Degenerative Valvular Disease Research Articles

Asthma has been associated with the development and progression of various cardiovascular diseases but its relationship with degenerative valvular heart disease (VHD) remains unclear. This study investigated the association between asthma and incident degenerative VHD, including aortic stenosis (AS), aortic regurgitation (AR), mitral regurgitation (MR) and pulmonary regurgitation (PR). We analysed 483 735 participants from the UK Biobank (median age 56.5 years; 45.2% male) who were free of VHD at baseline. Asthma status was self-reported at recruitment. Incident VHD was ascertained through hospital admission and mortality records using International Classification of Diseases, Tenth Revision codes. Cox proportional hazards models were used to estimate HRs and 95% CIs for each VHD subtype, adjusting for demographic, lifestyle and clinical covariates. Sensitivity analyses accounted for asthma medications, duration of asthma and competing risks. Over a median follow-up of 13.8 years, 5388 participants developed AS, 2650 AR, 6088 MR and 821 PR. Asthma was associated with increased risk of AS (HR 1.31; 95% CI 1.21 to 1.41), AR (HR 1.24; 95% CI 1.11 to 1.39), MR (HR 1.19; 95% CI 1.10 to 1.28) and PR (HR 1.34; 95% CI 1.10 to 1.62). The association with AR was attenuated after adjusting for asthma medications (HR 1.12; 95% CI 0.97 to 1.30). Results were robust across multiple sensitivity analyses, including adjustment for asthma duration and exclusion of participants with pre-existing cardiovascular disease. Asthma is independently associated with a modestly increased risk of several degenerative VHDs, particularly aortic and mitral valve diseases. These findings suggest a potential shared inflammatory pathway and highlight the need for heightened cardiovascular surveillance in individuals with asthma.

Accumulating evidence indicates that degenerative valvular heart disease (VHD) and rheumatoid arthritis (RA) share overlapping risk factors and intersecting inflammatory processes; however, their interrelationship remains insufficiently explored. Among 492 745 UK Biobank participants without VHD at baseline, Cox proportional hazards models were conducted to assess the association between prevalent RA and new-onset degenerative VHD, with sequential adjustments for demographic factors, lifestyle variables, and comorbidities. The end points of degenerative VHD in this study included 8 subtypes: aortic stenosis, aortic regurgitation, mitral stenosis, mitral regurgitation, tricuspid stenosis, tricuspid regurgitation, pulmonary stenosis, and pulmonary regurgitation. Among participants with RA (n=6673), 359 cases of degenerative VHD were recorded over a median follow-up of 13.71 (interquartile range, 12.71-14.55) years, compared with 13 518 cases in those without RA (n=486 072) over a median follow-up of 13.78 (interquartile range, 12.96-14.51) years. After full adjustment, RA was significantly associated with a higher risk of 3 types of new-onset degenerative VHD: aortic stenosis (hazard ratio [HR], 1.64 [95% CI, 1.40-1.92]), aortic regurgitation (HR, 1.69 [95% CI, 1.34-2.13]), and mitral regurgitation (HR, 1.54 [95% CI, 1.32-1.81]), while no significant association was observed between RA and other degenerative VHD subtypes. Moreover, sex subgroup analyses revealed an interaction between sex and RA in the occurrence of aortic stenosis (P for interaction=0.02) and mitral regurgitation (P for interaction=0.04), indicating a higher risk in women. The presence of RA indicated an elevated risk of new-onset degenerative aortic stenosis, aortic regurgitation, and mitral regurgitation, which required further investigation and better disease management.

