Pathophysiology, Diagnosis, and Treatment of Patients with Concomitant Severe Aortic Stenosis and Coronary Artery Disease: A Closer Look to the Unresolved Perplexity.
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ABSTRACT:
SUBMITTER: Di Gioia G
PROVIDER: S-EPMC8070187 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background As younger patients are being considered for transcatheter aortic valve implantation (TAVI), the assessment and treatment of concomitant coronary artery disease is taking on increased importance. Methods and Results Thirteen contemporary lower-risk patients with TAVI with severe aortic stenosis (AS) and moderate-severe coronary lesions were included. Patients underwent assessment of coronary hemodynamics in the presence of severe AS (pre-TAVI), in the absence of severe AS (immediately post-TAVI), and at longer-term follow-up (6 months post-TAVI). Fractional flow reserve decreased from 0.85 (0.76-0.88) pre-TAVI to 0.79 (0.74-0.83) post-TAVI, and then to 0.71 (0.65-0.77) at 6-month follow-up (P<0.001 for all comparisons). Conversely, instantaneous wave-free ratio was not significantly different: 0.82 (0.80-0.90) pre-TAVI, 0.83 (0.77-0.88) post-TAVI, and 0.83 (0.73-0.89) at 6 months (P=0.735). These changes are explained by the underlying coronary flow. Hyperemic whole-cycle coronary flow (fractional flow reserve flow) increased from 26.36 cm/s (23.82-31.82 cm/s) pre-TAVI to 30.78 cm/s (29.70-34.68 cm/s) post-TAVI (P=0.012), to 40.20 cm/s (32.14-50.00 cm/s) at 6-month follow-up (P<0.001 for both comparisons). Resting flow during the wave-free period of diastole was not significantly different: 25.48 cm/s (21.12-33.65 cm/s) pre-TAVI, 24.54 cm/s (20.74-27.88 cm/s) post-TAVI, and 25.89 cm/s (22.57-28.96 cm/s) at 6 months (P=0.500). Conclusions TAVI acutely improves whole-cycle hyperemic coronary flow, with ongoing sustained improvements at longer-term follow-up. This enhanced response to hyperemic stimuli appears to make fractional flow reserve assessment less suitable for patients with severe AS. Conversely, resting diastolic flow is not significantly influenced by the presence of severe AS. Resting indices of coronary stenosis severity, therefore, appear to be more appropriate for this patient population, although large-scale prospective randomized trials will be required to determine the role of coronary physiology in patients with severe AS.
| S-EPMC7335578 | biostudies-literature
Project description:The study sought to contrast risk profiles and compare outcomes of patients with severe aortic stenosis (AS) and coronary artery disease (CAD) who underwent aortic valve replacement (AVR) and coronary artery bypass grafting (AS+CABG) with those of patients with isolated AS who underwent AVR alone.In patients with severe AS, CAD is often an incidental finding with underappreciated survival implications.From October 1991 to July 2010, 2,286 patients underwent AVR+CABG and 1,637 AVR alone. A propensity score was developed and used for matched comparisons of outcomes (1,082 patient pairs). Analyses of long-term mortality were performed for each group, then combined to identify common and unique risk factors.Patients with AS+CAD versus isolated AS were older, more symptomatic, and more likely to be hypertensive, and had lower ejection fraction and greater arteriosclerotic burden but less severe AS. Hospital morbidity and long-term survival were poorer (43% vs. 59% at 10 years). Both groups shared many mortality risk factors; however, early risk among AS+CAD patients reflected effects of CAD; late risk reflected diastolic left ventricular dysfunction expressed as ventricular hypertrophy and left atrial enlargement. Patients with isolated AS and few comorbidities had the best outcome, those with CAD without myocardial damage had intermediate outcome equivalent to propensity-matched isolated AS patients, and those with CAD, myocardial damage, and advanced comorbidities had the worst outcome.Cardiovascular risk factors and comorbidities must be considered in managing patients with severe AS. Patients with severe AS and CAD risk factors should undergo early diagnostics and AVR+CABG before ischemic myocardial damage occurs.
