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.

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.

Clinical Outcomes of Various Management Strategies for Symptomatic Bradycardia.

OBJECTIVE: To determine clinical outcomes of various management strategies for reversible and irreversible causes of symptomatic bradycardia in the inpatient setting. DESIGN: Retrospective observational study. SETTING: Emergency room and inpatient. PARTICIPANTS: Patients presenting to the emergency department with symptomatic bradycardia. METHODS: We retrospectively reviewed electronic health records of 518 patients from two Mayo Clinic campuses (Rochester and Phoenix) who presented to the emergency department with symptomatic bradycardia (heart rate ≤50 beats/minute) from January 1, 2010 through December 31, 2015. Sinus bradycardia was excluded. The following management strategies were compared: observation, non-invasive management (medications with/without transcutaneous pacing), early permanent pacemaker (PPM) implantation (≤2 days), and delayed PPM implantation (≥3 days). Study endpoints included length of stay and adverse events related to bradycardia (syncope, central line-associated bloodstream infections, cardiac arrest, and in-hospital mortality). Patients who received a PPM were further stratified by weekend hospital admission. RESULTS: Heart block occurred in 200 (38.6%) patients, and atrial arrhythmias with slow ventricular response occurred in 239 (46.1%) patients. Reversible causes of bradycardia included medication toxicity in 22 (4.2%) patients and hyperkalemia in 44 (8.5%) patients. Adverse events were similar in patients who underwent early compared to delayed PPM implantation (6.6% vs 12.5%, P=.20), whereas adverse events were higher in patients who received temporary transvenous pacing (19.1% vs 3.4%, P<.001). Weekend admissions were associated with increased temporary transvenous pacing, prolonged median time to PPM implantation by 1 day, and prolonged median length of stay by 2 days. CONCLUSIONS: Delayed PPM implantation was not associated with an increase in adverse events. Weekend PPM implantation should be considered to reduce temporary transvenous pacing and shorten length of stay.

Burden of hospitalization in clinically diagnosed peripheral artery disease: A community-based study.

The burden and predictors of hospitalization over time in community-based patients with peripheral artery disease (PAD) have not been established. This study evaluates the frequency, reasons and predictors of hospitalization over time in community-based patients with PAD. We assembled an inception cohort of 1798 PAD cases from Olmsted County, MN, USA (mean age 71.2 years, 44% female) from 1 January 1998 through 31 December 2011 who were followed until 2014. Two age- and sex-matched controls ( n = 3596) were identified for each case. ICD-9 codes were used to ascertain the primary reasons for hospitalization. Patients were censored at death or last follow-up. The most frequent reasons for hospitalization were non-cardiovascular: 68% of 8706 hospitalizations in cases and 78% of 8005 hospitalizations in controls. A total of 1533 (85%) cases and 2286 (64%) controls ( p < 0.001) were hospitalized at least once; 1262 (70%) cases and 1588 (44%) controls ( p < 0.001) ≥ two times. In adjusted models, age, prior hospitalization and comorbid conditions were independently associated with increased risk of recurrent hospitalizations in both groups. In cases, severe PAD (ankle-brachial index < 0.5) (HR: 1.25; 95% CI: 1.15, 1.36) and poorly compressible arteries (HR: 1.26; 95% CI: 1.16, 1.38) were each associated with increased risk for recurrent hospitalization. We demonstrate an increased rate of hospitalization in community-based patients with PAD and identify predictors of recurrent hospitalizations. These observations may inform strategies to reduce the burden of hospitalization of PAD patients.

Occupational musculoskeletal pain in cardiac sonographers compared to peer employees: a multisite cross-sectional study.

OBJECTIVES: The purpose of this study was to compare the prevalence and impact of work-related musculoskeletal pain in cardiac sonographers to a large control group of peer employees with similar demographics. BACKGROUND: Cardiac sonographers are known to have high levels of occupational musculoskeletal pain. Comparative studies with other employees within cardiology/radiology departments have never been performed. METHODS: An electronic survey was administered to Mayo Clinic employees at six major patient care facilities in four different states. RESULTS: There were 2682 employees within the departments of cardiology and radiology who were contacted, and 1532 (57%) completed the survey. After excluding those who wore protective lead aprons, 517 employees comprised the control group and 66 cardiac sonographers made up the study group. Cardiac sonographers reported work-related musculoskeletal pain more frequently than the control group (88% vs 40%; P<.001). This association persisted after multivariable adjustment for age, sex, body mass index, length of current employment, and history of preexisting musculoskeletal pain (OR 11.6; [95% CI 5.32, 25.5]; P<.001). Cardiac sonographers sought medical care for their work-related pain more often (55% vs 21%; P<.001) and missed more work due to pain (35% vs 12%, P<.001). In a secondary analysis, cardiac sonographers also experienced more work-related musculoskeletal pain than nurses, technicians, and physicians working in the interventional laboratory who regularly wear a protective lead apron (P<.001). CONCLUSIONS: In this multisite cross-sectional study, cardiac sonographers experienced significantly more work-related pain and missed more work due to pain than peer employees within cardiology/radiology departments.

