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of patients with HFpEF&#44; if the aetiological study is performed correctly&#44; the final diagnosis would be ATTR&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> Given that HHD and cardiac transthyretin amyloidosis &#40;ATTR&#41; are 2 common aetiologies in HFpEF&#44; and that many final diagnoses of ATTR are misdiagnoses of HHD&#44; it is appropriate to investigate whether they have differential characteristics or whether there is a different prognostic evolution between the two causes of HFpEF&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Thus&#44; the objective of this study was to describe the clinical&#44; electrocardiographic and echocardiographic characteristics of patients with ATTR and HHD&#46; We also studied the prognostic evolution of both heart diseases in terms of all-cause mortality&#44; hospital admissions due to heart failure&#44; the need for a pacemaker &#40;PPM&#41;&#44; and time until the first episode of atrial fibrillation &#40;AF&#41;&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Material and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Type of study</span><p id="par0020" class="elsevierStylePara elsevierViewall">An observational&#44; retrospective&#44; longitudinal and analytical study was conducted at the Reina Sofia University Hospital of Cordoba &#40;HURS&#41; from January 2016 to December 2021&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Patients</span><p id="par0025" class="elsevierStylePara elsevierViewall">The study included patients from the outpatients clinic as well as patients discharged after hospital admission for heart failure &#40;HF&#41;&#46; The diagnosis of ATTR or HHD was made according to the following criteria&#58;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">&#8226;</span><p id="par0030" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Patients diagnosed with ATTR</span><a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a>&#58; those with Perugrini grade 2 or 3 cardiac uptake in the <span class="elsevierStyleSup">99m</span>Tc-Diphosphonates &#40;DPD scintigraphy&#41;&#44; and in whom there was no evidence of monoclonal gammopathy &#40;absence of paraprotein in blood&#44; kappa and lambda light chains in serum and urine immunofixation&#44; and a normal kappa&#47;lambda ratio&#41;&#46; Genetic studies were carried out on all patients&#46; Patients with a final diagnosis of cardiac amyloidosis other than ATTR were excluded from the analysis&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">&#8226;</span><p id="par0035" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Patients with a diagnosis of HHD&#58;</span> patients with long-standing HF&#44; LVH and HT&#44; whose hypertrophy could not be justified by any other cause&#46;</p></li></ul></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Clinical and laboratory variables</span><p id="par0040" class="elsevierStylePara elsevierViewall">Data related to the final aetiological diagnosis &#40;HHD&#47;ATTR&#41;&#44; age at diagnosis &#40;years&#41;&#44; sex&#44; creatinine level &#40;mg&#47;dl&#41;&#44; hs-Tnl level &#40;ng&#47;l&#41; and NT-proBNP level &#40;pg&#47;mL&#41; at diagnosis were analysed&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Electrocardiographic variables</span><p id="par0045" class="elsevierStylePara elsevierViewall">Baseline electrocardiogram data were analysed for&#58; rhythm at diagnosis &#40;sinus rhythm or atrial fibrillation&#41;&#44; presence of a pseudoinfarction pattern&#44;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> low voltage pattern&#44;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> AV block of any type&#44; complete left bundle branch block&#44; complete right bundle branch block&#44; or the need for cardiac pacing by a PPM at the time of diagnosis&#46; The presence of conduction disturbances was defined according to the American Heart Association diagnostic criteria for standardisation and interpretation of the surface electrocardiogram&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Echocardiographic variables</span><p id="par0050" class="elsevierStylePara elsevierViewall">Data from the transthoracic echocardiogram &#40;TTE&#41; baseline evaluation&#44; at the time of diagnosis&#44; were analysed&#46; Variables of interest were&#58; LVEF &#40;&#37;&#41;&#44; determined by Teicholz or Simpson method&#59; interventricular septum &#40;IVS&#41; thickness &#40;mm&#41;&#44; dilated atrium &#40;Yes&#47;No&#41;&#44; mean E&#47;e&#39; value &#40;absolute number&#41;&#44; presence of pericardial effusion &#40;Yes&#47;No&#41; and speckle pattern &#40;Yes&#47;No&#41;&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Outcome variables</span><p id="par0055" class="elsevierStylePara elsevierViewall">Prognosis was evaluated by the development of all-cause mortality&#44; hospital admissions for heart failure&#44; need for a PPM&#44; and time until the first episode of atrial fibrillation&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Statistical study</span><p