What are the prognostic implications and factors relating to exercise induced electrocardiographic ST segment changes in the setting of a non-ischemic stress echocardiogram?

BACKGROUND: Electrocardiographic (ECG) changes during stress testing are a common and perplexing finding during non-ischemic stress echocardiography (niSE). Research has provided conflicting results regarding the implications. METHODS: SE was performed after maximal Bruce protocol treadmill exercise. RESULTS: 3020 consecutive patients, mean age 58 ± 12 years, 36% female, were followed-up for up to 9 years (mean 36 ± 21 months) post niSE. Time to first cardiac event (composite of heart failure admission, worsening New York Heart Association class, worsening ejection fraction, acute coronary syndrome, revascularization, angina or cardiovascular death) was analysed and adjusted using Cox proportional hazards regression. Prognostic significance was found with 1.5 mm of downsloping or horizontal ST depression. Adjusting for baseline differences, increased risk of composite major adverse cardiac events was shown with at least 1.5 mm of exercise induced ST depression (Hazard ratio [HR] of 2.47, 95% Confidence ratio [CI] 1.67-3.72, p < 0.0001). Patients achieving high level exercise capacity (≥13 metabolic equivalents or METs) with ST depression lower risk of cardiac events during follow-up. CONCLUSION: Patients with ST segment depression but non-ischemic stress imaging have a poorer prognosis compared to patients with niSE with normal stress ECGs. ST depression of 1.5 mm or more was established as a prognostically significance value. High exercise capacity was associated with an improved prognosis, and ECG changes in that setting can be regarded as false positives. All niSE have low risk of a cardiac event in the very short term (<12 months). Overall, ST depression during non-ischaemic stress imaging is not a benign finding.

The prognostic value of estimating stroke volume before and after exercise during treadmill stress echocardiography.

BACKGROUND: Stress echocardiography (SE) is an established technique for assessment of coronary artery disease (CAD) which is difficult to perform and interpret. Left ventricular stroke volume (SV) is readily estimated with Doppler echocardiography. It can be affected by myocardial ischemia, with possible adjunctive value during SE. METHODS: Patients underwent Bruce protocol SE with SV estimated before and after maximal treadmill exertion post routine regional wall analysis. Incremental change in SV (ΔSV) with exercise was measured. RESULTS: A derivation cohort (n = 273) was established to test the hypothesis. An optimal cutoff for detection on inducible ischemia was ΔSV ≤ +10 mL. The validation cohort of consecutive patients (n = 1093, 376 [34%] female; age 59 ± 12 years) were followed clinically after SE for 20 460 patient-months. There were 1000 patients with nonischemic SE, and 93 patients with studies suggestive of myocardial ischemia. Secondary analysis yielded 831 patients with a normal exercise response (ΔSV > +10 mL) and 192 with an abnormal ΔSV ≤ +10 mL. Time to first combined adverse cardiac event (composite of angina, acute coronary syndrome, cardiac revascularization, worsening New York Heart Association (NYHA) class, a reduction in EF, and cardiovascular death) was analyzed and adjusted using Cox proportional hazards regression. The hazard ratio for an adverse event with an abnormal ΔSV response (≤10 mL) was 10.3 (95% confidence intervals 5.6-19.1, P < .0001). CONCLUSIONS: Stroke volume assessment during SE is feasible and readily performed. It is simple, practical, and has incremental diagnostic and prognostic value when added to exercise regional wall-motion analysis.

Incremental Value of ePLAR-The Echocardiographic Pulmonary to Left Atrial Ratio in the Assessment of Sub-Massive Pulmonary Emboli.

