Left Atrial Strain in the Assessment of Diastolic Function in Heart Failure: A Machine Learning Approach.

BACKGROUND: Diastolic dysfunction (DD) assessment in heart failure is still challenging. Peak atrial longitudinal strain (PALS) is strongly related to end-diastolic pressure and prognosis, but it is still not part of standard DD assessment. We tested the hypothesis that a machine learning approach would be useful to include PALS in DD classification and refine prognostic stratification. METHODS: In a derivation cohort of 864 heart failure patients in sinus rhythm (age, 66.6±12 years; heart failure with reduced ejection fraction, n=541; heart failure with mildly reduced ejection fraction, n=129; heart failure with preserved ejection fraction, n=194), machine learning techniques were retrospectively applied to PALS and guideline-recommended diastolic variables. Outcome (death/heart failure rehospitalization) of the identified DD-clusters was compared with that by guidelines-based classification. To identify the best combination of variables able to classify patients in one of the identified DD-clusters, classification and regression tree analysis was applied (with DD-clusters as dependent variable and PALS plus guidelines-recommended diastolic variables as explanatory variables). The algorithm was subsequently validated in a prospective cohort of 189 heart failure outpatients (age, 65±13 years). RESULTS: Three distinct echocardiographic DD-clusters were identified (cluster-1, n=212; cluster-2, n=376; cluster-3 DD, n=276), with modest agreement with guidelines-recommended classification (kappa=0.40; P<0.001). DD-clusters were predicted by a simple algorithm including E/A ratio, left atrial volume index, E/e' ratio, and PALS. After 36.5±29.4 months follow-up, 318 events occurred. Compared to guideline-based classification, DD-clusters showed a better association with events in multivariable models (C-index 0.720 versus 0.733, P=0.033; net reclassification improvement 0.166 [95% CI, 0.035-0.276], P=0.013), without interaction with ejection fraction category. In the validation cohort (median follow-up: 18.5 months), cluster-based classification better predicted outcome than guideline-based classification (C-index 0.80 versus 0.78, P=0.093). CONCLUSIONS: Integrating PALS by machine learning algorithm in DD classification improves risk stratification over recommended current criteria, regardless of ejection fraction status. This proof of concept study needs further validation of the proposed algorithm to assess generalizability to other populations.

Impact of diabetes on cardiopulmonary function: the added value of a combined cardiopulmonary and echocardiography stress test.

Type 2 diabetes mellitus (T2DM) represents a major health issue worldwide, as patients with T2DM show an excess risk of death for cardiovascular causes, twice as high as the general population. Among the many complications of T2DM, heart failure (HF) deserves special consideration as one of the leading causes of morbidity and reduced life expectancy. T2DM has been associated with different phenotypes of HF, including HF with reduced and preserved ejection fraction. Cardiopulmonary exercise testing (CPET) can evaluate the metabolic and ventilatory alterations related to myocardial dysfunction and/or peripheral impairment, representing a unique tool for the clinician to study the whole HF spectrum. While CPET allows for a thorough evaluation of functional capacity, it cannot directly differentiate central and peripheral determinants of effort intolerance. Combining CPET with imaging techniques could provide even higher accuracy and further insights into the progression of the disease since signs of left ventricular systolic and diastolic dysfunction can be detected during exercise, even in asymptomatic diabetic individuals. This review aims to dissect the alterations in cardiopulmonary function characterising patients with T2DM and HF to improve patient risk stratification.

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.

Acute pericarditis as a major clinical manifestation of long COVID-19 syndrome.

