B. Fitzgerald

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 (Fishers 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.

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.

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.

Female False Positive Exercise Stress ECG Testing – Fact Verses 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.

Regression of cardiac amyloidosis following stem cell transplantation: a comparison between echocardiography and cardiac magnetic resonance imaging in long-term survivors

Background AL amyloidosis and multiple myeloma result in extracellular deposition of insoluble fibrillary protein in tissue and organs. Untreated median survival is very poor, and even worse with cardiac involvement. Chemotherapy and peripheral blood stem cell transplantation (PBSCT) have been shown to dramatically improve survival, with hematologic remission documented. Regression of cardiac changes has previously been shown, as assessed by echocardiography (TTE) and cardiac magnetic resonance imaging (CMR). This study is a comparison of TTE and CMR in long-term survivors of cardiac amyloidosis with regression. Results Four long-term survivors with cardiac amyloidosis and regression of cardiac features on TTE were identified. Mean age was 60 years and average survival was 139 months from the time of diagnosis of cardiac involvement. Statistically significant regression of the cardiac features of cardiac amyloidosis were demonstrated on TTE. In these survivors, post-PBSCT structural assessments were similar between TTE and CMR. Classical strain imaging features of cardiac amyloidosis were only present in 50%. All patients had diffuse, patchy gadolinium enhancement on CMR after PBSCT. Conclusions Treatment of cardiac amyloidosis with chemotherapy and PBSCT may result in regression of abnormalities on TTE with marked improvement in survival. Post treatment, TTE and CMR structural assessments appear similar. Gadolinium imaging suggests that microscopic residual infiltration persists despite macroscopic regression. Significant cardiac improvements with prolonged survival are seen nonetheless. Multimodality imaging has a vital role in the management of cardiac amyloidosis.

Regression of the Anatomic Cardiac Features of Amyloid Light Chain Cardiac Amyloidosis Accompanied by Normalization of Global Longitudinal Strain

Graphical abstract

Transthyretin Cardiac Amyloidosis: A Noninvasive Multimodality Approach to Diagnosis Using Transthoracic Echocardiography, 99m-Tc-Labeled Phosphate Bone Scanning, and Cardiac Magnetic Resonance Imaging

Graphical abstract

ePLAR: the echocardiographic pulmonary to left atrial ratio - conceptualising a new parameter for the assessment of pulmonary hypertension. Foundation data from 16,356 normal echocardiograms

Background: ePLAR = TRVmax/E:E’ (maximum tricuspid regurgitation continuous wave Doppler velocity divided by the transmitral E wave: mitral annular DTI E’ wave ratio) is proposed for differentiating pre-capillary pulmonary hypertension (Pre-cap PHT high trans-pulmonary gradient, normal pulmonary wedge pressure) from post-capillary physiology (Post-cap elevatedwedge pressure, +/elevated trans-pulmonary gradient) secondary to left heart disease. Methods: Patients with right ventricular systolic pressure >35mmHg were classified by right heart catheterisation as pre-cap, post-cap PHT or not pulmonary hypertensive (mean pulmonary arterypressure 0.23 had high discriminatory power by ROC analysis (AUC = 0.832). The ePLAR for 1000 population normal echocardiograms (mean age 56±16yrs) was 0.30±0.09. Conclusions: ePLAR is a simple echocardiographic parameter which can accurately differentiate pre-capillary pulmonary hypertension from the more common postcapillary aetiology. The use of ePLAR has the potential to streamline screening of patients for specific pulmonary vasodilator therapy.