| S-EPMC4262244 | biostudies-literature
Project description:Coronary artery disease (CAD) and the frequently coexisting aortic valve stenosis (AS) are the heart diseases accounting for the highest proportion of cardiac surgeries. Routine biomarkers for an earl detection of either of these atherosclerotic-rooted conditions would be important to anticipate the diagnosis and to evaluate their severity with imaging techniques before they become advanced to the point where intervention or surgery have limited therapeutic benefit. Urine is an attractive biofluid for biomarker assessment, provided the noninvasive nature of its collection. Therefore, we conducted a shotgun proteomics analysis of urine collected from 12 CAD and/or AS patients and 11 cardiovascular disease-free controls, aiming at identification of putative molecular candidates that could differentiate these diseases from healthy subjects
2022-12-18 | PXD036800 | Pride
Project description:Circulating microparticles (MPs) derived from endothelial cells and blood cells bear procoagulant activity and promote thrombin generation. Thrombin exerts proinflammatory effects mediating the progression of atherosclerosis. Aortic valve stenosis may represent an atherosclerosis-like process involving both the aortic valve and the vascular system. The aim of this study was to investigate whether MP-induced thrombin generation is related to coronary atherosclerosis and aortic valve calcification.In a cross-sectional study of 55 patients with severe aortic valve stenosis, we assessed the coronary calcification score (CAC) as indicator of total coronary atherosclerosis burden, and aortic valve calcification (AVC) by computed tomography. Thrombin-antithrombin complex (TATc) levels were measured as a marker for thrombin formation. Circulating MPs were characterized by flow cytometry according to the expression of established surface antigens and by measuring MP-induced thrombin generation.Patients with CAC score below the median were classified as patients with low CAC, patients with CAC Score above the median as high CAC. In patients with high CAC compared to patients with low CAC we detected higher levels of TATc, platelet-derived MPs (PMPs), endothelial-derived MPs (EMPs) and MP-induced thrombin generation. Increased level of PMPs and MP-induced thrombin generation were independent predictors for the severity of CAC. In contrast, AVC Score did not differ between patients with high and low CAC and did neither correlate with MPs levels nor with MP-induced thrombin generation.In patients with severe aortic valve stenosis MP-induced thrombin generation was independently associated with the severity of CAC but not AVC indicating different pathomechanisms involved in coronary artery and aortic valve calcification.
| S-EPMC4807100 | biostudies-literature
Project description:With the increasing prevalence of aortic stenosis (AS) due to a growing elderly population, a proper understanding of its physiology is paramount to guide therapy and define severity. A better understanding of the microvasculature in AS could improve clinical care by predicting left ventricular remodeling or anticipate the interplay between epicardial stenosis and myocardial dysfunction. In this review, we combine five decades of literature regarding microvascular, coronary, and aortic valve physiology with emerging insights from newly developed invasive tools for quantifying microcirculatory function. Furthermore, we describe the coupling between microcirculation and epicardial stenosis, which is currently under investigation in several randomized trials enrolling subjects with concomitant AS and coronary disease. To clarify the physiology explained previously, we present two instructive cases with invasive pressure measurements quantifying coexisting valve and coronary stenoses. Finally, we pose open clinical and research questions whose answers would further expand our knowledge of microvascular dysfunction in AS. These trials were registered with NCT03042104, NCT03094143, and NCT02436655.
