The interaction of forced expiratory volume in 1 s and N-terminal pro-B-type natriuretic peptide with outcomes after transcatheter aortic valve replacement.

OBJECTIVES: Low forced expiratory volume in 1 s (FEV1) and elevated N-terminal pro-B-type natriuretic peptide (NT-Pro-BNP) have been individually associated with poor outcomes after transcatheter aortic valve replacement (TAVR). We hypothesized a combination of the 2 would provide prognostic indication after TAVR. METHODS: We categorized 871 patients who received TAVR from 2008 to 2018 into 4 groups according to baseline FEV1 (<60% or ≥60% predicted) and NT-Pro-BNP (<1601 or ≥1601 pg/ml): group A (n = 312, high FEV1, low NT-Pro-BNP), group B (n = 275, high FEV1, high NT-Pro-BNP), group C (n = 123 low FEV1, low NT-Pro-BNP) and group D (n = 161, low FEV1, high NT-Pro-BNP). The primary end point was survival at 1 and 5 years. RESULTS: Patients in group A had more severe aortic stenosis and achieved the best long-term survival at 1 [93% (95% CI: 90-96)] and 5 [45.3% (95% CI: 35.4-58)] years. Low FEV1 and high NT-Pro-BNP (group D) patients had more severe symptoms, higher Society of Thoracic Surgeons predicted risk of operative mortality, lower ejection fraction and aortic valve gradient at baseline. Patients in group D had the worst survival at 1 [76% (95% CI: 69-83)] and 5 years [13.1% (95% CI: 7-25)], hazard ratio compared to group A: 2.29 (95% CI: 1.6-3.2, P < 0.001) with 25.7% of patients in New York Heart Association class III-IV. Patients in groups B and C had intermediate outcomes. CONCLUSIONS: The combination of FEV1 and NT-Pro-BNP stratifies patients into 4 groups with distinct risk profiles and clinical outcomes. Patients with low FEV1 and high NT-Pro-BNP have increased comorbidities, poor functional outcomes and decreased long-term survival after TAVR.

Partial Anomalous Pulmonary Venous Connection With Intact Atrial Septum: Early and Midterm Outcomes.

BACKGROUND: Partial anomalous pulmonary venous return with intact atrial septum warrants greater understanding and evaluation in the literature. METHODS: From January 1993 to December 2018, 293 patients with partial anomalous pulmonary venous return underwent surgical repair. Of these, 45 patients (15.3%) had an intact atrial septum. The median age was 36 years (interquartile range, 24-48). Direct reimplantation was used in 17 patients (38%), intracardiac baffling in 15 (33%), and caval division (Warden) technique in 13 (29%). Descriptive statistics were used to assess the data, and Kaplan-Meier analysis was used to assess survival. RESULTS: Anomalous veins were right-sided in 27 patients (60%), left-sided in 16 patients (36%), and bilateral in 2 patients (4%). The insertion sites were the superior vena cava in 23 patients (51%), innominate vein in 12 (27%), inferior vena cava in 6 (13%), coronary sinus in 2 (4%), right atrium in 1 patient (2%), and unknown in 1 patient (2%). Scimitar syndrome was noted in 8 patients (18%). There was no postoperative mortality or residual defects. Postoperative echocardiography excluded any obstruction of pulmonary or systemic veins. Postoperative complications included atrial fibrillation in 9 patients (20%) and pneumothorax requiring chest tube in 5 patients (11%). Survival at 1, 5, and 10 years was 100%, 95%, and 95%, respectively. Two patients underwent pulmonary vein dilation, one at 3 years and the other at 7 years. CONCLUSIONS: Surgical repair of partial anomalous pulmonary venous connection with intact atrial septum can be performed with excellent early and midterm outcomes. The overall incidence of midterm systemic or pulmonary vein stenosis is low.

Early and Late Outcomes of the Warden and Modified Warden Procedure.

BACKGROUND: Operative repair of partial anomalous pulmonary venous connection (PAPVC) remains challenging due to risks of sinus node dysfunction, baffle obstruction, and superior vena cava (SVC) obstruction. METHODS: Traditional or modified Warden procedures were performed in 75 of 318 consecutive patients (24%) with PAPVC repaired surgically at our institution during 1993 to 2021. Clinical characteristics, echocardiography data, operative details, and early and late outcomes were collected. Cumulative incidence of reintervention and Kaplan-Meier survival analysis are reported. RESULTS: Median age was 39 years (interquartile range, 21-57 years). Fifty-nine (79%) had normal sinus rhythm preoperatively. Seventeen (23%) had intact atrial septa. Traditional and modified Warden procedures were performed in 15 (20%) and 60 (80%), respectively. Frequent concomitant procedures included 15 (20%) tricuspid valve repairs and 12 (16%) atrial fibrillation procedures. There were no early deaths. Postoperative complications included atrial fibrillation in 17 (23%), sinus node dysfunction in 15 (20%), pneumothorax in 3 (4%), pleural effusion in 2 (3%), and pacemaker implantation in 1 (1%). At hospital discharge, sinus node dysfunction persisted in 8 (11%). Over a median follow-up of 6 years (interquartile range, 4-10 years), baffle obstruction developed in 1 patient and SVC obstruction developed in 7. None required reoperation and 6 were treated with SVC stents. At 1, 5, and 10 years, the cumulative incidence of reintervention was 5%, 7%, and 14%, and survival was 99%, 94%, and 94%, respectively. CONCLUSIONS: Traditional and modified Warden procedures can be performed with satisfactory early and late survival. Persistent sinus node dysfunction and need for permanent pacing are low. Late SVC obstruction is uncommon and can often be managed nonoperatively.

