Two-Year Outcomes of Valve-in-Valve Using New-Generation Transcatheter Devices Compared With Redo-SAVR.

Few studies have compared the clinical outcomes between valve-in-valve transcatheter aortic valve replacement (ViV-TAVR) with new-generation valves and re-operative surgical aortic valve replacement (Redo-SAVR). We compared the clinical outcomes of patients who underwent ViV-TAVR with those of patients who underwent Redo-SAVR at Cedars-Sinai Medical Center between 2015 and 2021. New-generation valves were used for ViV-TAVR. A propensity score-matched (PSM) analysis was performed to adjust for differences in baseline characteristics. The primary end point was all-cause mortality at 30 days and 2 years. In-hospital procedural and clinical outcomes were also compared between the groups. A total of 256 patients (140 who underwent ViV-TAVR and 116 who underwent Redo-SAVR) were eligible for PSM. In the unmatched cohort, patients in the ViV-TAVR group were older and had more co-morbidities than those in the Redo-SAVR group. After PSM, there were no significant differences in all-cause death between the ViV-TAVR and Redo-SAVR groups at 30 days (3.9% vs 2.6%, p = 0.65) or 2 years (6.5% vs 7.8%, p = 0.75). The incidences of stroke and heart failure rehospitalization were similar at 30 days and 2 years. The cumulative complication rates during hospitalization were significantly lower in the ViV-TAVR group than in the Redo-SAVR group (11.7% vs 28.6% p = 0.015). The long-term outcomes of ViV-TAVR using new-generation valves were similar to those of Redo-SAVR, although ViV-TAVR was associated with lower rates of in-hospital complications.

Coronary artery calcium scoring for cardiovascular risk assessment in patients with inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease (IBD) is associated with higher incidence of atherosclerotic cardiovascular disease (ASCVD). Data investigating the role of coronary artery calcium (CAC) scoring in identifying subclinical atherosclerotic disease in IBD patients is scarce. METHODS: Using data obtained from the CLARIFY registry, a prospective study of no-charge coronary artery calcium (CAC) testing at University Hospitals, we reviewed patients with ulcerative colitis (UC) or Crohn's disease (CD) who underwent CAC scoring from 2014 to 2020. We investigated the concordance between CAC risk and 10-year estimated ASCVD risk by AHA/ACC pooled cohort equation using pre-established thresholds for statin prescription (CAC≥100, 10-year ASCVD risk ≥7.5%). We additionally investigated the association between CAC, preventive therapy initiation and Major Adverse Cardiovascular Events (MACE). RESULTS: A total of 369 patients with IBD were included (174 UC, 195 CD), with median age of 60 years. The median CAC score was 14.9 with no significant difference between UC and CD (P = .76). Overall, 151 (41%) had CAC of 0, 108 (29%) had CAC 1-99, 61 (17%) had CAC 100 to 399, and 49 (13%) had CAC ≥400 with no difference in CAC distribution between CD and UC (P = .17). There was no difference in median CAC between IBD or age/sex-matched controls (P = .34). Approximately half of the patients (52%) with IBD had 10-year estimated ASCVD risk of 7.5% or higher. Among patients with ASCVD risk <7.5% (n = 163), 29 (18%) had CAC≥100 and among patients with ASCVD risk ≥7.5% (n = 178), 102 (57%) had CAC <100. There was no difference between CAC<100 vs CAC≥100 with respect to CRP, use of immunosuppressive or amino-salicylate therapy, IBD severity or complications. CAC score (AUROC 0.67 [0.56-0.78]), but not PCE ASCVD risk (AUROC 0.60 [0.48-0.73]), was predictive of MACE. The best cut-off for CAC score was 76 (sensitivity = 60%, specificity = 69%), and was associated with 4-fold increase in MACE (Hazard Ratio 4.0 [2.0-8.1], P < .001). CONCLUSION: Subclinical atherosclerosis, as evaluated by CAC scoring, is prevalent in patients with IBD, and is associated with cardiovascular events. Further studies are needed to understand underlying biological processes of increased atherosclerotic disease risk among adults with IBD.

