Normal-Flow Low-Gradient Aortic Stenosis: Comparing the U.S. and European Guidelines.

Patients with normal-flow low-gradient (NFLG) severe aortic stenosis present both diagnostic and management challenges, with debate about the whether this represents true severe stenosis and the need for valve replacement. Studies exploring the natural history without intervention have shown similar outcomes of patients with NFLG severe aortic stenosis to those with moderate aortic stenosis and better outcomes after valve replacement than those with low-flow low-gradient severe aortic stenosis. Most studies (all observational) have shown that aortic valve replacement was associated with a survival benefit vs surveillance. Based on available data, the European Society of Cardiology/European Association for Cardio-Thoracic Surgery guidelines and European Association of Cardiovascular Imaging/American Society of Echocardiography suggest that these patients are more likely to have moderate aortic stenosis. This clinical entity is not mentioned in the American Heart Association/American College of Cardiology guidelines. Here we review the definition of NFLG severe aortic stenosis, potential diagnostic algorithms and points of error, the data supporting different management strategies, and the differing guidelines and outline the unanswered questions in the diagnosis and management of these challenging patients.

Mitral Valve Transcatheter Edge-to-Edge Repair After TAVR: A Nationwide Analysis.

Patients with persistent severe mitral regurgitation after transcatheter aortic valve replacement (TAVR) may benefit from mitral transcatheter edge-to-edge repair (M-TEER). Using the Nationwide Readmission Database, we identified patients who had M-TEER within 6 months after TAVR and compared their outcomes with patients who had M-TEER without previous recent TAVR during the same calendar year between 2014 and 2020. Because Nationwide Readmission Database data do not cross years, analysis was restricted to the last half of each calendar year. End points included in-hospital mortality and 30-day and 90-day postdischarge rehospitalization rates. In 23,885 M-TEER patients, 396 (1.7%) had a previous recent TAVR. The number of post-TAVR M-TEER procedures increased progressively over time from 16 in 2014 to 92 in 2020. Patients who had M-TEER after a recent TAVR versus those without previous TAVR had similar in-hospital mortality (adjusted odds ratio 0.38, 95% confidence interval [CI] 0.12 to 1.23, p = 0.11), but higher rates of 30-day all-cause hospitalization and heart failure hospitalization (adjusted odds ratios 1.34, 95% CI 1.11 to 1.79, p = 0.04 and 1.63, 95% CI 1.13 to 2.36, p = 0.009, respectively). Nonetheless, in patients who underwent M-TEER post-TAVR, the cumulative 90-day all-cause hospitalization and heart failure hospitalization rates were less after M-TEER compared with before M-TEER (from 45.7% to 31.5%, p = 0.007, and from 29.0% to 16.6%, respectively, both p = 0.005). In conclusion, M-TEER procedures after TAVR in the United States are increasing. Patients with M-TEER after TAVR had similar in-hospital mortality as those who underwent M-TEER without recent TAVR, but higher 30-day hospitalization rates. Nonetheless, 90-day hospitalization rates were decreased after M-TEER in patients with previous TAVR.

Circumstances of Hospitalization Impact Outcomes of Pulmonary Embolism.

Clinical tools that stratify risk of acute pulmonary embolism (PE) are useful in guiding therapeutic decision making, although may neglect pragmatic and potentially impactful characteristics of hospitalization during care of venous thromboembolism (VTE). Using a retrospective cohort design, consecutive patients discharged after inpatient care for acute PE were retrospectively evaluated for features of hospitalization, including patient characteristics, treatment efficiency, and circumstances of hospitalization. A proportional hazards model incorporated nontraditional risk factors to assess their association with a primary composite endpoint of in-hospital bleeding or death after adjusting for conventional PE risk estimators, including the Pulmonary Artery Severity Index (PESI) and right ventricular/left ventricular (RV/LV) ratio. From January 2016 to December 2018, 822 patients were discharged after treatment for acute PE, including high-risk (5.0%), intermediate-risk (64.2%), and low-risk (30.8%) PE. In-hospital death was 10-fold higher among those with high-risk PE compared to intermediate risk PE (36.6% vs 3.0%, P < 0.001). Overall, 60.4% of hospitalizations were primarily attributed to presentation with VTE. High risk PE was observed more frequently as a secondary event during hospitalizations ostensibly unrelated to VTE (26.8%). After adjustment for PESI score and RV/LV ratio, hypoalbuminia, IVC filter, and non-VTE hospitalization had strong associations with the primary composite outcome. Along with known markers of risk associated with PE, hypoalbuminia, IVC filter placement, and PE complicating hospitalization for circumstances not primarily related to VTE had strong associations with bleeding and death. These findings highlight the complex circumstances of acute PE care and need to refine practical risks.

