Global left ventricular myocardial work index and medium-term adverse cardiovascular events after ST-elevation myocardial infarction.

BACKGROUND: Left ventricular global longitudinal strain (GLS) has incremental prognostic value over ejection fraction (EF) in patients with ST-segment-elevation myocardial infarction (STEMI), but it is also load dependent. It has been recently demonstrated that Myocardial work (MW), integrating blood pressure with GLS, predicts long-term all-cause mortality. We aimed to further explore the prognostic value of MW for cardiovascular endpoints in patients with STEMI. METHODS AND RESULTS: Retrospective study of 200 consecutive patients admitted with a STEMI, mean age of 62 (SD 12) years, 79.5% males, that survived to discharge. Transthoracic echocardiography was performed before discharge (5 ± 3 days after admission). Mean follow-up was 790 days. The primary outcome was a composite of cardiovascular death, non-fatal myocardial infarction, and unplanned cardiovascular admission (ACE). During follow-up, 26 patients had a ACE. In univariable Cox regression analysis, male gender, body mass index, GRACE risk score and Global Work Index (GWI) were selected to the multivariable analysis, in which, only GWI (per 100 mmHg% decrease: hazard ratio estimate 1.19, 95% confidence interval 1.07-1.34, p-value = 0.002) remained independently associated with ACE, with effective reclassification of non-events. The best GWI cut-off to predict ACE was ≤1165 mmHg% (Log-rank, p = 0.034). CONCLUSIONS: LV GWI is independently associated with medium-term ACE. Nevertheless, prospective studies in a larger sample of patients are warranted to confirm this finding.

Permanent pacemaker implantation after alcoholic septal ablation induced complete heart block: Long-term impact.

INTRODUCTION AND OBJECTIVES: Patients with hypertrophic obstructive cardiomyopathy (HOCM) that remain symptomatic despite optimized medical therapy often undergo alcohol septal ablation (ASA). One of the most frequent complications is complete heart block (CHB), requiring a permanent pacemaker (PPM) in variable rates of up to 20% of patients. The long-term impact of PPM implantation in these patients remains unclear. This study aimed to evaluate the long-term clinical outcomes in patients who implant PPM after ASA. METHODS: Patients who underwent ASA at a tertiary center were consecutively and prospectively enrolled. Patients with previous PPM or implantable cardio-defibrillator were excluded from this analysis. Patients with and without PPM implantation after ASA were compared based on their baseline characteristics, procedure data and three-year primary endpoint of composite of all-cause mortality and hospitalization and secondary endpoint of composite of all-cause mortality and cardiac cause hospitalization. RESULTS: Between 2009 and 2019, 109 patients underwent ASA, 97 of whom were included in this analysis (68% female, mean age 65.2 years old). 16 patients (16.5%) required PPM implantation for CHB. In these patients, no vascular access, pacemaker pocket or pulmonary parenchyma complications were noted. The baseline characteristics of comorbidities, symptoms, echocardiographic and electrocardiographic findings were identical in the two groups, with higher mean age (70.6±10.0 years vs. 64.1±11.9 years) and lower beta-blocker therapy rate (56% vs. 84%) in the PPM group. Procedure-related data showed higher creatine kinase (CK) peaks in the PPM group (1692 U/L vs. 1243 U/L), with no significant difference in the alcohol dose. At three years after ASA procedure, there were no differences in the primary and secondary endpoints between the two groups. CONCLUSIONS: Permanent pacemaker after ASA induced CHB do not affect long term prognosis in hypertrophic obstructive cardiomyopathy patients.

Evaluation of left atrial strain imaging and integrated backscatter as predictors of recurrence in patients with paroxysmal, persistent, and long-standing persistent atrial fibrillation undergoing catheter ablation.

