Uncommon presentations of type A quadricuspid aortic valve in the Septuagenarian.

BACKGROUND: Quadricuspid aortic valve (QAV) is a rare congenital anomaly characterized by the presence of four cusps instead of the usual three. It is estimated to occur in less than 0.05% of the population, with Type A (four equal-sized leaflets) accounting for roughly 30% of QAV subtypes. Based on limited clinical series, the usual presentation is progressive aortic valve regurgitation (AR) with symptoms occurring in the fourth to sixth decade of life. Severe aortic valve stenosis (AS) and acute AR are very uncommon. CASE PRESENTATION: We describe two cases of Type A QAV in patients who remained asymptomatic until their seventies with very uncommon presentations: one with severe AS and one with acute, severe AR and flail leaflet. In Case A, a 72-year-old patient with history of moderate AS presents to clinic with progressive exertional dyspnea. During work-up for transcatheter vs. surgical replacement pre-operative computed tomography angiogram (CTA) reveals a quadricuspid aortic valve with severe AS, and the patient undergoes surgical aortic valve replacement. Pre-discharge transthoracic echocardiography (TTE) shows good prosthetic valve function with no gradient or regurgitation. In Case B, a 76-year-old patient is intubated upon arrival to the hospital for acute desaturation, found to have wide open AR on catheterization, and transferred for emergent intervention. Intraoperative TEE reveals QAV with flail leaflet and severe AR. Repair is considered but deferred ultimately due to emergent nature. Post-operative TTE demonstrates good prosthetic valve function with no regurgitation and normal biventricular function. CONCLUSIONS: QAV can present as progressive severe AS and acute AR, with symptoms first occurring in the seventh decade of life. The optimal treatment for QAV remains uncertain. Although aortic valve repair or transcatheter option may be feasible in some patients, aortic valve replacement remains a tenable option.

Recent updates on asymptomatic and symptomatic aortic valve stenosis its diagnosis, pathogenesis, management and future perspectives.

Aortic stenosis (AS) is very common in mid-aged and elderly patients, and it has been reported to have a negative impact on both short and long-term survival with a high mortality rate. The current study identified methods of diagnosis, incidence, and causes of AS, pathogenesis, intervention and management and future perspectives of Asymptomatic and Symptomatic Aortic stenosis. A systematic literature search was conducted using PubMed, Scopus and CINAHL, using the Mesh terms and key words "Aortic stenosis", "diagnostic criteria", "pathogenesis", "incidence and causes of AS" and" intervention and management strategies". Studies were retained for review after meeting strict inclusion criteria that included studies evaluating Asymptomatic and Symptomatic AS. Studies were excluded if duplicate publication, overlap of patients, subgroup studies of a main study, lack of data on AS severity, case reports and letters to editors. Forty-five articles were selected for inclusion. Incidence of AS across the studies ranged from 3 % to 7 %. Many factors have been associated with incidence and increased risk of AS, highest incidence of AS was described after aortic valve calcification, rheumatic heart disease, degenerative aortic valve disease, bicuspid aortic valve and other factors. AS is common and can be predicted by aortic root calcification volume, rheumatic heart disease, degenerative aortic valve disease, bicuspid aortic valve. Intervention and management for AS patients is a complex decision that takes into consideration multiple factors. On the other hand, there is not enough progress in preventive pharmacotherapy to slow the progression of AS.

Role of aortic valve replacement in moderate aortic stenosis: a 10-year outcomes study.