BACKGROUND: The long COVID-19 syndrome has been recently described and some reports have suggested that acute pericarditis represents important manifestation of long COVID-19 syndrome. The aim of this study was to identify the prevalence and clinical characteristics of patients with long COVID-19, presenting with acute pericarditis. METHODS: We retrospectively included 180 patients (median age 47 years, 62% female) previously diagnosed with COVID-19, exhibiting persistence or new-onset symptoms ≥12 weeks from a negative naso-pharyngeal SARS CoV2 swamp test. The original diagnosis of COVID-19 infection was determined by a positive swab. All patients had undergone a thorough physical examination. Patients with suspected heart involvement were referred to a complete cardiovascular evaluation. Echocardiography was performed based on clinical need and diagnosis of acute pericarditis was achieved according to current guidelines. RESULTS: Among the study population, shortness of breath/fatigue was reported in 52%, chest pain/discomfort in 34% and heart palpitations/arrhythmias in 37%. Diagnosis of acute pericarditis was made in 39 patients (22%). Mild-to-moderate pericardial effusion was reported in 12, while thickened and bright pericardial layers with small effusions (< 5 mm) with or without comet tails arising from the pericardium (pericardial B-lines) in 27. Heart palpitations/arrhythmias (OR:3.748, p = 0.0030), and autoimmune disease and allergic disorders (OR:4.147, p = 0.0073) were independently related to the diagnosis of acute pericarditis, with a borderline contribution of less likelihood of hospitalization during COVID-19 (OR: 0.100, p = 0.0512). CONCLUSION: Our findings suggest a high prevalence of acute pericarditis in patients with long COVID-19 syndrome. Autoimmune and allergic disorders, and palpitations/arrhythmias were frequently associated with pericardial disease.

Deformation Imaging by Strain in Chronic Heart Failure Over Sacubitril-Valsartan: A Multicenter Echocardiographic Registry.

AIMS: Sacubitril/valsartan has changed the treatment of heart failure with reduced ejection fraction (HFrEF), due to the positive effects on morbidity and mortality, partly mediated by left ventricular (LV) reverse remodelling (LVRR). The aim of this multicenter study was to identify echocardiographic predictors of LVRR after sacubitril/valsartan administration. METHODS AND RESULTS: Patients with HFrEF requiring therapy with sacubitril/valsartan from 13 Italian centres were included. Echocardiographic parameters including LV global longitudinal strain (GLS) and global peak atrial longitudinal strain by speckle tracking echocardiography were measured to find the predictors of LVRR [= LV end-systolic volume reduction ≥10% and ejection fraction (LVEF) improvement ≥10% at follow-up] at 6 month follow-up as the primary endpoint. Changes in symptoms [New York Heart Association (NYHA) class] and neurohormonal activations [N-terminal pro-brain natriuretic peptide (NT-proBNP)] were also evaluated as secondary endpoints; 341 patients (excluding patients with poor acoustic windows and missing data) were analysed (mean age: 65 ± 10 years; 18% female, median LVEF 30% [inter-quartile range: 25-34]). At 6 month follow-up, 82 (24%) patients showed early complete response (LVRR and LVEF ≥ 35%), 55 (16%) early incomplete response (LVRR and LVEF < 35%), and 204 (60%) no response (no LVRR and LVEF < 35%). Non-ischaemic aetiology, a lower left atrial volume index, and a higher GLS were all independent predictors of LVRR at multivariable logistic analysis (all P < 0.01). A baseline GLS < -9.3% was significantly associated with early response (area under the curve 0.75, P < 0.0001). Left atrial strain was the best predictor of positive changes in NYHA class and NT-proBNP (all P < 0.05). CONCLUSIONS: Speckle tracking echocardiography parameters at baseline could be useful to predict LVRR and clinical response to sacubitril-valsartan and could be used as a guide for treatment in patients with HFrEF.

Right heart failure in left heart disease: imaging, functional, and biochemical aspects of right ventricular dysfunction.

For decades, cardiologists have largely underestimated the role of the right heart in heart failure due to left heart disease. Nowadays, the importance of evaluating right ventricular (RV) structure and function in left heart failure is well documented and this concept has been emphasized in the most recent heart failure guidelines. However, several relevant questions remain unanswered such as the following: (a) which imaging technique (standard or 3D echocardiography or strain imaging or cardiac magnetic resonance) and, more, which parameters should be used to grade the severity of RV dysfunction? (b) do less widespread and less applied diagnostic tools such as cardiopulmonary stress testing and bioelectrical impedance analysis play a role in this field? (c) are there specific biochemical aspects of RV failure? (d) why notion of pathophysiology of heart and lung interaction are so well appreciated at an academic level but are not applied in the clinical setting? The present review has been prepared by the Heart Failure (HF) working group of the Italian Society of Cardiology and its main objective is to improve our understanding on RV dysfunction in heart failure.

