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1.
Eur J Heart Fail ; 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38840564

RESUMO

AIMS: Cardiopulmonary exercise testing (CPET) combined with exercise echocardiography (CPETecho) allows simultaneous assessments of cardiac, pulmonary, and ventilation in heart failure (HF) with preserved ejection fraction (HFpEF). This study sought to determine whether simultaneous assessment of CPET variables could provide additive predictive value over exercise stress echocardiography in patients with dyspnoea. METHODS AND RESULTS: CPETecho was performed in 443 patients with suspected HFpEF (240 HFpEF and 203 controls without HF). Patients with HFpEF were divided based on peak oxygen consumption (VO2, ≥10 or <10 ml/min/kg) or the slope of minute ventilation to carbon dioxide production (VE vs. VCO2 slope ≥45.0 or <45.0). The primary endpoint was defined as a composite of all-cause mortality, HF hospitalization, unplanned hospital visits requiring intravenous diuretics, or intensification of oral diuretics. During a median follow-up of 399 days, the composite outcome occurred in 57 patients. E/e' ratio during peak exercise was associated with adverse outcomes. Patients with HFpEF and lower peak VO2 had increased risks of the composite event (hazard ratio [HR] 5.05, 95% confidence interval [CI] 2.65-9.62, p < 0.0001 vs. controls; HR 3.14, 95% CI 1.69-5.84, p = 0.0003 vs. HFpEF with higher peak VO2). Elevated VE versus VCO2 slope was also associated with adverse events in HFpEF. The addition of either the presence of abnormal peak VO2 or VE versus VCO2 slope increased the predictive ability over the model based on age, sex, atrial fibrillation, left atrial volume index, and exercise E/e' (p < 0.05). CONCLUSION: These data provide new insights into the role of CPETecho in patients with HFpEF.

2.
Eur J Heart Fail ; 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38837599

RESUMO

AIMS: This study aimed to evaluate the clinical significance of secondary mitral regurgitation (MR) in patients with heart failure with preserved ejection fraction (HFpEF). METHODS AND RESULTS: We conducted a prospective study enrolling consecutively evaluated patients with HFpEF undergoing invasive haemodynamic exercise testing with simultaneous echocardiography. Compared to HFpEF without MR (n = 145, 79.7%), those with mild or moderate MR (n = 37, 20.3%) were older, more likely to be women, had more left ventricular (LV) systolic dysfunction, and more likely to have left atrial (LA) myopathy reflected by greater burden of atrial fibrillation, more LA dilatation, and poorer LA function. Pulmonary artery (PA) wedge pressure was higher at rest in HFpEF with MR (17 ± 5 mmHg vs. 20 ± 5 mmHg, p = 0.005), but there was no difference with exercise. At rest, only 2 (1.1%) patients had moderate MR, and none developed severe MR. Pulmonary vascular resistance was higher, and right ventricular (RV)-PA coupling was more impaired in patients with HFpEF and MR at rest and exercise. LV and LA myocardial dysfunction remained more severe in patients with MR during stress compared to those without MR, characterized by greater LA dilatation during all stages of exertion, lower LA emptying fraction and compliance, steeper and rightward-shifted LA pressure-volume relationships, and reduced LV longitudinal contractile function. CONCLUSIONS: Patients with HFpEF and mild or moderate MR have more severe LV systolic dysfunction, LA myopathy, RV-PA uncoupling, and more severe pulmonary vascular disease. Mitral valve incompetence in this setting is a phenotypic marker of more advanced disease but is not a causal factor in development of HFpEF.

3.
Artigo em Inglês | MEDLINE | ID: mdl-38754750

RESUMO

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome requiring improved phenotypic classification. Previous studies have identified subphenotypes of HFpEF, but the lack of exercise assessment is a major limitation. The aim of this study was to identify distinct pathophysiologic clusters of HFpEF based on clinical characteristics, and resting and exercise assessments. METHODS: A total of 265 patients with HFpEF underwent ergometry exercise stress echocardiography with simultaneous expired gas analysis. Cluster analysis was performed by the K-prototype method with 21 variables (10 clinical and resting echocardiographic variables and 11 exercise echocardiographic parameters). Pathophysiologic features, exercise tolerance, and prognosis were compared among phenogroups. RESULTS: Three distinct phenogroups were identified. Phenogroup 1 (n = 112 [42%]) was characterized by preserved biventricular systolic reserve and cardiac output augmentation. Phenogroup 2 (n = 58 [22%]) was characterized by a high prevalence of atrial fibrillation, increased pulmonary arterial and right atrial pressures, depressed right ventricular systolic functional reserve, and impaired right ventricular-pulmonary artery coupling during exercise. Phenogroup 3 (n = 95 [36%]) was characterized by the smallest body mass index, ventricular and vascular stiffening, impaired left ventricular diastolic reserve, and worse exercise capacity. Phenogroups 2 and 3 had higher rates of composite outcomes of all-cause mortality or heart failure events than phenogroup 1 (log-rank P = .02). CONCLUSION: Exercise echocardiography-based cluster analysis identified three distinct phenogroups of HFpEF, with unique exercise pathophysiologic features, exercise capacity, and clinical outcomes.