id="par0060" class="elsevierStylePara elsevierViewall">A descriptive study of the qualitative variables was carried out&#44; calculating absolute and relative frequencies&#46; The descriptive study of the quantitative variables calculated the arithmetic mean and standard deviation when these variables followed a normal distribution&#44; using the Shapiro-Wilk test&#46; When the quantitative variables did not follow a normal distribution&#44; the median and interquartile range &#40;IQR&#41; were calculated&#46; The 95&#37; confidence interval was estimated for safety&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">A bivariate analysis compared the data collected for the variables between the ATTR and HHD groups&#44; using appropriate parametric and non-parametric tests&#44; depending on whether the data were normally distributed or not&#58;<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">&#8226;</span><p id="par0070" class="elsevierStylePara elsevierViewall">To compare quantitative variables&#44; a Student&#39;s t-test for independent data or the Mann&#8211;Whitney U-test was used&#44; as appropriate&#46;</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">&#8226;</span><p id="par0075" class="elsevierStylePara elsevierViewall">To compare nominal qualitative variables&#44; the Chi-square statistic or Fisher&#39;s exact test was used as appropriate&#46;</p></li></ul></p><p id="par0080" class="elsevierStylePara elsevierViewall">Event-free survival &#40;time to death from any cause&#44; first admission for HF&#44; need for a PPM and development of AF&#41; was analysed using the Kaplan-Meier method and the two groups were compared using the log-rank test&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">All contrasts were bilateral and those where p was less than 0&#46;05 were considered significant&#46; Data were collected&#44; processed and analysed with SPSS&#174; statistical software version 26&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Ethical considerations</span><p id="par0090" class="elsevierStylePara elsevierViewall">The study was approved by the Ethics Committee of the HURS&#44; via the Andalusian Biomedical Research Ethics Portal &#40;Code TFG-JLMM-2020&#44; dated 09&#47;12&#47;2020&#41;&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">This project has followed the standards of good clinical practice and has been conducted in accordance with the principles set out in the Declaration of Helsinki&#46; The data has been anonymised&#44; respecting the confidentiality of the same&#44; in accordance with Regulation &#40;EU&#41; 2016&#47;679 of the European Parliament and Organic Law 3&#47;2018 of 5 December on the Protection of Personal Data and guarantee of digital rights&#46;</p></span></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Results</span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Clinical features</span><p id="par0100" class="elsevierStylePara elsevierViewall">The study cohort included 72 patients with a previous diagnosis of HHD who had undergone a DPD scintigraphy study to screen for ATTR&#44; and a light chain study to rule out amyloidosis &#40;AL&#41;&#46; Of these&#44; 33 patients were finally diagnosed with ATTR &#40;46&#37;&#41; and 39 patients had a final diagnosis of HHD &#40;54&#37;&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; The genetic study was positive in only 6 patients &#40;18&#37;&#41; giving the diagnosis as hereditary ATTR &#40;hATTR&#41;&#44; and negative in 27 patients &#40;82&#37;&#41; giving the diagnosis as wild-type ATTR &#40;ATTRwt&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0105" class="elsevierStylePara elsevierViewall">No differences were found between the median age at diagnosis of the two groups &#40;p&#8239;&#61;&#8239;0&#46;058&#41;&#46; The median age at diagnosis for the group diagnosed with ATTR was 80 years &#40;IQR&#58; 72&#46;5&#8722;85&#46;5&#41; and for the group diagnosed with HHD it was 75 years &#40;IQR&#58; 68&#46;5&#8722;80&#46;5&#41;&#46; The sex variable showed a higher frequency of males in the ATTR diagnosed group compared to the HHD diagnosed group &#40;69&#46;7 vs&#46; 38&#46;5&#37;&#59; p&#8239;&#61;&#8239;0&#46;01&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0110" class="elsevierStylePara elsevierViewall">The presence of AF &#40;pre-study or developed during follow-up&#41; was 78&#46;8&#37; in the ATTR group and 59&#37; in the HHD group&#44; with no statistically significant differences &#40;p&#8239;&#61;&#8239;0&#46;072&#41;&#46; As for the need for a PPM&#44; it was higher in ATTR patients &#40;27&#46;3&#37;&#41; compared to HHD patients &#40;7&#46;7&#37;&#41;&#59; p&#8239;&#61;&#8239;0&#46;026 &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Analytical results</span><p id="par0115" class="elsevierStylePara elsevierViewall">With respect to blood test variables&#44; statistically significant differences were detected between hs-Tnl and NT-proBNP levels in both groups&#44; with higher levels in the ATTR group compared to patients diagnosed with HHD &#40;double the hs-Tnl value&#44; and up to four times