Usefulness of 99mTc-HMDP scintigraphy for the etiologic diagnosis and prognosis of cardiac amyloidosis

Background: Amyloidosis is characterized by extracellular deposits of insoluble proteins that cause tissue damage. The three main types are monoclonal light chain (AL), wild-type transthyretin (wt-TTR) and mutated transthyretin (m-TTR) amyloidosis. Cardiac amyloidosis (CA) raises diagnostic challenges.

Objective: To assess the diagnostic accuracy of ^99mTc-HMDP-scintigraphy for typing CA, differentiating CA from non-amyloid left ventricle hypertrophy (LVH), and predicting outcomes.

Methods: 121 patients with suspected CA underwent ^99mTc-HMDP-scintigraphy in addition to standard investigations.

Results: CA was diagnosed in all AL (n?=?14) and wt-TTR (n?=?21). Among m-TTR (n?=?34), 26 had CA, 4 neuropathy without CA and 4 were asymptomatic carriers. Of the 52 patients with non-amyloid heart disease, 37 had LVH and served as controls. ^99mTc-HMDP cardiac uptake occurred in all wt-TTR, in m-TTR with CA except two and in one AL. A visual score?≥?2 was 100% specific for diagnosing TTR-CA. Among TTR-CA, heart-to-skull retention (HR/SR) correlated with CA severity (LVEF and NT-proBNP). Median follow-up was 111 days (50;343). In a multivariate Cox model including clinical, echocardiographic and scintigraphic variables, NYHA III-IV and HR/SR?>?1.94 predicted acute heart failure and/or death.

Conclusions: This preliminary study suggests that ^99mTc-HMDP-scintigraphy may aid differentiation between transthyretin and AL-CA as well as CA from other LVHs. ^99mTc-HMDP-scintigraphy appears to provide prognostic information in CA.     

Plasma hepatocyte growth factor is a novel marker of AL cardiac amyloidosis

Abstract

Background: Cardiac amyloidosis is an infiltrative cardiomyopathy that is challenging to diagnose. We hypothesized that the novel biomarkers hepatocyte growth factor (HGF), galectin-3 (GAL-3), interleukin-6 (IL-6), and vascular endothelial growth factor (VEGF) would be elevated in cardiac amyloidosis and may be able to discriminate from non-cardiac systemic amyloidosis or other cardiomyopathies with similar clinical or morphologic characteristics.

Methods: Patients were selected from the Vanderbilt Main Heart Registry according to the following groups: (1) amyloid light-chain (AL) cardiac amyloidosis (n?=?26); (2) transthyretin (ATTR) cardiac amyloidosis (n?=?7); (3) left ventricular hypertrophy (LVH) (n?=?45); (4) systolic heart failure (n?=?42); and (5) non-cardiac systemic amyloidosis (n?=?7). Biomarkers were measured in stored plasma samples. Biomarkers' discrimination performance in predicting AL cardiac amyloidosis (i.e., Concordance index) was reported. A survival analysis was used to explore the relationship between HGF levels and mortality among AL cardiac amyloidosis patients.

Results: HGF levels were markedly elevated in patients with AL cardiac amyloidosis (median?=?622, interquartile range (IQR): 299–1228?pg/mL) compared with the other groups, including those with non-cardiac systemic amyloidosis (median?=?134, IQR: 94–163?pg/mL, p?<?0.001). HGF was not a specific marker for ATTR amyloidosis. Gal-3 was elevated in all groups with amyloidosis but could not differentiate between those with and without cardiac involvement. There was no difference in IL-6 or VEGF between those with AL cardiac amyloidosis compared to other groups (p?=?0.13 and 0.057, respectively).

Conclusions: HGF may be a specific marker that distinguishes AL cardiac amyloidosis from other cardiomyopathies with similar clinical or morphologic characteristics. Further studies are necessary to determine whether HGF levels predict the likelihood of survival.     