BACKGROUND: Acute pulmonary embolism (PE) is characterized hemodynamically by abrupt obstruction in trans-pulmonary blood flow. The echocardiographic Pulmonary to Left Atrial ratio (ePLAR, tricuspid regurgitation Vmax/mitral E/e') has been validated as a non-invasive surrogate for trans-pulmonary gradient (TPG) that accurately differentiates pre-capillary from post-capillary chronic pulmonary hypertension. This study assessed ePLAR as an incremental echocardiographic assessment tool compared with traditional measures of right ventricular pressure and function. METHODS: In total, 110 (57.4 ± 17.6 years) patients with confirmed sub-massive pulmonary emboli with contemporaneous echocardiograms (0.3 ± 0.9 days) were compared with 110 age-matched controls (AMC). RESULTS: Tricuspid velocities were higher than AMC (2.6 ± 0.6 m/s vs. 2.4 ± 0.3 m/s, p < 0.05), although still consistent with "normal" right ventricular systolic pressures (34.2 ± 13.5 mmHg vs. 25 ± 5.3 mmHg, p < 0.05) with lower mitral E/e' values (8.2 ± 3.8 vs. 10.8 ± 5.1, p < 0.05). ePLAR values were higher than AMC (0.36 ± 0.14 m/s vs. 0.26 ± 0.10, p < 0.05) suggesting significantly elevated TPG. Detection of abnormal echocardiographic findings increased from 29% (TRVmax ≥ 2.9 m/s) and 32% (reduced tricuspid annular plane systolic excursion) to 70% with ePLAR ≥ 0.3 m/s. CONCLUSIONS: Raised ePLAR values in acute sub-massive pulmonary embolism suggest elevated trans-pulmonary gradients even in the absence of acutely increased pulmonary artery pressures. ePLAR dramatically increases the sensitivity of echocardiography for detection of hemodynamic perturbations in sub-massive pulmonary embolism patients, which may offer clinical utility in diagnosis and management.

The Prognostic Value of the Diastolic Stress Test in Patients Undergoing Treadmill Stress Echocardiography.

BACKGROUND: Exercise stress echocardiography (SE) is well validated for the evaluation of myocardial ischemia. Diastolic stress testing (DST) is recommended in the 2016 American Society of Echocardiography and European Association of Cardiovascular Imaging Guidelines for unexplained dyspnea. This study's aim was to prognostically evaluate the DST prospectively in a large stress testing population. METHODS: Patients underwent SE with mitral E/e' measured before and after maximal treadmill exertion to estimate diastolic function. Patients were divided into four groups: group 1 (n = 201)-ischemic; group 2 (n = 1,563)-negative DST (E/e'pre < 12, E/e'post < 12); group 3 (n = 68)-positive DST (E/e'pre < 12, E/e'post ≥ 12); group 4 (n = 314)-high baseline E/e' (E/e'pre ≥ 12). RESULTS: Consecutive patients (n = 2,201, 770 [35%] female; 58 ± 12 years) were followed after SE for 27,964 patient-months. Time to first heart failure event (composite of heart failure admission, worsening New York Heart Association class, worsening ejection fraction, or cardiovascular death) was analyzed and adjusted using Cox proportional hazards regression. Ischemic patients hazard ratio (HR) was 28, 95% CI, 17-44, P < .0005, for subsequent heart failure compared with negative DST patients. Nonischemic, positive DSTs were highly predictive (HR = 4.2; 95% CI, 1.6-11.0; P = .001); while high E/e'pre was not predictive (HR = 1.3; 95% CI, 0.7-2.4; P = .49) of future heart failure events. CONCLUSIONS: DST differentiates heart failure prognosis in patients with induced diastolic dysfunction. Ischemia predictably portends the worst heart failure outcomes, and nonischemic, positive diastolic stress tests predicted more events compared with negative tests. These prognostic data support and add to the recommendations of the 2016 guidelines.

Female False Positive Exercise Stress ECG Testing - Fact Versus Fiction.