higher in NT-proBNP value&#41;&#46; However&#44; there were no differences in creatinine levels in patients diagnosed with ATTR compared to patients with HHD &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Electrocardiographic parameters</span><p id="par0120" class="elsevierStylePara elsevierViewall">Some differences were found in the electrocardiographic parameters&#46; The ATTR group showed a higher frequency of <span class="elsevierStyleItalic">pseudoinfarction</span> pattern &#40;54&#46;5 vs&#46; 25&#46;6&#37;&#59; p&#8239;&#61;&#8239;0&#46;009&#41;&#44; AV block of any type &#40;48&#46;4 vs&#46; 15&#46;4&#37;&#59; p&#8239;&#61;&#8239;0&#46;005&#41;&#44; conduction disturbances in general &#40;63&#46;6 vs&#46; 31&#37;&#59; p&#8239;&#61;&#8239;0&#46;007&#41; and specifically LBBB &#40;21&#46;1 vs&#46; 2&#46;6&#37;&#59; p&#8239;&#61;&#8239;0&#46;024&#41;&#46; In contrast&#44; no differences were found between the two groups regarding the presence of low voltage pattern &#40;39 vs&#46; 30&#46;7&#37;&#59; p&#8239;&#61;&#8239;0&#46;379&#41; or for the presence of RBBB &#40;6&#46;1 vs&#46; 7&#46;7&#37;&#59; p&#8239;&#61;&#8239;0&#46;799&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Echocardiographic data</span><p id="par0125" class="elsevierStylePara elsevierViewall">Differences were also found in the TTE variables&#58; patients with ATTR had greater IVS thickness &#40;median 16&#8239;mm &#91;IQR of 14&#8722;19&#8239;mm&#93; vs&#46; median 14&#8239;mm &#91;IQR of 12&#8722;16&#8239;mm&#93;&#44; p&#8239;&#61;&#8239;0&#46;001&#41;&#44; higher mean E&#47;e&#39; value &#40;mean 14&#46;6&#8239;&#177;&#8239;5&#46;4 vs&#46; mean of 10&#46;2&#8239;&#177;&#8239;4&#46;3&#59; p&#8239;&#61;&#8239;0&#46;007&#41; and higher presence of myocardial granular speckling &#40;42&#46;4 vs&#46; 5&#46;1&#37;&#59; p&#8239;&#61;&#8239;0&#46;001&#41;&#46; On the other hand&#44; the presence of preserved LVEF was lower in the ATTR group &#40;48&#46;5&#37;&#41; than in the HHD group &#40;97&#46;4&#37;&#41;&#59; p&#8239;&#61;&#8239;0&#46;001&#46; No differences were found in the presence of dilated atrium &#40;75&#46;8 vs&#46; 62&#46;9&#37;&#59; p&#8239;&#61;&#8239;0&#46;285&#41; or pericardial effusion &#40;9&#46;1 vs&#46; 15&#46;4&#37;&#59; p&#8239;&#61;&#8239;0&#46;489&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">Prognosis&#58; mortality&#44; readmission for heart failure&#44; need for pacemaker and development of atrial fibrillation&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">In the prognostic study&#44; with a mean follow-up of 49&#46;9&#8239;&#177;&#8239;42&#46;2 months of patients with both nosological entities&#44; patients with ATTR had a higher need for a PPM at follow-up &#40;log-rank&#8239;&#61;&#8239;0&#46;034&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46; However&#44; no statistically significant differences were found for all-cause mortality &#40;log-rank&#8239;&#61;&#8239;0&#46;06&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#44; time to development of AF &#40;log-rank&#8239;&#61;&#8239;0&#46;720&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>&#41; or admission for heart failure &#40;log-rank&#8239;&#61;&#8239;0&#46;650&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0025">Fig&#46; 5</a>&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia><elsevierMultimedia ident="fig0025"></elsevierMultimedia></span></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Discussion</span><p id="par0140" class="elsevierStylePara elsevierViewall">ATTR is a disease that is clearly underdiagnosed&#46; It frequently remains hidden under other diagnostic entities &#40;such as the aforementioned HHD&#44; hypertrophic cardiomyopathy&#44; ischaemic heart disease or aortic stenosis&#44; among others&#41;&#44; and only when sufficient clinical suspicion is established are the appropriate complementary tests requested for the diagnosis of this entity&#46; However&#44; the implementation of non-invasive diagnosis of ATTR&#44; using a combination of DPD scintigraphy and an analytical study of light chains in urine&#44; has led to an increase in the number of diagnosed cases of ATTR in recent years&#44; in contrast to the data from years prior to this study protocol&#44; when a histological study was the gold standard&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> Despite this progress&#44; there is evidence that this entity is still seriously under-diagnosed&#44; supporting the need to accurately characterise it&#46; For example&#44; some studies report that up to 70&#37; of patients obtained a definitive diagnosis of ATTR after having been assessed by 3 or more different specialists&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> A phenomenon to be taken into account as a result of the new diagnostic algorithm for this disease is the possibility of a false-negative DPD scintigraphy result in patients with ATTR&#44; especially in hATTR associated with the Phe84Leu and Ser97Tyr mutation&#46; Therefore&#44; the prevalence in our population could be higher than that observed because no patient diagnosed