4.
J Gastroenterol ; 59(3): 179-186, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38252140

RESUMO

BACKGROUNDS: Patients with systemic sclerosis (SSc) often have esophageal motility abnormalities and weak esophago-gastric junction (EGJ) barrier function, which causes proton pump inhibitor (PPI)-refractory reflux esophagitis (RE). The aims of this study were to clarify the current management of RE and prevalence and risk factors of medication-refractory RE in patients with SSc in Japan. METHODS: A total of 188 consecutive patients with SSc who underwent both esophageal high-resolution manometry (HRM) and esophagogastroduodenoscopy (EGD) were reviewed. The presence of RE and grades of the gastroesophageal flap valve (GEFV) were assessed. Esophageal motility was assessed retrospectively according to the Chicago classification v3.0. When RE was seen on a standard dose of PPI or any dose of vonoprazan (VPZ), it was defined as medication-refractory RE. RESULTS: Approximately 80% of patients received maintenance therapy with acid secretion inhibitors regardless of esophageal motility abnormalities. Approximately 50% of patients received maintenance therapy with PPI, and approximately 30% of patients received VPZ. Medication-refractory RE was observed in 30 patients (16.0%). In multivariable analyses, the number of EGD and absent contractility were significant risk factors for medication-refractory RE. Furthermore, combined absent contractility and GEFV grade III or IV had higher odds ratios than did absent contractility alone. CONCLUSIONS: Patients with persistent reflux symptoms and those with absent contractility and GEFV grade III or IV should receive maintenance therapy with strong acid inhibition to prevent medication-refractory RE.


Assuntos
Esofagite Péptica , Pirróis , Escleroderma Sistêmico , Sulfonamidas , Humanos , Esofagite Péptica/tratamento farmacológico , Esofagite Péptica/epidemiologia , Esofagite Péptica/etiologia , Japão/epidemiologia , Prevalência , Estudos Retrospectivos , Fatores de Risco , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/tratamento farmacológico , Inibidores da Bomba de Prótons , Manometria
5.
Eur Heart J Cardiovasc Imaging ; 25(2): 220-228, 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-37738627

RESUMO

AIMS: Heart failure with preserved ejection fraction (HFpEF) is a syndrome characterized by multiple cardiac reserve limitations during exercise. Cardiac power output (CPO) is an index of global cardiac performance and can be estimated non-invasively by echocardiography. We hypothesized that CPO reserve during exercise would be associated with impaired cardiovascular reserve, exercise intolerance, and adverse outcomes in HFpEF. METHODS AND RESULTS: Exercise stress echocardiography was performed in 425 dyspnoeic patients [217 HFpEF and 208 non-heart failure (HF) controls] to estimate CPO at rest and during exercise. We classified patients with HFpEF based on the median value of changes in CPO from rest to peak exercise (ΔCPO >0.49 W/100 g). Patients with HFpEF and a lower CPO reserve had poorer biventricular systolic function, impaired chronotropic response during exercise, and worse aerobic capacity than controls and those with a higher CPO reserve. During a median follow-up of 358 days, a composite outcome of all-cause mortality or HF events occurred in 30 patients. Patients with a lower CPO reserve had four-fold and nearly 10-fold increased risks of the outcomes compared with those with a higher CPO reserve and controls, respectively [hazard ratio (HR) 4.05, 95% confidence interval (CI) 1.16-10.1, P = 0.003 and HR 9.61, 95% CI 3.58-25.8, P < 0.0001]. We further found that a lower CPO reserve had an incremental prognostic value over the H2FPEF score and exercise duration. In contrast, resting CPO did not predict clinical outcomes in patients with HFpEF. CONCLUSION: A lower CPO reserve was associated with biventricular systolic dysfunction, chronotropic incompetence, exercise intolerance, and adverse outcomes in patients with HFpEF.


Assuntos
Insuficiência Cardíaca , Humanos , Volume Sistólico/fisiologia , Prognóstico , Débito Cardíaco , Ecocardiografia/métodos , Tolerância ao Exercício/fisiologia , Teste de Esforço , Função Ventricular Esquerda
6.
J Cardiol ; 83(2): 113-120, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37419310

RESUMO

BACKGROUND: Exercise intolerance is the primary symptom of patients with heart failure with preserved ejection fraction (HFpEF). Chronotropic incompetence has been considered to be common and contribute to poor exercise capacity in HFpEF. However, clinical characteristics, pathophysiology, and outcomes of chronotropic incompetence in HFpEF remain poorly understood. METHODS: Patients with HFpEF (n = 246) underwent ergometry exercise stress echocardiography with simultaneous expired gas analysis. The patients were divided into two groups based on the presence of chronotropic incompetence, which was defined by heart rate reserve <0.80. RESULTS: Chronotropic incompetence was common in HFpEF (n = 112, 41 %). Compared to HFpEF patients with a normal chronotropic response (n = 134), those with chronotropic incompetence had higher body mass index, a higher prevalence of diabetes, more frequent ß-blocker use, and worse New York Heart Association class. During peak exercise, patients with chronotropic incompetence demonstrated less increase in cardiac output and arterial oxygen delivery (cardiac output × saturation × hemoglobin × 1.34 × 10), higher metabolic work (peak oxygen consumption [VO2]/watt), an inability to increase arteriovenous oxygen difference, and poorer exercise capacity (lower peak VO2) than those without. Chronotropic incompetence was associated with higher rates of a composite of all-cause mortality or worsening HF events (hazard ratio, 2.66, 95 % confidence intervals, 1.16-6.09, p = 0.02). CONCLUSION: Chronotropic incompetence is common in HFpEF, and is associated with unique pathophysiologic characteristics during exercise and clinical outcomes.


