Transvalvular Flow,Sex, and Survival After Valve Replacement Surgery in Patients With Severe Aortic Stenosis

BackgroundThe respective impacts of transvalvular flow, gradient, sex, and their interactions on mortality in patients with severe aortic stenosis undergoing surgical aortic valve replacement (AVR) are unknown.ObjectivesThis study sought to compare the impact of pre-operative flow-gradient patterns on mortality after AVR and to examine whether there are sex differences.MethodsThis study analyzed clinical, echocardiographic, and outcome data prospectively collected in 1,490 patients (544 women [37%]), with severe aortic stenosis and preserved left ventricular ejection fraction who underwent AVR.ResultsIn this cohort, 601 patients (40%) had normal flow (NF) with high gradient (HG), 405 (27%) NF with low gradient (LG), 246 (17%) paradoxical low flow (LF)/HG, and 238 (16%) LF/LG. During a median follow-up of 2.42 years (interquartile range: 1.04 to 4.29 years), 167 patients died. Patients with LF/HG exhibited the highest mortality after AVR (hazard ratio [HR]: 2.01; 95% confidence interval [CI]: 1.33 to 3.03; p < 0.01), which remained significant after multivariate adjustment (HR: 1.96; 95% CI: 1.29 to 2.98; p < 0.01). Both LF/LG and NF/LG patients had comparable outcome to NF/HG (p ≥ 0.47). Optimal thresholds of stroke volume index were obtained for men (40 ml/m²) and women (32 ml/m²). Using these sex-specific cutpoints, paradoxical LF was independently associated with increased mortality in both women (adjusted HR: 2.05; 95% CI: 1.21 to 3.47; p < 0.01) and men (adjusted HR: 1.54; 95% CI: 1.02 to 2.32; p = 0.042), whereas guidelines’ threshold (35 ml/m²) does not.ConclusionsParadoxical LF/HG was associated with higher mortality following AVR, suggesting that a reduced flow is a marker of disease severity even in patients with HG aortic stenosis. Early surgical AVR (i.e., before gradient attains 40 mm Hg) might be preferable in these patients. Furthermore, the use of sex-specific thresholds (<40 ml/m² for men and <32 ml/m² for women) to define low-flow outperforms the guidelines’ threshold of 35 ml/m² in risk stratification after AVR.     

Transvalvular Pressure Gradients and All-Cause Mortality Following TAVR: A Multicenter Echocardiographic and Invasive Registry

BackgroundLow ejection fraction (EF) and low flow as determined by an echocardiographic stroke volume index (SVi) <35 mL/m² are associated with low transvalvular gradients and increased mortality in both severe aortic stenosis (AS) and post–transcatheter aortic valve replacement (TAVR). Absence of an elevated echocardiographic transaortic gradient post-TAVR is considered a marker of procedural success despite the absence of data on its impact on mortality.ObjectivesThe authors sought to examine the association of invasive and echocardiographic gradients post-TAVR with all-cause mortality in relation to flow and EF.MethodsIn a multicenter retrospective registry of patients undergoing TAVR, Cox models with regression splines explored the relationship between invasive and echocardiographic gradients post-TAVR with 2-year mortality. An invasive gradient <5 mm Hg was considered low, between ≥5 and <10 mm Hg was considered intermediate, and ≥10 mm Hg was considered high. An echocardiographic gradient <10 mm Hg was considered low, ≥10 and <20 mm Hg was considered intermediate, and ≥20 mm Hg was considered high.ResultsHigher mortality occurred in low echocardiographic gradients at discharge relative to intermediate gradients (P < 0.001), and low gradient was associated with lower EF and echocardiographic SVi (P < 0.001 and P < 0.008, respectively). Lower mortality occurred in low invasive gradients relative to intermediate gradients (P = 0.012) with no difference in EF and echocardiographic SVi between groups (P = 0.089 and P = 0.947, respectively). There were insufficient observations to determine the impact of high echocardiographic and invasive gradients on mortality.ConclusionsIn this large retrospective analysis, the impact of transaortic gradients on mortality after TAVR was not linear and complex, showing opposite results among echocardiographic and invasive measurements in low-gradient patients.     

Prognosis of Severe Low-Flow,Low-Gradient Aortic Stenosis by Stroke Volume Index and Transvalvular Flow Rate

ObjectivesThis study determined whether flow state classified by stroke volume index (SVi) or transvalvular flow rate (FR) improved risk stratification of all-cause mortality, hospitalization due to heart failure, and aortic valvular interventions for patients with severe aortic stenosis (AS).BackgroundSVi is a widely accepted classification for flow state in severe low-flow, low-gradient (LFLG) AS. Recent studies suggest that FR more closely approximates true AS severity and provides more useful prognostication than SVi.MethodsPatients with severe AS over a 7-year period were subclassified by echocardiographic parameters. LFLG-AS was defined as severe AS (aortic valve area index [AVAi]: <0.6 cm²/m²), with a mean transvalvular pressure gradient of <40 mm Hg in the setting of low flow state: SVi of <35 ml/m² and/or FR of <200 ml/s and subclassified into preserved (≥50%; paradoxical) or reduced (<50%; classical) left ventricular ejection fraction (LVEF).ResultsAmong 621 consecutive patients with severe AS, the proportions of patients classified as LFLG-AS were different between SVi and FR (p < 0.001). Classification using SVi, FR, and LVEF was a strong predictor of the composite endpoint at the 2-year follow-up. The addition of SVi to the echocardiographic and clinical model provided significant improvement in reclassification (net reclassification improvement: 0.089; 95% confidence interval [CI]: 0.045 to 0.133; p = 0.04), whereas addition of FR did not (net reclassification improvement: 0.061; 95% CI: 0.016 to 0.106; p = 0.17). C-statistics indicated improved risk discrimination when AVAi, LVEF, and SVi or FR were added as predictive variables to the clinical model (p = 0.006).ConclusionsLow SVi or FR was associated with adverse cardiovascular events and showed improvement in discrimination, but only SVi, not FR, significantly improved risk reclassification compared to other conventional clinical and echocardiographic predictors. This suggests that FR is not superior to SVi in distinguishing true severe from pseudosevere forms of AS and identification of patients with LFLG-AS who have worse outcomes.     