OBJECTIVE: Patients with moderate aortic stenosis (AS) exhibit high morbidity and mortality. Limited evidence exists on the role of aortic valve replacement (AVR) in this patient population. To investigate the benefit of AVR in moderate AS on survival and left ventricular function. METHODS: In a retrospective cohort study, patients with moderate AS between 2008 and 2016 were selected from the Cleveland Clinic echocardiography database and followed until 2018. Patients were classified as receiving AVR or managed medically (clinical surveillance). All-cause and cardiovascular mortality were assessed by survival analyses. Temporal haemodynamic and structural changes were assessed with longitudinal analyses using linear mixed effects models. RESULTS: We included 1421 patients (mean age, 75.3±5.4 years and 39.9% women) followed over a median duration of 6 years. Patients in the AVR group had lower risk of all-cause (adjusted HR (aHR)=0.51, 95% CI: 0.34 to 0.77; p=0.001) and cardiovascular mortality (aHR=0.50, 95% CI: 0.31 to 0.80; p=0.004) compared with those in the clinical surveillance group irrespective of sex, receipt of other open-heart surgeries and underlying malignancy. These findings were seen only in those with preserved left ventricular ejection fraction (LVEF) ≥50%. Further, patients in the AVR group had a significant trend towards an increase in LVEF and a decrease in right ventricular systolic pressure compared with those in the clinical surveillance group. CONCLUSIONS: In patients with moderate AS, AVR was associated with favourable clinical outcomes and left ventricular remodelling.

Elevated Lp(a): Guidance for Identifying and Managing Patients.

Lipoprotein(a) (Lp(a)) is a unique low-density lipoprotein-like lipoprotein that is considered an independent and causal risk factor for atherosclerotic cardiovascular disease (ASCVD) and calcific aortic valve stenosis. The Lp(a) molecule also contains apolipoprotein A and apolipoprotein B, which collectively promote atherosclerosis, thrombosis, and inflammation. Lp(a) is highly genetic and minimally responsive to nonpharmacological measures. Lp(a) serum levels ≥125 nmol/L are associated with increased ASCVD risk, but this threshold has not been accepted universally. Elevated Lp(a) is the most common genetic dyslipidemia affecting approximately 20% of the general population. Certain currently available lipid-lowering drugs, including the proprotein convertase subtilisin/kexin type 9 therapies, produce moderate reductions in Lp(a); however, none are indicated for the treatment of elevated Lp(a). There are currently four investigational RNA-based therapeutic agents that reduce Lp(a) by 70% to 100%. Two of these agents are being evaluated for ASCVD risk reduction in adequately powered outcomes trials, with results expected in 2 to 3 years. Until such therapies become available and demonstrate favorable clinical outcomes, strategies for elevated Lp(a) primarily involve early and intensive ASCVD risk factor management.

Non-invasive assessment of left ventricular filling pressure in aortic stenosis.

BACKGROUND: The assessment of left ventricular (LV) filling pressure (FP) is important for the management of aortic stenosis (AS) patients. Although, it is often restricted for predict LV FP in AS because of mitral annular calcification and a certain left ventricular hypertrophy. Thus, we tested the predictive ability of the algorithm for elevated LV FP in AS patients and also applied a recently-proposed echocardiographic scoring system of LV FP, visually assessed time difference between the mitral valve and tricuspid valve opening (VMT) score. METHODS: We enrolled consecutive 116 patients with at least moderate AS in sinus rhythm who underwent right heart catheterization and echocardiography within 7 days. Mean pulmonary artery wedge pressure (PAWP) was measured as invasive parameter of LV FP. LV diastolic dysfunction (DD) was graded according to the ASE/EACVI guidelines. The VMT score was defined as follows: time sequence of opening of mitral and tricuspid valves was scored to 0-2 (0: tricuspid valve first, 1: simultaneous, 2: mitral valve first). When the inferior vena cava was dilated, one point was added and VMT score was finally calculated as 0-3. RESULTS: Of the 116 patients, 29 patients showed elevated PAWP. Ninety patients (93%) and 67 patients (63%) showed increased values for left atrium volume index (LAVI) and E/e', respectively when the cut-off values recommended by the guidelines were applied and thus the algorism predicted elevated PAWP with a low specificity and positive predictive value (PPV). VMT ≥ 2 predicted elevated PAWP with a sensitivity of 59%, specificity of 90%, PPV of 59%, and negative predictive value of 89%. An alternative algorithm that applied tricuspid regurgitation velocity and VMT scores was tested, and its predictive ability was markedly improved. CONCLUSION: VMT score was applicable for AS patients. Alternative use of VMT score improved diagnostic accuracy of guideline-recommended algorism.

