Prognostic value of peak stress cardiac power in patients with normal ejection fraction undergoing exercise stress echocardiography.

AIMS: Cardiac power is a measure of cardiac performance that incorporates both pressure and flow components. Prior studies have shown that cardiac power predicts outcomes in patients with reduced left ventricular (LV) ejection fraction (EF). We sought to evaluate the prognostic significance of peak exercise cardiac power and power reserve in patients with normal EF. METHODS AND RESULTS: We performed a retrospective analysis in 24 885 patients (age 59 ± 13 years, 45% females) with EF ≥50% and no significant valve disease or right ventricular dysfunction, undergoing exercise stress echocardiography between 2004 and 2018. Cardiac power and power reserve (developed power with stress) were normalized to LV mass and expressed in W/100 g of LV myocardium. Endpoints at follow-up were all-cause mortality and diagnosis of heart failure (HF). Patients in the higher quartiles of power/mass (rest, peak stress, and power reserve) were younger and had higher peak blood pressure and heart rate, lower LV mass, and lower prevalence of comorbidities. During follow-up [median 3.9 (0.6-8.3) years], 929 patients died. After adjusting for age, sex, metabolic equivalents (METs) achieved, ischaemia/infarction on stress test results, medication, and comorbidities, peak stress power/mass was independently associated with mortality [adjusted hazard ratio (HR), highest vs. lowest quartile, 0.5, 95% confidence interval (CI) 0.4-0.6, P < 0.001] and HF at follow-up [adjusted HR, highest vs. lowest quartile, 0.4, 95% CI (0.3, 0.5), P < 0.001]. Power reserve showed similar results. CONCLUSION: The assessment of cardiac power during exercise stress echocardiography in patients with normal EF provides valuable prognostic information, in addition to stress test findings on inducible myocardial ischaemia and exercise capacity.

Prognostic Significance of Elevated Left Ventricular Filling Pressures with Exercise: Insights from a Cohort of 14,338 Patients.

BACKGROUND: Exercise echocardiography can assess for cardiovascular causes of dyspnea other than coronary artery disease. However, the prevalence and prognostic significance of elevated left ventricular (LV) filling pressures with exercise is understudied. METHODS: We evaluated 14,338 patients referred for maximal symptom-limited treadmill echocardiography. In addition to assessment of LV regional wall motion abnormalities (RWMAs), we measured patients' early diastolic mitral inflow (E), septal mitral annulus relaxation (e'), and peak tricuspid regurgitation velocity before and immediately after exercise. RESULTS: Over a mean follow-up of 3.3 ± 3.4 years, patients with E/e' ≥15 with exercise (n = 1,323; 9.2%) had lower exercise capacity (7.3 ± 2.1 vs 9.1 ± 2.4 metabolic equivalents, P < .0001) and were more likely to have resting or inducible RWMAs (38% vs 18%, P < .0001). Approximately 6% (n = 837) had elevated LV filling pressures without RWMAs. Patients with a poststress E/e' ≥15 had a 2.71-fold increased mortality rate (2.28-3.21, P < .0001) compared with those with poststress E/e' ≤ 8. Those with an E/e' of 9 to 14, while at lower risk than the E/e' ≥15 cohort (hazard ratio [HR] = 0.58 [0.48-0.69]; P < .0001), had higher risk than if E/e' ≤8 (HR = 1.56 [1.37-1.78], P < .0001). On multivariable analysis, adjusting for age, sex, exercise capacity, LV ejection fraction, and presence of pulmonary hypertension with stress, patients with E/e' ≥15 had a 1.39-fold (95% CI, 1.18-1.65, P < .0001) increased risk of all-cause mortality compared with patients without elevated LV filling pressures. Compared with patients with E/e' ≤ 15 after exercise, patients with E/e' ≤15 at rest but elevated after exercise had a higher risk of cardiovascular death (HR = 8.99 [4.7-17.3], P < .0001). CONCLUSION: Patients with elevated LV filling pressures are at increased risk of death, irrespective of myocardial ischemia or LV systolic dysfunction. These findings support the routine incorporation of LV filling pressure assessment, both before and immediately following stress, into the evaluation of patients referred for exercise echocardiography.