Prognostic Value of N-Terminal Pro–B-Type Natriuretic Peptide in Elderly Patients With Valvular Heart Disease

BackgroundN-terminal pro–B-type natriuretic peptide (NT-proBNP) may reflect early prognosis in patients with valvular heart disease (VHD).ObjectivesThe aim of this study was to examine the association between NT-proBNP and mortality in elderly patients with VHD.MethodsA total of 5,983 elderly patients (age ≥60 years) with moderate or severe VHD underwent echocardiography and NT-proBNP measurement. VHD examined included aortic stenosis, aortic regurgitation, mitral stenosis, mitral regurgitation, tricuspid regurgitation, and multivalvular heart disease. NT-proBNP ratio was defined as measured NT-proBNP relative to the maximal normal values specific to age and sex. Disease-specific thresholds were defined on the basis of penalized splines and maximally selected rank statistics.ResultsThe cohort had a mean age of 71.1 ± 7.6 years. At 1-year follow-up, 561 deaths (9.4%) had occurred. In penalized splines, relative hazards showed a monotonic increase with greater NT-proBNP ratio for death with different VHDs (p < 0.001 for all) except mitral stenosis. Higher NT-proBNP ratio, categorized by disease-specific thresholds, was independently associated with mortality (overall adjusted hazard ratio: 1.99; 95% confidence interval: 1.76 to 2.24; p < 0.001). Different subtypes of VHD all incurred excess mortality with elevated NT-proBNP ratio, with the strongest association detected for aortic stenosis (adjusted hazard ratio: 10.5; 95% confidence interval: 3.9 to 28.27; p < 0.001). The addition of NT-proBNP ratio to the prediction algorithm including traditional risk factors improved outcome prediction (overall net reclassification index = 0.28; 95% CI: 0.24 to 0.34; p < 0.001; likelihood ratio test p < 0.001). Results remained consistent in patients under medical care, with normal left ventricular ejection fractions, and with primary VHD.ConclusionsNT-proBNP provides incremental prognostic information for mortality in various VHDs. It could aid in risk stratification as a pragmatic and versatile biomarker in elderly patients.     

CT-Determined Tricuspid Annular Dilatation Is Associated With Increased 2-Year Mortality in TAVR Patients

ObjectivesThe aim of this study was to investigate the prevalence and prognostic impact of tricuspid annular dilatation (TAD) measured in multislice computed tomography datasets in patients undergoing transfemoral transcatheter aortic valve replacement for severe aortic stenosis.BackgroundTAD is an increasingly recognized entity associated with poor outcomes in patients with valvular heart disease.MethodsThe maximal septolateral diameter of the tricuspid annulus was measured in consecutive patients with 3-dimensional multidetector row computed tomographic datasets undergoing transfemoral transcatheter aortic valve replacement. Receiver-operating curve characteristic analysis was performed to obtain an ideal, body surface area–normalized cutoff for TAD. Ethical approval was obtained from the institutional ethics board.ResultsThe study included 1,137 patients, of whom 299 died within a mean follow-up period of 1.8 ± 1.0 years. TAD was identified in 446 patients (39.2%) on the basis of a receiver-operating characteristic cutoff of 23 mm/m². TAD had no impact on procedural outcomes, including device failure defined according to Valve Academic Research Consortium–2 criteria. Patients with TAD experienced significantly greater mortality (hazard ratio: 1.99; 95% confidence interval: 1.59 to 2.51; p < 0.001). Multivariate analysis including clinical and echocardiographic parameters confirmed the predictive value of TAD (hazard ratio: 1.78; 95% confidence interval: 1.33 to 2.38; p < 0.001), while echocardiographic variables, including estimated pulmonary artery pressure and the severity of tricuspid regurgitation, did not reach statistical significance. The predictive value of TAD was incremental to a baseline model of clinical and echocardiographic parameters (continuous net reclassification improvement 0.204; p < 0.01) and incremental to the Society of Thoracic Surgeons score (continuous net reclassification improvement 0.209; p < 0.001).ConclusionsTAD is an independent predictor of all-cause mortality in patients with severe aortic stenosis undergoing transcatheter aortic valve replacement.     