BackgroundBiological aging is a critical risk factor of age-related diseases, but its impact on diabetic individuals remains unclear. This study aimed to examine the associations of biological aging with the incident cardiovascular diseases (CVDs) and life expectancy loss in diabetic individuals.MethodsWe included 12,828 diabetic individuals in UK biobank. Biological aging was calculated by Klemera-Doubal method Biological Age (KDMAge) and phenotypic age (PhenoAge). Cox proportional hazard models were fitted to investigate the associations of biological aging with incident coronary heart disease (CHD), atrial fibrillation (AF), heart failure (HF), stroke, and degenerative valvular heart disease (VHD) in diabetic individuals. We also evaluated life expectancy loss in accelerated aging individuals, the interactions between biological aging and clonal hematopoiesis of indeterminate potential (CHIP), and performed causal mediation analysis.ResultsDuring a median follow-up of 13.1 years, we documented 3794 incident CVDs in diabetic individuals. PhenoAge accelerated aging was significantly associated with all CVD subtypes, with hazard ratios ranging from 1.23 to 1.62, and KDMAge showed even stronger associations. Accelerated biological aging was also associated with over 2 years of life expectancy loss. CHIP and PhenoAge accelerated aging had a significant synergistic effect on CHD, HF, and VHD. Inflammatory activation contributed significantly to accelerated aging-associated CHD and HF.ConclusionsBiological aging significantly increases CVD risk and reduces life expectancy in diabetic population, with effects modified by CHIP status. Targeting biological aging mechanisms may help prevent CVDs and premature mortality in diabetic population.Graphical abstractAF, atrial fibrillation; CHD, coronary heart disease; CHIP, clonal hematopoiesis of indeterminate potential; CI, confidence interval; CVD, cardiovascular disease; HF, heart failure; HR, hazard ratio; KDMAge, Klemera-doubal method biological age; PAR, partial population attributable risk; PhenoAge, phenotypic age; VHD, valvular heart disease.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12933-025-02855-w.

Epidemiology of Valvular Heart Disease in Asia Pacific Region.

There are no effective medications to prevent the onset of degenerative valvular heart disease (VHD). Sweetened beverage consumption may contribute to the development of VHD by affecting metabolic disorders, systemic inflammation, and calcification processes. This study aimed to prospectively assess the association between sweetened beverage consumption and the risk of degenerative VHD. This prospective study included 167,801 participants from the UK Biobank who completed at least one dietary questionnaire. During a median follow-up of 14.53 years, 1,464 cases of aortic valve stenosis (AS) events, 584 cases of aortic valve regurgitation (AR) events, and 1,744 cases of mitral valve regurgitation (MR) events were recorded. Compared with non-consumers, participants consuming more than one drink per day of artificially sweetened beverages (ASBs) had a higher risk of AS (HR: 1.36, 95% CI: 1.10-1.68), AR (HR: 1.42, 95% CI: 1.02-2.00), MR (HR: 1.35, 95% CI: 1.10-1.64). Similarly, the consumption of more than one drink of sugar-sweetened beverages (SSBs) was associated with an increased incidence of MR (HR: 1.47, 95% CI: 1.22-1.77). In contrast, no significant association was observed between the consumption of natural juices (NJs) and VHD risk. Results for VHD-related interventions, deaths, or cardiovascular events were largely consistent. Substituting SSBs or ASBs per day with NJs was associated with a reduced risk of MR (HR: 0.83, 95% CI: 0.72-0.94) events or AS (HR: 0.81, 95% CI: 0.69-0.94) events, respectively. Lower consumption of SSBs or ASBs may reduce the risk of degenerative VHD and VHD-related events.

The cardiovascular-kidney-metabolic (CKM) health approach emphasizes the importance of multidisciplinary early-stage disease prevention. This study aimed to explore sex differences in CKM risk factors associated with common degenerative valvular heart disease (VHD). A total of 436,184 participants (54.4% women; mean age, 58 years) free of VHD or heart failure at baseline and with complete information about CKM risk factors were included from the UK Biobank cohort. We assessed sex differences in hazard ratios (HRs) and population-attributable risk (PAR) for incident VHD and VHD-related interventions or mortality, focusing on five CKM risk factors: hypertension, diabetes, obesity, hypertriglyceridemia, and chronic kidney disease (CKD). At baseline, 81.06% of participants had one or more CKM risk factors: 75.61% had hypertension, 4.80% had diabetes, 24.14% had obesity, 22.26% had hypertriglyceridemia, and 2.32% had CKD. Over a median follow-up period of 13.80 years, incidences of aortic valve stenosis (AS), aortic valve regurgitation (AR), and mitral valve regurgitation (MR) were 11.18 and 5.42, 3.64 and 2.19, and 10.39 and 6.94 events per 10,000 person-years for men and women, respectively. Hypertension was consistently the largest attributable risk factor for incident VHD in both sexes, with PARs of 29.07% and 25.17% for AS, 24.21% and 16.51% for AR, and 19.55% and 13.01% for MR in women and men, respectively. Compared to men, women had higher risks of AS with obesity (HR: 1.17 [1.04-1.32]), AR with CKD (1.59 [1.01-2.49]), and MR with either hypertension (1.25 [1.07-1.47]) or hypertriglyceridemia (1.22 [1.07-1.39]). Tailoring the prioritization of CKM risk factors based on gender has the potential to enhance the effectiveness of VHD prevention strategies.

