Epidemiology and pathophysiology: In the elderly, degenerative AS is one of the most common types of valvular heart disease. The prevalence of AS has been reported to be between 12% and 26% depending on the diagnostic criteria employed[1,11]. In the study by Lindroos et al, critical AS was defined as a valve area < 0.8 cm2 or velocity ratio of < 0.35. In the 75- to 86-year-old group, the reported prevalence of disease was 2.9% (95%CI: 1.4% to 5.1%). Overall, 40% of patients with severe AS were considered to be at high surgical risk. It must be emphasized that although AS is clearly associated with adverse outcomes, even aortic sclerosis can create an increased risk of cardiovascular morbidity and mortality mainly by its being a significant risk factor for progression to AS. Degenerative calcific disease accounts for most cases of severe AS; however, a large study reported that 22% percent of octogenarians presenting for surgery for isolated AS had bicuspid valve disease[13-15].
Calcific aortic valve disease evolves over the years at a different rate in every subject. The development and progression of AS is at least in part related to active processes that have pathophysiological mechanisms in common with atherosclerotic disease. First, several studies suggested that calcific degenerative AS and atherosclerosis have common risk factors such as age, smoking, hypertension, hypercholesterolemia, diabetes mellitus, and metabolic syndrome[15-18]. Since valve leaflets may have anatomic heterogeneity, different shear stresses may lead to endothelial dysfunction at the ventricular surface of the valve. Second, the loss of endothelial integrity allows lipid accumulation and cellular migration (inflammatory cells, macrophages, and T cells) in the subendothelial matrix with neurohormonal activation. Plaque-like subendothelial deposits may lead to downward displacement and fragmentation of the subjacent elastic lamina. The osteoblast-like activity of interstitial cells may be responsible for valvular calcification over time with a decrease in leaflet mobility.
Epidemiology and pathophysiology: Isolated AR is significantly less common than pure AS. Degenerative and bicuspid aortic valve disease shows a different degree of both regurgitation and left ventricular obstruction; however, stenosis is usually pre-eminent. More frequently, AR is a consequence of aortic dilation and the deformation of the annulus valve. Overall prevalence of significant native AR has been reported in between 2.0% and 2.5% of patients 70 years to 83 years of age, without gender differences[22,23] although smaller studies reported a higher incidence of up to 13%. Age, aortic valve fibrocalcification, and female sex were considered independent factors related to AR, while several studies failed to find a relationship with arterial hypertension.
Treatment of aortic valve diseases: Surgical aortic valve replacement (SAVR) has been, for a long time, the treatment of choice for severe aortic valve disease. Improved survival and quality of life have been clearly demonstrated even in elderly patients[25-27]. Nevertheless, a non-negligible number of elderly patients are considered at very high or prohibitive risk for conventional surgical procedures, and about 30% of symptomatic subjects will never undergo surgery.
Non-surgical options, in particular transcatheter aortic valve replacement (TAVR), have developed as a suitable alternative to SAVR. In humans, the first transcatheter aortic stent valve was implanted in 2002, using femoral vein access and a transeptal approach. In 2005, technical developments allowed for changing the approach to the transfemoral artery. Transapical TAVR (TA-TAVR) has been proposed in patients with unsuitable vascular access. Several studies compared safety and efficacy between the transfemoral TAVR (TF-TAVR) and TA-TAVR. The transfemoral approach, whenever feasible, should be considered the preferable access route.
Initially, the indication for TAVR was limited to severely symptomatic AS with high surgical risk according to validated risk scores [Society of Thoracic Surgeons (STS) or European System for Cardiac Operative Risk Evaluation (EuroSCORE)]. At present, indications for percutaneous treatment may be extended to intermediate risk subjects. Nevertheless the use of STS-risk score (or EuroSCORE) may be misleading in very old people (aged > 80 years) since a high risk of perioperative complications may exist due to overall age and frailty per se[31-33]. Frailty, limited functional capacity according to Barthel scale, inadequate nutrition, and the need for non-cardiac surgery (most frequently oncologic or orthopedic surgery) are good indicators for TAVR, which allows a faster recovery and improved quality of life.
The randomized PARTNER 1B study first showed a decrease in death from any cause and death from cardiovascular causes in patients who underwent TAVR vs a conservative treatment. The PARTNER 1A trial randomized 699 high-risk patients with severe AS to TAVR (using transfemoral or the transapical approach) or SAVR. Death from any cause at 1 year was similar in the two groups, while major vascular complications (11.0% vs 3.2%, P < 0.001) and stroke (8.3% vs 4.3%, P < 0.05) were more frequent in TAVR than in SAVR. At 2 years follow-up, TAVR was associated with an increased late mortality mainly related to mechanical complications of the valve such as paravalvular leak. With first generation devices, residual AR due to para-valvular leaks was found postoperatively in about 20% of patients. Minimally invasive aortic valve replacement was proposed to manage carefully selected patients with the aim of decreasing permanent pacemaker implantation and other vascular complications that would be critical to changing patient prognosis.
In the study by Hirji et al, 1028 octogenarians underwent isolated aortic valve replacement between 2002 and 2015. Three hundred and six were treated by TAVR and 722 by SAVR (344 conventional and 378 minimally invasive valve replacement). Median follow-up was 35 mo. TAVR patients were relatively older (86.2 years vs 84.2 years) and in more cases had several co-morbidities. Operative mortality and mid-term survival were similar for TAVR (regardless of approach), SAVR, and minimally invasive aortic valve replacement after adjustment for confounding factors. The median in-hospital length of stay was statistically higher for the SAVR group (P < 0.05). Independent predictors of mortality were age, class III/IV New York Heart Association (NYHA), preoperative creatinine, severe chronic lung disease, and prior cardiac surgery (all P < 0.05). The authors concluded that treatment decisions should be addressed by a multi-disciplinary heart team, taking into account patient comorbidities, frailty, and quality of life.
