Hereditary transthyretin-related amyloidosis is frequent in polyneuropathy and cardiomyopathy of no obvious aetiology.

BACKGROUND: Hereditary Transthyretin-Related Amyloidosis, a clinically heterogeneous autosomal dominant disease caused by pathogenic variants in the TTR gene, is characterized by the deposition of insoluble misfolded protein fibrils. The diagnosis, especially in non-endemic areas, is typically delayed by 4-5 years; a misdiagnosis due to clinical heterogeneity is common. The study objective was to define the prevalence of Hereditary Transthyretin-Related Amyloidosis in patients with polyneuropathy and/or cardiomyopathy of no obvious aetiology. METHOD: A multicenter observational "Epidemiological analysis for the hereditary Transthyretin-Related AMyloidosis"-TRAM study was performed in Germany, Austria, and Switzerland. RESULTS: A total of 5141 participants were recruited by 50 neurologic and 27 cardiologic specialized centres. Genetic analysis demonstrated a 1.1% Hereditary Transthyretin-Related Amyloidosis positivity rate among patients with polyneuropathy and/or cardiomyopathy of not obvious aetiology. Twenty-one various TTR variants (TTR-positive) were identified. Body Mass Index was lower in the TTR-positive patients as an indicator for the involvement of the autonomic nervous system; the age of onset of clinical manifestations was higher in TTR-positive patients. There were no other genotype-phenotype correlations or the prevalence of specific clinical manifestations in TTR-positive patients. CONCLUSIONS: Our data support the fact that Hereditary Transthyretin-Related Amyloidosis is underdiagnosed in polyneuropathy and cardiomyopathy patients. Routine implementation of genetic testing is recommended in patients with unexplained polyneuropathy and/or cardiomyopathy to accelerate the earlier diagnosis and the time-sensitive treatment initiation.KEY MESSAGESMore than 5.000 participants with CM and/or PNP of no obvious aetiology were recruited in the observational "Epidemiological analysis for the hereditary Transthyretin-Related AMyloidosis" TRAM study and screened for pathogenic TTR variants.The study demonstrated >1% of patients with CM and/or PNP of unclear aetiology are positive for a pathogenic TTR variant.Routine genetic testing is recommended in patients with unexplained CM and/or PNP to accelerate the initial diagnosis and timely treatment initiation.

The initial slope of the VCO2/VO2-curve (s1) in cardiopulmonary exercise testing is a strong and independent predictor of outcome in patients with previous myocardial infarction.

BACKGROUND: Detecting heart failure (HF) patients at risk is a relevant clinical problem. Our goal was to define associations of clinical HF-markers and exercise parameters with respect to their prognostic power in HF-patients. METHODS: We performed cardiopulmonary exercise testing (CPET) in 103 ischemic HF-patients. CPET-parameters included peak VO(2), VO(2) at AT, peak oxygen pulse, minimal CO(2) and O(2) equivalents, VE/VCO(2) and s1, a motivation-independent and submaximal parameter representing the initial slope of the VCO(2)/VO(2)-curve that has not been described in HF-patients so far. RESULTS: Median follow-up was 668 days. The combined endpoint of cardiovascular death and rehospitalization due to HF occurred in 14 patients. Patients with/without events differed significantly regarding their age, NYHA-class, LVEF and NT-proBNP serum-levels. Patients with events had significantly lower peak VO(2)- and higher s1-values. NT-proBNP serum-levels, NYHA-class and LVEF were significantly correlated with peak VO(2). Only age, peak VO(2) and s1 were independent predictors of adverse events. Using multivariate analysis, s1 was a strong and independent parameter with good sensitivity and specificity. CONCLUSION: s1 is an independent and powerful predictor in HF-patients. Since s1 is independent of maximal exercise capacity, s1 might be more accurate for the evaluation of HF-patients not willing or unable to perform maximal exercise.

Multidetector-row cardiac CT: diagnostic value of calcium scoring and CT coronary angiography in patients with symptomatic, but atypical, chest pain.

The aim of this study was to investigate the accuracy of multidetector-row cardiac CT (MDCT), calcium scoring (Ca-Sc), and MDCT coronary angiography (MD CTA) in the assessment of coronary atherosclerosis. Thirty-eight patients underwent invasive coronary angiography (CA) and MDCT (collimation 4x1 mm, pitch 1.5 mm, TI 500 ms, 120 kV, 300 mAs, and retrospective ECG-gating). Calcium scoring was calculated for the total coronary artery territory and for RCA, LCA, and LCX separately. The MD CTA served to assess the degree and the localization of stenoses. All findings were compared to invasive coronary angiography. Approximately 68.4% (390 of 570) of all coronary segments could be visualized by MDCT. Correlation coefficient for MD CTA and CA amounted to r=0.58, showing distinct differences for the individual segments. Proximal segments generally showed better correlation (range 0.81-0.77) than medial segments (range 0.91-0.20), distal segments (range 0.55-0.04), or side branches (range 0.76-0.00). Patients with hemodynamically relevant (>75%) stenoses were detected by MD CTA with 72.2% sensitivity (13 of 18) and 100% specificity (20 of 20). For Ca-Sc sensitivity ranged between 94.7% (17 of 18) and 66.7% (12 of 18), specificity between 20% (4 of 20) and 80% (16 of 20) respectively, depending on the prevailing cutoff value. Combination of both methods led to 83.3% sensitivity (15 of 18) and 100% specificity (20 of 20), reaching no level of significance as compared with Ca-Sc (p=0.73) or MD CTA (p=0.23) alone. Calcium scoring as a single method showed highest sensitivity in the detection of coronary atherosclerosis but at the expense of low specificity. In patients with no or moderate calcifications, combination with MD CTA helped to distinctly increase specificity and NPV.