Severe aortic stenosis (AS) is the most common degenerative valvular heart disease. Given the global aging of the population, it is estimated that the prevalence of severe AS will increase by 300% by year 2050. Surgical replacement of the stenotic aortic valve is still the standard treatment protocol for patients with low and intermediate operative risk. In routine practice of surgical treatment of severe AS in people older than 65 years, biological valves (biovalves) have gradually replaced the mechanical valves. Biovalves can be stented (sutured) or sutureless. Sutured valves are implanted to the aortic annulus using a surgical thread, while sutureless valves are implanted using a pressurized balloon. Previous studies have shown that the advantages of the easier technique of implantation of sutureless valve over the stented valves are the shortening of the operative period, i.e. reduction in time of cardiac arrest and extracorporeal circulation and minimally invasive surgical approach. It must be pointed out that the price of new sutureless valves is on average 10 times more expensive than the price of the stented biovalves. Therefore, the use of these valves in healthcare systems with limited resources can be considered only in patients in whom they would prevent many potential complications during and after the aortic valve replacement. For example, the implantation of a sutureless valve allows less manipulation of the aorta, which is especially important in patients whose aortic root is calcified and worn off, and to prevent the operioperative stroke. Also, patients with a small aortic annulus have a greater benefit from the implantation of a sutureless valve due to the larger effective orifice area, which gives way to better hemodynamic characteristics. Considering that sutureless valves have only been implanted for the past ten years in Europe, numerous studies are limited to the assessment of early and midterm outcomes (on average 5 years of follow-up), such as survival, structural valvular deterioration rate, infective endocarditis rate and reoperation rate. Therefore, prospective cohort studies evaluating long-term outcomes after sutureless valve implantation are warranted.

Recent evidence indicates that degenerative valvular heart disease (VHD) and psoriasis share overlapping risk factors and simultaneous presence of inflammation, yet this relationship has not been thoroughly explored. Drawing on the prospective cohort data from the UK Biobank, baseline information on psoriasis and the incidence of eight specific types of degenerative VHD-aortic stenosis (AS), aortic regurgitation, mitral stenosis, mitral regurgitation, tricuspid stenosis, tricuspid regurgitation, pulmonary stenosis, and pulmonary regurgitation-during the follow-up period were recorded. Cox proportional hazards models were conducted to estimate the association between psoriasis and the risk of degenerative VHD, adjusted for demographic indicators, lifestyle factors, comorbidities, and medication. A total of 494 510 participants were included in the study. Among the participants without psoriasis, 13 672 events of degenerative VHD were observed during a median follow-up of 13.78 years, yielding an incidence rate of 2.14 per 1000 person-years. In contrast, in the psoriasis group (n=10 917), 422 events of degenerative VHD were reported during a median follow-up of 13.70 years, corresponding to an incidence rate of 2.93 per 1000 person-years. After fully adjusting, participants with psoriasis had a significantly increased risk of AS (hazard ratio, 1.24; 95% confidence interval, 1.07-1.43), yet no significant associations were observed between psoriasis and the risk of other degenerative valve diseases. In sex subgroup analyses, there was an interaction between sex and psoriasis in the occurrence of AS (P for interaction=0.039), suggesting a high risk in women. Psoriasis was significantly associated with the risk of new-onset AS and may be more distinct in females, while no significant associations were observed between psoriasis and the risk of developing other degenerative valve diseases.

