Structural Heart Imaging Using 3-Dimensional Intracardiac Echocardiography: JACC Cardiovascular Imaging Position Statement.

3-dimensional (3D) intracardiac echocardiography (ICE) is emerging as a promising complement and potential alternative to transesophageal echocardiography for imaging guidance in structural heart interventions. To establish standardized practices, our multidisciplinary expert position statement serves as a comprehensive guide for the appropriate indications and utilization of 3D-ICE in various structural heart procedures. The paper covers essential aspects such as the fundamentals of 3D-ICE imaging, basic views, and workflow recommendations specifically tailored for ICE-guided structural heart procedures, such as transeptal puncture, device closure of intracardiac structures, and transcatheter mitral and tricuspid valve interventions. Current challenges, future directions, and training requirements to ensure operator proficiency are also discussed, thereby promoting the safety and efficacy of this innovative imaging modality to support expanding its future clinical applications.

Multimodality Imaging Approach for Planning and Guiding Direct Transcatheter Tricuspid Valve Annuloplasty.

Interest in transcatheter treatment of tricuspid regurgitation (TR) has grown significantly in recent years due to increasing evidence correlating TR severity with mortality and to limited availability of surgical options often considered high-risk in these patients. Although edge-to-edge repair is currently the main transcatheter therapeutic strategy, tricuspid valve direct annuloplasty can also be performed safely and effectively to reduce TR and improve heart failure symptoms and quality of life. In the annuloplasty procedure, an adjustable band is implanted around the tricuspid annulus to reduce valvular size and improve TR. Patient selection and careful preoperative imaging, including transthoracic echocardiography, transesophageal echocardiography, and computed tomography, are critical for procedural success and proper device implantation. Compared to edge-to-edge repair, perioperative imaging with transesophageal echocardiography and fluoroscopy is particularly challenging. Alignment and insertion of the anchors are demanding but essential to achieve good results and avoid damaging the surrounding structures. The presence of shadowing artifacts due to cardiac devices makes the acquisition of good-quality images even more challenging. In this review, we discuss the current role of multimodality imaging in planning direct transcatheter tricuspid valve annuloplasty and describe all procedural steps focusing on echocardiographic monitoring.

The Positive Impact of Early Frailty Levels on Mortality in Elderly Patients with Severe Aortic Stenosis Undergoing Transcatheter/Surgical Aortic Valve Replacement.

Background: Frailty is highly common in older patients (pts) undergoing transcatheter aortic valve replacement (TAVR), and it is associated with poor outcomes. The selection of patients who can benefit from this procedure is necessary and challenging. The aim of the present study is to evaluate outcomes in older severe aortic valve stenosis (AS) pts, selected by a multidisciplinary approach for surgical, clinical, and geriatric risk and referred to treatment, according to frailty levels. Methods: A total of 109 pts (83 ± 5 years; females, 68%) with AS were classified by Fried's score in pre-frail, early frail, and frail and underwent surgical aortic valve replacement SAVR/TAVR, balloon aortic valvuloplasty, or medical therapy. We evaluated geriatric, clinical, and surgical features and detected periprocedural complications. The outcome was all-cause mortality. Results: Increasing frailty was associated with the worst clinical, surgical, geriatric conditions. By using Kaplan-Meier analysis, the survival rate was higher in pre-frail and TAVR groups (p < 0.001) (median follow-up = 20 months). By using the Cox regression model, frailty (p = 0.004), heart failure (p = 0.007), EF% (p = 0.043), albumin (p = 0.018) were associated with all-cause mortality. Conclusions: According to tailored frailty management, elderly AS pts with early frailty levels seem to be the most suitable candidates for TAVR/SAVR for positive outcomes because advanced frailty would make each treatment futile or palliative.

Treatment of multiple valve disease: surgery, structural intervention, or both?