BMI,Infarct Size,and Clinical Outcomes Following Primary PCI: Patient-Level Analysis From 6 Randomized Trials

ObjectivesThe aim of this study was to examine the association between body mass index (BMI), infarct size (IS) and clinical outcomes.BackgroundThe association between obesity, IS, and prognosis in patients undergoing primary percutaneous coronary intervention (pPCI) for ST-segment elevation myocardial infarction is incompletely understood.MethodsAn individual patient-data pooled analysis was performed from 6 randomized trials of patients undergoing pPCI for ST-segment elevation myocardial infarction in which IS (percentage left ventricular mass) was assessed within 1 month (median 4 days) after randomization using either cardiac magnetic resonance (5 studies) or ^99mTc sestamibi single-photon emission computed tomography (1 study). Patients were classified as normal weight (BMI <25 kg/m²), overweight (25 kg/m² ≤BMI <30 kg/m²), or obese (BMI ≥30 kg/m²). The multivariable models were adjusted for age, sex, hypertension, hyperlipidemia, current smoking, left main or left anterior descending coronary artery infarct, baseline TIMI (Thrombolysis In Myocardial Infarction) flow grade 0 or 1, prior myocardial infarction, symptom–to–first device time, and study.ResultsAmong 2,238 patients undergoing pPCI, 644 (29%) were normal weight, 1,008 (45%) were overweight, and 586 (26%) were obese. BMI was not significantly associated with IS, microvascular obstruction, or left ventricular ejection fraction in adjusted or unadjusted analysis. BMI was also not associated with the 1-year composite risk for death or heart failure hospitalization (adjusted hazard ratio: 1.21 [95% confidence interval: 0.74 to 1.71] for overweight vs. normal [p = 0.59]; adjusted hazard ratio: 1.21 [95% confidence interval 0.74 to 1.97] for obese vs. normal [p = 0.45]) or for death or heart failure hospitalization separately. Results were consistent when BMI was modeled as a continuous variable.ConclusionsIn this individual patient-data pooled analysis of 2,238 patients undergoing pPCI for ST-segment elevation myocardial infarction, BMI was not associated with IS, microvascular obstruction, left ventricular ejection fraction, or 1-year rates of death or heart failure hospitalization.     

Functional Mitral Regurgitation Outcome and Grading in Heart Failure With Reduced Ejection Fraction

ObjectivesThis study aims to define excess-mortality linked to functional mitral regurgitation (FMR) quantified in routine-practice.BackgroundAppraisal of FMR in heart failure with reduced ejection fraction (HFrEF) is challenging because risks of excess mortality remain uncertain and guidelines diverge.MethodsCases of HFrEF (ejection-fraction <50%) Stage B-C that were diagnosed between 2003 and 2011 and had routine-practice FMR quantitation (FMR cohort, n = 6,381) were analyzed for excess mortality thresholds/rates within the cohort and in comparison to the general population. These were also compared to those of a degenerative mitral regurgitation (DMR) simultaneous cohort (DMR cohort, n = 2,416).ResultsIn the FMR cohort (age: 70 ± 11 years, ejection fraction: 36 ± 10%, effective regurgitant orifice area [EROA]: 0.09 ± 0.13 cm²), EROA distribution was skewed towards low-values (≥0.40 cm² in only 8% vs 38% for the DMR cohort; P < 0.0001). One-year mortality was high (15.6%), increasing steeply from 13.3% without FMR to 28.5% with EROA ≥0.30 cm² (adjusted odds ratio: 1.57 [95% CI: 1.19-2.97]; P = 0.001). In the long term, 3,538 FMR cohort patients died with excess mortality threshold ∼0.10 cm² (vs ∼0.20 cm² in the DMR cohort), with 0.10 cm² EROA increments independently associated with considerable mortality increment (adjusted HR: 1.11 [95% CI: 1.08-1.15]; P < 0.0001) and with no detectable interaction. Compared to the general population, FMR excess mortality increased exponentially with higher EROA (risk ratio point estimates 2.8, 3.8, and 5.1 at EROA 0.20, 0.30, and 0.40 cm², respectively), and was much steeper than that of the DMR cohort (P < 0.0001). In nested models, individualized EROA was the strongest FMR survival marker, and a new expanded FMR grading scale based on 0.10 cm² EROA increments provided incremental power over current American Heart Association–American College of Cardiology/European Society of Cardiology guidelines (all P < 0.03).ConclusionsIn HFrEF, FMR is skewed towards smaller EROA. Nevertheless, when measured in routine practice, EROA is the strongest independent FMR determinant of survival after diagnosis. Excess mortality increases exponentially above the threshold of 0.10 cm², with a much steeper slope than in DMR, for any EROA increment. An expanded EROA-based stratification, superior to existing grading schemes in determining survival, should allow guideline harmonization.     

First 24-h Sardjito Cardiovascular Intensive Care (SCIENCE) admission risk score to predict mortality in cardiovascular intensive care unit (CICU)

Background and objectivesThe application of prognostic scoring systems to identify risk of death within 24 h of CICU admission has significant consequences for clinical decision-making. Previous score of parameters collected after 24 h was considered too late to predict mortality. As a result, we attempted to develop a CICU admission risk score to predict hospital mortality using indicators collected within 24 h.MethodsData were obtained from SCIENCE registry from January 1, 2021 to December 21, 2021. Outcomes of 657 patients (mean age 58.91 ± 12.8 years) were recorded retrospectively. Demography, risk factors, comorbidities, vital signs, laboratory and echocardiography data at 24-h of patient admitted to CICU were analysed by multivariate logistic regression to create two models of scoring system (probability and cut-off model) to predict in-hospital mortality of any cause.ResultsFrom a total of 657 patients, the hospital mortality was 15%. The significant predictors of mortality were male, acute heart failure, hemodynamic instability, pneumonia, baseline creatinine ≥1.5 mg/dL, TAPSE <17 mm, and the use of mechanical ventilator within first 24-h of CICU admission. Based on Receiver Operating Characteristic (ROC) curve analysis a cut off of ≥3 is considered to be a high risk of in-hospital mortality (sensitivity 75% and specificity 65%).ConclusionThe initial 24-h SCIENCE admission risk rating system can be used to predict in-hospital mortality in patients admitted to the CICU with a high degree of sensitivity and specificity,     

