Long-term Stroke and Mortality Risk in Nonagenarians Following Transcatheter Aortic Valve Insertion.

BACKGROUND: Limited data exist on the long-term outcomes of transcatheter aortic valve insertion (TAVI) in nonagenarian patients. The purpose of this study is to investigate the relationship between patient baseline comorbidity and frailty on the long-term outcome of the nonagenarian population. METHODS: Retrospective analysis of 187 consecutive nonagenarian patients who underwent TAVI from 2009 to 2020. Multivariable models were utilized to analyze the association between basleline patient and frailty variables and mortality, stroke, and repeat hospitalization. Long-term survival was compared to an age- and sex-matched US population. RESULTS: The median STS-predicted risk of mortality (STS-PROM) was 10% (IQR, 7-17%). Frailty was met in 72% of patients based on the five-meter walk test, 13% based on KCCQ-12 score, 12% based on KATZ activities of daily living, and 8% based on serum albumin levels. Procedure-related mortality occured in 3 (2%) patients and stroke in 8 (4%). The median duration of follow-up was 3.4 years. Outcomes included death in 150 (80%) patients, stroke in 15, and repeat hospitalization in 114. Multivariable analysis identified no association between any of the baseline patient variables with mortality, stroke, repeat hospitalization, or the combined outcomes (all P>0.05). One- and five-year survival rates in TAVI-treated nonagenarians were similar to age- and sex-matched controls (P=0.27). CONCLUSIONS: Long-term death or stroke is independent of STS-PROM and frailty risk variables in this nonagenarian patient population who received TAVI. Furthermore, survival is similar to age- and sex-matched controls.

Patients With Coronary Microvascular Dysfunction Have Less Circulating α-Klotho.

BACKGROUND: Coronary microvascular dysfunction (CMD) represents an early functional characteristic of coronary vascular aging. Klotho (α-klotho) is a circulating protein inversely linked to physiological aging. We examined low klotho as a potential marker for vascular aging in patients with CMD and no coronary artery disease. METHODS AND RESULTS: Patients undergoing nonurgent angiogram for chest pain who had no coronary artery disease underwent invasive coronary microvascular and endothelial function testing. CMD was defined by ≤50% increase in coronary blood flow (percentage change in coronary blood flow) in response to intracoronary acetylcholine or coronary flow reserve ≤2. Fresh arterial whole blood was used to analyze circulating endothelial progenitor cells with flow cytometry. Stored arterial plasma was used for klotho analysis by ELISA. Participants with CMD (n=62) were compared with those without CMD (n=36). Those with CMD were age 55±10 years (versus 51±11 years; P=0.07) and 73% women (versus 81%; P=0.38). Traditional risk factors for coronary artery disease were similar between groups. Patients with CMD had less klotho (0.88±1.50 versus 1.75±2.38 ng/mL; P=0.03), and the odds of low klotho in CMD were significant in a logistic regression model after adjusting for traditional cardiovascular risk factors (odds ratio [OR], 0.80 [95% CI, 0.636-0.996]; P=0.05). Higher klotho was associated with higher numbers of endothelial progenitor cells with vascular regenerative potential (CD34+ and CD34+CD133+KDR+). Among a subgroup of patients with atherosclerotic cardiovascular disease risk <5% (n=58), CMD remained associated with lower klotho (OR, 0.80 [95% CI, 0.636-0.996]; P=0.047). CONCLUSIONS: Klotho may be a biomarker for CMD and may be a therapeutic target for groups of patients without significant traditional cardiovascular risk.

High Baseline High-Sensitivity Cardiac Troponin T Concentrations and Risk of Index Acute Myocardial Infarction.