Prognostic value of left ventricular and left atrial strain imaging in moderate to severe aortic stenosis: Insights from an Asian population.

BACKGROUND: Data regarding the prognostic value of left atrial (LA) strain in aortic stenosis (AS) is scarce, especially in Asian population and moderate AS. METHOD: Left ventricular global longitudinal strain (LVGLS), LA reservoir strain (LASr), conduit strain (LAScd), and contractile strain (LASct) were measured using automated speckle-tracking echocardiography in consecutive patients with moderate or severe AS. The primary endpoint was a composite of all-cause death (ACD) and major adverse cardiovascular events (MACE; myocardial infarction, syncope, and heart failure hospitalization). RESULTS: Of 712 patients (mean age, 78 ± 12 years; 370 [52%] moderate AS; 342 [48%] severe AS), average LV ejection fraction (LVEF) was 68 with SD of 12%. At a median follow-up of 18 months (interquartile range, 11-26 months), the primary endpoint occurred in 93 patients (60 deaths and 35 MACEs) and 221 patients underwent surgical or transcatheter aortic valve replacement (AVR). In the entire cohort, separate multivariable models adjusted for age, Charlson index, symptomatic status, time-dependent AVR, AS-severity, LA volume index and LVEF demonstrated that only LASr was associated with MACE+ACD (Hazard ratio, 0.97; P = 0.014). Subgroup analysis for MACE+ACD demonstrated consistent prognostication for LASr in moderate and severe AS; LVGLS was prognostic only in severe AS (all P ≤ 0.023). The optimal MACE+ACD cutoff for LASr from spline curves was 21.3%. Adjusted Kaplan-Meier curves demonstrated better event-free survival in patients with LASr >21.3% versus those with LASr ≤21.3% (P = 0.04). CONCLUSIONS: In both moderate and severe AS, only LASr robustly predicted outcomes; thus, including LASr in the AS staging algorithm should be considered.

Evaluation of Instantaneous Wave-Free Ratio and Fractional Flow Reserve in Severe Aortic Valve Stenosis.

BACKGROUND: The optimal functional evaluation of coronary artery stenosis in patients with severe aortic stenosis (AS) has not been established. The objective of the study was to evaluate the instantaneous wave-free ratio (iFR) and fractional flow reserve (FFR) in patients with and without severe AS. METHODS: We retrospectively investigated 395 lesions in 293 patients with severe AS and 2257 lesions in 1882 patients without severe AS between 2010 and 2022 from a subgroup of the Interventional Cardiology Research In-Cooperation Society FFR Registry. All patients had FFR values, and iFR was analyzed post hoc using dedicated software only in lesions with adequate resting pressure curves (311 lesions in patients with severe AS and 2257 lesions in patients with nonsevere AS). RESULTS: The incidence of iFR ≤0.89 was 66.6% and 31.8% (P<0.001), while the incidence of FFR ≤0.80 was 45.3% and 43.9% (P=0.60) in the severe AS group and the nonsevere AS group, respectively. In the severe AS group, most lesions (95.2%) with iFR >0.89 had FFR >0.80, while 36.2% of lesions with iFR ≤0.89 had FFR >0.80. During a median follow-up of 2 years, FFR ≤0.80 was significantly associated with deferred lesion failure (adjusted hazard ratio, 2.71 [95% CI, 1.08-6.80]; P=0.034), while iFR ≤0.89 showed no prognostic value (adjusted hazard ratio, 1.31 [95% CI, 0.47-3.60]; P=0.60) in the severe AS group. Lesions with iFR ≤0.89 and FFR >0.80, in particular, were not associated with a higher rate of deferred lesion failure at 3 years compared with lesions with iFR >0.89 (15.4% versus 17.0%; P=0.58). CONCLUSIONS: This study suggested that FFR appears to be less affected by the presence of severe AS and is more associated with prognosis. iFR may overestimate the functional severity of coronary artery disease without prognostic significance, yet it can be useful for excluding significant stenosis in patients with severe AS.