Ticagrelor or Prasugrel in Patients With Acute Coronary Syndrome in Relation to Estimated Glomerular Filtration Rate

ObjectivesThe aim of this study was to assess the safety and efficacy of ticagrelor versus prasugrel for patients with acute coronary syndrome (ACS) according to their estimated glomerular filtration rates (eGFRs).BackgroundThe outcomes of ticagrelor versus prasugrel in patients with ACS according to eGFR have not been defined.MethodsPatients (n = 4,012) were categorized into 3 groups: low eGFR (<60 mL/min/1.73 m²), intermediate eGFR (≥60 and <90 mL/min/1.73 m²), and high eGFR (≥90 mL/min/1.73 m²). The primary endpoint was a composite of all-cause death, myocardial infarction, and stroke; the secondary safety endpoint was Bleeding Academic Research Consortium types 3 to 5 bleeding, both at 1 year.ResultsPatients with low eGFRs had a higher risk for the primary endpoint compared with patients with intermediate eGFRs (adjusted HR: 1.89; 95% CI: 1.46-2.46]) and those with high eGFRs (adjusted HR: 2.33; 95% CI: 1.57-3.46). A risk excess for low eGFR was also observed for bleeding (adjusted HR: 1.55 [95% CI: 1.12-2.13] vs intermediate eGFR; adjusted HR: 1.59 [95% CI: 1.01-2.50] vs high eGFR). However, eGFR did not affect the relative efficacy and safety of ticagrelor versus prasugrel. In patients with low eGFR, the primary endpoint occurred in 20.5% with ticagrelor and in 14.7% with prasugrel (HR: 1.47; 95% CI: 1.04-2.08; P = 0.029); there was no significant difference in bleeding.ConclusionsThese results show that among patients with ACS, reduction of eGFR is associated with increased risk for ischemic and bleeding events but has no significant impact on the relative efficacy and safety of ticagrelor versus prasugrel. (Prospective, Randomized Trial of Ticagrelor Versus Prasugrel in Patients With Acute Coronary Syndrome [ISAR-REACT 5]; NCT01944800)     

Low Transvalvular Flow Rate Predicts Mortality in Patients With Low-Gradient Aortic Stenosis Following Aortic Valve Intervention

ObjectivesThis study aimed to assess the value of low transvalvular flow rate (FR) for the prediction of mortality compared with low stroke volume index (SVi) in patients with low-gradient (mean gradient: <40 mm Hg), low aortic valve area (<1 cm²) aortic stenosis (AS) following aortic valve intervention.BackgroundTransaortic FR defined as stroke volume/left ventricular ejection time is also a marker of flow; however, no data exist comparing the relative prognostic value of these 2 transvalvular flow markers in patients with low-gradient AS who had undergone valve intervention.MethodsWe retrospectively followed prospectively assessed consecutive patients with low-gradient, low aortic valve area AS who underwent aortic valve intervention between 2010 and 2014 for all-cause mortality.ResultsOf the 218 patients with mean age 75 ± 12 years, 102 (46.8%) had low stroke volume index (SVi) (<35 ml/m²), 95 (43.6%) had low FR (<200 ml/s), and 58 (26.6%) had low left ventricular ejection fraction <50%. The concordance between FR and SVi was 78.8% (p < 0.005). Over a median follow-up of 46.8 ± 21 months, 52 (23.9%) deaths occurred. Patients with low FR had significantly worse outcome compared with those with normal FR (p < 0.005). In patients with low SVi, a low FR conferred a worse outcome than a normal FR (p = 0.005), but FR status did not discriminate outcome in patients with normal SVi. By contrast, SVi did not discriminate survival either in patients with normal or low FR. Low FR was an independent predictor of mortality (p = 0.013) after adjusting for age, clinical prognostic factors, European System for Cardiac Operative Risk Evaluation II, dimensionless velocity index, left ventricular mass index, left ventricular ejection fraction, heart rate, time, type of aortic valve intervention, and SVi (p = 0.59).ConclusionsIn patients with low-gradient, low valve area aortic stenosis undergoing aortic valve intervention, low FR, not low SVi, was an independent predictor of medium-term mortality.     