Predicting the risk of iliofemoral vascular complication in complex transfemoral-TAVR using new generation transcatheter devices.

Objective: Design a predictive risk model for minimizing iliofemoral vascular complications (IVC) in a contemporary era of transfemoral-transcatheter aortic valve replacement (TF-TAVR). Background: IVC remains a common complication of TF-TAVR despite the technological improvement in the new-generation transcatheter systems (NGTS) and enclosed poor outcomes and quality of life. Currently, there is no accepted tool to assess the IVC risk for calcified and tortuous vessels. Methods: We reconstructed CT images of 516 propensity-matched TF-TAVR patients using the NGTS to design a predictive anatomical model for IVC and validated it on a new cohort of 609 patients. Age, sex, peripheral artery disease, valve size, and type were used to balance the matched cohort. Results: IVC occurred in 214 (7.2%) patients. Sheath size (p = 0.02), the sum of angles (SOA) (p < .0001), number of curves (NOC) (p < .0001), minimal lumen diameter (MLD) (p < .001), and sheath-to-femoral artery diameter ratio (SFAR) (p = 0.012) were significant predictors for IVC. An indexed risk score (CSI) consisting of multiplying the SOA and NOC divided by the MLD showed 84.3% sensitivity and 96.8% specificity, when set to >100, in predicting IVC (C-stat 0.936, 95% CI 0.911-0.959, p < 0.001). Adding SFAR > 1.00 in a tree model increased the overall accuracy to 97.7%. In the validation cohort, the model predicted 89.5% of the IVC cases with an overall 89.5% sensitivity, 98.9% specificity, and 94.2% accuracy (C-stat 0.842, 95% CI 0.904-0.980, p < .0001). Conclusion: Our CT-based validated-model is the most accurate and easy-to-use tool assessing IVC risk and should be used for calcified and tortuous vessels in preprocedural planning.

The safety of early discharge following transfemoral transcatheter aortic valve replacement under general anesthesia.

Background: There is growing evidence of the safety of same-day discharge for low-risk conscious sedated TAVR patients. However, the evidence supporting the safety of early discharge following GA-TAVR with routine transesophageal echocardiography (TEE) is limited. Aims: To assess the safety of early discharge following transcatheter aortic valve replacement (TAVR) using General Anesthesia (GA-TAVR) and identify predictors for patient selection. Materials and methods: We used data from 2,447 TEE-guided GA-TAVR patients performed at Cedars-Sinai between 2016 and 2021. Patients were categorized into three groups based on the discharge time from admission: 24 h, 24-48 h, and >48 h. Predictors for 30-day outcomes (cumulative adverse events and death) were validated on a matched cohort of 24 h vs. >24 h using the bootstrap model. Results: The >48 h group had significantly worse baseline cardiovascular profile, higher surgical risk, low functional status, and higher procedural complications than the 24 h and the 24-48 h groups. The rate of 30-day outcomes was significantly lower in the 24 h than the >48 h but did not differ from the 24-48 h (11.3 vs. 15.5 vs. 11.7%, p = 0.003 and p = 0.71, respectively). Independent poor prognostic factors of 30-day outcomes had a high STS risk of ≥8 (OR 1.90, 95% CI 1.30-2.77, E-value = 3.2, P < 0.001), low left ventricle ejection fraction of <30% (OR 6.0, 95% CI 3.96-9.10, E-value = 11.5, P < 0.001), and life-threatening procedural complications (OR 2.65, 95% CI 1.20-5.89, E-value = 4.7, P = 0.04). Our formulated predictors showed a good discrimination ability for patient selection (AUC: 0.78, 95% CI 0.75-0.81). Conclusion: Discharge within 24 h following GA-TAVR using TEE is safe for selected patients using our proposed validated predictors.