with HHD underwent additional screening for CA&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> Following along these lines&#44; as already mentioned this algorithm avoids a histological study&#44; and therefore could overlook the possibility of patients with 2 types of simultaneous cardiac amyloidosis&#44; as has been reported in the literature&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p><p id="par0145" class="elsevierStylePara elsevierViewall">One of the main differential diagnoses of ATTR is HHD&#44; as both can present as HFpEF&#58; they increase in prevalence with age&#44; share symptoms &#40;exertional dyspnoea&#44; lower limb oedema&#44; weakness&#44; tachycardia&#44; etc&#46;&#41; and have a high prevalence of AF&#46; On the other hand&#44; these entities present certain clinical differences&#58; on a symptomatic level&#44; the presence of chest pain is more frequent in HHD&#44; while extracardiac manifestations such as carpal tunnel syndrome&#44; peripheral neuropathy&#44; lumbar spinal stenosis or even ocular disorders &#40;glaucoma&#44; myodesopsias&#44; scalloped pupil&#41; would be more suggestive of ATTR&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> Other differences would be gender distribution &#40;ATTR is more prevalent in men while HHD is more prevalent in women&#41; and the need for a PPM &#40;more common in ATTR than in HHD&#41;&#44; as in the findings found in our series&#46; The higher prevalence of ATTR in men than in women found in our cohort coincides with the evidence available to date on the prevalence of this disease&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> Some authors suggest that this may be due to the protective effect of oestrogens in women&#44; based on a study that showed that ATTR in women appears mainly after the menopause&#46; Also&#44; this disease may be underdiagnosed in females due to a more latent clinical presentation&#44; as a retrospective study found that post-mortem diagnosis of ATTR was higher in females than in males &#40;31 vs&#46; 9&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> Although no significant differences regarding age were found in our study&#44; the HHD group tended to be younger than the ATTR group&#46; The ATTR group being older could also have to do with the delay in the diagnostic process that has traditionally taken place in this disease&#46; On the other hand&#44; given that high blood pressure &#40;HBP&#41; usually begins at a much younger age&#44; in principle it seems logical that patients with HHD are younger than those diagnosed with ATTR&#44; and the reduced difference between the two groups could be due to the fact that therapeutic advances in the control of HBP allow a delay in the progression to heart disease&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> Although we do not have age-adjusted prognostic results for the events studied&#44; these would be interesting&#44; when we consider the older age of patients with ATTR and the mean follow-up of 4 years&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">Our study also found a similar prevalence of AF in both entities&#46; This result was to be expected given that the pathophysiological mechanism that triggers this arrhythmia in both populations is fundamentally the compensatory left atrial enlargement due to chronic elevated left atrial pressure&#44;<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">15&#44;16</span></a> although in our study we found no differences between the two groups in terms of the prevalence of left atrial enlargement&#46; We also found no differences in the time required to develop atrial fibrillation in the evolution of both nosological entities &#40;<a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>&#41;&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">On the other hand&#44; both entities often present as HFpEF&#44; an increasingly prevalent clinical syndrome&#44; accounting for up to 50&#37; of all cases of HF in some series&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> HFpEF is a catch-all for diseases of very diverse origins such as HHD&#44; ATTR&#44; sarcoidosis&#44; other infiltrative cardiomyopathies&#44; hypertrophic cardiomyopathy&#44; etc&#46;&#44; with one aspect in common - the increase in the degree of hypertrophic cardiomyopathy&#46; A multifactorial origin has been postulated for this increase&#44; where the different cardiovascular risk factors &#40;HBP&#44; diabetes&#44; ageing&#44; obesity&#44; chronic kidney disease&#44; etc&#46;&#44;&#41; contribute towards generating a state of low-grade systemic inflammation and neurohumoral activation &#40;mainly through the renin-angiotensin-aldosterone axis&#41;&#46; This would trigger ventricular hypertrophy as a compensatory mechanism in the short term&#44; but would subsequently become disproportionate&#44; ultimately triggering the clinical syndrome of heart failure&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a></p><p id="par0160" class="elsevierStylePara elsevierViewall">In terms of analytical parameters&#44; it seems logical that