Citations

Abstract Aims Cardiac power is a measure of cardiac performance that incorporates both pressure and flow components. Prior studies have shown that cardiac power predicts outcomes in patients with reduced left ventricular (LV) ejection fraction (EF). We sought to evaluate the prognostic significance of peak exercise cardiac power and power reserve in patients with normal EF. Methods and results We performed a retrospective analysis in 24 885 patients (age 59 ± 13 years, 45% females) with EF ≥50% and no significant valve disease or right ventricular dysfunction, undergoing exercise stress echocardiography between 2004 and 2018. Cardiac power and power reserve (developed power with stress) were normalized to LV mass and expressed in W/100 g of LV myocardium. Endpoints at follow-up were all-cause mortality and diagnosis of heart failure (HF). Patients in the higher quartiles of power/mass (rest, peak stress, and power reserve) were younger and had higher peak blood pressure and heart rate, lower LV mass, and lower prevalence of comorbidities. During follow-up [median 3.9 (0.6–8.3) years], 929 patients died. After adjusting for age, sex, metabolic equivalents (METs) achieved, ischaemia/infarction on stress test results, medication, and comorbidities, peak stress power/mass was independently associated with mortality [adjusted hazard ratio (HR), highest vs. lowest quartile, 0.5, 95% confidence interval (CI) 0.4–0.6, P < 0.001] and HF at follow-up [adjusted HR, highest vs. lowest quartile, 0.4, 95% CI (0.3, 0.5), P < 0.001]. Power reserve showed similar results. Conclusion The assessment of cardiac power during exercise stress echocardiography in patients with normal EF provides valuable prognostic information, in addition to stress test findings on inducible myocardial ischaemia and exercise capacity.

Calf muscle pump (CMP) promotes venous return from the lower extremity and contributes to preload and cardiac output. Impaired CMP function may reflect a measure of frailty or cumulative disease burden or may impede cardiac function. The study objective was to test the hypothesis that impaired CMP negatively impacts survival. Consecutive adult patients who underwent venous strain gauge plethysmography at the Mayo Clinic Gonda Vascular Laboratory (January 1, 1998 – December 31, 2011) were assessed for overall survival. Patients with venous incompetence, venous obstruction or unilateral calf pump dysfunction were excluded. Risk of mortality was assessed with Cox proportional hazard ratios and after adjusting for Charlson Comorbidity Index variables. Over the study period, 2728 patients were included in the analysis. Compared to patients with normal CMP, those with impaired CMP were older ( p < 0.001), predominantly female ( p = 0.01) and had higher mean Charlson scores ( p < 0.001). Patients with impaired CMP had a higher mortality rate at 5 (8.9% vs 2.4%), 10 (17.5% vs 5.9%), and 15 years (22.8% vs 8.3%) compared to those with normal CMP ( p < 0.001 for each comparison). Of patients with heart failure, those with impaired CMP had worse survival at each 5-year increment compared to those with normal CMP ( p < 0.05 at each increment). In conclusion, impaired CMP appears to be an independent predictor of poor outcomes after adjusting for variables within the Charlson Comorbidity Index. The association between impaired CMP, heart failure, and mortality may represent a negative impact on circulatory function or a surrogate measure of frailty.

ABSTRACT Introduction Regional heterogeneity of the human heart plays an important role in left ventricular (LV) and right ventricular (RV) function and may contribute to enhanced myocardial efficiency in the athlete’s heart. Purpose This study comprehensively characterized regional and transmural myocardial tissue deformation (strain) in recreationally active (RA) and endurance-trained (ET) men to determine if regional nonuniformity evolves alongside morphological adaptations associated with endurance training. Methods Echocardiography was used to measure LV and RV global, regional (apical, mid, basal) and transmural (endocardial, epicardial) longitudinal strain in 30 endurance-trained (ET) (age, 31 ± 2 yr; body mass index, 23.1 ± 0.5 kg·m −2 ; V˙O 2peak , 60.2 ± 6.5 mL·kg −1 ·min −1 ) and 30 RA (age: 29 ± 2 yr; body mass index, 23.4 ± 0.4 kg·m −2 ; V˙O 2peak : 42.6 ± 4.6 mL·kg −1 ·min −1 ). Nonuniformity was characterized using apex-to-base and transmural (endocardial-to-epicardial) strain gradients. Results Global longitudinal strain was similar in ET and RA in the left (−17.4% ± 0.4% vs −17.8% ± 0.5%, P = 0.662) and right ventricle (−25.8% ± 0.8% vs 26.4% ± 1.0%, P = 0.717). The apex-to-base strain gradient was greater in ET than RA in the left (−6.5% ± 0.7% vs −2.7% ± 0.8%, P = 0.001) and right ventricle (−9.6% ± 1.8% vs −3.0% ± 1.6%, P = 0.010). The LV transmural strain gradient was greater than RV in both groups, but similar in ET and RA (−4.7% ± 0.2% vs −4.7% ± 0.2%, P = 0.850), whereas RV transmural strain gradient was greater in ET than RA (−3.4% ± 0.3% vs −1.6% ± 0.4%, P = 0.003). RV apex-to-base and transmural strain gradients correlated with RV end-diastolic area ( R = 0.536 & 0.555, respectively, P < 0.01) and V˙O 2peak ( R = 0.415 & 0.677, respectively, P < 0.01). Conclusions Transmural nonuniformity is more pronounced in the left ventricle than the RV free wall; however, RV functional nonuniformity develops markedly after endurance training. Differences in myocardial architecture and exercise-induced wall stress in the left and right ventricles are possible explanations for the marked functional nonuniformity throughout the myocardium and in response to endurance exercise training.

