Prevalence and significance of relative apical sparing in aortic stenosis: insights from an echo and cardiovascular magnetic resonance study of patients referred for surgical aortic valve replacement

Abecasis, João; Lopes, P; Santos, Rita Reis; Maltes, S; Guerreiro, S; Ferreira, António Miguel; Freitas, P; Ribeiras, Regina; Andrade, Maria João; Manso, Rita; Ramos, Sância; Gil, Víctor; Masci, Pier Giorgio; Cardim, Nuno

doi:10.1093/ehjci/jead032

Cited by 27 publications

(14 citation statements)

References 31 publications

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“…Echocardiography also demonstrates a longitudinal strain pattern in ATTR cardiomyopathy characterized by normal or near-normal longitudinal strain values in the apical LV segments and reduced strain values in the basal LV segments . These strain abnormalities have been observed in other diseases, such as aortic stenosis, and are not specific for ATTR …”

Section: Discussionmentioning

confidence: 90%

Cardiac Amyloidosis Due to Transthyretin Protein

Ruberg,

Maurer

2024

JAMA

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ImportanceSystemic amyloidosis from transthyretin (ATTR) protein is the most common type of amyloidosis that causes cardiomyopathy.ObservationsTransthyretin (TTR) protein transports thyroxine (thyroid hormone) and retinol (vitamin A) and is synthesized predominantly by the liver. When the TTR protein misfolds, it can form amyloid fibrils that deposit in the heart causing heart failure, heart conduction block, or arrhythmia such as atrial fibrillation. The biological processes by which amyloid fibrils form are incompletely understood but are associated with aging and, in some patients, affected by inherited variants in the TTR genetic sequence. ATTR amyloidosis results from misfolded TTR protein deposition. ATTR can occur in association with normal TTR genetic sequence (wild-type ATTR) or with abnormal TTR genetic sequence (variant ATTR). Wild-type ATTR primarily manifests as cardiomyopathy while ATTR due to a genetic variant manifests as cardiomyopathy and/or polyneuropathy. Approximately 50 000 to 150 000 people in the US have heart failure due to ATTR amyloidosis. Without treatment, heart failure due to ATTR amyloidosis is associated with a median survival of approximately 5 years. More than 130 different inherited genetic variants in TTR exist. The most common genetic variant is Val122Ile (pV142I), an allele with an origin in West African countries, that is present in 3.4% of African American individuals in the US or approximately 1.5 million persons. The diagnosis can be made using serum free light chain assay and immunofixation electrophoresis to exclude light chain amyloidosis combined with cardiac nuclear scintigraphy to detect radiotracer uptake in a pattern consistent with amyloidosis. Loop diuretics, such as furosemide, torsemide, and bumetanide, are the primary treatment for fluid overload and symptomatic relief of patients with ATTR heart failure. An ATTR-directed therapy that inhibited misfolding of the TTR protein (tafamidis, a protein stabilizer), compared with placebo, reduced mortality from 42.9% to 29.5%, reduced hospitalizations from 0.7/year to 0.48/year, and was most effective when administered early in disease course.Conclusions and RelevanceATTR amyloidosis causes cardiomyopathy in up to approximately 150 000 people in the US and tafamidis is the only currently approved therapy. Tafamidis slowed progression of ATTR amyloidosis and improved survival and prevented hospitalization, compared with placebo, in people with ATTR-associated cardiomyopathy.