New adverse coronary events in valve-in-valve TAVR and native TAVR-A 2-year matched cohort.

Objective: To assess the incidence of new adverse coronary events (NACE) following transcatheter aortic valve replacement (TAVR) and valve-in-valve TAVR (ViV-TAVR). Background: ViV-TAVR is an accepted treatment for degenerative prostheses among patients with high surgical-risk. TAVR studies have suggested an increased risk of coronary artery obstruction and flow stasis causing thrombus formation. Whether contemporary ViV-TAVR is associated with higher rate of coronary events compared to TAVR is unknown. Methods: We used data from 1,224 TAVR patients between 2016 and 2021. We propensity-matched patients following ViV-TAVR and TAVR by significant predictors to overcome confounders in patients' baseline characteristics and procedural factors. Results: The matched population included 129 patients in each group. In line with prior reports, there was a higher in-hospital coronary artery obstruction rate with ViV-TAVR (3.1 vs. 1.6%; p = 0.23). Despite this, 2-year cumulative NACE rates were similar between groups (4.7 vs. 6.2%, respectively, p = 0.79), with no difference between its components: myocardial infarction (MI) (p = 0.210), unplanned coronary catheterization (p = 0.477), or coronary artery bypass grafting (CABG) (p = 0.998). Moreover, hypoattenuated leaflets thickening (HALT) at 30-day CT was observed in nearly a quarter of the patients with no difference between groups (23.9 vs. 23.1%, HR 1.02, 95% CI 0.50-1.28, p = 0.872). The progression rate of the coronary artery calcium score (CACS), assessed in a third of patients, was similar between groups (p log-rank = 0.468, 95% CI 0.12-1.24). Low coronary artery height was an unfavorable predictor for in-hospital coronary obstruction and 2-year NACE rate (HR 1.20 and HR 1.25, p = 0.001 and p < 0.0001, respectively). Conclusion: At 2-year follow-up, ViV-TAVR was not associated with a higher rate of myocardial infarction, unplanned catheterization, coronary artery bypass grafting, or hypoattenuated leaflet thickening.

Comparison Between Echocardiography and Cardiac Computed Tomography in the Evaluation of Diastolic Dysfunction and Prediction of Heart Failure.

Recent data indicate that left atrial (LA) function assessment by cardiac computed tomography (CT) is closely related to diastolic dysfunction (DD). Therefore, we aimed to perform a direct comparison between CT and echocardiography for diagnosis of advanced DD and prediction of future heart failure or cardiovascular death. We identified 340 patients who had both spiral cardiac CT and a proximate echocardiogram. LA total emptying fraction (LATEF), a measure of global LA function, was automatically calculated from CT data, as a surrogate for diastolic function and was compared with echocardiographic grades of diastolic function. The area under the receiver operating characteristic curve for LATEF to differentiate between advanced DD (grades 2 and 3) and all other grades was 0.84 (0.79 to 0.88). Over a median of 4 years, 69 events (admissions for heart failure and cardiovascular deaths) occurred. By multivariate Cox analysis, LATEF <40% provided incremental prognostic information after adjustments for advanced DD by echocardiography (hazard ratio 2.15, 95% confidence interval 1.13 to 3.94). There was a significant interaction (p = 0.03) between LATEF and echocardiography-based diastolic grades. Stratified analyses within the diastolic function groups revealed that LATEF <40% was equivalent to echocardiography in predicting events in the subgroup with advanced DD by echocardiography (p = 0.20) but was associated with a significantly higher event rates in patients with normal filling pressures (p = 0.0001) or indeterminate diastolic function (p = 0.04) by echocardiography. In conclusion, LA function derived from CT can accurately detect advanced DD diagnosed by echocardiography and has additive value to echocardiography-derived DD.