Using PAH-SYMPACT to assess quality of life in patients with pulmonary hypertension associated with chronic lung disease.

Chronic lung disease (CLD) is the second leading cause of pulmonary hypertension (PH) and is associated with significant morbidity and mortality. Although PH associated with CLD (PH-CLD) leads to impaired health-related quality of life (HRQOL), there are no validated tools to assess HRQOL in PH-CLD. The Pulmonary Arterial Hypertension-Symptoms and Impact Questionnaire (PAH-SYMPACT) is an HRQOL instrument aimed at assessing the symptoms and impact of PH on overall function and well-being. We performed a single-center prospective cohort study using PAH-SYMPACT scores to compare symptoms, exercise capacity and HRQOL in patients with PAH and PH-CLD. One hundred and twenty-five patients (99 patients with idiopathic/heritable PAH and 26 with PH-CLD) completed the PAH-SYMPACT questionnaire which consists of 22 questions that assess HRQOL across four domains: cardiopulmonary (CP) symptoms, cardiovascular (CV) symptoms, physical impact (PI), and cognitive/emotional (CE) impact. Higher scores indicate worse HRQOL. We compared patients with PAH and PH-CLD using a Wilcoxon rank sum or chi-squared test as appropriate. Multivariate linear regression analysis was used to assess the relationship between PH classification and SYMPACT scores. Compared to PAH, patients with PH-CLD were older, more likely to use oxygen and had worse functional class and exercise capacity. While there was no significant difference between the two groups in CP, CV, or CE domain scores, patients with PH-CLD had significantly worse PI scores by univariate (1.79 vs. 1.13, p < 0.001) and multivariate analysis (1.61 vs. 1.17, p = 0.02) and overall worse SYMPACT scores (1.19 vs. 0.91, p = 0.03). In conclusion, patients with PH-CLD have worse HRQOL as assessed by the PAH-SYMPACT questionnaire versus patients with PAH. Although PAH-SYMPACT has not been validated in PH-CLD, the results of this study can guide clinicians in understanding the symptoms and impact of PH-CLD relative to PAH.

Incidence of Severe Adverse Drug Reactions to Ultrasound Enhancement Agents in a Contemporary Echocardiography Practice.

OBJECTIVES: Prior data indicate a very rare risk of serious adverse drug reaction (ADR) to ultrasound enhancement agents (UEAs). We sought to evaluate the frequency of ADR to UEA administration in contemporary practice. METHODS: We retrospectively reviewed 4 US health systems to characterize the frequency and severity of ADR to UEA. Adverse drug reactions were considered severe when cardiopulmonary involvement was present and critical when there was loss of consciousness, loss of pulse, or ST-segment elevation. Rates of isolated back pain and headache were derived from the Mayo Clinic Rochester stress echocardiography database where systematic prospective reporting of ADR was performed. RESULTS: Among 26,539 Definity and 11,579 Lumason administrations in the Mayo Clinic Rochester stress echocardiography database, isolated back pain or headache was more frequent with Definity (0.49% vs 0.04%, P < .0001) but less common with Definity infusion versus bolus (0.08% vs 0.53%, P = .007). Among all sites there were 201,834 Definity and 84,943 Lumason administrations. Severe and critical ADR were more frequent with Lumason than with Definity (0.0848% vs 0.0114% and 0.0330% vs 0.0010%, respectively; P < .001 for each). Among the 3 health systems with >2,000 Lumason administrations, the frequency of severe ADR with Lumason ranged from 0.0755% to 0.1093% and the frequency of critical ADR ranged from 0.0293% to 0.0525%. Severe ADR rates with Definity were stable over time but increased in more recent years with Lumason (P = .02). Patients with an ADR to Lumason since the beginning of 2021 were more likely to have received a COVID-19 vaccination compared with matched controls (88% vs 75%; P = .05) and more likely to have received Moderna than Pfizer-Biotech (71% vs 26%, P < .001). CONCLUSION: Severe and critical ADR, while rare, were more frequent with Lumason, and the frequency has increased in more recent years. Additional work is needed to better understand factors, including associations with recently developed mRNA vaccines, which may be contributing to the increased rates of ADR to UEA since 2021.