BACKGROUND: Exercise stress testing is a well validated cardiovascular investigation. Accuracy for treadmill stress electrocardiograph (ECG) testing has been documented at 60%. False positive stress ECGs (exercise ECG changes with non-obstructive disease on anatomical testing) are common, especially in women, limiting the effectiveness of the test. This study investigates the incidence and predictors of false positive stress ECG findings, referenced against stress echocardiography (SE) as a standard. METHODS: Stress echocardiography was performed using the Bruce treadmill protocol. False positive stress ECG tests were defined as greater than 1mm of ST depression on ECG during exertion, without pain, with a normal SE. Potential causes for false positive tests were recorded before the test. RESULTS: Three thousand (3,000) consecutive negative stress echocardiograms (1,036 females, 34.5%) were analysed (age 59+/-14 years. False positive (F+) stress ECGs were documented in 565/3,000 tests (18.8%). F+ stress ECGs were equally prevalent in females (194/1,036, 18.7%) and males (371/1,964, 18.9%, p=0.85 for the difference). Potential causes (hypertension, left ventricular hypertrophy, known coronary disease, arrhythmia, diabetes mellitus, valvular heart disease) were recorded in 36/194 (18.6%) of the female F+ ECG tests and 249/371 (68.2%) of the male F+ ECG tests (p<0.0001 for the difference). CONCLUSIONS: These data suggest that F+ stress ECG tests are frequent and equally common in women and men. However, most F+ stress ECGs in men can be predicted before the test, while most in women cannot. Being female may be a risk factor in itself. These data reinforce the value of stress imaging, particularly in women.

Estimation of the Blood Pressure Response With Exercise Stress Testing.

BACKGROUND: The blood pressure response to exercise has been described as a significant increase in systolic BP (sBP) with a smaller change in diastolic BP (dBP). This has been documented in small numbers, in healthy young men or in ethnic populations. This study examines these changes in low to intermediate risk of myocardial ischaemia in men and women over a wide age range. METHODS: Consecutive patients having stress echocardiography were analysed. Ischaemic tests were excluded. Manual BP was estimated before and during standard Bruce protocol treadmill testing. Patient age, sex, body mass index (BMI), and resting and peak exercise BP were recorded. RESULTS: 3,200 patients (mean age 58±12years) were included with 1,123 (35%) females, and 2,077 males, age range 18 to 93 years. Systolic BP increased from 125±17mmHg to 176±23mmHg. The change in sBP (ΔsBP) was 51mmHg (95% CI 51,52). The ΔdBP was 1mmHg (95% CI 1, 1), from 77 to 78mmHg, p<0.001). The upper limit of normal peak exercise sBP (determined by the 90th percentile) was 210mmHg in males and 200mmHg in females. The upper limit of normal ΔsBP was 80mmHg in males and 70mmHg in females. The lower limit of normal ΔsBP was 30mmHg in males and 20mmHg in females. CONCLUSIONS: In this large cohort, sBP increased significantly with exercise. Males had on average higher values than females. Similar changes were seen with the ΔsBP. The upper limit of normal for peak exercise sBP and ΔsBP are reported by age and gender.

Cardiac Amyloidosis Shows Decreased Diastolic Function as Assessed by Echocardiographic Parameterized Diastolic Filling.

