Sheth T, Rodes Cabau J, Poon K
… +17 more, Paradis JM, Fam N, Murdoch D, Al-Nasser S, Chandavimol M, Chavarria J, Dick A, Bizios A, Diamantouros P, Yap J, Chatfield A, Ihdayhid AR, Palmer S, Said Vega N, Velianou J, Parpia S, Suleman M
BACKGROUND: This study evaluated the ability of the ABC Bicuspid Sizing Algorithm to predict aortic root rupture in patients treated with transcatheter aortic valve replacement using SAPIEN 3 valves. METHODS: We conducte...BACKGROUND: This study evaluated the ability of the ABC Bicuspid Sizing Algorithm to predict aortic root rupture in patients treated with transcatheter aortic valve replacement using SAPIEN 3 valves. METHODS: We conducted a retrospective multicenter study among 15 centers in 7 countries of aortic root rupture cases and controls without root complications. Computed tomography analysis was performed blinded to rupture status. The ABC algorithm was applied to classify risk (high-risk criteria): (1) annular oversizing >10%, (2) intercommissural distance - valve diameter ≤1 mm, (3) maximum sinus diameter - valve diameter <6 mm alone, or (4) maximum sinus diameter - valve diameter 6 to 8 mm with contrast calcium volume >1000 mm and raphe + contralateral or ipsilateral leaflet calcium volume >800 mm, (5) protruding nodular intercommissural distance calcium or full-length calcification of both leaflet edges. RESULTS: A total of 170 patients were included (23 ruptures and 147 controls). Cases exhibited higher total calcium volume (median: 1498 mm versus 826 mm; <0.001), smaller intercommissural distance difference (median: -0.15 versus 1.19 mm; =0.009), smaller maximum sinus difference (median: 6.79 versus 9.19 mm; <0.001), and greater annular oversizing (median: 6.57% versus 3.51%; =0.047). The presence of any high-risk criterion had a sensitivity of 100% (95% CI, 85.7%-100%) and a specificity of 89.1% (95% CI, 83.1%-93.2%) for the identification of rupture cases. The diagnostic odds ratio was 374.5 (95% CI, 21.7-6459.9), with a positive likelihood ratio of 9.19 and a negative likelihood ratio of 0.023. CONCLUSIONS: High calcium volume, narrow sinus dimensions, and excessive valve oversizing were associated with aortic root rupture. The ABC algorithm showed promising performance for risk stratification of patients with bicuspid anatomy being considered for treatment with a SAPIEN 3 valve.
BACKGROUND: Spontaneous automaticity of sinoatrial node cells (SANCs) is driven by a system that couples ion channels, membrane clock and Caclock, the sarcoplasmic reticulum generated LCRs (local subsarcolemmal Carelease...BACKGROUND: Spontaneous automaticity of sinoatrial node cells (SANCs) is driven by a system that couples ion channels, membrane clock and Caclock, the sarcoplasmic reticulum generated LCRs (local subsarcolemmal Careleases). Although LCRs are critically dependent on high basal cAMP and both PKA (protein kinase A)- and CaMKII (Ca2+/calmodulin dependent protein kinase II)-dependent protein phosphorylation, the link between cAMP and CaMKII remains unclear. Here, we tested a hypothesis that high cAMP activates EPAC (exchange protein directly activated by cAMP) which increases basal CaMKII activity, reinforcing the coupled clock pacemaker system, to boost LCRs and accelerate spontaneous SANC firing. METHODS: Real-time quantitative polymerase chain reaction, Western blot, immunostaining, whole-cell patch clamp, and line-scan confocal microscopy were employed to study EPAC-dependent regulation of rabbit SANC firing. RESULTS: Both EPAC isoforms were expressed and active in SANC. Selective inhibition of EPAC1 (CE3F4) or EPAC2 (HJC0350) similarly suppressed basal CaMKII activity, CaMKII-dependent phosphorylation of Ca-cycling proteins (PLB [phospholamban] and RyR [ryanodine receptors]) and reduced the amplitude of L-type Cacurrent. EPAC1 and EPAC2 inhibitors significantly decreased LCR number, size, and prolonged the LCR period (interval between prior AP-induced Catransient and LCR) reducing spontaneous SANC firing by ≈30%. In contrast, EPAC activator (8-pCPT) increased LCR number and size, shortened the LCR period and accelerated spontaneous firing by≈18%. EPAC-mediated effects were implemented in PKC-dependent manner via EPAC-PLC-PKC-CaMKII signaling pathway, since PKC inhibitor reproduced effects of EPAC inhibition on CaMKII activity, CaMKII-dependent phosphorylation of Ca-cycling proteins, LCR parameters, and spontaneous SANC firing. CONCLUSIONS: EPAC is an essential component of basal cardiac pacemaker function, which accelerates spontaneous automaticity of SANC via an increase in basal CaMKII-dependent phosphorylation of Ca-cycling proteins (PLB, RyR, L-type Cachannels, and likely others), leading to amplification of LCR parameters, shortening of LCR timing and resultant spontaneous cycle length. Consequently, EPAC might represent a novel therapeutic target to regulate resting heart rate and treat sinoatrial node dysfunction.