Identification and risk stratification of coronary disease by artificial intelligence-enabled ECG.

Background: Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death worldwide, driven primarily by coronary artery disease (CAD). ASCVD risk estimators such as the pooled cohort equations (PCE) facilitate risk stratification and primary prevention of ASCVD but their accuracy is still suboptimal. Methods: Using deep electronic health record data from 7,116,209 patients seen at 70+ hospitals and clinics across 5 states in the USA, we developed an artificial intelligence-based electrocardiogram analysis tool (ECG-AI) to detect CAD and assessed the additive value of ECG-AI-based ASCVD risk stratification to the PCE. We created independent ECG-AI models using separate neural networks including subjects without known history of ASCVD, to identify coronary artery calcium (CAC) score ≥300 Agatston units by computed tomography, obstructive CAD by angiography or procedural intervention, and regional left ventricular akinesis in ≥1 segment by echocardiogram, as a reflection of possible prior myocardial infarction (MI). These were used to assess the utility of ECG-AI-based ASCVD risk stratification in a retrospective observational study consisting of patients with PCE scores and no prior ASCVD. The study period covered all available digitized EHR data, with the first available ECG in 1987 and the last in February 2023. Findings: ECG-AI for identifying CAC ≥300, obstructive CAD, and regional akinesis achieved area under the receiver operating characteristic (AUROC) values of 0.88, 0.85, and 0.94, respectively. An ensembled ECG-AI identified 3, 5, and 10-year risk for acute coronary events and mortality independently and additively to PCE. Hazard ratios for acute coronary events over 3-years in patients without ASCVD that tested positive on 1, 2, or 3 versus 0 disease-specific ECG-AI models at cohort entry were 2.41 (2.14-2.71), 4.23 (3.74-4.78), and 11.75 (10.2-13.52), respectively. Similar stratification was observed in cohorts stratified by PCE or age. Interpretation: ECG-AI has potential to address unmet need for accessible risk stratification in patients in whom PCE under, over, or insufficiently estimates ASCVD risk, and in whom risk assessment over time periods shorter than 10 years is desired. Funding: Anumana.

Relationship between diastolic function and heart rate recovery after symptom-limited exercise.

BACKGROUND: Autonomic abnormalities have been implicated in both diastolic dysfunction and abnormal heart rate (HR) recovery; however, few studies have assessed whether diastolic dysfunction is associated with abnormal HR recovery and whether both modify exercise capacity. METHODS AND RESULTS: Exercise echocardiography with diastolic assessment was performed in 2,826 patients with normal wall motion responses to symptom-limited exercise testing. HR recovery was defined as the difference in HR from peak exercise to 1 minute in recovery; abnormal HR recovery was defined as the lowest quartile. Mean HR recovery was 32 ± 14 beats per minute. Patients with diastolic dysfunction or abnormal HR recovery had lower exercise capacity, and those with both had the lowest exercise capacity (P < .0001 compared with normal responses). Indices of abnormal diastolic function were correlated with abnormal HR recovery. In multivariable analysis, after age diastolic dysfunction (referent: normal diastolic function) was the strongest predictor of abnormal HR recovery (adjusted odds ratio [OR] 1.47, 95% confidence interval [CI] 1.20-1.80) and incrementally predictive of chronotropic incompetence (adjusted OR 1.42, 95% CI 1.16-1.74). CONCLUSIONS: Diastolic dysfunction is independently associated with abnormal HR recovery after symptom-limited exercise. Further studies are needed to determine if diastolic function modifies the adverse outcomes observed in those with abnormal HR recovery.