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.

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

BACKGROUND: Limited data exist on the long-term outcomes of transcatheter aortic valve insertion (TAVI) in nonagenarian patients. This study investigated the relationship between patient baseline comorbidity and frailty on the long-term outcome of the nonagenarian population. METHODS: A retrospective analysis was conducted of 187 consecutive nonagenarian patients who underwent TAVI from 2009 to 2020. Multivariable models were used to analyze the association between baseline patient and frailty variables and mortality, stroke, and repeat hospitalization. Long-term survival was compared with an age- and sex-matched United States population. RESULTS: The median Society of Thoracic Surgeons predicted risk of mortality was 10% (interquartile range, 7%-17%). Frailty was met in 72% of patients based on the 5-meter walk test, 13% based on the Kansas City Cardiomyopathy Questionnaire 12-item instrument score, 12% based on Katz Index of Independence in Activities of Daily Living, and 8% based on serum albumin levels. Procedure-related death occurred in 3 patients (2%) and stroke in 8 (4%). The median duration of follow-up was 3.4 years. Outcomes included death in 150 patients (80%), 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 > .05). The 1- and 5-year survival rates in TAVI-treated nonagenarians were similar to age- and sex-matched controls (P = .27). CONCLUSIONS: Long-term death or stroke is independent of The Society of Thoracic Surgeons predicted risk of mortality and frailty risk variables in this nonagenarian patient population who received TAVI. Furthermore, survival is similar to age- and sex-matched controls.

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.

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.

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.

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.

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.

Efficacy and safety of percutaneous mitral balloon valvotomy in patients with mitral stenosis: A systematic review and meta-analysis.

AIMS: Percutaneous mitral balloon valvotomy PMBV is an acceptable alternative to Mitral valve surgery for patients with mitral stenosis. The purpose of this study was to explore the immediate results of PMBV with respect to echocardiographic changes, outcomes, and complications, using a meta-analysis approach. METHODS: MEDLINE, and EMBASE databases were searched (01/2012 to 10/2018) for original research articles regarding the efficacy and safety of PMBV. Two reviewers independently screened references for inclusion and abstracted data including article details and echocardiographic parameters before and 24-72 h after PMBV, follow-up duration, and acute complications. Disagreements were resolved by third adjudicator. Quality of all included studies was evaluated using the Newcastle-Ottawa Scale NOS. RESULTS: 44/990 references met the inclusion criteria representing 6537 patients. Our findings suggest that PMBV leads to a significant increase in MVA (MD = 0.81 cm2; 0.76-0.87, p < 0.00001), LVEDP (MD = 1.89 mmHg; 0.52-3.26, p = 0.007), LVEDV EDV (MD = 5.81 ml; 2.65-8.97, p = 0.0003) and decrease in MPG (MD = -7.96 mmHg; -8.73 to -7.20, p < 0.00001), LAP (MD = -10.09 mmHg; -11.06 to -9.12, p < 0.00001), and SPAP (MD = -15.55 mmHg; -17.92 to -13.18, p < 0.00001). On short term basis, the pooled overall incidence estimates of repeat PMBV, mitral valve surgery, post-PMBV severe MR, and post-PMBV stroke, and systemic thromboembolism were 0.5%, 2%, 1.4%, 0.4%, and 0.7%% respectively. On long term basis, the pooled overall incidence estimates of repeat PMBV, mitral valve surgery, post-PMBV severe MR, and post-PMBV stroke, systemic thromboembolism were 5%, 11.5%, 5.5%, 2.7%, and 1.7% respectively. CONCLUSION: PMBV represents a successful approach for patients with mitral stenosis as evidenced by improvement in echocardiographic parameters and low rate of complications.

Prognostic Risk Stratification of Patients with Moderate Aortic Stenosis.