BACKGROUND: Impaired left atrial (LA) strain predicts atrial fibrillation (AF) recurrence after catheter ablation (CA), but currently there is no cut-off to guide patient selection for CA. Integrated backscatter (IBS) is a promising tool for noninvasive quantification of myocardial fibrosis. The aim of this study was to compare LA strain and IBS between paroxysmal, persistent, and long-standing persistent AF and evaluate their association with AF recurrence after CA. METHODS: Analysis of consecutive patients with symptomatic paroxysmal and persistent AF who underwent CA. LA phasic strain, strain rate and IBS were assessed by two-dimensional speckle-tracking at baseline. RESULTS: We analyzed 78 patients, 31% with persistent AF (46% long-standing AF), 65% male, mean age 59 ± 14 years, who underwent CA and were followed-up for 12 months. AF recurrence occurred in 22 (28%) patients. LA phasic strain parameters were significantly impaired in patients with AF recurrence and were independent predictors of AF recurrence in a multivariable analysis. LA reservoir strain (LASr) < 18% predicted AF recurrence with 86% sensitivity and 71% specificity, with a higher predictive power compared to LA volume index (LAVI). LASr < 22% in paroxysmal AF and LASr < 12% in persistent AF correlated with AF recurrence. Increased IBS was a predictor of AF recurrence in patients with paroxysmal AF. CONCLUSION: LA phasic strain parameters were predictors of AF recurrence after CA, independently of LAVI and AF subtype. LASr < 18% showed a higher predictive power compared to LAVI. Further studies are needed to investigate the role of IBS as a predictor of AF recurrence.

Three-dimensional echocardiography for the evaluation of hypertrophic cardiomyopathy patients: relation to symptoms and exercise capacity.

Patients with hypertrophic cardiomyopathy may exhibit impaired functional capacity, associated with increased morbidity and mortality. Systolic function is one of the determinants of functional capacity. Early identification of systolic disfunction may identify patients at risk for adverse outcomes. Myocardial deformation parameters, derived from three-dimensional (3D) speckle-tracking echocardiography (3DSTE) are useful tools to assess left ventricular systolic function, and are often abnormal before a decline in ejection fraction is seen. The aim of this study was to evaluate the correlation between myocardial deformation parameters obtained by 3DSTE and functional capacity in patients with hypertrophic cardiomyopathy. Seventy-four hypertrophic cardiomyopathy adult patients were prospectively evaluated. All patients underwent a dedicated 2D and 3D echocardiographic examination and cardiopulmonary exercise testing (CPET). Values of 3D global radial (GRS), longitudinal (3DGLS) and circumferential strain (GCS) were overall reduced in our population: 99% (n = 73) of the patients had reduced GLS, 82% (n = 61) had reduced GRS and all patients had reduced GCS obtain by 3DSTE. Average peak VO2 was 21.01 (6.08) ml/Kg/min; 58% (n = 39) of the patients showed reduced exercise tolerance (predicted peak VO2 < 80%). The average VE/VCO2 slope was 29.0 (5.3) and 16% (n = 11) of the patients had impaired ventilatory efficiency (VE/VCO2 > 34). In multivariable analysis, 3D GLS (ß1 = 0.10, 95%CI: 0.03;0.23, p = 0.014), age (ß1 = -0.15, 95%CI: -0.23; -0.05, p = 0.002) and female gender (ß1 = -5.10, 95%CI: -7.7; -2.6, p < 0.01) were independently associated with peak VO2. No association was found between left ventricle ejection fraction obtain and peak VO2 (r = 0.161, p = 0.5). Impaired myocardial deformation parameters evaluated by 3DSTE were associated with worse functional capacity assessed by peak VO2.

Microvascular Dysfunction Is Associated With Impaired Myocardial Work in Obstructive and Nonobstructive Hypertrophic Cardiomyopathy: A Multimodality Study.

Background Two-dimensional speckle tracking echocardiography has been shown to correlate with microvascular dysfunction, a hallmark of hypertrophic cardiomyopathy (HCM). We hypothesized that there is an association between myocardial work and left ventricular ischemia, with incremental value to global longitudinal strain, in patients with HCM. Methods and Results We performed a prospective assessment of patients with HCM, undergoing 2-dimensional speckle tracking echocardiography and stress perfusion cardiac magnetic resonance. Results were stratified according to obstructive or nonobstructive HCM and the presence of significant replacement fibrosis (late gadolinium enhancement ≥15% of left ventricular mass). Seventy-five patients with HCM (63% men, age 55±15 years) were evaluated, 28% with obstructive HCM (mean gradient 89±60 mm Hg). Perfusion defects were found in 90.7%, involving 22.5±16.9% of left ventricular mass, and 38.7% had late gadolinium enhancement ≥15%. In a multivariable analysis, a lower global work index (r=-0.519, ß-estimate -10.822; P=0.001), lower global work efficiency (r=-0.379, ß-estimate -0.123; P=0.041), and impaired global constructive work (r=-0.532, ß-estimate -13.788; P<0.001) significantly correlated with ischemia. A segmental analysis supported these findings, albeit with lower correlation coefficients. A global work index cutoff ≤1755 mm Hg% was associated with hypoperfusion with a sensitivity of 88% and a specificity of 71%, while the best cutoff for global longitudinal strain (>-15.5%) had a sensitivity of 64% and a specificity of 57%. The association between myocardial work and perfusion defects was significant independently of late gadolinium enhancement ≥15% and obstructive HCM. Conclusions Impaired myocardial work was significantly correlated with the extent of ischemia in cardiac magnetic resonance, independently of the degree of left ventricular hypertrophy or fibrosis, with a higher predictive power than global longitudinal strain.