Association of Pulmonary Hypertension and Monoclonal Gammopathy of Undetermined Significance.

Objective: To determine the prevalence of monoclonal gammopathy of undetermined significance (MGUS) in patients with PH as well as precapillary PH. Methods: Olmsted County residents with PH, diagnosed between 1/1/1995 and 9/30/2017, were identified, and age and sex were matched to a normal control group. The PH group and normal control group were then cross-referenced with the Mayo Clinic MGUS database. Charts were reviewed to verify MGUS and PH. Heart catheterization data were then analyzed in these patients for reference to the gold standard for diagnosis. Results: There were 3419 patients diagnosed with PH by echocardiography between 1995 and 2017 in Olmsted County that met the criteria of our study. When the PH group (N = 3313) was matched to a normal control group (3313), a diagnosis of MGUS was significantly associated with PH 10.2% (OR = l.84 [95% CI 1.5-2.2], p < 0.001), compared with controls 5.8% based on echo diagnosis. Using heart catheterization data (484 patients), a diagnosis of MGUS was associated with PH 13.0% (OR = 3.94 [95% CI 2.28-6.82], p < 0.001). For pulmonary artery hypertension (N = 222), a diagnosis of MGUS was associated with PH at similar 12.2% (OR = 4.50 [95%CI 1.86-10.90], p < 0.001. Conclusions: There is a higher prevalence of MGUS in patients with PH and precapillary PH compared with normal controls. This association cannot be explained fully by other underlying diagnoses associated with PH. Assessing for this in patients with PH of unclear etiology may be reasonable in the workup of patients found to have PH.

Prognostic Role of Cardiac Power in a Large Cohort of Patients with Normal Ejection Fraction Referred for Dobutamine Stress Echocardiography.

BACKGROUND: Cardiac power reflects cardiac performance in terms of energy transferred by the left ventricle to the aorta per unit time. Peak stress cardiac power has been shown to predict outcomes in patients with reduced left ventricular ejection fraction (LVEF) and, more recently, in patients with normal LVEF referred for exercise stress echocardiography. The aim of this study was to evaluate the prognostic significance of cardiac power in patients with normal LVEF referred for dobutamine stress echocardiography. METHODS: Data were studied from 15,576 patients with LVEF ≥ 50% and no significant valvular or right ventricular dysfunction who underwent dobutamine stress echocardiography. Cardiac power at rest and peak stress and power reserve (peak stress minus rest power) were calculated and normalized to left ventricular mass. Outcome end points were all-cause mortality and new-onset heart failure (HF). RESULTS: The mean age was 66 ± 13 years, and 49% patients were women. Resting and peak stress power/mass were 0.7 ± 0.2 and 1.6 ± 0.6 W/100 g left ventricular myocardium, respectively. During follow-up (median, 3.3 years; interquartile range, 0.7-7.3 years), 2,278 patients died and 2,137 developed HF. After adjusting for age, sex, comorbidities, and stress test results, lower peak stress power/mass was independently associated with mortality (adjusted hazard ratio, highest vs lowest quartile, 0.84; 95% CI, 0.74-0.95; P = .004) and HF at follow-up (adjusted hazard ratio, 0.67; 95% CI, 0.59-0.76; P < .0001). Power reserve showed similar associations with outcomes. CONCLUSIONS: Assessment of cardiac power during dobutamine stress echocardiography in patients with normal LVEF provides valuable prognostic information regarding risk for mortality and future HF, in addition to stress test results. It is an important research tool to study cardiac performance, and the development of risk scores incorporating this novel index could be considered after further validation in prospective studies.