Multiple valve heart disease refers to the simultaneous presence of several valvular anomalies, while mixed valvular heart disease refers to the combination of stenotic lesions or regurgitation affecting the same valve. The pathophysiology of multiple and mixed valvular heart disease depends on the combination of affected valves and the severity of the individual valvular defects. Imaging is essential for diagnosis and assessment of disease severity. The treatment of combined valvular defects currently represents a challenge for both cardiac surgeons and interventional cardiologists since only few data in the literature address the clinical and therapeutic decision-making process related to these complex lesions. These are heterogeneous conditions, which differ from each other in the combination of the valves involved, in the pathogenesis with which they develop, in the severity of the individual lesions, in the associated surgical risk, in the possibility of being repaired, and in the undergoing transcatheter treatments. In addition to the severity of the individual valve defects, the choice of treatment also depends on the ventricular function and the general condition of the patient. This work aims to provide a review of the state of the art regarding the possible management strategies of the most common multiple valve diseases in clinical practice.

Prognostic role of CRP-independent inflammatory patterns in patients undergoing primary percutaneous interventions.

BACKGROUND: Despite the key pathophysiological role of inflammation in the development of coronary artery disease (CAD), the evaluation of inflammatory status has not been clearly established in patients presenting with acute coronary syndrome (ACS). The aim of this study is to evaluate the prevalence of CRP-independent inflammatory patterns in patients referred for primary percutaneous coronary intervention (pPCI) and to determine their one-year relationship with adverse clinical outcomes. METHODS: We carried out a single-centre, observational study consecutively enrolling all patients presenting at a large-volume PCI hub with a diagnosis of ST-segment elevation myocardial infarction (STEMI) and treated with pPCI. Systemic immune-inflammatory index (SII) was calculated at admission and discharge. According to different SII trajectories patients were divided into four patterns: 'persistent-low', 'down-sloping', 'up-sloping' and 'persistent-high' patterns. The primary endpoint was a composite of all-cause of death and myocardial infarction (MI) at a one-year follow-up. RESULTS: Among the total 2353 subjects enrolled, 44% of them belonged to 'persistent-low', 31% to 'down-sloping', 4% to 'up-sloping' and 21% to 'persistent-high' pattern. The primary endpoint was observed in 8% of patients with a 'persistent-low', 12% with a 'down-sloping', 27% with an 'up-sloping' and 25% with a persistent-high pattern (p = 0.001). After multivariate analysis, 'up-sloping' (OR: 3.2 [1.59-3.93]; p = 0.001) and 'persistent-high' (OR: 4.1 [3.03-4.65]; p = 0.001) patterns emerged as independent predictors of one-year adverse events. CONCLUSIONS: 'Persistent-high' and 'up-sloping' CRP-independent inflammatory patterns in patients undergoing primary PCI are associated with an increased risk of adverse events at one-year follow-up. The prognostic value of these inflammatory patterns might be helpful to individualize potential therapeutic targets.

Additional value of T1 and T2 mapping techniques for early detection of myocardial involvement in scleroderma.

BACKGROUND: We evaluated the prevalence of myocardial involvement by native T1 and T2 mapping, the diagnostic performance of mapping in addition to conventional Lake Louise Criteria (LLC), as well as correlations between mapping findings and clinical or conventional cardiovascular magnetic resonance (CMR) parameters in systemic sclerosis (SSc) patients. METHODS: Fifty-five SSc patients (52.31 ± 13.24 years, 81.8% female) and 55 age- and sex-matched healthy subjects underwent clinical, bio-humoral assessment, and CMR. The imaging protocol included: T2-weighted, early post-contrast cine sequences, native T1 and T2 mapping by a segmental approach, and late gadolinium enhancement (LGE) technique. RESULTS: Global myocardial T1 and T2 values were significantly higher in SSc patients than in healthy subjects. An increase in native T1 and/or T2 was present in the 62.1% of patients with normal conventional CMR techniques (negative LGE and T2-weighted images). Respectively, 13.5% and 59.6% of patients fulfilled original and updated LLC (overall agreement = 53.9%). Compared with patients with normal native T1, patients with increased T1 (40.0%) featured significantly higher left ventricular end-diastolic volume index and cardiac index, biventricular stroke volume indexes, and global heart T2 values, and more frequently had a history of digital ulcers. Biochemical and functional CMR parameters were comparable between patients with normal and increased T2 (61.8%). CONCLUSION: T1 and T2 mapping are sensitive parameters that should be included in the routine clinical assessment of SSc patients for detecting early/subclinical myocardial involvement.

