Clinical and Prognostic Implications of Cardiopulmonary Exercise Stress Echocardiography in Asymptomatic Degenerative Mitral Regurgitation.

The current guidelines recommend intervention in severe degenerative mitral regurgitation (MR) in symptomatic patients or asymptomatic patients with left ventricular dilatation or dysfunction. The insidious onset of symptoms may mean that patients do not report their symptoms. The role of systematic exercise testing for symptoms in MR is not clearly defined. A total of 97 patients with moderate to severe asymptomatic MR underwent exercise echocardiography combined with cardiopulmonary exercise testing. The predictors of exercise-induced dyspnea, symptom-free survival, and mitral valve intervention were identified. A total of 18 patients (19%) developed limiting dyspnea on exercise. Spontaneous symptom-free survival at 24 months was significantly higher in those without exercise-induced symptoms than those with exercise-induced symptoms, p <0.0001. The only independent predictors of spontaneous symptoms at 2 years were effective regurgitant orifice area (odds ratio 27.45, 95% confidence interval [CI] 1.43 to 528.40, p = 0.03) and exercise-induced symptoms (odds ratio 11.56, 95% CI 1.71 to 78.09, p = 0.01). The only independent predictor of surgery was indexed left ventricular systolic volumes (odds ratio 1.17, 95% CI 1.04 to 1.30, p = 0.006). Where only the patients who underwent surgery due to symptoms were included, the only independent predictor was exercise-induced symptoms (odds ratio 13.94, 95% CI 1.39 to 140.27, p = 0.025). In conclusion, in patients with primary asymptomatic degenerative MR, 1/5 develop revealed symptoms during exercise. This predicts a subsequent development of spontaneous symptoms and mitral valve intervention due to symptoms.

Determinants of post-operative left ventricular dysfunction in degenerative mitral regurgitation.

AIMS: Chronic degenerative mitral regurgitation leads to volume overload causing left ventricular (LV) enlargement and eventually LV impairment. Current guidelines determining thresholds for intervention are based on LV diameters and ejection fraction (LVEF). There are sparse data examining the value of LV volumes and newer markers of LV performance on outcomes of surgery in mitral valve prolapse. The aim of this study is to identify the best marker of LV impairment after mitral valve surgery. METHODS AND RESULTS: Prospective, observational study of patients with mitral valve prolapse undergoing mitral valve surgery. Pre-operative LV diameters, volumes, LVEF, global longitudinal strain (GLS), and myocardial work measured. Post-operative LV impairment defined as LVEF < 50% at 1 year post-surgery. Eighty-seven patients included. Thirteen percent developed post-operative LV impairment. Patients with post-operative LV dysfunction showed significantly larger indexed LV end-systolic diameters, indexed LV end-systolic volumes (LVESVi), lower LVEF, and more abnormal GLS than patients without post-operative LV dysfunction. In multivariate analysis, LVESVi [odds ratio 1.11 (95% CI 1.01-1.23), P = 0.039] and GLS [odds ratio 1.46 (95% CI 1.00-2.14), P = 0.054] were the only independent predictors of post-operative LV dysfunction. The optimal cut-off of 36.3 mL/m2 for LVESVi had a sensitivity of 82% and specificity of 78% for detection of post-operative LV impairment. CONCLUSION: Post-operative LV impairment is common. Indexed LV volumes (36.3 mL/m2) provided the best marker of post-operative LV impairment.

Comparison of the Recent Updates to the ACC/AHA and ESC Guidelines for the Management of Valvular Heart Disease: Similarities and Differences.

PURPOSE OF REVIEW: There have been several advances in the diagnosis and management of valvular heart disease (VHD) over the last decade. These have been reflected in the latest European and North American guidelines, although both contain significant similarities and differences. In this review, we highlight the important overlaps and variations between the updated guidelines and their previous versions to help guide the general cardiologist. RECENT FINDINGS: There has been extensive revision on the use of percutaneous treatments, the indications for intervention in asymptomatic VHD, and perioperative bridging therapies. The updated guidelines provide new recommendations in many aspects of VHD; however, there remain significant gaps in the role of biomarkers in VHD and the long-term outcomes of novel oral anticoagulants (NOACs) and transcatheter therapies.

