Can echocardiography and ECG discriminate hereditary transthyretin V30M amyloidosis from hypertrophic cardiomyopathy?

OBJECTIVE: Hereditary transthyretin (ATTR) amyloidosis with increased left ventricular wall thickness could easily be misdiagnosed by echocardiography as hypertrophic cardiomyopathy (HCM). Our aim was to create a diagnostic tool based on echocardiography and ECG that could optimise identification of ATTR amyloidosis. METHODS: Data were analysed from 33 patients with biopsy proven ATTR amyloidosis and 30 patients with diagnosed HCM. Conventional features from ECG were acquired as well as two dimensional and Doppler echocardiography, speckle tracking derived strain and tissue characterisation analysis. Classification trees were used to select the most important variables for differentiation between ATTR amyloidosis and HCM. RESULTS: The best classification was obtained using both ECG and echocardiographic features, where a QRS voltage >30 mm was diagnostic for HCM, whereas in patients with QRS voltage <30 mm, an interventricular septal/posterior wall thickness ratio (IVSt/PWt) >1.6 was consistent with HCM and a ratio <1.6 supported the diagnosis of ATTR amyloidosis. This classification presented both high sensitivity (0.939) and specificity (0.833). CONCLUSION: Our study proposes an easily interpretable classification method for the differentiation between HCM and increased left ventricular myocardial thickness due to ATTR amyloidosis. Our combined echocardiographic and ECG model could increase the ability to identify ATTR cardiac amyloidosis in clinical practice.

Residual compromised myocardial contractile reserve after valve replacement for aortic stenosis.

OBJECTIVE: Despite recovery of left ventricular (LV) function and morphology after aortic valve replacement (AVR) for aortic stenosis (AS), its relationship with exercise capacity remains unknown. Twenty-one AVR patients (age 61 ± 12 years, 14 male) with normal ejection fraction (EF, 64 ± 7%) and 21 age- and sex-matched controls (57 ± 9 years, 10 male, EF 68 ± 8%) were studied. METHODS AND RESULTS: All subjects performed semi-supine bicycle exercise and speckle tracking echocardiography (STE) study. Peak oxygen consumption (pVO(2)) was collected during semi-supine bicycle exercise. Systolic (GLSRs) and early diastolic (GLSRe) longitudinal strain rate using STE and Doppler echocardiographic parameters were measured at rest, submaximal, peak exercise, and 4 min after exercise. The two groups had comparable resting echocardiographic measurements. At peak exercise, pVO(2) was lower in patients than controls (18.5 ± 4.5 vs. 22.1 ± 4.3 L/min/kg, P < 0.05). GLSRs (0.98 ± 0.28 vs. 1.55 ± 0.30 1/s, P < 0.001), septal Sm (7.9 ± 1.4 vs. 11.1 ± 2.3 cm/s, P < 0.001) and their changes between rest and peak exercise (ΔGLSRs: 0.16 ± 0.33 vs. 0.68 ± 0.27 1/s, P < 0.001; ΔSm 2.29 ± 2.23 vs. 4.63 ± 2.29 cm/s, P < 0.01) were significantly lower in patients than controls. There was no correlation between pVO(2) and any echocardiographic measurements in controls. In patients, pVO(2) correlated with peak exercise GLSRs (r = 0.60, P = 0.0007), septal Sm (r = 0.65, P = 0.002), and Em (r = 0.57, P = 0.009). In a multivariate model, peak exercise GLSRs (ß = 7.18, P = 0.03) was the only independent predictor of pVO(2) in the patients group. CONCLUSION: Exercise capacity is subnormal after AVR for AS, irrespective of normal LVEF suggesting residual compromised myocardial functional reserve.

New insights into the clinical evaluation of hereditary transthyretin amyloidosis patients: a single center's experience.

Over the last decade, new medical treatment modalities have emerged based on increased insights into amyloid formation. With the increased possibilities for treatment of amyloidosis caused by transthyretin (TTR) amyloid deposits comes the need for diagnostic procedures for early diagnosis and better tools to follow disease progression. This is of particular importance in clinical trials evaluating the efficacy of new treatments. Until recently, the treatment of TTR amyloidosis (ATTR) was based solely on liver transplantation, a procedure that has halted disease progression in many patients. Liver transplantation has been especially effective in patients under the age of 50 years carrying the TTR V30M mutation, whereas the outcome of the procedure has been variable for others, particularly elderly male patients and those carrying a non-V30M mutation. This review concentrates on new insights derived from our center's experience with liver transplantation, how to implement this experience in evaluation of new treatment modalities for ATTR, and how to facilitate early diagnosis of neuropathy with easily available diagnostic tools. Attention has focused on manifestations of the disease that involve the heart and the peripheral nervous system; change in peripheral nerve function has been the primary endpoint in two controlled clinical trials, one finished and one ongoing. New insights into the amyloid formation process and the lessons learned from liver transplantation give the opportunity to design potentially effective treatment modalities for ATTR. It appears reasonable to suspect that a combination of different treatment modalities may be required to treat the disease, and that different treatment regimes will be designed according to the phenotype of the disease. For the patients and their relatives there is now a solid foundation for optimism, with prospects of several effective medical treatment possibilities within the coming decade.