Sacubitril/Valsartan Improves Left Atrial and Ventricular Strain and Strain Rate in Patients with Heart Failure with Reduced Ejection Fraction.

BACKGROUND: Data on the impact of sacubitril/valsartan (SV) therapy on phasic left atrial (LA) and left ventricular (LV) strain in heart failure with reduced ejection fraction (HFrEF) are limited. The aim of this study was to evaluate changes in two-dimensional speckle tracking (2D-STE) parameters with SV therapy in HFrEF patients. METHODS: Prospective evaluation of HFrEF patients receiving optimized medical therapy. Two-dimensional speckle tracking (2D-STE) parameters were assessed at baseline and after 6 months of SV therapy. LA strain and strain rate (SR) in reservoir, conduit, and contraction phases were compared with LV longitudinal, radial, and circumferential strain and SR and stratified according to heart rhythm and HFrEF etiology. RESULTS: A total of 35 patients completed the 6-month follow-up, with a mean age of 59 ± 11 years, 40% in atrial fibrillation, 43% with ischemic etiology, and LVEF of 29 ± 6%. There were significant improvements in LA reservoir, conduit, and contractile strain and SR following SV therapy, particularly among patients in sinus rhythm. There were significant improvements in longitudinal, radial, and circumferential LV function indices. CONCLUSION: SV therapy in HFrEF was associated with improved longitudinal, radial, and circumferential function, particularly among patients in sinus rhythm. These findings can provide insights into the mechanisms underlying the improvement of cardiac function and help assess subclinical responses to the treatment.

Malignant Primary and Metastatic Cardiac Tumors: A Single-Center 27-Year Case Review.

BACKGROUND: Malignant primary cardiac tumors are exceedingly rare, and despite surgical exeresis or chemotherapy, their prognosis remains poor. Cardiac invasion by metastatic tumors, while more common, also entails an unsatisfactory outcome. This study aimed to review patients diagnosed with malignant primary and secondary cardiac tumors in a tertiary center between 1995 and 2022. METHODS: Clinical data, echocardiographic, computed tomography, and magnetic resonance assessments of tumor location and morphology, histology, treatment, and survival were retrospectively analyzed. RESULTS: Sixty malignant cardiac tumors were diagnosed: 17 primary (A) and 43 metastatic (B) tumors. A: the most common types were angiosarcoma (41%), undifferentiated sarcoma (23%), and fibrosarcoma (18%). Patients with primary tumors were younger than patients with metastatic tumors (41 ± 13 years vs. 57 ± 18 years, p = 0.001), with no significant gender difference. The most frequent presentations were heart failure (59%) and arrhythmia (23%). The most prevalent tumor location was the right heart chambers (71%), mostly in the right atrium (35%). 47% were submitted to tumor resection, and 29% received chemotherapy. The mortality rate was 82% with a median survival of 6.0 (interquartile range: 1.0-11.8) months after diagnosis (minimum of 12 days and maximum of 19 years). One patient with fibrosarcoma underwent heart transplantation and was still alive and well after 19 years. B: regarding metastatic cardiac invasion, the most common primary tumor sites were lung carcinomas (38%), thymomas (17%), and lymphomas (14%). Presentation with pericardial effusion was common (33%). The mortality rate was 72%, with a median survival of 3.6 (1.0-13.4) months (minimum of 7 days, maximum of 5 years). CONCLUSION: Diagnosis of metastatic cardiac tumors was more common than that of malignant primary tumors, both with a dismal prognosis. When radical exeresis is not possible, heart transplantation can be an option with a favorable outcome in carefully selected patients with sarcomas.