Cardiac rehabilitation performance predicts 1-year major adverse cardiovascular events.

BACKGROUND: Cardiac Rehabilitation is an essential following major adverse cardiovascular events however there is no current data correlating rehab performance to long term outcomes. HYPOTHESIS: Patient exercise performance during cardiac rehabilitation reliably predicts future cardiovascular events. METHODS: We conducted a single-center study of 486 consecutive patients who participated in a CR program between January 2018 and August 2021. We assessed patient performance using a novel index, the CR-score, which integrated duration, speed of work, and workload conducted on each training device (TD). We used a binary recursive partition model to determine the optimal thresholds for cumulative CR score. We used Cox regression analysis to assess the mortality rate among patients who developed MACE ("study group") and those who did not ("control group"). RESULTS: Among 486 eligible patients, 1-year MACE occurred in 27 (5.5%) patients and was more common in patients with prior cerebrovascular accident or transient ischemic attack (14.8% vs. 3.5%, p < .001). Age, gender, comorbidities, heart failure, and medical treatment did not significantly affect the outcome. The median cumulative CR score of the study group was significantly lower than the control group (595 ± 185.6 vs. 3500 ± 1104.7, p < .0001). A cumulative CR-score of ≥1132 correlated with the outcome (98.5% sensitivity, 99.6% specificity, 95% CI: 0.985-0.997, area 0.994, p < .0001). Patients older than 55 with a cumulative CR score of <1132 were at particularly high risk (OR: 7.4, 95% CI: 2.84-18.42) for 1-year MACE (log-rank p = .03). CONCLUSION: Our proposed CR-score accurately identifies patients at high risk for 1-year MACE following the rehabilitation program. Multicenter validation is required.

Sex-Differences in Atrial Fibrillation Patients: Bias or Proper Management?

Background: Studies analyze the degree to which gender-based differences are affected by age and comorbidities show mixed results. Methods: Using a retrospective cohort study, we analyzed 327 consecutive patients who presented to the emergency department (ED) due to Atrial Fibrillation (AF) from 2014 to 2017 with follow-up at one year. Results: Females with AF were older (p < 0.001), with higher Body Mass Indexes (BMI) (p < 0.001), and a higher rate of hypertension (p < 0.001), hyperlipidemia (p = 0.01), diabetes mellitus (p = 0.05), valvular heart disease (p = 0.05), and thyroid dysfunction (18.3% vs 1.8%, p < 0.001). AF males had higher rate of coronary artery disease (p < 0.001) and heart failure with reduced ejection fraction (p < 0.001). Females were managed with rate control medications more frequently than with antiarrhythmic (p < 0.001). After adjusting gender to age and comorbidities, females continued to have higher rates of heart failure hospitalization (Odds Ratio (OR) 2.73 95% Confidence Interval (CI) 1.04-5.89, P-value <0.001) and recurrent AF (OR 3.86, P-value=0.02). Thyroid dysfunction and the lack of antiarrhythmic treatments significantly increased the risk of AF (OR 5.95 95% CI 3.15-9.73, OR 3.42, respectively, P-value <0.001 for both) regardless of gender. The mortality rate differs only in a sub-group of females ≥75 years of age (OR 1.60, P < 0.001). Conclusion: AF males and females differ significantly in baseline characteristics and tend to be treated unnecessarily differently for AF. Heart failure hospitalizations and recurrent AF continued to be associated with female AF patients, even after adjusting gender to age and comorbidities. Thyroid dysfunction and AF treatment may explain the higher rates of recurrent AF in female patients.

Profile trends of non-COVID patients admitted to the cardiac intensive care unit during the 2020 COVID pandemic.