Association of Asymptomatic Diastolic Dysfunction Assessed by Left Atrial Strain With Incident Heart Failure

ObjectivesThis study is to establish the association of left atrial reservoir strain (LARS) with incident heart failure (HF), and the impact of substituting LARS for left atrial (LA) volume index (LAVI) in diastolic assessment.BackgroundLARS measures passive LA stretch and is a sensitive marker of left ventricular diastolic dysfunction (DD). The potential contribution of LARS to diastolic assessment is unclear.MethodsBaseline clinical and echocardiographic assessments were obtained in 758 asymptomatic, community-dwelling elderly subjects (age 70 [interquartile range: 67 to 74] years, 53% women) with nonischemic HF risk factors. LARS-defined DD (LARS-DD) was assessed by speckle-tracking echocardiography, and grades were assigned as normal (>35%), grade 1 (25% to 35%) and grade 2 (≤24%). DD grade using current recommendations was compared with grading using LARS <24% in place of LAVI >34 ml/m². Patients were followed for up to 2 years for incident HF.ResultsLA strain analysis was feasible in 738 (97%) patients; average LARS was 39% (range 34% to 43%). Incident HF was associated with LARS-DD grade; 8 (36%) of those had grade 2+, 14 (10%) had grade 1, and 39 (9%) had normal function (p < 0.001). LARS-DD grade 2+ predicted incident HF after adjustment for clinical and echocardiographic markers (adjusted hazard ratio: 2.5; 95% confidence interval: 1.02 to 6.3; p = 0.049); there was no significant HF risk associated with LARS-DD grade 1. Dichotomized abnormal LARS <24% had an adjusted hazard ratio of 2.9 (95% confidence interval: 1.25 to 6.79; p = 0.013). Substituting LARS for LAVI provided a 75% reduction in indeterminate diastolic function; all were recategorized as normal. There was no increased risk associated normal diastolic function by this grading compared to conventional grading (C-statistic = 0.76 for both models).ConclusionsLARS-DD grade 2+ is associated with incident HF in the elderly, independent of LAVI. The substitution of LARS for LAVI reduces the number of indeterminate cases without impacting prognosis in normal diastolic function and grade 1 DD.     

Burden and Outcomes of Heart Failure Hospitalizations in Adults With Chronic Kidney Disease

BackgroundData on rates of heart failure (HF) hospitalizations, recurrent hospitalizations, and outcomes related to HF hospitalizations in chronic kidney disease (CKD) are limited.ObjectivesThis study examined rates of HF hospitalizations and re-hospitalizations within a large CKD population and evaluated the burden of HF hospitalizations with the risk of subsequent CKD progression and death.MethodsThe prospective CRIC (Chronic Renal Insufficiency Cohort) study measured the estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (ACR) at baseline. The crude rates and rate ratios of HF hospitalizations and 30-day HF re-hospitalizations were calculated using Poisson regression models. Cox regression was used to assess the association of the frequency of HF hospitalizations within the first 2 years of follow-up with risk of subsequent CKD progression and death.ResultsAmong 3,791 participants, the crude rate of HF admissions was 5.8 per 100 person-years (with higher rates of HF with preserved ejection fraction vs. HF with reduced ejection fraction). The adjusted rate of HF was higher with a lower eGFR (vs. eGFR >45 ml/min/1.73 m²); the rate ratios were 1.7 and 2.2 for eGFR 30 to 44 and <30 ml/min/1.73 m² (vs. >45 ml/min/1.73 m²), respectively. Similarly, the adjusted rates of HF hospitalization were significantly higher in those with higher urine ACR (vs. urine ACR <30 mg/g); the rate ratios were 1.9 and 2.6 for urine ACR 30 to 299 and ≥300 mg/g, respectively. Overall, 20.6% of participants had a subsequent HF re-admission within 30 days. HF hospitalization within 2 years of study entry was associated with greater adjusted risks for CKD progression (1 hospitalization: hazard ratio [HR]: 1.93; 95% confidence interval [CI]: 1.40 to 2.67; 2+ hospitalizations: HR: 2.14; 95% CI: 1.30 to 3.54) and all-cause death (1 hospitalization: HR: 2.20; 95% CI: 1.71 to 2.84; 2+ hospitalizations: HR: 3.06; 95% CI: 2.23 to 4.18).ConclusionsWithin a large U.S. CKD population, the rates of HF hospitalizations and re-hospitalization were high, with even higher rates across categories of lower eGFR and higher urine ACR. Patients with CKD hospitalized with HF had greater risks of CKD progression and death. HF prevention and treatment should be a public health priority to improve CKD outcomes.     

Impact of Pre-Existing and New-Onset Atrial Fibrillation on Outcomes After Transcatheter Aortic Valve Replacement

ObjectivesThis study sought to evaluate impact of new-onset and pre-existing atrial fibrillation (AF) on transcatheter aortic valve replacement (TAVR) long-term outcomes compared with patients without AF.BackgroundPre-existing and new-onset AF in patients undergoing TAVR are associated with poor outcomes.MethodsThe study identified 72,660 patients ≥65 years of age who underwent nonapical TAVR between 2014 and 2016 using Medicare inpatient claims. History of AF was defined by diagnoses on claims during the 3 years preceding the TAVR, and new-onset AF was defined as occurrence of AF during the TAVR admission or within 30 days after TAVR in a patient without prior history of AF. Outcomes included all-cause mortality, and readmission for bleeding, stroke, and heart failure (HF).ResultsOverall, 40.7% had pre-existing AF (n = 29,563) and 6.8% experienced new-onset AF (n = 2,948) after TAVR. Mean age was 81.3, 82.4, and 83.8 years in patients with no AF, pre-existing, and new-onset AF, respectively. Pre-existing AF patients had the highest burden of comorbidities. After follow-up of 73,732 person-years, mortality was higher with new-onset AF compared with pre-existing and no AF (29.7, 22.6, and 12.8 per 100 person-years, respectively; p < 0.001). After adjusting for patient characteristics and hospital TAVR volume, new-onset AF remained associated with higher mortality compared with no AF (adjusted hazard ratio: 2.068, 95% confidence interval [CI]: 1.92 to 2.20; p < 0.01) and pre-existing AF (adjusted hazard ratio: 1.35; 95% CI: 1.26 to 1.45; p < 0.01). In competing risk analysis, new-onset AF was associated with higher risk of bleeding (subdistribution hazard ratio [sHR]: 1.66; 95% CI: 1.48 to 1.86; p < 0.01), stroke (sHR: 1.92; 95% CI: 1.63 to 2.26; p < 0.01), and HF (sHR: 1.98; 95% CI: 1.81 to 2.16; p < 0.01) compared with pre-existing AF.ConclusionsIn patients undergoing TAVR, new-onset AF is associated with increased risk of mortality and bleeding, stroke, and HF hospitalizations compared with pre-existing AF or no AF.     