Background: Despite the increasing prevalence of degenerative valvular heart disease (VHD), recommended preventive interventions are notably lacking. The cardiovascular-kidney-metabolic (CKM) health approach advocates for multidisciplinary early-stage disease prevention. We aimed to explore sex differences in CKM risk factors associated with VHD. Methods: Using data from UK Biobank, participants without a history of VHD or heart failure at baseline were included. We assessed the sex differences in hazard ratios (HRs) and population-attributable risk (PAR) for incident aortic valve stenosis (AS), aortic valve regurgitation (AR), and mitral valve regurgitation (MR) associated with five CKM risk factors: hypertension, diabetes, obesity, high lipoprotein(a), and chronic kidney disease (CKD). Results: Among 463,496 participants (54.4% women), AS, AR, and MR cases were observed at incidence of 1.05 and 0.52, 0.37 and 0.22, 1.04 and 0.70 events per 1000 person-years for men and women, respectively. Hypertension consistently accounted for the largest attributable risk factor for incident VHD in both sexes, with PARs of 29.96% and 26.61% for AS, 23.51% and 16.02% for AR, and 17.56% and 13.09% for MR in women and men, respectively. Compared to men, obesity, CKD, and hypertension were associated with higher risks of AS, AR, and MR in women (women-to-men ratios of HRs: 1.11[1.09–1.36], 1.62[1.01–2.63], and 1.27[1.09–1.49], respectively). Conclusions: This study offers comprehensive insights into the profiles of CKM risk factors for degenerative VHD among middle-aged individuals. Tailoring the prioritization of risk factors based on gender has the potential to improve the precision and effectiveness of VHD prevention strategies.

Platelet to Lymphocyte Ratio (PLR) As a Marker for Aortic Stenosis Development in a Mouse Model: Relationship to Platelet TGFβ1

Background and Objectives: The aim of this study was to estimate the prevalence of silent coronary artery disease (CAD) in asymptomatic patients with severe aortic stenosis (AS) and assess long-term prognosis in terms of major adverse cardiovascular event (MACE)-free survival. Materials and Methods: This was a prospective study conducted at the Clinic for Cardiac Surgery, University Clinical Center of Serbia, in asymptomatic patients with severe AS, normal LVEF and stress test without signs of myocardial ischemia. Adverse cardiovascular events (cardiac death, myocardial infarction and any hospitalization due to heart disease) was monitored during one year of follow up. Results: A total of 116 asymptomatic patients with severe AS were included in the study. The average age was 67.3 ± 9.6 years, and 56.9% of patients were men. The most common cause of AS was degenerative valvular disease (83.5%). The incidence of significant CAD was 30 out of 116 patients (25.9%). The median Society for Thoracic Surgeons (STS) predicted risk of mortality score was 1.62% (25th to 75th percentile: 1.15-2.76%). The overall mean gradient across aortic valve (Pmean) was 52.30 mmHg ± 12.16, and the mean indexed AVA (AVAi) was 0.37 ± 0.09 cm2/m2. The mean LVEF was 68.40% ± 8.01%. Early surgery for aortic valve replacement was performed in 55 patients (55.2%), while 52 (44.8%) patients received conservative treatment. Twenty-two patients (42.3%) in the conservative treatment group underwent surgery during follow up. There were a total of 44 (37.9%) patients with MACE during one year of follow up. Univariate Cox regression analyses identified the following significant risk factors for MACE-free survival: presence of CAD and early conservative treatment (p = 0.004), age (p = 0.003), diabetes mellitus (p = 0.016) and STS score (p = 0.039). According to multivariate analysis, the presence of CAD with early conservative treatment was the most important predictor of MACE-free survival in asymptomatic patients with severe aortic stenosis (p ≤ 0.001). Conclusions: Early surgery for aortic valve replacement in asymptomatic patients with severe AS and concomitant CAD is beneficial for long-term survival.

Background: Aortic valve stenosis (AS) is the most common degenerative valvular heart disease, significantly impacting the outcome. Current guidelines recommend valve replacement only for symptomatic patients, but advanced cardiovascular imaging, particularly cardiac magnetic resonance (CMR), may refine these recommendations. Feature-tracking CMR (FT-CMR) effectively assesses left ventricular (LV) strain and shows promise in predicting major adverse cardiovascular events (MACEs), though data on AS are limited. This study explored the role of CMR-derived LV strain in predicting MACEs occurrence in patients with severe AS. Method: We prospectively assessed 84 patients with severe AS and 84 matched controls. Global longitudinal (GLS), circumferential (GCS), and radial strain (GRS) were evaluated using FT-CMR. A composite endpoint-cardiac death, ventricular tachyarrhythmias, and heart failure hospitalization-was analyzed over a median follow-up of 31 months. Results: GLS was considerably reduced in AS patients (-15.8% vs. -19.7%, p < 0.001) and significantly predicted MACEs (HR = 1.24, p = 0.002) after adjusting for LVEF, 6 min walk distance, native T1, and late gadolinium enhancement. This underscores GLS's unique and robust predictive capability for MACEs in severe AS patients. Kaplan-Meier curves and ROC analysis both showed that GLS had the highest predictive performance for MACEs, with an AUC of 0.857. Conclusions: GLS provided independent incremental predictive value for outcome.

