Pellikka, Patricia A

Background: Lung ultrasound detects pulmonary congestion as B-lines at rest, and more frequently, during exercise stress echocardiography (ESE). Methods: We performed ESE plus lung ultrasound (4-site simplified scan) in 4392 subjects referred for semi-supine bike ESE in 24 certified centers in 9 countries. B-line score ranged from 0 (normal) to 40 (severely abnormal). Five different populations were evaluated: control subjects (n=103); chronic coronary syndromes (n=3701); heart failure with reduced ejection fraction (n=395); heart failure with preserved ejection fraction (n=70); ischemic mitral regurgitation ≥ moderate at rest (n=123). In a subset of 2478 patients, follow-up information was available. Results: During ESE, B-lines increased in all study groups except controls. Age, hypertension, abnormal ejection fraction, peak wall motion score index, and abnormal heart rate reserve were associated with B-lines in multivariable regression analysis. Stress B lines (hazard ratio, 2.179 [95% CI, 1.015–4.680]; P =0.046) and ejection fraction <50% (hazard ratio, 2.942 [95% CI, 1.268–6.822]; P =0.012) were independent predictors of all-cause death (n=29 after a median follow-up of 29 months). Conclusions: B-lines identify the pulmonary congestion phenotype at rest, and more frequently, during ESE in ischemic and heart failure patients. Stress B-lines may help to refine risk stratification in these patients. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT 03049995.

Background The aim of this study was to establish prognostic hemodynamic parameters in patients with mitral stenosis secondary to mitral annular calcification. Methods and Results A retrospective cohort of 105 patients undergoing transseptal catheterization for hemodynamic evaluation of mitral annular calcification–related mitral stenosis between 2004 and 2020 was studied. Mitral valve gradient (MVG) and mitral valve area (MVA; calculated by the Gorlin formula) were measured using direct left atrial and left ventricular pressures. The median age of the patients was 70.3 years (58.4–76.7 years), and 53.3% were women. The median MVA was 1.7 cm 2 (1.3–2.3 cm 2 ) and MVG was 7.3 mm Hg (5.3–10.3 mm Hg); left ventricular end‐diastolic pressure was 17.6±28.3 mm Hg. During a median of 2.1 years (0.7–4.5 years), there were 63 deaths; 1‐ and 5‐year survival were 76% and 40%, respectively. There was no association between left ventricular end‐diastolic pressure and survival. After adjusting for age and comorbidities, both MVA (hazard ratio [HR], 0.50 per cm 2 ; 95% CI, 0.34–0.73) and MVG (HR, 1.1 per mm Hg; 95% CI, 1.05–1.20) were independent predictors of death. Atrial fibrillation was also independently associated with mortality. When added to a combined model, MVA remained associated with death (HR, 0.51 per cm 2 ; 95% CI, 0.33–0.79) while MVG was not. Conclusions In patients with mitral annular calcification–related mitral stenosis, survival was poor. MVA and MVG were independently associated with death, but MVA was a better predictor of outcomes.

Background: Patients evaluated for coronary artery disease have a range of symptoms and underlying risk. The relationships between patient-described symptoms, clinician conclusions, and subsequent clinical management and outcomes remain incompletely described. Methods: In this secondary analysis, we examined the association between 4 types of presenting symptoms (substernal/left-sided chest pain, other chest/neck/arm pain, dyspnea, and other symptoms) and patient risk, noninvasive test results, clinical management, and outcomes for stable outpatients randomized in the PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) trial. Multivariable regression models were used to evaluate differences in noninvasive test result, all-cause death/myocardial infarction/unstable angina hospitalization and cardiovascular death/myocardial infarction by symptom type. Results: Among 9996 patients, most presented with chest pain (47.2% substernal, 29.2% other), followed by dyspnea (14.9%), and other symptoms (8.7%). Patients with dyspnea were older (median age 63 versus 60, P ≤0.02) with higher baseline risk (78.2% with atherosclerotic cardiovascular disease >7.5% versus 67.6%, P ≤0.02). Using patients with substernal chest pain as a reference, there was no difference in noninvasive test positivity across symptom groups (all P >0.05), but test-positive patients with dyspnea (adjusted odds ratio, 0.66 [95% CI, 0.51–0.85]) or other symptoms (adjusted odds ratio, 0.65 [95% CI, 0.47–0.90]) were less likely to be referred for cardiac catheterization. While symptom type alone was not associated with outcomes, symptom presentation with chest pain or dyspnea did modify the association between a positive noninvasive test and clinical outcome (interaction P =0.025 for both all-cause death/myocardial infarction/unstable angina hospitalization and cardiovascular death/MI). Conclusions: Among low-risk outpatients evaluated for coronary artery disease, typicality of symptoms was not closely associated with higher baseline risk but was related to differences in processes of care and the prognostic value of a positive test. Adverse events were not associated with clinician risk estimates or symptoms alone. These unexpected findings highlight the limitation of relying solely on symptom presentation or clinician risk estimation to evaluate patients for suspected coronary artery disease. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01174550.