The feasibility and value of assessing patient-reported outcomes in pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a progressive pulmonary vascular disease that negatively impacts health-related quality of life (HRQOL). The PAH-symptoms and impact (PAH-SYMPACT) questionnaire is a validated disease-specific patient-reported outcome (PRO) instrument that assesses a patient's symptoms and the impact of PAH and its treatment on well-being. We performed a single-center prospective cohort study of patients with PAH to determine the feasibility of assessing PROs in clinical practice and to determine the association between PAH-SYMPACT domains and clinical characteristics and outcomes. One hundred and ten patients completed the 1-day version of the PAH-SYMPACT questionnaire which consists of 22 Likert-scale questions that assess HRQOL across four domains: cardiopulmonary (CP) symptoms, cardiovascular (CV) symptoms, physical impact (PI), and cognitive and emotional (CE) impact. Higher scores indicate worse HRQOL. Patients were predominantly female (n = 86, 78%) with a mean age of 57.8 ± 16.2 years. While several patient characteristics were associated with CP and PI domains, few were associated with CV and CE domains. PI and CE impact scores were associated with recent hospitalizations and mortality and CE impact score was independently associated with an increased risk of death after adjustment for disease severity (hazard ratio: 3.29, 95% confidence interval: 1.56-6.91, p = 0.002). In conclusion, the assessment of PROs in clinical practice using the PAH-SYMPACT questionnaire is both feasible and valuable. PAH-SYMPACT scores have independent prognostic value and are not adequately reflected by traditional measures of disease severity. These findings underscore the importance of assessing HRQOL in clinical practice.

High Prevalence of Severe Aortic Stenosis in Low-Flow State Associated With Atrial Fibrillation.

BACKGROUND: Atrial fibrillation (AF) is a low-flow state and may underestimate aortic stenosis (AS) severity. Single-high Doppler signals (HS) consistent with severe AS (peak velocity ≥4 m/s or mean gradient ≥40 mm Hg) are averaged down in current practice. The objective for the study was to determine the significance of HS in AF low-gradient AS (LGAS). METHODS: One thousand five hundred forty-one patients with aortic valve area ≤1 cm2 and left ventricular ejection fraction ≥50% were identified and classified as high-gradient AS (HGAS) (≥40 mm Hg) and LGAS (<40 mm Hg), and AF versus sinus rhythm (SR). Available computed tomography aortic valve calcium scores (AVCS) were retrieved from the medical record. Outcomes were assessed. RESULTS: Mean age was 76±11 years, female 47%. Mean gradient was 51±12 in SR-HGAS, 48±10 in AF-HGAS, 31±5 in SR-LGAS, and 29±7 mm Hg in AF-LGAS, all P≤0.001 versus SR-HGAS; HS were present in 33% of AF-LGAS. AVCS were available in 34%. Compared with SR-HGAS (2409 arbitrary units; interquartile range, 1581-3462) AVCS were higher in AF-HGAS (2991 arbitrary units; IQR1978-4229, P=0.001), not different in AF-LGAS (2399 arbitrary units; IQR1817-2810, P=0.47), and lower in SR-LGAS (1593 arbitrary units; IQR945-1832, P<0.001); AVCS in AF-LGAS were higher when HS were present (P=0.048). Compared with SR-HGAS, the age-, sex-, comorbidity index-, and time-dependent aortic valve replacement-adjusted mortality risk was higher in AF-HGAS (hazard ratio=1.82 [1.40-2.36], P<0.001) and AF-LGAS with HS (hazard ratio=1.54 [1.04-2.26], P=0.03) but not different in AF-LGAS without HS or SR-LGAS (both P=not significant). CONCLUSIONS: Severe AS was common in AF-LGAS. AVCS in AF-LGAS were not different from SR-HGAS. AVCS were higher and mortality worse in AF-LGAS when HS were present.

Impact of Anemia on Exercise and Pharmacologic Stress Echocardiography.