BACKGROUND: During the COVID-19 outbreak, numerous reports indicated a higher mortality rate among cardiovascular patients. We investigated how this trend applied to patients admitted to the cardiac intensive care unit (CICU). METHODS: We retrospectively compared CICU patients admitted during the initial peak of the COVID outbreak between February and May 2020 (Covid Era, CE group) to a control group in pre-pandemic time in 2019. We interviewed patients to determine the symptom onset time and the time interval between symptomology and hospital arrival. RESULTS: The data of 292 patients were used in the analysis (119 patients in the CE group and 173 in the control group). CE patients had a higher incidence of ischemic heart disease (IHD) (p<.03), heart failure (p<.04), and psychiatric disorders (p<.001). During COVID time, more patients were hospitalized with myocarditis (OR: 26.45), arrhythmias (OR: 2.88), and new heart failure (HF) (p<.001) and less with STEMI (OR: 0.39; 95% CI: 0.24-0.63). Fewer PCIs were performed in the CE group (p<.001), with an overall lower success rate (p<.05) than reported in the control group. Patients in the CE group reported a longer period between symptom onset to hospital arrival (p<.001, χ2 = 12.42). The six-month survival rate was significantly lower in CE patients (χ2 = 7.01, P = 0.008). CONCLUSIONS: Among CICU patients admitted to our center during the initial period of the COVID pandemic, STEMI events were less frequent while cases of newly diagnosed HF sharply increased. Patients waited longer after symptom onset before seeking medical care during the pandemic. The delay may have resulted in clinical deterioration that could explain the high mortality rate and the new HF admission rate.

The impact of anxiety level on decision to seek medical care of non-COVID cardiac patients during the pandemic outbreak-single-center experience in Israel.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has significantly the delivery of healthcare all around the world. In part, an abnormal and unexplained high non-COVID-related cardiovascular mortality rate was reported during the outbreak. We assess the correlation between anxiety level and decision to seek medical care (DSMC) during the COVID-19 pandemic. MATERIALS AND METHODS: We recruited patients with cardiovascular complaints admitted to the emergency department in a single institute in Israel between February and September 2020. Anxiety level was measured using available questionnaires. DSMC was assessed with a newly designed questionnaire (DM-19). RESULTS: Two-hundreds seventy patients were included in the study. The mean age was 52.6 ± 14.9 (females represent 36.2%). 23.6% of the patients had at least moderate cardiovascular risk. High anxiety levels were (HAL) reported in nearly half of the patients (57.1% and 49.8% for General Anxiety Disorder Assessment [GAD-7] and Beck Anxiety Inventory [BAI], respectively). It was more prevalent in old, married, and unemployed patients (significant p-value for all in both questionnaires). Age was an independent factor (χ2 = 6.33, p < 0.001, odds-ratio: 4.8) and had a positive correlation on anxiety level (r = 0.81, p < 0.001 and r = 0.62, p < 0.001, for GAD-7 and BAI, respectively). The DM-19 revealed a strong and positive correlation of seeking medical care with anxiety level (R2 linear = 0.44, r = 0.70, p < 0.001 and R2 linear = 0.30, r = 0.58, p < 0.001 for GAD-7 and BAI, respectively) and results in deferring medical care for several days than patient with low anxiety level (p = 0.02). CONCLUSIONS: We observed an abnormal prevalence of a high level of anxiety among non-COVID patients with cardiovascular complaints, which affected the patient's likelihood to seek medical care and resulted in an unreasonable postponement of medical treatment. Our results may explain cardiovascular mortality trends during the outbreak and should be considered in health crisis management. Future studies will involve multi-institutional efforts to address reproducibility of our findings across geographic regions in the state of the global impact. Additionally, it is imperative to understand the effects of the coronavirus vaccine on patient consideration to seek medical care.

Left atrial function by cardiac computed tomography is a predictor of heart failure and cardiovascular death.