Cardiac amyloidosis is a rare but serious condition with poor survival. One of the early findings by echocardiography is impaired diastolic function, even before the development of cardiac symptoms. Early diagnosis is important, permitting initiation of treatment aimed at improving survival. The parameterized diastolic filling (PDF) formalism entails describing the left ventricular filling pattern during early diastole using the mathematical equation for the motion of a damped harmonic oscillator. We hypothesized that echocardiographic PDF analysis could detect differences in diastolic function between patients with amyloidosis and controls. Pulsed-wave Doppler echocardiography of transmitral flow was measured in 13 patients with amyloid heart disease and 13 age- and gender matched controls. E- waves (2 to 3 per subject) were analyzed using in-house developed software. Nine PDF-derived parameters were obtained in addition to conventional echocardiographic parameters of diastolic function. Compared to controls, cardiac amyloidosis patients had a larger left atrial area (23.7 ± 7.5 cm2 vs. 18.5 ± 4.8 cm2, p = 0.04), greater interventricular septum wall thickness (14.4 ± 2.6 mm vs. 9.3 ± 1.3 mm, p < 0.001), lower e' (0.06 ± 0.02 m/s vs. 0.09 ± 0.02 m/s, p < 0.001) and higher E/e' (18.0 ± 12.9 vs. 7.7 ± 1.3, p = 0.001). The PDF parameter peak resistive force was greater in cardiac amyloidosis patients compared to controls (17.9 ± 5.7 mN vs. 13.1 ± 3.1 mN, p = 0.03), and other PDF parameters did not differ. PDF analysis revealed that patients with cardiac amyloidosis had a greater peak resistive force compared to controls, consistent with a greater degree of diastolic dysfunction. PDF analysis may be useful in characterizing diastolic function in amyloid heart disease.

ePLAR - The echocardiographic Pulmonary to Left Atrial Ratio - A novel non-invasive parameter to differentiate pre-capillary and post-capillary pulmonary hypertension.

BACKGROUND: Right heart catheterisation is the gold-standard for differentiating pre-capillary pulmonary hypertension (high mean pulmonary artery pressure, normal pulmonary wedge pressure) from post-capillary physiology (elevated pulmonary wedge pressure). The new non-invasive parameter, ePLAR (echocardiographic Pulmonary to Left Atrial Ratio) is calculated from the maximum tricuspid regurgitation continuous wave Doppler velocity (m/s) divided by the transmitral E-wave:septal mitral annular Doppler Tissue Imaging e'-wave ratio (TRVmax/E:e'). METHODS: Pulmonary hypertension patients (mean pulmonary artery pressure>25mmHg, n=133, 66 male, average 65.0±16.8years) were classified by right heart catheterisation as pre-capillary or post-capillary [subdivided into isolated post-capillary (diastolic pulmonary gradient <7mmHg) or combined pre- and post-capillary cases]. The ePLAR values of these groups were compared to each other and to a population sample of 16,356 population reference echocardiograms. RESULTS: ePLAR values for the normal reference population of 16,356 echocardiograms (age 56±16.6years) were 0.30±0.09m/s. Pre-capillary pulmonary hypertension patients (n=35, 26 male, PAPsys 63.9±16.6mmHg, PAPdiast 24.1±7.3mmHg, PAPmean 37.9±9.4mmHg, PCWP 10.6±2.7mmHg) had significantly higher ePLAR values than post-capillary cases (n=98, 40 male, PAPsys 59.9±17.6mmHg, PAPdiast 25.0±7.4mmHg, PAPmean 38.1±9.8mmHg, PCWP 23.5±6.4mmHg)-ePLAR 0.44±0.22m/s vs 0.20±0.11m/s (p<0.001). ePLAR values were significantly lower in isolated post-capillary pulmonary hypertension than in combined pre- and post-capillary cases (0.18±0.08m/s vs 0.28±0.18m/s, p<0.001). CONCLUSIONS: ePLAR is a simple echocardiographic parameter which can accurately differentiate the smaller subset of patients with pre-capillary pulmonary hypertension from the more common post-capillary aetiology. The use of this easily obtained echocardiographic parameter has the potential to enhance non-invasive triage of patients for specific pulmonary vasodilator therapy.

The New Dimension in Aortic Measurements - Use of the Inner Edge Measurement for the Thoracic Aorta in Australian Patients.