Heyde's syndrome: a challenging case of severe aortic stenosis and gastrointestinal bleeding.

We present the case of an elderly man with a history of diastolic congestive heart failure, severe aortic stenosis and atrial fibrillation, who presented with fatigue, weakness, coffee ground emesis and black tarry stool. Haemoglobin was 68 g/L. Lactate dehydrogenase was elevated at 1038. Evaluation by cardiology and gastroenterology specialists revealed reflux oesophagitis and a mild hiatal hernia on oesophagogastroduodenoscopy, normal colonoscopy and small bowel series without obstruction. Capsule endoscopy identified angiodysplasia in the small intestine.The patient was diagnosed with Heyde's syndrome based on the triad of severe aortic stenosis, gastrointestinal bleeding from angiodysplasia and acquired von Willebrand syndrome. The patient underwent transcatheter aortic valve replacement, resulting in the resolution of symptoms.Heyde's syndrome represents a challenging clinical entity requiring a multidisciplinary approach for accurate diagnosis and management. Early recognition, prompt intervention and interdisciplinary collaboration are crucial in optimising patient outcomes.

Acute Mitral Valve Regurgitation Caused by Left Ventricular Pacing Wire During Transcatheter Aortic Valve Replacement.

Transcatheter aortic valve replacement is quickly becoming the standard of care for patients with severe aortic stenosis thanks to its minimally invasive nature and favorable outcomes. Recently, left ventricular pacing has been proposed as a safer alternative to traditional right heart pacing, which could simplify the transcatheter aortic valve replacement procedure overall, although procedural complications may still occur. This report describes a rare case of left ventricular pacing wire-induced acute severe mitral valve regurgitation during transcatheter aortic valve replacement.

Kissing shockwave balloon in a case of extensive calcified abdominal aorta during transfemoral TAVI.

An 84-year-old man with extensive calcified atherosclerosis of the infrarenal abdominal aorta was diagnosed with severe aortic valve stenosis, presenting with dyspnea. To facilitate transfemoral approach during the TAVI procedure, IVUS-guided intravascular lithotripsy was successfully performed using Kissing Shockwave Balloon Technique.

Identification of hub genes in calcific aortic valve disease.

Calcific aortic valve disease (CAVD) is a heart valve disorder characterized primarily by calcification of the aortic valve, resulting in stiffness and dysfunction of the valve. CAVD is prevalent among aging populations and is linked to factors such as hypertension, dyslipidemia, tobacco use, and genetic predisposition, and can result in becoming a growing economic and health burden. Once aortic valve calcification occurs, it will inevitably progress to aortic stenosis. At present, there are no medications available that have demonstrated effectiveness in managing or delaying the progression of the disease. In this study, we mined four publicly available microarray datasets (GSE12644 GSE51472, GSE77287, GSE233819) associated with CAVD from the GEO database with the aim of identifying hub genes associated with the occurrence of CAVD and searching for possible biological targets for the early prevention and diagnosis of CAVD. This study provides preliminary evidence for therapeutic and preventive targets for CAVD and may provide a solid foundation for subsequent biological studies.

Risk of supranormal left ventricular ejection fraction in patients with aortic stenosis.

