Cardiac amyloidosis is not a single disease: a multiparametric comparison between the light chain and transthyretin forms.

AIMS: Systemic amyloidosis represents a heterogeneous group of diseases resulting from amyloid fibre deposition. The purpose of this study is to establish a differential diagnosis algorithm targeted towards the two most frequent subtypes of CA. METHODS AND RESULTS: We prospectively included all consecutive patients with ATTR and AL evaluated between 2018 and 2022 in two centres in a score derivation cohort and a different validation sample. All patients had a complete clinical, biomarker, electrocardiographic, and imaging evaluation. Confirmation of the final diagnosis with amyloid typing was performed according to the current international recommendations. The study population included 81 patients divided into two groups: ATTR (group 1, n = 32: 28 variant and 4 wild type) and AL (group 2, n = 49). ATTR patients were younger (50.7 ± 13.9 vs. 60.2 ± 7.3 years, P = 0.0001), and significantly different in terms of NT-proBNP [ATTR: 1472.5 ng/L (97-4218.5) vs. AL 8024 ng/L (3058-14 069) P = 0.001], hs-cTn I [ATTR: 10 ng/L (4-20) vs. AL 78 ng/L (32-240), P = 0.0002], GFR [ATTR 95.4 mL/min (73.8-105.3) vs. AL: 68.4 mL/min (47.8-87.4) P = 0.003]. At similar left ventricular (LV) wall thickness and ejection fraction, the ATTR group had less frequently pericardial effusion (ATTR: 15% vs. AL: 33% P = 0.0027), better LV global longitudinal strain (ATTR: -13.1% ± 3.5 vs. AL: -9.1% ± 4.3 P = 0.04), RV strain (ATTR: -21.9% ± 6.2 vs. AL: -16.8% ± 6 P = 0.03) and better reservoir function of the LA strain (ATTR: 22% ± 12 vs. AL: 13.6% ± 7.8 P = 0.02). Cut-off points were calculated based on the Youden method. We attributed to 2 points for parameters having an AUC > 0.75 (NT-proBNP AUC 0.799; hs-cTnI AUC 0.87) and 1 point for GFR (AUC 0.749) and TTE parameters (GLS AUC 0.666; RV FWS AUC 0.649, LASr AUC 0.643). A score of equal or more than 4 points has been able to differentiate between AL and ATTR (sensitivity 80%, specificity 62%, AUC = 0.798). The differential diagnosis score system was applied to the validation cohort of 52 CA patients showing a sensitivity of 81% with specificity of 77%. CONCLUSIONS: CA is a complex entity and requires extensive testing for a positive diagnosis. This study highlights a series of non-invasive checkpoints, which can be useful in guiding the decision-making process towards a more accurate and rapid differential diagnosis.

Cardiac "hypertrophy" phenotyping: differentiating aetiologies with increased left ventricular wall thickness on echocardiography.

Aims: Differentiating phenotypes of cardiac "hypertrophy" characterised by increased wall thickness on echocardiography is essential for management and prognostication. Transthoracic echocardiography is the most commonly used screening test for this purpose. We sought to identify echocardiographic markers that distinguish infiltrative and storage disorders that present with increased left ventricular (LV) wall thickness, namely, cardiac amyloidosis (CA) and Anderson-Fabry disease (AFD), from hypertensive heart disease (HHT). Methods: Patients were retrospectively recruited from Westmead Hospital, Sydney, and Princess Alexandra Hospital, Brisbane. LV structural, systolic, and diastolic function parameters, as well as global (LVGLS) and segmental longitudinal strains, were assessed. Previously reported echocardiographic parameters including relative apical sparing ratio (RAS), LV ejection fraction-to-strain ratio (EFSR), mass-to-strain ratio (MSR) and amyloidosis index (AMYLI) score (relative wall thickness × E/e') were evaluated. Results: A total of 209 patients {120 CA [58 transthyretin amyloidosis (ATTR) and 62 light-chain (AL) amyloidosis], 31 AFD and 58 HHT patients; mean age 64.1 ± 13.7 years, 75% male} comprised the study cohort. Echocardiographic measurements differed across the three groups, The LV mass index was higher in both CA {median 126.6 [interquartile range (IQR) 106.4-157.9 g/m2]} and AFD [median 134 (IQR 108.8-152.2 g/m2)] vs. HHT [median 92.7 (IQR 79.6-102.3 g/m2), p < 0.05]. LVGLS was lowest in CA [median 12.29 (IQR 10.33-15.56%)] followed by AFD [median 16.92 (IQR 14.14-18.78%)] then HHT [median 18.56 (IQR 17.51-19.97%), p < 0.05]. Diastolic function measurements including average e' and E/e' were most impaired in CA and least impaired in AFD. Indexed left atrial volume was highest in CA. EFSR and MSR differentiated secondary (CA + AFD) from HHT [receiver operating curve-area under the curve (ROC-AUC) of 0.80 and 0.91, respectively]. RAS and AMYLI score differentiated CA from AFD (ROC-AUC of 0.79 and 0.80, respectively). A linear discriminant analysis with stepwise variable selection using linear combinations of LV mass index, average e', LVGLS and basal strain correctly classified 79% of all cases. Conclusion: Simple echocardiographic parameters differentiate between different "hypertrophic" cardiac phenotypes. These have potential utility as a screening tool to guide further confirmatory testing.

Prognostic Implications of Right Ventricular Systolic Dysfunction in Cardiac Amyloidosis.