Combining echo-derived haemodynamic phenotypes and myocardial strain for risk stratification of chronic heart failure with reduced ejection fraction.

AIMS: Echocardiography has shown to categorize heart failure (HF) patients according to haemodynamic profiles. Whether left ventricular (LV) global longitudinal strain (LV-GLS) could integrate echo-derived haemodynamic profiles to risk stratify chronic HF patients is still unknown. METHODS AND RESULTS: Chronic HF outpatients with LV ejection fraction (LV-EF) <50% (n = 351) and LV-GLS assessment were evaluated and divided according to four haemodynamic phenotypes based on LV stroke volume index (SVI), LV filling pressure (LVFP), and right ventricular (RV) function: normal output-normal LVFP (NO-NP), normal output-high LVFP (NO-HP), low output-no RV dysfunction (LO-NRVD), and low output-RV dysfunction (LO-RVD). RV function was defined using the tricuspid annular plane systolic excursion and RV free-wall longitudinal strain. The median follow-up duration was 3.3 years. The combination of all-cause mortality and HF hospitalization was the primary endpoint. Secondary endpoints were all-cause mortality and cardiovascular mortality. The prevalence of NO-NP, NO-HP, LO-NRVD, and LO-RVD were 38%, 22%, 30%, and 10%, respectively. The haemodynamic model independently predicted primary and secondary outcomes, with incremental prognostic information over LV-EF (all P-values <0.001 for C-statistics). When univariate Cox regression analysis was performed to assess the prognostic stratification capability of LV-GLS in different haemodynamic subgroups, we observed a reduction in LV-GLS hazard ratios from the NO-NP to the LO-RVD for every endpoint. CONCLUSION: There was a continuum in LV-GLS impairment across the spectrum of haemodynamic phenotypes and its prognostic value resulted variable depending on the types of chronic HF patients. The highest prognostic information added by LV-GLS was in patients with normal SVI.

Echocardiographically defined haemodynamic categorization predicts prognosis in ambulatory heart failure patients treated with sacubitril/valsartan.

AIM: Echo-derived haemodynamic classification, based on forward-flow and left ventricular (LV) filling pressure (LVFP) correlates, has been proposed to phenotype patients with heart failure and reduced ejection fraction (HFrEF). To assess the prognostic relevance of baseline echocardiographically defined haemodynamic profile in ambulatory HFrEF patients before starting sacubitril/valsartan. METHODS AND RESULTS: In our multicentre, open-label study, HFrEF outpatients were classified into 4 groups according to the combination of forward flow (cardiac index; CI:< or ≥2.0 L/min/m2 ) and early transmitral Doppler velocity/early diastolic annular velocity ratio (E/e': ≥ or <15): Profile-A: normal-flow, normal-pressure; Profile-B: low-flow, normal-pressure; Profile-C: normal-flow, high-pressure; Profile-D: low-flow, high-pressure. Patients were started on sacubitril/valsartan and followed-up for 12.3 months (median). Rates of the composite of death/HF-hospitalization were assessed by multivariable Cox proportional-hazards models. Twelve sites enrolled 727 patients (64 ± 12 year old; LVEF: 29.8 ± 6.2%). Profile-D had more comorbidities and worse renal and LV function. Target dose of sacubitril/valsartan (97/103 mg BID) was more likely reached in Profile-A (34%) than other profiles (B: 32%, C: 24%, D: 28%, P < 0.001). Event-rate (per 100 patients per year) progressively increased from Profile-A to Profile-D (12.0%, 16.4%, 22.9%, and 35.2%, respectively, P < 0.0001). By covariate-adjusted Cox model, profiles with low forward-flow (B and D) remained associated with poor outcome (P < 0.01). Adding this categorization to MAGGIC-score and natriuretic peptides, provided significant continuous net reclassification improvement (0.329; P < 0.001). Intermediate and high-dose sacubitril/valsartan reduced the event's risk independently of haemodynamic profile. CONCLUSIONS: Echocardiographically-derived haemodynamic classification identifies ambulatory HFrEF patients with different risk profiles. In real-world HFrEF outpatients, sacubitril/valsartan is effective in improving outcome across different haemodynamic profiles.