A Living, Interactive Systematic Review and Network Meta-analysis of First-line Treatment of Metastatic Renal Cell Carcinoma.

CONTEXT: Identifying the most effective first-line treatment for metastatic renal cell carcinoma (mRCC) is challenging as rapidly evolving data quickly outdate the existing body of evidence, and current approaches to presenting the evidence in user-friendly formats are fraught with limitations. OBJECTIVE: To maintain living evidence for contemporary first-line treatment for previously untreated mRCC. EVIDENCE ACQUISITION: We have created a living, interactive systematic review (LISR) and network meta-analysis for first-line treatment of mRCC using data from randomized controlled trials comparing contemporary treatment options with single-agent tyrosine kinase inhibitors. We applied an advanced programming and artificial intelligence-assisted framework for evidence synthesis to create a living search strategy, facilitate screening and data extraction using a graphical user interface, automate the frequentist network meta-analysis, and display results in an interactive manner. EVIDENCE SYNTHESIS: As of October 22, 2020, the LISR includes data from 14 clinical trials. Baseline characteristics are summarized in an interactive table. The cabozantinib + nivolumab combination (CaboNivo) is ranked the highest for the overall response rate, progression-free survival, and overall survival, whereas ipilimumab + nivolumab (NivoIpi) is ranked the highest for achieving a complete response (CR). NivoIpi, and atezolizumab + bevacizumab (AteBev) were ranked highest (lowest toxicity) and CaboNivo ranked lowest for treatment-related adverse events (AEs). Network meta-analysis results are summarized as interactive tables and plots, GRADE summary-of-findings tables, and evidence maps. CONCLUSIONS: This innovative living and interactive review provides the best current evidence on the comparative effectiveness of multiple treatment options for patients with untreated mRCC. Trial-level comparisons suggest that CaboNivo is likely to cause more AEs but is ranked best for all efficacy outcomes, except NivoIpi offers the best chance of CR. Pembrolizumab + axitinib and NivoIpi are acceptable alternatives, except NivoIpi may not be preferred for patients with favorable risk. Although network meta-analysis provides rankings with statistical adjustments, there are inherent biases in cross-trial comparisons with sparse direct evidence that does not replace randomized comparisons. PATIENT SUMMARY: It is challenging to decide the best option among the several treatment combinations of immunotherapy and targeted treatments for newly diagnosed metastatic kidney cancer. We have created interactive evidence summaries of multiple treatment options that present the benefits and harms and evidence certainty for patient-important outcomes. This evidence is updated as soon as new studies are published.

Management of Subaortic Left Ventricular Outflow Tract Obstruction After Aortic Valve Replacement.

BACKGROUND: Residual or new left ventricular outflow tract (LVOT) obstruction after an aortic valve replacement poses special challenges with respect to operative techniques. Our study assesses this gap. METHODS: From January 1993 to May 2019, 18 patients underwent a septal myectomy at Mayo Clinic for subaortic obstruction after aortic valve replacement. We evaluated their demographics, clinical presentation, and echocardiograms, and the type of prior valve replacement, need for repeat replacement, and their short- and long-term outcomes. The data were analyzed using descriptive statistics. RESULTS: All patients underwent septal myectomy for LVOT obstruction at a median interval of 7 years (interquartile range, 3-15 years) from their prior aortic valve procedure. Preoperatively, the median left ventricular outflow tract gradient was 57 mm Hg (interquartile range, 44-77 mm Hg); 10 patients (55.5%) had systolic anterior motion (SAM) of the mitral leaflets. Repeat replacement of the aortic valve at the time of myectomy was needed in 14 patients, and septal myectomy alone was performed in 4 patients. One hospital death occurred 34 days after myectomy and aortic valve replacement, and 2 patients needed permanent pacemaker placement for complete heart block. CONCLUSIONS: Septal myectomy after aortic valve replacement may be performed with repeat replacement of the valve, if there is coexisting prosthetic dysfunction, through a normally functioning bioprosthesis or through an apical approach when visualization through the aortic prosthesis is poor. The complexity of reoperation supports a liberal approach to myectomy at the time of aortic valve replacement when there is significant subaortic septal hypertrophy.

Septal Myectomy in patients with previous coronary revascularization - hypertrophic cardiomyopathy masquerading as ischemic heart disease.