OBJECTIVE: To evaluate the diagnostic performance of the previously recommended baseline high-sensitivity cardiac troponin T (hs-cTnT) thresholds of 52 and 100 ng/L in identifying patients at high risk of acute myocardial infarction (AMI). PATIENTS AND METHODS: This study compared the positive predictive value (PPV) for index AMI of these high-risk hs-cTnT thresholds in adult patients in the emergency department undergoing hs-cTnT measurement. RESULTS: The adjudicated MAyo Southwest Wisconsin 5th Gen Troponin T ImplementatiON cohort included 2053 patients, with 157 (7.6%) who received a diagnosis of AMI. The hs-cTnT concentrations of greater than 52 and greater than 100 ng/L resulted in PPVs of 41% (95% CI, 35%-48%) and 57% (95% CI, 48%-66%). In patients with chest discomfort, hs-cTnT concentrations greater than 52 ng/L resulted in a PPV of 66% (95% CI, 56%-76%) and hs-cTnT concentrations greater than 100 ng/L resulted in a PPV of 77% (95% CI, 65%-87%). The CV Data Mart Biomarker cohort included 143,709 patients, and 3003 (2.1%) received a diagnosis of AMI. Baseline hs-cTnT concentrations greater than 52 and greater than 100 ng/L resulted in PPVs of 12% (95% CI, 11%-12%) and 17% (95% CI, 17%-19%), respectively. In patients with chest pain and hs-cTnT concentrations greater than 52 ng/L, the PPV for MI was 17% (95% CI, 15%-18%) and in those with concentrations greater than 100 ng/L, only 22% (95% CI, 19%-25%). CONCLUSION: In unselected patients undergoing hs-cTnT measurement, the hs-cTnT thresholds of greater than 52 and greater than 100 ng/L provide suboptimal performance for identifying high-risk patients. In patients with chest discomfort, an hs-cTnT concentration of greater than 100 ng/L, but not the European Society of Cardiology-recommended threshold of greater than 52 ng/L, provides an acceptable performance but should be used only with other clinical features.

Changes in vascular function and correlation with cardiotoxicity in women with newly diagnosed breast cancer undergoing HER2-directed therapy with and without anthracycline/cyclophosphamide.

Aims: The objective of this study was to assess the effect of HER2-directed therapy (HER2-Tx) on peripheral vasoreactivity and its correlation with cardiac function changes and the additive effects of anthracycline/cyclophosphamide (AC) therapy and baseline cardiovascular risk. Methods and results: Single-centre, prospective cohort study of women with newly diagnosed stage 1-3 HER2-positive breast cancer undergoing HER2-Tx +/- AC. All participants underwent baseline and 3-monthly evaluations with Endo-Peripheral Arterial Tonometry (Endo-PAT), vascular biomarkers [C-type natriuretic peptide (CNP) and neuregulin-1 beta (NRG-1ß)], and echocardiography. Cardiotoxicity was defined as a decrease in the left ventricular ejection fraction (LVEF) of >10% to a value <53%. Of the 47 patients enrolled, 20 (43%) received AC in addition to HER2-Tx. Deterioration of reactive hyperaemia index (RHI) on Endo-PAT by ≥20% was more common in patients receiving HER-Tx plus AC than HER2-Tx alone (65% vs. 22%; P = 0.003). A decrease in CNP and log NRG-1ß levels by 1 standard deviation did not differ significantly between the AC and non-AC groups (CNP: 20.0% vs. 7.4%; P = 0.20 and NRG-1ß: 15% vs. 11%; P = 0.69) nor did GLS (35% vs. 37%; P = 0.89). Patients treated with AC had a significantly lower 3D LVEF than non-AC recipients as early as 3 months after exposure (mean 59.3% (SD 3) vs. 63.8% (SD 4); P = 0.02). Reactive hyperaemia index and GLS were the only parameters correlating with LVEF change. Conclusion: Combination therapy with AC, but not HER2-Tx alone, leads to a decline in peripheral vascular and cardiac function. Larger studies will need to define more precisely the causal correlation between vascular and cardiac function changes in cancer patients.

Ten-year outcomes post percutaneous coronary intervention in cardiac transplant recipients.

BACKGROUND: Cardiac allograft vasculopathy (CAV) is one of the major late causes of mortality in cardiac transplant recipients beyond the first year. Given the lack of longer term data for PCI in cardiac transplant recipients, we report ten year follow up of such cardiac transplant recipients who underwent PCI at Mayo Clinic. METHODS: A retrospective observational study was conducted that included cardiac transplant recipients who underwent PCI at the Mayo Clinic. Continuous variables were presented as mean (SD) or median (IQR) and discrete variables were presented as frequency (percentage). RESULTS: Thirty-eight consecutive cardiac transplant recipients underwent PCI from January 1, 1995, to June 30, 2023, at the Mayo Clinic. The median age of the cohort was 61.00 years (IQR:51.00-70.00) comprised predominantly of men (65.80%), and 47.40% of the cohort presented with an acute coronary syndrome. The antirejection therapy prior to the PCI included steroids (47.30%), cyclosporine (26.30%), tacrolimus (15.80%), mycophenolate (42.10%), azathioprine (13.10%), & sirolimus (31.57%). Intravascular ultrasound during PCI was utilized in 10.50% of the cases. The median time duration between heart transplant and PCI was 9.00 years (IQR:6.00-13.00 years). Two individuals needed repeat heart transplant for severe CAV. In hospital mortality was 5.20% and the long-term median survival was 7.20 years with a 10-year mortality rate of 65.70%. CONCLUSIONS: This is the first publication reporting ten-year outcomes for PCI in cardiac transplant patients. The salient features for our cohort were a 65.70% mortality rate at 10 years and a median survival of 7.20 years.