Assuntos
Insuficiência Cardíaca , Humanos , Insuficiência Cardíaca/diagnóstico , Volume Sistólico/fisiologia , Prognóstico , Teste de Esforço , Consumo de Oxigênio/fisiologia , Tolerância ao Exercício/fisiologia , Oxigênio
7.
Eur J Heart Fail ; 26(2): 288-298, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38059338

RESUMO

AIM: Left atrial (LA) myopathy is increasingly recognized as an important phenotypic trait in heart failure (HF) with preserved ejection fraction (HFpEF). Right atrial (RA) remodelling and dysfunction also develop in HFpEF, but little data are available regarding the clinical characteristics and pathophysiology among patients with isolated LA, RA, or biatrial myopathy. METHODS AND RESULTS: Patients with HFpEF underwent invasive haemodynamic exercise testing, comprehensive imaging including speckle tracking strain echocardiography, and clinical follow-up at Mayo Clinic between 2006 and 2018. LA myopathy was defined as LA volume index >34 ml/m2 and/or LA reservoir strain ≤24% and RA myopathy by RA volume index >39 ml/m2 in men and >33 ml/m2 in women and/or RA reservoir strain ≤19.8%. Of 476 consecutively evaluated patients with HFpEF defined by invasive exercise testing with evaluable atrial structure/function, 125 (26%) had no atrial myopathy, 147 (31%) had isolated LA myopathy, 184 (39%) had biatrial myopathy, and 20 (4%) had isolated RA myopathy. Patients with HFpEF and biatrial myopathy had more atrial fibrillation, poorer left ventricular systolic and diastolic function, more severe pulmonary vascular disease, tricuspid regurgitation, ventricular interdependence and right ventricular dysfunction, and poorer cardiac output reserve with exercise. There were 94 patients with events over a median follow-up of 2.9 (interquartile range 1.4-4.6) years. Individuals with biatrial myopathy had an 84% higher risk of HF hospitalization or death as compared to those with isolated LA myopathy (hazard ratio 1.84; 95% confidence interval 1.16-2.92, p = 0.01). CONCLUSIONS: Biatrial myopathy identifies patients with more advanced HFpEF characterized by more severe pulmonary vascular disease, right HF, poorer cardiac reserve, and a greater risk for adverse outcomes. Further study is required to define optimal strategies to treat and prevent biatrial myopathy in HFpEF.


Assuntos
Insuficiência Cardíaca , Doenças Musculares , Doenças Vasculares , Masculino , Humanos , Feminino , Volume Sistólico/fisiologia , Ecocardiografia/métodos , Função Ventricular Esquerda/fisiologia
8.
Eur J Heart Fail ; 26(3): 564-577, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38156712

RESUMO

AIMS: We aimed to clarify the extent to which cardiac and peripheral impairments to oxygen delivery and utilization contribute to exercise intolerance and risk for adverse events, and how this relates to diversity and multiplicity in pathophysiologic traits. METHODS AND RESULTS: Individuals with heart failure with preserved ejection fraction (HFpEF) and non-cardiac dyspnoea (controls) underwent invasive cardiopulmonary exercise testing and clinical follow-up. Haemodynamics and oxygen transport responses were compared. HFpEF patients were then categorized a priori into previously-proposed, non-exclusive descriptive clinical trait phenogroups, including cardiometabolic, pulmonary vascular disease, left atrial myopathy, and vascular stiffening phenogroups based on clinical and haemodynamic profiles to contrast pathophysiology and clinical risk. Overall, patients with HFpEF (n = 643) had impaired cardiac output reserve with exercise (2.3 vs. 2.8 L/min, p = 0.025) and greater reliance on peripheral oxygen extraction augmentation (4.5 vs. 3.8 ml/dl, p < 0.001) compared to dyspnoeic controls (n = 219). Most (94%) patients with HFpEF met criteria for at least one clinical phenogroup, and 67% fulfilled criteria for multiple overlapping phenogroups. There was greater impairment in peripheral limitations in the cardiometabolic group and greater cardiac output limitations and higher pulmonary vascular resistance during exertion in the other phenogroups. Increasing trait multiplicity within a given patient was associated with worse exercise haemodynamics, poorer exercise capacity, lower cardiac output reserve, and greater risk for heart failure hospitalization or death (hazard ratio 1.74, 95% confidence interval 1.08-2.79 for 0-1 vs. ≥2 phenogroup traits present). CONCLUSIONS: Though cardiac output response to exercise is limited in patients with HFpEF compared to those with non-cardiac dyspnoea, the relative contributions of cardiac and peripheral limitations vary with differing numbers and types of clinical phenotypic traits present. Patients fulfilling criteria for greater multiplicity and diversity of HFpEF phenogroup traits have poorer exercise capacity, worsening haemodynamic perturbations, and greater risk for adverse outcome.