Sacubitril/valsartan reduces indications for arrhythmic primary prevention in heart failure with reduced ejection fraction: insights from DISCOVER-ARNI, a multicenter Italian register.

Aims: This sub-study deriving from a multicentre Italian register [Deformation Imaging by Strain in Chronic Heart Failure Over Sacubitril-Valsartan: A Multicenter Echocardiographic Registry (DISCOVER)-ARNI] investigated whether sacubitril/valsartan in addition to optimal medical therapy (OMT) could reduce the rate of implantable cardioverter-defibrillator (ICD) indications for primary prevention in heart failure with reduced ejection fraction (HFrEF) according to European guidelines indications, and its potential predictors. Methods and results: In this observational study, consecutive patients with HFrEF eligible for sacubitril/valsartan from 13 Italian centres were included. Lack of follow-up or speckle tracking data represented exclusion criteria. Demographic, clinical, biochemical, and echocardiographic data were collected at baseline and after 6 months from sacubitril/valsartan initiation. Of 351 patients, 225 (64%) were ICD carriers and 126 (36%) were not ICD carriers (of whom 13 had no indication) at baseline. After 6 months of sacubitril/valsartan, among 113 non-ICD carriers despite having baseline left ventricular (LV) ejection fraction (EF) ≤ 35% and New York Heart Association (NYHA) class = II-III, 69 (60%) did not show ICD indications; 44 (40%) still fulfilled ICD criteria. Age, atrial fibrillation, mitral regurgitation > moderate, left atrial volume index (LAVi), and LV global longitudinal strain (GLS) significantly varied between the groups. With receiver operating characteristic curves, age ≥ 75 years, LAVi ≥ 42 mL/m2 and LV GLS ≥-8.3% were associated with ICD indications persistence (area under the curve = 0.65, 0.68, 0.68, respectively). With univariate and multivariate analysis, only LV GLS emerged as significant predictor of ICD indications at follow-up in different predictive models. Conclusions: Sacubitril/valsartan may provide early improvement of NYHA class and LVEF, reducing the possible number of implanted ICD for primary prevention in HFrEF. Baseline reduced LV GLS was a strong marker of ICD indication despite OMT. Early therapy with sacubitril/valsartan may save infective/haemorrhagic risks and unnecessary costs deriving from ICDs.

Arterial Hypertension and Cardiopulmonary Function: The Value of a Combined Cardiopulmonary and Echocardiography Stress Test.

Arterial hypertension (AH) is a global burden and the leading risk factor for mortality worldwide. Haemodynamic abnormalities, longstanding neurohormonal and inflammatory activation, which are commonly observed in patients with AH, promote cardiac structural remodeling ultimately leading to heart failure (HF) if blood pressure values remain uncontrolled. While several epidemiological studies have confirmed the strong link between AH and HF, the pathophysiological processes underlying this transition remain largely unclear. The combined cardiopulmonary-echocardiography stress test (CPET-ESE) represents a precious non-invasive aid to detect alterations in patients at the earliest stages of HF. The opportunity to study the response of the cardiovascular system to exercise, and to differentiate central from peripheral cardiovascular maladaptations, makes the CPET-ESE an ideal technique to gain insights into the mechanisms involved in the transition from AH to HF, by recognizing alterations that might be silent at rest but influence the response to exercise. Identifications of these subclinical alterations might allow for a better risk stratification in hypertensive patients, facilitating the recognition of those at higher risk of evolution towards established HF. This may also lead to the development of novel preventive strategies and help tailor medical treatment. The purpose of this review is to summarise the potential advantages of using CPET-ESE in the characterisation of hypertensive patients in the cardiovascular continuum.

Biomarkers Predict In-Hospital Major Adverse Cardiac Events in COVID-19 Patients: A Multicenter International Study.