Benefit from sacubitril/valsartan is associated with hemodynamic improvement in heart failure with reduced ejection fraction: An echocardiographic study.

BACKGROUND: Sacubitril/valsartan improves outcome in patients with heart failure (HF) with reduced left ventricular (LV) ejection fraction (EF, HFrEF). However, little is known about possible mechanisms underlying this favourable effect. PURPOSE: To assess changes in echocardiographically-derived hemodynamic profiles induced by sacubitril/valsartan and their impact on outcome. METHODS: In this multicenter, open-label study, 727 HFrEF outpatients underwent comprehensive echocardiography at baseline (before starting sacubitril/valsartan) and after 12 months. Estimated LV filling pressure (E/e') and cardiac index (CI, l/min/m2) were combined to determine 4 hemodynamic profiles: profile-A (normal-flow/normal-pressure); profile-B (low-flow/normal-pressure); profile-C: (normal-flow/high-pressure); profile-D: (low-flow/high-pressure). Changes among categories were recorded, and their associations with rates of the composite of death/HF-hospitalization were assessed by multivariable Cox analysis. RESULTS: At baseline, 29% had profile-A, 15% had profile-B, 32% profile-C, and 24% profile-D. After 12 months, the hemodynamic profile improved in 53% of patients (all profile-A achievers, or profile-D patients achieving either C or B profile), while it remained unchanged in 39% patients and worsened in 9%. Prevalence of improved profile progressively increased with increasing dose of sacubitril/valsartan (P < 0.0001). After the second echocardiography, patients were followed up 12.6 ± 7.6 months: event-rate was lower in patients with improved profile (12.3%, 95%CI: 9.4-16.1) compared to patients in whom hemodynamic profile remained unchanged (29.9%, 24.0-37.3) or worsened (31.2%, 20.7-46.9, P < 0.0001). Improved hemodynamic profile was associated with favourable outcome independent of LVEF and other covariates (HR 0.65, 95%CI: 0.45-0.95, P < 0.05). CONCLUSION: In HFrEF patients, the beneficial prognostic effects of sacubitril/valsartan are associated with improvement in hemodynamic conditions.

Improved diastolic dysfunction is associated with higher forward flow and better prognosis in chronic heart failure.

The benefit of repeat assessment of left ventricular (LV) systolic and diastolic function in heart failure (HF) remains uncertain. We assessed the prognostic value of repeat echocardiographic assessment of LV filling pressure (LVFP) and its interaction with cardiac index (CI) in ambulatory patients with chronic HF and reduced ejection fraction (HFrEF). We enrolled 357 patients (age 68 ± 11 years; 22% female) with chronic HFrEF. Patients underwent a clinical and echocardiographic examination at baseline. LVFP as assessed by the 2016 Guidelines and Doppler-derived CI were estimated. After the second echocardiographic examination, patients were followed for a median time of 30 months. The study endpoint included all-cause death and hospitalization for worsening HF. Patients who normalized LVFP or showed persistently normal LVFP at the follow-up examination had a significantly lower mortality rate than those with worsening or persistently raised LVFP (p < 0.0001). After stratification by CI, patients with elevated LVFP and CI < 2.0 l/min/m2 had a further worse outcome than those with elevated LVFP and CI ≥ 2.0 l/min/m2 (p < 0.0001). Multivariate survival analysis confirmed an independent prognostic impact of changes in LVFP, incremental to that of established clinical, laboratory and echocardiographic predictors. Repeat assessment of LVFP and CI significantly improved risk stratification of chronic HFrEF outpatients compared to baseline evaluation.

Left atrial structural and mechanical remodelling in heart failure with reduced ejection fraction.