Impact of repaired aortic coarctation in left ventricular myocardial work.

AIMS: Myocardial strain analysis enables more precise assessment of cardiac performance but is relatively load dependent. New tools have been developed with afterload adjustment. Our objective was to assess myocardial work (MW) in patients with repaired aortic coarctation (rACo). METHODS: Prospective study of consecutive patients with rACo who underwent a routine transthoracic echocardiogram in 2018 and 2019 at our center. Patients with significant aortic valve disease, pacemaker, or other congenital heart diseases (except for mild bicuspid aortic valve disease) were excluded. Global longitudinal strain with two dimensional speckle tracking analysis and MW were obtained (GWI:Global Work Index; GCW: Global Constructive Work; GWW: Global Wasted Work; GWE: Global Work Efficiency). Blood pressure was measured in the patient's right arm. RESULTS: We included 42 patients in the analysis, mean age of 37±10 years, 38% males. In this group, 52% had hypertension and 64% had a concomitant bicuspid aortic valve. In comparison to previously published reference values, patients with rACo had significantly lower GWI (1807 vs. 1896 mmHg%) and GCW (2173 vs. 2232 mmHg%) (p<0.001), particularly in males. Systolic blood pressure is an independent predictor for GWI (ß=0.432) and for GCW (ß=0.534) and GLS an independent predictor of all MW parameters (ß>0.594). Neither age nor gender were independent predictors. CONCLUSIONS: In patients with rACo, there are some signs of left ventricular dysfunction with a reduction in GCW and GWI and with preserved GWE, despite normal ejection fraction and strain.

Blunted coronary flow velocity reserve is associated with impairment in systolic function and functional capacity in hypertrophic cardiomyopathy.

BACKGROUND: Coronary microvascular dysfunction constitutes an important pathophysiological feature in hypertrophic cardiomyopathy (HCM). We aimed to assess the association between impaired coronary flow velocity reserve (CFVR) and ventricular systolic function and functional capacity. METHODS: Eighty-three patients with HCM were enrolled in this prospective cohort study. Patients underwent echocardiogram to evaluate ventricular performance and CFVR in the left anterior descending artery (LAD) and posterior descending artery (PD). Diastolic coronary flow velocity was measured in basal conditions and in hyperemia. CFVR was calculated as the ratio of hyperemic and basal peak diastolic flow velocities. Functional capacity was evaluated by cardiopulmonary exercise testing (CPET). The link between CFVR and biventricular systolic function and peak VO2 was studied. RESULTS: Age was 55.0(14.4)years, 50 patients (60%) were male; 59 patients (71%) had nonobstructive HCM. Mean CFVR LAD was 1.81(0.49) and CFVR PD was 1.73(0.55). Lower CFVR PD was associated with impaired global longitudinal strain (GLS) 2D (ß-estimate:-3.240,95%CI:-4.634;-1.846, p < 0.001), GLS 3D (ß-estimate:-2.559,95%CI:-3.932;-1.186, p < 0.001) and area strain (ß-estimate:-3.044,95%CI:-5.373;-0.716, p = 0.011). Lower values of CFVR PD related to worse global work index (ß-estimate:267.824,95%CI:75.964;459.683, p = 0.007), global constructive work (ß-estimate:217.300,95%CI:38.750;395.850, p = 0.018) and global work efficiency (ß-estimate:5.656,95%CI:2.229;9.084, p = 0.002). Impaired CFVR LAD (ß-estimate:2.826, 95%CI:0.913;4.739, p = 0.004) and CFVR PD (ß-estimate:2.801,95%CI:0.657;4.945, p = 0.011) were associated with lower TAPSE. Lower values of CFVR LAD (ß-estimate:2.580, 95%CI:0.169;4.991, p = 0.036) and CFVR PD (ß-estimate:3.163, 95%CI: 0.721;5.606, p = 0.012) were associated with worse peak VO2. CONCLUSION: Lower CFVR was associated with impairment in biventricular systolic function parameters and functional capacity assessed by pVO2.

Myocardial Work Brings New Insights into Left Ventricular Remodelling in Cardio-Oncology Patients.