Preprocedural Prognostic Factors in Acute Decompensated Aortic Stenosis.

Acute decompensated aortic stenosis (ADAS) is common and associated with poor outcomes. Myocardial remodeling and function, including a novel echo staging classification (0 to 4, representing increasing degrees of cardiac damage/dysfunction), impact outcomes in stable aortic stenosis. However, this has not been assessed in patients with ADAS. This study aims to evaluate the impact of the myocardium, echo staging classification, and clinical parameters on mortality in ADAS. ADAS was defined as an acute deterioration in symptoms (New York Heart Association 4, Canadian Cardiovascular Society 3/4, or syncope) that warranted admission to the hospital and urgent aortic valve replacement. Using a retrospective observational study design, 292 consecutive patients with ADAS who underwent transcatheter aortic valve implantation (TAVI) were identified and included in this study. Echocardiographic and clinical characteristics were evaluated using regression analysis. The outcome was all-cause mortality after TAVI. At 1 year after TAVI, advanced echo staging (>2) independently predicted mortality (hazards ratio: 1.85, 95% confidence interval: 1.01 to 3.39; p = 0.045). At a follow-up of 2.4 ± 1.4 years, myocardial, valvular, and clinical parameters did not predict mortality, except for frailty (hazards ratio: 2.31, 95% confidence interval: 1.38 to 3.85; p = 0.001). In patients with ADAS, short-term mortality after TAVI is influenced by more advanced cardiac damage/dysfunction based on the echo staging classification, whereas mid-term mortality is driven by frailty rather than echo staging classification.

Moderate Aortic Stenosis: What is it and When Should We Intervene?

Current guidelines recommend aortic valve replacement in patients with severe aortic stenosis in the presence of symptoms or a left ventricular ejection fraction <50%. However, patients with less than severe aortic stenosis may also experience symptoms and recent literature suggests that the prognosis is not as benign as previously reported. There are no recommendations for patients with moderate aortic stenosis and left ventricular dysfunction, despite the high associated morbidity and mortality. There is also some evidence that these patients may benefit from early aortic valve intervention. It is recognised that aortic stenosis not only affects the valve but also has a complex myocardial response. This review discusses the natural history of moderate aortic stenosis along with the role of multimodality imaging in risk stratification in these patients.

Direct in vivo assessment of global and regional mechanoelectric feedback in the intact human heart.

BACKGROUND: Inhomogeneity of ventricular contraction is associated with sudden cardiac death, but the underlying mechanisms are unclear. Alterations in cardiac contraction impact electrophysiological parameters through mechanoelectric feedback. This has been shown to promote arrhythmias in experimental studies, but its effect in the in vivo human heart is unclear. OBJECTIVE: The purpose of this study was to quantify the impact of regional myocardial deformation provoked by a sudden increase in ventricular loading (aortic occlusion) on human cardiac electrophysiology. METHODS: In 10 patients undergoing open heart cardiac surgery, left ventricular (LV) afterload was modified by transient aortic occlusion. Simultaneous assessment of whole-heart electrophysiology and LV deformation was performed using an epicardial sock (240 electrodes) and speckle-tracking transesophageal echocardiography. Parameters were matched to 6 American Heart Association LV model segments. The association between changes in regional myocardial segment length and activation-recovery interval (ARI; a conventional surrogate for action potential duration) was studied using mixed-effect models. RESULTS: Increased ventricular loading reduced longitudinal shortening (P = .01) and shortened ARI (P = .02), but changes were heterogeneous between cardiac segments. Increased regional longitudinal shortening was associated with ARI shortening (effect size 0.20 [0.01-0.38] ms/%; P = .04) and increased local ARI dispersion (effect size -0.13 [-0.23 to -0.03] ms/%; P = .04). At the whole organ level, increased mechanical dispersion translated into increased dispersion of repolarization (correlation coefficient r = 0.81; P = .01). CONCLUSION: Mechanoelectric feedback can establish a potentially proarrhythmic substrate in the human heart and should be considered to advance our understanding and prevention of cardiac arrhythmias.

Natriuretic peptide release during exercise in patients with valvular heart disease: A systematic review.

