Evaluation of high left atrial pressure with quality of life in stable heart failure patients with reduced ejection fraction
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/ACVI.ACVI_6_19
Keywords: Diastolic dysfunction, echocardiography, exercise capacity
The primary determinant of functional capacity is the integrity of the cardiovascular, respiratory, and skeletal muscle systems. Although it is been reported that patients diagnosed with heart failure (HF) demonstrate a compromised functional capacity, the precise mechanism of diminished functional capacity remains unclear.[1],[2] Most mechanistic investigations have focused on associations with systolic and endothelial function.[3] However, ejection fraction (EF) is strongly load-dependent and poorly predicts functional capacity in patients with congested HF (CHF).[4] Diastolic function abnormalities contribute to the symptoms of HF.[5],[6] One mechanism by which diastolic parameters may affect functional capacity relates to their role in generating a maximal cardiac output. During exercise, the maintenance of adequate left ventricular filling to ensure a normal cardiac output includes the ability to achieve diastolic filling rates greater than the ejection rates during systole. In the setting of exercise-induced tachycardia, abnormalities in diastolic relaxation and filling of the left ventricle can result in filling rates that might be too low to achieve adequate cardiac output during exercise, especially in patients with low ventricular systolic properties. Doppler echocardiography can characterize left ventricular diastolic function through a combination of measurements. It can also provide an estimate of left ventricular filling pressures and one component of diastolic function is that it reflects pulmonary capillary wedge pressure. In prior small series, the parameters, including transmitral flow, myocardial diastolic velocity, and diastolic relaxation, correlate with the functional capacity of patients with CHF.[7] However, the data in this field are limited. We, therefore, sought the association of filling pressure and diastolic function with functional capacity in patients with CHF.
Patient and settings This case-series study was conducted from December 2017 to December 2018 at the Department of Heart, Modarres University Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Patients with moderately reduced systolic EF (30%-40%) in echocardiography were included in the study. Exclusion criteria for the study were patients with the prosthetic mitral valve, structural mitral valve disorders, and nonsinus rhythm and patients who cannot do an exercise test. The study was approved by the Ethics Committee at Shahid Beheshti University of Medical Sciences, and informed consent was obtained from each patient before the inclusion of the participant in the study. Most patients were in New York Heart Association functional Class II (25 patients). The demographic and clinical characteristics, including comorbid diseases, are listed in [Table 1].
Doppler echocardiography Two-dimensional echocardiography was done with the patient in the supine left lateral decubitus position. Images were obtained using a 3.5 MHz transducer at the 16-cm depth in five standard views: 2 parasternal (long and short axes) and 3 apical (long axis, 4 and 2 chambers). Mitral E and A peak velocities (E and A; centimeters per se cond) were measured. Left ventricular EF (LVEF) was calculated using Simpson's biplane method. Color tissue Doppler data were acquired in each apical view, using frame rates from 80 to 115 frames/s (depending on sector width), with aliasing velocities from 16 to 32 cm/s. Digital storage of cardiac cycle loops triggered to the QRS complex was saved on a magneto-optical disk for offline analysis using standard software (Echopac Version 6.2, General Electric-Vingmed) by readers blinded to visual wall motion analysis. Peak long-axis systolic velocities within each segment were obtained by locating the sample volume in the middle of each segment at rest.[8] As many of the patients had ischemic cardiomyopathy and may, therefore, demonstrate regional rather than global hypokinesia,[9] the septal early diastolic velocity was measured separately and averaged. Peak early diastolic mitral annulus velocity (Ea) has been validated as a noninvasive marker of ventricular relaxation, likely to identify pseudonormal filling in patients with stable HF.[10],[11] Left atrial pressures (LAPs) were estimated with the following formula: 1.9 + E/Ea × 1.24. Exercise testing All participants underwent exercise testing on a cycle ergometer with a 10-W/min stepped protocol. The electrocardiogram was continuously monitored for ST-segment changes and arrhythmias; blood pressure and 12-lead electrocardiograms were recorded before exercise, every 2 min during the test and during the recovery period after exercise. Tests were symptom-limited; usual endpoints were dyspnea, leg fatigue, or angina, with a few studies limited by arrhythmia and decreased or exaggerated blood pressure response. The primary endpoint was maximal exercise tolerance defined by the achieved metabolic equivalents (METs). Statistical analysis Data are expressed in mean and standard deviation or in numbers and percentages. Multiple comparisons of continuous variables were made with the analysis of variance. Categorical data were compared by the Chi-square test. Pearson test was used to evaluate the correlation. We performed the analysis using the SPSS software (version 18.0 for Windows, IBM company, Chicago, USA). The statistical significance was set to P < 0.05.