Right ventricular longitudinal strain: a tool for diagnosis and prognosis in light-chain amyloidosis

Objectives: Light-chain (AL) amyloidosis can lead to an infiltrative cardiomyopathy with increased wall thickness (IWT) of very poor prognosis. Our primary aim was to analyse the right ventricle (RV) in patients with IWT to discriminate AL amyloidosis from IWT due to hypertrophic cardiomyopathy (HCM) or to arterial hypertension (HTN). Our secondary aim was to assess if RV dysfunction predicts overall mortality in cardiac AL amyloidosis.

Methods: We retrospectively and consecutively compared clinical, biological and echocardiographic data of 315 patients with IWT: 105 biopsy-proven AL amyloidosis patients, 105 patients with HCM and 105 patients with HTN. The prognostic value of these parameters was analysed in the AL amyloidosis group.

Results: Free-wall right ventricular longitudinal strain (FWRVLS) worse than ?21.2% discriminates AL amyloidosis [area under the curve (AUC)?=?0.744)] from patients with IWT due to other aetiologies. In AL amyloidosis, FWRVLS is the strongest echocardiographic prognostic marker with AUC =0.722 and ?16.5% as the optimal cut-off value, beyond which overall mortality increases significantly. It is also the only independent echocardiographic predictor of overall mortality (HR =1.113; 95%CI 1.029–1.204; p?=?.007), even when adjusted to the Mayo stage and global left ventricular longitudinal strain.

Conclusions: FWRVLS should be considered in the diagnostic and prognostic workup in light-chain amyloidosis.     

Reduced left atrial myocardial deformation irrespective of cavity size: a potential cause for atrial arrhythmia in hereditary transthyretin amyloidosis

Background: Cardiac amyloidosis (CA) is a myocardial disease and commonly under-diagnosed condition. In CA patients, atrial fibrillation might occur in the absence of left atrial (LA) enlargement.

Objectives: The aim of this study is to assess LA size and function, and its relationship with atrial arrhythmia in patients with hereditary transthyretin amyloidosis (ATTR).

Methods: Forty-six patients with confirmed ATTR amyloidosis on abdominal biopsy were studied. Assessment with 2D echocardiography and 2D strain showed 31 patients had increased LV wall thickness (LVWT) (septal thickness >12?mm), and 15 had normal LVWT. In addition to conventional measurements, LV and LA global longitudinal strain (GLS%) and strain rate (SR) were obtained. Western blot analysis was done to assess fibril type. ATTR patients with increased LVWT were compared with 23 patients with hypertrophic cardiomyopathy (HCM) and 31 healthy controls. ATTR amyloidosis patients also underwent 24?hour Holter monitoring to determine the presence of atrial arrhythmia.

Results: Atrial deformation during atrial systole was reduced in ATTR amyloidosis patients with increased LVWT independent of LA size and in contrast to HCM. Twenty of the ATTR amyloidosis patients (54%) had ECG evidence of significant atrial arrhythmic events. LA strain rate, during atrial systole, was the only independent predictor of atrial arrhythmia (β?=?3.28, p?=?.012).

Conclusion: In ATTR cardiomyopathy with increased LVWT, LA myocardial function is abnormal, irrespective of atrial cavity size. Reduced LA myocardial SR during atrial systole, irrespective of cavity volume, E/e′ and LV deformation, is also a strong predictor for atrial arrhythmic events.     

Renal functions in obstructive sleep apnea patients

Purpose

The aim of this study is to investigate possible factors influencing glomerular filtration rate (GFR) in obstructive sleep apnea (OSA).

Methods

Data of OSA patients admitted to Gaziantep University sleep clinic from January 2005 to January 2010 were retrospectively evaluated. GFR is calculated with the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Patients younger than 18 years old were excluded.

