHT) trial is an investigator initiated, double blind, randomized, placebo-controlled trial designed to assess dapagliflozin's effect on kidney function in heart transplant recipients. Adults heart transplanted at least one year prior to randomization are eligible. Exclusion criteria include an estimated glomerular filtration rate (eGFR) <25 mL/min/1.73 m, diabetes type I, and contraindication to study medication. Four hundred and thirty patients will be randomized 1:1 to receive 12 months blinded treatment with dapagliflozin 10 mg o.d. or placebo, followed by 24-months open-label treatment. The primary endpoint is the chronic slope of the eGFR from two weeks to 12 months after starting randomized treatment. The open-label phase evaluates dapagliflozin's long-term effects on kidney function, clinical outcomes, safety, and tolerability. Enrolment began in June 2022. As of December 18, 2024, 300 patients were enrolled. The mean baseline creatinine was 104 ± 28 µmol/L with corresponding eGFR of 66 ± 22 mL/min/1.73 m. Estimated last patient visit is in September, 2028. CONCLUSION: The DAPARHT trial will test whether dapagliflozin improves eGFR slope compared to placebo during one year of follow-up, providing the first randomized evidence of the efficacy of SGLT2i in heart transplant recipients. TRIAL REGISTRATION: Dapagliflozin for Renal protection in Heart Transplant recipients (DAPARHT), NCT05321706, clinicaltrials.gov.
RATIONALE: Patients with a Fontan circulation suffer from progressive multiorgan dysfunction, yet central biochemical drivers remain poorly defined. Our recent work exploring metabolomic analyses have identified - elevat...RATIONALE: Patients with a Fontan circulation suffer from progressive multiorgan dysfunction, yet central biochemical drivers remain poorly defined. Our recent work exploring metabolomic analyses have identified - elevated circulating bile acids (BAs) in adult Fontan patients compared with healthy controls. Elevated BAs, especially secondary and hydrophobic ones produced by the gut microbiome were found to correlate with worse exercise capacity, greater frailty, and impaired hemodynamics. PRIMARY HYPOTHESIS: Bile acid accumulation may contribute to Fontan pathophysiology. Colesevelam, a nonabsorbed bile acid sequestrant, offers a potential targeted therapy to reduce BA levels and interrupt this disease pathway. DESIGN: The MYSTIC trial is a prospective, randomized, double-blind, placebo-controlled cross-over pilot study in 25 adult Fontan patients (with 25 age- and sex-matched healthy controls for baseline comparisons) to evaluate the safety, tolerability, and efficacy of colesevelam in lowering plasma BA levels. Primary outcomes include safety/tolerability and change in total plasma BA levels. Secondary outcomes include changes in noninvasive hemodynamics, gut microbiome composition, fecal bile acid excretion, and biochemical profiles. SITES: Single center. ESTIMATED ENROLLMENT: 25 patients and 25 healthy subjects. ENROLLMENT DATES: September 2025 to August 2027. TRIAL REGISTRATION: NCT06197763 This manuscript describes the rationale and design of the MYSTIC study, which to our knowledge is the first interventional trial targeting a Fontan-specific metabolic derangement. The results will inform the feasibility of BA sequestration therapy in Fontan patients and guide future larger studies aimed at improving outcomes in this growing high-risk population.