Abstract Funding Acknowledgements None Background/Purpose: Anemia is a common condition in patients with cardiovascular disease. The effect of anemia in exercise stress testing has not been evaluated in a large cohort of patients. Methods We performed a retrospective review of patients undergoing exercise stress echocardiography over a 10 year period who had blood hemoglobin assessed within 48 hours of stress testing. World Health Organization cutoffs were used in defining the degree of anemia. The effect of anemia on exercise capacity and stress testing safety outcomes was assessed. Results In 15,652 patients, 90.3% were non-anemic, 7.6% mildly anemic, 2.1% moderately anemic, and 0.1% severely anemic. The incidence of serious supraventricular or ventricular arrhythmias and need to transfer to the hospital was low (0.1%) and did not correlate to anemia severity (p = 0.25). There was an increased incidence of non-sustained SVT or atrial fibrillation with moderate anemia and increased incidence of hypotension with stress testing with mild and moderate anemia. There was a significant reduction in duration of exercise (p &lt; 0.001) and METS (p &lt; 0.001) achieved with worsening anemia. Conclusion Our study demonstrates that exercise stress testing is safe in patients with mild and moderate anemia, albeit with reduced exercise capacity. Low numbers of severely anemic patients despite a large study population limit generalizability of these results in this group. Exercise Capacity Severe Anemia (N = 9) Moderate Anemia (N = 332) Mild Anemia (N = 1183) Non-anemic (N = 14128) P value Resting heart rate 81 ± 13 # 79 ± 14 # 72 ± 14 74 ± 13 &lt;0.001* Peak heart rate 148 ± 22 139 ± 24 # 138 ± 23 # 147 ±22 &lt;0.001* Exercise duration 5.3 ± 2.5 # 6.3 ± 2.1 # 7.2 ± 2.5 # 8.6 ± 2.7 &lt;0.001* METS 6.3 ± 2.5 # 7.1 ± 2.2 # 8.0 ± 2.5 # 9.5 ± 2.7 &lt;0.001* Safety Hypotension with stress 0 (0%) 31 (9.4%) # 94 (8.0%) # 437 (3.1%) &lt;0.001* Mild supraventricular arrhythmia 1 (11.1%) 15 (4.5%) # 20 (1.7%) # 237 (2.3%) 0.04* Severe supraventricular arrhythmia 0 (0%) 0 (0%) 0 (0%) 7 (0.1%) 0.99 Mild ventricular arrhythmia 0 (0%) 20 (6.0%) 74 (6.3%) 756 (5.4%) 0.94 Moderate ventricular arrhythmia 0 (0%) 3 (0.9%) 13 (1.1%) 182 (1.3%) 0.78 Severe ventricular arrhythmia 0 (0%) 1 (0.3%) 2 (0.2%) 1 (0.0%) 0.02 Transfer to hospital 0 (0%) 2 (0.6%) 1 (0.1%) 9 (0.1%) 0.29 Any severe arrhythmia or hospitalization 0 (0%) 2 (0.6%) 3 (0.3%) 17 (0.1%) 0.25 # Multi-comparison adjusted P-value &lt;0.05 compared to non-anemic when group P &lt; 0.05

Abstract Aims Right ventricular dysfunction (RVD) is an important determinant of functional status and survival in various diseases states. Data are sparse on the epidemiology and outcome of patients with severe RVD. This study examined the characteristics, aetiology, and survival of patients with severe RVD. Methods and results Retrospective study of consecutive patients with severe RVD diagnosed by transthoracic echocardiography (TTE) between 2011 and 2015 in a single tertiary referral institution. Patients with prior cardiac surgery, mechanical assist devices, and congenital heart disease were excluded. Primary endpoint was all-cause mortality. In 64 728 patients undergoing TTE, the prevalence of ≥mild RVD was 21%. This study focused on the cohort of 1299 (4%) patients with severe RVD; age 64 ± 16 years; 61% male. The most common causes of severe RVD were left-sided heart diseases (46%), pulmonary thromboembolic disease (18%), chronic lung disease/hypoxia (CLD; 17%), and pulmonary arterial hypertension (PAH; 11%). After 2 ± 2 years of follow-up, 701 deaths occurred, 66% within the first year of diagnosis. The overall probability of survival at 1- and 5 years for the entire cohort were 61% [95% confidence interval (CI) 58–64%] and 35% (95% CI 31–38%), respectively. In left-sided heart diseases, 1- and 5-year survival rates were 61% (95% CI 57–65%) and 33% (95% CI 28–37%), respectively; vs. 76% (95% CI 68–82%) and 50% (95% CI 40–59%) in PAH, vs. 71% (95% CI 64–76%) and 49% (95% CI 41–58%) in thromboembolic diseases, vs. 42% (95% CI 35–49%) and 8% (95% CI 4–15%) in CLD (log-rank P &lt; 0.0001). Presence of ≥moderate tricuspid regurgitation portended worse survival in severe RVD. Conclusion One-year mortality of patients with severe RVD was high (∼40%) and dependent on the aetiology of RVD. Left-sided heart diseases is the most common cause of severe RVD but prognosis was worst in CLD.