BACKGROUND: Currently risk stratification of moderate aortic stenosis (AS) is still incipient. The aim of this study was to identify prognostic factors in patients with moderate AS. METHODS: The prognosis of patients with moderate AS (1 < aortic valve area ≤ 1.5 cm2) stratified by left ventricular ejection fraction (LVEF; 50%), stroke volume index (SVI; 35 mL/m2), and elevated E/e' ratio (average, 14) was compared with that of the age- and sex-matched general population. RESULTS: Of 696 patients (median age, 77 years; aortic valve area 1.3 cm2; 57% men), 279 (40%) died during a median follow-up period of 3.4 years. Mortality was higher in patients with moderate AS than reference (mortality ratio, 2.43; 95% CI, 2.17-2.72). LVEF < 50%, SVI < 35 mL/m2, and elevated E/e' ratio were present in 113 (17%), 54 (8%), and 330 (54%) patients; mortality ratios were 3.89 (95% CI, 3.07-4.85), 6.40 (95% CI, 4.57-8.71), and 2.58 (95% CI, 2.21-3.00), respectively. Even if LVEF or SVI was preserved, the mortality ratio was more than twice than reference (P < .001), but elevated E/e' ratio could discriminate additional patients at higher risk (hazard ratio [HR], 2.71; 95% CI, 1.88-3.91). Two hundred one patients (29%) underwent aortic valve replacement at a median of 2.3 years after the diagnosis of moderate AS. LVEF < 50% (HR, 2.98; 95% CI, 1.39-6.56), SVI < 35 mL/m2 (HR, 3.34; 95% CI, 1.02-10.90) and elevated E/e' ratio (HR, 2.73; 95% CI, 1.26-5.94) were all associated with worse prognosis even if aortic valve replacement was performed. CONCLUSIONS: In patients with moderate AS, those with decreased LVEF and/or SVI are at high risk. Even if these parameters are preserved, patients with elevated E/e' ratios are at intermediate risk. Further investigation is warranted to assess whether earlier intervention could improve outcomes and reduced cardiac-related death among patients at high and intermediate risk.

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.

Prospective Study of TMVR Using Balloon-Expandable Aortic Transcatheter Valves in MAC: MITRAL Trial 1-Year Outcomes.

OBJECTIVES: The aim of this study was to evaluate 1-year outcomes of valve-in-mitral annular calcification (ViMAC) in the MITRAL (Mitral Implantation of Transcatheter Valves) trial. BACKGROUND: The MITRAL trial is the first prospective study evaluating the feasibility of ViMAC using balloon-expandable aortic transcatheter heart valves. METHODS: A multicenter prospective study was conducted, enrolling high-risk surgical patients with severe mitral annular calcification and symptomatic severe mitral valve dysfunction at 13 U.S. sites. RESULTS: Between February 2015 and December 2017, 31 patients were enrolled (median age 74.5 years [interquartile range (IQR): 71.3 to 81.0 years], 71% women, median Society of Thoracic Surgeons score 6.3% [IQR: 5.0% to 8.8%], 87.1% in New York Heart Association functional class III or IV). Access was transatrial (48.4%), transseptal (48.4%), or transapical (3.2%). Technical success was 74.2%. Left ventricular outflow tract obstruction (LVOTO) with hemodynamic compromise occurred in 3 patients (transatrial, n = 1; transseptal, n = 1; transapical, n = 1). After LVOTO occurred in the first 2 patients, pre-emptive alcohol septal ablation was implemented to decrease risk in high-risk patients. No intraprocedural deaths or conversions to open heart surgery occurred during the index procedures. All-cause mortality at 30 days was 16.7% (transatrial, 21.4%; transseptal, 6.7%; transapical, 100% [n = 1]; p = 0.33) and at 1 year was 34.5% (transatrial, 38.5%; transseptal, 26.7%; p = 0.69). At 1-year follow-up, 83.3% of patients were in New York Heart Association functional class I or II, the median mean mitral valve gradient was 6.1 mm Hg (IQR: 5.6 to 7.1 mm Hg), and all patients had ≤1+ mitral regurgitation. CONCLUSIONS: At 1 year, ViMAC was associated with symptom improvement and stable transcatheter heart valve performance. Pre-emptive alcohol septal ablation may prevent transcatheter mitral valve replacement-induced LVOTO in patients at risk. Thirty-day mortality of patients treated via transseptal access was lower than predicted by the Society of Thoracic Surgeons score. Further studies are needed to evaluate safety and efficacy of ViMAC.

Non-invasive vocal biomarker is associated with pulmonary hypertension.