BACKGROUND: The safety and diagnostic accuracy of stress testing in anemic patients have not been well studied. Despite a lack of data, significant anemia may be considered a relative contraindication to stress testing because of safety concerns related to insufficient myocardial oxygen supply. METHODS: The authors reviewed 28,829 consecutive patients with blood hemoglobin drawn within 48 hours of stress echocardiography (15,624 exercise and 13,205 dobutamine). The associations of blood hemoglobin concentration with arrhythmia and other stress echocardiographic findings were examined. Additionally, the effect of anemia on the positive predictive value of stress echocardiography for the detection of significant coronary artery stenosis (≥50%) was assessed in patients who subsequently underwent coronary angiography. RESULTS: Anemia was present in 6,401 patients (22.2%) and was severe (hemoglobin < 8.0 g/dL) in 52. Stress testing with either exercise or dobutamine was safe, with no significant increase in serious arrhythmia events or need for hospitalization. In the exercise cohort, worsening anemia was associated with reduced treadmill exercise time, lower peak heart rate, peak rate-pressure product, and achieved workload. In the dobutamine stress cohort, worsening anemia was associated with higher resting heart rate, more use of atropine, and fewer patients attaining target heart rate. The positive predictive value of stress echocardiography was higher in patients with moderate anemia compared with those without anemia (71.8% vs 60.2%, P = .01). CONCLUSIONS: This study demonstrates that stress testing is safe in patients with mild and moderately anemia, albeit with a small increase in mild supraventricular arrhythmias with exercise. However, worsening anemia was associated with a significant reduction in exercise capacity. Additionally, worsening anemia was associated with an improvement in the positive predictive value of stress echocardiography. Extrapolation of these data to patients with severe anemia should be performed with caution given the limited number of patients with severe anemia in this study.

Atrial fibrillation is not an independent predictor of outcome in patients with aortic stenosis.

OBJECTIVES: To examine the prognostic significance of atrial fibrillation (AF) versus sinus rhythm (SR) on the management and outcomes of patients with severe aortic stenosis (AS). METHODS: 1847 consecutive patients with severe AS (aortic valve area ≤1.0 cm2 and aortic valve systolic mean Doppler gradient ≥40 mm Hg or peak velocity ≥4 m/s) and left ventricular ejection fraction ≥50% were identified. The independent association of AF and all-cause mortality was assessed. RESULTS: Age was 76±11 years and 46% were female; 293 (16%) patients had AF and 1554 (84%) had SR. In AF, 72% were symptomatic versus 71% in SR. Survival rate at 5 years for AF (41%) was lower than SR (65%) (age- and sex-adjusted HR=1.66 (1.40-1.98), p<0.0001). In multivariable analysis, factors associated with mortality included age (HR per 10 years=1.55 (1.42-1.69), p<0.0001), dyspnoea (HR=1.58 (1.33-1.87), p<0.0001), ≥ moderate mitral regurgitation (HR=1.63 (1.22-2.18), p=0.001), right ventricular systolic dysfunction (HR=1.88 (1.52-2.33), p<0.0001), left atrial volume index (HR per 10 mL/m2=1.13 (1.07-1.19), p<0.0001) and aortic valve replacement (AVR) (HR=0.44 (0.38-0.52), p<0.0001). AF was not a predictor of mortality independent of variables strongly correlated HR=1.02 (0.84-1.25), p=0.81). The 1-year probability of AVR following diagnosis of severe AS was lower in AF (49.8%) than SR (62.5%) (HR=0.73 (0.62-0.86), p<0.001); among patients with AF not referred for AVR, symptoms were frequently attributed to AF instead of AS. CONCLUSION: AF was associated with poor prognosis in patients with severe AS, but apparent differences in outcomes compared with SR were explained by factors other than AF including concomitant cardiac abnormalities and deferral of AVR due to attribution of cardiac symptoms to AF.

Preoperative Dobutamine Stress Echocardiography and Clinical Factors for Assessment of Cardiac Risk after Noncardiac Surgery.