BACKGROUND: The COVID-19 pandemic carries a high burden of morbidity and mortality worldwide. We aimed to identify possible predictors of in-hospital major cardiovascular (CV) events in COVID-19. METHODS: We retrospectively included patients hospitalized for COVID-19 from 10 centers. Clinical, biochemical, electrocardiographic, and imaging data at admission and medications were collected. Primary endpoint was a composite of in-hospital CV death, acute heart failure (AHF), acute myocarditis, arrhythmias, acute coronary syndromes (ACS), cardiocirculatory arrest, and pulmonary embolism (PE). RESULTS: Of the 748 patients included, 141(19%) reached the set endpoint: 49 (7%) CV death, 15 (2%) acute myocarditis, 32 (4%) sustained-supraventricular or ventricular arrhythmias, 14 (2%) cardiocirculatory arrest, 8 (1%) ACS, 41 (5%) AHF, and 39 (5%) PE. Patients with CV events had higher age, body temperature, creatinine, high-sensitivity troponin, white blood cells, and platelet counts at admission and were more likely to have systemic hypertension, renal failure (creatinine ≥ 1.25 mg/dL), chronic obstructive pulmonary disease, atrial fibrillation, and cardiomyopathy. On univariate and multivariate analysis, troponin and renal failure were associated with the composite endpoint. Kaplan-Meier analysis showed a clear divergence of in-hospital composite event-free survival stratified according to median troponin value and the presence of renal failure (Log rank p < 0.001). CONCLUSIONS: Our findings, derived from a multicenter data collection study, suggest the routine use of biomarkers, such as cardiac troponin and serum creatinine, for in-hospital prediction of CV events in patients with COVID-19.

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.

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.

Prognostic relevance of Doppler echocardiographic re-assessment in HFrEF patients.

BACKGROUND: Current guidelines do not recommend periodically repeating echocardiograms in the follow-up of stable heart failure patients with reduced ejection fraction (HFrEF). The objective of the study was to verify the additional prognostic information provided by a comprehensive re-assessment of their cardiac function and hemodynamic profile at Doppler echocardiography in HFrEF patients. METHODS: Retrospective analysis of 769 stable HFrEF outpatients who underwent two complete echocardiograms, at baseline and at re-assessment. Main candidate predictors of prognosis were: left ventricular (LV) filling pattern, pulmonary artery systolic pressure (PASP) and right ventricular function (TAPSE). Age, LV ejection fraction, mitral regurgitation severity, NYHA class, brain natriuretic peptide plasma levels at baseline, and their changes at 12 months, were used as covariates. Median follow-up was 30 months. All-cause death was the study end-point. RESULTS: At baseline, restrictive filling pattern and low TAPSE were significant predictors of poor prognosis. At re-evaluation, persistently restrictive/worsened filling pattern, persistently-low/worsened TAPSE and worsened PASP, were associated with poorer survival. A significant interaction between changes in TAPSE, PASP and LV filling pattern was observed: in the restrictive pattern subgroup, survival was poorer in worsened/persistently low TAPSE (p < 0.01); in non-restrictive pattern subgroup, survival was poorer in worsened/persistently elevated PASP (p = 0.01). The re-assessment model improved the C-index from 0.69 to 0.74 (P < 0.01) compared to baseline model. CONCLUSIONS: Doppler echocardiographic re-assessment of LV filling pattern, PASP and TAPSE allows a better prognostic stratification of HFrEF outpatients than baseline evaluation and is additional to changes in BNP and NYHA class.

Bedside wireless lung ultrasound for the evaluation of COVID-19 lung injury in senior nursing home residents.