Incidence and outcomes of high bleeding risk patients with type 1 and type 2 myocardial infarction in a community-based cohort: Application of the Academic Research Consortium High Bleeding Risk Criteria.

BACKGROUND AND AIMS: The incidence and outcomes of high bleeding risk (HBR) patients in a community cohort according to the Academic Research Consortium (ARC) criteria is not known. We hypothesized that HBR is common and associated with worse outcomes for all-comers with myocardial infarction. METHODS: We prospectively collected all patients with cardiac troponin T > 99th percentile upper limit of normal (≥0.01 ng/mL) in Olmsted County between 2003 and 2012. Events were retrospectively classified as type 1 myocardial infarction (T1MI), type 2 myocardial infarction (T2MI), or myocardial injury. Patients were further classified as HBR based on the "ARC-HBR definition." Outcomes included all-cause mortality, cardiovascular mortality, recurrent MI, stroke, and major bleeding. RESULTS: 2419 patients were included in the final study; 1365 were classified as T1MI and 1054 as T2MI. Patients were followed for a median of 5.5 years. ARC-HBR was more common in T2MI than T1MI (73% vs 46%, p < 0.001). Among patients with T1MI, HBR was associated with higher all-cause mortality (HR 3.7, 95% CI 3.2-4.5, p < 0.001), cardiovascular mortality (4.7, 3.6-6.3, p < 0.001), recurrent MI (2.1, 1.6-2.7, p < 0.001), stroke (4.9, 2.9-8.4, p < 0.001), and major bleeding (6.5, 3.7-11.4, p < 0.001). For T2MI, HBR was similarly associated with higher all-cause mortality (HR 2.1, 95% CI 1.8-2.5, p < 0.001), cardiovascular mortality (2.7, 1.8-4.0, p < 0.001), recurrent MI (1.7, 1.1-2.6, p = 0.02) and major bleeding (HR 15.6, 3.8-63.8, p < 0.001). CONCLUSION: HBR is common among unselected patients with T1MI and T2MI and is associated with increased overall and cardiovascular mortality, recurrent cardiovascular events, and major bleeding on long-term follow up.

5-Year Prospective Evaluation of Mitral Valve-in-Valve, Valve-in-Ring, and Valve-in-MAC Outcomes: MITRAL Trial Final Results.

BACKGROUND: The MITRAL (Mitral Implantation of Transcatheter Valves) trial is the first prospective trial to evaluate the safety and feasibility of balloon-expandable aortic transcatheter heart valves in patients with failed surgical bioprostheses or annuloplasty rings and severe mitral annular calcification treated with mitral valve-in-valve (MViV), valve-in-ring (MViR), or valve-in-mitral annular calcification (ViMAC). OBJECTIVES: The aim of this study was to evaluate 5-year outcomes among these patients. METHODS: A multicenter prospective study was conducted among patients at high surgical risk at 13 U.S. sites. Patients underwent MViV (n = 30), MViR (n = 30), or ViMAC (n = 31) and were followed annually for 5 years. Kansas City Cardiomyopathy Questionnaire scores were obtained at baseline and follow-up visits. Echocardiograms were analyzed at independent core laboratories. RESULTS: A total of 91 patients underwent transcatheter mitral valve replacement (February 2015 to December 2017). The mean age was 74.3 ± 8.9 years. At 5-year follow-up, the lowest all-cause mortality was observed in the MViV group (21.4%), 94.7% of patients were in NYHA functional class I or II, and the mean mitral gradient was 6.6 ± 2.5 mm Hg. The MViR and ViMAC groups had higher all-cause mortality (65.5% and 67.9%), most survivors were in NYHA functional classes I and II (50% and 55.6%), and mean mitral gradients remained stable (5.8 ± 0.1 and 6.7 ± 2.5 mm Hg). Significant improvements in Kansas City Cardiomyopathy Questionnaire scores were observed when all 3 arms were pooled. CONCLUSIONS: MViV, MViR, and ViMAC procedures were associated with sustained improvement of heart failure symptoms and quality of life among survivors at 5 years. Transcatheter heart valve function remained stable in all 3 groups. Patients treated with MViV had excellent survival at 5 years, whereas survival was lower in the MViR and ViMAC groups, consistent with underlying disease severity. Patients with more residual mitral regurgitation had higher mortality.

