Pitfalls of mitral regurgitation assessment in the presence of mitral valve prolapse.

Adequate grading of mitral regurgitation (MR) in patients with mitral valve prolapse (MVP) in the presence of mid-late systolic jets can represent a major challenge. In this entity, jets are commonly overestimated by echocardiography. Correct quantification is crucial and highly relevant for the further management and prognosis of these oftentimes young patients. This case points out potential pitfalls and underlines the importance to systematically include qualitative, quantitative, and semi-quantitative parameters into the echocardiographic assessment.

Left atrial strain predicts exercise capacity in heart failure independently of left ventricular ejection fraction.

AIMS: We hypothesized that left atrial (LA) remodelling and function are associated with poor exercise capacity as prognostic marker in chronic heart failure (CHF) across a broad range of left ventricular ejection fraction (LVEF). METHODS AND RESULTS: One hundred seventy-one patients with CHF were analysed [age 65 ± 11 years, 136 males (80%); 86 heart failure with reduced ejection fraction (HFrEF), 27 heart failure with mid-range ejection fraction (HFmrEF), 58 heart failure with preserved ejection fraction (HFpEF)]. All patients underwent echocardiography and maximal cardiopulmonary exercise testing and were classified according to a prognostic cut-off of peak VO2 (pVO2 ; 14 mL/kg/min). Seventy-seven (45%) patients reached pVO2  < 14 and 94 (55%) pVO2  ≥ 14 mL/kg/min. Between the two groups, there was a considerable difference in both left atrial volume (LAVi, 53 ± 24 vs. 44 ± 18 mL/m2 , P = 0.005) and function (LA reservoir strain 12 ± 5 vs. 20 ± 10%, P < 0.0001). Receiver-operating characteristic curves identified LA reservoir strain (area under the curve: 0.73 [0.65-0.80], P < 0.0001) as strong predictor for impaired pVO2 among all echocardiographic variables; LA reservoir strain < 23% had 37% specificity but a very high sensitivity (96%) in identifying a severely reduced pVO2 . In logistic regression analysis, LA reservoir strain < 23% was associated with a highly increased risk of pVO2  < 14 mL/kg/min (odds ratio 16.0 [4.7-54.6]; P < 0.0001). The multivariate analysis showed that a reduced LA reservoir strain was associated with pVO2  < 14 mL/kg/min after adjustment for age, body mass index (BMI), and clinical variables, that is, New York Heart Association class, atrial fibrillation, haemoglobin, and creatinine (b 0.22 [95% confidence interval, CI, 0.12-0.31]; P < 0.0001), and after adjustment for echocardiographic variables, that is, LVEF or left ventricular global longitudinal strain (LVGLS) and tricuspid annular plane systolic excursion (TAPSE) (b 0.16 [95% CI 0.08-0.24]; P < 0.0001). Patients with HFrEF, HFmrEF, and HFpEF were separately analysed. Among LA reservoir strain, LAVi, LVEF, LVGLS, and TAPSE, LA reservoir strain was the only one significantly associated with pVO2 in all subgroups (after adjustment for sex and BMI, P = 0.003, 0.04, and 0.01, respectively). CONCLUSIONS: In patients with CHF, an impaired LA reservoir function is independently associated with a severely reduced pVO2 . LA dysfunction represents a marker of poor prognosis across LVEF borders in the CHF population.

Functional tricuspid regurgitation, related right heart remodeling, and available treatment options: good news for patients with heart failure?