| S-EPMC7396014 | biostudies-literature
Project description:More than half of patients with severe aortic stenosis (AS) over 70 years old have coronary artery disease (CAD). Exertional angina is often present in AS-patients, even in the absence of significant CAD, as a result of oxygen supply/demand mismatch and exercise-induced myocardial ischemia. Moreover, persistent myocardial ischemia leads to extensive myocardial fibrosis and subsequent coronary microvascular dysfunction (CMD) which is defined as reduced coronary vasodilatory capacity below ischemic threshold. Therefore, angina, as well as noninvasive stress tests, have a low specificity and positive predictive value (PPV) for the assessment of epicardial coronary stenosis severity in AS-patients. Moreover, in symptomatic patients with severe AS exercise testing is even contraindicated. Given the limitations of noninvasive stress tests, coronary angiography remains the standard examination for determining the presence and severity of CAD in AS-patients, although angiography alone has poor accuracy in the evaluation of its functional severity. To overcome this limitation, the well-established invasive indices for the assessment of coronary stenosis severity, such as fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR), are now in focus, especially in the contemporary era with the rapid increment of transcatheter aortic valve replacement (TAVR) for the treatment of AS-patients. TAVR induces an immediate decrease in hyperemic microcirculatory resistance and a concomitant increase in hyperemic flow velocity, whereas resting coronary hemodynamics remain unaltered. These findings suggest that FFR may underestimate coronary stenosis severity in AS-patients, whereas iFR as the non-hyperemic index is independent of the AS severity. However, because resting coronary hemodynamics do not improve immediately after TAVR, the coronary vasodilatory capacity in AS-patients treated by TAVR remain impaired, and thus the iFR may overestimate coronary stenosis severity in these patients. The optimal method for evaluating myocardial ischemia in patients with AS and co-existing CAD has not yet been fully established, and this important issue is under further investigation. This review is focused on challenges, limitations, and future perspectives in the functional assessment of coronary stenosis severity in these patients, bearing in mind the complexity of coronary physiology in the presence of this valvular heart disease.
| S-EPMC8961810 | biostudies-literature
Project description:BackgroundPrevalence of both degenerative severe aortic stenosis (AS) and transthyretin cardiac amyloidosis (ATTR-CA) increases with age. Dual disease (AS+myocardial ATTR-CA) occurs in significant proportion of patients undergoing surgical aortic valve replacement (SAVR).ObjectivesThis study aimed to determine the prevalence of ATTR-CA in severe AS in the Indian population, identify noninvasive predictors of its diagnosis, and understand its impact on prognosis.MethodsSymptomatic severe AS patients aged ≥65 years undergoing SAVR were enrolled. ATTR-CA diagnosis was based on preoperative 99m-technetium pyrophosphate (PYP) scan and intraoperatively obtained basal interventricular septum biopsy for myocardial ATTR-CA, and excised native aortic valve for isolated valvular ATTR-CA. Primary amyloidosis was excluded by serum/urine protein electrophoresis with serum immunofixation.ResultsSAVR was performed in 46 AS patients (age 70 ± 5 years, 70% men). PYP scan was performed for 32 patients, with significant PYP uptake in 3 (n = 3 of 32, 9.4%), suggestive of myocardial ATTR-CA. On histopathological examination, none of the interventricular septum biopsy specimens had amyloid deposits, whereas 33 (71.7%) native aortic valves showed amyloid deposits, of which 19 (57.6%) had transthyretin deposition suggestive of isolated valvular amyloidosis. Noninvasive markers of dual disease included low myocardial contraction fraction (median [interquartile range], 28.8% [23.8% to 39.1%] vs 15.3% [9.3% to 16.1%]; P = 0.006), deceleration time (215 [144 to 236] ms vs 88 [60 to 106] ms; P = 0.009) and global longitudinal strain (-18.7% [-21.1% to -16.9%] vs -14.2% [-17.0% to -9.7%]; P = 0.030). At 1-year follow-up, 2 patients died (4.3%); 1 each in myocardial ATTR-CA negative and positive groups (3.4% vs 33.3%; P = 0.477).ConclusionsDual disease is not uncommon in India. Isolated valvular amyloidosis in severe AS is much more common.