Goldstein SA, Edwards LA, Nilles EK
… +10 more, Chiswell K, D'Ottavio A, Reeder MR, Wood K, Sethi N, Raskind-Hood CL, Book WM, Feldkamp ML, Li JS, Botto LD
BACKGROUND: Infants born to women with congenital heart disease (CHD) are at increased risk for adverse outcomes compared with the general population. There are few large, contemporary studies examining the relationship...BACKGROUND: Infants born to women with congenital heart disease (CHD) are at increased risk for adverse outcomes compared with the general population. There are few large, contemporary studies examining the relationship between CHD severity, maternal risk factors and neonatal outcomes. METHODS: Data on women with CHD who had a live birth from 2011 through 2014 in geographic areas in Georgia, North Carolina and Utah were analyzed. Maternal CHD was identified from clinical and administrative data collected for the CDC Lifespan CHD surveillance project. CHD was categorized as severe and non-severe (shunt, valve or shunt+valve lesions). Linked birth certificates provided information on neonatal outcomes and neonatal, maternal and pregnancy characteristics. Neonatal outcomes included preterm delivery (<37 weeks), low birth weight (<2,500 grams), small for gestational age (SGA), neonatal intensive care unit (NICU) admission, a composite of any adverse outcome (one or more of preterm delivery, SGA or NICU admission), and CHD. Neonatal outcomes were summarized using descriptive statistics. Differences by maternal CHD severity were assessed using Wilcoxon rank-sum and Chi-square tests for continuous and categorical variables, respectively. The association of maternal and pregnancy characteristics (race, pregestational diabetes (PGDM), hypertensive disorders of pregnancy (HDP), prior preterm birth, non-singleton pregnancy, maternal age, previous living live birth and CHD severity) with neonatal outcomes were assessed using logistic regression fit using generalized estimating equations clustered on mother and adjusted for mother's age, birth year and geographical location of delivery. RESULTS: Of the 2,411 liveborn infants born to 1,982 women with CHD (34% with severe CHD), 19% were preterm, 18% were of low birth weight, 14% were SGA and 4.2% were diagnosed with CHD. Of the included infants, 25% required NICU and 40% experienced the composite adverse outcome. Infants born to mothers with severe CHD (vs non-severe) were more likely to experience the composite adverse outcome (aOR 2.1 [1.8, 2.5]) and CHD recurrence (aOR 17.1 [9.3, 31.5]). In a multivariable analysis, severe CHD (vs non-severe, aOR 2.2 [1.8, 2.7]), Black race (vs White, aOR 1.8 [1.4, 2.3]), PGDM (aOR 2.5 [1.3, 5.0]), hypertensive disorder of pregnancy (aOR 2.1 [1.5, 3.1]), prior preterm birth (aOR 2.0 [1.3, 3.1]), and non-singleton pregnancy (aOR 6.7 [3.8, 11.6]) were associated with increased risk of the composite adverse outcome. CONCLUSIONS: Nearly half of infants born to women with CHD experienced the adverse composite neonatal outcome, with the highest risk among those born to women with severe CHD. In addition to CHD severity, risk factors for adverse neonatal outcomes among women with CHD included black race, hypertensive disorders of pregnancy, PGDM, prior preterm birth and non-singleton pregnancy. These findings can help provide individualized counseling about neonatal risks for women with CHD.
Tsigkas G, Trigka-Vasilakopoulou A, Apostolos A
… +24 more, Papafaklis M, Colletti G, Mugnolo A, Ruzsa Z, Ungureanu C, Nikas D, Xaplanteris P, Gasparini GL, Sciahbasi A, Tsiafoutis I, Poulimenos LE, Didagelos M, Pappas L, Stougiannos P, Hamilos M, Ziakas A, Timpilis F, Karanasos A, Moulias A, Sgueglia GA, Aminian A, Iglesias JF, Michalis L, Davlouros P
RATIONALE: Transradial access (TRA) constitutes the cornerstone for cardiac catheterization and is recommended by the multiple recent guidelines, irrespective of clinical presentation. The existing literature has evaluat...RATIONALE: Transradial access (TRA) constitutes the cornerstone for cardiac catheterization and is recommended by the multiple recent guidelines, irrespective of clinical presentation. The existing literature has evaluated distal transradial access (dTRA), as a feasible and safe approach in patients with chronic and acute coronary syndrome, excluding although patients presenting with ST- elevation myocardial infraction (STEMI). PRIMARY HYPOTHESIS: The current randomized clinical trial compares dTRA versus conventional TRA access in patients with STEMI undergoing coronary angiography and interventions regarding peri‑ and postprocedural characteristics. DESIGN: DR-STEMI is a prospective, open label, European, multicenter randomized-control trial which will include 554 patients (277 patients in each treatment arm). Patients with STEMI, will be screened on an all-comers basis for study inclusion and exclusion criteria, and those eligible will be allocated randomly (1:1), to dTRA versus TRA approach. The primary hypothesis of the study is that dTRA is noninferior to conventional TRA regarding the required time between the puncture of the radial artery and wire crossing of the infarct-related artery (i.e., needle-to-wire time). CURRENT STATUS: Enrollment for the DR-STEMI trial began in May 2024, and as of April 15th 2025, 309 patients have been enrolled in the study. Recruitment is expected to continue for approximately 12 months. TRIAL REGISTRATION: clinicaltrials.gov: NCT05605288.