Assuntos
Teste de Esforço , Tolerância ao Exercício , Insuficiência Cardíaca , Volume Sistólico , Humanos , Insuficiência Cardíaca/fisiopatologia , Tolerância ao Exercício/fisiologia , Feminino , Masculino , Volume Sistólico/fisiologia , Idoso , Pessoa de Meia-Idade , Teste de Esforço/métodos , Consumo de Oxigênio/fisiologia , Fenótipo , Dispneia/fisiopatologia , Dispneia/etiologia , Hemodinâmica/fisiologia
9.
Mayo Clin Proc ; 99(2): 206-217, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38127015

RESUMO

OBJECTIVE: To determine whether nitrite can enhance exercise training (ET) effects in heart failure with preserved ejection fraction (HFpEF). METHODS: In this multicenter, double-blind, placebo-controlled, randomized trial conducted at 1 urban and 9 rural outreach centers between November 22, 2016, and December 9, 2021, patients with HFpEF underwent ET along with inorganic nitrite 40 mg or placebo 3 times daily. The primary end point was peak oxygen consumption (VO2). Secondary end points included Kansas City Cardiomyopathy Questionnaire overall summary score (KCCQ-OSS, range 0 to 100; higher scores reflect better health status), 6-minute walk distance, and actigraphy. RESULTS: Of 92 patients randomized, 73 completed the trial because of protocol modifications necessitated by loss of drug availability. Most patients were older than 65 years (80%), were obese (75%), and lived in rural settings (63%). At baseline, median peak VO2 (14.1 mL·kg-1·min-1) and KCCQ-OSS (63.7) were severely reduced. Exercise training improved peak VO2 (+0.8 mL·kg-1·min-1; 95% CI, 0.3 to 1.2; P<.001) and KCCQ-OSS (+5.5; 95% CI, 2.5 to 8.6; P<.001). Nitrite was well tolerated, but treatment with nitrite did not affect the change in peak VO2 with ET (nitrite effect, -0.13; 95% CI, -1.03 to 0.76; P=.77) or KCCQ-OSS (-1.2; 95% CI, -7.2 to 4.9; P=.71). This pattern was consistent across other secondary outcomes. CONCLUSION: For patients with HFpEF, ET administered for 12 weeks in a predominantly rural setting improved exercise capacity and health status, but compared with placebo, treatment with inorganic nitrite did not enhance the benefit from ET. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02713126.


Assuntos
Insuficiência Cardíaca , Humanos , Insuficiência Cardíaca/tratamento farmacológico , Nitritos/farmacologia , Nitritos/uso terapêutico , Volume Sistólico , Exercício Físico , Nível de Saúde , Qualidade de Vida , Tolerância ao Exercício
10.
Int J Cardiol Heart Vasc ; 48: 101255, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37794956

RESUMO

Aims: Anemia is common in patients with heart failure with preserved ejection fraction (HFpEF) and is associated with exercise intolerance. However, there are limited data on how anemia contributes to reduced exercise capacity in patients with HFpEF. We aimed to characterize exercise capacity, cardiovascular and ventilatory reserve, and the oxygen (O2) pathway in anemic patients with HFpEF. Methods: A total of 238 patients with HFpEF and 248 dyspneic patients without HF underwent ergometry exercise stress echocardiography with simultaneous expired gas analysis. Patients with HFpEF were classified into two groups based on the presence of anemia (hemoglobin < 13.0 g/dL in men and < 12.0 g/dL in women). Results: Anemic HFpEF patients (n = 112) had worse nutritional status and renal function, lower iron levels, and greater left ventricular (LV) remodeling and plasma volume expansion than those without anemia (n = 126). Exercise capacity, assessed by peak oxygen consumption, exercise intensity, and exercise duration, was lower in the anemic HFpEF group than in the other groups. Despite a similar cardiac output during exercise, anemic patients with HFpEF demonstrated limitations in arterial O2 delivery, lower arteriovenous O2 content difference, and ventilatory inefficiency (higher minute ventilation vs. carbon dioxide production slope) during peak exercise. Conclusion: Anemic HFpEF patients demonstrated unique pathophysiological features with greater LV remodeling and plasma volume expansion, limitations in arterial O2 delivery and peripheral O2 extraction, and ventilatory inefficiency, which may contribute to reduced exercise capacity. Further studies are needed to develop an optimal approach for treating anemia in patients with HFpEF.