Results

The mean age of OSA (n?=?634) and control group (n?=?62) were 51.13?±?11.61 and 50.69?±?13.88 years, respectively (p?=?0.81). The mean estimated GFR (eGFR) was 90.73?±?19.59 ml/min/1.73 m² in OSA patients and 94.14?±?18.81 ml/min/1.73 m² in control subjects (p?=?0.19). GFR was 84.25?±?20.87 ml/min/1.73 m² in patients with left ventricular hypertrophy (LVH) while it was 93.94?±?18.44 ml/min/1.73 m² in patients without LVH (p?=?0.00). GFR of male subjects was 92.1?±?19.23 in OSA and 95.84?±?20.08 ml/min/1.73 m² in controls (p?=?0.33). GFR of female and male patients in the OSA were 87.45?±?20.10 and 92.91?±?18.02 ml/min/1.73 m², respectively (p?=?0.13). Serum creatinine was higher in OSA patients compared to controls (p?=?0.01). GFR was 92.30?±?19.27 in male and 88.33?±?19.84 ml/min/1.73 m² in female subjects (p?=?0.01). GFR was 84.86?±?19.95 in hypertensive patients while it was 95.11?±?18.20 ml/min/1.73 m² in normotensive subjects (p?=?0.00). GFR was 89.30?±?19.96 in patients with metabolic syndrome (MetS) and it was 93.46?±?18.68 ml/min/1.73 m² in patients without MetS (p?=?0.00).

Conclusions

GFR values were lower in sleep apneic patients with MetS as well as in patients with hypertension and LVH.

     

Prognostic value of right ventricular systolic function in cardiac amyloidosis

Abstract

Background: Right ventricular (RV) dysfunction is a strong predictor of poor outcomes in heart failure. Its prognostic meaning in cardiac amyloidosis (CA) is under-investigated.

Methods: Hundred and twenty nine patients with suspected CA and an interventricular septum thickness (IVST)?≥?12?mm underwent echocardiography with measurement of left ventricular (LV) and RV longitudinal strain (LS), late gadolinium-enhancement (LGE) cardiac MRI, and standard evaluation.

Results: Among 82 confirmed CA, types were immunoglobulin light chain (AL, n?=?26), hereditary transthyretin (m-TTR, n?=?37) and senile (WT-TTR, n?=?19). Compared to those without, CA patients had significantly lower RV fractional shortening (RV-FS), tricuspid annular plane systolic excursion (TAPSE), tissue Doppler systolic velocity, and global RV-LS, without any difference among the CA types. RV-LGE, observed in 62% of CA patients, was associated with lower global and basal RV-FS. Median follow-up was 8(2; 16) months. Using multivariate analysis, NYHA-class and low TAPSE independently predicted major adverse cardiac event (MACE) defined as death, heart transplantation and acute heart failure. Independent determinants of TAPSE?<?14?mm, the best cut-off value, were LV ejection fraction (LVEF), estimated filling pressure (E/E′), NT-proBNP and pulmonary artery pressure, but not RV-LGE.

Conclusions: RV dysfunction is common in CA. Its routine evaluation by a simple TAPSE may be an aid in assessing the prognosis of CA patients.     

Muscle performance and fatigue in compensated chronic liver disease

Abstract

Background: A common and debilitating symptom in patients with chronic liver disease is fatigue (CLD). Muscle dysfunction has been suggested to be a key mechanism of fatigue in CLD.

Objective: We aimed to evaluate fatigue and the potential association with muscle performance and physical activity in outpatients with CLD.

Methods: Two-hundred seventy outpatients with CLD were included, (52?±?15 years, mean?±?SD; 151 females) with autoimmune hepatitis (n?=?49), primary biliary cholangitis (n?=?45), primary sclerosing cholangitis (n?=?46), chronic hepatitis B (n?=?57) or C (n?=?73). Patients with a Child-Pugh >6 were excluded. The questionnaire Fatigue Impact Scale (FIS) was used to evaluate fatigue, and physical activity was evaluated through a self-reported level of physical activity. Muscle function was assessed with four muscle tests, walking speed, handgrip strength, standing heel-rise test (SHT) and ‘Timed Up and Go’ test (TUG).

Results: The median total FIS score was 30 (40% had FIS > 40, considered high-fatigue). Diminished muscle performance was observed in the SHT (% of predicted value: 53?±?26%) and with maximum grip strength (85?±?20%). The FIS score was significantly different between groups of CLDs (p?=?.004). In multivariate analysis the TUG (p?=?.001), SHT (p?=?.005), antidepressants (p?p?=?.001) were associated with fatigue (R²?=?29%). Subjects with higher levels of physical activity had lower FIS (p?Conclusions: In patients with CLD, fatigue was associated with low muscle performance and reduced level of physical activity, which could be a potential therapeutic target.     