BACKGROUND: Patients with obstructive hypertrophic cardiomyopathy (HCM) may have symptoms mimicking ischemic heart disease, including chest pain and shortness of breath. Some patients undergo coronary revascularization which may not lead to symptomatic improvement. This study assesses clinical presentations and outcomes of patients with previous coronary revascularization undergoing septal myectomy. METHOD: From 08/1996 to 07/2017, 166 adult patients with obstructive HCM underwent septal myectomy at our Clinic with a history of percutaneous coronary intervention (PCI, N = 153) or coronary artery bypass grafting (CABG, N = 13). We assessed their functional status before and after coronary intervention and outcomes following myectomy. RESULTS: The median (IQR) age was 65 (59-71) years, and 106 (64%) were male. Among 150 patients whose extent of disease was known, single vessel disease was identified in 109 (73%) who had PCI and 1 (9%) who had CABG. Following revascularization, many (59%) reported no improvement in shortness of breath from preoperative status. Myectomy was performed at a median of 3.2 (1.0-6.3) years following coronary revascularization, and 40 (25%) required myectomy within 1 year. Patients whose shortness of breath persisted after PCI/CABG (N = 90) underwent myectomy earlier than those whose symptoms initially improved (N = 63) after coronary revascularization (1.4 [0.6-4.0] years vs. 5.1 [2.8-9.5] years, p < .001). CONCLUSION: Almost 25% of patient's required septal myectomy within 1 year of coronary intervention for continued symptoms originally thought to be due to ischemic heart disease. These findings highlight the overlap of obstruction and ischemic symptoms and the importance of complete evaluation for dynamic obstruction in HCM.

Usefulness of Right Ventricular Volumetric and Afterload Indices for Risk Stratification in Patients With Tetralogy of Fallot.

Right ventricular (RV) volume overload due to chronic pulmonary regurgitation is the common mechanism for hemodynamic deterioration after tetralogy of Fallot (TOF) repair. As a result, RV volumetric indices are used for clinical risk stratification in this population. Since RV afterload is a determinant of RV hemodynamic performance, we hypothesized that afterload-adjusted RV volumetric indices will have a better correlation with disease severity compared with RV volumetric indices alone in patients with TOF. Cross-sectional study of adults with previous TOF repair that received care at Mayo Clinic, 2002-2015. We defined disease severity as atrial arrhythmia and/or impaired exercise capacity. We created afterload-adjusted RV volumetric indices by indexing these indices to RV systolic pressure (RVSP) as follows: RV end-diastolic volume (RVEDVi)/RVSP, RV end-systolic volume (RVESVi)/RVSP, and RV ejection fraction (RVEF)/RVSP. The RV volumetric indices were: RVEDVi 141 ± 43 ml/m2, RVESVi 79 ± 38 ml/m2, and RVEF 44 ± 10%, and RVSP was 48 ± 9 mm Hg. RVESVi was the only RV volumetric parameter that was associated with disease severity (odds ratio [OR] 1.13, 95% confidence interval [CI] 1.01 to 1.32, p = 0.041) with area under the curve (AUC) of 0.612. In contrast RVEF/RVSP (OR 0.73, 95% CI 0.38 to 0.92, p = 0.037, AUC 0.649), and RVESVi/RVSP (OR 1.28, 95% CI 1.14-1.55, p = 0.008, AUC 0.798) were associated with disease severity. Compared with RV volumetric indices alone, the combined RV volumetric and afterload indices had better correlation with disease severity as measured by AUC. Afterload-adjusted RV volumetric indices had better correlation with disease severity, and may potentially improve risk stratification in this population.

Mechanism and Risk Factors for Death in Adults With Tetralogy of Fallot.

One of the goals of lifelong care in adults with tetralogy of Fallot (TOF) is early identification and treatment of patients at high risk for adverse events. Clinical risk stratification tools are critical for achieving this goal. We reviewed the Mayo Adult Congenital Heart Disease database and identified 465 TOF patients (age 37 ± 14 years, men 223 [48%]) seen at Mayo Clinic Rochester between 1990 and 2017. The aim was to determine the risk factors for death and/or heart transplant through a comprehensive analysis of 8 groups of variables (demographics, co-morbidities, medications, heart rhythm, echocardiography, cardiac magnetic resonance imaging, cardiac catheterization, and cardiopulmonary exercise test data) using univariable and multivariable Cox proportional hazard models. The end point of death and/or transplant occurred in 57 (12%) patients during a follow-up of 13.6 ± 8.2 years, yielding an event rate of 0.9% per year. Independent risk factors were age >42 years, atrial fibrillation, ≥moderate QRS fragmentation, left ventricular ejection fraction <50%, right ventricular end-diastolic pressure >16 mm Hg, and left ventricle end-diastolic pressure >16 mm Hg. There is nearly a twofold increase in the risk of death and/or transplant per unit increase in number of risk factors (hazard ratio 1.92, 95% confidence interval 1.62 to 2.27, p <0.001). In conclusion, the current study provides risk stratification indices based on a comprehensive risk model of all clinical variables in an unselected TOF population. Further studies are required to determine whether interventions targeted at modifying these risk factors will alter the annual event rate.