Chaikijurajai, Thanat

BACKGROUND: Left atrial (LA) stiffening augments the LA V wave, pressurizing the pulmonary artery (PA) out of proportion to left ventricular end-diastolic pressure. We characterized the pathophysiologic, diagnostic, and clinical implications of LA stiffening, as defined by prominent V waves, in heart failure with preserved ejection fraction. METHODS: In this retrospective cohort study, patients with heart failure with preserved ejection fraction and less than moderate mitral regurgitation at rest underwent invasive hemodynamic exercise testing. Patients with heightened operant LA stiffening were defined by the PA wedge pressure (PAWP) V wave exceeding mean PAWP by ≥10 mm Hg. A previously used formula for V wave–corrected PAWP was validated against the PAWP waveform pressure-time-area to explore impact of the V wave on transpulmonary pressure gradients. Clinical, echocardiographic, hemodynamic, and outcome data were compared for patients with and without prominent V waves. RESULTS: Compared with patients without prominent V waves (n=844, 79%), those with prominent V waves (n=225, 21%) were older and more likely to be women, with more severe LA myopathy, evidenced by greater LA volume index (42.2±15.0 versus 32.5±13.0 mL/m 2 , P <0.001), lower LA reservoir strain (16.4±7.5% versus 23.2±8.3%, P <0.001), more atrial fibrillation (61.3% versus 22.9%, P <0.001), and increased operant LA reservoir stiffness (0.59±0.25 versus 0.23±0.24 mm Hg/mL, P <0.001). Patients with prominent V waves had markedly higher PA systolic pressure than those without (54±16 versus 38±12 mm Hg, P <0.001) despite no difference in end-diastolic PAWP-PA pressure gradient (3±5 versus 3±4 mm Hg, P =0.950). Incorporating the V wave into PAWP improved correlation between directly measured PAWP pressure-time integral compared with mid–A wave PAWP (R 2 =0.96 versus R 2 =0.86, P <0.001 for comparison). In patients with prominent V waves, the prevalence of combined pre- and postcapillary pulmonary hypertension decreased from 60.2% to 29.3% after V wave correction for the transpulmonary pressure gradients. Despite similar corrected pulmonary vascular resistances in patients with and without prominent V waves, apparent PA compliance was much lower in patients with prominent V waves (3.03±1.56 versus 4.90±2.27 mL/mm Hg, P <0.001), augmenting right ventricular afterload, and these changes were coupled with more severe right ventricular dysfunction, tricuspid regurgitation, blunted cardiopulmonary exercise reserve, and increased risk of hospitalization for heart failure or death in patients with versus without prominent V waves (adjusted hazard ratio, 2.09 [95% CI, 1.53–2.86]; P <0.001). CONCLUSIONS: More than 1 in 5 patients with heart failure with preserved ejection fraction display prominent V waves in excess of end-diastolic PAWP. This augments right ventricular afterload due to backward transmission of the V wave, contributing to right heart failure that is independent of the pulmonary vasculature. Failure to account for the V wave during hemodynamic assessment overestimates the severity of pulmonary vascular disease present.

Abstract Aims We recently demonstrated the combined prognostic value of the following two simple non-invasive parameters obtained from treadmill exercise testing in patients with heart failure (HF) with reduced ejection fraction: the Haemodynamic Gain Index (HGI) and peak rate-pressure product (RPP). However, their prognostic value is yet to be validated in patients with undifferentiated HF syndrome. Methods and results We identified consecutive HF patients undergoing treadmill exercise testing for symptom evaluation between January 1991 and February 2015. The HGI was calculated from [(SBPpeak × heart ratepeak) – (SBPrest × heart raterest)]/(SBPrest × heart raterest), and the peak RPP was calculated from SBPpeak × heart ratepeak. Hazard ratios per standard deviation increase of the HGI and peak RPP for all-cause mortality were estimated using multivariable Cox regression models with adjustment for traditional cardiovascular risk factors and exercise-testing parameters (Chronotropic Reserve Index, estimated metabolic equivalents, abnormal heart rate recovery, and total exercise time). In our cohort of 5940 patients with symptomatic HF diagnosis with a median follow-up of 7.1 years, 2222 (37.4%) patients died. Higher values of both HGI and peak RPP were associated with a lower risk of mortality [adjusted hazard ratio per standard deviation increase 0.80 (0.73–0.88) and 0.85 (0.78–0.91), respectively, all P &lt; 0.001]. Optimal cut-off values for HGI and peak RPP for discriminating all-cause mortality were 1.06 and 180 966, respectively. Conclusion Both HGI and peak RPP are predictors of mortality in patients with chronic HF and may be tools to signal the need for advanced HF therapy evaluation.