12.
JACC Heart Fail ; 11(11): 1549-1561, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37565977

RESUMO

BACKGROUND: Interleukin (IL)-6 is a central inflammatory mediator and potential therapeutic target in heart failure (HF). Prior studies have shown that IL-6 concentrations are elevated in patients with HF, but much fewer data are available in heart failure with preserved ejection fraction (HFpEF). OBJECTIVES: This study aims to determine how IL-6 relates to changes in cardiac function, congestion, body composition, and exercise tolerance in HFpEF. METHODS: Clinical, laboratory, body composition, exercise capacity, physiologic and health status data across 4 National Heart, Lung, and Blood Institute-sponsored trials were analyzed according to the tertiles of IL-6. RESULTS: IL-6 was measured in 374 patients with HFpEF. Patients with highest IL-6 levels had greater body mass index; higher N-terminal pro-B-type natriuretic peptide, C-reactive protein, and tumor necrosis factor-α levels; worse renal function; and lower hemoglobin levels, and were more likely to have diabetes. Although cardiac structure and function measured at rest were similar, patients with HFpEF and highest IL-6 concentrations had more severely impaired peak oxygen consumption (12.3 ± 3.3 mL/kg/min 13.1 ± 3.1 mL/kg/min 14.4 ± 3.9 mL/kg/min, P < 0.0001) as well as 6-minute walk distance (276 ± 107 m vs 332 ± 106 m vs 352 ± 116 m, P < 0.0001), even after accounting for increases in IL-6 related to excess body mass. IL-6 concentrations were associated with increases in total body fat and trunk fat, more severe symptoms during submaximal exercise, and poorer patient-reported health status. CONCLUSIONS: IL-6 levels are commonly elevated in HFpEF, and are associated with greater symptom severity, poorer exercise capacity, and more upper body fat accumulation. These findings support testing the hypothesis that therapies that inhibit IL-6 in patients with HFpEF may improve clinical status. (Clinical Trial Registrations: Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Diastolic Heart Failure [RELAX], NCT00763867; Nitrate's Effect on Activity Tolerance in Heart Failure With Preserved Ejection Fraction, NCT02053493; Inorganic Nitrite Delivery to Improve Exercise Capacity in HFpEF, NCT02742129; Inorganic Nitrite to Enhance Benefits From Exercise Training in Heart Failure With Preserved Ejection Fraction [HFpEF], NCT02713126).


Assuntos
Insuficiência Cardíaca , Humanos , Interleucina-6/farmacologia , Interleucina-6/uso terapêutico , Volume Sistólico/fisiologia , Nitritos/farmacologia , Nitritos/uso terapêutico , Coração , Tolerância ao Exercício/fisiologia
13.
Circulation ; 148(10): 834-844, 2023 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-37534453

RESUMO

BACKGROUND: Sodium-glucose cotransporter-2 inhibitors reduce risk of hospitalization for heart failure in patients who have heart failure with preserved ejection fraction (HFpEF), but the hemodynamic mechanisms underlying these benefits remain unclear. This study sought to determine whether treatment with dapagliflozin affects pulmonary capillary wedge pressure (PCWP) at rest and during exercise in patients with HFpEF. METHODS: This was a single-center, double-blinded, randomized, placebo-controlled trial testing the effects of 10 mg of dapagliflozin once daily in patients with HFpEF. Patients with New York Heart Association class II or III heart failure, ejection fraction ≥50%, and elevated PCWP during exercise were recruited. Cardiac hemodynamics were measured at rest and during exercise using high-fidelity micromanometers at baseline and after 24 weeks of treatment. The primary end point was a change from baseline in rest and peak exercise PCWPs that incorporated both measurements, and was compared using a mixed-model likelihood ratio test. Key secondary end points included body weight and directly measured blood and plasma volumes. Expired gas analysis was performed evaluate oxygen transport in tandem with arterial lactate sampling. RESULTS: Among 38 patients completing baseline assessments (median age 68 years; 66% women; 71% obese), 37 completed the trial. Treatment with dapagliflozin resulted in reduction in the primary end point of change in PCWP at rest and during exercise at 24 weeks relative to treatment with placebo (likelihood ratio test for overall changes in PCWP; P<0.001), with lower PCWP at rest (estimated treatment difference [ETD], -3.5 mm Hg [95% CI, -6.6 to -0.4]; P=0.029) and maximal exercise (ETD, -5.7 mm Hg [95% CI, -10.8 to -0.7]; P=0.027). Body weight was reduced with dapagliflozin (ETD, -3.5 kg [95% CI, -5.9 to -1.1]; P=0.006), as was plasma volume (ETD, -285 mL [95% CI, -510 to -60]; P=0.014), but there was no significant effect on red blood cell volume. There were no differences in oxygen consumption at 20-W or peak exercise, but dapagliflozin decreased arterial lactate at 20 W (-0.70 ± 0.77 versus 0.37 ± 1.29 mM; P=0.006). CONCLUSIONS: In patients with HFpEF, treatment with dapagliflozin reduces resting and exercise PCWP, along with the favorable effects on plasma volume and body weight. These findings provide new insight into the hemodynamic mechanisms of benefit with sodium-glucose cotransporter-2 inhibitors in HFpEF. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04730947.