Fibrinolytic Status and Risk of Death After Acute Pulmonary Embolism.

BACKGROUND: Acute pulmonary embolism (PE) is a heterogeneous disease process with variable presentation and outcomes. The endogenous fibrinolytic system is a complex framework of regulatory pathways that maintains homeostasis by dissolving overabundant thrombi. We sought to investigate phenotypic profiles of the endogenous fibrinolytic system among patients presenting with acute PE and their impact on mortality. METHODS: We enrolled all consecutive patients with acute PE in our institutional Pulmonary Embolism Response Team registry. We collected blood samples at the time of PE diagnosis and analyzed concentrations of plasminogen activator inhibitor 1 (PAI-1), thrombin-activatable fibrinolysis inhibitor (TAFI), and alpha-2-antiplasmin (A2A). We assessed the association of concentration of fibrinolytic inhibitors and 1-year all-cause mortality and various echocardiographic markers of right ventricular (RV) dysfunction. RESULTS: There is significant variability of PAI-1, A2A, and TAFI concentrations across the spectrum of PE risk profiles with high PAI-1, low TAFI, and low A2A (herein referred to as a high-risk biomarker profile) correlating with worse PE severity. High-risk biomarker profile correlated with high-risk echocardiographic features of RV dysfunction, including increased RV/left ventricular (LV) ratio, low tricuspid annular plane systolic excursion, and low right ventricular outflow tract velocity time integral. Higher-risk biomarker profile was able to discriminate and independently identify patients at high risk of all-cause mortality (Group 2 HR 6 95% CI 1.3-27.8, Group 3 HR 12, 95% CI 1.7-86). CONCLUSIONS: Further studies are needed to assess the exact pathophysiological link between fibrinolytic status and poor outcome after acute PE and to ascertain the impact of anti-inhibitors of the fibrinolytic system on response to therapy and outcomes after acute PE.

Association between cancer, CHA2DS2VASc risk, and in-hospital ischaemic stroke in patients hospitalized for atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is commonly encountered in cancer patients. We investigated the CHA2DS2VASc score, and its association with in-hospital ischaemic stroke in patients with cancer who were hospitalized for AF. METHODS AND RESULTS: Using the United States National Inpatient Sample, all hospitalizations with principal diagnosis of AF between October 2015 and December 2018 were stratified by cancer diagnosis, type, and CHA2DS2VASc risk categories (low risk, low-moderate risk, moderate-high risk). In-hospital ischaemic stroke and its association with the CHA2DS2VASc risk score was assessed across the groups using hierarchical multivariable logistic regression with adjusted odds ratios (aOR) and 95% confidence intervals (95% CI). Discrimination of CHA2DS2VASc score for in-hospital ischaemic stroke was evaluated with Receiver Operating Characteristic and Area Under the Curve (AUC). Among 1 341 870 included hospitalizations, 71 965 (5.4%) had comorbid cancer. Cancer patients had a higher proportion of moderate-high CHA2DS2VASc risk compared with their non-cancer counterparts (86.5% vs. 82.3%, P < 0.001). Compared with their low CHA2DS2VASc risk counterparts, cancer patients in low-moderate and moderate-high risk scores had similar odds of developing stroke (aOR 1.28 95% CI 0.22-7.63 and aOR 1.78 95% CI 0.41-7.66, respectively). The CHA2DS2VASc risk score had poor discrimination for ischaemic stroke in the cancer group (AUC 0.538 95% CI 0.477-0.598). CONCLUSION: Cancer patients with AF have high CHA2DS2VASc risk. Discrimination of CHA2DS2VASc for ischaemic stroke is lower in cancer than non-cancer patients, and CHA2DS2VASc may not be adequate in determining ischaemic risk in cancer population.

Trends in invasive treatment of patients hospitalized with aortic stenosis complicated by cardiogenic shock.