Initially, 84 patients were enrolled for the study, of which 54 of them were excluded from the final analysis. Of those 54 patients, 8 patients had a prosthetic mitral valve, 12 patients had structural mitral valve disorders, 18 patients had nonsinus rhythm, and 16 patients could not do exercise the test. The remaining 30 patients were included in the study who underwent Doppler echocardiography, following to it exercise tolerance test was performed for each patient. All patients had stable systolic HF and were stable on therapy for at least 1 month before testing. In the present study, of 30 patients, 27 (90%) patients were male. Mild diastolic dysfunction was observed in 13 (43.3%) patients, and moderate/severe diastolic dysfunction was observed in 17 (56.7%) patients. Echocardiography and exercise tolerance test characteristics are shown in [Table 2].
In Pearson analysis, data showed systolic pulmonary arterial pressure (SPAP), left atrial volume index (LAVI), E/Ea, LAP, and tricuspid annular plane systolic excursion (TAPSE), which were significantly higher in patients with higher age (P< 0.05). Increasing in E/Ea was significantly related to higher SPAP (P< 0.001), lower METs (P< 0.001), higher LAVI (P< 0.001), higher LAP (P< 0.001), higher TAPSE (P< 0.001), and higher S tissue (P = 0.02). LAP and E/Ea were conversely correlating with METs significantly (P< 0.001).
In the present study, it was found that the diastolic function and high-LAP apart from the LVEF are associated with exercise tolerance in patients with stable functional Class I-III HF and reduced LVEF. Although ventricular systolic/diastolic dysfunction may decrease exercise tolerance, indexes of LV systolic are poor predictors of exercise capacity,[12] whereas diastolic function indexes have not been fully studied. In the past decade, several authors have described associations between exercise capacity and diastolic function more accurately using tissue Doppler indexes.[13],[14] However, controversial results were reported, and this topic still remains unclear. Gardin et al.[12] also found a correlation between diastolic function and exercise tolerance in a large population of HF patients with reduced LVEF and NYHA functional class ≥II. In that study, it was suggested that mitral valve E/A and E/e' indexes were more strongly related to exercise performance than was LVEF. Brucks et al.[15] and Fukuta and Little[16] showed that, regardless of LVEF and the severity of symptoms, the degree of diastolic dysfunction was closely associated with the prognosis and exercise intolerance in HF patients in Class ≥II. With all this information, we included stable patients whose performance on the exercise test suggested mild or moderate physical limitations. Our findings indicated that patients with systolic HF who are oligosymptomatic with pharmacologic treatment have a reduced physical capacity associated with decreased LV diastolic function. A possible explanation for our results is that physical activity increases heart rate, impairing atrial emptying, and thus raising the pressure in the left atrium. These events would cause pulmonary congestion and exercise intolerance.[17] Diastolic function was evaluated using tissue Doppler imaging (TDI) of mitral annular motion (E/e'). This index is an excellent predictor of diastolic filling in subsets of patients. Furthermore, the TDI parameter that had the best correlation with the invasive mean LV diastolic pressure which was the E/e' ratio; this correlation was better in patients with LVEF <50%.[18] Therefore, limitations on exercise would more likely be related to dyspnea caused by increased pressure in the left atrium than to a reduced oxygen supply related to decreasing cardiac output. It is important to note that HF patients with systolic dysfunction and reduced cardiac output may have decreased respiratory and skeletal muscle performance, which would reduce their ability to perform the exercise.[19],[20] This condition decreases oxidative Type I fibers and increases glycolytic Type IIb fibers. Other consequences that have been described include impaired endothelial function, negative changes in vasodilatory capacity, excessive sympathetic stimulation causing vasoconstriction, decreased blood flow to skeletal muscles, and enhanced ergoreflex response.[21] In the present study, because these alterations were not evaluated, we are unable to draw conclusions concerning their effects on the patients' physical capacity.
We conclude that, despite the small number of patients, this study offers evidence that high-LA pressure and diastolic function are associated with physical capacity and should be considered along with EJ in patients with compensated systolic HF. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.
[Table 1], [Table 2]
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