AIM: Serum biomarkers have a potential role in the risk stratification of patients with heart valve disease and may help determine the optimal timing of intervention. Much of the published literature relates to biomarker sampling in a resting state, but the relationship of exercise biomarkers is less well described. We performed a systematic review to examine the significance of exercise natriuretic peptides on echocardiographic variables and cardiovascular events, in valvular heart disease. METHODS: A search for studies that assessed exercise biomarkers in patients with moderate to severe valve lesions was performed. We examined the relationship between rest and exercise BNP and also the endpoints of symptoms, haemodynamic or echocardiographic variables and clinical outcomes. RESULTS: Eleven prospective studies were identified (844 participants). 61% were male and the mean age was 55.2 ± 9.6 years. The majority of the blood samples were taken at baseline and within 3 minutes of stopping exercise. There was a significant increase in exercise BNP compared with rest, in patients with aortic stenosis, mitral regurgitation and mitral stenosis. Elevated exercise BNP levels correlated with mean gradient and left atrial area, and there was a relationship between a higher exercise BNP and a blunted blood pressure response, in aortic stenosis. Furthermore, exercise BNP was independently associated with cardiac events, over and above resting values, in patients with mitral regurgitation and aortic stenosis. CONCLUSION: The results suggesting that exercise natriuretic peptide levels may have additive prognostic importance over resting levels, as well as demographic and echocardiographic data.

Multimodality Imaging Markers of Adverse Myocardial Remodeling in Aortic Stenosis.

Aortic stenosis (AS) causes left ventricular remodeling (hypertrophy, remodeling, fibrosis) and other cardiac changes (left atrial dilatation, pulmonary artery and right ventricular changes). These changes, and whether they are reversible (reverse remodeling), are major determinants of timing and outcome from transcatheter or surgical aortic valve replacement. Cardiac changes in response to AS afterload can either be adaptive and reversible, or maladaptive and irreversible, when they may convey residual risk after intervention. Structural and hemodynamic assessment of AS therefore needs to evaluate more than the valve, and, in particular, the myocardial remodeling response. Imaging plays a key role in this. This review assesses how multimodality imaging evaluates AS myocardial hypertrophy and its components (cellular hypertrophy, fibrosis, microvascular changes, and additional features such as cardiac amyloid) both before and after intervention, and seeks to highlight how care and outcomes in AS could be improved.

The importance of contractile reserve in predicting exercise tolerance in asymptomatic patients with severe aortic stenosis.

BACKGROUND: Mortality dramatically rises with the onset of symptoms in patients with severe aortic stenosis (AS). Surgery is indicated when symptoms become apparent or when there is ventricular decompensation. Cardiopulmonary exercise testing (CPET) in combination with exercise echocardiography can unmask symptoms and provides valuable information regarding contractile reserve. The aim of the present study was to determine the prevalence of reduced exercise tolerance and the parameters predicting adverse cardiovascular events. METHODS: Thirty-two patients with asymptomatic severe AS were included in this study. Patients were followed up as part of an enhanced surveillance clinic. RESULTS: Age was 69 ± 15.7 years, 75% of patients were male. Patients had a raised NT-ProBNP of 301 pg/mL. VO2peak was 19.5 ± 6.2 mL/kg/min. Forty-one percent of patients had a reduced %VO2peak and this predicted unplanned cardiac hospitalisation (P = 0.005). Exercise systolic longitudinal velocity (S') and age were the strongest independent predictors for VO2peak (R 2 = 0.76; P < 0.0001). Exercise S' was the strongest independent predictor for NT-ProBNP (R 2 = 0.48; P = 0.001). CONCLUSION: A large proportion of patients had a lower than predicted VO2peak. The major determinant of exercise and NT-ProBNP is the ability of the left ventricle (LV) to augment S' on exercise rather than the severity of aortic valve obstruction or resting structural remodelling of the LV. Reduced exercise tolerance and more adverse remodelling, rather than valve obstruction predicted unplanned hospitalisation. This study demonstrates that for those patients, in whom a watchful waiting is an agreed strategy, a detailed assessment should be undertaken including CPET, exercise echocardiography and biomarkers to ensure those with exercise limitation and risk of decompensation are detected early and treated appropriately.

Non-Invasive Detection of Mechanical Alternans Utilizing Photoplethysmography.

