Introduction
This new format of the ‘Year in Cardiovascular Medicine’ series brings the challenge to select only 10 papers published in 2022 the authors believe to be the most important in their topic. We restricted our search to the New England Journal of Medicine, British Medical Journal, Journal of the American Medical Association, Lancet, European Heart Journal, Circulation and Journal of the American College of Cardiology. The selection is a consensus of the three authors. There are of course definitely more papers that would deserve to be cited. Our selection remains subjective and besides quality, we also considered the potential impact on clinical practice and future research, as well as publications we felt may be of most interest to our readers (Figure 1).
Role of lipoprotein (a) in calcific aortic stenosis
There is strong evidence of a causal role of lipoprotein (a) [Lp(a)] in the pathogenesis of calcific aortic valve disease but its impact on aortic stenosis (AS) progression remained elusive. Kaiser et al. (1) assessed the association of Lp(a) with incidence and progression of aortic valve calcium (AVC) in 922 individuals of the population-based Rotterdam Study with available Lp(a) measurements and repeated non-contrast computed tomography [median follow-up (FU) 14 years]. Like LDL-cholesterol and prior experience with statins, Lp(a) was robustly associated with baseline and new-onset of AVC but not with AVC progression. These results have important implications for the design of future trials with Lp(a) lowering agents suggesting to focus on patients with elevated Lp(a) and/or the pre-calcific disease phase.
Vitamin K2 and D in calcific aortic stenosis
Vitamin K2 is the most effective cofactor for the carboxylation of proteins involved in the inhibition of arterial calcification and has been suggested to reduce the progression of AVC. Diederichsen et al. (2) studied in a randomized, placebo-controlled trial, the effect of 720μg vitamin K2 plus 25μg vitamin D daily over 24 months in 365 men (71±4 years) with an AVC score >300 arbitrary units (AU). There was no difference in ΔAVC score (primary outcome), overall and in subsets with AVC scores 300–600 or >600 AU. Although the potential benefit of higher dosages and longer treatment duration cannot be excluded, this study rather discourages further trials with vitamin K2.
Aortic valve replacement in asymptomatic aortic stenosis
The timing of surgery in asymptomatic AS remains controversial. In the AVATAR Trial, (3) 157 patients with severe asymptomatic AS confirmed by a negative exercise test and preserved left ventricular ejection fraction (LVEF) were randomly allocated to early surgery or conservative treatment. After a median FU of 32 months, the early surgery group had a significantly lower incidence (15 vs. 35%) of the primary composite endpoint (all-cause mortality, acute myocardial infarction, stroke, or unplanned hospitalization for heart failure) than the conservative treatment group. There was no difference in cardiovascular deaths (9.5 vs. 9.1%) but a trend towards lower all-cause death (10 vs. 20%, P=0.16). These results require confirmation in larger populations, ongoing studies evaluating transcatheter therapies instead of surgery, and the identification of subsets that might benefit the most from an early intervention strategy (e.g. myocardial fibrosis).
Transcatheter aortic valve implantation vs. surgical aortic valve replacement for aortic stenosis
The choice of treatment modality for AS remains controversial. The randomized UK transcatheter aortic valve implantation (TAVI) Trial (4) with the primary endpoint of all-causemortality included 913 patients aged 70 years or older (median 81 years) with severe symptomatic AS and low-to-moderate operative risk (median STS score 2.6%). The trial confirms the non-inferiority of TAVI. There was no difference in stroke, and the rate of severe bleeding was higher with surgical aortic valve replacement, while vascular complications, pacemaker implantation, and paravalvular regurgitation were more frequent with TAVI. In contrast to previous trials, this trial was pragmatic, publicly funded, and designed to compare a TAVI strategy using any valve type and access route vs. surgery in a broad range of patients included according to clinical equipoise regarding the treatment options and not bound by prespecified risk score.
Cerebral embolic protection during transcatheter aortic valve implantation
Stroke due to embolization of debris during the procedure remains a devastating complication of TAVI. Kapadia et al. (5) randomized 3000 transfemoral TAVI patients to use or no use of the Sentinel embolic protection device. The use of the protection device appeared to be safe but the incidence of all stroke within 72 h post-intervention or before discharge (primary endpoint) was overall low and did not differ between groups (2.3 vs. 2.9%). No subgroup by age or potential risk factors could be identified that demonstrated a benefit of cerebral embolic protection. This study does not support the routine use of embolic protection devices. A more selective individualized approach in high-risk–risk patients and its impact on disabling stroke deserve further evaluation.