The Annual Report on Cardiovascular Health and Diseases in China (2022) intricate landscape of cardiovascular health in China. In connection with the previous section, this ninth section of the report offers a comprehensive analysis of valvular heart disease and cardiomyopathy. Although rheumatic valve disease is still the main cause of valvular heart disease in China, with the aging of the population and the improvement of living standards, the prevalence of degenerative valvular heart disease is on the rise. Because many patients with valvular heart disease have only mild to moderate valve stenosis or insufficiency, and no symptoms, the detection rate in the population is low and late, resulting in many patients been in the severe late stage of disease at visit, increasing the difficulty of treatment and affecting effectiveness and prognosis. Therefore, we should strengthen the examination and screening of valvular heart disease in order to find and prevent it as early as possible. In addition, compared with other diseases, the treatment of valvular heart disease needs more and higher technical support (surgery, intervention, etc). However, not all hospitals can provide relevant technologies. At present, the treatment of valvular heart disease is still mainly concentrated in the provincial hospitals. It is necessary to carry out more professional training so that more doctors and hospitals can participate in the treatment of valvular heart disease. Cardiomyopathy is a group of myocardial diseases with abnormal myocardial structure and/or function, but couldn't be explained by hypertension, coronary atherosclerosis, valvular heart disease and congenital heart disease. It includes hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), arrhythmogenic cardiomyopathy (also known as arrhythmogenic right ventricular cardiomyopathy), restrictive cardiomyopathy (RCM) and undifferentiated cardiomyopathy.

Quantification of anatomical aortic valve area by multi-detector computed tomography: A pilot 3D-morphological modeling of the stenotic aortic valve

The relationship between physical frailty, age-related conditions, and the incidence of degenerative valvular heart disease (VHD) remains unclear. This study aimed to investigate the potential association between physical frailty and the development of degenerative VHD. Participants from the UK Biobank who were initially free of VHD and heart failure were categorized into 3 groups based on the frailty phenotype: non-frailty, pre-frailty, and frailty. The frailty phenotype was determined by evaluating the following 5 components: weight loss, exhaustion, reduced physical activity, slow gait speed, and low grip strength. The incidence of degenerative VHD, including mitral valve regurgitation (MR), aortic valve regurgitation (AR), and aortic valve stenosis (AS), was assessed using hospital admission or death registries. Among the 331642 participants, 11885 (3.6%) exhibited frailty and 143379 (43.2%) were categorized as pre-frailty. During a median follow-up of 13.8 years, there were 3684 MR, 1205 AR, and 3166 AS events. Compared to non-frailty participants, those with pre-frailty and frailty showed significantly increased risks for MR (hazard ratio [HR], HRpre-frailty:1.19, 95% confidence interval [CI]: 1.11-1.28; HRfrailty: 1.50, 95% CI: 1.30-1.74), AR (HRpre-frailty:1.19, 95% CI: 1.05-1.34; HRfrailty: 1.58, 95% CI: 1.22-2.04), and AS (HRpre-frailty:1.19, 95% CI: 1.11-1.29; HRfrailty: 1.74, 95% CI: 1.51-2.00). Among the 5 components, slow gait speed showed the strongest association with the risk of various types of VHD (HRMR: 1.50, 95% CI: 1.34-1.65; HRAR: 1.50, 95% CI: 1.24-1.80; HRAS: 1.46, 95% CI: 1.32-1.62), followed by exhaustion, low grip strength, and weight loss. Pre-frailty and frailty were associated with a higher risk of all 3 types of degenerative VHD. Early detection and intervention for pre-frailty and frailty in middle-aged and older individuals may assist in preventing or delaying the onset of degenerative VHD.

Wearable device-measured moderate to vigorous physical activity and risk of degenerative aortic valve stenosis.