BACKGROUND AND SIGNIFICANCE: Mechanical alternans (MA) is a biomarker associated with mortality and life-threatening arrhythmias in heart failure patients. Despite showing prognostic value, its use is limited by the requirement of measuring the continuous blood pressure (BP), which is costly and impractical. OBJECTIVE: To develop and test, for the first time, non-invasive MA surrogates based on photoplethysmography (PPG). METHODS: Continuous BP and PPG were recorded during clinical procedures and tests in 35 patients. MA was induced either by ventricular pacing (Group A, N = 19) or exercise (Group B, N = 16). MA was categorized as sustained or intermittent if MA episodes were observed in at least 20 or between 12 and 20 consecutive beats, respectively. Eight features characterizing the pulse morphology were derived from the PPG, and MA surrogates were evaluated. RESULTS: Sustained alternans was observed in 9 patients (47%) from Group A, whereas intermittent alternans was observed in 13 patients (68%) from Group A and in 10 patients (63%) from Group B. The PPG-based MA surrogate showing the highest accuracy, V'M, was based on the maximum of the first derivative of the PPG pulse. It detected both sustained and intermittent MA with 100% sensitivity and 100% specificity in Group A and intermittent MA with 100% sensitivity and 83% specificity in Group B. Furthermore, the magnitudes of MA and its PPG-based surrogate were linearly correlated (R2 = 0.83, p < 0.001). CONCLUSION: MA can be accurately identified non-invasively through PPG analysis. This may have important clinical implications for risk stratification and remote monitoring.

Stress echocardiography in valvular heart disease.

INTRODUCTION: The management of patients with heart valve disease can be complex. Patients may have symptoms disproportionate to the severity or the severity may be unclear. In addition, the optimal timing of intervention in patients with severe disease may be controversial. Areas covered: This article examines the role of stress echocardiography for assessment of patients with low-flow, low-gradient aortic stenosis, asymptomatic severe valve disease and patients where symptoms are discordant to the resting severity of valve disease. Expert commentary: Stress echocardiography helps clinicians determine the true severity of valve disease and may identify the cause of symptoms in patients with only mild/moderate disease. The data provided by stress echocardiography will help determine the appropriate management strategy and the correct timing of intervention.

Sex Dimorphism in the Myocardial Response to Aortic Stenosis.

OBJECTIVES: The goal of this study was to explore sex differences in myocardial remodeling in aortic stenosis (AS) by using echocardiography, cardiac magnetic resonance (CMR), and biomarkers. BACKGROUND: AS is a disease of both valve and left ventricle (LV). Sex differences in LV remodeling are reported in AS and may play a role in disease phenotyping. METHODS: This study was a prospective assessment of patients awaiting surgical valve replacement for severe AS using echocardiography, the 6-min walking test, biomarkers (high-sensitivity troponin T and N-terminal pro-brain natriuretic peptide), and CMR with late gadolinium enhancement and extracellular volume fraction, which dichotomizes the myocardium into matrix and cell volumes. LV remodeling was categorized into normal geometry, concentric remodeling, concentric hypertrophy, and eccentric hypertrophy. RESULTS: In 168 patients (age 70 ± 10 years, 55% male, indexed aortic valve area 0.40 ± 0.13 cm2/m2, mean gradient 47 ± 4 mm Hg), no sex or age differences in AS severity or functional capacity (6-min walking test) were found. CMR captured sex dimorphism in LV remodeling not apparent by using 2-dimensional echocardiography. Normal geometry (82% female) and concentric remodeling (60% female) dominated in women; concentric hypertrophy (71% male) and eccentric hypertrophy (76% male) dominated in men. Men also had more evidence of LV decompensation (pleural effusions), lower left ventricular ejection fraction (67 ± 16% vs. 74 ± 13%; p < 0.001), and higher levels of N-terminal pro-brain natriuretic peptide (p = 0.04) and high-sensitivity troponin T (p = 0.01). Myocardial fibrosis was higher in men, with higher focal fibrosis (late gadolinium enhancement 16.5 ± 11.2 g vs. 10.5 ± 8.9 g; p < 0.001) and extracellular expansion (matrix volume 28.5 ± 8.8 ml/m2 vs. 21.4 ± 6.3 ml/m2; p < 0.001). CONCLUSIONS: CMR revealed sex differences in associations between AS and myocardial remodeling not evident from echocardiography. Given equal valve severity, the myocardial response to AS seems more maladaptive in men than previously reported. (Regression of Myocardial Fibrosis After Aortic Valve Replacement [RELIEF-AS]; NCT02174471).