BACKGROUND: Cerebral embolization is a common complication following transcatheter aortic valve replacement (TAVR). Cerebral embolic protection (CEP) devices have the potential to reduce embolic burden to the cerebral ci...BACKGROUND: Cerebral embolization is a common complication following transcatheter aortic valve replacement (TAVR). Cerebral embolic protection (CEP) devices have the potential to reduce embolic burden to the cerebral circulation; however, their effectiveness in real-world patients at high risk of stroke remains insufficiently studied. METHODS: As part of imaging study of the prospective Sentinel registry (NCT05217888), we evaluated the effect of CEP on new cerebral embolism as determined by brain magnetic resonance imaging (MRI) in patients undergoing transfemoral TAVR who were considered at high risk for stroke. The primary endpoint was the number and volume of new cerebral lesions on brain MRI at postprocedure (2 to 7 days) compared to baseline in protected brain territories. The control group consists of enrolled patients in the ADAPT-TAVR trial (NCT03284827), in which TAVR was performed without the use of a CEP device. RESULTS: A total of 219 patients was included (49 in the SENTINEL registry and 170 patients in the ADAPT-TAVR trial). For the primary endpoint, the number and volume of new cerebral lesions was significantly lower in the CEP group than in the control group: the median no. of lesions; 1 (interquartile range [IQR], 1 to 2) vs 6 (IQR, 3 to 10), respectively; difference, -4 [IQR, -6 to -3]; P < .001, and the median volume of lesions; 113.5 mm (IQR, 42.4-206.9) vs 283.5 mm (IQR, 129.7-682.4), respectively; difference, -145.9 [IQR, -296.7 to -67.1]; P < .001). Strokes at 30 days occurred in 1 patient (2.0%) in the CEP group and 2 patients (1.2%) in the control group (P = .64). CONCLUSIONS: Among patients who are at high risk for stroke undergoing TAVR, the use of CEP was associated with a significant reduction of new cerebral embolism in protected brain territories. Because the study was underpowered to detect clinically relevant events, the results cannot be considered clinically directive. CLINICAL TRAIL REGISTRATION: http://ClinicalTrials.gov (Identifier: NCT05217888).
BACKGROUND: Concerns regarding side-effects of beta-blockers (BBs) are frequent but data regarding the incidence of side-effects are conflicting and real-world data are sparse. Hence, we aimed to investigate the absolute...BACKGROUND: Concerns regarding side-effects of beta-blockers (BBs) are frequent but data regarding the incidence of side-effects are conflicting and real-world data are sparse. Hence, we aimed to investigate the absolute and relative risks of BB side-effects in clinical practice. METHODS: Using Danish nationwide registers, we included Danish hypertensive patients initiating antihypertensive treatment with a BB or calcium-channel blocker (CCB). We computed crude as well as standardized 1-year risks and adjusted risk ratios of BB side-effects (depression, anxiety/insomnia, gastrointestinal side-effects, erectile dysfunction, and dizziness/fainting) compared with CCB treatment. RESULTS: We included 64,722 patients initiating treatment with a BB and 181,880 patients initiating treatment with a CCB. In patients initiated on BB, the standardized 1-year risk of any outcome, erectile dysfunction exempt, was 13.7% (95% CI: 13.4%-13.9%). The 1-year risk of specific BB side-effects was the highest for anxiety/insomnia (6.2%, 95% CI: 6.0%-6.3%), gastrointestinal side-effects (4.6%, 95% CI: 4.4%-4.7%), and erectile dysfunction (4.7%, 95% CI: 4.5%-4.9%). The risk of side-effects was consistently increased when comparing BB treatment with CCBs including depression (Risk Ratio [RR] 1.48, 95% CI 1.41-1.55), anxiety/insomnia (RR 1.53, 95% CI 1.47-1.59), gastrointestinal side-effects (1.31, 95% CI 1.25-1.36), and dizziness/fainting (RR 1.50, 95% CI 1.38-1.61), but not erectile dysfunction (RR 0.91, 95% CI, 0.85-0.96). CONCLUSIONS: In a large nationwide cohort, the incidence of BB side-effects was clinically relevant and consistently increased compared with CCBs with the exception of erectile dysfunction, which carried similar risks for both treatments.
