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.

Recreational marathon running does not cause exercise-induced left ventricular hypertrabeculation.

BACKGROUND: Marathon running in novices represents a natural experiment of short-term cardiovascular remodeling in response to running training. We examine whether this stimulus can produce exercise-induced left ventricular (LV) trabeculation. METHODS: Sixty-eight novice marathon runners aged 29.5 ± 3.2 years had indices of LV trabeculation measured by echocardiography and cardiac magnetic resonance imaging 6 months before and 2 weeks after the 2016 London Marathon race, in a prospective longitudinal study. RESULTS: After 17 weeks unsupervised marathon training, indices of LV trabeculation were essentially unchanged. Despite satisfactory inter-observer agreement in most methods of trabeculation measurement, criteria defining abnormally hypertrabeculated cases were discordant with each other. LV hypertrabeculation was a frequent finding in young, healthy individuals with no subject demonstrating clear evidence of a cardiomyopathy. CONCLUSION: Training for a first marathon does not induce LV trabeculation. It remains unclear whether prolonged, high-dose exercise can create de novo trabeculation or expose concealed trabeculation. Applying cut off values from published LV noncompaction cardiomyopathy criteria to young, healthy individuals risks over-diagnosis.

Cardiovascular Remodeling Experienced by Real-World, Unsupervised, Young Novice Marathon Runners.

AIMS: Marathon running is a popular ambition in modern societies inclusive of non-athletes. Previous studies have highlighted concerning transient myocardial dysfunction and biomarker release immediately after the race. Whether this method of increasing physical activity is beneficial or harmful remains a matter of debate. We examine in detail the real-world cardiovascular remodeling response following competition in a first marathon. METHODS: Sixty-eight novice marathon runners (36 men and 32 women) aged 30 ± 3 years were investigated 6 months before and 2 weeks after the 2016 London Marathon race in a prospective observational study. Evaluation included electrocardiography, cardiopulmonary exercise testing, echocardiography, and cardiovascular magnetic resonance imaging. RESULTS: After 17 weeks unsupervised marathon training, runners revealed a symmetrical, eccentric remodeling response with 3-5% increases in left and right ventricular cavity sizes, respectively. Blood pressure (BP) fell by 4/2 mmHg (P < 0.01) with reduction in arterial stiffness, despite only 11% demonstrating a clinically meaningful improvement in peak oxygen consumption with an overall non-significant 0.4 ml/min/kg increase in peak oxygen consumption (P = 0.14). CONCLUSION: In the absence of supervised training, exercise-induced cardiovascular remodeling in real-world novice marathon runners is more modest than previously described and occurs even without improvement in cardiorespiratory fitness. The responses are similar in men and women, who experience a beneficial BP reduction and no evidence of myocardial fibrosis or persistent edema, when achieving average finishing times.

Training for a First-Time Marathon Reverses Age-Related Aortic Stiffening.

BACKGROUND: Aging increases aortic stiffness, contributing to cardiovascular risk even in healthy individuals. Aortic stiffness is reduced through supervised training programs, but these are not easily generalizable. OBJECTIVES: The purpose of this study was to determine whether real-world exercise training for a first-time marathon can reverse age-related aortic stiffening. METHODS: Untrained healthy individuals underwent 6 months of training for the London Marathon. Assessment pre-training and 2 weeks post-marathon included central (aortic) blood pressure and aortic stiffness using cardiovascular magnetic resonance distensibility. Biological "aortic age" was calculated from the baseline chronological age-stiffness relationship. Change in stiffness was assessed at the ascending (Ao-A) and descending aorta at the pulmonary artery bifurcation (Ao-P) and diaphragm (Ao-D). Data are mean changes (95% confidence intervals [CIs]). RESULTS: A total of 138 first-time marathon completers (age 21 to 69 years, 49% male) were assessed, with an estimated training schedule of 6 to 13 miles/week. At baseline, a decade of chronological aging correlated with a decrease in Ao-A, Ao-P, and Ao-D distensibility by 2.3, 1.9, and 3.1 × 10-3 mm Hg-1, respectively (p < 0.05 for all). Training decreased systolic and diastolic central (aortic) blood pressure by 4 mm Hg (95% CI: 2.8 to 5.5 mm Hg) and 3 mm Hg (95% CI: 1.6 to 3.5 mm Hg). Descending aortic distensibility increased (Ao-P: 9%; p = 0.009; Ao-D: 16%; p = 0.002), while remaining unchanged in the Ao-A. These translated to a reduction in "aortic age" by 3.9 years (95% CI: 1.1 to 7.6 years) and 4.0 years (95% CI: 1.7 to 8.0 years) (Ao-P and Ao-D, respectively). Benefit was greater in older, male participants with slower running times (p < 0.05 for all). CONCLUSIONS: Training for and completing a marathon even at relatively low exercise intensity reduces central blood pressure and aortic stiffness-equivalent to a ∼4-year reduction in vascular age. Greater rejuvenation was observed in older, slower individuals.