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Section: Discussionmentioning

confidence: 90%

Cardiac Amyloidosis Due to Transthyretin Protein

Ruberg,

Maurer

2024

JAMA

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“…In another study the relative apical sparing criterion was present in much more (88%) patients with severe aortic valve stenosis before transcatheter aortic valve implantation (TAVI) and after TAVI it was found in only 77% of the patients 15 . The latter two studies 18,19 showed that the presence of relative apical sparing was associated with more severe aortic valve disease, left ventricular dysfunction and hypertrophy, which was in some or most cases reversible after aortic valve replacement.…”

Section: Discussionmentioning

confidence: 97%

“…The presence of relative apical sparing was also reported in patients with primary hyperoxaluria type 1, a hereditary cause of progressive nephrocalcinosis, that commonly leads to end‐stage renal failure due to relatively lower accumulation of oxalate crystals in the apex compared with the basal and mid segments 17 . The relative apical sparing criterion was present in 15.3% of patients with severe, symptomatic valvular aortic stenosis in whom CA was ruled out by histological examination, and proved to be mostly (in 91% of cases) reversible after aortic valve replacement surgery 18 . In another study the relative apical sparing criterion was present in much more (88%) patients with severe aortic valve stenosis before transcatheter aortic valve implantation (TAVI) and after TAVI it was found in only 77% of the patients 15 .…”

Section: Discussionmentioning

confidence: 99%

Novel electrocardiographic criteria may render possible the more accurate recognition of cardiac amyloidosis

Vereckei,

Katona,

Szénási

et al. 2024

ESC Heart Failure

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AimsThe early diagnosis of cardiac amyloidosis (CA) is paramount, since there are effective therapies that improve patient survival. The diagnostic accuracy of classical electrocardiographic (ECG) signs, such as low voltage, pseudoinfarct pattern, and conduction disturbances in the diagnosis of CA, is inferior to that of the echocardiographic myocardial deformation criteria; therefore, our aim was to find more accurate novel ECG criteria for this purpose.MethodsWe tested the diagnostic value of five novel ECG criteria, two of them devised by us, in 34 patients with confirmed CA (20 transthyretin amyloidosis and 14 AL amyloidosis) and 45 control patients with left ventricular hypertrophy on echocardiography due to hypertension, valvular aortic stenosis and hypertrophic cardiomyopathy. The following novel ECG criteria, that suggested CA, were tested: QRS amplitude in lead I < 0.55 mV (I < 0.55); QRS amplitude in lead aVR < 0.5 mV (aVR < 0.5); average QRS amplitude of leads I + aVR < 0.575 mV [(I + aVR) < 0.575]; average QRS amplitude of leads I + aVR/average QRS amplitude of leads V1–4 < 0.375 [(I + aVR)/(V1–4) < 0.375]; average QRS amplitude of leads I + aVR/longest intrinsicoid deflection in leads I,aVL,V1–6 < 0.0115 [(I + aVR)/I,aVL,V1–6ID < 0.0115].ResultsThe I < 0.55, aVR < 0.5, (I + aVR) < 0.575, (I + aVR)/(V1–4) < 0.375, (I + aVR)/I,aVL,V1–6ID < 0.0115 test accuracy (TA) were 81%, 84.8%, 82.3%, 84.8%, and 83.3%, respectively; the sensitivity (SE): 76.5%, 82.4%, 85.3%, 82.4%, and 76.9%; specificity (SP): 84.4%, 86.7%, 80%, 86.7%, and 87.5%; positive predictive values (PPV): 78.8%, 82.4%, 76.3%, 82.4%, and 80%; negative predictive values (NPV): 82.6%, 86.7%, 87.8%, 86.7%, and 85.4%; area under curve (AUC) values: 0.8922, 0.8794, 09016, 0.8824, and 0.8462 were respectively. These parameters of the novel ECG criteria were at least as good as those reported by other authors in the literature of the qualitative (TA: 67%, SE: 80%, SP: 34%, PPV: 75%, NPV: 42%, AUC: 0.57) and quantitative apical sparing (TA: 64–80%, SE: 66–81.3%, SP: 55–78.3%, PPV: 33–83.9%, NPV: 41–75%, AUC: 0.62–0.68) and left ventricular ejection fraction/global longitudinal strain >4.1 (TA: 77%, SE: 93%, SP: 38%, PPV: 79%, NPV: 69%, AUC: 0.65) echocardiographic criteria. Among the classical criteria, the low voltage in limb leads criterion was present most frequently (in 73.5%) in patients with CA, with slightly worse diagnostic value than the novel ECG criteria (TA: 78.5%, SE: 73.5%, SP: 82.2%, PPV: 75.8%, NPV: 80.4%).ConclusionsThe novel ECG criteria [mostly the aVR < 0.5, (I + aVR)/(V1–4) < 0.375] seem at least as reliable in the diagnosis of CA as the best echocardiographic myocardial deformation criteria and might be used either together with the echocardiographic criteria or as stand‐alone criteria to diagnose CA in the future.