Sex Differences in LV Remodeling and Hemodynamics in Aortic Stenosis: Sex-Specific Criteria for Severe Stenosis?

BackgroundThe current criteria for aortic stenosis (AS) severity have not incorporated sex-related differences.ObjectivesThe authors investigated sex-related serial changes in left ventricular (LV) structure/function and hemodynamics in AS.MethodsSerial echocardiograms of patients with severe AS (time 0; aortic valve area [AVA] ≤1 cm²) and ≥1 previous echocardiogram were compared between sexes.ResultsOf 927 patients (time 0: AVA 0.87 ± 0.11 cm², peak velocity 4.03 ± 0.65 m/s, mean Doppler systolic pressure gradient [MG] 40.6 ± 13.1 mm Hg), 393 (42%) were women. Women had smaller body surface area (BSA) (1.77 ± 0.22 m² vs 2.03 ± 0.20 m²; P < 0.001), lower stroke volume (SV) (81.1 ± 17.2 mL vs 88.3 ± 18.6 mL; P < 0.001), and more frequent low-gradient severe AS (n = 196 [50%] vs n = 181 [34%]; P < 0.001). Women consistently had smaller AVA, indexed AVA (AVAi), peak velocity, and MG than men. The difference in aortic valve gradient lessened when AVAi ≤0.6 cm²/m² was applied as severe AS (n = 694, women 43%, AVA 0.95 ± 0.17 cm², AVAi 0.50 ± 0.07 cm²/m²). Peak velocity (3.83 ± 0.66 m/s) and MG (36.5 ± 13.2 mm Hg) were lower based on AVAi severity criteria compared to those based on AVA. Men had a lower left ventricular ejection fraction (LVEF) (55.8% ± 14.8% vs 61.1% ± 11.7%; P < 0.001) and greater reduction in SV (?13.3 ± 19.6 mL vs ?7.4 ± 16.4 mL; P < 0.001) as AS progressed from moderate to severe. Concentric LV hypertrophy was more common and E/e? higher in women (21.2 ± 10.9 vs 18.8 ± 9.1; P < 0.001). SV, LVEF, AVA, peak velocity, and MG became precipitously worse when AVA reached 1.2 cm² in both sexes.ConclusionsSmaller BSA in women yields lower SV, resulting in lower aortic valve gradient than men. Indexed parameters by BSA are thus important in sex-related differences of aortic valve hemodynamics, but AVAi ≤0.6 cm²/m² includes individuals with moderate AS. Elevated filling pressure is more common in women. Men experience a larger reduction in SV and LVEF as AS progresses. The definition of AS severity may require different criteria between sexes.     

MIRACLE2 Score and SCAI Grade to Identify Patients With Out-of-Hospital Cardiac Arrest for Immediate Coronary Angiography

ObjectivesThe purpose of this study was to evaluate the impact of performing immediate coronary angiography (CAG) after out-of-hospital cardiac arrest (OHCA) with stratification of predicted neurologic injury and cardiogenic shock on arrival to a center.BackgroundThe role of immediate CAG for patients with OHCA is unclear, which may in part be explained by the majority of patients dying of hypoxic brain injury.MethodsBetween May 2012 and July 2020, patients from 5 European centers were included in the EUCAR (European Cardiac Arrest Registry). Patients were retrospectively classified into low vs high neurologic risk (MIRACLE₂ score 0-3 vs ≥4) and degree of cardiogenic shock on arrival (Society for Cardiovascular Angiography and Interventions [SCAI] grade A vs B-E). A multivariable logistic regression analysis including immediate CAG was performed for the primary outcome of survival with good neurologic outcome (Cerebral Performance Category 1 or 2) at hospital discharge.ResultsNine hundred twenty-six patients were included in the registry, with 405 (43.7%) in the low-risk group and 521 (56.3%) in the high-risk group. Immediate CAG was independently associated with improved survival with good neurologic outcome in the low MIRACLE₂ risk group with ST-segment elevation myocardial infarction (OR: 11.80; 95% CI: 2.24-76.74; P = 0.048) and with SCAI grade B to E shock (OR: 3.23; 95% CI: 1.10-9.50; P = 0.031). No subgroups, including those with ST-segment elevation myocardial infarction and with SCAI grade B to E shock, achieved any benefit from early CAG in the high MIRACLE₂ group.ConclusionsCombined classification of patients with OHCA with 12-lead electrocardiography, MIRACLE₂ score 0 to 3, and SCAI grade B to E identifies a potential cohort of patients at low risk for neurologic injury who benefit most from immediate CAG.     