Serial transthoracic echocardiographic (TTE) assessment of 2D left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) are the gold standard screening methods for cancer therapeutics-related cardiac dysfunction (CTRCD). Non-invasive left ventricular (LV) pressure-strain loop (PSL) provides a novel method of quantifying myocardial work (MW) with potential advantages to evaluate the impact of cardiotoxic treatments on heart function. We prospectively assessed breast cancer female patients undergoing cancer therapy through serial monitoring by 2D and 3D TTE. Patients were evaluated at T0, T1 and T2 (before, 4-6 and 12-14 months after starting therapy, respectively). Through PSL analysis, MW indices were calculated. A total of 122 patients, with a mean age of 54.7 years, who received treatment with anthracyclines (77.0%) and anti-HER2 (75.4%) were included. During a mean follow-up of 14.9 ± 9.3 months, LVEF and GLS were significantly diminished, and 29.5% developed CTRCD. All MW indices were significantly reduced at T1 compared with baseline and tended to return to baseline values at T2. Global work index and global work efficiency showed a more pronounced variation in patients with CTRCD. The presence of more than one cardiovascular risk factor, obesity and baseline left atrium volume were predictors of changes in MW parameters. In conclusion, breast cancer treatment was associated with LV systolic dysfunction as assessed by MW, with its peak at 4-6 months and a partial recovery afterwards. Assessment of myocardial deformation parameters allows a more detailed characterization of cardiac remodelling and could enhance patient screening and selection for cardioprotective therapeutics.

Prevalence and prognostic impact of apical sparing contractility pattern in patients with aortic stenosis referred for transcatheter aortic valve implantation.

INTRODUCTION: Prolonged afterload increase in aortic stenosis (AS) may alter left ventricular (LV) contractility, irrespective of LV ejection fraction (LVEF). The prevalence and morbimortality associated with the apical sparing strain pattern (ASP), a typical finding of cardiac amyloidosis (CA), are not fully understood in patients with AS. We assessed the prevalence of the ASP in patients with severe AS and its clinical impact after transcatheter aortic valve implantation (TAVI). METHODS: Eighty-nine consecutive patients with severe AS and LV hypertrophy referred for TAVI were included. Baseline clinical and echocardiographic data were assessed, including the ASP in bull's eye plots (ASPB), relative apical longitudinal strain (RALS) and EF to global longitudinal strain (EF/GLS) ratio. We analysed all-cause mortality; a composite of all-cause mortality, stroke, and heart failure hospitalizations; and the rate of pacemaker implantation, after TAVI. RESULTS: Mean age was 82 ± 6 years and mean LVEF was 57 ± 10%. ASPB and RALS >1 were present in 43.8% and 24.7% of patients, respectively. Over a median follow-up of 13 months (IQR 6-32), ASPB was associated with higher rates of all-cause mortality (log-rank P=0.001) and was an independent predictor of all-cause mortality in multivariate analysis. Combination of the ASPB and GLS or EF/GLS ratio improved the risk stratification. Patients with RALS >1 were more likely to have new BBB and an indication for pacemaker implantation (P=0.048). CONCLUSION: The ASP, as assessed by the ASPB and RALS, was frequent in patients with AS regardless of the diagnosis of CA. The ASPB may refine risk stratification in patients referred for TAVI.

Paravalvular leak closure: Still a challenge with unpredictable results.

