For the podcast associated with this article, please visit https://academic.oup.com/eurheartj/pages/Podcasts.
Aortic valve disease increases in prevalence and incidence with age, particularly after age 60. As the biology of this disease is still poorly understood,1 the only current treatment is valve replacement. Until recently, this was the field for surgeons; however, with the development of transarterial valve implantation or TAVI, interventional cardiologists expanded their therapeutic spectrum substantially, initially in high-risk2 and more recently even in low-risk patients.3 This Focus Issue on valvular heart disease starts with the ‘The year in cardiology: valvular heart disease’ by Bernard Prendergast from the John Radcliffe Hospital in Oxford, UK, and colleagues.4 They remind us that after decades as a Cinderella discipline, valvular heart disease now occupies the centre stage of cardiovascular medicine. Changing societal demographics and an ageing population (with increasing prevalence of degenerative disease), advances in imaging, and the explosion of interest in TAVI (supported by a series of landmark clinical trials) have attracted clinicians, researchers, engineers, device manufacturers, and investors, and transformed the landscape of clinical management. Indeed, a recent meta-analysis concluded that compared with surgical valve replacement, TAVI is associated with a reduction in all-cause mortality and stroke up to 2 years irrespective of baseline surgical risk and type of system used.5 However, the incidence of stroke and pacemaker implantation was lower in those undergoing TAVI with balloon-expandable compared with self-expandable valves. In contrast, patients treated with new-generation balloon-expandable valves more often suffered from major or life-threatening bleedings than those with new-generation self-expandable valves, while mortality at 30 days was not different. Thus, 2019 has been a ‘leap’ year for valvular heart disease, and TAVI procedures will further increase.6
Based on these recent developments, TAVI has become the preferred procedure in patients with aortic stenosis in many countries. This is further analysed in the article entitled ‘Contemporary trends in the management of aortic stenosis in the USA’ by Mohamad Alkhouli and colleagues from the Mayo Clinic College of Medicine and Science in Rochester, Minnesota, USA (Figure 1).7 They utilized the National-Inpatient-Sample to assess temporal trends in the incidence, cost, and outcomes of aortic stenosis interventions between 2003 and 2016. During that period, aortic stenosis interventions increased from 96 to 137 per 100 000 individuals over 60 years of age. In-hospital expenditure almost doubled from US$2.28 billion in 2003 to US$4.33 in 2016. Among patients who underwent aortic valve replacement, the proportion of TAVI increased from 11.9% in 2012 to 43.2% in 2016. Males and Hispanics had lower proportions of TAVI compared with females and White patients. Adjusted in-hospital mortality of isolated surgery decreased from 5.4% in 2003 to 3.3% in 2016, while it decreased from 4.7% in 2012 to 2.2% in 2016 for TAVI. The incidence of new dialysis, permanent pacemaker implantation, and blood transfusion decreased after both TAVI and surgery between 2012 and 2016. However, the rate of post-operative stroke did not decrease significantly. Length of stay and cost of hospitalization decreased after both surgery and TAVI, although the latter remained higher with TAVI. Rates of non-home discharge decreased over time after TAVI but remained stable after isolated surgery. Thus, this nationwide survey documents the increasing incidence of interventions for aortic stenosis, the rising cost of care, and the paradigm shift in aortic valve replacement practice in the USA. The manuscript is accompanied by a balanced Editorial by Catherine M. Otto from the University of Washington in Seattle, Washington, USA.8
Figure 1
Temporal changes in the proportion of transcatheter aortic valve implantation for aortic stenosis. (A) Annual change in the proportions of TAVI among all aortic stenosis patients >60 undergoing aortic valve replacement. (B) Proportion of TAVI to all aortic valve replacement in different age groups. (C) Proportion of TAVI to all aortic valve replacement in males and females. (D) Proportion of TAVI to all aortic valve replacement in different racial groups. AS, aortic stenosis; TAVI, transcatheter aortic valve replacement. *P-values were <0.001 for all trend lines (from Alkhouli M, Alqahtani F, Ziada KM, Aljohani S, Holmes DR, Mathew V. Contemporary trends in the management of aortic stenosis in the USA. See pages 921–928).