| S-EPMC8551518 | biostudies-literature
Project description:Aortic stenosis (AS) has different clinical phenotypes, including AS with or without concomitant coronary artery disease (CAD). It is unknown whether these phenotypes share the same risk factors. In particular, lipoprotein(a) [Lp(a)] and apolipoproteins (Apo) are associated with AS, but it is unknown whether these associations differ among phenotypes. In this prospective analysis we examined the impact of Lp(a) and Apo in subgroups of patients with AS.We identified 336 patients (mean age at survey 56.7 years, 48% female) who underwent surgery for AS after a median 10.9 years (interquartile range 9.3 years), participants in 1 of 3 large population surveys. For each patient, 2 matched referents were allocated. Lp(a) and Apo were analyzed in the baseline samples. Uni- and multivariable logistic regression analyses were used to estimate risks related to a 1 (ln) standard deviation increase in Lp(a) and the ratio of Apo B to Apo A1 (Apo B/A1 ratio). High levels of Lp(a) predicted surgery for AS in 203 patients with concomitant CAD (odds ratio [95% confidence intervals]) (1.29 [1.07-1.55]), but not in 132 patients without CAD (1.04 [0.83-1.29]) in the fully adjusted model. Similarly, a high Apo B/A1 ratio predicted surgery in patients with concomitant CAD (1.43 [1.16-1.76]) but not in those without CAD (0.87 [0.69-1.10]).High levels of Lp(a) and a high Apo B/A1 ratio were associated with surgery for AS in patients with concomitant CAD but not in those with isolated AS. This finding may lead to a new avenue of research for targeted risk factor interventions in this population.
| S-EPMC5779030 | biostudies-literature
Project description:BackgroundThere is an incomplete understanding of the natural course of mild to moderate aortic stenosis (AS). We aimed to evaluate the natural course of patients with mild to moderate AS and its association with coronary artery disease (CAD).MethodsWe retrospectively analyzed 787 patients diagnosed with mild to moderate AS using echocardiography between 2004 and 2010. Cardiac death and aortic valve replacement (AVR) for AS were assessed.ResultsA median follow-up period was 92 months. Compared to the general population, patients with mild to moderate AS had a higher risk of cardiac death (hazard ratio [HR], 17.16; 95% confidence interval [CI], 13.65-21.59; P < 0.001). Established CAD was detected in 22.4% and associated with a significantly higher risk of cardiac mortality (adjusted HR, 1.62; 95% CI, 1.04-2.53; P = 0.033). The risk of cardiac death was lower when patients were taking statin (adjusted HR, 0.64; 95% CI, 0.41-0.98; P = 0.041), which was clear only after 7 years. Both patients with CAD and on statin tended to undergo more AVR, but the difference was not statistically significant (the presence of established CAD; adjusted HR, 1.63; 95% CI, 0.51-3.51; P = 0.214 and the use of statin; adjusted HR, 1.86; 95% CI, 0.76-4.58; P = 0.177).ConclusionMild to moderate AS does not have a benign course. The presence of CAD and statin use may affect the long-term prognosis of patients with mild to moderate AS.
| S-EPMC7870422 | biostudies-literature
Project description:BackgroundCoronary Artery Disease (CAD) is the narrowing or blockage of the coronary arteries. It is closely associated with numerous genetics and environmental factors that have been extensively evaluated in various populations. In recent studies, severe phenotypes have been strongly linked to genetic risk factors.MethodsThis study investigated the association of clinical, demographic, and genetic factors with severe coronary artery stenosis phenotypes in our population composed of 1734 individuals with severe coronary stenosis (≥ 50% in coronary vessels) and comparing them to 757 controls with no evidence of stenosis on angiography. We performed generalized linear model (GLM) genome-wide association studies to evaluate three stratification models and their associations to characteristics of the clinical disease. In model 1, patients were not stratified. In model 2, patients were stratified based on presence or absence of CAD family history (FxCAD). In model 3, patients were stratified by young age of CAD onset.ResultsEight SNPs (single nucleotide polymorphism) were significantly associated with severe CAD phenotypes in the various models [Formula: see text], four of these SNPs were associated with severe CAD and the four others were specifically significant for young CAD patients. While these SNPs were not previously reported for association with CAD, six of them are present in genes that have already been linked to coronary disease.ConclusionIn conclusion, this study presents new genetic factors associated with severe stenosis and highlights different risk factors associated with a young age at diagnosis of CAD.
| S-EPMC7993530 | biostudies-literature