AVR = aortic valve replacement. HF = heart failure. RCT = randomized controlled trial. SAVR = surgical aortic valve replacement. TAVR = transcatheter aortic valve replacement.

3. The Kansas City Cardiomyopathy Questionnaire: A Tool to Evaluate HF Symptoms

The aim of AVR is to improve both longevity and health status (symptoms, physical functioning, and quality of life). Changes in health status after AVR can be accurately and reliably measured using the Kansas City Cardiomyopathy Questionnaire (KCCQ). The KCCQ was originally developed as a tool for measuring the symptoms, social and physical limitations, quality of life, and self-efficacy in HF patients and has been validated as a reliable instrument for measuring the health status of severe AS patients ^[29][30][32,33]. It is a 23-item self-administered questionnaire that measures 7 specific health domains relevant to HF. The domain scores and 3 summary scores are each represented on a 0–100 scale, with higher scores indicating a better health status ^[31][34]. An abbreviated 12-item version, the KCCQ-12, has been validated and has an excellent concordance with the original 23-item scale. The KCCQ overall summary score (KCCQ-OS) is commonly reported as a summary assessment of the health status of AS patients before and after AVR. To improve their interpretability, KCCQ-OS scores are often analyzed in 25-point ranges (0–24, 25–49, 50–74, and 75–100), representing very poor to poor, poor to fair, fair to good, and good to excellent health statuses ^[31][34]. Both TAVR and SAVR have shown remarkable improvements in KCCQ-OS from baseline to 1 year in recent clinical trials (Figure 2). Despite a large average treatment effect of AVR being evidenced by these clinical trial results, a substantial proportion of patients continue to remain symptomatic with HF after AVR. This discrepancy highlights the importance of identifying patients with residual HF symptoms despite a successful AVR procedure. A major advance in this area was the development of a “poor outcome” after TAVR, a concept that was introduced by Arnold et al. in 2013 ^[32][35]. In the current era, a “poor outcome” after TAVR is defined as death, KCCQ-OS of <60, or a decline in KCCQ-OS by 10 or more points from baseline to 1-year post-TAVR. This framework allows investigators to identify patients who either did not survive or are living with a low or declining health status 1 year after AVR. Remarkably, in practice, a large proportion of patients meet the definition of a poor outcome 1 year after TAVR, and, although this is declining ^[37][40], the decline in poor outcomes is far less than the rate of decline in 1-year post-TAVR mortality. In 2018, the rate of poor outcomes after TAVR was 32%, with 19% of patients having a low or declining health status [12]. These data highlight that, even in the modern era of TAVR, 1 out of 3 patients die or suffer from a substantial HF symptom burden with a low or declining health status 1 year after TAVR. This observation underscores the need for strategies to better identify and treat these patients longitudinally pre- and post-AVR.

4. Risk Factors for Poor Outcome and HF after AVR

Various risk models have been developed to predict patients at risk of poor outcomes based on pre-procedure patient characteristics ^[38][41]. Among the high-risk patients treated in PARTNER I, predictors of a poor outcome at 1 year included a higher baseline creatinine level, oxygen-dependent lung disease, a lower baseline mean aortic valve gradient, a lower baseline score on the Mini-Mental Status Examination, and a shorter baseline 6 min walk test distance ^[38][41]. An updated model from the TVT Registry reported a lower baseline KCCQ-OS, a lower mean aortic valve gradient, home oxygen use, a higher baseline creatinine level, atrial fibrillation or flutter, and diabetes mellitus as significant predictors of 1-year poor outcomes ^[37][40]. A similar model was developed among the high-risk patients treated in the CoreValve US Pivotal Extreme and High-Risk trials of self-expanding TAVR devices, which identified the same key clinical variables (KCCQ-OS, mean aortic valve gradient, home oxygen, creatinine level, cognitive function, atrial fibrillation or flutter, and diabetes), but further added frailty as a component ^[39][42]. These risk models highlight that poor outcomes after AVR, either with death or a low health status, are associated with major non-cardiac comorbidities such as chronic lung disease, renal dysfunction, diabetes, and frailty. Risk factors for HF hospitalization after TAVR have also been studied and are largely similar to the factors associated with the poor outcome metric (Table 2). A recent analysis of 3403 pooled TAVR and SAVR patients across the low-, intermediate-, and high-risk cohorts from the PARTNER trials identified a low baseline aortic valve mean gradient, atrial fibrillation or flutter, and prior coronary revascularization as factors associated with 1-year HF hospitalization ^[18][14]. Several prior registry studies have identified atrial fibrillation, renal insufficiency, a lower aortic valve mean gradient, higher surgical risk scores, diabetes mellitus, and a lower LV ejection fraction as risk factors for HF hospitalization after TAVR ^{[19][20][21][22][40][41][42]}[16,23,24,25,43,44,45]. In addition to baseline patient characteristics, several post-procedure issues may also increase the risk of HF symptoms and hospitalization. Paravalvular regurgitation ^[43][46], patient–prosthesis mismatch ^[44][45][47,48], new-onset left bundle branch block, and the need for permanent pacemaker implantation ^[46][47][49,50] are associated with an increased incidence of HF hospitalization after TAVR.