Clinical Significance of Biological Age in Patients Undergoing Percutaneous Coronary Intervention.

OBJECTIVE: To test whether biological age calculated using deficits, functional impairments, or their combination will provide improved estimation of long-term mortality among older adults undergoing percutaneous coronary intervention. PATIENTS AND METHODS: Cardiovascular deficits, noncardiovascular deficits, and functional impairments were prospectively studied in 535 patients aged 55 years or older from August 1, 2014, to March 31, 2018. Models for biological age included deficits (acquired, increase with age, associated with worse prognosis, did not saturate early), functional impairments (subjective-help with daily activities, difficulty with sensory input, continence, weight, balance, mobility; or objective-timed up and go, functional reach), or their combination. RESULTS: The mean ± SD age of the study patients was 72.1±9.5 years. For every 5-year increase in chronological age, the mean number of cardiovascular deficits increased from 2.36 among patients younger than 70 years to 3.44 in nonagenarians. The mean number of functional impairments increased from 2.15 for those younger than 70 years to 6.74 for nonagenarians. During a median follow-up of 2.05 years, 99 patients died. Significant improvement in the Harrell concordance index (C index) for prediction of long-term all-cause mortality was noted with biological age calculated from deficits and impairments compared with chronological age (0.77 vs 0.65; P<.001) and when estimating biological age via functional impairments alone vs chronological age (0.75 vs 0.65; P<.001) but not via deficits alone (0.71 vs 0.65; P=.08). Biological age estimates from subjective functional impairments captured most of the prognostic information related to all-cause and noncardiac mortality, whereas deficit-based estimation favored cardiovascular mortality. CONCLUSION: The derivation of biological age from deficits and functional impairments provides a major improvement in the estimation of survival as estimated by chronological age.

Left Atrial Appendage Occlusion in Patients With Atrial Fibrillation and Cancer.

Background: The prevention of stroke in patients with atrial fibrillation (AF) and cancer is challenging because patients are at increased bleeding and thrombotic risk. Objectives: The authors sought to assess left atrial appendage occlusion (LAAO) as a safe and effective strategy for reducing stroke at no increased bleeding risk in cancer patients with AF. Methods: We reviewed patients with nonvalvular AF who underwent LAAO at Mayo Clinic sites from 2017 to 2020 and identified those who had undergone prior or current treatment for cancer. We compared the incidence of stroke, bleeding, device complications, and death with a control group who underwent LAAO without malignancy. Results: Fifty-five patients were included; 44 (80.0%) were male, and the mean age was 79.0 ± 6.1 years. The median CHA2Ds2-VASc score was 5 (Q1-Q3: 4-6), with 47 (85.5%) having a prior bleeding event. Over the first year, ischemic stroke occurred in 1 (1.4%) patient, bleeding complications in 5 (10.7%) patients, and death in 3 (6.5%) patients. Compared with controls who underwent LAAO without cancer, there was no significant difference in ischemic stroke (HR: 0.44; 95% CI: 0.10-1.97; P = 0.28), bleeding complication (HR: 0.71; 95% CI: 0.28-1.86; P = 0.19), or death (HR: 1.39; 95% CI: 0.73-2.64; P = 0.32). Conclusions: Within our cohort, LAAO in cancer patients was achieved with good procedural success and offered a reduction in stroke at no increased bleeding risk similar to noncancer patients.

The Brain Disorders Debate, Chekhov, and Mental Health Humanities.

The contemporary brain disorders debate echoes a century-long conflict between two different approaches to mental suffering: one that relies on natural sciences and another drawing from the arts and humanities. We review contemporary neuroimaging studies and find that neither side has won. The study of mental differences needs both the sciences and the arts and humanities. To help develop an approach mindful of both, we turn to physician-writer Anton Chekhov's story "A Nervous Breakdown." We review the value of the arts and humanities as a coequal partner with natural sciences in the creation of a robust mental health humanities.