INTRODUCTION: Paravalvular leak (PVL) is a common serious complication associated with prosthetic valve implantation. OBJECTIVE: The aim of this study was to report our single-center experience in a retrospective review and to analyze possible predictors of success. METHODS: We performed 33 percutaneous PVL closures in 26 patients (54% female, mean age 65±13 years). All mitral prostheses were studied previously with 3D transesophageal echocardiography (TEE), and aortic prostheses with 2D/3D TEE. 3D TEE and fluoroscopy were used for the assessment, planning, and guidance of the interventions. Twelve patients also underwent computed tomography angiography for better characterization of anatomic details. RESULTS: Eighteen patients (69.2%) were admitted due to heart failure (New York Heart Association [NYHA] III or IV, seven (26.9%) because of heart failure and hemolysis, and one (3.8%) due to hemolysis only. Regarding the leaks, 46.2% were in aortic and 53.8% in mitral prostheses, 88.5% in mechanical and 7.7% in biological prostheses, and 3.8% in transcatheter aortic valve implants. All the aortic patients had severe aortic regurgitation. Furthermore, all mitral patients but one had moderate to severe or severe mitral regurgitation. Closure was successful in 17 patients (65.4%), partially successful in four (15.4%) and unsuccessful in five (19.2%). After the procedure, 69% were in NYHA I-II. Hemolysis worsened in three patients despite successful closure; all required further valvular surgery and two died. Regarding angiographic and echocardiographic procedural success, we analyzed age, gender, type of prosthesis (mechanical or biological), location (aortic or mitral), clinical data, maximum leak diameter, anatomic regurgitant orifice, leak location (anterior, posterior, inferior and lateral for mitral leaks and left, right and non-coronary sinus for aortic leaks), and number of devices (plugs) used for closure. No parameters presented a significant relationship with success excepting previous hemolysis. There was a relationship between clinical improvement and reduction of PVL (p=0.0001). In follow-up, cardiac-related events (new hospital admissions, cardiac valvular surgery, need for transfusion) were more frequent in patients with partially successful or unsuccessful closure (p=0.012). There was a relationship between cardiac-related events and death (p=0.029). CONCLUSION: Percutaneous PVL closure has emerged as an alternative treatment for PVL. Predictors of procedural success are difficult to establish. Survival is related to reduction of regurgitation and improvement in NYHA functional class.

Myocardial work is associated with significant left ventricular myocardial fibrosis in patients with hypertrophic cardiomyopathy.

Late gadolinium enhancement on cardiac magnetic resonance adds prognostic information in patients with hypertrophic cardiomyopathy. Whether Myocardial work, a new parameter on transthoracic echocardiographic, can be associated with significant fibrosis in hypertrophic cardiomyopathy patients is unknown. In a single-centre prospective evaluation of hypertrophic cardiomyopathy patients in whom transthoracic echocardiographic and cardiac magnetic resonance were performed, Myocardial work and related indices were calculated from global longitudinal strain and from estimated left ventricular pressure curves. The extent of late gadolinium enhancement was quantitatively assessed. Late gadolinium enhancement ≥ 15% was chosen to define significant fibrosis. Logistic regression analysis was used to find the variables associated with late gadolinium enhancement ≥ 15% and cut-off values were determined. Among the forty-six patients analysed mean age was 56 ± 15 years, 28 (61%) were male patients and the mean left ventricular ejection fraction by transthoracic echocardiographic was 67 ± 8%. Global constructive work and global work index were significantly related to late gadolinium enhancement ≥ 15%, while global longitudinal strain nearly reached statistical significance. A cut-off ≤ 1550 mmHg% of global constructive work was associated with significant fibrosis with a sensitivity of 91% and a specificity of 84%, while the best cut-off for global longitudinal strain (> - 15%) had a sensitivity of 67% and a specificity of 76%. In our study cohort, global constructive work was associated with significant left ventricular myocardial fibrosis in cardiac magnetic resonance, suggesting its utility in patients who may not be able to have a cardiac magnetic resonance study.

Melhora no Consumo Máximo de Oxigênio e na Ventilação após Tratamento com Sacubitril-Valsartana / Maximal Oxygen Uptake and Ventilation Improvement Following Sacubitril-Valsartan Therapy

Resumo Fundamento O tratamento com sacubitril-valsartana teve seu benefício prognóstico confirmado no ensaio PARADIGM-HF. No entanto, dados sobre alterações no teste de esforço cardiopulmonar (TECP) com o uso de sacubitril-valsartana são escassos. Objetivo O objetivo deste estudo foi comparar os parâmetros do TECP antes e depois do tratamento com sacubitril-valsartana. Métodos Avaliação prospectiva de pacientes com insuficiência cardíaca (IC) crônica e fração de ejeção do ventrículo esquerdo ≤40%, mesmo sob terapia padrão otimizada, que iniciaram tratamento com sacubitril-valsartana, sem expectativa de tratamentos adicionais para a IC. Os dados do TECP foram coletados na semana anterior e 6 meses depois do tratamento com sacubitril-valsartana. Diferenças estatísticas com valor p <0,05 foram consideradas significativas. Resultados De 42 pacientes, 35 (83,3%) completaram o seguimento de 6 meses, uma vez que 2 (4,8%) morreram e 5 (11,9%) interromperam o tratamento devido a eventos adversos. A média de idade foi de 58,6±11,1 anos. A classe NYHA (classificação da New York Heart Association) melhorou em 26 (74,3%) pacientes. O consumo máximo de oxigênio (VO2max) (14,4 vs. 18,3 ml/kg/min, p<0,001), a inclinação VE/VCO2 (36,7 vs. 31,1, p<0,001) e a duração do exercício (487,8 vs. 640,3 s, p<0,001) também melhoraram com o uso de sacubitril-valsartana. O benefício foi mantido mesmo com a dose de 24/26 mg (13,5 vs. 19,2 ml/kg/min, p=0,018) de sacubitril-valsartana, desde que esta tenha sido a maior dose tolerada. Conclusões O tratamento com sacubitril-valsartana está associado a uma melhora acentuada do VO2max, da inclinação VE/VCO2 e da duração do exercício no TECP. (Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0)