patients with ATTR have higher levels of hs-Tnl and NT-ProBNP than patients with HHD&#44; as the pathophysiological mechanism leading to this disease is infiltrative cardiomyopathies&#46; This initially causes diastolic dysfunction&#44; resulting in increased left ventricular filling pressure and parietal stress&#44; which disproportionately increases NT-ProBNP values&#46; Additionally&#44; amyloid deposits cause cardiomyocyte necrosis and fibrosis&#44; and ischaemia in relation to intramural vessel obstruction&#44; which may lead to persistent elevation of hs-Tnl&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> In our series&#44; creatinine levels were similar and within normal ranges&#46; In both ATTR and HHD&#44; the deterioration of renal function is multifactorial&#44; especially affected by the prolonged activation of the renin-angiotensin-aldosterone axis&#46; While the activation in ATTR may be caused by amyloid infiltration of glomeruli&#44; arterioles and renal arteries&#44;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> in HHD the system is activated by decreased renal perfusion due to congestive HF or&#44; more commonly&#44; by prerenal vasoconstriction as a compensatory mechanism against HBP&#44; long before the onset of congestive HF&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a></p><p id="par0165" class="elsevierStylePara elsevierViewall">Regarding the surface electrocardiogram findings&#44; the higher frequency of any type of atrioventricular and intraventricular conduction disturbances seen in ATTR could be explained by amyloid deposition on the conduction tissue&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> Furthermore&#44; in vitro studies show that numerous transthyretin variants are cytotoxic to human cardiomyocytes in a concentration-dependent manner&#44; causing oxidative stress&#44; apoptosis and altered intracellular calcium signalling&#44; the latter resulting in action potential prolongation&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> Early sympathetic nerve fibre loss has been evidenced in ATTR&#44; which may be due to amyloid deposition in the interstitial space&#44; promoting interstitial remodeling&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> Although this causal relationship has not yet been demonstrated&#44; the fact that transthyretin is neurotoxic both in vitro and in vivo supports this hypothesis&#44; and could also explain the conduction disturbances&#46;<a class="elsevierStyleCrossRefs" href="#bib0120"><span class="elsevierStyleSup">24&#44;25</span></a> Due to the prevalence of atrioventricular and intraventricular conduction disturbances in ATTR&#44; patients will more likely end up needing a PPM&#44; as identified in our series&#46; In fact&#44; a study by Pericet et al&#46; showed that patients diagnosed with CA who presented a complete bundle branch block on ECG were more likely to require a PPM at follow-up&#44; especially if the diagnosis is ATTR&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> In our series&#44; there was an ATTR trend towards a greater increase in the need for a PPM in a shorter time after symptom onset &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46; Also&#44; our series shows a higher percentage of pseudoinfarction pattern in ATTR&#44; which coincides with the evidence already available where up to 70&#37; of patients with CA present this alteration in the ECG&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a> In both diseases this pattern could be due to two aetiopathogenic mechanisms&#58; LVH &#40;more prominent in ATTR than in HHD&#41; and fibrosis&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a> The presence of low ECG voltages&#44; although classically described in amyloidosis&#44; was only seen in one third of patients in our series&#44; and without statistically significant differences with respect to HHD&#46; In ATTR&#44; the presence of low voltages could be due to the fact that the greater degree of hypertrophy caused in this infiltrative disease is not due to an increase in muscle mass&#44; but rather due to a greater deposit of amyloid material in the interstitial space&#46; This would not generate electrical voltage&#44; hence the electrocardiographic expression of low voltage for the greater degree of hypertrophy visualised in the imaging test&#46; Fibrosis could also explain this finding in HHD&#46; It is therefore understandable that in our series a similar presence of low voltages was found in both diseases&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a></p><p id="par0170" class="elsevierStylePara elsevierViewall">The TTE of ATTR shows higher ventricular filling pressures &#40;assessed by the E&#47;e&#39; ratio&#41;&#46; These are to be expected as already mentioned&#44; due to the mechanism of infiltrative cardiomyopathies&#44; which in turn explains the higher LVH<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a>&#59; this rise in intraventricular pressure results in a retrograde increase in atrial cavity pressures&#44; with the consequent dilatation of this