Corrigendum: A wolf in sheep's clothing-aortic stenosis and cardiac amyloidosis: "RAISE"ing awareness in clinical practice.

[This corrects the article DOI: 10.3389/fcvm.2024.1323023.].

A wolf in sheep's clothing-aortic stenosis and cardiac amyloidosis: "RAISE"ing awareness in clinical practice.

Aesop's fable of the wolf in sheep's clothing encourages us to look beneath the exterior appearance of a situation and evaluate the truth that lies beneath. This concept should be applied when managing older patients with severe aortic stenosis. This population of patients is increasingly being identified as having concomitant cardiac amyloidosis, which is an underrecognized cause of common cardiac conditions. The presence of cardiac amyloidosis negatively affects the outcome of patients with aortic stenosis, these patients undergo transcatheter aortic valve replacement (TAVR) with increasing frequency and have a significantly higher overall mortality rate than patients with aortic stenosis alone. Although left ventricular wall hypertrophy is expected in patients with aortic stenosis, it should not be assumed that this is caused only by aortic stenosis. A suspicion of cardiac amyloidosis should be raised in patients in whom the degree of hypertrophy is disproportionate to the degree of aortic stenosis severity. The remodeling, age, injury, systemic, and electrical (RAISE) score was developed to predict the presence of cardiac amyloidosis in patients with severe aortic stenosis. This article highlights the value of increased clinical suspicion, demonstrates the use of the multiparameter RAISE score in daily clinical practice, and illustrates the scoring system with case studies. In elderly patients being considered for TAVR, systematic testing for cardiac amyloidosis should be considered as part of the preoperative workup.

Renal Artery Stenosis in Patients with Peripheral Artery Disease: Prevalence, Risk Factors and Long-term Prognosis.

OBJECTIVE/BACKGROUND: The objective was to determine the prevalence and clinical determinants of renal artery stenosis (RAS) in patients undergoing digital subtraction angiography (DSA) for the assessment of peripheral artery disease (PAD), and to evaluate its prognostic significance. METHODS: All DSAs performed from January 2000 to January 2006 were retrospectively reviewed for assessment of PAD in patients naive for any prior revascularisation of lower-limb arteries. All DSA studies were read by two senior physicians blinded to outcome, and consensus was reached in cases of disagreement. RAS was defined as the presence of ≥50% stenosis in either renal artery. Patients' electronic medical files were systematically reviewed and follow-up was completed by contact with family physicians until January 2014. The primary outcome was composite, including death, peripheral revascularisation, or any limb amputation. Secondary outcomes were all-cause mortality, and another composite, including death and non-fatal myocardial infarction or stroke or coronary or carotid revascularisation. RESULTS: In total, 400 consecutive patients having a first DSA of lower extremities, two thirds of whom were for critical limb ischaemia, were studied. Thirteen patients were excluded owing to poor renal artery imaging. RAS was detected in 57 patients (14%). Only two factors were independently and significantly associated with RAS in multivariate analysis: diffuse PAD (involving both proximal and distal segments [odds ratio {OR} 3.50, 95% confidence interval {CI} 1.16-10.54; p = .026]) and decreased glomerular filtration rate (OR 0.55 per 30 mL/minute/1.73 m2, 95% CI 0.41-0.75; p < .001). During follow-up (mean ± SD 62 ± 47 months), 25% experienced limb amputation and 54% died. In multivariate analysis, no significant association was found between RAS and primary outcome (hazard ratio 0.80; 95% CI 0.57-1.10). No significant association was found with secondary outcomes. CONCLUSION: Incidental RAS is frequent (14%) among patients with PAD undergoing lower extremity imaging. No difference in outcome in patients with RAS versus those without RAS was seen. Larger studies are necessary to draw definite conclusions.

[AL amyloidosis]. / Amylose AL.