Association of Spontaneous Coronary Artery Dissection With Atrial Arrhythmias.

The co-morbidities and long-term complications of spontaneous coronary artery dissection (SCAD) are incompletely understood. This study investigated the association of atrial arrhythmias (AA), defined as atrial fibrillation and atrial flutter, with SCAD in a patient registry and population-based cohort. This observational study was performed in 2 parts. The first was a retrospective study reviewing patients diagnosed with AA in the Mayo Clinic SCAD Registry. The second was a population-based, case-control study to assess AA in patients with SCAD compared with age- and gender-matched controls. Of 1,214 patients in the Mayo Clinic SCAD Registry, 45 patients (3.7%) with SCAD were identified with an AA. A total of 8 of those patients (17.8%) had a pre-SCAD AA; 20 (44.4%) had a peri-SCAD AA; and 17 (37.8%) had a post-SCAD AA. The univariate analysis did not reveal significant associations with traditional cardiovascular risk factors. In the population-based cohort, 5 patients with SCAD (4%) and 4 controls (1%) developed an AA before the date of SCAD for each patient (odds ratio 4.5, 95% confidence interval [CI] 1.05 to 19.0, p = 0.04). A total of 5 patients with SCAD (4%) and 3 controls (1%) developed an AA in the 10 years after SCAD (hazard ratio 6.3, 95% CI 1.2 to 32.8, p = 0.03). A subgroup of patients with SCAD experienced AA before and after SCAD. Patients with a history of SCAD were more likely to develop AA in the next 10 years than were age- and gender-matched healthy controls.

2-Year Outcomes of Transcatheter Mitral Valve Replacement in Patients With Annular Calcification, Rings, and Bioprostheses.

BACKGROUND: The MITRAL (Mitral Implantation of Transcatheter Valves) trial is the first prospective study for valve-in-mitral annular calcification (ViMAC), mitral valve-in-ring (MViR), and mitral valve-in-valve (MViV) using balloon-expandable aortic transcatheter heart valves. Procedural outcomes beyond 1 year are not well described. OBJECTIVES: This study evaluated 2-year outcomes in ViMAC, MViR, and MViV in the MITRAL trial. METHODS: This multicenter prospective study enrolled patients with severe MAC, prior failed mitral annuloplasty ring repair, or prior failed bioprosthetic MV replacement who were at high surgical risk at 13 U.S. sites. RESULTS: Between February 1, 2015, and December 31, 2017, 91 patients were enrolled (31 with ViMAC, 30 with MViR, and 30 with MViV). In the ViMAC group, 2-year all-cause mortality was 39.3%, 66.7% were New York Heart Association (NYHA) functional class I-II, and mean MV gradient was 5.6 ± 2.0 mm Hg. In the MViR group, 2-year all-cause mortality was 50%, 65% were NYHA functional class I-II, and mean MV gradient was 6.5 ± 2.7 mm Hg. In the MViV group, 2-year all-cause mortality was 6.7%, 85% were NYHA functional class I-II, and mean MV gradient was 6.9 ± 2.4 mm Hg. At 2 years, all patients had ≤mild mitral regurgitation and survivors in all 3 arms showed sustained improvement in Kansas City Cardiomyopathy Questionnaire scores compared to baseline. CONCLUSIONS: Use of balloon-expandable aortic transcatheter heart valves in selected patients with severe MAC, failed annuloplasty ring, and bioprosthetic MV dysfunction is associated with improvements in symptoms, quality of life, and stable prosthesis function at 2-year follow-up. Between 1 and 2 years, the MViR group experienced higher mortality rates than the MViV and ViMAC groups.

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

BACKGROUND: The current criteria for aortic stenosis (AS) severity have not incorporated sex-related differences. OBJECTIVES: The authors investigated sex-related serial changes in left ventricular (LV) structure/function and hemodynamics in AS. METHODS: Serial echocardiograms of patients with severe AS (time 0; aortic valve area [AVA] ≤1 cm2) and ≥1 previous echocardiogram were compared between sexes. RESULTS: Of 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. CONCLUSIONS: Smaller 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.

Multimorbidity and Mortality Models to Predict Complications Following Percutaneous Coronary Interventions.