BACKGROUND: Cardiovascular events are increasing in patients with supranormal left ventricular ejection fraction (snLVEF). However, the effect of snLVEF in patients with aortic stenosis (AS) remains unclear, especially in patients with moderate AS. HYPOTHESIS: This study aimed to evaluate the prognosis of mortality and heart failure (HF) in patients with LVEF ≥ 50% and moderate or severe AS. METHODS: This retrospective study targeted patients with moderate or severe AS and LVEF > 50%. LVEF of 50%-65% was classified as normal LVEF (nLVEF, nEF group) and >65% as snLVEF (snEF group). AS severity was stratified based on the aortic valve area into moderate (1.0-1.5 cm²) and severe (<1.0 cm²). Primary outcomes included all-cause mortality and HF hospitalization. RESULTS: A total of 226 participants were included in this study. There were 67 and 65 participants with moderate AS in snEF (m-snEF) and nEF groups (m-nEF), respectively, and 41 and 53 participants with severe AS in the snEF (s-snEF) and nEF groups (s-nEF), respectively. During the observation period (median: 554 days), the primary composite outcome occurred in 108 individuals. Cox hazard analysis revealed no significant differences among the four groups in primary composite outcomes. With respect to HF hospitalization, the adjusted hazard ratios (95% confidence intervals) with m-snEF as the reference were as follows: m-nEF, 0.41 (0.19-0.89); s-nEF, 1.43 (0.76-2.67); and s-snEF, 1.83 (1.00-3.35). CONCLUSIONS: The risk of HF hospitalization for m-snLVEF was higher than m-nLVEF and not significantly different from s-nLVEF.

Hybrid robotic-assisted coronary revascularization and transcatheter aortic valve replacement: a single-center experience.

OBJECTIVES: The efficacy of hybrid robotic-assisted coronary artery bypass grafting (CABG) and transcatheter aortic valve replacement (TAVR) for coronary and aortic valve disease is poorly reported. Herein, we report our experience with this hybrid approach. METHODS: Between January 2018 and June 2022, 10 (7 male, 3 female) patients with a mean age of 81 years underwent the hybrid procedure. Coronary revascularization was performed prior to TAVR with robotic-assisted left internal mammary artery-to-left anterior descending (LAD) bypass grafting for left main or proximal LAD lesions with or without multivessel disease with or without hybrid percutaneous coronary intervention (PCI). RESULTS: Five patients had left main disease, and 5 had proximal LAD disease with or without multivessel disease. All patients tolerated the robotic-assisted CABG procedure well; 9 patients were extubated in the operating room and all patients were ambulatory on postoperative day 1. Five patients underwent hybrid PCI for non-LAD lesions. TAVR was subsequently performed at intervals ranging from 3 days to 5 months after CABG. One patient with end-stage renal disease on hemodialysis required hospitalization for heart failure during the interval period. The 1-year mortality rate was 0%, and 3 patients died during late follow-up (24-43 months). CONCLUSIONS: This innovative, less invasive approach demonstrates the potential for early recovery in appropriately selected patients with complex coronary and aortic valve disease with promising mid-term outcomes.

Optimal oversizing in transcatheter aortic valve replacement with the self-expanding Evolut valve system.

OBJECTIVES: Valve oversizing has been associated with reduced paravalvular leaks (PVL) and valve migration risk. However, no optimal cut-off oversizing value has been defined for the Evolut system (Medtronic). The aim of this study was to assess the relationship between the degree of oversizing and moderate-to-severe PVL and determine the optimal oversizing cut-off value. METHODS: We conducted a multicenter study that included 740 consecutive patients with multidetector computed tomography (CT) data. Valve size was selected according to manufacturer recommendations, with oversizing ranging from 10% to 30%. The primary endpoint was moderate-to-severe PVL. RESULTS: The median age was 84 years (79-87 years), with 58.4% women, and a median EuroSCORE II of 4.1% (2.4-7.3%). Moderate-to-severe PVL was observed in 7.0% of the patients. An inverse relationship was found between oversizing and both PVL (11.3%, 8.6%, 5.4%, and 2.7% for quartiles Q1 to Q4; P = .007) and the need for post-dilation (P = .016). The multivariable analysis showed an association between oversizing and PVL (OR: 0.915 for each 1%-increase, P = .002). The optimal oversizing cut-off value to predict PVL was 20%, and PVL was significantly higher in patients with oversizing less than 20% (10.5% vs.4.2%, P less than .001). There were no differences in major clinical events according to the degree of oversizing, and a higher oversizing did not translate into an increased risk of permanent pacemaker (18.4% vs18.3%, P = .976). CONCLUSIONS: In TAVR with the Evolut valve, a higher oversizing was associated with lower rates of moderate-to-severe PVL and a lower need for post-dilation, with no negative impact on procedural and early clinical outcomes. A 20% oversizing threshold could be suggested to reduce PVLs. Further prospective studies are warranted to validate optimal oversizing for this valve system.