1-Year Survival After TAVR of Patients With Low-Flow,Low-Gradient and High-Gradient Aortic Valve Stenosis in Matched Study Populations

ObjectivesThis study sought to examine whether the prognosis of patients with severe aortic stenosis (AS) having high versus low transvalvular mean pressure gradients (MPGs) is intrinsically different after transcatheter aortic valve replacement (TAVR), even after strict matching of baseline parameters.BackgroundPatients with low MPG are characterized by higher cardiovascular risk and more comorbidities than other AS patients are.MethodsIn this retrospective, single-center study involving 2,282 patients, 3 groups were derived according to the following criteria: 1) high-gradient AS (HG-AS) (MPG ≥40 mm Hg); 2) low-flow, low-gradient AS (LFLG-AS) (MPG <40 mm Hg, ejection fraction [EF] ≤40%, stroke volume index ≤35 ml/m²); 3) paradoxical LFLG-AS (pLFLG-AS) (similar to LFLG-AS but with EF ≥50%). Propensity score matching that included EF was used to compare 1-year survival.ResultsA total of 136 patients with HG-AS or LFLG-AS were identified. Kaplan-Meier survival curves were significantly different (p = 0.039), with death occurring in 11 versus 21 patients (hazard ratio: 2.12; 95% confidence interval: 1.02 to 4.39; p = 0.044), respectively. A total of 226 patients with HG-AS or pLFLG-AS were identified and here the curves were identical (p = 0.468), with death occurring in 18 versus 21 patients (hazard ratio: 1.26; 95% confidence interval: 0.67 to 2.38; p = 0.469).ConclusionsThis is the first study comparing survival after TAVR of patients with high versus low MPG in matched study populations. Mortality in patients with LFLG-AS was twice that of HG-AS patients. However, it appears that patients with pLFLG-AS might benefit from TAVR to the same extent as patients with HG-AS. There must be still unmasked factors that influence mortality of patients with LFLG-AS.     

Long-Term Outcomes in Patients With New-Onset Persistent Left Bundle Branch Block Following TAVR

ObjectivesThe aim of this study was to determine the impact of new-onset persistent (NOP) left bundle branch block (LBBB) on long-term (>2 year) outcomes after transcatheter aortic valve replacement (TAVR).BackgroundThe impact of NOP-LBBB after TAVR remains controversial and no data exist regarding long-term outcomes.MethodsA total of 1,020 consecutive patients without pre-existing LBBB or permanent pacemaker implantation (PPI) undergoing TAVR were included. NOP-LBBB was defined as any new LBBB post-TAVR that persisted at hospital discharge. Follow-up clinical and echocardiographic data were obtained at a median of 3 years (interquartile range: 2 to 5 years) post-TAVR.ResultsNOP-LBBB occurred in 212 patients (20.1%) following TAVR. There were no differences between NOP-LBBB and no NOP-LBBB groups, except for a higher use of the self-expandable CoreValve system in the NOP-LBBB group (p < 0.001). At follow-up, there were no differences between NOP-LBBB and no NOP-LBBB groups in all-cause mortality (45.3% vs. 42.5%; adjusted hazard ratio [HR]:1.09; 95% confidence interval [CI]: 0.82 to 1.47; p = 0.54), cardiovascular mortality (14.2% vs. 14.4%; adjusted HR: 1.02; 95% CI: 0.56 to 1.87; p = 0.95), or heart failure rehospitalization (19.8% vs. 15.6%; adjusted HR: 1.44; 95% CI: 0.85 to 2.46; p = 0.18). NOP-LBBB was associated with an increased risk of permanent pacemaker implantation at follow-up (15.5% vs. 5.4%; adjusted HR: 2.45; 95% CI: 1.37 to 4.38; p = 0.002), with the highest risk within the first 12 months. Left ventricular ejection fraction increased over time in patients with no NOP-LBBB but slightly decreased in those with NOP-BBB (p < 0.001 for changes in left ventricular ejection fraction between groups).ConclusionsAfter a median follow-up of 3 years post-TAVR, NOP-LBBB was not associated with a higher mortality or heart failure rehospitalization. However, NOP-LBBB increased the risk of permanent pacemaker implantation and negatively impacted left ventricular function over time. These results should inform future efforts for improving the management of patients with NOP-LBBB post-TAVR.     

Comparative Analysis of Patient Characteristics in Cardiogenic Shock Studies: Differences Between Trials and Registries

ObjectivesThis study sought to evaluate the differences in cardiogenic shock patient characteristics in trial patients and real-life patients.BackgroundCardiogenic shock (CS) is a leading cause of mortality in patients presenting with acute myocardial infarction (AMI). However, the enrollment of patients into clinical trials is challenging and may not be representative of real-world patients.MethodsWe performed a systematic review of studies in patients presenting with AMI-related CS and compared patient characteristics of those enrolled into randomized controlled trials (RCTs) with those in registries.ResultsWe included 14 RCTs (n = 2,154) and 12 registries (n = 133,617). RCTs included more men (73% vs 67.7%, P < 0.001) compared with registries. Patients enrolled in RCTs had fewer comorbidities, including less hypertension (61.6% vs 65.9%, P < 0.001), dyslipidemia (36.4% vs 53.6%, P < 0.001), a history of stroke or transient ischemic attack (7.1% vs 10.7%, P < 0.001), and prior coronary artery bypass graft surgery (5.4% vs 7.5%, P < 0.001). Patients enrolled in RCTs also had lower lactate levels (4.7 ± 2.3 mmol/L vs 5.9 ± 1.9 mmol/L, P < 0.001) and higher mean arterial pressure (73.0 ± 8.8 mm Hg vs 62.5 ± 12.2 mm Hg, P < 0.001). Percutaneous coronary intervention (97.5% vs 58.4%, P < 0.001) and extracorporeal membrane oxygenation (11.6% vs 3.4%, P < 0.001) were used more often in RCTs. The in-hospital mortality (23.9% vs 38.4%, P < 0.001) and 30-day mortality (39.9% vs 45.9%, P < 0.001) were lower in RCT patients.ConclusionsRCTs in AMI-related CS tend to enroll fewer women and lower-risk patients compared with registries. Patients enrolled in RCTs are more likely to receive aggressive treatment with percutaneous coronary intervention and extracorporeal membrane oxygenation and have lower in-hospital and 30-day mortality.     