Patients with aortic stenosis are typically of older age. Clonal haematopoiesis of indeterminate potential (CHIP9), defined as the presence of an expanded somatic blood cell clone without other haematological abnormalities, was recently shown to increase with age and is associated with coronary disease and calcification. In their Fast Track manuscript ‘Clonal haematopoiesis in patients with degenerative aortic valve stenosis undergoing transcatheter aortic valve implantation’ Andreas Michael Zeiher and colleagues from the Goethe University in Frankfurt, Germany note that the most commonly mutated CHIP genes, DNMT3A and TET2, regulate inflammatory pathways of circulating leucocytes.10 The incidence of calcified aortic valve stenosis increases with age and correlates with chronic inflammation. They therefore assessed the incidence of CHIP and its association with inflammatory blood cell phenotypes in patients with aortic stenosis undergoing TAVI. Targeted amplicon sequencing for DNMT3A and TET2 was performed in 279 patients with severe aortic stenosis undergoing TAVI. Somatic DNMT3A- or TET2-CHIP-driver mutations with a variant allele frequency ≥2% were detected in one-third of the patients, with an age-dependent increase in the incidence from 25% in 55 to 69 year olds to 52.9% in 90 to 100 year olds. Patients with DNMT3A- or TET2-CHIP-driver mutations did not differ from patients without it in clinical parameters, concomitant atherosclerotic disease, blood cell counts, inflammatory markers, or procedural characteristics. However, those with DNMT3A- or TET2-CHIP-driver mutations had an increased medium-term all-cause mortality following TAVI. Differential myeloid and T-cell distributions revealed pro-inflammatory T-cell polarization in DNMT3A mutation carriers and increased pro-inflammatory non-classical monocytes in TET2 mutation carriers. Thus, acquired somatic mutations in the most commonly mutated CHIP-driver genes occur frequently in aortic stenosis and are associated with increased pro-inflammatory leucocyte subsets, and confer increased mortality following TAVI. These novel and intriguing findings are further discussed in an Editorial by Benjamin Ebert from the Harvard Cancer Center in Boston, Massachusetts, USA.11
Left ventricular pressure overload is associated with activation of the cardiac renin–angiotensin system, which may contribute to myocardial fibrosis and worse clinical outcomes. Thus, drugs interfering with this neurohumoral system are widely used in hypertension,12 after myocardial infarction,13 and in heart failure.14 In their manuscript entitled ‘Impact of renin–angiotensin system inhibitors on clinical outcomes in patients with severe aortic stenosis undergoing transcatheter aortic valve replacement: an analysis of from the PARTNER 2 trial and registries’, Shmuel Chen from the Cardiovascular Research Foundation in New York, USA and colleagues sought to assess the association between treatment with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) at baseline and clinical outcomes in patients with symptomatic, severe aortic stenosis undergoing TAVI in the PARTNER 2 trial and registries.15 A total of 3979 intermediate-, high-, or prohibitive-risk patients who underwent TAVI in the PARTNER 2 trial and registries were included in the study. At baseline, 43.6% were treated and 56.4% were not treated with an ACEI or ARB. Treatment with an ACEI or ARB was associated with lower 2-year all-cause mortality (18.6% vs. 27.5%), cardiovascular mortality (12.3% vs. 17.9%), and non-cardiovascular mortality (7.2% vs. 11.7%). ACEI or ARB treatment at baseline remained independently associated with a lower hazard of 2-year all-cause and cardiovascular mortality after multivariable adjustment and propensity score matching, Thus, in patients with severe symptomatic aortic stenosis, ACEI or ARB treatment at baseline was independently associated with a lower risk of 2-year all-cause and cardiovascular mortality and thus should be considered in such patients. These intriguing findings are complemented by an Editorial by Marc A. Pfeffer from the Brigham and Women’s Hospital in Boston, Massachusetts, USA.16
B-type natriuretic peptide (BNP) is a cardiac neurohormone that is secreted in response to ventricular volume expansion and pressure overload in patients with coronary artery disease,17 acute coronary syndromes,18 and heart failure.19 Although many patients with aortic stenosis have elevated filling pressures, there are conflicting data regarding BNP levels and outcomes after TAVI. In their article ‘Low and elevated B-type natriuretic peptide levels are associated with increased mortality in patients with preserved ejection fraction undergoing transcatheter aortic valve replacement: an analysis of the PARTNER II trial and registry’ Brian R. Lindman and colleagues from the Vanderbilt School of Medicine in Nashville, Tennessee, USA assessed the association between baseline BNP and adverse outcomes in 1782 patients with symptomatic, severe aortic stenosis and left ventricle ejection fraction or LVEF ≥50%, undergoing TAVI in the PARTNER 2 Trial and Registry (Figure 2).20 After adjustment, spline curves revealed a non-linear association between log-transformed BNP and all-cause and cardiovascular mortality in which both the lowest and highest values were associated with increased mortality. Two-year all-cause mortality rates for those with low, normal, moderately elevated, and markedly elevated baseline BNP were 20, 9.8, 17.7, and 26.1%, respectively. In adjusted models, compared with a normal baseline BNP, low BNP provided an adjusted hazard ratio (aHR) of 2.6, moderately elevated BNP provided an aHR of 1.6, and markedly elevated BNP provided an a HR of 2.1 which were associated with increased all-cause mortality, driven by cardiovascular mortality. Thus, in patients with severe symptomatic aortic stenosis and preserved LVEF undergoing TAVI, all-cause and cardiovascular mortality rates at 2 years were elevated in those with both low and markedly elevated BNP levels. These surprising findings are put into context in an Editorial by Speranza Rubattu from the School of Medicine and Psychology at Sapienza University in Rome Italy.21
Figure 2
Adjusted association between log-transformed baseline B-type natriuretic peptide and the 2-year clinical outcomes. Multivariable Cox proportional hazards regression using a spline function to model log-transformed baseline B-type natriuretic peptide as a continuous metric for all-cause death (from Chen S, Redfors B, O‘Neill BP, Clavel M-A, Pibarot P, Elmariah S, Nazif T, Crowley A, Ben-Yehuda O, Finn MT, Alu MC, Vahl TP, Kodali S, Leon MB, Lindman BR. Low and elevated B-type natriuretic peptide levels are associated with increased mortality in patients with preserved ejection fraction undergoing transcatheter aortic valve replacement: an analysis of the PARTNER II trial and registry. See pages 958–969).
The editors hope that readers of this issue of the European Heart Journal will find it of interest.
With thanks to Amelia Meier-Batschelet for help with compilation of this article.
0 σχόλια:
Δημοσίευση σχολίου