OBJECTIVES: We sought to evaluate cardiac CT angiography (CCTA)-based assessment of left atrial (LA) function as a predictor of hospitalizations for heart failure (HF) and cardiovascular (CV) mortality. METHODS: LA function was evaluated using automatic derivation of LA volumes to calculate LA total emptying fraction (LATEF) in 788 consecutive patients with normal sinus rhythm who had undergone spiral CT scans. The relationship between LATEF evaluated by CCTA and the composite endpoint of admission for HF or CV mortality was analyzed using Cox models. RESULTS: During a median follow-up of 4 years, there were 100 events, 62 HF hospitalizations, and 38 cardiovascular deaths. Mean LATEF was 30.7 ± 10.7% and 40.5 ± 11.2% in patients with and without events, respectively (p < 0.0001). A high LATEF (upper tertile > 46%) was associated with a very low event rate (3.5% at 6 years [95% CI 1.7-7.1%]). The adjusted HR for HF or CV mortality was 4.37 (95% CI 1.99-9.60) in the lowest LATEF tertile, and 2.29 (95% CI 1.03-5.14) in the middle tertile, relative to the highest tertile. For the endpoint of HF alone, adjusted HR for the lowest LATEF tertile was 5.93 (95% CI 2.23-15.82) and for the middle tertile 2.89 (95% CI 1.06-7.86). The association of LATEF with outcome was similar for patients with both reduced and preserved left ventricular (LV) ejection fraction (Pinteraction = 0.724). Reduced LATEF was associated with a high event rate, even when coupled with normal LA volume. CONCLUSION: CCTA-derived LA function is a predictor of HF hospitalization or CV death, independent of clinical risk factors, LA volume, and LV systolic function. KEY POINTS: • Left atrial function can be automatically derived from cardiac CTA scans. • Cardiac CTA-derived left atrial function is a predictor of hospitalization for heart failure and cardiovascular death. • Evaluation of left atrial function could be useful in identifying patients at risk of heart failure.

Transcatheter Aortic Valve Replacement for Bicuspid Aortic Insufficiency After Valve-Sparing Aortic Root Replacement.

Bicuspid aortic insufficiency (BAI) patients with root aneurysm often require aortic valve and root replacement in a composite procedure. The valve-sparing root replacement (VSARR) procedure is aimed at preserving the native valve when possible. This case highlights a successful transcatheter aortic valve replacement procedure in a BAI patient previously treated with VSARR. (Level of Difficulty: Intermediate.).

Risk of Worsening Renal Function Following Repeated Exposures to Contrast Media During Percutaneous Coronary Interventions.

Background Multiple contrast media exposures are common, but their cumulative effect on renal function is unknown. We aimed to investigate the renal consequences of repeated exposures to contrast media with coronary interventions. Methods and Results We studied 2942 patients who underwent between 1 and 9 procedures. The primary end point was a persistent creatinine increase of ≥50% above baseline at ≥90 days after the last procedure. The effect of cumulative contrast media dose was assessed using Cox models, with cumulative exposure as a time-dependent variable, and propensity score matching. The primary end point occurred in 190 patients (6.5%), with 6.1%, 6.8%, and 6.2% of patients with 1, 2 or 3, and ≥4 procedures, respectively (P=0.75). In the multivariable Cox model, baseline renal function, diabetes, anemia, acute coronary syndrome, and heart failure were independent predictors of the primary end point (all P≤0.01), whereas cumulative contrast dose was not (hazard ratio [HR], 1.29 [95% CI, 0.89-1.88] for the fourth contrast quartile [>509 mL] versus first contrast quartile [<233 mL]). Propensity score matching yielded 384 patient pairs with similar characteristics and either 1 or 2 to 9 contrast exposures (median cumulative dose, 160 and 480 mL, respectively). Despite large differences in the cumulative contrast exposure, there were similar rates of the primary end points (7.3% versus 6.3%, respectively; HR, 0.76 [95% CI, 0.44-1.32]). Conclusions In patients with multiple exposures to contrast media, worsening of renal function over time is associated with known risk factors for the progression of kidney disease but not with cumulative contrast volume.