cavity&#44; which leads to a greater fall in AF&#46; As a result of this infiltration caused by amyloid in the myocardial tissue&#44; a granular speckling of the myocardium may occur&#44; which occurs much more frequently in ATTR than in HHD and this would be the most characteristic echocardiographic manifestation of infiltrative cardiomyopathy&#46; In contrast&#44; in our population there are no differences of pericardial effusion presence&#44; and this differs from previous studies&#44; which have shown a high prevalence of pericardial effusion in CA&#44;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a> whereas in HHD it occurs sporadically&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">With regard to prognosis&#44; it should be borne in mind that both cardiopathies progress in advanced stages to HFrEF&#46; In the pathogenesis of HFrEF&#44; as in HFpEF&#44; neurohumoral activation plays a relevant role&#44; but the presence of cardiomyocyte damage is undoubtedly essential&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> Given that the main cause of death in CA is cardiovascular events&#44;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a> it seems logical that our study shows a trend towards higher mortality in a shorter time for patients with ATTR&#44; since&#44; as already mentioned&#44; compared to HHD&#44; ATTR progresses more frequently towards HFrEF&#44; is more arrhythmogenic&#44; elevates cardiac markers more frequently and modifies the cardiac architecture more&#46; Similarly&#44; the underdiagnosis of ATTR that we have been pointing out would adversely affect the prognosis of patients suffering from it&#44; since&#44; although therapy in both entities is aimed at improving quality of life and avoiding hospitalisation for heart failure&#44; in the case of HHD there are many highly effective drugs for the HBP and thus slow progression&#44; while in ATTR&#44; therapeutic advances to date have been limited&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">Finally&#44; in our series&#44; the time to hospitalisation for HF from the onset of symptoms is similar in both diseases&#46; In our series&#44; the time to hospitalisation was analysed taking into account only HF as the reason for admission&#44; but it is true that many of these patients are also admitted for other reasons that may be more or less attributable to their disease&#46; It is known that only 20&#37; of patients with HFpEF who are hospitalised are admitted for HF&#44; with non-cardiovascular causes being more common due to concomitant comorbidities&#46; This fits perfectly with the type of patient in our cohort&#44; whose median age is 76 years&#44; and who has multiple comorbidities&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a></p><p id="par0185" class="elsevierStylePara elsevierViewall">The main limitation of this study is its small sample size&#44; as it is a single-centre study&#44; and it has not been possible to recruit a larger number of patients so far&#46; Therefore&#44; it would be necessary to carry out future studies with a larger cohort and a longer follow-up period to clarify the reality of the findings of the present study&#46;</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Conclusions</span><p id="par0190" class="elsevierStylePara elsevierViewall">Patients with ATTR showed significant clinical&#44; electrocardiographic and echocardiographic differences compared to patients with HHD&#46; These differences may serve to guide the diagnostic suspicion towards one or the other disease in daily clinical practice&#46; We found that patients with ATTR had a greater need for a PPM at follow-up&#44; but no differences in mortality&#44; hospital admissions for heart failure or development of atrial fibrillation&#44; compared to patients with HHD&#46;</p><p id="par0195" class="elsevierStylePara elsevierViewall">This study has been approved by the Cordoba Research Ethics Committee&#58; TFG-JLMM-2020&#46;</p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Funding</span><p id="par0200" class="elsevierStylePara elsevierViewall">The authors declare that they have not received any funding for this work&#46;</p></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0155">Conflict of interest</span><p id="par0205" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflict of interest&#46;</p></span></span>"
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    "fechaRecibido" => "2023-05-15"
    "fechaAceptado" => "2023-10-10"
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            0 => "Cardiac amyloidosis"
            1 => "Hypertensive heart disease"
            2 => "Heart failure"
            3 => "Pacemaker"
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            0 => "Amiloidosis card&#237;aca por transtirretina"
            1 => "Cardiopat&#237;a hipertensiva"
            2 => "Insuficiencia card&#237;aca"
            3 => "Marcapasos"
