Diastolic dysfunction and clinical outcomes after transcatheter or surgical aortic valve replacement in patients with atypical aortic valve stenosis.

BACKGROUND: Diastolic dysfunction is a predictor of poor outcomes in many cardiovascular conditions. At present, it is unclear whether diastolic dysfunction predicts adverse outcomes in patients with atypical aortic stenosis who undergo aortic valve replacement (AVR). METHODS: Five hundred and twenty-three patients who underwent transcatheter AVR (TAVR) (n = 303) and surgical AVR (SAVR) (n = 220) at a single institution were included in our analysis. Baseline left and right heart invasive hemodynamics were assessed. Baseline transthoracic echocardiograms were reviewed to determine aortic stenosis subtype and parameters of diastolic dysfunction. Aortic stenosis subtype was categorized as typical (normal flow, high-gradient) aortic stenosis, classical, low-flow, low-gradient (cLFLG) aortic stenosis, and paradoxical, low-flow, low-gradient (pLFLG) aortic stenosis. Cox proportional hazard models were utilized to examine the relation between invasive hemodynamic or echocardiographic variables of diastolic dysfunction, aortic stenosis subtype, and all-cause mortality. Propensity-score analysis was performed to study the relation between aortic stenosis subtype and the composite outcome [death/cerebrovascular accident (CVA)]. RESULTS: The median STS risk was 5.3 and 2.5% for TAVR and SAVR patients, respectively. Relative to patients with typical aortic stenosis, patients with atypical (cLFLG and pLFLG) aortic stenosis displayed a significantly higher prevalence of diastolic dysfunction (LVEDP ≥ 20mmHg, PCWP ≥ 20mmHg, echo grade II or III diastolic dysfunction, and echo-PCWP ≥ 20mmHg) and, independently of AVR treatment modality, had a significantly increased risk of death. In propensity-score analysis, patients with atypical aortic stenosis had higher rates of death/CVA than typical aortic stenosis patients, independently of diastolic dysfunction and AVR treatment modality. CONCLUSION: We demonstrate the novel observation that compared with patients with typical aortic stenosis, patients with atypical aortic stenosis have a higher burden of diastolic dysfunction. We corroborate the worse outcomes previously reported in atypical versus typical aortic stenosis and demonstrate, for the first time, that this observation is independent of AVR treatment modality. Furthermore, the presence of diastolic dysfunction does not independently predict outcome in atypical aortic stenosis regardless of treatment type, suggesting that other factors are responsible for adverse clinical outcomes in this higher risk cohort.

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.

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.

Fibrous Cap Thickness Predicts Stable Coronary Plaque Progression: Early Clinical Validation of a Semiautomated OCT Technology.

Background: Imaging-based characteristics associated with the progression of stable coronary atherosclerotic lesions are poorly defined. Utilizing a combination of optical coherence tomography (OCT) and intravascular ultrasound (IVUS) imaging, we aimed to characterize the lesions prone to progression through clinical validation of a semiautomated OCT computational program. Methods: Patients with stable coronary artery disease underwent nonculprit vessel imaging with IVUS and OCT at baseline and IVUS at the 12-month follow-up. After coregistration of baseline and follow-up IVUS images, paired 5-mm segments from each patient were identified, demonstrating the greatest plaque progression and regression as measured by the change in plaque burden. Experienced readers identified plaque features on corresponding baseline OCT segments, and predictors of plaque progression were assessed by multivariable analysis. Each segment then underwent volumetric assessment of the fibrous cap (FC) using proprietary software. Results: Among 23 patients (70% men; median age, 67 years), experienced-reader analysis demonstrated that for every 100 µm increase in mean FC thickness, plaques were 87% less likely to progress (P = .01), which persisted on multivariable analysis controlling for baseline plaque burden (P = .05). Automated FC analysis (n = 17 paired segments) confirmed this finding (P = .01) and found thinner minimal FC thickness (P = .01) and larger FC surface area of <65 µm (P = .02) and <100 µm (P = .04) in progressing segments than in regressing segments. No additional imaging features predicted plaque progression. Conclusions: A semiautomated FC analysis tool confirmed the significant association between thinner FC and stable coronary plaque progression along entire vessel segments, illustrating the diffuse nature of FC thinning and suggesting a future clinical role in predicting the progression of stable coronary artery disease.

Immersive educational curriculum on intracoronary optical coherence tomography image analysis among naïve readers.

