P1743 The contribution of left atrial dysfunction to exercise intolerance in early heart failure with preserved left ventricular ejection fraction

Abstract

Background Diagnosis of early heart failure with preserved ejection fraction (HFpEF) may be challenging because exertional dyspnea is not specific for heart failure, and biomarkers and indicators of volume overload may be absent at rest. We aimed to characterize the contribution of abnormal left atrial (LA) mechanical properties to exercise intolerance in early HFpEF (normal left ventricular filling pressures at rest but elevated during exercise). Methods Diastolic stress testing (DST) was performed in 104 patients with left ventricular ejection fraction ≥50%, in sinus rhythm, and no more than LV diastolic dysfunction grade I, referred for assessment of exertional dyspnoea. Patients exercised supine cycle ergometry at 60 rpm starting with a 3-min period of low-level 25-W workload followed by 25-W increments in 3-minute stages to maximum tolerated levels. According to DST, 43 patients were diagnosed with HFpEF (average mitral E-to-annular e′ ratio [E/e′] > 14, and peak TR velocity >2.8 m/sec at maximal exertion) and 61 as non-cardiac dyspnea (NCD). During the test, two-dimensional images, mitral E/e′, peak tricuspid regurgitation (TR) velociry, and two-dimensional LA mechanical parameters (longitudinal LA strain [LASR] and strain rate [LASRR] during reservoir phase and LA stiffness assessed as a ratio of mitral E/e′ ratio to LASR) were analysed at baseline, and at peak. Results HFpEF and NCD patients were similar in regard to the LA volume index (34.4 [30.2;39.4] vs. 33.6 [28.4;37.1] ml/m2), and NT-proBNP level (132 [80;238] vs. 129 [80;197] pg/ml). As compared with NCD patients, HFpEF patients displayed reduced LA reservoir function assessed by LASR (22.3 [18.9;25.6] vs. 24.2 [21.2;29.8] % at rest, and 25.3 [21.4;30.2] vs. 29.0 [24.2;33.3] % with exercise) and LASRR (0.78 [0.58;0.96] vs. 0.90 [0.68;1.12] /s at rest, and 1.10 [0.79;1.31] vs. 1.24 [1.03;1.56] s–1 with exercise) with increased LA stiffness (0.57 [0.44;0.70] vs. 0.42 [0.30;0.49] mmHg/% at rest, and 0.61 [0.46;0.74] vs. 0.40 [0.32;0.51] mmHg/% with exercise, all P < 0.05). Additionally, HFpEF patients showed smaller exercise elevation in LASRR (+31 [-5;77] vs. +47 [12;85] % as compared with resting values, P < 0.05). Exercised LA stiffness and reservoir strain correlated with exercise LV filling pressures estimated by mitral E/e′ ratio (r = 0.72 and r =–0.35, P < 0.001). LA stiffness showed a good diagnostic accuracy (area under the curve 0.75), and LA stiffness > 0.46 mmHg/% demonstrated reasonable sensitivity (79%) and specificity (71%) to diagnose HFpEF. Neither LV global longitudinal strain and ejection fraction at rest nor their exercise-induced elevation differed between HFpEF and NCD. Conclusion Impaired LA reservoir function and increased stiffness are associated with exercise intolerance in patients with early HFpEF, while LV systolic function seems preserved in this stage of the disease. LA stiffness provides HFpEF diagnostic potential in ambulatory patients with dyspnea

Left atrial dysfunction as the major driver of heart failure with preserved ejection fraction syndrome

“…Reservoir phase strain (LASr) is calculated as the difference between the onset of LV filling and end-diastole, conduit phase strain (LAScd) as the difference between the onset of LA contraction and the onset of LV filling, and contraction phase strain (LASct) as the difference between end-diastole and the onset of LA filling (estimated as blunted increase in LA reservoir strain during exercise) compared to patients with noncardiac dyspnoea. 54 Similarly, LA reservoir function was significantly impaired during passive leg elevation in patients with HFpEF. 32 These alterations in LA strain may occur early in HFpEF, before significant volume overload develops.…”

“…LA dysfunction is currently considered the earliest manifestation of HFpEF syndrome and commonly precedes its development (being an independent predictor of incident HF) 5,53 . Patients with initial HFpEF (i.e., grade I LVDD with normal NT‐proBNP levels and LA volume) have a decreased LA reserve (estimated as blunted increase in LA reservoir strain during exercise) compared to patients with noncardiac dyspnoea 54 . Similarly, LA reservoir function was significantly impaired during passive leg elevation in patients with HFpEF 32 .…”

Use of Statins in Heart Failure with Preserved Ejection Fraction: Current Evidence and Perspectives

“…In an observational study, patients with HFpEF treated with statins were less likely to experience atrial fibrillation [154]. In a prospective study, involving 59 statin-naïve patients with HFpEF, statin therapy consistently reduced blood levels of inflammatory biomarkers (hsCRP and MCP-1), and a biomarker of LV wall stress N-terminal pro-B-type natriuretic peptide (NT-proBNP (NT-proBNP), which was associated with improvement in LVDD and reduction in LV filling pressures [155]. One of the most frequent complications of HFpEF is pulmonary hypertension, occurring in the majority of patients with HFpEF and associated with a poor prognosis [156].…”

The Molecular and Cellular Mechanisms Associated with a Microvascular Inflammation in the Pathogenesis of Heart Failure with Preserved Ejection Fraction

“…В отечественном ретроспективном когортном исследовании, проведенном среди 223 больных с компенсированным (бессимптомным) гипертоническим сердцем, отсутствие приема статинов стало независимым предиктором последующего развития СНсФВ; прием же статинов был ассоциирован с трехкратным снижением риска развития СНсФВ и двукратным снижением риска прогрессирования диастолической дисфункции левого желудочка (увеличения ее степени) [78]. Согласно предварительным данным отечественного одноцентрового проспективного клинического исследования прием розувастатина и аторвастатина больными с СНсФВ, ранее их не принимавшими, сопровождался значительным улучшением переносимости нагрузки, что сопровождалось восстановлением диастолического резерва и снижением давления наполнения левого желудочка как в покое, так и на высоте нагрузки [79]. В недавнем крупном метаанализе показано, что у больных с сердечной недостаточностью и фракцией выброса >40% прием статинов ассоциирован с достоверным снижением общей смертности на 15%, сердечно-сосудистой смертности на 17% и частоты госпитализаций из-за обострения сердечной недостаточности на 24% [80].…”