The haemodynamic basis of lung congestion during exercise in heart failure with preserved ejection fraction.

AIMS: Increases in extravascular lung water (EVLW) during exercise contribute to symptoms, morbidity, and mortality in patients with heart failure and preserved ejection fraction (HFpEF), but the mechanisms leading to pulmonary congestion during exercise are not well-understood. METHODS AND RESULTS: Compensated, ambulatory patients with HFpEF (n = 61) underwent invasive haemodynamic exercise testing using high-fidelity micromanometers with simultaneous lung ultrasound, echocardiography, and expired gas analysis at rest and during submaximal exercise. The presence or absence of EVLW was determined by lung ultrasound to evaluate for sonographic B-line artefacts. An increase in EVLW during exercise was observed in 33 patients (HFpEFLW+, 54%), while 28 (46%) did not develop EVLW (HFpEFLW-). Resting left ventricular function was similar in the groups, but right ventricular (RV) dysfunction was two-fold more common in HFpEFLW+ (64 vs. 31%), with lower RV systolic velocity and RV fractional area change. As compared to HFpEFLW-, the HFpEFLW+ group displayed higher pulmonary capillary wedge pressure (PCWP), higher pulmonary artery (PA) pressures, worse RV-PA coupling, and higher right atrial (RA) pressures during exercise, with increased haemoconcentration indicating greater loss of water from the vascular space. The development of lung congestion during exercise was significantly associated with elevations in PCWP and RA pressure as well as impairments in RV-PA coupling (area under the curve values 0.76-0.84). CONCLUSION: Over half of stable outpatients with HFpEF develop increases in interstitial lung water, even during submaximal exercise. The acute development of lung congestion is correlated with increases in pulmonary capillary hydrostatic pressure that favours fluid filtration, and systemic venous hypertension due to altered RV-PA coupling, which may interfere with fluid clearance. CLINICAL TRIAL REGISTRATION: NCT02885636.

Effects of intrathoracic pressure, inhalation time, and breath hold time on lung diffusing capacity.

The single breath hold maneuver for measuring lung diffusing capacity for carbon monoxide (DLCO) and nitric oxide (DLNO) incorporates multiple sources of variability. This study examined how changes in intrathoracic pressure, inhalation time, and breath hold time affect DLCO, DLNO, alveolar-capillary membrane conductance (DmCO) and pulmonary capillary blood volume (Vc) at rest and during submaximal exercise. Thirteen healthy subjects (mean ±â€¯SD; age = 26 ±â€¯3y) performed duplicate tests at rest and during submaximal exercise. DLCO and Vc were lower with a positive versus negative intrathoracic pressure during the breath hold at rest (DLCO: 22.2 ±â€¯5.5 vs. 22.7 ±â€¯5.5 ml/min/mmHg, p = 0.028; Vc: 46.5 ±â€¯11.6 vs. 48.2 ±â€¯11.7 ml, p = 0.018). However, during exercise, DLCO and Vc were higher with positive versus negative pressure (DLCO: 26.7 ±â€¯5.5 vs. 25.7 ±â€¯5.7 ml/min/mmHg, p = 0.014; Vc: 56.2 ±â€¯12.6 vs. 53.9 ±â€¯13.1 ml, p = 0.039). The inhalation time did not significantly affect DLCO, DLNO, DmCO or Vc. Short breath hold times (<4s) may yield high DLNO/DLCO ratios and non-physiologic DmCO values. The single breath hold maneuver is useful for evaluating gas transfer at rest and during exercise, however intrathoracic pressure, inhalation time, and breath hold time should be kept consistent between repeated tests.

Assessment of Thoracic Blood Volume by Computerized Tomography in Patients With Heart Failure and Periodic Breathing.

BACKGROUND: Periodic breathing (PB) is often observed in patients with HF at rest, with sleep and during exercise. However, mechanisms underlying abnormal ventilatory control are not entirely established. METHODS: Eleven subjects with HF (10 males, age = 69 ± 12 y) and 12 age-matched control subjects (8 males, age = 65 ± 9 y) participated in the study. PB was defined as a peak in the 0.003-0.04 Hz frequency range of the flow signal during 6 minutes of awake resting breathing. Thoracic blood volumes (Vt, thorax; Vh, heart; Vp, pulmonary), mean transit times (MTTs), and extravascular lung water (EVLW) were quantified using computerized tomography. RESULTS: PB was observed in 7 subjects with HF and was associated with worse functional status. The HF PB-present group had thoracic blood volumes nearly double those of control and HF PB-absent subjects (volumes reported as mL/m2 body surface area, P values vs control: control = 813 ± 246, HF PB-absent = 822 ± 161 P = .981, HF PB-present = 1579 ± 548 P = .002). PB was associated with longer pulmonary MTT (control = 6.7 ± 1.2 s, HF PB-absent = 6.0 ± 0.8 s, HF PB-present = 8.4 ± 1.6 s; P = .033, HF PB-present vs HF PB-absent). EVLW was not elevated in the PB group. CONCLUSIONS: Subjects with HF and PB at rest have greater centralization of blood volume.