Abstract Background Sacubitril/valsartan had its prognosis benefit confirmed in the PARADIGM-HF trial. However, data on cardiopulmonary exercise testing (CPET) changes with sacubitril-valsartan therapy are scarce. Objective This study aimed to compare CPET parameters before and after sacubitril-valsartan therapy. Methods Prospective evaluation of chronic heart failure (HF) patients with left ventricular ejection fraction ≤40% despite optimized standard of care therapy, who started sacubitril-valsartan therapy, expecting no additional HF treatment. CPET data were gathered in the week before and 6 months after sacubitril-valsartan therapy. Statistical differences with a p-value <0.05 were considered significant. Results Out of 42 patients, 35 (83.3%) completed the 6-month follow-up, since 2 (4.8%) patients died and 5 (11.9%) discontinued treatment for adverse events. Mean age was 58.6±11.1 years. New York Heart Association class improved in 26 (74.3%) patients. Maximal oxygen uptake (VO2max) (14.4 vs. 18.3 ml/kg/min, p<0.001), VE/VCO2slope (36.7 vs. 31.1, p<0.001), and exercise duration (487.8 vs. 640.3 sec, p<0.001) also improved with sacubitril-valsartan. Benefit was maintained even with the 24/26 mg dose (13.5 vs. 19.2 ml/kg/min, p=0.018) of sacubitril-valsartan, as long as this was the highest tolerated dose. Conclusions Sacubitril-valsartan therapy is associated with marked CPET improvement in VO2max, VE/VCO2slope, and exercise duration. (Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0)

Maximal Oxygen Uptake and Ventilation Improvement Following Sacubitril-Valsartan Therapy. / Melhora no Consumo Máximo de Oxigênio e na Ventilação após Tratamento com Sacubitril-Valsartana.

BACKGROUND: Sacubitril/valsartan had its prognosis benefit confirmed in the PARADIGM-HF trial. However, data on cardiopulmonary exercise testing (CPET) changes with sacubitril-valsartan therapy are scarce. OBJECTIVE: This study aimed to compare CPET parameters before and after sacubitril-valsartan therapy. METHODS: Prospective evaluation of chronic heart failure (HF) patients with left ventricular ejection fraction ≤40% despite optimized standard of care therapy, who started sacubitril-valsartan therapy, expecting no additional HF treatment. CPET data were gathered in the week before and 6 months after sacubitril-valsartan therapy. Statistical differences with a p-value <0.05 were considered significant. RESULTS: Out of 42 patients, 35 (83.3%) completed the 6-month follow-up, since 2 (4.8%) patients died and 5 (11.9%) discontinued treatment for adverse events. Mean age was 58.6±11.1 years. New York Heart Association class improved in 26 (74.3%) patients. Maximal oxygen uptake (VO2max) (14.4 vs. 18.3 ml/kg/min, p<0.001), VE/VCO2slope (36.7 vs. 31.1, p<0.001), and exercise duration (487.8 vs. 640.3 sec, p<0.001) also improved with sacubitril-valsartan. Benefit was maintained even with the 24/26 mg dose (13.5 vs. 19.2 ml/kg/min, p=0.018) of sacubitril-valsartan, as long as this was the highest tolerated dose. CONCLUSIONS: Sacubitril-valsartan therapy is associated with marked CPET improvement in VO2max, VE/VCO2slope, and exercise duration. (Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0).

