Prevalence and Outcomes of Concomitant Aortic Stenosis and Cardiac Amyloidosis

BACKGROUND: Older patients with severe aortic stenosis (AS) are increasingly identified as having cardiac amyloidosis (CA). It is unknown whether concomitant AS-CA has worse outcomes or results in futility of transcatheter aortic valve replacement (TAVR). OBJECTIVES: This study identified clinical characteristics and outcomes of AS-CA compared with lone AS. METHODS: Patients who were referred for TAVR at 3 international sites underwent blinded research core laboratory 99mtechnetium-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) bone scintigraphy (Perugini grade 0: negative; grades 1 to 3: increasingly positive) before intervention. Transthyretin-CA (ATTR) was diagnosed by DPD and absence of a clonal immunoglobulin, and light-chain CA (AL) was diagnosed via tissue biopsy. National registries captured all-cause mortality. RESULTS: A total of 407 patients (age 83.4 6.5 years; 49.8% men) were recruited. DPD was positive in 48 patients (11.8%; grade 1: 3.9% [n ¼ 16]; grade 2/3: 7.9% [n ¼ 32]). AL was diagnosed in 1 patient with grade 1. Patients with grade 2/3 had worse functional capacity, biomarkers (N-terminal pro-brain natriuretic peptide and/or high-sensitivity troponin T), and biventricular remodeling. A clinical score (RAISE) that used left ventricular remodeling (hypertrophy/diastolic dysfunction), age, injury (high-sensitivity troponin T), systemic involvement, and electrical abnormalities (right bundle branch block/low voltages) was developed to predict the presence of AS-CA (area under the curve: 0.86; 95% confidence interval: 0.78 to 0.94; p < 0.001). Decisions by the heart team (DPD-blinded) resulted in TAVR (333 [81.6%]), surgical AVR (10 [2.5%]), or medical management (65 [15.9%]). After a median of 1.7 years, 23% of patients died. One-year mortality was worse in all patients with AS-CA (grade: 1 to 3) than those with lone AS (24.5% vs. 13.9%; p ¼ 0.05). TAVR improved survival versus medical management; AS-CA survival post-TAVR did not differ from lone AS (p ¼ 0.36). CONCLUSIONS: Concomitant pathology of AS-CA is common in older patients with AS and can be predicted clinically. AS-CA has worse clinical presentation and a trend toward worse prognosis, unless treated. Therefore, TAVR should not be withheld in AS-CA. (J Am Coll Cardiol 2021;77:128–39) © 2021 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Prognostic value of SPECT myocardial perfusion imaging when exercise is submaximal

Introduction. For patients undergoing myocardial perfusion imaging (MPI), pharmacological stress is increasingly recommended when there is any doubt about exercise capacity. This approach is based on the observation that the sensitivity for detecting coronary disease is reduced when exercise stress is submaximal. This would be of little importance clinically if the sensitivity for predicting irreversible cardiac events were maintained. We investigated the prognostic value of a normal SPECT MPI study when exercise produced submaximal stress. Methods. Between 1995-1998, 1398 patients underwent SPECT MPI (73% 99mTc-tetrofosmin, 27% 201Tl), 1290 (92%) with exercise stress (72% treadmill, 28% upright bicycle). 574 (41%) failed to achieve 80% of the maximum predicted heart rate: age 60±10 years, 63% male, 5% diabetic, 19% previous myocardial infarction, 28% previous revascularisation, 18% angiographically documented coronary disease. 203 (35%) of these MPI studies were normal, and the patients were followed-up by GP questionnaire with review of the hospital notes. Cardiac events were cardiac death or nonfatal myocardial infarction. Results. Follow-up was complete for 155 patients, with a mean (±SD) duration of 2.2±0.8 years. 3 patients died, all of definite noncardiac causes. There was 1 cardiac event (nonfatal myocardial infarction) in a patient who had previously had coronary artery bypass surgery. Conclusion. A normal SPECT MPI study following submaximal exercise predicts a very low risk of cardiac events during follow-up in a relatively high risk population. Patients with reduced exercise capacity do not automatically require pharmacological stress for accurate risk assessment

Exercise equilibrium radionuclide angiography predicts long-term cardiac prognosis in patients with abdominal aortic aneurysm being considered for surgery.