BACKGROUND: Previous percutaneous coronary intervention risk models were focused on single outcome, such as mortality or bleeding, etc, limiting their applicability. Our objective was to develop contemporary percutaneous coronary intervention risk models that not only determine in-hospital mortality but also predict postprocedure bleeding, acute kidney injury, and stroke from a common set of variables. METHODS: We built risk models using logistic regression from first percutaneous coronary intervention for any indication per patient (n=19 322, 70.6% with acute coronary syndrome) using the Mayo Clinic registry from January 1, 2000 to December 31, 2016. Approval for the current study was obtained from the Mayo Foundation Institutional Review Board. Patients with missing outcomes (n=4183) and those under 18 (n=10) were removed resulting in a sample of 15 129. We built both models that included procedural and angiographic variables (Models A) and precatheterization model (Models B). RESULTS: Death, bleeding, acute kidney injury, and stroke occurred in 247 (1.6%), 650 (4.3%), 1184 (7.8%), and 67 (0.4%), respectively. The C statistics from the test dataset for models A were 0.92, 0.70, 0.77, and 0.71 and for models B were 0.90, 0.67, 0.76, and 0.71 for in-hospital death, bleeding, acute kidney injury, and stroke, respectively. Bootstrap analysis indicated that the models were not overfit to the available dataset. The probabilities estimated from the models matched the observed data well, as indicated by the calibration curves. The models were robust across many subgroups, including women, elderly, acute coronary syndrome, cardiogenic shock, and diabetes. CONCLUSIONS: The new risk scoring models based on precatheterization variables and models including procedural and angiographic variables accurately predict in-hospital mortality, bleeding, acute kidney injury, and stroke. The ease of its application will provide useful prognostic and therapeutic information to both patients and physicians.

Rapid Exclusion of Acute Myocardial Injury and Infarction With a Single High-Sensitivity Cardiac Troponin T in the Emergency Department: A Multicenter United States Evaluation.

BACKGROUND: There are good data to support using a single high-sensitivity cardiac troponin T (hs-cTnT) below the limit of detection of 5 ng/L to exclude acute myocardial infarction. Per the US Food and Drug Administration, hs-cTnT can only report to the limit of quantitation of 6 ng/L, a threshold for which there are limited data. Our goal was to determine whether a single hs-cTnT below the limit of quantitation of 6 ng/L is a safe strategy to identify patients at low risk for acute myocardial injury and infarction. METHODS: The efficacy (proportion identified as low risk based on baseline hs-cTnT<6 ng/L) of identifying low-risk patients was examined in a multicenter (n=22 sites) US cohort study of emergency department patients undergoing at least 1 hs-cTnT (CV Data Mart Biomarker cohort). We then determined the performance of a single hs-cTnT<6 ng/L (biomarker alone) to exclude acute myocardial injury (subsequent hs-cTnT >99th percentile in those with an initial hs-cTnT<6 ng/L). The clinically intended rule-out strategy combining a nonischemic ECG with a baseline hs-cTnT<6 ng/L was subsequently tested in an adjudicated cohort in which the diagnostic performance for ruling out acute myocardial infarction and safety (myocardial infarction or death at 30 days) were evaluated. RESULTS: A total of 85 610 patients were evaluated in the CV Data Mart Biomarker cohort, among which 24 646 (29%) had a baseline hs-cTnT<6 ng/L. Women were more likely than men to have hs-cTnT<6 ng/L (38% versus 20%, P<0.0001). Among 11 962 patients with baseline hs-cTnT<6 ng/L and serial measurements, only 1.2% developed acute myocardial injury, resulting in a negative predictive value of 98.8% (95% CI, 98.6-99.0) and sensitivity of 99.6% (95% CI, 99.5-99.6). In the adjudicated cohort, a nonischemic ECG with hs-cTnT<6 ng/L identified 33% of patients (610/1849) as low risk and resulted in a negative predictive value and sensitivity of 100% and a 30-day rate of 0.2% for myocardial infarction or death. CONCLUSIONS: A single hs-cTnT below the limit of quantitation of 6 ng/L is a safe and rapid method to identify a substantial number of patients at very low risk for acute myocardial injury and infarction.

The impact of pulmonary hypertension on outcomes of transcatheter mitral valve replacement in mitral annular calcification.