AIMS: In patients with heart failure with reduced ejection fraction (HFrEF), an association between left atrial (LA) dilatation and dysfunction is expected, but the degree of coexistence of the two abnormalities and their relative prognostic role is not known. METHODS AND RESULTS: A total of 626 HFrEF patients formed the study population. All of them underwent a comprehensive echocardiographic evaluation. LA maximal volume was indexed to body surface area (LAVi); LA function was assessed using strain analysis during the reservoir phase: peak atrial longitudinal strain (PALS) analysis. Study primary endpoint was overall mortality or hospitalization for worsening heart failure. Four groups of patients were included in this study according to LAVi (≤34 or >34 mL/m2 ) and PALS (≤23% or >23%); 61 (10%) patients had normal LA volume and function (Group 1), 58 (9%) had LA dilatation but normal function (Group 2), 100 (16%) had normal volume but abnormal function (Group 3), and 407 (65%) had enlarged left atrium and abnormal function (Group 4). PALS was associated with primary endpoint in patients with both normal-size [Groups 1 and 3: hazard ratio (HR) 0.92, 95% confidence interval (CI) 0.88-0.96; P = 0.0006] and dilated left atria (Groups 2 and 4: HR 0.93, 95% CI 0.91-0.96; P < 0.0001). In contrast, LAVi was associated with the primary endpoint in patients with abnormal LA function (Groups 3 and 4: HR 1.018, 95% CI 1.011-1.024; P < 0.00001) but not in those with normal PALS (Groups 1 and 2: HR 1.023, 95% CI 0.99-1.057; P = 0.1). CONCLUSIONS: Left atrial dilatation and dysfunction frequently but not invariably coexist. PALS emerged as a significant prognostic parameter in HFrEF even in the absence of LA dilation.

Global longitudinal strain in heart failure with reduced ejection fraction: Prognostic relevance across disease severity as assessed by automated cluster analysis.

BACKGROUND: Ejection fraction (EF) is still widely used to categorize heart failure (HF) patients but has limitations. Global longitudinal strain (GLS) has emerged as a new prognosticator in HF, independent of EF. AIM: We investigated the incremental predictive benefit of GLS over different risk profiles as identified by automated cluster analysis of simple echocardiographic parameters. METHODS AND RESULTS: In 797 HFrEF patients (age 66 ± 12y; mean EF 30 ± 7%), unsupervised cluster analysis of 10 routine echocardiographic variables (without GLS) was performed. Median follow-up was 37 months. End-point was all-cause mortality. Association between risk profiles, GLS, and mortality was assessed by Cox proportional-hazard modeling with interaction term. Cluster analysis allocated patients to 3 different risk phenogroups (PG): PG-1 (mild diastolic dysfunction [DD], moderate systolic dysfunction, no pulmonary hypertension, normal right ventricular [RV] function); PG-2 (moderate DD, mild pulmonary hypertension, normal RV function); PG-3 (severe DD, advanced systolic dysfunction, pulmonary hypertension, RV dysfunction). Compared to PG-1, PG-2 and PG-3 showed increased adjusted-hazard ratio (1.71; 95% CI:1.05-2.77, P = 0.30; and 2.58; 95% CI:1.50-4.44, P < 0.001, respectively). GLS was independently associated with outcome in the whole population (adjusted-HR: 1.11; 95% CI: 1.05-1.17, P = 0.001); however, profile membership modified the relationship between GLS and outcome which was no longer significant in PG-3 (P for interaction = 0.003). CONCLUSIONS: Within HFrEF populations, clustering of routine echocardiography parameters can automatically identify patients with different risk profiles; further assessment by GLS may be useful for patients with not advanced disease.

Left atrial stiffness predicts cardiac events in patients with heart failure and reduced ejection fraction: The impact of diabetes.