Objective To evaluate informal physician judgement versus pretest probability scores in estimating risk in patients with suspected coronary artery disease (CAD). Methods We included 4533 patients from the PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) trial. Physicians categorised a priori the pretest probability of obstructive CAD (≥70% or ≥50% left main); Diamond-Forrester (D-F) and European Society of Cardiology (ESC) pretest probability estimates were calculated. Agreement was calculated using the κ statistic; logistic regression evaluated estimates of pretest CAD probability and actual CAD (as determined by CT coronary angiography), and clinical outcomes were modelled using Cox proportional hazard models. Results Physician estimates agreed poorly with D-F (κ 0.16; 95% CI 0.14 to 0.18) and ESC (κ 0.04; 95% CI 0.02 to 0.05). Actual obstructive CAD was significantly more prevalent in both the high-likelihood (OR 3.30; 95% CI 2.30 to 4.74) and the intermediate-likelihood (OR 1.43; 95% CI 1.16 to 1.76) physician-estimated groups versus the low-likelihood group; ESC similarly differentiated between the three groups (OR 9.07; 95% CI 2.87 to 28.70; and OR 3.87; 95% CI 1.22 to 12.28). However, using D-F, only the high-probability group differed (OR 2.49; 95% CI 1.74 to 3.54). Only physician estimates were associated with a higher incidence of adjusted death/myocardial infarction/unstable angina hospitalisation in the high-probability versus low-probability group (HR 2.68; 95% CI 1.52 to 4.74); neither pretest probability score provided prognostic information. Conclusions Compared with D-F and ESC estimates, physician judgement more accurately identified obstructive CAD and worse patient outcomes. Integrating physician judgement may improve risk prediction for patients with stable chest pain. Trial registration number NCT01174550 .

AbstractObjectivesTo compare all‐cause mortality in patients with mitral annulus calcification (MAC) and severe mitral valve dysfunction (MVD) who received standard mitral intervention versus no intervention.BackgroundPatients with MAC often have high surgical risk due to advanced age, comorbidities, and technical challenges related to calcium. The impact of a mitral intervention on outcomes of patients with MAC and severe MVD is not well known.MethodsRetrospective review of patients with MAC by transthoracic echocardiography (TTE) in 2015 at a single institution. Patients with severe mitral stenosis (MS) or regurgitation (MR) were analyzed and stratified into two groups: surgical or transcatheter intervention performed <1 year after the index TTE, and no or later intervention. The primary endpoint was all‐cause mortality.ResultsOf 5502 patients with MAC, 357 had severe MVD (MS = 27%, MR = 73%). Of those, 108 underwent mitral intervention (surgery = 87; transcatheter = 21). They were younger (73 ± 11 vs. 76 ± 11 years, p < 0.01) and less frequently had cardiovascular diseases compared with no‐intervention. Frequency in women was similar (45% vs. 50%, p = 0.44). During median follow‐up of 3.2 years, the intervention group had higher estimated survival than those without intervention (80% vs. 72% at 1 year and 55% vs. 35% at 4 year, p < 0.01). Adjusted for age, eGFR, LVEF < 50%, and pulmonary hypertension, mitral intervention was an independent predictor of lower mortality (hazard ratio = 0.66, 95% confidence interval 0.43–0.99, p = 0.046).ConclusionPatients with MAC and severe MVD who underwent mitral intervention <1 year from index TTE had lower mortality than those without intervention. Mitral intervention was independently associated with lower mortality.

