Pellikka, Patricia A.

Background— Pulmonary arterial hypertension (PAH) is characterized by pulmonary vascular remodeling and right heart failure. The right (RV) and left ventricles (LV) do not function in isolation, sharing a common pericardial sac and interventricular septum. We sought to define the clinical and prognostic significance of ventricular interdependence in PAH and its association with LV filling patterns through speckle-tracking strain echocardiography. Methods and Results— Echocardiography was performed in 71 adults with a new diagnosis of PAH. To analyze LV and RV function separately, we measured peak systolic longitudinal and circumferential strain of the LV and RV. Survival was assessed >2 years. Patients had dilated right-sided chambers (right atrial volume index, 44±19 mL/m 2 ; RV end-diastolic area, 34±9 cm 2 ), and reduced RV function (RV fractional area change, 28±12%). Speckle-tracking echocardiography revealed significant reductions in RV free wall peak systolic strain (−15±3%). Despite normal LV size and normal conventional measures of LV systolic function (end-diastolic dimension, 42±6 mm; ejection fraction, 65±8%; cardiac index, 2.6±0.8 L/min per m 2 ), patients had reduced LV free wall systolic strain (−15±3%). Decreased LV free wall systolic strain was associated with a delayed relaxation mitral inflow Doppler pattern, P =0.0002. During 2-year follow-up, 19 patients (27%) died. LV strain was associated with increased mortality (unadjusted hazard ratio, 2.40 per 5% decrease in LV free wall strain, 1.22–4.68), which remained significant when adjusted for age, sex, World Health Organization functional class, and PAH pathogenesis (hazard ratio, 3.11, 1.38–7.20). Conclusions— The pressure loading in PAH results in geometric alterations and functional decline of the RV, with marked reduction in RV systolic strain. Despite preservation of LV ejection fraction, LV systolic strain was also reduced and associated with early mortality, highlighting the significance of ventricular interdependence in PAH.

Background Plasma fibulin‐1 levels have been associated with N‐terminal pro–B‐type natriuretic peptide levels and left atrial size and shown to be predictive of mortality in patients with diabetes. The mechanisms behind these connections are not fully understood but are probably related to its roles as an extracellular matrix protein in cardiovascular tissues. Methods and Results One hundred twenty‐five patients with severe aortic stenosis who were scheduled for aortic valve replacement ( AVR ) were evaluated with preoperative echocardiography and their plasma fibulin‐1 levels were determined with ELISA . The cohort was followed for a median of 4 years after AVR . Increased restrictive left ventricular ( LV ) filling pattern was observed with increased plasma fibulin‐1 levels (2% versus 29% versus 24% in low, middle, and high plasma fibulin‐1 tertile groups, P =0.004). Likewise, reduced longitudinal systolic LV function (6.6±1.1 versus 6.1±1.3 versus 5.7±1.5 cm/s, P =0.05) and increased LV filling pressures was systolic velocity of the mitral annulus observed with increasing plasma fibulin‐1 concentrations (ratio of early transmitral flow velocity to early diastolic flow velocity of the mitral annulus 13±4 versus 15±5 versus 16±6 in the fibulin‐1 tertile groups, P =0.04). Conclusions In patients with symptomatic severe aortic stenosis undergoing AVR, plasma fibulin‐1 is associated with restrictive filling of the LV , decreased longitudinal systolic function of the LV , and increased LV filling pressures. Clinical Trial Registration URL: www.clinicaltrial.gov with Identifier: NCT00294775

Background— Global longitudinal systolic strain (GLS) is often reduced in aortic stenosis despite normal ejection fraction. The importance of reduced preoperative GLS on long-term outcome after aortic valve replacement is unknown. Methods and Results— A total of 125 patients with severe aortic stenosis and ejection fraction >40% scheduled for aortic valve replacement were evaluated preoperatively and divided into 4 groups according to GLS quartiles. Patients were followed up for 4 years. The primary end points were major adverse cardiac events (MACEs) defined as cardiovascular mortality and cardiac hospitalization because of worsening of heart failure; the secondary end point was cardiovascular mortality. MACE and cardiac mortality were significantly increased in patients with lower GLS. Estimated 5-year MACE was increased: first quartile 19% (n=6) / second quartile 20% (n=6) / third quartile 35% (n=11) / fourth quartile 49% (n=15); P =0.04. Patients with increased age, left ventricular hypertrophy, and left atrial dilatation were at increased risk. In Cox regression analysis, after correcting for standard risk factors and ejection fraction, GLS was found to be significantly associated with cardiac morbidity and mortality. In a stepwise Cox model with forward selection, GLS was the sole independent predictor: hazard ratio=1.13 (95% confidence interval, 1.02–1.25), P =0.04. Comparing the overall log likelihood χ 2 of the predictive power of the multivariable model containing GLS was statistically superior to models based on EuroScore, history with ischemic heart disease, and ejection fraction. Conclusions— In patients with symptomatic severe aortic stenosis undergoing aortic valve replacement, reduced GLS provides important prognostic information beyond standard risk factors. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00294775.

