Senile systemic amyloidosis: clinical features at presentation and outcome.

BACKGROUND: Cardiac amyloidosis is a fatal disease whose prognosis and treatment rely on identification of the amyloid type. In our aging population transthyretin amyloidosis (ATTRwt) is common and must be differentiated from other amyloid types. We report the clinical presentation, natural history, and prognostic features of ATTRwt compared with cardiac-isolated AL amyloidosis and calculate the probability of disease diagnosis of ATTRwt from baseline factors. METHODS AND RESULTS: All patients with biopsy-proven ATTRwt (102 cases) and isolated cardiac AL (36 cases) seen from 2002 to 2011 at the UK National Amyloidosis Center were included. Median survival from the onset of symptoms was 6.07 years in the ATTRwt group and 1.7 years in the AL group. Positive troponin, a pacemaker, and increasing New York Heart Association (NYHA) class were associated with worse survival in ATTRwt patients on univariate analysis. All patients with isolated cardiac AL and 24.1% of patients with ATTRwt had evidence of a plasma cell dyscrasia. Older age and lower N-terminal pro-B-type natriuretic peptide (NT pro-BNP) were factors significantly associated with ATTRwt. Patients aged 70 years and younger with an NT pro-BNP <183 pmol/L were more likely to have ATTRwt, as were patients older than 70 years with an NT pro-BNP <1420 pmol/L. CONCLUSIONS: Factors at baseline associated with a worse outcome in ATTRwt are positive troponin T, a pacemaker, and NYHA class IV symptoms. The age of the patient at diagnosis and NT pro-BNP level can aid in distinguishing ATTRwt from AL amyloidosis.

Abnormal regional left ventricular mechanics in treated hypertensive patients with 'normal left ventricular function'.

Global systolic and diastolic LV function assessed by conventional echocardiographic indices is often normal in patients with controlled hypertension, with or without left ventricular hypertrophy. However, it is not certain whether regional myocardial function in these patients remains normal. We investigated 26 patients and 10 age matched normal controls, by means of long axis M-mode echocardiography. There was no significant difference in age, sex distribution, heart rate, blood pressure and routine ECG measurements between the two groups. Although there was significant LVH in patients compared to normal controls, LV cavity size and global systolic function, assessed by shortening fraction, ejection fraction and mean velocity of circumferential fibre shortening did not differ between the two groups, nor did LV diastolic function, assessed by the mitral flow pattern. However, LV regional mechanics, as assessed by multiple long axis M-mode echocardiograms differed significantly, in both systole and diastole, between the two groups. Compared to controls, the total longitudinal systolic excursion in both LV free wall and ventricular septum were significantly reduced in patients, and so was maximum early relaxation and atrial contraction in the LV free wall. The mean rate of systolic excursion in all 3 sites did not differ between the two groups, but the mean rate of early relaxation in both LV free wall and ventricular septum was significantly decreased in patients compared to normal controls. In conclusion, the evaluation of LV dysfunction in patients who have achieved good blood pressure control requires more than a conventional echocardiographic assessment. The assessment of regional mechanics described in the present paper offers an easy and sensitive method for the detection of subtle signs of LV mechanical inefficiency associated with LVH.

Vasculopathy in Turner syndrome: arterial dilatation and intimal thickening without endothelial dysfunction.

CONTEXT: Women with Turner syndrome (TS) have an increased cardiovascular mortality rate from both structural and ischemic heart disease, especially aortic dissection. OBJECTIVE: We hypothesized that TS women have a fundamental arterial wall defect that may be due to genetic factors or estrogen deficiency. DESIGN, SETTING, AND PATIENTS: TS women (n = 93) were compared with normal controls (n = 25) and women with 46,XX primary amenorrhea (PA) (n = 11) with a similar history of estrogen deficiency. Clinical parameters, aortic root diameter, extraaortic arterial structure [common carotid (CD), brachial artery diameter, and carotid intima-media thickness (IMT)], arterial stiffness (pulse-wave velocity, augmentation index), and endothelial function (flow-mediated dilatation) were assessed. MAIN OUTCOME MEASURES: These included arterial diameters and vascular physiology parameters. RESULTS: Differences in arterial structure were observed among TS, normal controls, and 46,XX PA women: IMT (0.61 +/- 0.07 vs. 0.55 +/- 0.06 vs. 0.60 +/- 0.05 mm, respectively; P < 0.001), CD (5.71 +/- 0.64 vs. 5.27 +/- 0.34 vs. 5.22 +/- 0.38 mm; P < 0.001), and brachial artery diameter (3.29 +/- 0.44 vs. 3.06 +/- 0.36 vs. 2.97 +/- 0.30 mm; P = 0.006). Aortic root diameter was greater in TS than normal control women. TS status, height, weight, and IMT were independently associated with increased CD after multivariate adjustment (P < 0.05). TS status, age, diastolic blood pressure, and CD remained independently associated with increased IMT after multivariate adjustment (P < 0.05). Pulse-wave velocity and flow-mediated dilatation were similar among the three groups. CONCLUSION: Women with TS have greater IMT and conduit artery diameters than normal controls. Similarly, increased IMT in TS and 46,XX PA women suggests that estrogen deficiency contributes to intimal thickening. Interventional studies are required to determine the extent to which blood pressure and estrogen deficiency may be appropriate therapeutic targets to reduce cardiovascular risk in TS.

A comparison of echocardiography and magnetic resonance imaging in cardiovascular screening of adults with Turner syndrome.

The high mortality rate from aortic dissection of women with Turner syndrome (TS) achieving ovum donation pregnancies has highlighted the need for a refinement of cardiac screening protocols. Echocardiography and magnetic resonance imaging (MRI) are used to assess the risk factors, aortic root dilatation, bicuspid aortic valve, and coarctation, but the relative merits of each modality are unclear. Cardiovascular screening was performed in 128 unselected women with TS (mean age +/- SD, 31.1 +/- 8.5 yr) using echocardiography (n = 120) and MRI (n = 115) and in 36 age-matched normal control women. Clinical history, anthropometric measurements, blood pressure, and metabolic parameters were recorded. Echocardiography was normal in 53% of women with TS; MRI was normal in 34%. Aortic root dilatation was identified in 16% of women by echocardiography, 33% on MRI criteria, and 7% by both modalities. Height-adjusted echocardiographic aortic root dimensions were greater in TS than controls (2.90 vs. 2.62 cm; P = 0.010). Bicuspid aortic valve and increasing age were associated with greater aortic dimensions; the latter effect was more marked in TS than controls. On MRI, ascending aortic diameter was greater in TS than control women (2.83 vs. 2.52 cm; P = 0.029), but descending aortic diameter and ascending/descending aortic ratio were not, because these may be affected by the presence of coarctation. The two techniques are complementary and identify different aspects of cardiovascular pathology. Ascending/descending ratio on MRI circumvents issues of stature, but may be influenced by descending aortic abnormalities. We present reference ranges for absolute aortic dimensions in a TS population to aid future interpretation of these measurements.