BACKGROUND: Patients with an abdominal aortic aneurysm (AAA) have a high prevalence of coronary disease and are at risk for cardiac events. This may offset the prognostic benefit of surgical repair. We investigated whether preoperative exercise equilibrium radionuclide angiography (ERNA) could be used to identify patients at high risk for cardiac events after successful AAA repair. METHODS: Between 1990 and 1995, 173 patients with an AAA were referred for supine bicycle exercise ERNA preoperatively. Follow-up information was obtained from a questionnaire sent to each patient's family physician. Cardiac events were defined as cardiac death or nonfatal myocardial infarction. RESULTS: A total of 139 patients were able to exercise and did not die or suffer myocardial infarction perioperatively. The median follow-up period was 3.8 years. Diabetes mellitus, an exercise ejection fraction (EF) below 0.50, and a fall in EF with exercise were univariable predictors of cardiac risk during the follow-up period (P &lt; .05). On multivariable analysis, diabetes mellitus (risk ratio [RR], 6.9; 95% CI 1.5 to 32.0) and an EF fall (RR, 4.1; 95% CI 1.5 to 11.4) emerged as the most important predictors. CONCLUSIONS: Exercise ERNA predicts long-term cardiac events in patients being considered for elective AAA repair. Such predictive information may influence the decision to operate, for example, on small unthreatening aneurysms, or lead to invasive cardiological management to minimize risk

Transthoracic echocardiography using second harmonic imaging with Valsalva manoeuvre for the detection of right to left shunts.

AIMS: To assess transthoracic echocardiography (TTE) using second harmonic imaging with Valsalva manoeuvre compared to transesophageal echocardiography (TEE) for the diagnosis of right to left cardiac and pulmonary shunts. METHODS AND RESULTS: One hundred and ten patients referred for TEE underwent TTE with bubble contrast. Bubbles in the left atrium within three cardiac cycles were considered diagnostic for a patent foramen ovale (PFO) and later as a pulmonary shunt. Greater than 20 bubbles in the left atrium was considered a large shunt and less than 20 a small shunt. TEE was performed immediately afterwards and read blinded to the TTE results. Pick-up rates were similar with 19 TEE positive (13 PFO) and 18 TTE positive (14 PFO) patients. There were five TEE positive/TTE negative cases who had significantly poorer TTE image quality score (2.7 +/- 0.8 vs 1.9 +/- 0.6, p &lt; 0.05). There were six TEE negative/TTE positive cases, two cases requiring Valsalva manoeuvre to become positive. The Valsalva manoeuvre significantly increased the number of bubbles shunting (10 +/- 11 vs 20 +/- 19, p &lt; 0.005). CONCLUSION: TTE with Valsalva manoeuvre is as good as TEE in diagnosing shunts. Valsalva manoeuvre increases the size of shunt. Both techniques produce false negative results

Quantitative regional analysis of myocardial wall motion.

This paper presents a new technique for semiautomatic quantification of regional heart function from 2-D echocardiography. It uses a novel left ventricular border tracking algorithm based on shape-space ideas that we have recently described. In this paper, we show how to decompose the tracked output into clinically meaningful segmental parameters (wall excursion and thickening), using what we call a computational interpretational space (CIS). This leads to a quantitative and automatic scoring scheme for endocardial excursion and myocardial thickening. The method is illustrated on data from a patient with a myocardial infarct in the apical anterior/inferior region of the heart and is also assessed in a small retrospective dobutamine stress echocardiography clinical case study

Is the "Warm-up effect" in angina mediated by improved myocardial perfusion?

Introduction. Considerable doubt remains about whether the "warm-up" effect in angina represents ischaemic preconditioning (IPC), or is simply due to improved myocardial perfusion via acute recruitment of collaterals. We investigated the latter possibility using quantitative tetrofosmin SPECT. Methods. 11 patients (age 63±8 years, 8 male) with coronary disease and preserved left ventricular function underwent symptom-limited treadmill exercise off antianginal medication. On three separate days at weekly intervals, 99mTc-tetrofosmin 400-450MBq was injected at rest, during a single exercise test (Ex1), and during the second of two exercise tests separated by 30 minutes (Ex2a and Ex2b). Exercise injections were given at equivalent heart rates. SPECT acquisitions were obtained 1-2 hours after each tetrofosmin injection. Quantitative analysis was performed by comparing polar plots derived from radial slices with a normal database. The "hypoperfusion index" was the product of perfusion defect extent and mean severity. Results. Haemodynamic and ECG indices were comparable between Ex1 and Ex2a. Compared with Ex2a, 1mm ST depression occurred later and at a higher heart rate during Ex2b. The reversible component of the hypoperfusion index was equivalent for Ex1 compared with Ex2b. Ex1 Ex2a Ex2b 1 mm time (min) 3.5±1.8 3.3±2.1 4.6±2.1* 1 mm HR (bpm) 130±15 128±16 139+20* Peak time (min) 6.8±1.8 7.0±1.7 7.3±1.2 Peak HR (bpm) 146±16 148±18 151±21 Data expressed as mean±SD * P&lt;0.01 versus Ex2a Conclusion. The warm-up effect is not associated with a detectable improvement in myocardial perfusion using quantitative tetrofosmin SPECT. This supports IPC as the underlying cause. (Graph Presented)