The hemodynamic effects of a central iliac arteriovenous anastomosis at 6 months in patients with resistant and uncontrolled hypertension.

A central iliac arteriovenous anastomosis, termed the "coupler" (ROX Medical), results in a significant reduction in blood pressure (BP) in hypertensive patients. This study assessed functional and hemodynamic changes induced by the device. Twenty-one patients with resistant and/or uncontrolled hypertension underwent stress echocardiography and cardiopulmonary exercise testing (CPET) at baseline and 6 months post-coupler implantation. End points were selected to best evaluate cardiac function including Doppler stroke volume (SV), septal and lateral E/E', and right ventricular systolic velocity S' (RV S'). CPET VO2 peak demonstrated total cardiopulmonary performance. SV increased from 76.4 SD12.2 mL to 92.1 SD22.7 mL 6 months post-coupler insertion; P = .002. No changes in RV S', septal or lateral E/E', or VO2 peak were observed. Five patients experienced increased diuretic requirement ≥3 times baseline. RV S' fell from 19.0 SD1.87 cm/s to 16.80 SD3.43 cm/s in these patients (P > .05). A significant increase in SV 6 months post-coupler insertion was observed. In patients with increased diuretic requirement, the device was associated with a lower RV S' suggesting occult RV dysfunction as the mechanism of this pre-specified adverse outcome.

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.

Central arteriovenous anastomosis for the treatment of patients with uncontrolled hypertension and paroxysmal AF.

A central iliac arteriovenous anastomosis, the 'coupler' (ROX Medical, California, USA) results in a significant reduction in blood pressure in hypertensive patients. This study assessed the change in AF burden following coupler implantation in patients with paroxysmal AF (PAF) and hypertension. Good blood pressure control using the coupler results in a significant reduction in AF burden.

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.

Prognostic importance of tissue velocity imaging during exercise echocardiography in patients with systolic heart failure.

Resting echocardiography measurements are poor predictors of exercise capacity and symptoms in patients with heart failure (HF). Stress echocardiography may provide additional information and can be expressed using left ventricular ejection fraction (LVEF), or diastolic parameters (E/E'), but LVEF has some major limitations. Systolic annular velocity (S') provides a measure of longitudinal systolic function, which is relatively easy to obtain and shows a good relationship with exercise capacity. The objective of this study was to investigate the relationship among S', E/E' and LVEF obtained during stress echocardiography and both mortality and hospitalisation. A secondary objective was to compare S' measured using a simplified two-wall model. A total of 80 patients with stable HF underwent exercise stress echocardiography and simultaneous cardiopulmonary exercise testing. Volumetric and tissue velocity imaging (TVI) measurements were obtained, as was peak oxygen uptake (VO2 peak). Of the total number of patients, 11 died and 22 required cardiac hospitalisation. S' at peak exertion was a powerful predictor for death and hospitalisation. Cut-off points of 5.3 cm/s for death and 5.7 cm/s for hospitalisation provided optimum sensitivity and specificity. This study suggests that, in patients with systolic HF, S' at peak exertion calculated from the averaged spectral TVI systolic velocity of six myocardial segments, or using a simplified measure of two myocardial segments, is a powerful predictor of future events and stronger than LVEF, diastolic velocities at rest or exercise and VO2 peak. Results indicate that measuring S' during exercise echocardiography might play an important role in understanding the likelihood of adverse clinical outcomes in patients with HF.