BACKGROUND: The role of dobutamine stress echocardiography (DSE) in the risk stratification of patients undergoing noncardiac surgery in the current era is unclear. The aim of this study was to evaluate the yield of DSE and the additive role of DSE to clinical criteria for preoperative risk stratification of patients undergoing noncardiac surgery. METHODS: The study included 4,494 patients undergoing DSE ≤90 days before noncardiac surgery. The primary outcome was a composite of postoperative myocardial infarction, cardiac arrest, and all-cause mortality ≤30 days after noncardiac surgery. RESULTS: The overall 30-day postoperative cardiac event rate was 2.3%. The mortality rate was 0.9% overall and 0.7% and 1.3% after normal and abnormal results on DSE, respectively. Among clinical variables, the modified Revised Cardiac Risk Index score demonstrated the strongest association with postoperative risk (P < .001). Patients with Revised Cardiac Risk Index scores of ≥3 had an event rate of 7.5%. The event rates for patients with wall motion score index ≥1.7 at baseline, left ventricular ejection fractions <40% at peak stress, or ischemic thresholds <70% of age-predicted maximal heart rate were 7.1%, 8.6%, and 7.9%, respectively. After adjusting for clinical variables, the overall result of DSE (P < .001), baseline and peak-stress wall motion score index (P < .001 and P = .014, respectively), peak-stress left ventricular ejection fraction (P < .001), and the number of ischemic segments (P = .027) were all associated with postoperative cardiac events. Incremental multivariate analysis demonstrated that an overall abnormal result on DSE, added to clinical variables, was associated with an increased risk for postoperative cardiac events (odds ratio, 2.07; 95% CI, 1.35-3.17; P < .001). CONCLUSIONS: Baseline and peak-stress findings on preoperative DSE add to the prognostic utility of clinical variables for stratifying cardiac risk after noncardiac surgery.

Left ventricular function and exercise capacity.

CONTEXT: Limited information exists regarding the role of left ventricular function in predicting exercise capacity and impact on age- and sex-related differences. OBJECTIVES: To determine the impact of measures of cardiac function assessed by echocardiography on exercise capacity and to determine if these associations are modified by sex or advancing age. DESIGN: Cross-sectional study of patients undergoing exercise echocardiography with routine measurements of left ventricular systolic and diastolic function by 2-dimensional and Doppler techniques. Analyses were conducted to determine the strongest correlates of exercise capacity and the age and sex interactions of these variables with exercise capacity. SETTING: Large tertiary referral center in Rochester, Minnesota, in 2006. PARTICIPANTS: Patients undergoing exercise echocardiography using the Bruce protocol (N = 2867). Patients with echocardiographic evidence of exercise-induced ischemia, ejection fractions lower than 50%, or significant valvular heart disease were excluded. MAIN OUTCOME MEASURE: Exercise capacity in metabolic equivalents (METs). RESULTS: Diastolic dysfunction was strongly and inversely associated with exercise capacity. Compared with normal function, after multivariate adjustment, those with moderate/severe resting diastolic dysfunction (-1.30 METs; 95% confidence interval [CI], -1.52 to -0.99; P < .001) and mild resting diastolic dysfunction (-0.70 METs; 95% CI, -0.88 to -0.46; P < .001) had substantially lower exercise capacity. Variation of left ventricular systolic function within the normal range was not associated with exercise capacity. Left ventricular filling pressures measured by resting E/e' of 15 or greater (-0.41 METs; 95% CI, -0.70 to -0.11; P = .007) or postexercise E/e' of 15 or greater (-0.41 METs; 95% CI, -0.71 to -0.11; P = .007) were similarly associated with a reduction in exercise capacity, each in separate multivariate analyses. Individuals with impaired relaxation (mild dysfunction) or resting E/e' of 15 or greater had a progressive increase in the magnitude of reduction in exercise capacity with advancing age (P < .001 and P = .02, respectively). Other independent correlates of exercise capacity were age (unstandardized beta coefficient, -0.85 METs; 95% CI, -0.92 to -0.77, per 10-year increment; P < .001), female sex (-1.98 METs; 95% CI, -2.15 to -1.84; P < .001), and body mass index greater than 30 (-1.24 METs; 95% CI, -1.41 to -1.10; P < .001). CONCLUSION: In this large cross-sectional study of those referred for exercise echocardiography and not limited by ischemia, abnormalities of left ventricular diastolic function were independently associated with exercise capacity.