Aortic stenosis (AS) is the most prevalent degenerative valvular disease in western countries. Transthoracic echocardiography (TTE) is considered, nowadays, to be the main imaging technique for the work-up of AS due to high availability, safety, low cost, and excellent capacity to evaluate aortic valve (AV) morphology and function. Despite the diagnosis of AS being considered straightforward for a very long time, based on high gradients and reduced aortic valve area (AVA), many patients with AS represent a real dilemma for cardiologist. On the one hand, the acoustic window may be inadequate and the TTE limited in some cases. On the other hand, a growing body of evidence shows that patients with low gradients (due to systolic dysfunction, concentric hypertrophy or coexistence of another valve disease such as mitral stenosis or regurgitation) may develop severe AS (low-flow low-gradient severe AS) with a similar or even worse prognosis. The use of complementary imaging techniques such as transesophageal echocardiography (TEE), multidetector computed tomography (MDTC), or cardiac magnetic resonance (CMR) plays a key role in such scenarios. The aim of this review is to summarize the diagnostic challenges associated with patients with AS and the advantages of a comprehensive multimodality cardiac imaging (MCI) approach to reach a precise grading of the disease, a crucial factor to warrant an adequate management of patients.

Cross-sectional and longitudinal profiling of full sets of nucleic acids, peptides, or proteins as well as metabolites expressed in biospecimens acquired via a cardiovascular disease-oriented biobank may aid in the elucidation of the disease pathways and mechanisms underlying individual cardiovascular diseases, such as degenerative valvular heart disease. This may promote the development of novel and effective, personalized diagnostic and therapeutic strategies to efficiently reduce cardiovascular mortality and morbidity as well as its health and economic burden. This brief report aims to describe the unique, standardized, interdisciplinary, and interprofessional approach to cross-sectional and longitudinal cardiovascular biobanking and databasing at the University Hospital Augsburg. Moreover, we present the study protocol of a specific, well-defined, prospective, single-center research project involving cross-sectional and longitudinal cardiovascular biobanking. The aim of this project is to gain a better insight into the molecular mechanisms underlying aortic valve disease-induced cardiomyopathy and the long-term effect of surgical correction of the aortic valve pathology on the left ventricular myocardial molecule profile.

Plasma Transforming Growth Factor-β1 (TGF-β1) Levels Increase with Age and Aortic Stenosis Progression and Low-Dose Galunisertib Attenuates Disease Progression in Mice

Hypothesis: This study aimed to examine the impact of moderate-to-vigorous intensity physical activity (MVPA) on the prevention of left-sided degenerative valvular heart disease (VHD) among middle-aged adults. Methods: In the UK biobank study, data from wrist-worn accelerometer and physical activity questionnaires were utilized to assess the role of MVPA volume on the incidence of aortic valve stenosis (AS), aortic valve regurgitation (AR), and mitral valve regurgitation (MR). The primary cohort involved 90,865 participants ( median 8.1-year follow-up period) without prevalent VHD and heart failure, who wore accelerometers for one week. The validation cohort included 397,335 participants (median 13.8-year follow-up period) who completed physical activity questionnaires. MVPA volume was categorized according to the American Heart Association’s recommendation. Results: Accelerometer-measured MVPA showed a curvilinear relationship with reduced AS risk, with the risk reduction plateauing above 300 min/week. Compared to no MVPA, those engaging in 150-299 minutes of MVPA per week showed the most significant risk reduction [1-149 min/week: adjusted hazard ratio (HR), 0.79 (0.58, 1.08); 150-299 min/week: HR, 0.52 (0.36, 0.75); ≥300 min/week: HR, 0.57 (0.39, 0.83)]. Similar results were found when repeating the above analyses in self-reported MVPA cohort, with a relatively smaller reduction in HR ratio [150-299 min/week: HR, 0.81 (0.73, 0.91)]. No significant association was found between the MVPA volume and the risk of AR and MR in both cohorts. Conclusions: Meeting current MVPA recommendations (150-300 min/week) was associated with the lowest AS risk. Targeting adherence to accelerometer-measured MVPA thresholds may enhance AS risk reduction. Additionally, MVPA showed limited effectiveness in preventing valvular regurgitation, indicating distinct mechanisms between stenotic lesions and regurgitation lesions in degenerative VHD.