BACKGROUND: The aim of this study was to investigate the relationship between diabetes mellitus (DM) and left atrial (LA) remodelling in a group of patients with heart failure and reduced ejection fraction (HFrEF), and their combined impact on cardiac events (CE). METHODS: This study included 136 consecutive HFrEF patients (65 ± 11 years), 36 had DM, and 86 had increased LA stiffness (LASt). All patients underwent complete conventional and tissue Doppler echocardiographic measurements were made including LA volumes and function. LASt was calculated using the formula: LASt = E/e' ratio / PALS. RESULTS: At 55 ± 37 months follow-up, free survival from CE was 69% in patients without DM and 44.4% in those with DM (p < .0001). The CE free survival was lower in patients with increased LASt compared to normal LASt, (50 versus. 80%, p < .001), irrespective of the presence of DM (27 versus. 71%, p < .001).The best cut-off value of LASt for predicting CE in the group as a whole was ≥ 0.82% [81% sensitivity, 72% specificity and AUC 0.82 (p < .001)]. LASt ≥ 0.82% also predicted CE in no DM patients [78% sensitivity, 71% specificity and AUC 0.80 (p < .001)] and was a stronger predictor in DM patients [85% sensitivity, 71% specificity and AUC = 0.847 (p < .001)]. CONCLUSION: High LA stiffness is associated with poor clinical outcome in patients with HFrEF. Diabetes has an additional incremental value in determining clinical outcome in those patients.

Echocardiography of right ventricular-arterial coupling predicts survival of elderly patients with heart failure and reduced to mid-range ejection fraction.

Echocardiography of right ventricular (RV)-arterial coupling obtained by the estimation of the ratio of the longitudinal annular systolic excursion of the tricuspid annular plane and pulmonary artery systolic pressure (TAPSE/PASP) has been found to be a remarkable prognostic indicator in patients with HF. Our aim was to evaluate the impact of TAPSE, PASP and their ratio in the prognostic stratification of outpatients with HF aged ≥70 years and reduced to mid-range ejection fraction (EF). A complete echocardiographic examination was performed in 400 outpatients with chronic HF and left ventricular (LV) EF ≤50% who averaged 77 years in age. During a median follow-up period of 25 months (interquartile range: 8-46), there were 135 cardiovascular deaths. Two different Cox regression models were evaluated, one including TAPSE and PASP, separately, and the other with TAPSE/PASP. In the first model, LV end-systolic volume index, age, no angiotensin converting enzyme (ACE) inhibitor use, TAPSE, PASP and gender were found to be independently associated with the outcome after adjustment for demographics, clinical, biochemical, echocardiographic data. In the second model, TAPSE/PASP resulted the most important independent predictor of outcome (hazard ratio [HR]:0.07, p<0.0001) followed by LV end-systolic volume index, no ACE inhibitor use, age and gender. The use of the variable TASPE/PASP improved the predictive value of the new multivariable model (area under the curve [AUC] of 0.74 vs AUC of 0.71; p<0.05). TASPE/PASP improved the net reclassification (NRI = 14.7%; p<0.01) and the integrated discrimination (IDI = 0.04; p<0.01). In conclusion, the study findings showed that assessment of RV-arterial coupling by TAPSE/PASP was of major importance to assess the prognosis of patients with chronic HF and LV EF ≤50% aged ≥70 years.

Speckle Tracking-Derived Left Atrial Stiffness Predicts Clinical Outcome in Heart Failure Patients with Reduced to Mid-Range Ejection Fraction.

BACKGROUND AND AIM: Left atrial stiffness (LASt) is an important marker of cardiac function, especially in patients with heart failure (HF); it explains symptoms on the basis of pressure transfer to the pulmonary circulation. The aim of this study was to evaluate the relationship between LASt and cardiac events (CE) in HF patients with reduced to mid-range ejection fraction. METHODS: The study included 215 consecutive ambulatory HF patients with ejection fraction (EF) < 50% (162 HF reduced EF and 53 HF mid-range EF) of mean age 66 ± 11 years and 24.4% females. Peak LA strain (PALS) was measured by speckle tracking echocardiography and E/e' recorded from the apical four-chamber view. Non-invasive LASt was calculated using the equation: LASt = E/e' ratio/PALS. Documented cardiac events (CE) were HF hospitalization and cardiac death. RESULTS: During a median follow up of 41 ± 34 months, 65 patients (30%) had CE. In multivariate analysis model, only raised LV filling pressure (E/e') (OR = 0.292, (95% CI 0.099 to 0.859), p = 0.02), peak pulmonary artery pressure (PAP) (OR = 1.050 (1.009 to 1.094), p = 0.01), PALS (OR = 0.932 (0.873 to 0.994), p = 0.02) and LASt (OR = 3.781 (1.144 to 5.122), p = 0.001) independently predicted CE. LASt ≥ 0.76% was the most powerful predictor of CE, with 80% sensitivity and 73% specificity (AUC 0.82, CI = 0.73 to 0.87, p < 0.001) followed by PALS ≤ 16%, with 74% sensitivity and 72% specificity (AUC 0.77, CI = 0.71 to 0.84, p < 0.001). These results were consistent irrespective of EF (p < 0.05). CONCLUSION: In this cohort of ambulatory HFrEF and HFmrEF patients, LASt proved the most powerful predictor of clinical outcome.