Assuntos
Insuficiência Cardíaca , Inibidores do Transportador 2 de Sódio-Glicose , Idoso , Feminino , Humanos , Masculino , Cateterismo Cardíaco/métodos , Insuficiência Cardíaca/tratamento farmacológico , Lactatos/sangue , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Volume Sistólico , Função Ventricular Esquerda
14.
CJC Open ; 5(5): 380-391, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37377513

RESUMO

Background: Hospitalization with a first episode of heart failure (HF) is a serious event associated with poor clinical outcomes in HF with preserved ejection fraction (HFpEF). Identification of HFpEF via detection of elevated left ventricular filling pressure at rest or during exercise may allow early intervention. Benefits of treatment with mineralocorticoid receptor antagonists (MRAs) in established HFpEF have been reported, but use of MRAs is not well studied in early HFpEF without prior HF hospitalization. Methods: We retrospectively studied 197 patients with HFpEF who did not have prior hospitalization but had been diagnosed by exercise stress echocardiography or catheterization. We examined changes in natriuretic peptide levels and echocardiographic parameters reflecting diastolic function following MRA initiation. Results: Of the 197 patients with HFpEF, MRA treatment was initiated for 47 patients. After a median 3-month follow-up, reduction in N-terminal pro-B-type natriuretic peptide levels from baseline to follow-up was greater in patients treated with MRA than in those who were not (median, -200 pg/mL [interquartile range, -544 to -31] vs 67 pg/mL [interquartile range, -95 to 456], P < 0.0001 in 50 patients with paired data). Similar results were observed for the changes in B-type natriuretic peptide levels. Reduction in the left atrial volume index was also greater in the MRA-treated group than in the non-MRA-treated group after a median 7-month follow-up (77 patients with paired echocardiographic data). Patients with lower left ventricular global longitudinal strain experienced a greater reduction in N-terminal pro-B-type natriuretic peptide levels following MRA treatment. In the safety assessment, MRA modestly decreased renal function but did not change potassium levels. Conclusions: Our results suggest that MRA treatment has potential benefits for early-stage HFpEF.


Contexte: L'hospitalisation consécutive à un premier épisode d'insuffisance cardiaque (IC) est un événement grave associé à des résultats cliniques médiocres dans l'IC à fraction d'éjection préservée (ICFEP). Or, la détection d'une pression de remplissage ventriculaire gauche élevée au repos ou à l'effort peut permettre de déceler une ICFEP et d'intervenir de façon précoce. Par ailleurs, le recours à des antagonistes des récepteurs minéralocorticoïdes (ARM) serait bénéfique dans les cas d'ICFEP, mais leur utilisation n'a pas été bien étudiée dans l'ICFEP précoce sans hospitalisation préalable pour cause d'insuffisance cardiaque. Méthodologie: Nous avons étudié rétrospectivement 197 patients atteints d'ICFEP qui n'avaient pas été hospitalisés auparavant, mais dont la maladie avait été diagnostiquée par une échocardiographie de stress ou un cathétérisme. Après l'instauration des ARM, nous avons examiné les variations des taux de peptides natriurétiques et des paramètres échocardiographiques reflétant la fonction diastolique. Résultats: Sur les 197 patients atteints d'ICFEP, 47 ont entamé un traitement par des ARM. Après un suivi médian de trois mois, la réduction des taux de propeptides natriurétiques de type B N-terminal (NT-proBNP) entre la valeur initiale et le suivi était plus importante chez les patients traités par des ARM que chez ceux qui ne l'étaient pas (médiane : -200 pg/ml [écart interquartile : -544 à -31] contre 67 pg/ml [écart interquartile : -95 à 456], p < 0,0001 chez 50 patients ayant des données appariées). Des résultats similaires ont été observés pour la variation des taux de peptides natriurétiques de type B. La réduction du volume de l'oreillette gauche était également plus importante dans le groupe traité par des ARM que dans le groupe témoin après un suivi médian de sept mois (données échocardiographiques appariées pour 77 patients). Les patients présentant une déformation longitudinale globale du ventricule gauche plus faible ont connu une réduction plus importante des taux de NT-proBNP après le traitement par des ARM. Enfin, lors de l'évaluation de l'innocuité, les ARM ont légèrement altéré la fonction rénale, mais sans modifier les taux de potassium. Conclusions: Ces résultats semblent indiquer que le traitement par des ARM présente des avantages potentiels dans les cas d'ICFEP au stade précoce.