Clinical events and echocardiographic lesion progression rate in subjects with mild or moderate aortic regurgitation.

Background: The rate of progression of aortic regurgitation (AR) is not well described. Current guidelines state that asymptomatic patients with mild AR should be followed up every 3­5 years and 1­2 yearly for moderate AR. This study describes the lesion and clinical based progression of mild and moderate AR in a population of patients undergoing systematic follow-up. Methods and results: 341 patients with either mild or moderate AR were included. The rates of clinical events (death, aortic valve replacement and cardiac hospitalization) and progression of AR are reported. 341 patients were included; mean age was 71.1 years (IQR 66­80 years) and the median follow-up period was 4.6 (IQR 2­6.7) years. 292 patients did not have any events during follow-up. 3 patients required aortic valve replacement (2 of these due to severe aortic stenosis and 1 due to severe mitral regurgitation and co-existent moderate AR). 44 patients required cardiac hospitalization. 9 patients died during follow-up and 35 patients (10%) showed a progression of AR during follow-up with an average time of 4.0 ± 2.6 years. 8 patients (2.3% of the total) progressed to severe AR. Patients with mixed valvular pathology showed a greater increase in AR progression (27 (15%) vs 8 (5%); P = 0.004). Conclusions: Over medium term systematic follow-up progression and clinical events in patients with AR is rare, regardless of etiology. Patients who suffered from AR as an isolated valve pathology were less likely to show AR progression over time.

Aortic Stenosis, a Left Ventricular Disease: Insights from Advanced Imaging.

Aortic stenosis (AS) is the most common primary valve disorder in the elderly with an increasing prevalence. It is increasingly clear that it is also a disease of the left ventricle (LV) rather than purely the aortic valve. The transition from left ventricular hypertrophy to fibrosis results in the eventual adverse effects on systolic and diastolic function. Appropriate selection of patients for aortic valve intervention is crucial, and current guidelines recommend aortic valve replacement in severe AS with symptoms or in asymptomatic patients with left ventricular ejection fraction (LVEF) <50 %. LVEF is not a sensitive marker and there are other parameters used in multimodality imaging techniques, including longitudinal strain, exercise stress echo and cardiac MRI that may assist in detecting subclinical and subtle LV dysfunction. These findings offer potentially better ways to evaluate patients, time surgery, predict recovery and potentially offer targets for specific therapies. This article outlines the pathophysiology behind the LV response to aortic stenosis and the role of advanced multimodality imaging in describing it.

Role of Echocardiography Before Transcatheter Aortic Valve Implantation (TAVI).

Aortic stenosis (AS) is the most common primary valve disorder in the elderly with an increasing prevalence; transcatheter aortic valve implantation (TAVI) has become an accepted alternative to surgical aortic valve replacement (AVR) in the high risk or inoperable patient. Appropriate selection of patients for TAVI is crucial and requires a multidisciplinary approach including cardiothoracic surgeons, interventional cardiologists, anaesthetists, imaging experts and specialist nurses. Multimodality imaging including echocardiography, CT and MRI plays a pivotal role in the selection and planning process; however, echocardiography remains the primary imaging modality used for patient selection, intra-procedural guidance, post-procedural assessment and long-term follow-up. The contribution that contemporary transthoracic and transoesophageal echocardiography make to the selection and planning of TAVI is described in this article.

Structural cure for reflex syncope?

The ROX Coupler is a device that allows creation of a central arteriovenous anastomosis at the iliac level. The device has been shown to improve exercise capacity in patients with chronic obstructive pulmonary disease and is CE marked for the treatment of resistant and uncontrolled hypertension. Reflex syncope is a challenging clinical condition with limited proven therapeutic options. We describe the resolution of symptoms and tilt table response of a patient who underwent insertion of a ROX Coupler to treat hypertension, and also incidentally had pre-existing vasodepressor syncope.