Significant functional tricuspid regurgitation (FTR) represents a poor prognostic factor independent of right ventricular (RV) function. It is usually the consequence of left-sided cardiac diseases that induce RV dilatation and dysfunction, but it can also resulted from right atrial (RA) enlargement and consequent tricuspid annular dilatation. FTR is very frequent among patients with heart failure, particularly in those with reduced LVEF and concomitant functional mitral regurgitation. The development of three-dimensional echocardiography enabled detailed assessment of tricuspid valve anatomy, subvavlular apparatus, and RA and RV changes, as well as accurate evaluation of FTR etiology. Due to high in-hospital mortality risk in patients who were operatively treated for isolated FTR, it has been treated only medically for a long time. Percutaneous approach considers mainly transcatheter tricuspid valve repair (edge-to-edge and annuloplasty) and represents a very attractive option for the high-risk patients. Studies that investigated the effects of different devices showed excellent feasibility and safety, followed by significant reduction in FTR grade, improvement in functional capacity and NYHA class, quality of life, and reduction in hospitalization due to heart failure. Some investigations also reported a decreased mortality in FTR patients. Nevertheless, the results of these investigations should be interpreted with cautious due to the small number of participants and relatively short follow-up. The aim of this review was to summarize the existing data about the clinical importance of FTR and FTR-induced right heart remodeling and currently existing therapeutic approaches for treatment of FTR.

Left atrial function and maximal exercise capacity in heart failure with preserved and mid-range ejection fraction.

AIMS: Exercise intolerance is the leading manifestation of heart failure with preserved or mid-range ejection fraction (HFpEF or HFmrEF), and left atrial (LA) function might contribute to modulating left ventricular filling and pulmonary venous pressures. We aim to assess the association between LA function and maximal exercise capacity in patients with HFpEF or HFmrEF. METHODS AND RESULTS: Sixty-five patients, prospectively enrolled in the German HFpEF Registry, were analysed. Inclusion criteria were New York Heart Association functional class ≥ II, left ventricular ejection fraction > 40%, structural heart disease or diastolic dysfunction, and elevated levels of N terminal pro brain natriuretic peptide (NT-proBNP). LA function was evaluated through speckle-tracking echocardiography by central reading in the Charité Academic Echocardiography core lab. All patients underwent maximal cardiopulmonary exercise test and were classified according to a peak VO2 cut-off of prognostic value (14 mL/kg/min). NT-pro-BNP was measured. Twenty-nine patients (45%) reached a peak VO2  < 14 mL/kg/min (mean value 12.4 ± 1.5) and 36 patients (55%) peak VO2  ≥ 14 mL/kg/min (mean value 19.4 ± 3.9). There was no significant difference in left ventricular ejection fraction (60 ± 9 vs. 59 ± 8%), left ventricular mass (109 ± 23 vs. 112 ± 32 g/m2 ), LA volume index (45 ± 17 vs. 47 ± 22 mL/m2 ), or E/e´ (13.1 ± 4.7 vs. 13.0 ± 6.0) between these groups. In contrast, all LA strain measures were impaired in patients with lower peak VO2 (reservoir strain 14 ± 5 vs. 21 ± 9%, P = 0.002; conduit strain 9 ± 2 vs. 13 ± 4%, P = 0.001; contractile strain 7 ± 4 vs. 11 ± 6%, P = 0.02; reported lower limits of normality for LA reservoir, conduit and contractile strains: 26.1%, 12.0%, and 7.7%). In linear regression analysis, lower values of LA reservoir strain were associated with impaired peak VO2 after adjustment for age, sex, body mass index, heart rhythm (sinus/AFib), and log-NTproBNP [ß 0.29, 95% confidence interval (CI) 0.02-0.30, P = 0.02], with an odds ratio 1.22 (95% CI 1.05-1.42, P = 0.01) for peak VO2  < 14 mL/kg/min for LA reservoir strain decrease after adjustment for these five covariates. Adding left ventricular ejection fraction, it did not influence the results. On the other hand, the addition of LA strain to the adjustment parameters alone described above provided a significant increase of the predictive value for lower peak VO2 values (R2 0.50 vs. 0.45, P = 0.02). With receiver operating characteristic curve analysis, we identified LA reservoir strain < 22% to have 93% sensitivity and 49% specificity in predicting peak VO2  < 14 mL/kg/min. Using this cut-off, LA reservoir strain < 22% was associated with peak VO2  < 14 mL/kg/min in logistic regression analysis after comprehensive adjustment for age, sex, body mass index, heart rhythm, and log-NTproBNP [odds ratio 95% CI 10.4 (1.4-74), P = 0.02]. CONCLUSIONS: In this HFpEF and HFmrEF cohort, a reduction in LA reservoir strain was a sensible marker of decreased peak exercise capacity. Therefore, LA reservoir strain might be of clinical value in predicting exercise capacity in patients with HFpEF or HFmrEF.