            4 => "Pron&#243;stico"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">A significant percentage of patients eventually diagnosed with cardiac transthyretin amyloidosis &#40;TTRA&#41; was previously diagnosed with hypertensive heart disease &#40;HHD&#41;&#44; since both conditions usually present with heart failure &#40;HF&#41; with preserved ejection fraction &#40;HFpEF&#41; and ventricular hypertrophy&#46; Our objectives were to evaluate the clinical&#44; electrocardiographic and echocardiographic differences&#44; and to analyse whether there exists a differential prognosis between these two nosological entities&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Materials y methods</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">We retrospectively included all patients with HHD for whom a cardiac scintigraphy with <span class="elsevierStyleSup">99m</span>Tc-Diphosphonate &#40;GDPD&#41; and a free light chains test in blood and urine were ordered for ATTR screening in our centre&#44; in the period between 2016 and 2021&#46; Those diagnosed with other types of amyloidosis were excluded from the analysis&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">A total of 72 patients were analyzed&#58; 33 were finally diagnosed with TTRA and 39 with CHTA&#46; Patients with TTRA had higher levels of ultrasensitive troponin I &#40;TnI-US&#41; and N-terminal brain natriuretic propeptide &#40;NT-ProBNP&#41;&#59; in electrocardiography &#40;ECG&#41; they presented a <span class="elsevierStyleItalic">pseudo-infarction</span> pattern more frequently as well as conduction disturbances&#59; in echocardiography &#40;TTE&#41; they presented a higher degree of ventricular hypertrophy&#44; left ventricular dysfunction and worse diastolic function parameters&#44; with elevated filling pressures&#46; In the 4-year follow-up&#44; the ATTR group showed greater need for pacemaker &#40;PCM&#41;&#44; with no evidence regarding mortality&#44; development of atrial fibrillation &#40;AF&#41;&#44; or more admissions for herart failure &#40;HF&#41;&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">In our series&#44; patients with TTRA showed clinical&#44; electrocardiographic and echocardiographic differences compared to patients with HHD&#44; with increased risk of need for PCM&#46;</p></span>"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introducci&#243;n</span><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Un porcentaje importante de pacientes finalmente diagnosticados de amiloidosis card&#237;aca por transtirretina &#40;ATTR&#41; fueron previamente diagnosticados de cardiopat&#237;a hipertensiva &#40;CHTA&#41;&#44; ya que ambas enfermedades suelen cursar con insuficiencia card&#237;aca &#40;IC&#41; con fracci&#243;n de eyecci&#243;n preservada &#40;ICFEp&#41; e hipertrofia ventricular&#46; Nuestros objetivos fueron evaluar las diferencias cl&#237;nicas&#44; electrocardiogr&#225;ficas y ecocardiogr&#225;ficas&#44; y analizar si existe un pron&#243;stico diferencial entre ambas entidades nosol&#243;gicas&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Material y m&#233;todos</span><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Se incluyeron retrospectivamente todos los pacientes con CHTA a los que se solicit&#243; una gammagraf&#237;a card&#237;aca con <span class="elsevierStyleSup">99m</span>Tc-Difosfonatos &#40;GDPD&#41; y estudio de cadenas ligeras en sangre y orina para despistaje de ATTR en nuestro centro&#44; en el periodo 2016&#8722;2021&#46; Para el an&#225;lisis&#44; se excluyeron aquellos diagnosticados de otros tipos de amiloidosis&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Se analizaron un total de 72 pacientes&#58; 33 fueron diagnosticados de ATTR y 39 de CHTA&#44; finalmente&#46; Los pacientes con ATTR presentaron mayores niveles de troponina I ultrasensible &#40;TnI-US&#41; y pro-p&#233;ptido natriur&#233;tico cerebral N-terminal &#40;NT-ProBNP&#41;&#59; en electrocardiograma &#40;ECG&#41; presentaron m&#225;s frecuentemente patr&#243;n de <span class="elsevierStyleItalic">pseudoinfarto</span> y alteraciones de la conducci&#243;n&#59; en ecocardiograma &#40;ETT&#41; presentaron mayor grado de hipertrofia ventricular&#44; disfunci&#243;n ventricular izquierda y par&#225;metros de peor funci&#243;n diast&#243;lica&#44; con presiones de llenado m&#225;s elevadas&#46; En el seguimiento a 4 a&#241;os&#44; el grupo de ATTR mostr&#243; mayor necesidad de marcapasos &#40;MCP&#41;&#44; sin evidenciarse evidencias en cuanto a mortalidad&#44; desarrollo de fibrilaci&#243;n auricular&#44; o m&#225;s ingresos por IC&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">En nuestra serie&#44; los pacientes con ATTR presentaron diferencias cl&#237;nicas&#44; electrocardiogr&#225;ficas y ecocardiogr&#225;ficas respecto a aquellos con CHTA&#44; con mayor riesgo necesidad de marcapasos en el seguimiento&#46;</p></span>"
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            "titulo" => "Annex 1&#46; Working Group on Heart Failure of the Reina Sofia University Hospital of Cordoba"