Transcatheter edge-to-edge repair (TEER) in older patients with severe, symptomatic degenerative mitral regurgitation
Current guidelines recommend TEER in patients with severe degenerative mitral regurgitation (DMR) deemed inoperable or at high risk for surgery without definitive evidence. It is, however, unlikely that a randomized trial will ever be conducted to compare TEER, which is a Class II recommendation in high-risk patients with primary MR, with medical therapy. Benfari et al. (6) analysed large registries (MitraSwiss, Minneapolis Heart Institute, MIDA) including 1187 patients≥65 years with symptomatic severe DMR. TEER was associated with lower mortality adjusted for age, sex, EuroSCORE II, NYHA class, atrial fibrillation, and LVEF. After propensity matching (247 pairs with median EuroSCORE II of 3.0%), TEER consistently showed better survival compared with unoperated patients (49±6 vs. 37±3% at 4 years).
Procedural failure was infrequent in this registry of experienced operators but associated with excess mortality. These findings suggest extending indications of TEER in patients aged older than 65 years with severe DMR beyond the current recommendation in inoperable or high-risk patients.
Prediction of mortality after isolated tricuspid valve surgery
Isolated tricuspid valve surgery (ITVS) in non-congenital severe tricuspid regurgitation (TR) is considered a high-risk procedure but outcomevaries markedly depending on patient characteristics and appropriate risk assessment is crucial for decision-making. From data of 466 consecutive patients undergoing ITVS, Dreyfus et al. (7) derived and internally validated a new scoring system (TRI-SCORE –http://www.tri-score.com/) for in-hospital mortality prediction based on eight variables: age ≥70 years, NYHA Class III–IV, right-sided heart failure signs, daily dose of furosemide ≥125 mg, glomerular filtration rate <30 mL/min, elevated bilirubin, LVEF <60%, and moderate/severe right ventricular dysfunction. The TRI-SCORE provided excellent discrimination and calibration with observed and predicted in-hospital mortality increasing from 0% to 60% and from 1% to 65% with a score increase from 0 to ≥9. This score using easily available variables may guide the clinical decision-making process of patients with severe TR.
Concomitant tricuspid valve repair in patients with degenerative mitral regurgitation
Concomitant tricuspid valve repair (TVR) is liberally recommended in patients undergoing mitral valve (MV) surgery as persistent or developing severe TR has been demonstrated to be an important cause of late morbidity and mortality, but the evidence is weak. Gammie et al. (8) randomly assigned 401 patients with moderate TR or less-than-moderate TR but annular dilatation undergoing MV surgery for DMR to a mitral procedure with or without TVR. The primary 2-year endpoint—a composite of reoperation for TR, progression of TR by two grades from baseline or the presence of severe TR, or death was met but mainly driven by the progression of TR (particularly in patients with moderate TR at baseline) while mortality and morbidity were not significantly different. Remarkably, the patients with concomitant TVR had a significantly higher pacemaker implantation rate. While the latter remains a matter of concern, the negative impact of significant TR occurrence on long-term outcomes may not be detected with the short FU of 2 years.
Thombolysis or surgery in patients with obstructive mechanical valve thrombosis
The optimal treatment of obstructive mechanical valve thrombosis remains controversial. Current guidelines favour surgery as long as it can be performed with acceptable risk. Özkan et al. (9) aimed to prospectively evaluate the outcomes of thrombolytic therapy (TT) using slow (6 h) and/or ultraslow (25 h) infusion of low-dose tissue plasminogen activator (25 mg) and surgery. The success rate of TT was 90%. Event rates in the surgical (n = 75) and TT (n = 83) groups were as follows: minor complications 39 vs. 8%, major complications 41 vs. 6%, and 3-month mortality 19 vs. 2%, respectively. Although the study is observational with inherent selection and confounding bias and the number of patients is relatively small, the high success rate and markedly low complication rate of the proposed TT regime may influence our practice in obstructive mechanical valve thrombosis.
Non-vitamin K antagonist oral anticoagulation in rheumatic heart disease associated atrial fibrillation
Patients with rheumatic mitral stenosis and AF were excluded from prior studies comparing vitamin K antagonists (VKAs) and non-vitamin K antagonist oral anticoagulation in AF. The INVICTUS trial (10) randomly assigned 4565 patients with rheumatic heart disease associated atrial fibrillation (mean age: 51 years, 72% women and 85% with mitral stenosis) to standard doses of rivaroxaban or dose-adjusted VKA (open-label trial with blinded assessment of outcomes). Unexpectedly, VKA therapy led to lower rates of the primary endpoint (composite of cardiovascular events or death), stroke, all-cause death, and sudden death than rivaroxaban, without a higher bleeding rate. Possible explanations for these findings include the lower-than-expected stroke rate thereby reducing trial power, closer clinical monitoring, and better compliance in theVKAgroup.Differences in mortality were large and unlikely to be due to chance. The study supports current recommendations of VKA use in mitral stenosis.