Left ventricular hypertrophy on long-term cardiovascular outcomes in patients with ST-elevation myocardial infarction

Abstract

Background: Left ventricular hypertrophy (LVH) had been associated with increased adverse cardiovascular events in hypertensive patients. Prognostic significance of LVH in patients with ST-elevation myocardial infarction (STEMI) is not established. This study aimed to investigate prognostic impact of LVH on the patients with STEMI. Methods: We analyzed the data and clinical outcomes of 30-day survivors with STEMI who underwent successful coronary intervention from 2003 to 2009. Definition of LVH was LV mass index (LVMI) >115?g/m² in male and >95?g/m² in female. Patients were classified into a LVH group and a non-LVH group. Occurrence of major adverse cardiovascular events (MACE; death, recurrent MI, target vessel revascularization (TVR)) within 5 years was evaluated. Results: We enrolled 418 patients and mean follow-up duration was 43?±?17 months. Two hundred and fourteen patients (51%) had LVH. The survival of the patients with LVH was significantly worse than the patients without LVH (log-rank p?=?0.024). In a multivariate regression model, the presence of LVH was independently associated with increased risk for all-cause mortality (OR, 2.37; 95% CI, 1.096–5.123, p?=?0.028). When the end points were analyzed based on LVH severity, all-cause mortality was significantly correlated with LVH severity (p?=?0.011). The severe LVH was independently associated with increased risk for all-cause mortality (OR, 5.110; 95% CI, 1.454–17.9, p?=?0.001). Conclusion: LVH was associated with increased rate of adverse clinical outcomes in 30-day survivors after STEMI, who underwent successful coronary intervention.     

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.     

Outcomes of patients with AL amyloidosis and low serum free light chain levels at diagnosis

Abstract

Serum free light chains (sFLC) are independent prognostic markers of disease in light chain (AL) amyloidosis, and are used in the haematologic response criteria for treatment. However, up to 20% of patients have low sFLCs at diagnosis, with a difference between involved and uninvolved free light chains (dFLC) of less than 50?mg/L, making responses to treatment difficult to evaluate. In order to characterize this distinct subgroup of patients, we retrospectively analyzed 123 AL amyloidosis patients with dFLC <50?mg/L who were diagnosed between 2002 and 2013. The majority (n?=?117) were treated for their AL amyloidosis, with over half (n?=?68) receiving high-dose melphalan and autologous stem cell transplantation as first-line therapy. Overall they had a prolonged median survival of 9.2?years with less cardiac involvement (30%) and more renal involvement (76%). We also evaluated the newly proposed low dFLC partial response (PR) criteria, defined as a dFLC <10?mg/L if the initial dFLC 20–50?mg/L. The 14 patients with low dFLC PR had improved survival and organ responses compared with patients with no haematologic response. However, one-third of patients (n?=?41) had an initial dFLC <20?mg/L so could not be evaluated. More sensitive methods of monitoring response to treatment for this subgroup population are still needed.     

Electrocardiographic left ventricular hypertrophy predicts arrhythmia and mortality in patients with ischemic cardiomyopathy

Purpose

The relatively low incidence of device-treated ventricular arrhythmias in patients with ischemic cardiomyopathy (ICM) who receive implantable cardioverter defibrillators (ICDs) for primary prevention makes improved risk stratification of ICM patients a priority. Although Cornell product (CP) ECG left ventricular hypertrophy (LVH) has been associated with increased mortality in hypertensive patients and population-based studies, whether CP LVH can improve risk stratification of high-risk ICM patients is unclear. The aim of this study is to examine if electrocardiographic LVH predicts mortality and incident ventricular arrhythmia in patients with ICM.

Methods

All-cause mortality was examined in 317 patients with ICM and a history of non-sustained ventricular tachycardia (VT) who underwent electrophysiology testing. Incident VT and ventricular fibrillation (VF) were assessed in ICD recipients (n?=?186). ECG LVH was defined by CP criteria: [(R _aVL?+?S _V3)?+?6?mm in women]?×?QRS duration >2,440?mm?ms.