BACKGROUND: Right ventricular-pulmonary arterial coupling is a known prognostic marker in patients with tricuspid regurgitation (TR). However, its assessment by cardiac magnetic resonance and its clinical implications ha...BACKGROUND: Right ventricular-pulmonary arterial coupling is a known prognostic marker in patients with tricuspid regurgitation (TR). However, its assessment by cardiac magnetic resonance and its clinical implications have not been evaluated. We aimed to assess the prognostic role of a cardiac magnetic resonance surrogate of right ventricular-pulmonary arterial coupling in a large cohort of patients with a spectrum of TR severity. METHODS: Comprehensive data were collected from patients referred for cardiac magnetic resonance from 2019 to 2024 who had TR quantification. Right ventricular-pulmonary arterial coupling was calculated by dividing the forward right ventricular stroke volume (f-RVSV) by the right ventricular end-systolic volume (ESV). The outcome of interest was the composite of all-cause death and heart failure hospitalization, under medical management. RESULTS: In the 631 patients included, median age was 66 (interquartile range [IQR], 54-75) years, median tricuspid regurgitant volume was 18 (IQR, 12-30 mL), median left ventricular ejection fraction was 53 (IQR, 41-61)%, median RV ejection fraction was 53 (IQR, 45-58)%, and median f-RVSV/ESV ratio was 0.82 (IQR, 0.58-1.11). In restricted spline curve analysis, the f-RVSV/ESV ratio cutoff associated with a hazard >1 for the composite outcome was ≤0.57. At baseline, a low f-RVSV/ESV ratio was strongly associated with subjective and objective signs of right heart failure, higher TRI-SCORE, and worse right-sided chamber remodeling (all <0.001). After a median follow-up of 1.8 years (IQR, 1.5-2.0), patients with a low f-RVSV/ESV ratio showed worse survival (<0.001). After comprehensive adjustment for clinical and imaging confounders, f-RVSV/ESV ≤0.57 remained a powerful predictor of outcome (adjusted hazard ratio, 2.36 [95% CI, 1.27-4.37]; =0.004). Finally, patients with low f-RVSV/ESV displayed a worse long-term prognosis across mild, moderate, and severe TR groups (<0.001, <0.001, and =0.018, respectively). CONCLUSIONS: In this large cohort of patients with a wide spectrum of TR severity, right ventricular-pulmonary arterial coupling assessed by cardiac magnetic resonance was strongly associated with right-sided heart failure and worse long-term prognosis, even after comprehensive adjustment.