The assessment of pressure-volume relationship during exercise stress echocardiography predicts left ventricular remodeling and eccentric hypertrophy in patients with chronic heart failure.

BACKGROUND: The contractile response of patients with heart failure (HF) may be assessed by exercise stress echocardiography (ESE)-derived indexes. We sought to test whether ESE parameters are useful to identify the risk of adverse left ventricular (LV) remodeling in patients with chronic HF and reduced or mildly reduced LV ejection fraction (EF). METHODS: We enrolled 155 stabilized patients (age: 62 ± 11 years, 17% female, coronary artery disease 47%) with chronic HF, LV EF ≤50% and LV end-diastolic volume index > 75 ml/m2. All patients underwent a symptom-limited graded bicycle semi-supine ESE, with evaluation of peak stress LV EF, end-systolic pressure-volume relation (ESPVR, i.e. LV elastance) and cardiac power output to LV mass (CPOM). A complete echocardiographic study was performed at baseline and after 6 ± 3 months. Adverse LV remodeling was defined as the association of eccentric LV hypertrophy (LV mass: ≥115 g/m2 for male and ≥ 95 g/m2 for women, and relative wall thickness < 0.32) with an increase in LV end-systolic volume index ≥10% at six months. RESULTS: Adverse LV remodeling was detected in 34 (22%) patients. After adjustment for clinical, biochemical and echocardiographic data, peak ESPVR resulted in the most powerful independent predictor of adverse LV remodeling (OR: 12.5 [95% CI 4.5-33]; p < 0.0001) followed by ischemic aetiology (OR: 2.64 [95% 1.04-6.73]; p = 0.04). CONCLUSION: In patients with HF and reduced or mildly reduced EF, a compromised ESE-derived peak ESPVR, that reflects impaired LV contractility, resulted to be the most powerful predictor of adverse LV remodeling.

Effects of sacubitril/valsartan on B-type natriuretic peptide circulating levels and loop diuretic dose in a case series of stabilized heart failure patients with left ventricular ejection fraction ≤35.

Sacubitril/valsartan, an angiotensin receptor neprilysin inhibitor, was shown to improve outcome in patients with heart failure (HF) and reduced left ventricular ejection fraction (LVEF). There are reasons for believing that the concept that the lower the B-type natriuretic peptide (BNP) circulating level the better the prognosis may no longer be correct in patients treated with sacubitril/valsartan, since sacubitril may interfere with BNP clearance. We reported a case series of ten patients with stable chronic HF and LVEF ≤35% (mean age: 64 ± 8 years; 30% female), referred to our outpatient HF clinic, treated with sacubitril/valsartan, in whom the global amelioration of NYHA class and LVEF was coupled with a clinically significant decrease in BNP levels and a reduction of loop diuretic dose. Average sacubitril/valsartan daily dose was 220 mg. The median duration of treatment was 15 months (range: 6-21 months). Seventy percent of patients exhibited an improvement in exercise tolerance, as indicated by the change in NYHA class. There was also an improvement in LVEF from 28 ± 5% to 39 ± 7%. Clinically significant reductions in BNP levels were evident, with a median change from 181 pg/ml to 70 pg/ml. Furosemide daily dose decreased from a median of 43.3 mg to 12.5 mg. This case series suggests that BNP may still be valuable for the assessment of ambulatory HF patients, after the optimization of sacubitril/valsartan therapy.

The Added Value of Exercise Stress Echocardiography in Patients With Heart Failure.

