Rihal, Charanjit S.

Introduction: The treatment options for high and extreme-risk patients with severe symptomatic aortic stenosis have changed significantly over the past decade because of advances in transcatheter aortic valve replacement (TAVR). However new permanent pacemaker implant (PPI) remains an impending concern after TAVR. Hypothesis: We sought to determine the frequency, predictors and outcomes of patients requiring PPI after TAVR. Methods: We queried the National Inpatient Sample (NIS) database using the ICD-9-CM procedure code of 35.05 for transfemoral/transaortic and 35.06 for transapical replacement of aortic valve .We identified TAVR procedures associated with new permanent pacemaker implants using appropriate validated ICD-9-CM codes. Using multivariate analysis we further identified predictors of PPM implants Results: An estimated 8828 TAVR procedures were performed in United States between 2011-2012. 773 (8.7%) TAVR procedures were associated with PPIs. PPI were higher in older (age>80 years), White race, diabetics, left bundle branch block (LBBB), right bundle branch block (RBBB), transfemoral approach. The inhospital mortality ( 5.2% vs.4.6% ) , mean length of stay ( 9.8 vs. 8.3 days ) disposition to short term nursing facility was higher (38.2% vs. 32.1%) and mean total costs (82217$ vs. 52283$) was higher in TAVR + PPI group . On multivariate analysis, Age in 5 year increment [Odds ratio (OR) 1.11; Confidence interval (CI) 1.05-1.17, p<0.001], diabetes [OR 1.26; CI 1.07-1.49, p<0.001], LBBB [OR 1.99; CI 1.55-2.56, p<0.001], RBBB [OR 5.36; CI 3.80-7.55, p<0.001] were independent predictors of PPI. Transfemoral approach was associated with more PPI implants [OR 1.41; CI 1.12 -1.78, p<0.001] Conclusion: Age, baseline conduction system disturbances, diabetes, transfemoral approach emerged as independent predictors of PPI after TAVR. This study provides useful tools to identify high-risk patients for PPI after TAVR.

Introduction- Recent studies based on echocardiographic data have described an entity termed paradoxical low-flow, low-gradient severe aortic stenosis (AS) with preserved ejection fraction (EF). It is not clear whether this condition is also seen in patients who undergo hemodynamic catheterization. Objective- To determine the prevalence of low-flow in patients with low mean gradient (MG) severe AS despite preserved EF as determined by echocardiography who subsequently undergo hemodynamic catheterization. Methods- We retrospectively reviewed medical records of 259 patients who underwent hemodynamic catheterization at Mayo Clinic from 2000-2009 to assess the severity of AS within 6 months of their echocardiographic study. Results- A total of 35 patients (mean age 75±9yrs; 49% males) had MG (≤ 40 mm Hg) and aortic valve area (AVA ≤ 1 cm2) despite preserved EF (≥50%) as determined by echocardiography. A total of 7/35 patients (20%) had low flow by echocardiography, defined as stroke volume index (SVI) ≤ 35 ml/m2 (median SVI of 32 ml/m2, inter-quartile range 30-33 ml/m2). Among the same 35 patients, there were 23 patients who had both low MG (≤ 40 mm Hg) and severe AS (AVA ≤ 1 cm2), while a total of 14/35 patients (40%) had low MG, severe AS as well as low flow (median SVI of 32 ml/m2, inter-quartile range 29-33 ml/m2) as determined by hemodynamic catheterization. A statistically significant correlation with modest association was observed between invasive and noninvasive measurements of MG, SVI, and AVA (r=0.48 ; p = 0.003; r=0.48; p = 0.004 ; r=0.36; p=0.03 respectively) in our study group of 35 patients. In most patients (94%) MG by catheterization was also ≤ 40 mm Hg. However, agreement between echocardiography and catheterization to identify patients with paradoxical low-flow, low MG, severe AS was poor (kappa = 0.03). Conclusions- 1) Paradoxical low flow, low-gradient severe aortic stenosis is also observed in patients who undergo hemodynamic catheterization. 2) Further studies are needed to better understand the pathophysiology, best method for diagnosis and true prevalence of this entity.