The warm-up effect protects against ischemic left ventricular dysfunction in patients with angina.

OBJECTIVES: The goal of this study was to investigate whether the "warm-up" effect in angina protects against ischemic left ventricular (LV) dysfunction. BACKGROUND: After exercise, patients with coronary disease demonstrate persistent myocardial dysfunction, which may represent stunning, as well as warm-up protection against further angina, which may represent ischemic preconditioning. The effect of warm-up exercise on LV function during subsequent exercise has not been investigated. METHODS: Thirty-two patients with multivessel coronary disease and preserved LV function performed two supine bicycle exercise tests 30 min apart. Equilibrium radionuclide angiography was performed before, during and up to 60 min after each test. Global LV ejection fraction and volume changes and regional ejection fraction for nine LV sectors were calculated for each acquisition. RESULTS: Onset of chest pain or 1 mm ST depression was delayed and occurred at a higher rate-pressure product during the second exercise test. Sectors whose regional ejection fraction fell during the first test showed persistent reduction at 15 min (68 +/- 20 vs. 73 +/- 20%, p &lt; 0.0001). These sectors demonstrated increased function during the second test (71 +/- 20 vs. 63 +/- 20%, p = 0.0005). The reduction at 15 min and the increase during the second test were both in proportion to the reduction during the first test. Effects on global function were only apparent when the initial response to exercise was considered. CONCLUSIONS: The warm-up effect is accompanied by protection against ischemic regional LV dysfunction. The degree of stunning and protection after exercise is related to the severity of dysfunction during exercise, consistent with results from experimental models

Can a selective adenosine A1-agonist protect against exercise-induced ischaemic left ventricular dysfunction?

Introduction. The "warm-up" effect in angina may represent ischaemic preconditioning, which is mediated by adenosine A1-receptors in most models. Protection may also occur against ischaemic left ventricular (LV) dysfunction. We investigated whether warm-up can be reproduced by a selective adenosine A1-agonist, GR79236 (Glaxo-Wellcome). Methods. 25 patients with three vessel coronary disease and normal resting LV function entered a double-blind crossover study, receiving IV GR79236 10μg/kg or placebo on mornings one week apart. Two symptom-limited supine bicycle exercise (ex) tests were performed 30 minutes apart on each day. Equilibrium radionuclide angiography (ERNA) was used to derive regional ejection fractions (REFs) for 9 LV sectors. Sectors were defined as ischaemic or nonischaemic based on whether REF fell or not during the first test following placebo. Results. During the second of two ex tests following either placebo or drug, the onset of chest pain or 1mm ST depression was delayed and occurred at a higher rate-pressure product, whilst the mean REF of ischaemic sectors increased (P&lt;0.05). GR79236 did not affect resting or ex haemodynamic and ECG indices compared with placebo. For ischaemic sectors, the drug reduced the mean REF at rest, but increased it during the first ex test compared with placebo. Exercise test Ischaemic sectors (n=55) Noinschaemic sectors (n=89) Rest REF Exercise REF Rest REF Exercise REF Placebo 1 0.74±0.20 0.66±0.20 0.62±0.21 0.70±0.22 Placebo 2 0.74±0.19* 0.72±0.21* 0.63±0.24 0.69±0.22 Drug 1st 0.69±0.20* 0.69±0.21* 0.63±0.23 0.64±0.23* Drug 2nd 0.70±0.21 0.74±0.19*# 0.62±0.23 0.66±0.22# Data expressed as mean±SD * P&lt;0.05 versus Placebo 1st # P&lt;0.05 versus Drug 1st Conclusion. A selective adenosine A1-receptor agonist reduces ischaemic LV dysfunction during exercise. Warm-up protection still occurs suggesting that additional mechanisms may be involved