Results

During 3?years of follow-up, mortality was 20% (64 of 317) and death or incident VT or VF occurred in 35% of ICD recipients. CP LVH was associated with significantly greater 3-year mortality (28% vs 15%, p?=?0.015) and 3-year mortality or incident VT/VF in ICD patients (48% vs 35%, p?=?0.011). In Cox multivariate models, CP LVH was an independent predictor of mortality in all patients (hazard ratio (HR) 1.81, 95% confidence interval (CI) 1.11?C2.97, p?=?0.020) and of the composite endpoint of mortality or incident ventricular arrhythmia in ICD patients (HR 1.82, 95% CI 1.12?C3.00, p?=?0.016).

Conclusions

ECG LVH using CP criteria may enhance risk stratification in high-risk patients with ICM.     

Amyloid A deposition in rheumatoid arthritis: a retrospective clinicopathologic study of 161 autopsy patients

Abstract

Background: Familial amyloid polyneuropathy (FAP) mainly targets the peripheral nervous system and heart. Early noninvasive detection of cardiac impairment is critical for therapeutic management.

Aim: To assess if amino-terminal pro-brain natriuretic peptide (NT-proBNP) or troponin T (cTnT) can predict echocardiographic left-ventricle (LV) impairment in FAP.

Methods: Thirty-six asymptomatic carriers and patients with FAP had echocardiographic measurement of left-ventricular (LV) systolic function, hypertrophy (LVH) and estimation of filling pressure (FP).

Results: Overall, median age, NT-proBNP, and LV ejection fraction were, respectively, 59 years (41–74), 323?pg/ml (58–1960), and 60% (51–66). Twelve patients had increased cTnT. Prevalence of ATTR gene mutations was 53% for Val30Met. Four individuals were asymptomatic, 6 patients had isolated neurological clinical signs, and 26 had echo-LV abnormalities. The ROC curve identified NT-proBNP patients with echo-LV abnormalities (area: 0.92; (0.83–0.99), p?=?0.001) at a threshold >82?pg/ml with a sensitivity of 92%, and a specificity of 90%. Increased in NT-proBNP occurred in patients with SD and/or LVH with or without increase in FP. Elevated cTnT (>0.01ng/ml) was only observed in patients with LVH and systolic dysfunction, with or without FP.

Conclusion: In FAP, NT-proBNP was associated with cardiac impairment suggesting that NT-proBNP could be used in carriers or in FAP patients with only neurologic symptoms for identifying the appropriate time to start cardiac echocardiographic assessment and follow-up. cTnT identified patients with severe cardiac disease.     

Evaluation of preoperative prognostic factors in patients with resectable pancreatic ductal adenocarcinoma

Abstract

Objective: Upfront surgery is the standard treatment for resectable pancreatic ductal adenocarcinomas (R-PDACs); however, these tumors often recur. We investigated the factors governing recurrence and prognosis in patients with R-PDAC.

Methods: We analyzed 359 patients who underwent upfront surgery for R-PDAC between 2000 and 2016, and evaluated the relationship between clinicopathological factors and recurrence/outcomes.

Results: The rate of recurrence was 74% while the median time to recurrence was 1.2 years. On multivariate analysis, carbohydrate antigen 19-9 (CA19-9) >37?U/mL (hazard ratio [HR]: 2.02), tumor size >2.6?cm (HR: 1.50), pathological grade 3 (HR: 2.58), lymph node metastasis (LNM; HR: 1.65), residual tumor (HR: 1.47) and forgoing adjuvant chemotherapy (HR: 1.31) were risk factors for a shorter recurrence-free survival; the median survival time (MST) was 2.8 years. On multivariate analysis, CA19-9?>?37?U/mL (HR: 1.99), tumor size >2.6?cm (HR: 1.43), pathological grade 3 (HR: 2.93), pathological portal vein invasion (HR: 1.48), LNM (HR: 1.79) and forgoing adjuvant chemotherapy (HR: 1.39) were risk factors for shorter disease-specific survival intervals. When examining outcomes according to preoperatively measurable factors (CA19-9?>?37?U/mL and tumor size >2.6?cm), the median time to recurrence and MSTs of patients with none (n?=?83), one (n?=?112) and both (n?=?164) risk factors were 3.2, 1.8 and 0.8 years; and 7.2, 4.0 and 1.7 years, respectively.