15.
Eur J Heart Fail ; 25(9): 1593-1603, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37317621

RESUMO

AIMS: It is widely held that heart failure (HF) does not cause exertional hypoxaemia, based upon studies in HF with reduced ejection fraction, but this may not apply to patients with HF and preserved ejection fraction (HFpEF). Here, we characterize the prevalence, pathophysiology, and clinical implications of exertional arterial hypoxaemia in HFpEF. METHODS AND RESULTS: Patients with HFpEF (n = 539) and no coexisting lung disease underwent invasive cardiopulmonary exercise testing with simultaneous blood and expired gas analysis. Exertional hypoxaemia (oxyhaemoglobin saturation <94%) was observed in 136 patients (25%). As compared to those without hypoxaemia (n = 403), patients with hypoxaemia were older and more obese. Patients with HFpEF and hypoxaemia had higher cardiac filling pressures, higher pulmonary vascular pressures, greater alveolar-arterial oxygen difference, increased dead space fraction, and greater physiologic shunt compared to those without hypoxaemia. These differences were replicated in a sensitivity analysis where patients with spirometric abnormalities were excluded. Regression analyses revealed that increases in pulmonary arterial and pulmonary capillary pressures were related to lower arterial oxygen tension (PaO2 ), especially during exercise. Body mass index (BMI) was not correlated with the arterial PaO2 , and hypoxaemia was associated with increased risk for death over 2.8 (interquartile range 0.7-5.5) years of follow-up, even after adjusting for age, sex, and BMI (hazard ratio 2.00, 95% confidence interval 1.01-3.96; p = 0.046). CONCLUSION: Between 10% and 25% of patients with HFpEF display arterial desaturation during exercise that is not ascribable to lung disease. Exertional hypoxaemia is associated with more severe haemodynamic abnormalities and increased mortality. Further study is required to better understand the mechanisms and treatment of gas exchange abnormalities in HFpEF.


Assuntos
Insuficiência Cardíaca , Pneumopatias , Humanos , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/tratamento farmacológico , Volume Sistólico/fisiologia , Oxigênio , Hipóxia/etiologia , Teste de Esforço/métodos , Tolerância ao Exercício/fisiologia
16.
J Card Fail ; 29(3): 375-388, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-37162126

RESUMO

Heart failure (HF) with preserved ejection fraction (HFpEF) is a global health care problem, with diagnostic difficulty, limited treatment options and high morbidity and mortality rates. The prevalence of HFpEF is increasing because of the aging population and the increasing burden of cardiac and metabolic comorbidities, such as systemic hypertension, diabetes, chronic kidney disease, and obesity. The knowledge base is derived primarily from the United States and Europe, and data from Asian countries, including Japan, remain limited. Given that phenotypic differences may exist between Japanese and Western patients with HFpEF, careful characterization may hold promise to deliver new therapy specific to the Japanese population. In this review, we summarize the current knowledge regarding the epidemiology, pathophysiology and diagnosis of and the potential therapies for HFpEF in Japan.


Assuntos
Insuficiência Cardíaca , Humanos , Idoso , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/terapia , Japão/epidemiologia , Volume Sistólico , Coração , Envelhecimento
17.
Eur J Heart Fail ; 25(8): 1293-1303, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37062872

RESUMO

AIMS: Diagnosis of heart failure with preserved ejection fraction (HFpEF) remains challenging in patients presenting with chronic dyspnoea. We sought to determine the diagnostic value of reduced left atrial (LA) compliance during exercise to diagnose HFpEF. METHODS AND RESULTS: Ergometry exercise stress echocardiography was performed in 225 patients with HFpEF and 262 non-heart failure controls (non-cardiac dyspnoea [NCD]) in Protocol 1, where the diagnosis of HFpEF was defined by the HFA-PEFF algorithm. In Protocol 2, the diagnosis of HFpEF was ascertained by exercise right heart catheterization in 67 participants (49 HFpEF and 18 NCD). Speckle-tracking echocardiography was performed at rest and during exercise to determine LA compliance (ratio of LA reservoir strain to E/e'). As compared with NCD, patients with HFpEF demonstrated decreased LA reservoir strain and compliance at rest, and these differences further increased during exercise in Protocol 1. Exercise LA compliance discriminated HFpEF from NCD (area under the curve 0.87, p < 0.0001), with a superior diagnostic ability to exercise E/e' ratio (DeLong p = 0.005). Exercise LA compliance demonstrated incremental diagnostic value over clinical factors (age, systemic hypertension, and atrial fibrillation) and resting LA compliance (χ2 212.4 vs. 166.2, p < 0.0001). These findings were confirmed in Protocol 2. CONCLUSION: Left atrial compliance during exercise demonstrated superior diagnostic ability to exercise E/e' ratio, with incremental diagnostic value over the resting LA compliance. Exercise LA compliance may enhance the diagnosis of HFpEF among patients with dyspnoea.


Assuntos
Fibrilação Atrial , Insuficiência Cardíaca , Doenças não Transmissíveis , Humanos , Insuficiência Cardíaca/diagnóstico , Volume Sistólico , Fibrilação Atrial/diagnóstico , Ergometria , Dispneia/diagnóstico , Dispneia/etiologia , Função Ventricular Esquerda
18.
Eur J Heart Fail ; 25(7): 956-966, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37070138