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                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Total&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">ATTR-CMN&#8239;&#61;&#8239;33&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">HHDN&#8239;&#61;&#8239;39&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Value of p&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Age &#40;median&#44; IQR&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">76 &#40;69&#8722;83&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">80 &#40;72&#46;5&#8722;85&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">75 &#40;68&#46;5&#8722;80&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;058&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Male &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">38 &#40;52&#46;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">23 &#40;69&#46;7&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15 &#40;38&#46;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;010&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Analytical data</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Creatinine &#40;mg&#47;dl&#41; &#40;median&#44; IQR&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;00 &#40;0&#46;86&#8722;1&#46;74&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;12 &#40;0&#46;96&#8722;1&#46;82&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;95 &#40;0&#46;77&#8722;1&#46;64&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;767&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>hs-Tnl &#40;ng&#47;l&#41; &#40;median&#44; IQR&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">45&#46;5 &#40;12&#46;5&#8722;96&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">85 &#40;37&#8722;810&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">30 &#40;10&#8722;53&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>NT-ProBNP pg&#47;mL &#40;median&#44; IQR&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4477&#46;5 &#40;2684&#46;5&#8722;9590&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8770 &#40;6443&#8722;16246&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2756 &#40;1398&#8722;4477&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;010&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Electrocardiographic data</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Pseudo-infarction pattern&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">28 &#40;38&#46;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">18 &#40;54&#46;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10 &#40;25&#46;6&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;009&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Low voltage&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">25 &#40;34&#46;7&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13 &#40;39&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12 &#40;30&#46;7&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;379&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>AV block&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">22 &#40;30&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">16 &#40;48&#46;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6 &#40;15&#46;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;005&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>LBBB&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5 &#40;7&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;6&#46;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3 &#40;7&#46;7&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;799&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>RBBB&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8 &#40;11&#46;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7 &#40;21&#46;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;2&#46;6&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;024&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Any disturbance conduction&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">33 &#40;46&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">21 &#40;63&#46;6&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12 &#40;31&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;007&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Total AF&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">49 &#40;68&#46;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">26 &#40;78&#46;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">23 &#40;59&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;072&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>E&#47;e&#39; &#40;mean&#44; SD&#41;&nbsp;\t\t\t\t\t\t\n
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          "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Clinical&#44; analytical&#44; electrocardiographic and echocardiographic differential characteristics between ATTR and HHD&#46;</p>"
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                      "titulo" => "Research priorities for heart failure with preserved ejection fraction&#58; national heart&#44; lung&#44; and blood institute working group summary"
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