BACKGROUND: Optical coherence tomography (OCT) is an intravascular imaging modality for analysing coronary vessels. Image interpretation remains an obstacle for novice readers due to technical artefacts and uncertainty in tissue characterization. Despite an expanding clinical and research role for OCT, few training efforts exist, and there is an absence of a national standardized educational curriculum. We sought to determine whether an interactive, feedback-based OCT curriculum improved image interpretation among naive readers. METHODS: Naive OCT readers completed both a Standard curriculum, comprised of self-directed didactics and consensus statements, and an Augmented curriculum, which provided real-time digital feedback of feature identification and measurements. Modules were separated by a minimum one-week washout period. After each module, and blinded to the exam answers, subjects completed an identical expert-designed 413-item exam to assess technical knowledge and ability to identify and measure vessel features. Performances were compared using Exact Wilcoxon signed-rank tests. RESULTS: Among the 7 included subjects were 3 medical students, 3 internal medicine residents, and 1 cardiovascular medicine fellow with no prior OCT experience. The technical knowledge score (maximum 13) was significantly higher with the Augmented compared with the Standard curriculum (median 11 vs. 7, p = 0.03). After undergoing the Augmented curriculum, all 7 subjects were able to identify features of plaque rupture (Standard curriculum: 5/7 subjects, p = 0.5) and macrophages (Standard curriculum: 6/7 subjects, p = 0.99), differentiate the components between red and white thrombus (Standard curriculum: 6/7 subjects, p = 0.99), and characterize lipid plaque by attenuation, signal, homogeneity, and borders (Standard curriculum: 5/7 subjects, p = 0.5). Performances on the remaining exam portions did not differ between curricula. CONCLUSIONS: The need for standardized, effective training in OCT image interpretation is increasingly essential as the intravascular imaging modality becomes widely utilized among interventional cardiologists and trainees. A novel interactive OCT curriculum enhanced naive readers' technical knowledge and may supplement traditional self-learning in refining analytic skills.

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.

Impact of Transcatheter Aortic Valve Replacement on Hospitalization Rates: Insights From Nationwide Readmission Database.

Background Hospitalization rates after transcatheter aortic valve replacement (TAVR) remain high, given the age and comorbidities of patients undergoing TAVR. To better understand the impact of TAVR on hospitalization, we sought to compare hospitalization rates before and after TAVR and to examine if underlying patient comorbidities are associated with a differential effect of TAVR on hospitalizations. Methods and Results We used the Nationwide Readmissions Database to identify patients who underwent TAVR. As Nationwide Readmissions Database data do not cross over calendar years, we limited our index admission to hospitalizations during April to September of each calendar year to allow 90 days of observation before and after TAVRs. We calculated the daily risk of all-cause hospitalization and used a mixed-effects logistic regression model to explore interactions between patient characteristics, TAVR, and hospitalization risk. Among 39 249 patients who underwent TAVR in 2014 to 2017 (median age, 82 years [interquartile range, 76-87 years]; 45.7% women), 32.0% had at least one hospitalization in the 90 days before TAVR compared with 23.2% in the 90 days post-TAVR (relative reduction, 27.5%; P<0.001). In the mixed-effects logistic regression model, TAVR was associated with decreased all-cause hospitalization rate after TAVR in all comorbidity subgroups. However, younger patients and those with heart failure and reduced ejection fraction appeared to have more robust reduction in hospitalizations. Conclusions Although patients who are treated with TAVR have high rates of rehospitalization, TAVR is associated with an overall reduction in all-cause hospitalizations regardless of underlying patient comorbidities.

Relationship of Stress Test Findings to Anatomic or Functional Extent of Coronary Artery Disease Assessed by Coronary Computed Tomography Angiography-Derived Fractional Flow Reserve.

BACKGROUND: In the United States, functional stress testing is the primary imaging modality for patients with stable symptoms suspected to represent coronary artery disease (CAD). Coronary computed tomography angiography (CTA) is excellent at identifying anatomic coronary artery disease (CAD). The application of computational fluid dynamics to coronary CTA allows fractional flow reserve (FFR) to be calculated noninvasively (FFRCT). The relationship of noninvasive stress testing to coronary CTA and FFRCT in real-world clinical practice has not been studied. METHODS: We evaluated 206 consecutive patients at Loyola University Chicago with suspected CAD who underwent noninvasive stress testing followed by coronary CTA and FFRCT when indicated. Patients were categorized by stress test results (positive, negative, indeterminate, and equivocal). Duke treadmill score (DTS), METS, exercise duration, and chest pain with exercise were analyzed. Lesions ≥ 50%stenosis were considered positive by coronary CTA. FFRCT < 0.80 was considered diagnostic of ischemia. RESULTS: Two hundred and six patients had paired noninvasive stress test and coronary CTA/FFRCT results. The median time from stress test to coronary CTA was 49 days. Average patient age was 60.3 years, and 42% were male. Of the 206 stress tests, 75% were exercise (70% echocardiographic, 26% nuclear, and 4% EKG). There were no associations of stress test results with CAD > 50% or FFRCT < 0.80 (p = 0.927 and p = 0.910, respectively). Of those with a positive stress test, only 30% (3/10) had CAD > 50% and only 50% (5/10) had FFRCT < 0.80. Chest pain with exercise did not correlate with CAD > 50% or FFRCT < 0.80 (p = 0.66 and p = 0.12, respectively). There were no significant correlations between METS, DTS, or exercise duration and FFRCT (r = 0.093, p = 0.274; r = 0.012, p = 0.883; and r = 0.034, p = 0.680; respectively). CONCLUSION: Noninvasive stress testing, functional capacity, chest pain with exercise, and DTS are not associated with anatomic or functional CAD using a diagnostic strategy of coronary CTA and FFRCT.