Left ventricular (LV) systolic dysfunction in cardiac amyloidosis (CA) is associated with poor prognosis. This study aimed to investigate the prognostic implications of right ventricular (RV) systolic dysfunction in CA. A total of 93 patients diagnosed with CA who underwent standard and speckle-tracking echocardiography were included. During a median follow-up of 17 (5 to 38) months, 42 patients (45%) died. Nonsurvivors were more likely to present with immunoglobulin light-chain amyloidosis and New York Heart Association class III to IV heart failure symptoms. Regarding the echocardiographic characteristics, nonsurvivors had a higher LV apical ratio, worse LV diastolic function, and worse RV systolic function (evaluated with both tricuspid annular plane systolic excursion and RV free wall strain). RV free wall strain was independently associated with all-cause mortality in several multivariable Cox regression models and had incremental prognostic value over conventional parameters of RV function when added to a basal model (including heart failure symptoms, amyloidosis phenotype, and LV global longitudinal strain). Based on spline curve analysis and Youden index, a value of 16% for RV free wall strain was identified as the optimal cutoff to predict outcome and patients with RV free wall strain <16% had a significantly worse short- and long-term survival during follow-up (1- and 3-year cumulative survival: 81% vs 31% and 67% vs 20%, respectively, p <0.001). In conclusion, RV systolic dysfunction is independently associated with poor outcome in patients with CA and the use of advanced echocardiographic parameters, such as RV free wall strain, may be of aid for better risk stratification.

Assessment of left atrial electro-mechanical delay to predict atrial fibrillation in hypertrophic cardiomyopathy.

AIMS: Atrial fibrillation (AF) is frequently observed in hypertrophic cardiomyopathy (HCM) and is associated with poor clinical outcome. Total atrial conduction time, estimated by tissue Doppler imaging (TDI), the so-called PA-TDI duration, reflects the left atrial (LA) structural and electrical remodelling. The aim of this study was to evaluate the association between PA-TDI and new-onset AF in patients with HCM. METHODS AND RESULTS: From a large cohort of patients with HCM, 208 patients (64% male, mean age 53 ± 14 years) without AF were selected. PA-TDI duration was measured from the onset P wave on electrocardiogram to the peak A' wave of the lateral LA wall using TDI. The incidence of new-onset AF was 20% over a median follow-up of 7.3 (3.5-10.5) years. Patients with incident AF had longer PA-TDI duration when compared with patients without AF (133.7 ± 23.0 vs. 110.5 ± 30.0 ms, P < 0.001). PA-TDI duration was independently associated with new-onset AF (hazard ratio: 1.03, 95% confidence interval: 1.01-1.05, P < 0.001). CONCLUSION: Prolonged PA-TDI duration was independently associated with new-onset AF in patients with HCM. This novel parameter could be useful to risk-stratify patients with HCM who are at risk of having AF.

Heyde syndrome revisited: anaemia and aortic stenosis.

BACKGROUND: The association of anaemia with aortic stenosis (AS) has been recognised for over 50 years; however, although there have been several sporadic reports, there are few data on the prevalence of this syndrome. AIMS: We sought to compare the prevalence of anaemia in adults with AS with that of controls who had undergone coronary artery bypass grafting (CABG). METHODS: We conducted a retrospective cohort study comparing pre-procedural levels of haemoglobin in 1537 adults who underwent aortic valve replacement (AVR) for AS with 8025 contemporaneous patients who had CABG. We hypothesised that the prevalence of anaemia in patients with AS would be significantly higher than in the control group. RESULTS: A total of 30.1% in the AVR group was anaemic compared to 16.2% in the CABG group. The mean haemoglobin concentration measured across the whole population was significantly lower (132 g/L) in AVR patients than in those who underwent CABG (138 g/L). In a multivariable model, haemoglobin levels varied significantly by treatment group, gender and age. The adjusted marginal mean haemoglobin value was 135.6 g/L in AVR patients compared to 137.3 g/L in CABG patients. CONCLUSIONS: The prevalence of anaemia was significantly greater in patients with AS than in a contemporaneous cohort that underwent CABG. This may indicate that Heyde syndrome is more common than has been generally appreciated and should be considered in the evaluation of anaemia in patients with AS.

Routine angiography in survivors of out of hospital cardiac arrest with return of spontaneous circulation: a single site registry.

BACKGROUND: Coronary revascularization in resuscitated out of hospital cardiac arrest (OOHCA) patients has been associated with improved survival. METHODS: This was a retrospective review of patients with OOHCA between 01/07/2007 and 31/03/2009 surviving to hospital admission. Cardiac risk factors, demographics, treatment times, electrocardiogram (ECG), angiographic findings and in-hospital outcomes were recorded. RESULTS: Of the 78 patients, 63 underwent coronary angiography. Traditional cardiac risk factors were common in this group. Chest pain occurred in 33.3% pre-arrest, 59.0% were initially treated at a peripheral hospital, 83.3% had documented ventricular tachycardia or ventricular fibrillation, 55.1% had specific ECG changes, 65.4% had acute myocardial infarction (AMI) as the cause of OOHCA and the majority had multi-vessel disease. ST elevation strongly predicted AMI. The in-hospital survival was 67.9% with neurological deficit in 13.2% of survivors. The group of patients who had an angiogram were more likely to have AMI as a cause of cardiac arrest (71.4% vs 40.0%, p = 0.01) and more likely to have survived to discharge (74.6% vs 40.0%, p < 0.01). Poor outcome was associated with older age, cardiogenic shock, longer transfer times, diabetes, renal impairment and a long duration to return of spontaneous circulation. CONCLUSIONS: Acute myocardial infarction was the commonest cause of OOHCA and a high rate of survival to discharge was seen with a strategy of routine angiography and revascularization.