Thrombocytopenia independently predicts death in idiopathic PAH.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a progressive vascular disorder with a high mortality. Clinical experience and small case series suggest thrombocytopenia may be frequent in this population and associated with a poor prognosis. We sought to estimate the prevalence of thrombocytopenia in patients with PAH and characterize its association with disease characteristics and patient outcome. METHODS: Single center cohort study of 714 incident adult patients with Group 1 PH who were evaluated for baseline platelet count at the time of diagnosis. Pts were stratified into three groups: normal platelet count (>150 × 109/L), Grade 1 thrombocytopenia (75-149 × 109/L) and Grade 2-4 thrombocytopenia (<75 × 109/L). RESULTS: The median platelet count was 209 × 109/L (IQR 163, 264). There were 572 (80%) pts without thrombocytopenia, 107 (15%) with Grade 1 and 35 (5%) with Grade 2-4 thrombocytopenia. The median pt age was 55 years (IQR 44-65) with no difference between platelet groups (p = 0.85). Men were more likely to have thrombocytopenia (62, 34%) than women (80, 15%, p < 0.0001). Thrombocytopenia was frequent with portopulmonary PAH (84%) as opposed to idiopathic PAH (iPAH; 14%) or connective tissue disease associated PAH (12%). Platelet counts were not associated with functional class symptoms, the degree of right ventricular enlargement or dysfunction or tricuspid regurgitation by echocardiography. Invasive hemodynamics of right atrial pressure, mean pulmonary artery pressure and pulmonary vascular resistance were also similar between platelet groups. Thrombocytopenia was associated with higher mortality in iPAH patients (age- and sex-adjusted 5 year mortality [HR 1.95 (1.20, 3.08) p = 0.008] but not in other etiology groups. In a multivariate model of iPAH patients (adjusted for age, sex, DLCO, PVR, creatinine and 6MW distance) thrombocytopenia was most predictive of 5-year mortality [HR 1.68 (1.32, 2.12), p < 0.0001]. CONCLUSION: Thrombocytopenia in the context of iPAH portends a poor prognosis and is a simple independent factor to consider in judging severity of disease.

Cardiac Events after Noncardiac Surgery in Patients Undergoing Preoperative Dobutamine Stress Echocardiography: Findings From the Mayo Poce-DSE Investigators.

BACKGROUND: Current guidelines support the use of dobutamine stress echocardiography (DSE) prior to noncardiac surgery in higher-risk patients who are unable to perform at least 4 metabolic equivalents of physical activity. We evaluated postoperative outcomes of patients in different operative risk categories after preoperative DSE. METHODS: We collected data from the medical record on 4494 patients from January 1, 2006 to December 31, 2011 who had DSE up to 90 days prior to a noncardiac surgery. Patients were divided into low, intermediate, and high preoperative surgery-specific risk. Baseline demographic data and risk factors were abstracted from the medical record, as were postoperative cardiac events including myocardial infarction, cardiac arrest, and mortality within 30 days after surgery. RESULTS: There were 103 cardiac outcomes (2.3%), which included myocardial infarction (n = 57, 1.3%), resuscitated cardiac arrest (n = 26, 0.6%), and all-cause mortality (n = 40, 0.9%). Cardiac event rates were 0.0% (95% confidence interval [CI], 0.0%-3.9%) in the low-surgical-risk group, 2.1% (95% CI, 1.6%-2.5%) in the intermediate-surgical-risk group, and 3.4% (95% CI, 2.0%-4.4%) in the high-risk group. Thirty-day postoperative mortality rates were 0%, 0.9%, and 0.8% for the low-risk, intermediate-risk, and high-risk surgical groups, respectively, and were not statistically different. CONCLUSIONS: These findings demonstrate low cardiac event rates in patients who underwent a DSE prior to noncardiac surgery. The previously accepted construct of low-, intermediate-, and high-risk surgeries based on postoperative events of <1%, 1%-5%, and >5% overestimates the actual risk in contemporary settings.