AL amyloidosis belongs to the group of conformational diseases. It is the most common type of amyloidosis with an estimated 500 new cases per year in France. It is due to a small and usually indolent plasma cell clone which synthesizes an unstable, misfolded monoclonal immunoglobulin light chain that is prone to aggregate and form amyloid fibrils. Non-invasive biopsy such as abdominal fat aspiration or minor salivary gland biopsy should be performed to confirm the diagnosis and if negative, involved tissues have to be examined. Clinical presentation is very diverse, as AL amyloidosis can affect almost any organ or tissue in the body, other than the brain. The kidney is the most frequent organ involved, whereas heart disease characterized by restrictive cardiomyopathy is the most severe. Early diagnosis, before advanced cardiomyopathy, is essential for improving outcome. The association of alkylating agent and high-dose dexamethasone is effective in almost two-thirds of patients. Combinations of proteasome inhibitors, dexamethasone, and alkylating agents achieve high response rates. Close monitoring of clonal and organ response is mandatory to guide therapy changes and duration. New treatments designed to eliminate amyloid deposits are under development.

Hypoadiponectinemia is associated with valvular inflammation and faster disease progression in patients with aortic stenosis.

OBJECTIVES: Adiponectin is a protein secreted by adipocytes which has anti-inflammatory properties. The objective of this study was to examine the relationship between adiponectinemia and the hemodynamic progression of aortic stenosis (AS) as well as the degree of inflammation in the valve explanted at the time of aortic valve replacement (AVR). METHODS: The plasma level of adiponectin was measured in 122 patients undergoing AVR. The explanted aortic valves were analyzed and the density of leukocytes (CD45+), T cells (CD3+) and blood vessels (von Willebrand factor positive; vWF+) was documented. Also, a subset of patients (n = 67) had ≥2 echocardiographic studies separated by at least 6 months, thereby allowing assessment of the rate of progression of stenosis during the preoperative period. RESULTS: Patients with lower plasma levels of adiponectin (<5.4 µg/ml) had a faster progression rate of the mean transvalvular gradient before surgery than those with higher levels (9 ± 1 vs. 4 ± 1 mm Hg/year; p = 0.008). Moreover, these patients with hypoadiponectinemia had significantly more leukocytes (CD45+), T cells and blood vessels (vWF+) in their explanted valves compared to those with higher adiponectin levels. CONCLUSION: These findings support the concept that adiponectin may play a protective role against the inflammatory process and progression of calcific AS.

Association between circulating oxidised low-density lipoprotein and fibrocalcific remodelling of the aortic valve in aortic stenosis.

INTRODUCTION: Aortic stenosis (AS) is the most common valvular heart disease in westernized societies. AS is a disease process akin to atherosclerosis in which calcification and tissue remodelling play a crucial role. In patients with moderate/severe AS, we sought to determine whether the remodelling process would be in relationship with transvalvular gradients and circulating oxidised low-density lipoprotein (ox-LDL) levels. METHODS: In 105 patients with AS, the aortic valve and blood plasma were collected at the time of valve replacement surgery. The degree of valve tissue remodelling was assessed using a scoring system (Score: 1-4) and the amount of calcium within the valve cusps was determined. The standard plasma lipid profile, the size of LDL particles and the plasma level of circulating ox-LDL (4E6 antibody) were determined. RESULTS: After adjustment for covariables, aortic remodelling score was significantly related to transvalvular gradients measured by Doppler echocardiography before surgery. Patients with higher valve remodelling score had higher circulating ox-LDL levels (score 2: 27.3 (SEM 2.6) U/l; score 3: 32.2 (SEM 2.3) U/l; score 4: 38.3 (SEM 2.3) U/l; p = 0.02). After correction for age, gender, hypertension and HDL-C, the plasma level of ox-LDL remained significantly associated with the aortic valve remodelling score (p<0.001). The plasma level of ox-LDL was significantly associated with LDL-C (r = 0.41; p<0.001), apoB (r = 0.59; p<0.001), triglyceride (r = 0.39; p<0.001), Apo A-I (r = 0.23; p = 0.01) and cholesterol in small (<255 A) LDL particles (r = 0.22; p = 0.02). After correction for covariables, circulating ox-LDL levels remained significantly associated with apoB (p<0.001) and triglyceride (p = 0.01) levels. CONCLUSION: Increased level of circulating ox-LDL is associated with worse fibrocalcific remodelling of valvular tissue in AS. It remains to be determined whether circulating ox-LDL is a risk marker for a highly atherogenic profile and/or a circulating molecule which is actively involved in the pathogenesis of calcific aortic valve disease.