OBJECTIVES: To assess the impact of pulmonary hypertension (PH) on outcomes of patients with severe mitral annular calcification (MAC) undergoing transcatheter mitral valve replacement (TMVR). BACKGROUND: PH is associated with poor outcomes after mitral valve surgery. Whether the presence of PH in patients with MAC undergoing (TMVR) is associated with poor outcomes, is unknown. METHODS: Retrospective evaluation of 116 patients from 51 centers in 11 countries who underwent TMVR with valve in mitral annular calcification (ViMAC) using balloon-expandable aortic transcatheter valves (THVs) from September 2012 to March 2017. Pulmonary artery systolic blood pressure (PASP) by echocardiogram was available in 90 patients. The subjects were stratified based on PASP: No PH = PASP ≤35 mmHg (n = 11); mild to moderate PH = PASP 36-49 mmHg (n = 21) and severe PH = PASP ≥50 mmHg (n = 58). Clinical, procedural, and echocardiographic outcomes were assessed. RESULTS: Mean age was 72.7 (±12.8) years, 59 (65.6%) were female, Society of Thoracic Surgeons score was 15.8 + 11.8% and 90.0% where in New York Heart Association (NYHA) class III-IV. There was no significant difference in all-cause mortality at 30 days (no PH = 27.3%, mild-moderate PH = 19.0%, severe PH = 31.6%; p = 0.55) or at 1 year (no PH = 54.5%, mild-moderate PH = 38.1%, severe PH = 56.1%; p = 0.36). No difference in adverse events, NYHA class or amount of residual mitral regurgitation at 1 year were observed between the groups. CONCLUSION: This study suggests that the presence of PH in patients with predominantly mitral stenosis with MAC undergoing TMVR does not impact mortality or adverse events. Further studies are needed to fully understand the effect of PH in this group of patients.

Finite element analysis in clinical patients with atherosclerosis.

Endovascular plaque composition is strongly related to stent strut stress and is responsible for strut fatigue, stent failure, and possible in-stent restenosis. To evaluate the effect of plaque on artery wall resistance to expansion we performed in silico analysis of atherosclerotic vessels. We generated finite element models from in vivo intravascular ultrasound virtual histology images to determine local artery surface stiffness and determined which plaque structures have the greatest influence. We validated the predictive capacity of our modeling approach by testing an atherosclerotic peripheral artery ex vivo with pressure-inflation testing at physiological pressures ranging from 10 to 200 mmHg. For this purpose, the in silico deformation of the arterial wall was compared to that observed ex vivo. We found that calcification had a positive effect on surface stiffness with fibrous plaque and necrotic core having negative effects. Additionally, larger plaque structures demonstrated significantly higher average surface stiffness and calcification located nearer the lumen was also shown to increase surface stiffness. Therefore, more developed plaques will have greater resistance to expansion and higher stent strut stress, with calcification located near the lumen further increasing stress in localized areas. Thus, it may be expected that such plaque structures may increase the likelihood of localized stent strut fracture.

IMPROvE-CED Trial: Intracoronary Autologous CD34+ Cell Therapy for Treatment of Coronary Endothelial Dysfunction in Patients With Angina and Nonobstructive Coronary Arteries.

BACKGROUND: Coronary endothelial dysfunction (CED) causes angina/ischemia in patients with nonobstructive coronary artery disease (NOCAD). Patients with CED have decreased number and function of CD34+ cells involved in normal vascular repair with microcirculatory regenerative potential and paracrine anti-inflammatory effects. We evaluated safety and potential efficacy of intracoronary autologous CD34+ cell therapy for CED. METHODS: Twenty NOCAD patients with invasively diagnosed CED and persistent angina despite maximally tolerated medical therapy underwent baseline exercise stress test, GCSF (granulocyte colony stimulating factor)-mediated CD34+ cell mobilization, leukapheresis, and selective 1×105 CD34+ cells/kg infusion into left anterior descending. Invasive CED evaluation and exercise stress test were repeated 6 months after cell infusion. Primary end points were safety and effect of intracoronary autologous CD34+ cell therapy on CED at 6 months of follow-up. Secondary end points were change in Canadian Cardiovascular Society angina class, as-needed sublingual nitroglycerin use/day, Seattle Angina Questionnaire scores, and exercise time at 6 months. Change in CED was compared with that of 51 historic control NOCAD patients treated with maximally tolerated medical therapy alone. RESULTS: Mean age was 52±13 years; 75% were women. No death, myocardial infarction, or stroke occurred. Intracoronary CD34+ cell infusion improved microvascular CED (%acetylcholine-mediated coronary blood flow increased from 7.2 [-18.0 to 32.4] to 57.6 [16.3-98.3]%; P=0.014), decreased Canadian Cardiovascular Society angina class (3.7±0.5 to 1.7±0.9, Wilcoxon signed-rank test, P=0.00018), and sublingual nitroglycerin use/day (1 [0.4-3.5] to 0 [0-1], Wilcoxon signed-rank test, P=0.00047), and improved all Seattle Angina Questionnaire scores with no significant change in exercise time at 6 months of follow-up. Historic control patients had no significant change in CED. CONCLUSIONS: A single intracoronary autologous CD34+ cell infusion was safe and may potentially be an effective disease-modifying therapy for microvascular CED in humans. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03471611.