RESUMO

AIMS: Cardiac and extracardiac abnormalities play important roles in heart failure with preserved ejection fraction (HFpEF). Biventricular cardiac power output (BCPO) quantifies the total rate of hydraulic work performed by both ventricles, suggesting that it may help to identify patients with HFpEF and more severe cardiac impairments to better individualize treatment. METHODS AND RESULTS: Patients with HFpEF (n = 398) underwent comprehensive echocardiography and invasive cardiopulmonary exercise testing. Patients were categorized as low BCPO reserve (n = 199, < median of 1.57 W) or preserved BCPO reserve (n = 199). As compared to those with preserved BCPO reserve, those with low reserve were older and leaner, with more atrial fibrillation, higher N-terminal pro-B-type natriuretic peptide levels, worse renal function, more impaired left ventricular (LV) global longitudinal strain, worse LV diastolic function and right ventricular longitudinal function. Cardiac filling pressures and pulmonary artery pressures at rest were higher in low BCPO reserve, but central pressures were similar during exercise to those with preserved BCPO reserve. Exertional systemic and pulmonary vascular resistances were higher and exercise capacity was more impaired in those with low BCPO reserve. Reduced BCPO reserve was associated with increased risk for the composite endpoint of heart failure hospitalization or death over 2.9 (interquartile range 0.9-4.5) years of follow-up (hazard ratio 2.77, 95% confidence interval 1.73-4.42, p < 0.0001). CONCLUSIONS: Inability to enhance BCPO during exercise is associated with more advanced HFpEF, increased systemic and pulmonary vascular resistance, reduced exercise capacity and increased adverse events in patients with HFpEF. Novel therapies that enhance biventricular reserve merit further investigation for patients with this phenotype.


Assuntos
Insuficiência Cardíaca , Humanos , Volume Sistólico , Função Ventricular Esquerda , Ecocardiografia/métodos , Ventrículos do Coração/diagnóstico por imagem , Teste de Esforço
19.
Sci Rep ; 13(1): 4355, 2023 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-36928614

RESUMO

Cardiopulmonary exercise testing (CPET) may potentially differentiate heart failure (HF) with preserved ejection fraction (HFpEF) from noncardiac causes of dyspnea (NCD). While contemporary guidelines for HF recommend using CPET for identifying causes of unexplained dyspnea, data supporting this practice are limited. This study aimed to determine the diagnostic value of expired gas analysis to distinguish HFpEF from NCD. Exercise stress echocardiography with simultaneous expired gas analysis was performed in patients with HFpEF (n = 116) and those with NCD (n = 112). Participants without dyspnea symptoms were also enrolled as controls (n = 26). Exercise capacity was impaired in patients with HFpEF than in controls and those with NCD, evidenced by lower oxygen consumption (VO2), but there was a substantial overlap between HFpEF and NCD. Receiver operating characteristic curve analyses showed modest diagnostic abilities of expired gas analysis data in differentiating individuals with HFpEF from the controls; however, none of these variables clearly differentiated between HFpEF and NCD (all areas under the curve < 0.61). Expired gas analysis provided objective assessments of exercise capacity; however, its diagnostic value in identifying HFpEF among patients with symptoms of exertional dyspnea was modest.


Assuntos
Insuficiência Cardíaca , Doenças não Transmissíveis , Humanos , Volume Sistólico , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/complicações , Função Ventricular Esquerda , Teste de Esforço , Dispneia/diagnóstico , Dispneia/etiologia
20.
Eur J Heart Fail ; 25(5): 657-668, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36994635

RESUMO

AIMS: Ancillary analyses from clinical trials have suggested reduced efficacy for neurohormonal antagonists among patients with heart failure and preserved ejection fraction (HFpEF) and higher ranges of ejection fraction (EF). METHODS AND RESULTS: A total of 621 patients with HFpEF were grouped into those with low-normal left ventricular EF (LVEF) (HFpEF<65% , n = 319, 50% ≤ LVEF <65%) or HFpEF≥65% (n = 302, LVEF ≥65%), and compared with 149 age-matched controls undergoing comprehensive echocardiography and invasive cardiopulmonary exercise testing. A sensitivity analysis was performed in a second non-invasive community-based cohort of patients with HFpEF (n = 244) and healthy controls without cardiovascular disease (n = 617). Patients with HFpEF≥65% had smaller left ventricular (LV) end-diastolic volume than HFpEF<65% , but LV systolic function assessed by preload recruitable stroke work and stroke work/end-diastolic volume was similarly impaired. Patients with HFpEF≥65% displayed an end-diastolic pressure-volume relationship (EDPVR) that was shifted leftward, with increased LV diastolic stiffness constant ß, in both invasive and community-based cohorts. Cardiac filling pressures and pulmonary artery pressures at rest and during exercise were similarly abnormal in all EF subgroups. While patients HFpEF≥57% displayed leftward shifted EDPVR, those with HFpEF<57% had a rightward shifted EDPVR more typical of heart failure with reduced EF. CONCLUSION: Most pathophysiologic differences in patients with HFpEF and higher EF are related to smaller heart size, increased LV diastolic stiffness, and leftward shift in the EDPVR. These findings may help to explain the absence of efficacy for neurohormonal antagonists in this group and raise a new hypothesis, that interventions to stimulate eccentric LV remodelling and enhance diastolic capacitance may be beneficial for patients with HFpEF and EF in the higher range.


Assuntos
Insuficiência Cardíaca , Disfunção Ventricular Esquerda , Humanos , Volume Sistólico/fisiologia , Insuficiência Cardíaca/complicações , Função Ventricular Esquerda/fisiologia , Ventrículos do Coração/diagnóstico por imagem
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