Subclinical left atrial dysfunction profiles for prediction of cardiac outcome in the general population.

OBJECTIVE: Echocardiographic definitions of subclinical left atrial dysfunction based on epidemiological data remain scarce. In this population study, we derived outcome-driven thresholds for echocardiographic left atrial function parameters discriminating between normal and abnormal values. METHODS: In 1306 individuals (mean age, 50.7 years; 51.6% women), we echocardiographically assessed left atrial function and LV global longitudinal strain. We derived cut-off values for left atrial emptying fraction (LAEF), left atrial function index (LAFI) and left atrial reservoir strain (LARS) to define left atrial dysfunction using receiver-operating curve threshold analysis. Main outcome was the incidence of cardiac events and atrial fibrillation (AFib) on average 8.5 years later. RESULTS: For prediction of new-onset AFib, left atrial cut-offs yielding the best balance between sensitivity and specificity (highest Youden index) were: LAEF less than 55%, LAFI less than 40.5 and LARS less than 23%. Applying these cut-offs, abnormal LAEF, LAFI and LARS were, respectively, present in 27, 37.1 and 18.1% of the cohort. Abnormal LARS (<23%) was independently associated with higher risk for cardiac events and new-onset AFib (P ≤ 0.012). Participants with both abnormal LAEF and LARS presented a significantly higher risk to develop cardiac events (hazard ratio: 2.10; P = 0.014) and AFib (hazard ratio: 6.45; P = 0.0036) than normal counterparts. The concomitant presence of an impaired LARS and LV global longitudinal strain improved prognostic accuracy beyond a clinical risk model for cardiac events and the CHARGE-AF Risk Score for AFib. CONCLUSION: Left atrial dysfunction based on outcome-driven thresholds predicted cardiac events and AFib independent of conventional risk factors. Screening for subclinical left atrial and LV systolic dysfunction may enhance cardiac disease prediction in the community.

The effect of iron deficiency on cardiac resynchronization therapy: results from the RIDE-CRT Study.

AIMS: Cardiac resynchronization therapy (CRT) improves functional status, induces reverse left ventricular remodelling, and reduces hospitalization and mortality in patients with symptomatic heart failure, left ventricular systolic dysfunction, and QRS prolongation. However, the impact of iron deficiency on CRT response remains largely unclear. The purpose of the study was to assess the effect of functional and absolute iron deficiency on reverse cardiac remodelling, clinical response, and outcome after CRT implantation. METHODS AND RESULTS: The relation of iron deficiency and cardiac resynchronization therapy response (RIDE-CRT) study is a prospective observational study. We enrolled 77 consecutive CRT recipients (mean age 71.3 ± 10.2 years) with short-term follow-up of 3.3 ± 1.9 months and long-term follow-up of 13.0 ± 3.2 months. Primary endpoints were reverse cardiac remodelling on echocardiography and clinical CRT response, assessed by change in New York Heart Association classification. Echocardiographic CRT response was defined as relative improvement of left ventricular ejection fraction ≥ 20% or left ventricular global longitudinal strain ≥ 20%. Secondary endpoints were hospitalization for heart failure and all-cause mortality (mean follow-up of 29.0 ± 8.4 months). At multivariate analysis, iron deficiency was identified as independent predictor of echocardiographic (hazard ratio 4.97; 95% confidence interval 1.15-21.51; P = 0.03) and clinical non-response to CRT (hazard ratio 4.79; 95% confidence interval 1.30-17.72, P = 0.02). We found a significant linear-by-linear association between CRT response and type of iron deficiency (P = 0.004 for left ventricular ejection fraction improvement, P = 0.02 for left ventricular global longitudinal strain improvement, and P = 0.003 for New York Heart Association response). Iron deficiency was also significantly associated with an increase in all-cause mortality (P = 0.045) but not with heart failure hospitalization. CONCLUSIONS: Iron deficiency is a negative predictor of effective CRT therapy as assessed by reverse cardiac remodelling and clinical response. Assessment of iron substitution might be a relevant treatment target to increase CRT response and outcome in chronic heart failure patients.