Abstract Aims Pulmonary hypertension (PH) represents an important phenotype among the broader spectrum of patients with heart failure with preserved ejection fraction (HFpEF), but its mechanistic basis remains unclear. We hypothesized that activation of endothelin and adrenomedullin, two counterregulatory pathways important in the pathophysiology of PH, would be greater in HFpEF patients with worsening PH, and would correlate with the severity of haemodynamic derangements and limitations in aerobic capacity and cardiopulmonary reserve. Methods and results Plasma levels of C-terminal pro-endothelin-1 (CT-proET-1) and mid-regional pro-adrenomedullin (MR-proADM), central haemodynamics, echocardiography, and oxygen consumption (VO2) were measured at rest and during exercise in subjects with invasively-verified HFpEF (n = 38) and controls free of HF (n = 20) as part of a prospective study. Plasma levels of CT-proET-1 and MR-proADM were highly correlated with one another (r = 0.89, P &lt; 0.0001), and compared to controls, subjects with HFpEF displayed higher levels of each neurohormone at rest and during exercise. C-terminal pro-endothelin-1 and MR-proADM levels were strongly correlated with mean pulmonary artery (PA) pressure (r = 0.73 and 0.65, both P &lt; 0.0001) and pulmonary capillary wedge pressure (r = 0.67 and r = 0.62, both P &lt; 0.0001) and inversely correlated with PA compliance (r = −0.52 and −0.43, both P &lt; 0.001). As compared to controls, subjects with HFpEF displayed right ventricular (RV) reserve limitation, evidenced by less increases in RV s′ and e′ tissue velocities, during exercise. Baseline CT-proET-1 and MR-proADM levels were correlated with worse RV diastolic reserve (ΔRV e′, r = −0.59 and −0.67, both P &lt; 0.001), reduced cardiac output responses to exercise (r = −0.59 and −0.61, both P &lt; 0.0001), and more severely impaired peak VO2 (r = −0.60 and −0.67, both P &lt; 0.0001). Conclusion Subjects with HFpEF display activation of the endothelin and adrenomedullin neurohormonal pathways, the magnitude of which is associated with pulmonary haemodynamic derangements, limitations in RV functional reserve, reduced cardiac output, and more profoundly impaired exercise capacity in HFpEF. Further study is required to evaluate for causal relationships and determine if therapies targeting these counterregulatory pathways can improve outcomes in patients with the HFpEF-PH phenotype. Clinical trial registration NCT01418248; https://clinicaltrials.gov/ct2/results? term=NCT01418248&Search=Search

Abstract Abstract Background: Pulmonary hypertension (PH) is a significant preoperative risk factor. We aimed to determine predictors of perioperative morbidity and mortality after noncardiac surgery for patients with precapillary PH. Methods: We conducted a retrospective cohort study of adults with pulmonary hypertension having surgery at a single large medical referral center. The PH and surgical databases were reviewed from 2010 to 2017. Patients were excluded if PH was attributable to left-sided heart disease or they had undergone cardiac or transplant operations. To assess whether PH-specific diagnostic or cardiopulmonary testing parameters were predictive of perioperative complications, analyses were performed using generalized estimating equations. Results: Of 196 patients with PH undergoing noncardiac operations, 53 (27%) experienced 1 or more complications, including 5 deaths (3%) within 30 days. After adjustment for age and PH type, there were more complications in those undergoing moderate-to-high vs low-risk procedures (odds ratio [OR], 4.17 [95% CI, 2.07 to 8.40]; P<0.001). After adjustment for age, surgical risk, and PH type, the risk for complications was higher for patients with worse functional status (OR, 2.39 [95% CI, 1.19 to 4.78]; P=0.01 for class 3/4 vs class 1/2) and elevated serum N-terminal fragment of the prohormone brain natriuretic peptide (NT-proBNP) (OR, 2.28 [95% CI, 1.05 to 4.96]; P=0.04 for ≥300 vs. <300 pg/mL). From an analysis that included covariates for age, surgical risk, and functional status, elevated serum NT-proBNP levels remained associated with increased risk (OR, 2.23 [95% CI, 1.05 to 4.76]; P=0.04). Conclusions: Patients with PH undergoing noncardiac surgery with general anesthesia have a high frequency of perioperative complications. Specific clinical (functional status), diagnostic (serum NT-proBNP), and intraoperative factors (higher-risk surgery) are predictive of worse outcomes.