Objectives: We investigated the correlation between left ventricular global and regional longitudinal systolic strain (GLS and LRS) and coronary flow reserve (CFR) assessed by transthoracic echocardiography (TTE) in patients with a recent acute myocardial infarction (AMI). Furthermore, we investigated if LRS and GLS imaging is superior to conventional measures of left ventricle (LV) function. Methods: In a consecutive population of first time AMI patients, who underwent successful revascularization, we performed comprehensive TTE. GLS and LRS were obtained from the three standard apical views. Assessment of CFR by TTE was performed in a modified apical view using color Doppler guidance. Results: The study population consisted of 183 patients (51 females) with a median age of 63 [54;70] years. Eighty‐nine (49%) patients had a non‐ST elevation myocardial infarction and 94 (51%) patients had a ST elevation myocardial infarction. The GLS was −15.2 [−19.3;−10.1]% in the total population of 183 patients. Total wall motion score index (WMSI) in the population was 1.19 [1;1.5]. Eighty‐five patients suffered from culprit lesion in left anterior descending artery (LAD). The CFR in these patients was 1.86 [1.36;2.35] and the GLS was −14.3 [−18.9; −9.8]%. A significant difference was observed in the LRS in LAD territory in culprit LAD infarction patients with a CFR ≤ 2 (−9.6 [−13.77;−6.44]) compared with the LRS in LAD territory in culprit LAD infarction patients with a CFR > 2 (−19.33 [−21.1;−16.5]), P < 0.0001. We found no significant difference between WMSI in LAD territory in culprit LAD infarction patients with a CFR ≤ 2 (1.56 [1.06;2.23]) compared with WMSI in LAD territory in culprit LAD infarction patients with a CFR > 2 (1.37 [1.03;2.11]); P = 0.18. The same pattern was observed in both circumflex coronary artery (CX) and right coronary artery (RCA) territories. In the total population, we found a strong correlation between CFR and GLS (r = −0.85, P < 0.0001). This was also seen in the multivariate regression model adjusting for possible confounders including WMSI (P < 0.001). Conclusion: In this study, we have shown a close association between myocardial deformation in patients with a recent AMI and the degree of diminished microcirculation. We found that both GLS and LRS correlated with CFR. We conclude that GLS and LRS are significantly better tools to assess impaired CFR and LV function after a recent AMI, than conventional echocardiographic measurements.

Background —The prognostic value of treadmill exercise testing (TMET) has been studied in selected populations. The generalizability of these data to different populations and to women is uncertain. Methods and Results —A retrospective, population-based cohort study of all persons (1452 men and 741 women) who underwent TMET in years 1987 to 1989 in Olmsted County, Minnesota, was undertaken. Individuals were followed up for all-cause mortality and cardiac events (cardiac deaths, nonfatal myocardial infarction, or congestive heart failure). Sex-specific analyses were performed to determine whether the predictors of outcome and the magnitude of the associations were similar in both sexes. In men, 77 deaths and 106 cardiac events occurred during 8956 person-years of observation; in women, 46 deaths and 54 cardiac events occurred during 4801 person-years of follow-up. Exercise-induced angina, ECG changes, and workload achieved on the TMET were strongly associated with all-cause mortality and cardiac events in both sexes, and the strength of the association was similar. After adjustment, workload was the only TMET variable associated with outcome. A higher workload was associated with a reduction in the risk of cardiac events and of all-cause mortality; the protective effect of exercise capacity was strong and was similar in both sexes. Conclusions —In this population-based cohort, exercise capacity was the TMET variable that exhibited the strongest association with all-cause mortality and cardiac events. This protective effect of exercise capacity was observed in both sexes.

Background —Increasingly, dobutamine stress echocardiography has been used for detection of coronary artery disease. Less information exists regarding the incremental prognostic value of the test, including semiquantitative wall scoring, compared with clinical and rest echocardiographic variables. Methods and Results —Follow-up information was obtained from 860 patients who underwent dobutamine stress echocardiography over a 2-year period. To determine the value of dobutamine stress echocardiography in predicting cardiac events, including cardiac death and myocardial infarction, clinical and rest and stress echocardiographic data were considered in a stepwise Cox multivariate regression model. During follow-up of up to 52 months, 72 patients underwent coronary revascularization before any cardiac event and were censored. Eighty-six patients had cardiac events, including nonfatal myocardial infarction in 36 and cardiac death in 50. In a multivariate model, a history of congestive heart failure, the percentage of abnormal segments at peak stress, and an abnormal left ventricular end-systolic volume response to stress were independent predictors of cardiac events. The model that best predicted subsequent cardiac events included clinical and stress echocardiographic data. Conclusions —Dobutamine stress echocardiography with semiquantitative segmental wall scoring provides important incremental information in predicting subsequent cardiac events.

Background The use of exercise echocardiography for the diagnosis of coronary artery disease (CAD) has been validated in pilot studies but is not documented in clinical practice and in women comparatively with men. The objectives of this study were to determine the effects of sex and of test verification bias on the diagnostic performance of exercise echocardiography. Methods and Results Three thousand six hundred seventy-nine consecutive patients (1714 women, 1965 men) who underwent an exercise echocardiographic study were studied; the observed sensitivity, specificity, and correct classification rate were calculated among 340 patients (244 men, 96 women) who underwent angiography; to study the effect of test verification bias, sensitivity and specificity were estimated for all patients who underwent exercise echocardiography including those not referred to angiography. In the angiographic group, the prevalence of CAD was 60% in women and 80% in men. The observed sensitivity and specificity of exercise echocardiography was 78% and 44% in men and 79% and 37% in women. After adjustment for test verification bias, the estimated sensitivity was lower in women (32% versus 42% in men), whereas specificity was similar in both sexes. The positive predictive value was lower in women (66%) compared with men (84%). Conclusions In clinical practice, test verification bias results in a lower observed specificity and a higher sensitivity of exercise echocardiography. In women, positive predictive value and adjusted sensitivity are lower compared with that in men.