Prevalence and Outcomes of Patients With Discordant High-Gradient Aortic Stenosis.

BACKGROUND: Conflicting prognostic results have been reported in patients with discordant high-gradient aortic stenosis ([DHG-AS] the combination of a mean pressure gradient ≥40 mm Hg and an aortic valve area [AVA] >1 cm2). Moreover, existing studies only included selected patients without concomitant aortic regurgitation. OBJECTIVES: The authors assessed the prevalence and survival of patients presenting with DHG-AS in an unselected group of consecutive patients presenting to the echocardiography laboratory of a tertiary referral center. METHODS: A total of 3,547 adult patients with AVA ≤1.5 cm2 and peak aortic jet velocity ≥2.5 m/s or mean gradient ≥25 mm Hg who presented between 2005 and 2015 were included. Baseline clinical and echocardiographic data, and, when available, aortic valve calcium (AVC) score were collected in an institutional database, with subsequent retrospective analysis. The primary endpoint was all-cause mortality during follow-up. RESULTS: DHG-AS was observed in 163 patients (11.6% of patients with a high gradient). After adjustment for potential confounders, overall mortality rate of patients with DHG-AS was similar to that of patients with concordant severe aortic stenosis (HR: 0.98 [95% CI: 0.66-1.44]; P = 0.91), and patients with discordant low-gradient aortic stenosis (HR: 0.85 [95% CI: 0.58-1.26]; P = 0.42), and higher than concordant moderate aortic stenosis (HR: 0.54 [95% CI: 0.36-0.81]; P = 0.003). After adjustment for aortic velocities, aortic regurgitation had no significant impact on survival. AVC was higher than in patients with concordant moderate aortic stenosis and discordant low-gradient aortic stenosis, and not significantly different from that of concordant severe aortic stenosis. CONCLUSIONS: DHG-AS is not uncommon. Whereas AVA >1.0 cm2 is often seen as moderate aortic stenosis, a high-pressure gradient conveys a poor prognosis, whatever the AVA and the severity of concomitant aortic regurgitation.

Tumour necrosis factor-alpha serum level is an independent predictor of medium-term all-cause mortality after transcatheter aortic valve replacement.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) is a suitable treatment for patients with severe aortic stenosis and severely increased operative risk. There is need for a better preoperative risk assessment for TAVI candidates. AIM: To determine whether Tumour necrosis factor-alfa (TNFα) is an independent predictor of survival 500 days after TAVI. METHODS: Sixty patients undergoing TAVI were enrolled in the study. TNFα was determined. The CT measured low-density muscle fraction (LDM%) of the psoas muscle was determined. Operative risk assessment by Logistic EuroSCORE, EuroSCORE II, and STS score was performed. Frailty scores (FRAIL scale and Barthel index) were determined. RESULTS: Mean age was 81.01 ± 7.54 years. Twenty-six (43.3%) of the patients were males. In the univariable analyses, FRAIL scale and Barthel index were no predictors of survival after TAVI. In the multivariable analysis, including EuroSCORE II, LDM% and TNFα serum concentration, TNFα serum level was an independent predictor of survival 500 days after TAVI (HR: 3.167; 95%: 1.279-7.842; p = 0.013). The multivariable analysis, including TNFα as a categorical variable, showed that compared to patients in the conjugated first and second TNFα serum level tertile, patients in the third tertile had a hazard ratio (HR) of 10.606 (95%CI: 1.203 - 93.467) (p = 0.033). CONCLUSION: TNFα is an incremental independent predictor of long-term survival after TAVI.

Concomitant transthyretin cardiac amyloidosis in patients undergoing TAVR for aortic stenosis: A systemic review and meta-analysis.