Background: Depression is prevalent in adults with cardiovascular disease; however, the association between depression and death in older adults treated with percutaneous coronary intervention (PCI) is not known. Method: We prospectively studied 596 patients 65 years of age or older undergoing PCI at Mayo Clinic (Rochester, MN and Franciscan Skemp Hospital in La Crosse, WI) from October 2005 through September 2008. Depression was assessed using the validated and reliable Center for Epidemiological Studies Depression (CES-D) scale. Patients were categorized into groups by depression symptom severity: none/mild (CES-D <16; referent), moderate (CES-D 16-21), or moderate/severe (CES-D>21). Patients were followed annually for death. Results: Mean age of patients was 75.0±6.4 years; 31% were women, 98.0% were white. There were 461 patients (77.3%) that were not depressed and 135 patients (22.7%) that were depressed; 67 patients (11.3%) had moderate depressive scores (CES-D 16-21) and 68 patients (11.4%) had moderate/severe scores (CES-D >21). Groups were similar with respect to baseline characteristics. After a median follow-up of 36 months, there were 74 deaths, and patients with moderate/severe depressive symptom scores had a higher cumulative incidence of mortality (p = 0.036 by log-rank) (Figure). In multivariable analysis, CES-D score >21 was independently predictive of all-cause mortality (HR 1.90; 95% CI 1.02-3.53; p = 0.043), along with other covariates, including age (HR 1.88; 95% CI 1.31-2.68), comorbidity (Charlson Index) (HR 1.08; 95% CI 1.02-1.15), and diabetes mellitus (HR 2.04; 95% CI 1.26-3.30). Conclusion: Over one-fifth of older adults undergoing PCI met criteria for depression and those with high depressive scores reflecting greater self-perceived depressive symptoms had worse survival. Recognition of depressive symptoms in older adults treated with PCI identifies a cohort at higher risk of adverse outcomes.

Introduction: The Innovalve TMVR is a novel self-expandable trans-catheter mitral valve prosthesis, delivered trans-septally using femoral venous access. It is deployed in an intra-valvular posterior position after sub-valvular anchoring by rotation of 6 circumferential arms. LV outflow tract (LVOT) compromise is of great concern in TMVR. A predicted Neo LVOT area of 170 mm 2 is the currently accepted cut-off for LVOT obstruction. Hypothesis: CT can accurately predict the Neo LVOT area prior to Innovalve TMVR procedure. Methods: CT was performed as a screening tool to evaluate the Neo LVOT area prior to Innovalve TMVR procedure. CT protocol: Retrospectively ECG gated with full cardiac cycle coverage. CT was performed before and after the procedure. Predicted Neo LVOT (pNLVOT) was calculated using a dedicated simulation valve prior to TMVR, actual Neo LVOT (aNLVOT) was calculated with the inserted valve in place following TMVR. The native LVOT (nLVOT) area, the predicted % LVOT reduction (nLVOT area-pNLVOT area /nLVOT area), the actual % LVOT reduction (nLVOT area-aNLVOT area /nLVOT area) and the difference between them (pNLVOT%-aNLVOT%) were calculated. Results: One hundred patients were screened for Innovalve TMVR procedure based on Neo LVOT criteria. pNLVOT≥ 170 mm 2 was found in 11 patients (11%), (7 males) average age 68±10 years, these patients underwent Innovalve TMVR procedure. The median calculated LVOT was 647.8+/-260 mm 2 (range 373-1312), the median pNLVOT reduction was 16% ±15 (range 3-53), the median aNLVOT reduction was 5%±14 (range -5-40) and the median difference between the pNLVOT and aNLVOT was 8±12 (range -4-31). In 8/11 patients (73%), the aNLVOT was larger than the pNLVOT (range difference 1 to 31%). In 3/11 patients (27%), the aNLVOT was smaller than the pNLVOT (range difference -1 to -4%). Conclusions: Underestimation of neoLVOT reduction, was uncommon and documented only minor and clinically insignificant difference between the pNLVOT and aNLVOT. As overestimation of NLVOT reduction allows a margin of safety for MTVR, we conclude that CT can serve as reliable NLVOT screening tool.