Left Ventricular Structural and Functional Alterations in Patients With Pheochromocytoma/Paraganglioma Before and After Surgery

ObjectivesThis study sought to evaluate left ventricular (LV) structure and function in pheochromocytoma and paraganglioma (PPGL) patients before and after curative surgery.BackgroundData on catecholamine-induced effects on LV structure and function in patients with PPGL are limited and conflicting.MethodsThe study evaluated 81 consecutive patients with a PPGL, among whom 66 were evaluated 12 months after tumor removal. Fifty patients matched for age, sex, hypertension presence, and blood pressure (BP) levels served as a control group (non-PPGL group). Echocardiography was employed to assess the LV mass index (LVMI), systolic function including speckle tracking echocardiography, and diastolic function.ResultsPatients with PPGL were characterized by higher LVMI (median 103 [interquartile range (IQR): 88 to 132] g/m² vs. median 94 [IQR: 74 to 106] g/m²; p = 0.006) and frequency of LV hypertrophy (44.4% vs. 24.0%; p = 0.018) compared with the non-PPGL group. Patients with PPGLs were characterized by lower global longitudinal strain (GLS) and early diastolic mitral annular velocity compared with patients in the non-PPGL group (median –17.2% [IQR: 15.6% to 18.9%] vs. median –19.3% [IQR: 17.7% to 20.6%]; p < 0.001; and median 11.1 [IQR: 8.3 to 13.0] cm/s vs. median 12.3 [IQR: 10.6 to 14.6] cm/s; p = 0.018, respectively). Presence of LV hypertrophy and GLS were independently associated with plasma free metanephrine concentrations. In operated patients, there were lower frequencies of LV hypertrophy (39.4% vs. 22.7%; p = 0.003), LVMI (median 98 [IQR: 85 to 115] g/m² vs. median 90 [IQR: 76 to 109] g/m²; p < 0.001), and the ratio of transmitral early diastolic velocity to early diastolic mitral annular velocity (median 6.8 [IQR: 5.5 to 8.6] vs. median 6.0 [IQR: 5.0 to 7.6]; p = 0.005) but higher values for GLS (median –17.4 [IQR: –15.8 to 19.1] vs. median −18.5 [IQR: –17.1 to 20.1] p < 0.001) after compared with before surgery.ConclusionsCatecholamine excess in patients with PPGLs can lead not only to LV hypertrophy, but also to impairment of systolic LV function and subclinical alterations of diastolic LV function, independently of BP levels. These structural and functional changes are reversible after surgical intervention.     

The Association of Chronic Kidney Disease With Outcomes Following Percutaneous Left Atrial Appendage Closure

ObjectivesThe aim of this study was to investigate the associations of chronic kidney disease (CKD) and end-stage renal disease (ESRD) with in-hospital and short-term outcomes using a large national database representative of contemporary clinical practice.BackgroundCKD and ESRD are associated with increased risk for stroke and bleeding in patients with atrial fibrillation on oral anticoagulation. Left atrial appendage closure (LAAC) may provide a reasonable alternative for these patients; however, the impact of CKD and ESRD on in-hospital and short-term outcomes following LAAC remain largely unknown.MethodsThe Nationwide Readmissions Database was used to identify LAAC procedures from 2016 to 2017 in patients with no CKD, CKD (stages I-V), and ESRD. Multivariable logistic regression models were used to assess in-hospital and short-term outcomes. The primary outcome was in-hospital mortality.ResultsOf 21,274 patients who underwent LAAC during the study period, 3,954 (18.6%) had CKD and 571 (2.7%) had ESRD. ESRD was associated with increased risk for in-hospital mortality compared with no CKD (3.3% vs 0.4%; adjusted odds ratio: 6.48; 95% confidence interval: 3.35-12.50; P < 0.001) and CKD (3.3% vs 0.5%; adjusted odds ratio: 11.43; 95% confidence interval: 4.77-27.39; P < 0.001). CKD was associated with increased risk for in-hospital acute kidney injury or hemodialysis and stroke or transient ischemic attack. ESRD and CKD were associated with increased readmissions extending to 90 days compared with no CKD, and ESRD was associated with increased readmissions compared with CKD. There was no difference with respect to other in-hospital outcomes.ConclusionsESRD is associated with higher in-hospital mortality, and CKD is associated with higher rates of stroke or transient ischemic attack in patients undergoing LAAC. Further research is needed to assess the impact of CKD and ESRD on long-term outcomes in these patients.