BACKGROUND: The origins of left ventricular outflow tract premature ventricular contractions (PVCs) differ in depth and may involve preferential pathways, potentially requiring complex ablation. However, a noninvasive me...BACKGROUND: The origins of left ventricular outflow tract premature ventricular contractions (PVCs) differ in depth and may involve preferential pathways, potentially requiring complex ablation. However, a noninvasive method to preprocedurally estimate ablation complexity has not been established. METHODS: Sixteen patients with idiopathic left ventricular outflow tract PVCs (V2 transition ratio ≥0.6) underwent 2-dimensional speckle-tracking echocardiography during monomorphic PVCs. Endocardial peak systolic strain timing in 18 left ventricular segments was displayed on a bull's-eye map using 8 color-coded intervals (0-800 ms). Patients were classified as localized (n=6) when the earliest interval appeared in 1 segment and nonlocalized (n=10) when it involved ≥2 segments. Ablation outcomes were compared according to whether a simple ablation approach (PVC elimination within 30 s at a single site) was achieved. RESULTS: Baseline electrocardiographic characteristics were comparable between the groups. Ablation-related parameters, including contact force, power output, and impedance drop at the initial ablation site, were also similar. However, the nonlocalized group required statistically significantly greater total radiofrequency energy to eliminate the targeted PVCs (median, 22 206 versus 10 409 J; =0.031) and demonstrated a statistically significantly lower rate of successful simple ablation approach compared with the localized group (20.0% versus 83.3%; =0.035). Nonlocalized patterns may reflect conduction from deeper origins with preferential pathways, thereby requiring more complex ablation strategies. CONCLUSIONS: A localized earliest-strain pattern was associated with successful PVC elimination using a simple ablation approach, whereas a nonlocalized pattern indicated the need for more complex ablation. This simple, noninvasive metric may aid preprocedural planning for left ventricular outflow tract PVC ablation.
Adedinsewo DA, Brown HL, Hameed AB
… +8 more, McNamara D, Mogos MF, Skowronski J, Vaught A, Meng ML, Ogunniyi MO, Reza N, American Heart Association Women’s Health Science Committee of the Council on Clinical Cardiology; Council on Cardiovascular Surgery and Anesthesia; and Council on Cardiovascular and Stroke Nursing
Circulation
· 2026 Jun · PMID 42339539
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Heart failure in the perinatal period remains ambiguous in definition and management despite its recognition as a unique disease state. The true incidence and prevalence of heart failure or left ventricular systolic dysf...Heart failure in the perinatal period remains ambiguous in definition and management despite its recognition as a unique disease state. The true incidence and prevalence of heart failure or left ventricular systolic dysfunction during pregnancy and the postpartum period are unknown, although a prevalence as high as 1% to 2% has been reported in the general adult US population. Assessment of heart failure can be challenging in the pregnant or postpartum state, during which symptoms affecting physical function (eg, dyspnea, exercise intolerance, fatigue, and lower-extremity edema) are prevalent because of physiological changes. Delays in the recognition and diagnosis of heart failure during the perinatal period contribute to adverse maternal outcomes, highlighting the need for evidence-based definitions and thresholds, improved diagnostic criteria to aid disease recognition, and effective screening tools. This scientific statement focuses on heart failure with reduced and mildly reduced ejection fraction in the context of pregnancy and the postpartum period, caused by various forms of cardiomyopathy. It addresses challenges related to recognizing heart failure in obstetric patients, outlines established treatment standards, and underscores potential areas for research. To improve the management of preexisting and de novo heart failure in obstetric patients, standardization of disease definitions, specific therapeutic options, implementation of effective screening tools, and interventions to improve maternal health equity are imperative. Future directions include prioritizing the inclusion of pregnant and postpartum individuals in heart failure studies, implementing interventions that facilitate early disease detection, and ensuring the timely initiation of appropriate therapies with the goal of reducing adverse outcomes associated with perinatal heart failure.