BACKGROUND: Before the development of transcatheter aortic valve replacement (TAVR), balloon aortic valvuloplasty (BAV) was the only potential nonsurgical intervention for patients with aortic stenosis complicated by cardiogenic shock. Emergent TAVR is now an option and has shown acceptable outcomes compared with elective TAVR. We explored how treatment patterns for aortic stenosis and cardiogenic shock among patients received invasive intervention have shifted since TAVR was introduced. METHODS: We used the Nationwide In patients Sample to identify nonelective hospitalizations for patient with aortic stenosis complicated by cardiogenic shock who received invasive treatment (TAVR, BAV, or surgical aortic valve replacement [SAVR]). We explored the proportion treated with each treatment modality over time, the patient characteristics and in-hospital mortality associated with each treatment, and used multivariable logistic regression to examine whether changes in in-hospital mortality over time differed by treatment. RESULTS: Between 2010 and 2019, we identified 9899 hospitalizations for decompensated aortic stenosis with cardiogenic shock during which patients received invasive treatment (TAVR 17.7%, BAV 20.2%, SAVR 62.1%). Use of both TAVR and BAV has increased over time compared with SAVR (TAVR 6.6% ≥ 33.8%, BAV 8.4% ≥ 23.2%, SAVR 91.6% ≥ 43.0%; p < 0.001 for trend). The overall in-hospital mortality rate was 21.0%, which decreased over time for all treatments (TAVR 20.0% ≥ 18.8%, BAV 66.0% ≥ 25.5%, SAVR 17.7% ≥ 11.8%; linear trend p < 0.001 for each), with lower mortality for TAVR versus BAV at all time points. Patients treated with TAVR (vs. BAV) were less likely to require mechanical ventilation (36.8% vs. 46.3%, p < 0.001) or mechanical circulatory support (22.5% vs. 29.9%, p < 0.001). In the multivariable analysis, the interaction between treatment and time was not significant (p = 0.245), indicating the reduction in in-hospital mortality over time did not differ among the treatments. CONCLUSIONS: Since the introduction of TAVR, there has been a shift toward increased use of nonsurgical invasive treatments (both BAV and TAVR) for aortic stenosis and cardiogenic shock. Although in-hospital mortality has declined, it remains high in all groups, but particularly among patients treated with BAV, where the severity of cardiogenic shock appears to be higher than in those treated with other modalities.

Patient characteristics and survival outcomes of cardiac arrest in the cardiac catheterization laboratory: Insights from get with the Guidelines®-Resuscitation registry.

BACKGROUND: Characteristics and outcomes of patients with in-hospital cardiac arrest (IHCA) in the cardiac catheterization laboratory (CCL) have not been well-described. Thus, we compared the outcomes of patients with an IHCA in the CCL versus those in the intensive care unit (ICU) and operating rooms (OR). METHODS: Within the American Heart Association's Get With the Guidelines®-Resuscitation registry, we identified patients ≥ 18 years old with IHCA in the CCL, ICU, or OR between 2000-2019. Using hierarchical multivariable logistic regression, we compared rates of survival to discharge for patients with IHCA in the CCL versus ICU and OR. RESULTS: Across 428 hospitals, 193,950 patients had IHCA, of whom 6865, 181,905 and 5180 were in the CCL, ICU and OR, respectively. Overall, 2614 (38.1%) patients with IHCA in the CCL survived to discharge, whereas 30,830 (16.9%) and 2096 (40.5%) survived to discharge from the ICU and OR, respectively. After adjustment, patients with IHCA in CCL were more likely to survive to discharge as compared to those with IHCA in the ICU (odds ratio, 1.37 [95%CI: 1.29-1.46], p < 0.001). In contrast, those who had IHCA in the CCL were less likely to survive to discharge as compared to patients with IHCA in the OR (odds ratio, 0.81 [95%CI: 0.69-0.94], p = 0.006). CONCLUSION: IHCA in the CCL is not uncommon and has a lower survival rate when compared with IHCA in the OR. The reasons for this difference deserve further study given that cardiac arrest in both settings is witnessed and response time should be similar.

In-hospital and Readmission Outcomes With Percutaneous Balloon Mitral Valvuloplasty.