OBJECTIVE: Transcatheter aortic valve replacement (TAVR) is a successful treatment for aortic stenosis (AS) patients, and previous studies indicate favorable outcomes for those with concomitant aortic stenosis and transthyretin-associated cardiac amyloidosis (TTRCA-AS). However, the impact of TAVR on more adverse outcomes in TTRCA-AS patients compared to those with AS alone is still uncertain, with conflicting findings reported in the literature. METHODS: PubMed and Scopus were extensively searched from inception till August 2021. Studies were included if they reported data for prevalence and outcomes including mortality and cardiovascular-related hospitalization events in TTRCA-AS patients referred for TAVR. The data for these outcomes were pooled using a random effects model and forest plots were created. RESULTS: After initially screening 146 articles, 6 were shortlisted for inclusion in our analysis. Pooled analysis demonstrated a 13.3% [95% CI: 10.9-16.5; p = 0.307] prevalence of TTRCA in patients with AS undergoing TAVR. The incidence of mortality and cardiovascular (CV) hospitalization in patients with TTRCA-AS undergoing TAVR were 28.3% [95% CI: 18.7-39.0, p = 0.478] and 21.1% [95% CI: 10.2-34.5, p = 0.211], respectively. CONCLUSION: The overall pooled TTRCA-AS prevalence was reported to be 13.3% in AS patients who underwent TAVR. Furthermore, transthyretin-associated CA was found to be associated with an increased risk of mortality and hospitalization. Large patient population studies are required to assess the safety and efficacy of TAVR in TTRCA-AS patients, as current research report data from small patient cohorts.

mPAP/CO Slope and Oxygen Uptake Add Prognostic Value in Aortic Stenosis.

BACKGROUND: Recent guidelines redefined exercise pulmonary hypertension as a mean pulmonary artery pressure/cardiac output (mPAP/CO) slope >3 mm Hg·L-1·min-1. A peak systolic pulmonary artery pressure >60 mm Hg during exercise has been associated with an increased risk of cardiovascular death, heart failure rehospitalization, and aortic valve replacement in aortic valve stenosis. The prognostic value of the mPAP/CO slope in aortic valve stenosis remains unknown. METHODS: In this prospective cohort study, consecutive patients (n=143; age, 73±11 years) with an aortic valve area ≤1.5 cm2 underwent cardiopulmonary exercise testing with echocardiography. They were subsequently evaluated for the occurrence of cardiovascular events (ie, cardiovascular death, heart failure hospitalization, new-onset atrial fibrillation, and aortic valve replacement) during a follow-up period of 1 year. Findings were externally validated (validation cohort, n=141). RESULTS: One cardiovascular death, 32 aortic valve replacements, 9 new-onset atrial fibrillation episodes, and 4 heart failure hospitalizations occurred in the derivation cohort, whereas 5 cardiovascular deaths, 32 aortic valve replacements, 1 new-onset atrial fibrillation episode, and 10 heart failure hospitalizations were observed in the validation cohort. Peak aortic velocity (odds ratio [OR] per SD, 1.48; P=0.036), indexed left atrial volume (OR per SD, 2.15; P=0.001), E/e' at rest (OR per SD, 1.61; P=0.012), mPAP/CO slope (OR per SD, 2.01; P=0.002), and age-, sex-, and height-based predicted peak exercise oxygen uptake (OR per SD, 0.59; P=0.007) were independently associated with cardiovascular events at 1 year, whereas peak systolic pulmonary artery pressure was not (OR per SD, 1.28; P=0.219). Peak Vo2 (percent) and mPAP/CO slope provided incremental prognostic value in addition to indexed left atrial volume and aortic valve area (P<0.001). These results were confirmed in the validation cohort. CONCLUSIONS: In moderate and severe aortic valve stenosis, mPAP/CO slope and percent-predicted peak Vo2 were independent predictors of cardiovascular events, whereas peak systolic pulmonary artery pressure was not. In addition to aortic valve area and indexed left atrial volume, percent-predicted peak Vo2 and mPAP/CO slope cumulatively improved risk stratification.