Bayne J, Duan R, Rudov L
… +21 more, Mehta R, Phillippi R, Roeder M, Saraf S, Jackson JL, Lewis M, Saidi A, Kanter R, Sandhu S, Young T, Jacobsen R, Ruckdeschel E, Lubert A, Singh H, Zaidi A, Halpern DG, Leezer S, John AS, Carton T, Agarwal A, Congenital Heart Initiative-Redefining Outcomes and Navigation to an Adult-centered Care (CHI-RON) Investigators
BACKGROUND: Guidelines recommend lifelong care with adult congenital heart disease (ACHD) specialists for adults with congenital heart disease (CHD). However, such gaps in visits at specialized ACHD centers have not been...BACKGROUND: Guidelines recommend lifelong care with adult congenital heart disease (ACHD) specialists for adults with congenital heart disease (CHD). However, such gaps in visits at specialized ACHD centers have not been well-characterized from diverse US settings. METHODS: This retrospective study analyzed data from 12 centers in the national Patient-Centered Clinical Research Network. CHD conditions were classified using International Classification of Disease codes and a hierarchical algorithm. ACHD specialists were identified by investigators and encounter volumes. Data from the 'Pre-COVID' (2015-2019) and 'COVID' (2020-2022) periods were analyzed separately. Main outcome measures were: 1) Gaps in any ACHD specialist visit and recommended testing throughout the study period. 2) Gaps in recommended ACHD follow-up care. RESULTS: During pre-COVID (N = 18,934) and COVID (N = 22,453) periods, between 55.3%-55.8% were males, 27.2%-31.0% were 40+ years, 18.2%-19.6% had severe CHD, and 52.7%-55.0% had CHD physiologic class B-D conditions. Between 47.0%-54.5% had gaps in specialist visit and 13.0%-24.6% had gaps in all the testing. Patients with gaps in specialist visits were 6.33-9.44 times more likely to have gaps in testing. Gaps were more common among patients with moderate (adjusted odds ratio [AOR]: 2.61) and simple (AOR: 2.84) CHD, those aged 40+ (AOR: 1.53) and nonphysiologic class conditions (AOR 1.51). In both periods, 64.1%-71.5% of patients had gaps in follow-up care. CONCLUSIONS: Three-quarters of adults with CHD experienced gaps in specialized ACHD care while receiving services at high volume comprehensive tertiary health centers. To address these gaps, interventions such as fostering physician collaboration within tertiary centers might be needed, and targeted to patients with less severe CHD, nonphysiologic class conditions, and those aged 40+ years.