FUNDAMENTO: O tratamento com sacubitril-valsartana teve seu benefício prognóstico confirmado no ensaio PARADIGM-HF. No entanto, dados sobre alterações no teste de esforço cardiopulmonar (TECP) com o uso de sacubitril-valsartana são escassos. OBJETIVO: O objetivo deste estudo foi comparar os parâmetros do TECP antes e depois do tratamento com sacubitril-valsartana. MÉTODOS: Avaliação prospectiva de pacientes com insuficiência cardíaca (IC) crônica e fração de ejeção do ventrículo esquerdo ≤40%, mesmo sob terapia padrão otimizada, que iniciaram tratamento com sacubitril-valsartana, sem expectativa de tratamentos adicionais para a IC. Os dados do TECP foram coletados na semana anterior e 6 meses depois do tratamento com sacubitril-valsartana. Diferenças estatísticas com valor p <0,05 foram consideradas significativas. RESULTADOS: De 42 pacientes, 35 (83,3%) completaram o seguimento de 6 meses, uma vez que 2 (4,8%) morreram e 5 (11,9%) interromperam o tratamento devido a eventos adversos. A média de idade foi de 58,6±11,1 anos. A classe NYHA (classificação da New York Heart Association) melhorou em 26 (74,3%) pacientes. O consumo máximo de oxigênio (VO2max) (14,4 vs. 18,3 ml/kg/min, p<0,001), a inclinação VE/VCO2 (36,7 vs. 31,1, p<0,001) e a duração do exercício (487,8 vs. 640,3 s, p<0,001) também melhoraram com o uso de sacubitril-valsartana. O benefício foi mantido mesmo com a dose de 24/26 mg (13,5 vs. 19,2 ml/kg/min, p=0,018) de sacubitril-valsartana, desde que esta tenha sido a maior dose tolerada. CONCLUSÕES: O tratamento com sacubitril-valsartana está associado a uma melhora acentuada do VO2max, da inclinação VE/VCO2 e da duração do exercício no TECP. (Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0).

C-reactive protein reduction with sacubitril-valsartan treatment in heart failure patients.

OBJECTIVE: C-Reactive Protein (CRP) has emerged as an accessible measured product of inflammation. Whether systemic inflammation, a common feature of Heart Failure (HF), can be reduced by HF treatments in not well established. Sacubitril/Valsartan had prognosis benefit demonstrated in the PARADIGM-HF trial and was able to reduce proinflammatory cytokines in preclinical animal studies. However, no human studies evaluated if the benefits of this therapy are mediated by anti-inflammatory effects too. The aim of this study was to prospectively compare CRP values before and six months after Sacubitril-Valsartan therapy. METHODS: Prospective evaluation of chronic HF patients with left ventricular ejection fraction ≤ 40% despite optimized standard of care therapy, in which Sacubitril/Valsartan therapy was started and no additional HF treatment was expected to change. Clinical, laboratorial (including CRP values), electrocardiographic, transthoracic echocardiography and cardiopulmonary exercise test (CPET) data were gathered in the week before starting Sacubitril/Valsartan therapy and six months thereafter. RESULTS: There were 42 patients with a mean age of 59 ± 11 years, of which 35 completed the six months of follow-up, since 2 patients died and 5 discontinued treatment for adverse events. Patients with baseline CRP values above the median (> 2.5 mg/L) had a significantly higher percentage of New York Heart Association class ≥ III (65% vs. 33%, P=0.028) and a reduced exercise time in CPET (361 ± 297 vs. 575 ± 265 seconds, P=0.034). After 6 months of Sacubitril-Valsartan therapy, 24 (69%) patients had an improvement in CRP values with a significantly reduction as compared to baseline (median 2.5 mg/L (Interquartile range (IQR) 1.3-5.0) vs. 2.2 mg/L (IQR 0.9-4.0), P=0.014 in the Wilcoxon test). In the group of 17 (49%) patients with at least 25% improvement in CRP values with Sacubitril/Valsartan therapy, the benefit of several clinical, CPET and echocardiographic parameters were not significantly different from the benefit of patients with no improvement or an improvement inferior to 25% in CRP values. CONCLUSION: Sacubitril/Valsartan therapy was able to reduce CRP values in a chronic HF population. Whether this reduction was only a consequence of clinical improvement with Sacubitril/Valsartan or an anti-inflammatory effect is also present should be further evaluated.