Recently were reported the results of the FRench Aortic National CoreValve and Edwards (FRANCE-2) registry. In the study were included 2254 patients > 80 years of age who underwent TAVR. Thirty-day and 1-year mortality were not significantly different among patients aged 80 to 84 years, 85 to 89 years, and finally > 90 years (10.3% vs 9.5% vs 11.2%; P = 0.53 and respectively 19.8% vs 26.1% vs 27.7%; P = 0.16).
A recent study compared carefully selected patients > 90 years old, without many comorbidities, vs younger patients who underwent TAVR. Major complications were similar, and all-cause mortality at 30 days and 1 year was not statistically different (2.9% and 12.5% in patients aged ≥ 90 vs 2.8% and 12.3% in patients aged < 90, respectively).
The effects of TAVR were evaluated more recently in low-intermediate risk populations. An Italian observational, multicenter, “real-world” study included 1300 patients in a propensity-matched population. The authors did not find significant differences in mortality or major adverse cardiac and cardiovascular events between SAVR and TAVR.
In the PARTNER 2A randomized trial, TAVR was compared with SAVR in 2032 intermediate-risk patients. The primary endpoints were all-cause mortality or disabling stroke at 2 years. The authors did not find differences between groups. Although major vascular complications and paravalvular regurgitation were more frequent in TAVR, surgical replacement was associated with higher rates of acute kidney injury, severe bleeding, and new-onset AF.
The multicenter Surgical Replacement and Transcatheter Aortic Valve Implantation trial was a randomized, clinical trial that included 1746 patients at intermediate surgical risk, of whom 1660 underwent TAVR or surgical operation. The primary endpoint, a composite of death from any cause or disabling stroke at 24 mo, was 12.6% in TVAR and 14% in SAVR respectively. On the basis of these results, 2017 American Heart Association/America College of Cardiology gave a IIa indication for the TAVR procedure in intermediate surgical risk.
Data from studies of a low-risk group for surgery, showed that SAVR is still more advantageous than TAVR. Rosato et al reported that survival at 3 years was 72.0% after TAVR and 83.4% after SAVR (P = 0.0015). Further studies with new generation valve prostheses are necessary before expanding indications of TAVR in lower-risk patients.
Effects of coronary artery disease: Coronary artery disease (CAD) is frequently associated with AS, in particular in elderly patients. The coexistence of CAD leads to a worse prognosis for AS of comparable severity. Surgical treatment allows correction of valve disease and at the same time coronary revascularization. Data regarding elderly subjects are limited. Less is known about the effects of CAD in elderly patients undergoing TAVR.
To evaluate the effect of age on combined AVR and concomitant coronary artery bypass graft (CABG), 452 consecutive patients (mean age 64 years) were divided into three groups: Young (n = 114), middle-aged (n = 225), and elderly (n = 113). CAD was more extensive in the elderly group. Only 62.8% of elderly patients had complete myocardial revascularization in comparison to 94.1% and 76.2%, respectively, of the other two groups (P < 0.05). In-hospital mortality was 6.4% in the elderly in comparison to 2.0% and 5.3%, respectively in the other groups. Freedom from cardiac-related death at 12 mo and 60 mo was higher in young and middle-aged patients than in elderly patients.
How CAD impacts patient survival following TAVR has been investigated by a recent meta-analysis. Fifteen studies including 8013 patients were examined. The median age of patients was 81.3 years, 46.6% were men, and 3899 (48.7%) had CAD. All-cause mortality at 30 days post TAVR was not significantly different between patients with and without CAD. All-cause mortality however was significantly higher at 1 year in patients with CAD in comparison with patients without CAD (OR = 1.21; 95%CI: 1.07–1.36; P = 0.002). These results suggest the need to revisit the revascularization strategies for concomitant CAD in patients with TAVR.
AS and MR
In the elderly, AS is frequently associated with concomitant MR (22%-48%). In severe cases affecting both valves, surgical valve replacement has usually been considered the treatment of choice. Data regarding elderly subjects is limited. In the study by Yu et al, 43 high-risk patients with severe AS, aged 80 ± 6 years, underwent concomitant SAVR and mitral valve (MV) surgery. Nineteen (44%) had prior cardiac surgery, and 39 (91%) were in congestive heart failure. Five patients (11.6%) died during hospitalization or at 30 days. Mortality was 25% at 6 mo, 35% at 1 year, and 45% at 2 years. Patients often needed prolonged ventilation, and 10% developed new renal failure requiring dialysis. When AS in patients at high or prohibitive surgical risk is treated by percutaneous TAVR, concomitant significant MR usually is not corrected[48,49]. Untreated MR is associated with a significant increase in mortality and morbidity.
The recent availability of percutaneous devices for treating MV disease may offer an alternative for the management of MR after TAVR. Few limited case series reported a procedural success (decrease of degree of MR < 2+) comprised between 92% and 100% for edge to edge MV repair with MitraClipTM (Abbott Vascular, Menlo Park, CA, United States). Recurrent 3+ MR at 1 year however occurred in 21.4%. One year survival rate was 66.5%.
In conclusion, concomitant MV surgery in patients with MV disease undergoing aortic valve replacement did not give better results on long term survival than TAVR without correction of MV regurgitation. Therefore, individual assessment should guide procedural strategy in treating MR associated with severe AS.