Conclusions: CA19-9?>?37?U/mL and tumor size >2.6?cm were preoperative independent risk factors for early recurrence and poor outcomes in patients with R-PDAC. Therefore, preoperative treatment should be considered for such patients.     

Obesity is a significant susceptibility factor for idiopathic AA amyloidosis

Background: To investigate obesity as susceptibility factor in patients with idiopathic AA amyloidosis.

Methods: Clinical, biochemical and genetic data were obtained from 146 patients with AA amyloidosis. Control groups comprised 40 patients with long-standing inflammatory diseases without AA amyloidosis and 56 controls without any inflammatory disease.

Findings: Patients with AA amyloidosis had either familial Mediterranean fever (FMF) or long-standing rheumatic diseases as underlying inflammatory disease (n?=?111, median age 46 years). However, in a significant proportion of patients with AA amyloidosis no primary disease was identified (idiopathic AA; n?=?37, median age 60 years). Patients with idiopathic AA amyloidosis were more obese and older than patients with AA amyloidosis secondary to FMF or rheumatic diseases. Serum leptin levels correlated with the body mass index (BMI) in all types of AA amyloidosis. Elevated leptin levels of more than 30?µg/l were detected in 18% of FMF/rheumatic?+?AA amyloidosis and in 40% of patients with idiopathic AA amyloidosis (p?=?.018). Finally, the SAA1 polymorphism was confirmed as a susceptibility factor for AA amyloidosis irrespective of the type of the disease.

Conclusions: Obesity, age and the SAA1 polymorphism are susceptibility factors for idiopathic AA amyloidosis. Recent advances in treatment of FMF and rheumatic disorders will decrease the incidence of AA amyloidosis due to these diseases. Idiopathic AA, however, might be an emerging problem in the ageing and increasingly obese population.     

Do induced tachycardias within the scope of electrophysiological studies lead to elevated plasma troponin I levels?

Aims

Troponin I (TNI) is an established marker for the diagnosis of acute coronary syndrome (ACS). The study evaluated if (induced) tachycardiac arrhyhthmias within the scope of the electrophysiological studies (EPS) led to elevation of TNI serum levels.

Method

TNI was measured in the serum of 28?patients before and after the EPS. The left ventricular ejection fraction (LV-EF) was investigated by two-dimensional echocardiography. Left ventricle hypertrophy (LVH) was measured according to the recommendations of the American Society of Echocardiography. All patients underwent coronary angiography prior to the EPS, and significant coronary heart disease was defined as stenosis >?50%. The EPS revealed supraventricular and ventricular tachycardias using the 18-step protocol with one, two, and three extrastimuli.

Results

Indications for the EPS were syncope (n?=?15), atrioventricular tachycardia (n?=?4), non-sustained VT (n?=?6), and sustained VT (n?=?3). Coronary heart disease (CHD) was detected in 8?patients (1-vessel: n?=?3; 2-vessel: n?=?4; 3-vessel: n?=?1), and 2?patients underwent percutaneous coronary intervention before EPS. Echocardiography revealed normal LV-EF in 18?patients and a reduction in the others (low n?=?3, middle n?=?5, high n?=?2). Thirteen patients suffered from LVH. In 2?patients, external cardioversion was required during the EPS. TNI was elevated over 0.1?ng/ml (risk stratification cut-off for ACS) in 4?patients before and in 12?patients after EPS. There was no relationship between LV-EF, CHD, and the elevation of TNI after the EPS.

Conclusion

TNI can be elevated by (induced) tachycardias within the scope of electrophysiological studies without a relationship to LV-EF, LVH, and CHD.     

Penile ulcers complicating systemic AL amyloidosis: a case report

Abstract

Purpose: Transthyretin (ATTR) amyloidosis is a rare but serious infiltrative disease associated with a wide spectrum of morphologic and functional cardiac involvement. ^99mTc-labelled 3,3-diphosphono-1,2-propanodicarboxylic acid (DPD), initially developed as a bone-seeking radiotracer, is remarkably sensitive for imaging cardiac ATTR amyloid deposits. Our aim was to investigate the feasibility and utility of estimating ^99mTc-DPD uptake in myocardial tissue; this has the potential to yield reliable quantitative information on cardiac amyloid burden, which is urgently required to monitor disease progression and response to novel treatments.

