Correlation of Quantitative 99mTc DPD Scintigraphy With Echocardiographic Alterations in Left Atrial Parameters in Transthyretin Amyloidosis.

AIM: Cardiac transthyretin amyloidosis (ATTR) patients have high rates of atrial arrhythmias. We evaluated echocardiographic structural and functional left atrial (LA) parameters and correlated these with technetium-99m 3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) bone scintigraphy tracer uptake within the LA in ATTR patients. METHODS: ATTR patients (wild-type, hereditary and asymptomatic transthyretin [TTR] variant carriers) who had undergone 99mTc-DPD and transthoracic echocardiogram (TTE) were selected. Quantitative 99mTc-DPD uptake analysis and echocardiographic evaluation of LA structural and functional parameters was performed. RESULTS: Forty (40) ATTR patients (wild-type n=17; hereditary ATTR and TTR variant carriers n=23; median age 68.8±22 years) were included. TTE parameters including indexed LA minimum (LAVmin) (r=0.66), and LA maximum volumes (LAVmax) (r=0.64), LA emptying fraction (LAEF) (r=-0.68), LA function index (LAFI) (r=-0.70) and reservoir strain (ƐR) (r=-0.70) (p<0.001 for all) demonstrated good correlation to LA tracer uptake. Normal LA volume (LAVmin and LAVmax) and function (LAEF, LAFI and ƐR) was observed in hereditary ATTR and TTR variant carriers without cardiac tracer uptake. The subgroup of ATTR patients with atrial fibrillation/flutter demonstrated increased LAVmin and LAVmax with further reduction in LA function (LAEF, LAFI and ƐR). Receiver operating characteristic curves demonstrated strong diagnostic accuracies for LA structural (LAVmin and LAVmax; area under the curve [AUC] of 0.83 and 0.84 respectively) and functional (LAEF, LAFI and ƐR; AUC 0.81, 0.88 and 0.85, respectively) parameters. CONCLUSION: Left atrial structural and functional parameters demonstrated good correlations with quantitative 99mTc-DPD tracer LA uptake. Echocardiography and 99mTc-DPD scintigraphy may have significant roles in identification and surveillance of ATTR patients likely to develop atrial arrhythmias.

Echocardiographic predictors of ventricular arrhythmias in patients with non-ischemic cardiomyopathy.

OBJECTIVE: Ventricular arrhythmias (VA) portend a poor prognosis in non-ischemic cardiomyopathy (NICM). In this meta-analysis we evaluated if left ventricular (LV) global longitudinal strain (GLS) and LV mechanical dispersion (LVMD) are associated with VA, specifically in NICM patients. METHODS: A systematic review and meta-analysis was performed to determine the predictive value of LV GLS and LVMD for VA in NICM patients. VA endpoints were a composite of sudden cardiac death, VA events (including ventricular tachycardia or ventricular fibrillation), cardiac arrest and appropriate implantable cardioverter-defibrillator (ICD) therapy. Hazard or odds ratios for univariate models were extracted for the relationship between LV GLS and LVMD with VA endpoints. RESULTS: A total of 984 patients from 6 published studies were included; 231 patients (23.5%) experienced the composite endpoint. NICM patients who experienced VA endpoints had LV GLS impairment compared to those without (weighted mean difference -1.93%; 95% confidence interval (CI) -2.77 to -1.10; p < 0.001) and LV GLS was related to VA endpoints (hazard ratio: 1.12, 95% CI 1.07-1.17, p < 0.001; odds ratio: 1.22, 95% CI 1.08-1.38, p = 0.002). Four studies reported mean LVMD (weighted mean -10.05 ms; 95% CI -28.25 to 8.14; p = 0.28), with 3 reporting risk ratios (1 reported odds ratio and 2 hazard ratios). Only odds ratio demonstrated statistical significance (hazard ratio: 0.47, 95% CI 0.01-22.25, p = 0.70; odds ratio: 1.59, 95% CI 1.14-2.22, p = 0.007). CONCLUSION: LV GLS impairment demonstrates value for predicting VA endpoints in NICM patients. Inclusion of LV GLS may be appropriate in the surveillance, screening, and clinical management of NICM patients.

Electrocardiographic Characteristics and Their Correlation with Echocardiographic Alterations in Fabry Disease.

