Rossi, Andrea

Background: Left atrial assessment is complex, particularly in heart failure with reduced ejection fraction due to interactions with functional mitral regurgitation (FMR). Pilot data suggest that left atrial volumetric/mechanical coupling index (LACI) may be useful, but large outcome data are lacking. Methods: We enrolled a comprehensively characterized cohort of patients in sinus rhythm with heart failure with reduced ejection fraction diagnosis at Mayo Clinic from 2007 to 2011. Routinely measured left atrial volume index and tissue-doppler-imaging a’ allowed LACI calculation as (left atrial volume index)/(tissue-doppler-imaging a’). Survival was the outcome measured. Results: The cohort’s 4196 patients (69 [58–77] years, ejection fraction 40 [31–45]%) had mild FMR in 1505 and moderate-severe FMR in 1068. LACI was overall 5.06 (3.50–8.10) and increased with each FMR grade (3.86 [2.94–5.29] without FMR, 5.38 [3.80–8.02] with mild, 5.45 [1.49–8.07] with moderate/severe FMR; P <0.0001). At diagnosis, higher LACI was independently determined by more severe FMR and by higher left ventricular mass index, lower ejection fraction, higher E/e’, and lower glomerular filtration rate (all P <0.0001). During follow-up 1588 (38%) patients died. In spline modeling, excess mortality appeared around LACI=6 and steeply increased thereafter (5-year survival 72±1% with LACI<6 and 49±2% with LACI ≥6, P <0.0001). Multivariable comprehensive adjustment showed LACI strong association with excess mortality (adjusted hazard ratio, 1.41 [1.23–1.61], P <0.0001 for LACI ≥6). Independent link to mortality persistent across FMR grades (adjusted hazard ratio, 1.45 [1.13–1.86], P =0.004 without FMR, 1.42 [1.16–1.77], P =0.0008 with mild FMR, and 1.38 [1.01–1.66], P =0.04 with moderate/severe FMR) without interaction ( P =0.3). LACI independent impact on outcome was incremental to that of left atrial volume index, tissue-doppler-imaging a’, or any other characteristic including the Meta-Analysis Global Group in Chronic-score (least significant P =0.02). Conclusions: In this large cohort, left atrial volumetric/mechanical coupling measured by LACI in routine practice integrates the influence of several morphological/hemodynamic determinants but displays progressive deterioration with increasing FMR severity in heart failure with reduced ejection fraction. About outcome, higher LACI is strongly, independently, and incrementally associated with excess mortality, irrespective of FMR grade and in all subsets. Hence, LACI is a novel and critical measure in heart failure with reduced ejection fraction, quantifiable in routine practice, which should be integrated in prognostication and decision-making.

The need for multiple transducer positions, especially from right parasternal windows, is consistently mentioned in the recommendations for the accurate measurement of peak velocities across a stenotic aortic valve, but yet poorly adopted. We performed a subanalysis of the largest prospective series on the right parasternal acoustic windows in patients with aortic stenosis (330 consecutive) to calculate the degree of misalignment and estimate the potential outcome implication of this often-forgotten approach. The right parasternal view was highly feasible with an average estimated misalignment from the apical view of 14 ± 16 degree; in 10 cases, an estimated misalignment >40 degree. Right parasternal assessment (vs. apical alone) provided a significant reclassification from moderate to severe or even very-severe aortic valve stenosis. Considering a wellestablished survival benefit provided by either percutaneous or surgical valve replacement in patients with severe aortic stenosis the reclassification would result in approximately 1 life-year saved for every 30–35 patients in whom parasternal view were effectively utilized.

Background: Functional tricuspid regurgitation (FTR) is common in heart failure with reduced ejection fraction and mostly consequent to pulmonary hypertension. However, the intrinsic clinical implications of FTR are not fully understood. Methods: The cohort of all Mayo Clinic patients from 2003 to 2011 diagnosed with heart failure stage B-C and ejection fraction<50%, with FTR grading and systolic pulmonary artery pressure estimation by Doppler echocardiography was identified and outcomes were analyzed. Patients with pacemakers/defibrillators, organic valve disease, or previous valve surgery were excluded. The primary outcome measure was overall mortality (censored at implantation of a defibrillator, ventricular assist device, or cardiac transplantation), adjusting for clinical and echocardiographic associates with mortality and major comorbidities. Results: Among 13 026 patients meeting inclusion criteria, FTR was detected in 88% (N=11 507: 33% trivial, 32% mild, 17% moderate, and 6% severe), aged 68±14 years, 35% women, ejection fraction 36±10%, systolic pulmonary artery pressure 41±14 mm Hg with 20% atrial fibrillation. Covariates independently associated with FTR included elevated systolic pulmonary artery pressure, older age, female sex, lower ejection fraction, mitral regurgitation, and atrial fibrillation (all P <0.0001). FTR was independently associated with more dyspnea, impaired kidney function, and lower cardiac output ( P <0.003 for all). For long-term outcome, higher FTR degree compared with trivial tricuspid regurgitation was independently associated with higher mortality (adjusted hazard ratios 1.09 [1.01-1.17] for mild FTR, 1.21 [1.11-1.33] for moderate FTR and 1.57 [1.39-1.78] for severe FTR); hence, 5-year survival was substantially lower with increasing severity of functional FTR, 68±1% for trivial FTR, 58±2% for mild FTR, 45±2% for moderate FTR, and 34±4% for severe FTR. Conclusions: In this large cohort of patients with heart failure with reduced ejection fraction, FTR was common and independently associated with pulmonary hypertension, atrial fibrillation, and more severe heart failure presentation. Long-term, higher FTR severity is associated with considerably worse survival, independently of baseline characteristics. Given these untoward outcomes associated with FTR in patients with heart failure with reduced ejection fraction, clinical trials should be directed at testing FTR treatment.