Ahn DJ, Attia A, Nakayama T
… +4 more, Narang N, Khush KK, Parker W, Sasaki K
Circ Heart Fail
· 2026 Jun · PMID 42335275
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BACKGROUND: The 2018 heart allocation policy change substantially lowered the priority of candidates supported with durable left ventricular assist devices (LVADs) for heart transplantation. To provide stable candidates...BACKGROUND: The 2018 heart allocation policy change substantially lowered the priority of candidates supported with durable left ventricular assist devices (LVADs) for heart transplantation. To provide stable candidates supported by durable LVADs with a quicker path to transplantation before they suffer complications, the Organ Procurement and Transplantation Network (OPTN) approved a policy stipulating that stable patients supported by durable LVADs for 6 and 8 years will obtain statuses 3 and 2, respectively. METHODS: Using OPTN data, we identified all adult heart transplant candidates with a durable LVAD implanted between October 18, 2018 and May 31, 2025. We estimated the cumulative incidence of LVAD-related complications, treating transplantation and waitlist removal before experiencing complications as competing events. Furthermore, we assessed how the OPTN policy change would impact the status distribution of the waitlist. RESULTS: In our study cohort, 4967 adult patients who were listed for heart transplant received a durable LVAD. Transplant centers submitted 2879 justifications for status upgrades due to LVAD-related complications for 1812 (36.5%) patients. At 6 years after durable LVAD implantation, the cumulative incidence of complications and status upgrades was 42.1% (95% CI, 40.5%-43.8%), and that of transplantation was 36.0% (95% CI, 34.6%-37.6%). Of the 3779 patients who were not censored administratively, only 47 (1.2%) remained on the waitlist by 6 years after durable LVAD implantation. Had the 6- to 8-year OPTN policy change been implemented on June 1, 2025, only 4.7% of the waitlist would have changed statuses instantaneously. CONCLUSIONS: Almost all listed candidates with durable LVADs either experience a complication, status upgrade or are removed from the waitlist within 6 years of obtaining a durable LVAD. The upcoming OPTN policy is unlikely to prevent device complications before granting status upgrades and will likely impact a small percentage of candidates with durable LVADs.
Liao M, Zhou W, Wang W
… +16 more, Yang Y, Yao Y, Zhou G, Wu Z, Zhang X, Wei B, Liang G, Li Z, Wei Z, Lu J, Wu Z, Wang Y, Lin A, Chen Y, Zhang B, Guo S
BACKGROUND: Patients with renal dysfunction remain at high risk for contrast-associated acute kidney injury despite standard peri-procedural volume administration. This study aims to investigate whether peri-procedural o...BACKGROUND: Patients with renal dysfunction remain at high risk for contrast-associated acute kidney injury despite standard peri-procedural volume administration. This study aims to investigate whether peri-procedural oral nicorandil provides additional protection in this population, and to evaluate its potential dose-response relationship. METHODS: We conducted a prospective, multicenter, randomized controlled trial enrolling patients with percutaneous coronary intervention with renal dysfunction. Participants were randomized into 3 groups, including a high-dose nicorandil group (30 mg/d, 10 mg 3× daily), a conventional-dose nicorandil group (15 mg/d, 5 mg 3× daily), and a saline hydration-only control group. The primary end point was the incidence of contrast-associated acute kidney injury. Secondary end points included changes in serum creatinine, blood urea nitrogen, CysC (cystatin C), and CRP (C-reactive protein). RESULTS: A total of 585 patients were recruited and randomized. The incidence of contrast-associated acute kidney injury was significantly lower in both nicorandil groups, with 19.8% (39/197) in the control group, compared with 10.9% (21/193) in the conventional-dose group and 8.7% (17/195) in the high-dose group (<0.001). This represented a relative risk reduction of 50% and 61% for the conventional- and high-dose groups, respectively. CONCLUSIONS: Adjunctive nicorandil, particularly at a dose of 10 mg 3× daily, significantly reduced the incidence of contrast-associated acute kidney injury in percutaneous coronary intervention patients with renal dysfunction. Oral nicorandil represents a readily available, effective, and dose-dependent prophylactic strategy to enhance renoprotection. Future studies are warranted to evaluate the long-term clinical benefits of this intervention. REGISTRATION:URL: https://www.chictr.org.cn; Unique identifier: CTR2200064264.
Przybylski R, Norrish G, Claggett B
… +34 more, Ashley EA, Bhole V, Day SM, Delle Donne G, Fernandez A, Girolami F, Gray B, Helms AS, Ingles J, Kubus P, Lakdawala NK, Lampert RJ, Lin KY, Michels M, Miller E, Olivotto I, Owens A, Parikh VN, Passantino S, Radulescu CR, Rossano J, Russell MW, Ryan TD, Saberi S, Spentzou G, Stendahl JC, Ware JS, Weintraub RG, Ziolkowska L, Zwetsloot PP, Kaski JP, Ho CY, Abrams DJ, SHaRe and IPHCC Investigators
Circulation
· 2026 Jun · PMID 42330108
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