Left ventricular longitudinal systolic function analysed by 2D speckle-tracking echocardiography in heart failure with preserved ejection fraction: a meta-analysis.

BACKGROUND: The purpose of this meta-analysis was to confirm if the global longitudinal systolic function of the left ventricle (LV) is altered in patients with heart failure with preserved ejection fraction (HFpEF). METHODS: We searched in different databases (Medline, Embase and Cochrane) studies that analysed LV global longitudinal systolic strain (GLS) in patients with HFpEF and in controls (such as healthy subjects or asymptomatic patients with arterial hypertension, diabetes mellitus or coronary artery disease). RESULTS: Twenty-two studies (2284 patients with HFpEF and 2302 controls) were included in the final analysis. Patients with HFpEF had significantly lower GLS than healthy subjects (mean -15.7% (range -12% to -18.9%) vs mean -19.9% (range -17.1% to -21.5%), weighted mean difference -4.2% (95% CI -3.3% to -5.0%), p < 0.001, respectively). In addition, patients with HFpEF had also significantly lower GLS than asymptomatic patients (mean -15.5% (range -13.4% to -18.4%) vs mean -18.3% (range -15.1% to -20.4%), weighted mean difference -2.8%(95% CI -1.9% to -3.6%), p < 0.001, respectively). In line, 10 studies showed that the rate of abnormal GLS was significantly higher in patients with HFpEF (mean 65.4% (range 37%-95%)) than in asymptomatic subjects (mean 13% (range 0%-29.6%)). Regarding the prognostic relevance of abnormal GLS in HFpEF, two multicentre studies with large sample size (447 and 348) and high number of events (115 and 177) showed that patients with abnormal GLS had worse cardiovascular (CV) outcomes than those with normal GLS (HR for CV mortality and HF hospitalisation 2.14 (95% CI 1.26 to 3.66) and 1.94 (95% CI 1.22 to 3.07)), even adjusting these analyses for multiples clinical and echocardiographic variables. CONCLUSION: The present meta-analysis analysing 2284 patients with HFpEF and 2302 controls confirms that the longitudinal systolic function of the LV is significantly altered in high proportion of patients with HFpEF. Further large multicentre studies with the aim to confirm the prognostic role of abnormal GLS in HFpEF are warranted.

Left atrial strain predicts recurrence of atrial arrhythmias after catheter ablation of persistent atrial fibrillation.

INTRODUCTION: Success rates of catheter ablation (CA) of persistent atrial fibrillation (AF) are very variable. Identifying patients in whom sinus rhythm maintenance cannot be achieved after CA is a critical issue. METHODS: 2D speckle-tracking echocardiography was performed before the first CA procedure in consecutive patients with persistent AF. Left atrial (LA) strain was correlated with recurrence of atrial arrhythmias during the follow-up period of 15 months after one CA procedure with or without antiarrhythmic drugs (primary endpoint). In a secondary analysis, recurrences after two CA procedures were analysed. RESULTS: 102 patients were included. Patients with recurrence of atrial arrhythmias after one CA procedure (n=55) had significantly lower LA strain than those without recurrence (LA strain 9.7±2.4% vs 16.2±3.0%; p<0.001). Recurrence rate was significantly higher in patients with LA strain <10% than in those with LA strain between 10% and 14.5% and >14.5% (97.7%, 42.1% and 10.3%, respectively; p<0.001). In Cox regression analysis including age, comorbidities, left ventricular dysfunction and LA enlargement, low LA strain (<10%) was the strongest factor associated with recurrence of AF (HR 6.4 (2.4-16.9), p<0.001). Even after inclusion of a second CA procedure, LA strain <10% maintained a high predictive value for recurrence of atrial arrhythmias (86.4% (95% CI 73.3% to 93.6%)). CONCLUSION: In patients with persistent AF, LA strain imaging could be very useful to select those patients who have a high risk of not benefiting from CA.