BACKGROUND: Prior to 2025, Medicare Part D included a coverage gap during which beneficiaries were responsible for substantially higher portions of medication costs. The impact of this on oral anticoagulant (OAC) prescri...BACKGROUND: Prior to 2025, Medicare Part D included a coverage gap during which beneficiaries were responsible for substantially higher portions of medication costs. The impact of this on oral anticoagulant (OAC) prescription fills and subsequent stroke in patients with atrial fibrillation (AF) is not known. METHODS: Using Centers for Medicare and Medicaid Services claims data from 2016 to 2018, we evaluated OAC prescription fills in patients with AF by assessing their proportion of days covered on OAC before, during, and after their coverage gap. Hazard of stroke was assessed for patients who entered the coverage gap before entering, while in, and after exiting, the gap. RESULTS: Patients who entered the coverage gap had a 16% decrease in median proportion of days covered from pregap (0.92 [interquartile range 0.80, 0.97]) to in-gap (0.76 [0.41, 0.98]). Proportion of days covered continued to drop for patients who entered and then left the coverage gap, despite regaining coverage (pregap: 0.95 [0.85, 0.98]; in-gap: 0.88 [0.55, 0.97]; postgap: 0.70 [0.00, 1.00]). Patients who entered the gap were at significantly higher risk for stroke while in the gap (HR 2.21, 95% CI 1.91-2.54) and during the combined in-gap and postgap periods (HR 3.13, 95% CI 2.71-3.62). CONCLUSIONS: OAC use decreased upon entering the coverage gap and was associated with an increased stroke risk, that persisted for the rest of the calendar year. Health policy decisions regarding Medicare can have unintended adverse public health consequences, highlighting the importance of assessing the impact of such policy changes.
BACKGROUND: Randomized clinical trials from over 20 years ago demonstrated that an implantable cardioverter defibrillator (ICD) improved survival for patients with severely reduced left ventricular ejection fraction (LVE...BACKGROUND: Randomized clinical trials from over 20 years ago demonstrated that an implantable cardioverter defibrillator (ICD) improved survival for patients with severely reduced left ventricular ejection fraction (LVEF) after myocardial infarction (MI) compared with optimal medical therapy (OMT) alone. Since then advances in therapy have led to the reduction in the incidence of sudden cardiac death (SCD) in this population, whilst complication rates from ICD implantation are still substantial. OBJECTIVES: To determine whether OMT without ICD implantation is not inferior to OMT with ICD implantation with respect to all-cause mortality. DESIGN: The PROFID EHRA trial is an investigator-driven, prospective, parallel-group, randomized, open-label, blinded outcome assessment (PROBE), multi-center, noninferiority trial without dedicated investigational medical device (Proof of Strategy Trial) with 2 groups with 1:1 randomization. PROFID-EHRA will recruit approximately 3,595 patients with documented history of MI at least 3 months prior, LVEF ≤35%, on OMT for at least 3 months, and with New York Heart Association class II or III, who will be randomized to OMT or OMT plus ICD, to collect 374 first primary outcome events within a median observation period of around 28 months from about 180 clinical sites in an estimated 13 countries. The primary outcome is time from randomization to the occurrence of all-cause death. Secondary outcomes include time from randomization to death from cardiovascular causes, to SCD, to first hospital readmission for cardiovascular causes after date of randomization, the average length of hospital stay during follow-up, and quality of life trajectories. CLINICAL TRIAL: Trials.gov NCT05665608.
BACKGROUND: The impact of low-density lipoprotein cholesterol (LDL-C) on atherosclerotic cardiovascular disease (ASCVD) risk is influenced by both the magnitude and duration of exposure. Patients with nonobstructive coro...BACKGROUND: The impact of low-density lipoprotein cholesterol (LDL-C) on atherosclerotic cardiovascular disease (ASCVD) risk is influenced by both the magnitude and duration of exposure. Patients with nonobstructive coronary artery disease (NOCAD) and a CT-adapted Leaman score (CT-LeSc) >5 have a higher risk of cardiac events. The CT-LeSc semi-quantitatively assesses total coronary atherosclerotic burden via coronary computed tomography angiography (CCTA). Treatment with an antiproprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibody (mAb) leads to significant reductions in LDL-C levels. The addition of an anti-PCSK9 mAb to statin therapy produced greater LDL-C lowering and significant reduction in percent atheroma volume (PAV) and total atheroma volume (TAV) in patients with CAD. Inclisiran, a small-interfering ribonucleic