Introduction: Transcatheter Mitral Valve Replacement (TMVR) using a trans-septal approach is a new therapeutic option for patients with severe mitral regurgitation (MR). However, both surgical as well as currently under-testing trans-catheter approach, are shown to cause decrease in LV function. The Innovalve TMVR is a novel self-expandable transcatheter mitral valve prosthesis, delivered trans-septally using femoral venous access. It is deployed in an intravalvular posterior position after subvalvular anchoring by rotation of 6 circumferential arms Hypothesis: TMVR procedure (Innovalve system) leads to LV anatomical and functional changes Methods: CT was performed before the Innovalve TMVR procedure, and after 3 to 6 months. CT protocol included retrospective ECG gating with full cardiac cycle coverage. LV end diastolic and end systolic diameters (LVEDD, LVESD) were measured in the left ventricular outflow tract orientation at the most basal level. Tip to tip papillary muscle distance was measured in the short axis orientation at the most basal slice demonstrating the papillary muscle tips. LV ejection fraction (LVEF) was calculated using the end systolic and end diastolic volumes. All measurements were performed at end systole and end diastole before MTVR and after 3-6 months using a dedicated platform (3Mensio). Results: Ten patients (7 males) average age 69+/-10 years, underwent the Innovalve TMVR procedure. Average LVESD decreased from 52±15 mm at baseline to 44±15mm (P=0.016) at 3-6 months. Similarly, LVEDD decreased from 60±14 mm at baseline, to 52±13mm at 3-6 months (P=0.039). Average papillary muscle tip to tip distance at end diastole (ED) decreased from 31.7±7mm at baseline to 28.4±6.5mm at 3-6 months (P=0.047).A trend of LVEF improvement was evident with an increase from 35%±12 average at baseline compared with 39%±12 average after 3-6 months (P=0.346). Conclusions: These preliminary results show that the TMVR procedure using the Innovalve system may result in favourable LV reverse remodelling changes including reduction of LVESD, LVEDD and ED papillary muscle distances, with improved LVEF. This encouraging data might suggest favourable postprocedural structural LV change.

BACKGROUND: Alcohol septal ablation (ASA) is a minimally invasive treatment for drug-refractory obstructive hypertrophic cardiomyopathy. Detailed assessment of pressure changes and predictors of mortality and procedure success are not well defined. METHODS: This is a single-center study evaluating pressure changes and predictors of mortality and procedure success in transseptal ASA. Survival analysis and predictors of mortality were assessed using the Kaplan-Meier analysis and Cox regression, respectively. RESULTS: A total of 156 patients were included (mean age, 67.3 years; 46.8% women). Left atrial (LA) pressure and left ventricular outflow tract (LVOT) gradient decreased, whereas aortic pulse pressure (PP) increased post-ASA. Patients with lower baseline mean LA pressure (<median, 19 mm Hg), LVOT gradient reduction >82% (gradient change median), and PP increase >19% (PP change median) had superior survival. On Cox univariable regression, baseline mean LA pressure >median (19 mm Hg; hazard ratio [HR], 2.09 [95% CI, 1.05–4.18]; P =0.036), residual LVOT gradient (HR, 1.02 [95% CI, 1.01–1.03]; P =0.003), and LVOT gradient percent reduction <median (82%; HR, 2.92 [95% CI, 1.46–5.83]; P =0.002) were predictors of mortality. When adjusting for age and sex, baseline LA v wave >median (28 mm Hg; HR, 2.36 [95% CI, 1.17–4.76]; P =0.016), baseline mean LA pressure >median (19 mm Hg; HR, 2.70 [95% CI, 1.33–5.50]; P =0.006), percentage reduction in gradient <median (82%; HR, 2.74 [CI, 1.37–5.50]; P =0.005), and percentage increase in PP <median (19.3%; HR, 2.09 [CI, 1.05–4.16]; P =0.035) predicted survival free of all-cause mortality. CONCLUSIONS: ASA is associated with an acute decrease in the LVOT gradient and LA pressures and increase in aortic PP. Mean LA pressure, percentage decrease in LVOT gradient, and increase in PP are strong predictors of survival free of all-cause mortality following ASA and are important variables for procedural guidance.