Adverse dose-dependent effects of morphine therapy in acute heart failure.

BACKGROUND: Morphine has been a pivotal therapy in acute heart failure (AHF) for more than a century. The evidence for morphine therapy in AHF remains controversial. This study sought to assess the therapeutic effect of morphine on patients with AHF. METHODS: The study used a cohort of 13,788 patients admitted with a primary diagnosis of AHF. Propensity-score-matching was generated using 26 clinical variables. Primary endpoints included in-hospital mortality and invasive mechanical ventilation. Secondary endpoints included non-invasive ventilation, need for inotropes and acute kidney injury (AKI). RESULTS: 761 (5.5%) patients were treated with morphine in the first day following hospital admission. Propensity score matching yielded 672 patient pairs. The incidence of invasive ventilation was higher in the morphine-treated patients (7.4%) than in matched patients in the no-morphine cohort (3.6%), OR 2.13 (95% CI 1.32-3.57, P = 0.007). In-hospital mortality was also higher in the morphine group (17.4%) than in the matched no-morphine group (13.4%), OR 1.43 (95% CI 1.05 to 1.98, P = 0.024). For both the endpoint of invasive ventilation (Ptrend = 0.005) and mortality (Ptrend = 0.004), there was a significant linear dose-response relationship for the adverse effect of morphine. Morphine was associated with a significant increase in all secondary outcomes: Non-invasive ventilation (OR 2.78, 95% CI 1.95-3.96); Inotrope use (OR 3.50, 95% CI 2.10-5.82) and AKI (OR 1.81, 95% CI 1.39-2.36). A landmark analysis demonstrated no difference in post-discharge survival between cohorts. CONCLUSIONS: Morphine administration is associated with significant dose-dependent risk for in-hospital mortality and need for mechanical ventilation.

Isoproterenol Promotes Rapid Ryanodine Receptor Movement to Bridging Integrator 1 (BIN1)-Organized Dyads.

BACKGROUND: The key pathophysiology of human acquired heart failure is impaired calcium transient, which is initiated at dyads consisting of ryanodine receptors (RyRs) at sarcoplasmic reticulum apposing CaV1.2 channels at t-tubules. Sympathetic tone regulates myocardial calcium transients through ß-adrenergic receptor (ß-AR)-mediated phosphorylation of dyadic proteins. Phosphorylated RyRs (P-RyR) have increased calcium sensitivity and open probability, amplifying calcium transient at a cost of receptor instability. Given that bridging integrator 1 (BIN1) organizes t-tubule microfolds and facilitates CaV1.2 delivery, we explored whether ß-AR-regulated RyRs are also affected by BIN1. METHODS AND RESULTS: Isolated adult mouse hearts or cardiomyocytes were perfused for 5 minutes with the ß-AR agonist isoproterenol (1 µmol/L) or the blockers CGP+ICI (baseline). Using biochemistry and superresolution fluorescent imaging, we identified that BIN1 clusters P-RyR and CaV1.2. Acute ß-AR activation increases coimmunoprecipitation between P-RyR and cardiac spliced BIN1+13+17 (with exons 13 and 17). Isoproterenol redistributes BIN1 to t-tubules, recruiting P-RyRs and improving the calcium transient. In cardiac-specific Bin1 heterozygote mice, isoproterenol fails to concentrate BIN1 to t-tubules, impairing P-RyR recruitment. The resultant accumulation of uncoupled P-RyRs increases the incidence of spontaneous calcium release. In human hearts with end-stage ischemic cardiomyopathy, we find that BIN1 is also 50% reduced, with diminished P-RyR association with BIN1. CONCLUSIONS: On ß-AR activation, reorganization of BIN1-induced microdomains recruits P-RyR into dyads, increasing the calcium transient while preserving electric stability. When BIN1 is reduced as in human acquired heart failure, acute stress impairs microdomain formation, limiting contractility and promoting arrhythmias.