BACKGROUND: Historically, aortic measurements were established using M-mode echocardiography, measuring from the leading edge to leading edge. Improvements in echocardiographic imaging now permit accurate assessment using the blood-tissue interface. Normal values have not been established using this technique. METHODS: A prospective analysis of consecutive patients without pathology was conducted. Measurements of aortic dimensions were made using the blood-tissue interface and the leading edge methods at end-diastole, and at end-systole using the blood-tissue interface. Data collected included BSA, and aortic measurements (LVOT, root, ST junction, mid ascending aorta, aortic arch). RESULTS: The echocardiograms of 512 patients were evaluated. The mean age was 56 years, with 304 males (59%) and 208 females (41%). The average measurements (blood tissue interface) were: aortic root 31.2mm, sinotubular junction 25.9mm, mid ascending aorta 30.6 and aortic arch 23.4. On average, the leading edge method measurements were 1.5mm larger (p<0.0001), consistent with the added thickness of the anterior aortic wall. Ratios to BSA were also estimated. Tables have been created suggesting normal and abnormal values. CONCLUSIONS: Improvements in echocardiographic imaging permit the blood-tissue interface to be readily visualised. Reference ranges for the estimation of aortic sizes using this method are provided. More accurate and anatomical estimation of the aortic dimensions can now be achieved.

The return of the normal heart: resolution of cardiac amyloidosis after chemotherapy and bone marrow transplantation.

BACKGROUND: AL amyloidosis and multiple myeloma result in extracellular deposition of insoluble fibrillar protein in tissues and organs. Untreated median survival has been documented at 12 months. Cardiac infiltration decreases survival to five months. Chemotherapy and bone marrow transplantation (BMT) have been shown to improve survival when haematological remission is documented. This study aimed to assess if remission could result in cardiac structural improvement. METHODS: 269 patients were treated with BMT for amyloidosis from 1997 to 2010. Cardiac amyloidosis was identified in 30 patients by echocardiographic criteria. Echocardiography was performed before and after BMT. RESULTS: Thirteen of 30 patients with cardiac amyloidosis died during follow-up. No change in cardiac structure was seen in 11 patients. Average survival was 49 months from BMT for non-responders. Fifteen patients had cardiac normalisation (responders). The average time to normalisation was 25 months. Only two responders died. Average survival for responders was 71 months (p < 0.0001 compared with non-responders). Normalisation of cardiac structure was highly predictive of survival (Fisher's exact test p = 0.0025, relative risk 0.18). CONCLUSIONS: Cardiac amyloidosis patients with haematological remission after chemotherapy and BMT may subsequently normalise cardiac structure and function. Normalisation is highly predictive of survival.

Left atrial size--another differentiator for cardiac amyloidosis.

BACKGROUND: The "sparkled" echocardiographic appearance of amyloid has become less visually obvious in the era of harmonic imaging. Significantly dilated atria in the setting of a normal sized ventricle may be another easy visual marker for cardiac amyloidosis. METHODS: A retrospective analysis of echocardiograms of patients with biopsy-proven cardiac amyloid compared with patients with hypertension was conducted. There were 36 patients in each group, and they were matched for left ventricular wall thickness, as well as age and sex. RESULTS: Patients with cardiac amyloid had significantly larger atria than the group with hypertension (left atrial areas 29 cm(2) versus 19 cm(2), p<0.001, AUC 0.84, volumes 100 cm(3) versus 55 cm(3), p<0.001, AUC 0.915). A volume of 69 cm(3) produced a specificity and sensitivity of 85% for amyloidosis. CONCLUSIONS: Atrial dilatation can be used as a visual marker for cardiac amyloidosis. This may be a simple visual method to differentiate this infiltrative cardiomyopathy from left ventricular hypertrophy.

Stroke prevention in atrial fibrillation: current anticoagulation management and future directions.

Atrial fibrillation (AF) is an important cause of stroke, and stroke risk stratification is critical to the management of patients with AF. Anticoagulation with warfarin is the current standard of care for stroke prevention in these patients, despite the need for close monitoring. Aspirin alone is not as effective. Warfarin is recommended for patients with AF and valvular disease or with AF and one or more stroke risk factors. Other novel anticoagulants and antiplatelet combinations are under investigation. Curative procedures for AF are possible, but their long-term safety and effect on stroke risk are unknown.