Doppler echocardiography can provide reliable and repeatable measures of cardiac index (CI), whereas lung ultrasound (LUS) represents a quantitative approach to assess pulmonary congestion. We tested the hypothesis that simultaneous assessment of CI and LUS during exercise stress echocardiography (ESE) may define heart failure (HF) outpatients with different risk of adverse outcome. Standard transthoracic echocardiography and LUS (B-lines) evaluation were assessed during semisupine ESE. CI and B-lines were measured at baseline and peak exercise. Resting plasma B-type natriuretic peptide levels were also evaluated. We enrolled 105 HF patients (87 males; age 62 ± 11 years; New York Heart Association class I to III) with reduced left ventricular ejection fraction (30 ± 7%). Patients were classified into 4 profiles: (1) peak CI ≥4.0 l/min/m2 and peak B-lines <15 (no evidence of congestion or hypoperfusion, n = 47); (2) peak CI ≥4.0 l/min/m2 and peak B-lines ≥15 (congestion with adequate perfusion, n = 23); (3) peak CI <4.0 l/min/m2 and peak B-lines <15 (hypoperfusion without congestion, n = 13); and (4) peak CI <4.0 l/min/m2 and peak B-lines ≥15 (congestion and hypoperfusion, n = 22). There were 21 cardiovascular deaths and 18 hospitalizations for worsening HF during a median follow-up of 29 months. Multivariate predictors of the combined end point were peak hemodynamic profiles (hazard ratio [HR] 1.62, 95% confidence interval [CI] 1.19 to 2.21; p = 0.002), B-type natriuretic peptide (HR 1.00, 95% CI 1.00 to 1.01; p = 0.001), and rest E/e' (HR 1.09, 95% CI 1.03 to 1.15; p = 0.002). Survival analysis showed a worse survival in patients with ESE-derived D profile, followed by patients with C, B, and A profile (log-rank: chi-square = 40.5; p <0.0001). In conclusion, dual evaluation of CI and LUS during ESE is useful for risk stratification of HF patients with reduced ejection fraction. Evidence of pulmonary congestion and low CI at peak ESE identifies a subgroup with a very high risk of adverse outcome.

Echo- and B-Type Natriuretic Peptide-Guided Follow-Up versus Symptom-Guided Follow-Up: Comparison of the Outcome in Ambulatory Heart Failure Patients.

Recent European Society of Cardiology and American Heart Association/American College of Cardiology Guidelines did not recommend biomarker-guided therapy in the management of heart failure (HF) patients. Combination of echo- and B-type natriuretic peptide (BNP) may be an alternative approach in guiding ambulatory HF management. Our aim was to determine whether a therapy guided by echo markers of left ventricular filling pressure (LVFP), lung ultrasound (LUS) assessment of B-lines, and BNP improves outcomes of HF patients. Consecutive outpatients with LV ejection fraction (EF) ≤ 50% have been prospectively enrolled. In Group I (n=224), follow-up was guided by echo and BNP with the goal of achieving E-wave deceleration time (EDT) ≥ 150 ms, tissue Doppler index E/e' < 13, B-line numbers < 15, and BNP ≤ 125 pg/ml or decrease >30%; in Group II (n=293), follow-up was clinically guided, while the remaining 277 patients (Group III) did not receive any dedicated follow-up. At 60 months, survival was 88% in Group I compared to 75% in Group II and 54% in Group III (χ 2 53.5; p < 0.0001). Survival curves exhibited statistically significant differences using Mantel-Cox analysis. The number needed to treat to spare one death was 7.9 (Group I versus Group II) and 3.8 (Group I versus Group III). At multivariate Cox regression analyses, major predictors of all-cause mortality were follow-up E/e' (HR: 1.05; p=0.0038) and BNP >125 pg/ml or decrease ≤30% (HR: 4.90; p=0.0054), while BNP > 125 pg/ml or decrease ≤30% and B-line numbers ≥15 were associated with the combined end point of death and HF hospitalization. Evidence-based HF treatment guided by serum biomarkers and ultrasound with the goal of reducing elevated BNP and LVFP, and resolving pulmonary congestion was associated with better clinical outcomes and can be valuable in guiding ambulatory HF management.