Abstract Aims Concurrent mitral regurgitation (MR) influences treatment considerations in patients with severe aortic stenosis (sAS). Limited information exists regarding haemodynamic effects of sAS on MR severity and outcome of these patients. We assessed the impact of aortic valve replacement (AVR) on MR according to mechanism in patients with sAS and MR. Methods and results In patients with sAS who received surgical or transcatheter AVR from 2008 to 2017, those with effective mitral regurgitant orifice area (ERO) ≥ 10 mm2 prior to AVR were evaluated. The change in MR after AVR was considered significant when there was at least one grade difference. We compared the all-cause mortality of patients with and without improvement in MR. Of 234 patients with sAS and MR (age 80 ± 9 years, 52% male, ERO 19 ± 7 mm2), organic and functional MR were present in 166 (71%) and 68 (29%), respectively. MR improved in 136 (58%); improvement occurred with similar frequency in organic versus functional MR (59% and 57%, P = 0.88). Associated determinants were absence of atrial fibrillation in organic MR [odds ratio (OR) 2.09, 95% confidence interval (CI) 1.00–4.37; P = 0.049] and indexed aortic valve area (iAVA) ≤ 0.40 cm2 in functional MR (OR 3.28, 95% CI 1.13–9.47; P = 0.028). In the overall cohort, mitral annulus diameter &lt; 3 cm (OR 1.74, 95% CI 1.02–2.97; P = 0.041) and QRS duration &lt; 115 ms (OR 1.73, 95% CI 1.00–2.98; P = 0.049) were independently associated with improvement in MR. During median follow-up of 3.5 years, lack of improvement in MR was not associated with higher mortality in the overall cohort of patients with ERO ≥ 20 mm2 [adjusted hazard ratio (HR) 1.71, 95% CI 0.90–3.27; P = 0.10, adjusted for age, New York Heart Association III or IV, diabetes, and creatinine ≥ 2.0 mg/dL]. Lack of improvement in organic MR was associated with higher mortality (adjusted HR 3.36, 95% CI 1.40–8.05; P &lt; 0.01). In patients with functional MR, change in MR was not associated with mortality (HR 1.24, 95% CI 0.44–3.47; P = 0.68). Conclusions In nearly 60% of patients with sAS and MR, MR improved after AVR, even in the majority of patients with organic MR. Absence of atrial fibrillation in organic MR, iAVA ≤ 0.40 cm2 in functional MR, and mitral annulus diameter &lt; 3 cm and QRS duration &lt; 115 ms in the overall population were associated with MR improvement. Post-operative improvement in organic MR was associated with better survival.

With stress echo (SE) 2020 study, a new standard of practice in stress imaging was developed and disseminated: the ABCDE protocol for functional testing within and beyond CAD. ABCDE protocol was the fruit of SE 2020, and is the seed of SE 2030, which is articulated in 12 projects: 1-SE in coronary artery disease (SECAD); 2-SE in diastolic heart failure (SEDIA); 3-SE in hypertrophic cardiomyopathy (SEHCA); 4-SE post-chest radiotherapy and chemotherapy (SERA); 5-Artificial intelligence SE evaluation (AI-SEE); 6-Environmental stress echocardiography and air pollution (ESTER); 7-SE in repaired Tetralogy of Fallot (SETOF); 8-SE in post-COVID-19 (SECOV); 9: Recovery by stress echo of conventionally unfit donor good hearts (RESURGE); 10-SE for mitral ischemic regurgitation (SEMIR); 11-SE in valvular heart disease (SEVA); 12-SE for coronary vasospasm (SESPASM). The study aims to recruit in the next 5 years (2021–2025) ≥10,000 patients followed for ≥5 years (up to 2030) from ≥20 quality-controlled laboratories from ≥10 countries. In this COVID-19 era of sustainable health care delivery, SE2030 will provide the evidence to finally recommend SE as the optimal and versatile imaging modality for functional testing anywhere, any time, and in any patient.

Abstract Aim The aim of this study was to assess the prognostic value of ABCDE-SE in a prospective, large scale, multicentre, international, effectiveness study. Stress echocardiography (SE) was recently upgraded to the ABCDE protocol: step A, regional wall motion abnormalities; step B, B lines; step C, left ventricular contractile reserve; step D, Doppler-based coronary flow velocity reserve in left anterior descending coronary artery; and step E, electrocardiogram-based heart rate reserve. Methods and results From July 2016 to November 2020, we enrolled 3574 all-comers (age 65 ± 11 years, 2070 males, 58%; ejection fraction 60 ± 10%) with known or suspected chronic coronary syndromes referred from 13 certified laboratories. All patients underwent clinically indicated ABCDE-SE. The employed stress modality was exercise (n = 952, with semi-supine bike, n = 887, or treadmill, n = 65 with adenosine for step D) or pharmacological stress (n = 2622, with vasodilator, n = 2151; or dobutamine, n = 471). SE response ranged from score 0 (all steps normal) to score 5 (all steps abnormal). All-cause death was the only endpoint. Rate of abnormal results was 16% for A, 30% for B, 36% for C, 28% for D, and 37% for E steps. During a median follow-up of 21 months (interquartile range: 13–36), 73 deaths occurred. Global X 2 was 49.5 considering clinical variables, 50.7 after step A only (P = NS (not significant)) and 80.6 after B–E steps (P &lt; 0.001 vs. step A). Annual mortality rate ranged from 0.4% person-year for score 0 up to 2.7% person-year for score 5. Conclusion ABCDE-SE allows an effective prediction of survival in patients with chronic coronary syndromes.

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 cm 2 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.