Very long-term survival and durability of mitral valve repair for mitral valve prolapse.

BACKGROUND: Mitral regurgitation (MR) due to mitral valve prolapse (MVP) is often treatable by surgical repair. However, the very long-term (>10-year) durability of repair in both anterior leaflet prolapse (AL-MVP) and posterior leaflet prolapse (PL-MVP) is unknown. METHODS AND RESULTS: In 917 patients (aged 65+/-13 years, 68% male), surgical correction of severe isolated MR due to MVP (679 repairs and 238 replacements [MVRs]) was performed between 1980 and 1995. Survival after repair was better than survival after MVR for both PL-MVP (at 15 years, 41+/-5% versus 31+/-6%, respectively; P=0.0003) and AL-MVP (at 14 years, 42+/-8% versus 31+/-5%, respectively; P=0.003). In multivariate analysis adjusting for predictors of survival, repair was independently associated with lower mortality in PL-MVP (adjusted risk ratio [RR] 0.61, 95% CI 0.44 to 0.85; P=0.0034) and in AL-MVP (adjusted RR 0.67, 95% CI 0.47 to 0.96; P=0.028). The reoperation rate was not different after repair or MVR overall (at 19 years, 20+/-5% for repair versus 23+/-5% for MVR; P=0.4) or separately in PL-MVP (P=0.3) or AL-MVP (P=0.3). However, the reoperation rate was higher after repair of AL-MVP than after repair of PL-MVP (at 15 years, 28+/-7% versus 11+/-3%, respectively; P=0.0006). From the 1980s to the 1990s, the RR of reoperation after repair of AL-MVP versus PL-MVP did not change (RR 2.5 versus 2.7, respectively; P=0.58), but the absolute rate of reoperation decreased similarly in PL-MVP and AL-MVP (at 10 years, from 10+/-3% to 5+/-2% and from 24+/-6% to 10+/-2%, respectively; P=0.04). CONCLUSIONS: In severe MR due to MVP, mitral valve repair compared with MVR provides improved very long-term survival after surgery for both AL-MVP and PL-MVP. Reoperation is similarly required after repair or replacement but is more frequent after repair of AL-MVP. Recent improvement in long-term durability of repair suggests that it should be the preferred mode of surgical correction of MVP whether it affects anterior or posterior leaflets and is an additional incentive for early surgery of severe MR due to MVP.

Pathophysiologic determinants of third heart sounds: a prospective clinical and Doppler echocardiographic study.