Methods: Three methods of quantitation were developed and tested on 74 patients with proven cardiac ATTR amyloidosis who had recently undergone ^99mTc-DPD planar whole-body imaging and SPECT-CT. Quantitative results were compared to measurements of extracellular volume fraction (ECV) by cardiac magnetic resonance imaging, a validated technique for measuring amyloid burden.

Results: An experienced clinician graded uptake using a widely-used visual scoring system as 1 (n?=?15), 2 (n?=?39) or 3 (n?=?20). Linear correlations between the SPECT and ECV data (p?99mTc-DPD uptake in the heart was significantly greater in patients with grade-3 uptake than in those with grade-2 uptake.

Conclusions: Quantitation of ^99mTc-DPD uptake in cardiac transthyretin amyloid deposits is complex and is hindered by competition for radiotracer with amyloid in skeletal muscle. The latter underlies differences in uptake between grade-2 and grade-3 patients, not cardiac uptake.     

Bortezomib-based chemotherapy reduces early mortality and improves outcomes in patients with ultra-high-risk light-chain amyloidosis: a retrospective case control study

Background: Patients with amyloid light-chain (AL) amyloidosis who have advanced cardiac damage are at risk of premature mortality. Currently, bortezomib is the mainstay in the treatment of AL amyloidosis, but the benefits of bortezomib in patients with ultra-high-risk (2004 Mayo stage IIIb or 2012 Mayo stage IV) AL amyloidosis have not been proved definitively.

Methods: We performed a retrospective analysis of patients newly diagnosed with ultra-high-risk AL amyloidosis who received a bortezomib-based regimen or supportive treatment. We aimed to establish the effects of bortezomib on early mortality and long-term outcomes in this high-risk population.

Results: Patients receiving bortezomib-containing chemotherapy (n?=?62) and patients receiving no chemotherapy (n?=?24) were included. Median overall survival (OS) was 30?months in the bortezomib group and 2?months in the control group (p?<?.001), and median progression-free survival (PFS) was 15.8?months (bortezomib) and 2?months (control; p?<?.001). The early-death rate (within 6?months of treatment) was 32.3% (bortezomib) and 66.7% (control; p?<?.001). In a landmark analysis assessing outcomes in patients surviving beyond 6?months, the 2-year OS and PFS in the bortezomib group were 77.3% and 65.8%, respectively.

Conclusions: Bortezomib-based regimens can help to reduce early mortality and improve long-term survival in patients with ultra-high-risk AL amyloidosis.     

Multiparametric Echocardiography Scores for the Diagnosis of Cardiac Amyloidosis

ObjectivesThis study aimed to investigate the accuracy of a broad range of echocardiographic variables to develop multiparametric scores to diagnose CA in patients with proven light chain (AL) amyloidosis or those with increased heart wall thickness who had amyloid was suspected. We also aimed to further characterize the structural and functional changes associated with amyloid infiltration.BackgroundCardiac amyloidosis (CA) is a serious but increasingly treatable cause of heart failure. Diagnosis is challenging and frequently unclear at echocardiography, which remains the most often used imaging tool.MethodsWe studied 1,187 consecutive patients evaluated at 3 referral centers for CA and analyzed morphological, functional, and strain-derived echocardiogram parameters with the aim of developing a score-based diagnostic algorithm. Cardiac amyloid burden was quantified by using extracellular volume measurements at cardiac magnetic resonance.ResultsA total of 332 patients were diagnosed with AL amyloidosis and 339 patients with transthyretin CA. Concentric remodeling and strain-derived parameters displayed the best diagnostic performance. A multivariable logistic regression model incorporating relative wall thickness, E wave/e′ wave ratio, longitudinal strain, and tricuspid annular plane systolic excursion had the greatest diagnostic performance in AL amyloidosis (area under the curve: 0.90; 95% confidence interval: 0.87 to 0.92), whereas the addition of septal apical–to–base ratio yielded the best diagnostic accuracy in the increased heart wall thickness group (area under the curve: 0.80; 95% confidence interval: 0.85 to 0.90).ConclusionsSpecific functional and structural parameters characterize different burdens of CA deposition with different diagnostic performances and enable the definition of 2 scores that are sensitive and specific tools with which diagnose or exclude CA.     