ABSTRACT Aims Takotsubo syndrome (TTS) is associated with a substantial rate of adverse events. We sought to design a machine learning (ML)-based model to predict the risk of in-hospital death and to perform a clustering of TTS patients to identify different risk profiles. Methods and results A ridge logistic regression-based ML model for predicting in-hospital death was developed on 3482 TTS patients from the International Takotsubo (InterTAK) Registry, randomly split in a train and an internal validation cohort (75% and 25% of the sample size, respectively) and evaluated in an external validation cohort (1037 patients). Thirty-one clinically relevant variables were included in the prediction model. Model performance represented the primary endpoint and was assessed according to area under the curve (AUC), sensitivity and specificity. As secondary endpoint, a K-medoids clustering algorithm was designed to stratify patients into phenotypic groups based on the 10 most relevant features emerging from the main model. The overall incidence of in-hospital death was 5.2%. The InterTAK-ML model showed an AUC of 0.89 (0.85–0.92), a sensitivity of 0.85 (0.78–0.95) and a specificity of 0.76 (0.74–0.79) in the internal validation cohort and an AUC of 0.82 (0.73–0.91), a sensitivity of 0.74 (0.61–0.87) and a specificity of 0.79 (0.77–0.81) in the external cohort for in-hospital death prediction. By exploiting the 10 variables showing the highest feature importance, TTS patients were clustered into six groups associated with different risks of in-hospital death (28.8% vs. 15.5% vs. 5.4% vs. 1.0.8% vs. 0.5%) which were consistent also in the external cohort. Conclusion A ML-based approach for the identification of TTS patients at risk of adverse short-term prognosis is feasible and effective. The InterTAK-ML model showed unprecedented discriminative capability for the prediction of in-hospital death.

BACKGROUND: The financial burden linked to the diagnosis and treatment of patients with chest pain on the health care system is considerable. Angina and nonobstructive coronary artery disease (ANOCA) is common, associated with adverse cardiovascular events, and may lead to repeat testing or hospitalizations. Diagnostic certainty can be achieved in patients with ANOCA using coronary reactivity testing (CRT); however, its financial effect on the patient has not been studied. Our goal was to assess the effect of CRT on health care–related cost in patients with ANOCA. METHODS: Patients with ANOCA who underwent diagnostic coronary angiography (CAG) and CRT (CRT group) were matched to controls who had similar presentation but only underwent a CAG without CRT (CAG group). Standardized inflation-adjusted costs were collected and compared between the 2 groups on an annual basis for 2 years post the index date (CRT or CAG). RESULTS: Two hundred seven CRT and 207 CAG patients were included in the study with an average age of 52.3±11.5 years and 76% females. The total cost was significantly higher in the CAG group as compared with the CRT group ($37 804 [$26 933–$48 674] versus $13 679 [$9447–$17 910]; P <0.001). When costs are itemized and divided based on the Berenson-Eggers Type of Service categorization, the largest cost difference occurred in imaging (any type, including CAG; P <0.001), procedures (eg, percutaneous coronary intervention/coronary artery bypass grafting/thrombectomy) ( P =0.001), and test (eg, blood tests, EKG; P <0.001). CONCLUSIONS: In this retrospective observational study, assessment of CRT in patients with ANOCA was associated with significantly reduced annual total costs and health care utilization. Therefore, the study may support the integration of CRT into clinical practice.