Correlation of Intravascular Ultrasound and Instantaneous Wave-Free Ratio in Patients With Intermediate Left Main Coronary Artery Disease.

BACKGROUND: There is great degree of interobserver variability in the visual angiographic assessment of left main coronary disease (LMCD). Fractional flow reserve and intravascular ultrasound are often used in this setting. The use of instantaneous wave-free ratio (iFR) for evaluation of LMCD has not been well studied. The aim of this study is to evaluate the use of iFR in the assessment of angiographically intermediate LMCD. METHODS: This is an international multicenter retrospective observational study of patients who underwent both iFR and intravascular ultrasound evaluation for angiographically intermediate LMCD. An independent core laboratory performed blinded off-line analysis of all intravascular ultrasound data. A minimum lumen area of 6 mm2 was used as the cutoff for significant disease. RESULTS: One hundred twenty-five patients (mean age, 68.4±9.5 years, 84.8% male) were included in this analysis. Receiver operating curve analysis showed that an iFR of ≤0.89 identified minimum lumen area <6 mm2 with an area under the curve of 0.77 (77% sensitivity, 66% specificity; P<0.0001). Among the 69 patients without ostial left anterior descending artery or left circumflex artery disease, receiver operating curve analysis showed that an iFR of ≤0.89 identified minimum lumen area <6 mm2 with an area under the curve of 0.84 (70% sensitivity, 84% specificity; P<0.0001). The correlation was not significantly different when the body surface area was considered. CONCLUSIONS: In this study, in patients with intermediate LMCD, iFR of ≤0.89 correlates with intravascular ultrasound minimum lumen area <6 mm2 regardless of body surface area. The current study supports the use of iFR for the evaluation of intermediate LMCD.

Cancer Patients Have a Higher Risk of Thrombotic and Ischemic Events After Percutaneous Coronary Intervention.

OBJECTIVES: This study sought to define the risk of stent thrombosis (ST) and myocardial infarction (MI) in cancer patients compared with noncancer patients after percutaneous coronary intervention (PCI). BACKGROUND: Cancer patients are considered to be at high thrombotic risk, but data on whether this is the case after PCI remain inconclusive. METHODS: Cancer patients undergoing PCI at Mayo Clinic Rochester from January 1, 2003, to December 31, 2013, were identified by cross-linking institutional cancer and PCI databases and by propensity score matching to noncancer patients. The combined primary endpoint was all-cause mortality, MI, and revascularization rate at 5-year follow-up. Secondary endpoints were the individual primary endpoint components, cause of mortality, ST, and Bleeding Academic Research Consortium 2+ bleeding. RESULTS: The primary endpoint occurred in 48.6% of 416 cancer and in 33.0% of 768 noncancer patients (p < 0.001). In competing risk analyses, cancer patients had a higher rate of noncardiac death (24.0% vs. 10.5%; p < 0.001) and a lower rate of cardiac death (5.0% vs. 11.7%; p < 0.001). Cancer patients had a higher rate of MI (16.1% vs. 8.0%; p < 0.001), ST (6.0% vs. 2.3%; p < 0.001), repeat revascularization (21.2% vs. 10.0%; p < 0.001), and bleeding (6.7% vs. 3.9%; p = 0.03). The most critical period for ST in cancer patients was in the first year after PCI. The dual antiplatelet therapy score was predictive of thrombotic and ischemic events in both groups. CONCLUSIONS: Cancer patients have a higher risk of thrombotic and ischemic events after PCI, identifiable by a high dual antiplatelet therapy score. These findings have important implications for antiplatelet therapy decisions.