Aortic remodelling following the treatment and regression of hypertensive left ventricular hypertrophy: a cardiovascular magnetic resonance study

Abstract

Background: Increased arterial stiffness independently predicts adverse prognosis. While different antihypertensive strategies produce different magnitudes of left ventricular hypertrophy (LVH) regression, there are no comparative data on how these strategies affect arterial stiffness. The aim was to determine the longitudinal change in aortic stiffness following the treatment of essential hypertension with two mechanistically different antihypertensive treatment strategies. Methods and results: Forty-two patients with essential hypertension and CMR confirmed with LVH were randomly assigned to antihypertensive regimes for 6 months. Treatment strategies were designed either to inhibit the renin–angiotensin–aldosterone system (RAAS) and the sympathetic nervous system (SNS) (valsartan and moxonidine, group VM) or to have neutral effect on these systems (bendroflumethiazide and amlodipine, group BA). Both treatment groups underwent identical baseline and a 6-month follow-up CMR and were compared with a healthy age-matched control group. Baseline aortic distensibility (AD) was lower in both hypertensive groups compared with controls (2.8?×?10^?3?mmHg^?1 in group VM (p?=?0.001) and 3.3?×?10^?3?mmHg^?1 group BA (p?=?0.039) compared with 4.5?×?10^?3?mmHg^?1 in the control group). AD increased after antihypertensive therapy (VM: 2.8?×?10^?3?mmHg^?1–4.2?×?10^?3?mmHg^?1 (p?=?0.001); BA 3.3?×?10^?3?mmHg^?1–4.6?×?10^?3?mmHg^?1 (p?<?0.01)). In both treatment groups AD returned to a level comparable with the normal control group (p?=?0.81) after 6 months. Conclusions: In patients with essential hypertension and LVH, AD was lower than in matched normal controls. Despite the opposing pharmacological mechanisms utilised across the treatment groups, the improvement in AD was similar, suggesting that blood pressure reduction per se may be more important than RAAS and SNS inhibition for the improvement of aortic remodelling.     

Serum levels of NT-proBNP as surrogate for cardiac amyloid burden: new evidence from gadolinium-enhanced cardiac magnetic resonance imaging in patients with amyloidosis

Background.?The prognostic value of NT-proBNP has been recognized in patients with amyloidosis complicated by cardiac involvement. We aimed to use contrast enhanced cardiac magnetic resonance imaging (CMR) to identify functional and structural alterations related to levels of NT-proBNP better to understand the mechanisms of its release in cardiac amyloidosis.

Methods and Results.?CMR was performed on a 1.5-T scanner in 34 patients with biopsy proven amyloid light chain (AL; n?=?27) or hereditary transthyretin related (TTR; n?=?7) amyloidosis. NT-proBNP was higher in patients with (n?=?25) compared to patients without cardiac involvement (n?=?9) (2931 (IQR: 972–8629; min-max: 25–27,277) pg/ml vs. 177 (IQR: 71–1431; min-max: 22–7935) pg/ml, p?=?0.008). ROC analysis identified a NT-proBNP of <2426.5?pg/ml as optimal discriminator for event free survival (682?±?65 days). NT-proBNP did not correlate with LV- ejection fraction, end-diastolic and end-systolic volumes or stroke volume. There was a moderate correlation between NT-proBNP and LV-mass (R?=?0.52, p?=?0.003) and extent of late gadolinium enhancement (LGE; R?=?0.41, p?=?0.04).

Conclusions.?This study confirms the prognostic value of NT-proBNP in patients with AL and TTR amyloidosis and provides the novel finding that NT-proBNP correlates with surrogates of myocardial amyloid burden such as LV-mass and LGE, supporting the concept of NT-proBNP as a biomarker reflecting the severity of cardiac amyloid infiltration.