Introduction: Severe tricuspid regurgitation (TR) is associated with considerable morbidity/mortality in an elderly population with multiple comorbidities. There is interest in transcatheter interventions to manage severe TR in this population. Understanding right heart (RH) anatomy has implications for patient/device selection for transcatheter intervention. Hypothesis: We analyzed RH anatomy by CT of patients referred for TR therapy to determine transcatheter tricuspid intervention device sizing needs. Methods: Retrospective Mayo Clinic study of 29 patients considered for intervention of severe TR from 3/1/2016-12/15/2020; echocardiogram and CT angiogram obtained in all patients. Results: Mean age was 83±8 (83% female), 100% had atrial fibrillation, and 62% had chronic kidney disease ≥3a. 97% were symptomatic, 93% were prescribed loop diuretics, and 24% had device leads. Mean tricuspid annular plane systolic excursion 16.8±4.5 mm, effective regurgitant orifice area (EROA) 81±33 mm 2 , and cardiac index 2.6±0.6 L/min/m 2 . 41% had at least moderate right ventricular (RV) dysfunction with a mean RV systolic pressure of 46±16 mmHg. Patients receiving intervention had significantly larger EROA (101±33 v. 63±22 mm 2 , P=0.033), shorter tricuspid leaflet tenting length (6.5±3.0 v. 8.9±2.7 mm, P=0.042), and smaller annuloplasty diagnostic perimeter during diastole (120.1±16.6 v. 131.1±7.4 mm, P=0.041). Intervention patients tended to have better right ventricular function, smaller RV and IVC size, and more severe symptoms. Max tricuspid annulus diameter in systole and diastole was 51±5 and 53±7 mm, respectively. Conclusions: Severe TR patients referred for transcatheter intervention present with severe RH enlargement with a large proportion having tricuspid annulus dimensions outside the range for current devices available in clinical trials. These data have implications for device development/selection and procedural feasibility.

AbstractBackgroundImprovement in left atrial pressure (LAP) during transcatheter edge‐to‐edge repair (TEER) is associated with improved outcomes. We sought to investigate the predictors of optimal hemodynamic response to TEER.MethodsWe identified patients who underwent TEER at Mayo Clinic between May 2014 and February 2022. Patients with missing LAP data, an aborted procedure, and those undergoing a concomitant tricuspid TEER were excluded. We performed a logistic regression analysis to identify predictors of optimal hemodynamic response to TEER (defined as LAP ≤ 15 mmHg).ResultsA total of 473 patients were included (Mean age 78.5 ± 9.4 years, 67.2% males). Overall, 195 (41.2%) achieved an optimal hemodynamic response after TEER. Patients who did not achieve an optimal response had higher baseline LAP (20.0 [17–25] vs. 15.0 [12–18] mmHg, p < 0.001), higher prevalence of AF (68.3% vs. 55.9%, p = 0.006), functional MR (47.5% vs. 35.9%, p = 0.009), annular calcification (41% vs. 29.2%, p = 0.02), lower left ventricular EF (55% vs. 58%, p = 0.02), and more frequent postprocedural severe MR (11.9% vs. 5.1%, p = 0.02) and elevated mitral gradient >5 mmHg (30.6% vs. 14.4%, p < 0.001). In the multivariate logistic regression analysis, AF (OR = 0.58; 95% CI = 0.35–0.96; p = 0.03), baseline LAP (OR = 0.80; 95% CI = 0.75–0.84; p < 0.001) and postprocedural mitral gradient <5 mmHg (OR = 0.35; 95% CI = 0.19–0.65; p < 0.001), were independent predictors of achieving an optimal hemodynamic response. In the multivariate model, residual MR was not independently associated with optimal hemodynamic response.ConclusionsOptimal hemodynamic response is achieved in 4 in 10 patients undergoing TEER. AF, higher baseline LAP, and higher postprocedural mitral gradient were negative predictors of optimal hemodynamic response after TEER.