Emerging data suggest that noninvasive voice biomarker analysis is associated with coronary artery disease. We recently showed that a vocal biomarker was associated with hospitalization and heart failure in patients with heart failure. We evaluate the association between a vocal biomarker and invasively measured indices of pulmonary hypertension (PH). Patients were referred for an invasive cardiac hemodynamic study between January 2017 and December 2018, and had their voices recorded on three separate occasions to their smartphone prior to each study. A pre-established vocal biomarker was determined based on each individual recording. The intra-class correlation co-efficient between the separate voice recording biomarker values for each individual participant was 0.829 (95% CI 0.740-0.889) implying very good agreement between values. Thus, the mean biomarker was calculated for each patient. Patients were divided into two groups: high pulmonary arterial pressure (PAP) defined as ≥ 35 mmHg (moderate or greater PH), versus lower PAP. Eighty three patients, mean age 61.6 ± 15.1 years, 37 (44.6%) male, were included. Patients with a high mean PAP (≥ 35 mmHg) had on average significantly higher values of the mean voice biomarker compared to those with a lower mean PAP (0.74 ± 0.85 vs. 0.40 ± 0.88 p = 0.046). Multivariate logistic regression showed that an increase in the mean voice biomarker by 1 unit was associated with a high PAP, odds ratio 2.31, 95% CI 1.05-5.07, p = 0.038. This study shows a relationship between a noninvasive vocal biomarker and an invasively derived hemodynamic index related to PH obtained during clinically indicated cardiac catheterization. These results may have important practical clinical implications for telemedicine and remote monitoring of patients with heart failure and PH.

Coronary Endothelial Dysfunction Is Associated With Increased Risk of Incident Atrial Fibrillation.

Background Coronary artery disease risk factors are associated with atrial fibrillation (AF) and coronary endothelial dysfunction (CED). We hypothesized that CED is associated with increased risk of incident AF among patients with chest pain and nonobstructive coronary artery disease. Methods and Results Three hundred patients with chest pain, nonobstructive coronary artery disease, and no history of AF underwent intracoronary acetylcholine infusion for evaluation of baseline epicardial (decrease in mid-left anterior descending coronary artery diameter in response to acetylcholine) and microvascular (<50% increase in coronary blood flow in response to acetylcholine) CED. Primary outcome was incident AF over a mean follow-up period of 10.5±5.5 years. Mean age was 53.3±10.8 years, and 70% were women. Baseline clinical and echocardiographic characteristics were similar between patients with CED (n=256) and those with normal endothelial function (n=44). Overall, 35 of 300 (12%) patients developed AF, among whom 34 of 35 (97%) had CED at baseline. Compared with normal endothelial function, the presence of CED was associated with 11% increased absolute risk and 5.8-fold increased relative risk of incident AF. Moreover, CED (odds ratio, 3.87; 95% CI, 1.27-47.0) and increased (>34 mL/m2) left atrial volume index (odds ratio, 3.87; 95% CI, 1.60-9.11) were independent predictors of incident AF. Conclusions Patients with normal coronary endothelial function, as compared with those with CED and similar AF risk factors, have significantly lower incidence of AF on long-term follow-up. The potential mechanistic link between vascular dysfunction and AF development warrants further investigation.

Non-infarct related artery microvascular obstruction is associated with worse persistent diastolic dysfunction in patients with revascularized ST elevation myocardial infarction.

BACKGROUND: Infarct-artery (IRA) microvascular obstruction (MVO) is associated with diastolic dysfunction (DD) in STEMI patients. However, association between nonIRA MVO and DD in STEMI patients remains unknown. We hypothesized that revascularized STEMI patients with IRA and nonIRA MVO (IRA + nonIRA+), compared to those without nonIRA MVO (IRA + nonIRA-), have worse DD at presentation and long-term follow-up. METHODS: 87 IRA-revascularized STEMI patients had cardiac magnetic resonance imaging (MRI) [to evaluate MVO] and TTE (to evaluate diastolic function) within 1 week of presentation. Diastolic function was re-assessed by TTE at 3.97 ± 3.24 years. Baseline and follow-up DD prevalence and grade were studied in IRA + nonIRA + vs. IRA + nonIRA- MVO patients. RESULTS: 54 (62%) patients were IRA + nonIRA+ and 33 (38%) IRA + nonIRA-at baseline. IRA + nonIRA + patients had higher DD frequency at baseline (40.7 vs. 6.1%, p = 0.006) and follow-up (50.0 vs. 13.0%, p = 0.05). Only IRA + nonIRA + patients had increase in mitral medial E/e' (20.0%, p = 0.043) and trend towards increase in mitral E/A (31.1%, p = 0.063) at follow-up. IRA + nonIRA + patients had greater left atrial volume index increase (23.7%, p = 0.032 vs. 15.5%, p = 0.029) and smaller prolongation in deceleration time (15.4%, p = 0.018 vs. 18.7%, p = 0.044) at follow-up compared to IRA + nonIRA-. Grade 1 DD increased (60.9-73.9%) and combined grades 2/3 decreased (30.4-13.0%) at follow-up in IRA + nonIRA-patients. In contrast, grade 1 DD decreased (77.8-61.1%) and combined grades 2/3 increased (8.3-22.2%) at follow-up in IRA + nonIRA + patients. CONCLUSION: Concurrent IRA and nonIRA MVO in revascularized STEMI patients is associated with higher DD prevalence and worse DD grade on long-term follow-up.