Fabry disease (FD) is an X-linked disorder with α-galactosidase A deficiency. Males (>30 years) and females (>40 years) often present with cardiac manifestations, predominantly left ventricular hypertrophy (LVH). The aim of this study was to evaluate electrocardiographic (ECG) characteristics within FD patients to identify gender related differences, and to additionally explore the association of ECG parameters with structural and functional alterations on transthoracic echocardiography (TTE). Retrospective cross-sectional analysis of 45 FD patients with contemporaneous ECG and TTE was performed and compared to age and gender matched healthy controls. FD patients demonstrated alterations in several ECG parameters particularly in males, including prolonged P-wave duration (91 vs. 81 ms, p = 0.022), prolonged QRS duration (96 vs. 84 ms, p < 0.001), increased R-wave amplitude in lead I (8.1 vs. 5.7 mV, p = 0.047), increased Sokolow-Lyon index (25 vs. 19 mV, p = 0.002) and were more likely to meet LVH criteria (31% vs. 7%, p = 0.006). FD patients with impaired basal longitudinal strain (LS) on TTE were more likely to meet LVH criteria (41% vs. 0%, p = 0.018). Those with more advanced FD (increased LV wall thickness on TTE) were more likely to meet LVH criteria but additionally demonstrated prolonged ventricular depolarization (QRS duration 101 vs. 88 ms, p = 0.044). Therefore, alterations on ECG demonstrating delayed atrial activation, delayed ventricular depolarization and evidence of LVH were more often seen in male FD patients. Impaired basal LS, a TTE marker of early cardiac involvement, correlated with ECG abnormalities. Increased LV wall thickness on TTE, a marker of more advanced FD, was associated with more severe ECG abnormalities.

Correlation Between Quantitative Uptake of 99mTC-DPD and Echocardiographic Parameters in Cardiac ATTR: A Novel Follow-Up Strategy.

Aims: There has been a paradigm shift in diagnosis of cardiac transthyretin amyloidosis (ATTR) with non-invasive techniques including technetium-99m 3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) bone scintigraphy. We evaluated structural and functional biventricular alterations by transthoracic echocardiography (TTE) and determined the correlation with 99mTc-DPD tracer uptake in ATTR. Materials and Methods: ATTR patients (wild-type, hereditary or asymptomatic transthyretin [TTR] variant carriers) with 99mTc-DPD and TTE were selected; 99mTc-DPD uptake was analyzed quantitatively. TTE assessment of left ventricle (LV) and right ventricle (RV) parameters was performed. Results: Forty ATTR patients (wild-type n = 17; hereditary ATTR and TTR variant carriers n = 23; median age 68.8 ± 22 years) were included. TTE parameters displaying good correlation with 99mTc-DPD tracer uptake included LV average wall thickness (r = 0.837), LV indexed mass (LVMI; r = 0.802), RV wall thickness (r = 0.610), average e' (r = -0.830), E/e' ratio (r = 0.786), LV global longitudinal strain (GLS; r = 0.714) and RV GLS (r = 0.632; p < 0.001 for all). Hereditary ATTR and TTR variant carriers without cardiac tracer uptake had normal echocardiographic parameters. Receiver operating characteristic curves demonstrated strong diagnostic accuracies for structural (LV wall thickness, LVMI and RV wall thickness; area under the curve (AUC) of 0.96 for all) and functional (LV and RV GLS; AUC of 0.86 and 0.88, respectively) parameters. Conclusion: Good correlations between TTE biventricular structural and functional parameters were demonstrated with quantitative 99mTc-DPD uptake. Echocardiography may potentially assume a significant role in longitudinal follow-up for monitoring disease progression and for evaluating treatment response.

The value of endomyocardial biopsy in diagnosis and guiding therapy.

Endomyocardial biopsy (EMB) is a highly-specialised procedure that is associated with some controversy as to its diagnostic role due to its inconsistency in diagnosing a wide variety of cardiac diseases. Given the advances and sophistication in echocardiography and cardiac magnetic resonance imaging (MRI), the vast majority of cardiac diseases can be diagnosed by these non-invasive procedures. Under-sampling and the fact that biopsy site is limited to the right side of the interventricular septum further limits its value. In spite of all these limitations, there still remains a group of pathological conditions that require biopsy for a conclusive diagnosis such as myocarditis, amyloidosis, sarcoidosis and giant cell myocarditis. Correct patient selection and the quantity of tissue samples impart a significant influence on the accuracy of the diagnosis, and thus the value of EMB is variable for each patient. The purpose of this study was to evaluate the role of EMB in patient care, through its ability to either change clinical diagnosis or alter patient management. Our study was based in a single teaching centre. An audit of cardiac biopsies performed over a 10 year period identified 250 patients. We assessed indications, histology, electron microscopic findings, final clinical diagnosis and how they influenced patient management. A definite diagnosis on histology was given in 44 of 250 patients (17.6%). Non-specific findings were observed in the remaining 206 patients (82.4%). Histology influenced patient management in 73 (29.2%) patients. Histological examination in the remaining 177 biopsies (70.8%) did not provide a definite diagnosis or influence patient management. It was additionally found that the number of tissue fragments sampled has significant impact on diagnostic accuracy. A more accurate diagnosis of 45% was obtained when ≥5 fragments were sampled, as compared to 1-3 fragments where accuracy dropped to 20%. Our study indicated that sampling for electron microscopy has very limited value. We found that of 245 biopsies sampled for electron microscopy, only three biopsies (1.2%) had diagnostically useful findings. In our institution procedure related complications were observed in 7 of 250 patients (2.8%). The diagnostic value of EMB is important but limited. Strict triaging of patients according to clinical suspicion and adequate sampling of tissue may increase useful diagnostic information.