Percutaneous balloon mitral valvuloplasty (PBMV) is primarily performed for rheumatic mitral stenosis (MS). Therefore, limited data exist on PBMV in countries with a low incidence of rheumatic disease. Using the Nationwide Readmission Database, we examined trends in in-hospital mortality and 30-day readmission among patients who received PBMV for rheumatic and non-rheumatic MS. We also examined the change in 90-day hospitalization rate before vs after PBMV. Between 2016 and 2019, there were 1109 hospitalizations in which patients received PBMV for rheumatic (n = 955, 86.1%) vs non-rheumatic MS (n = 154, 13.9%). The all-cause in-hospital mortality for rheumatic and non-rheumatic MS did not change over time (0.9% → 2.0%, P = 0.94, and 5.9% → 9.5%, P = 0.09 respectively). Similarly, the 30-day readmission for patients with rheumatic and non-rheumatic MS did not change over time (12.4% → 9.9%, P = 0.26, and 4.4% → 10.5%, P = 0.30, respectively). The 90-day all-cause hospitalization rate remained the same before vs after PBMV for rheumatic and non-rheumatic MS (25.5% → 21.8%; P = 0.14, and 24.0% → 33.7%; P = 0.19, respectively). Although no statistically significant change was noted over time for trends in in-hospital mortality, 30-day readmission, or even in the change in 90-day all-cause hospitalizations before and after PBMV for both types of MS, among those with non-rheumatic MS, there was a signal of an increase in the in-hospital mortality, and 30-day readmission, even more, there was 29% relative increase in 90-day hospitalizations after PBMV. Future studies are needed to examine the role of PBMV in patients with non-rheumatic MS.

Meta-analysis Comparing Percutaneous Coronary Intervention With Coronary Artery Bypass Grafting for Non-ST Elevation Acute Coronary Syndrome in Patients With Multivessel or Left Main Disease.

Outcomes of patients presenting with non-ST-elevation acute coronary syndrome (NSTE-ACS) with multivessel coronary disease (MVD) and/or unprotected left main coronary artery disease (CAD) revascularized with percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) is not well defined. MEDLINE/PubMed and EMBASE/Ovid were queried for studies that investigated PCI vs CABG in this disease subset. The primary outcome was major cardiac adverse events (MACE) at 30 days and long-term follow-up (3-5 years). The final analysis included 9 studies with a total of 9299 patients. No significant difference was observed between PCI and CABG in 30 days MACE (risk ratio [RR] 0.96; 95% confidence interval [CI] 0.38-2.39, all-cause mortality, myocardial infarction, and stroke. A meta-regression analysis revealed patients with a history of PCI had higher risk of MACE with PCI as compared with CABG. At long-term follow-up, PCI compared with CABG was associated with higher risk of MACE (RR 1.52; 95% CI 1.28-1.81), myocardial infarction, and repeat revascularization, while no difference was observed in the risk of stroke and all-cause mortality. In patients with NSTE-ACS and MVD or unprotected left main CAD, no differences were observed in the clinical outcomes between PCI and CABG at 30 days follow-up. With long-term follow-up, PCI was associated with a higher risk of MACE.

Comparison of the Safety of Left Atrial Appendage Occlusion in Patients Aged <75 Versus Those Aged ≥75 Years (from a Nationwide Cohort Sample).

The mean age in clinical trials of percutaneous left atrial appendage occlusion (LAAO) has been <75 years. We aimed to better understand the safety of LAAO in older patients. National Inpatient Sample and International Classification of Diseases, Tenth Revision codes were used to identify patients with atrial fibrillation who underwent LAAO during the years 2016-2018. Patients were grouped by age <75 and ≥75 years. Baseline characteristics; length of stay; cost; hospital mortality; and other adverse events, including hematoma, vascular complications, perforation/tamponade, and stroke/ transient ischemic attack, were compared for the 2 groups. A total of 6,877 patients were identified, of whom 4,160 (60.4%) were aged ≥75 years. Length of stay and hospitalization costs were similar for the 2 groups. There were 10 deaths in patients aged ≥75 years and 1 death in patients aged <75 years (p = 0.059). The incidence of perforation/tamponade was 1.3% in patients aged ≥75 years versus 0.6% for those <75 years (p = 0.008). This difference persisted on multivariate analysis (odds ratio [OR] 1.76, 95% confidence interval [CI] 1.01 to 3.07). The risk of perforation/tamponade was also higher in female patients (OR 2.74, 95% CI 1.63 to 4.59). There was a trend toward higher combined procedure-related adverse events (OR 1.46, 95% CI 0.99 to 2.15) in patients ≥75 years. There was no difference in the individual components of hematoma, vascular complication, and stroke/transient ischemic attack between both groups. In conclusion, percutaneous LAAO was associated with a higher risk of perforation and tamponade in older patients, particularly women.