acid (siRNA) therapy, targets PCSK9 messenger ribonucleic acid (mRNA) to reduce LDL-C levels by approximately 50% providing sustained and effective long-term LDL-C reduction after an initial and 90-day dose and a favorable safety profile alongside maximally tolerated statins. A similar treatment impact on total atheroma volume reduction is therefore hypothetically expected with inclisiran, given its exceptional dosing interval. METHODS: VICTORION-PLAQUE is a multicenter, international, randomized, double-blind, placebo-controlled trial assessing inclisiran's efficacy in reducing total coronary atheroma volume in patients with NOCAD without prior cardiovascular (CV) events. Patients receive inclisiran or placebo in addition to maximally tolerated high-intensity statin therapy. The primary objective is to demonstrate inclisiran's superiority compared to placebo in reducing total coronary atheroma volume, measured by CCTA, from baseline to Month 24. The primary endpoint is percentage change from baseline to Month 24 in total coronary atheroma volume. Secondary endpoints include percentage change in LDL-C from baseline to Month 24, percentage change in low attenuation plaque volume evaluated by CCTA, percentage of participants with progression, regression, or no change in total plaque atheroma volume, and incidence and severity of treatment-emergent adverse event (TEAEs) and serious adverse event (SAEs) and their relationship with the study drug. In total, 608 patients have been randomized at 96 sites across 18 countries worldwide and enrolment was closed on October 25, 2024. SUMMARY: The VICTORION-PLAQUE study evaluates the efficacy of inclisiran, compared with placebo, on top of maximally tolerated statin therapy, in reducing total coronary atheroma volume in NOCAD patients, as assessed by CCTA. TRIAL REGISTRATION: ClinicalTrials.gov. Identifier: NCT05360446.
BACKGROUND: The high-dose inactivated influenza vaccine (HD-IIV) has been shown to reduce the incidence of influenza infection compared with standard-dose inactivated influenza vaccine (SD-IIV); however, its effectivenes...BACKGROUND: The high-dose inactivated influenza vaccine (HD-IIV) has been shown to reduce the incidence of influenza infection compared with standard-dose inactivated influenza vaccine (SD-IIV); however, its effectiveness in preventing severe respiratory and cardiovascular outcomes in the older general population has not yet been assessed in a fully powered individually randomized trial. METHODS: DANFLU-2 is an ongoing pragmatic, registry-based, open-label, active-controlled, individually randomized trial conducted in Denmark during the 2022/2023, 2023/2024, and 2024/2025 influenza seasons. Utilizing innovative electronic recruitment strategies and an online informed consent process, the trial has enrolled 332,438 older adults ≥65 years; enrollment was completed in October 2024. Participants were randomly allocated in a 1:1 ratio to either HD-IIV or SD-IIV. Baseline, endpoint, and safety data are primarily obtained from the nationwide Danish administrative health registries. The primary endpoint is hospitalization for influenza or pneumonia with the trial also powered to assess the first secondary endpoint of hospitalization for any cardio-respiratory disease. The additional secondary endpoints of all-cause hospitalization and mortality will be tested hierarchically. Key ancillary analyses include cost-effectiveness and health care resource consumption assessments as well as a home self-swab sub-cohort. DISCUSSION: DANFLU-2 is the largest individually randomized influenza vaccine trial ever conducted and will provide critical, high-quality evidence on the effectiveness of HD-IIV against cardio-respiratory hospitalizations and mortality in the older general population. TRIAL REGISTRATION: Clinicaltrials.gov: NCT05517174, registered August 24, 2022, https://clinicaltrials.gov/study/NCT05517174.
The low-risk TAVR vs SAVR RCTs - PARTNER-3, Evolut Low-Risk, DEDICATE, and NOTION-2 - demonstrate that TAVR is at least as effective as SAVR in terms of early mortality and disabling stroke, although outcomes varied acro...The low-risk TAVR vs SAVR RCTs - PARTNER-3, Evolut Low-Risk, DEDICATE, and NOTION-2 - demonstrate that TAVR is at least as effective as SAVR in terms of early mortality and disabling stroke, although outcomes varied across studies. The excellent outcomes observed in the PARTNER-3 trial reflect the highly selected patient population, while the NOTION-2 trial highlights the challenges posed by anatomical variations, such as bicuspid aortic valves (AV). These findings highlight the importance of a personalized approach guided by a multidisciplinary Heart Team, taking into account both clinical and anatomical aspects when choosing between TAVR and SAVR. Trial registration number: ClinicalTrials.gov NCT02825134.