PURPOSE: We sought to determine the importance of a third heart sound (S(3)) and its relation to hemodynamic and valvular dysfunction. SUBJECTS AND METHODS: We prospectively enrolled 580 patients who had isolated valvular regurgitation (mitral, n = 299; aortic, n = 121) or primary left ventricular dysfunction with or without functional mitral regurgitation (n = 160). We analyzed the associations between the clinical finding of an audible S(3) (as noted in routine clinical practice by internal medicine physicians) and hemodynamic alterations measured by comprehensive quantitative Doppler echocardiography. RESULTS: S(3) was more prevalent in patients with primary left ventricular dysfunction (46%, n = 73) than in organic mitral (16%, n = 47) or aortic (12%, n = 14) regurgitation (P <0.001). Patients with an S(3) were more likely to have class III-IV symptoms (55% [74 of 137] vs. 18% [80 of 443] of those without an S(3), P <0.001) and had a higher mean [+/- SD] pulmonary pressure (55 +/- 15 vs. 41 +/- 11 mm Hg, P <0.001). An S(3) was also related to a higher early filling velocity due to a greater filling volume, restrictive filling, or both. An S(3) was a marker of severe regurgitation (regurgitant fraction > or =40%) in patients with primary left ventricular dysfunction (odds ratio [OR] = 2.4; 95% confidence interval [CI]: 1.1 to 5.5), mitral regurgitation (OR = 17; 95% CI: 5.8 to 52), and aortic regurgitation (OR = 7.1; 95% CI: 1.8-28). An S(3) was also associated with restrictive filling in primary left ventricular dysfunction (OR = 3.0; 95% CI, 1.6 to 5.9), marked dilatation in mitral regurgitation (OR = 20; 95% CI: 6.8 to 58), and an ejection fraction (<50%) in aortic regurgitation (OR = 19; 95% CI: 6.0 to 62). CONCLUSION: An audible S(3) is an important clinical finding, indicating severe hemodynamic alterations, and should lead to a comprehensive assessment and consideration of vigorous medical or surgical treatment.

Evaluation of incidence, clinical significance, and prognostic value of circulating cardiac troponin I and T elevation in hemodynamically stable patients with suspected myocardial contusion after blunt chest trauma.

BACKGROUND: The frequency and prognostic influence of myocardial injury in patients with blunt chest trauma is controversial. We investigated the value of cardiac troponin I (cTn-I) and cardiac troponin T (cTn-T), highly specific markers of myocardial injury, to determine whether their measurement would improve the ability to detect myocardial contusion in stable patients with blunt chest trauma in comparison with conventional markers and whether they were associated with significantly worse late clinical outcome. METHODS AND RESULTS: Over an 18-month period, myocardial contusion was diagnosed in 26 of 94 patients (27.6%) with acute blunt chest trauma (motor vehicle crash; 81%), because of echocardiographic abnormalities (n = 12), electrocardiographic abnormalities (n = 29), or both. Patients with myocardial contusion had a significantly higher Injury Severity Score at the time of admission (p = 0.001) and a significantly longer hospital stay (p = 0.0008). All patients survived admission to hospital and were hemodynamically stable. None of the patients died or had severe in-hospital cardiac complications. The percentage of patients with elevated CK, (CK-MB/total CK) ratio, or CK-MB mass concentration was not significantly different between patients with or without myocardial contusion. However, there were significant differences between the two groups when we applied the commonly used threshold levels of CK-MB activity and myoglobin. The percentage of patients with elevated circulating cTn-I and cTn-T (> or = 0.1 microg/L) was significantly higher in patients with myocardial contusion (23% vs. 3%; p = 0.01 and 12% vs. 0%; p = 0.03, respectively). Complete changes in cTn-I and cTn-T correlated well (r = 0.91, p = 0.0001). Sensitivity, specificity, and negative and positive predictive values of cTn-I and cTn-T in predicting a myocardial contusion in blunt trauma patients were 23%, 97%, and 77%, 75%, and 12%, 100%, and 74%, 100%, respectively. Clinical follow-up was available in 83 patients (88%) (mean, 16 +/- 7.5 months). There were no deaths in either group directly attributed to cardiac complications. None of the patients had any long-term cardiac complications or myocardial failure related to blunt chest trauma. CONCLUSION: Although improved specificity of cTn-I and cTn-T compared with conventional markers, it should be emphasized that the main problem with cTn-I and cTn-T is low sensitivity as well as low predictive values in diagnosing myocardial contusion. cTn-I and cTn-T measurement is currently not an improved method in diagnosing blunt cardiac injury in hemodynamically stable patients. Moreover, there was no association of postmyocardial contusion cell injury and late outcome in these patients when cTn-I and cTn-T and other conventional markers were considered.