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“…Proposed echocardiographic scores are time intensive and still fail to reach a sensitivity of more than 61% (for indication of further tests) and 46% (for diagnosis of CA). 9,10 Hence, we need more precise and cost-effective screening tools to preselect AS patients for further CA testing. Here, proteomic biomarkers may yield valuable additional information.…”

Section: Discussionmentioning

confidence: 99%

“…7,8 Apical sparing-a suggested marker for CAalso does not seem to be typical of CA in AS. 9 Suggested echocardiographic scores show subpar sensitivity despite elaborate diastolic characterization. 10 Therefore, the preselection of AS patients for further CA screening remains difficult.…”

Section: Introductionmentioning

confidence: 99%

Histological assessment of cardiac amyloidosis in patients undergoing transcatheter aortic valve replacement

Beuthner,

Elkenani,

Evert

et al. 2024

ESC Heart Failure

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AimsStudies have reported a strongly varying co‐prevalence of aortic stenosis (AS) and cardiac amyloidosis (CA). We sought to histologically determine the co‐prevalence of AS and CA in patients undergoing transcatheter aortic valve replacement (TAVR). Consequently, we aimed to derive an algorithm to identify cases in which to suspect the co‐prevalence of AS and CA.Methods and resultsIn this prospective, monocentric study, endomyocardial biopsies of 162 patients undergoing TAVR between January 2017 and March 2021 at the University Medical Centre Göttingen were analysed by one pathologist blinded to clinical data using haematoxylin–eosin staining, Elastica van Gieson staining, and Congo red staining of endomyocardial biopsies. CA was identified in only eight patients (4.9%). CA patients had significantly higher N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) levels (4356.20 vs. 1938.00 ng/L, P = 0.034), a lower voltage‐to‐mass ratio (0.73 vs. 1.46 × 10−2 mVm2/g, P = 0.022), and lower transaortic gradients (Pmean 17.5 vs. 38.0 mmHg, P = 0.004) than AS patients. Concomitant CA was associated with a higher prevalence of post‐procedural acute kidney injury (50.0% vs. 13.1%, P = 0.018) and sudden cardiac death [SCD; P (log‐rank test) = 0.017]. Following propensity score matching, 184 proteins were analysed to identify serum biomarkers of concomitant CA. CA patients expressed lower levels of chymotrypsin (P = 0.018) and carboxypeptidase 1 (P = 0.027). We propose an algorithm using commonly documented parameters—stroke volume index, ejection fraction, NT‐proBNP levels, posterior wall thickness, and QRS voltage‐to‐mass ratio—to screen for CA in AS patients, reaching a sensitivity of 66.6% with a specificity of 98.1%.ConclusionsThe co‐prevalence of AS and CA was lower than expected, at 4.9%. Despite excellent 1 year mortality, AS + CA patients died significantly more often from SCD. We propose a multimodal algorithm to facilitate more effective screening for CA containing parameters commonly documented during clinical routine. Proteomic biomarkers may yield additional information in the future.

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Prevalence and significance of relative apical sparing in aortic stenosis: insights from an echo and cardiovascular magnetic resonance study of patients referred for surgical aortic valve replacement

Cited by 27 publications

References 31 publications

Cardiac Amyloidosis Due to Transthyretin Protein

Cardiac Amyloidosis Due to Transthyretin Protein

Novel electrocardiographic criteria may render possible the more accurate recognition of cardiac amyloidosis

Histological assessment of cardiac amyloidosis in patients undergoing transcatheter aortic valve replacement

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