Lung Ultrasound (LUS) is regarded to be potentially useful to diagnose lung injury in older adults living in nursing homes with suspected COVID-19 pneumonia. We aimed at evaluating presence lung injury among senior nursing home residents by LUS performed with portable wireless scanner echography. The study population consisted of 150 residents with a mean age of 88 years (85% female) residing in 12 nursing homes in Northern Italy. Subjects had to have a history of recent onset of symptoms compatible with COVID-19 pneumonia or have been exposed to the contagion of patients carrying the disease. COVID-19 testing was performed with SARS-CoV-2 nasal-pharyngeal (NP) swabs. Positive subjects to LUS scanning were considered those with non-coascelent B-lines in >3 zones, coalescent B-lines in >3 zones and with iperdensed patchy non-consolidated lungs. Sixty-three percent had positive NP testing and 65% had LUS signs of pulmonary injury. LUS had a sensitivity of 79% in predicting positive NP testing. Sixteen percent of residents tested negative for SARSCoV-2 carried the signs of COVID-19 lung injury at LUS. There were 92 patients (61%) with current or recent symptoms.Positivity to LUS scanning was reported in 73% of residents with symptoms, while it was 53% in those without (P=0.016). A positive NP testing was observed in 66% of residents with symptoms and in 57% of those without (P=0.27). We conclude that assessment of LUS by portable wireless scanner echography can be profitability utilized to diagnose lung injury among senior nursing home residents with or without symptoms compatible with COVID-19 pneumonia.

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.

Novel Echocardiographic Approach to Hemodynamic Phenotypes Predicts Outcome of Patients Hospitalized With Heart Failure.

BACKGROUND: Although in clinical practice heart failure (HF) patients are classified using left ventricular ejection fraction (LVEF), this categorization is insufficient for prognosis, especially when LVEF is preserved or there is a concomitant right ventricular (RV) dysfunction. We hypothesized that a combined noninvasive evaluation of LV forward flow, filling pressure, and RV function would be better than LVEF in predicting all-cause mortality of hospitalized patients with HF. METHODS: Transthoracic echocardiographic examinations of 603 patients hospitalized with HF were analyzed. In a subsample of 200 patients with HF, LV stroke volume index, LV filling pressure estimation, tricuspid annular plane systolic excursion, and systolic pulmonary artery pressure were combined to determine 4 hemodynamic profiles: normal flow-normal pressure, normal flow-high pressure, low flow without RV dysfunction, and low flow with RV dysfunction profile. This model was then applied in a validation cohort (n=403). RESULTS: Prognosis worsened from the normal flow-normal pressure profile to the low flow with right ventricular dysfunction profile. At the multivariate survival analysis, the model showed independent high risk-stratification capability (P<0.001), even in subgroups of patients with LVEF < or ≥50% (P=0.011 and P<0.001, respectively) and < or ≥40% (P=0.044 and P<0.001, respectively). LVEF and HF classification based on LVEF did not predict outcome. CONCLUSIONS: Echocardiographic-derived profiling of LV forward flow, filling pressure, and RV function allowed categorization of patients hospitalized with HF and predicted all-cause mortality independently of LVEF. This model is based on conventional echocardiography, is easy to apply, and is, therefore, suggested for clinical practice.

Estimation of increased pulmonary wedge pressure by an algorithm based on noninvasively measured pulmonary diastolic pressure in cardiac patients independent of left ventricular ejection fraction.

AIM: Pulmonary artery diastolic pressure (PADP) correlates closely with pulmonary wedge pressure (PAWP); therefore, we sought to evaluate whether an algorithm based on PADP assessment by the Doppler pulmonary regurgitation (PR) end-diastolic gradient (PRG) may aid in estimating increased PAWP in cardiac patients with reduced or preserved left ventricular (LV) ejection fraction (EF). METHODS AND RESULTS: Right heart catheterization, with estimation of PAWP, right atrial pressure (RAP), PADP, and Doppler echocardiography, was carried out in 183 patients with coronary artery disease (n = 63), dilated cardiomyopathy (n = 52), or aortic stenosis (n = 68). One-hundred and seventeen patients had LV EF <50%. We measured the pressure gradients across the tricuspid and pulmonary valves from tricuspid regurgitation (TRV) and PR velocities. Doppler-estimated PADP (e-PADP) was obtained by adding the estimated RAP to PRG. An algorithm based on e-PADP to predict PAWP, that included TRV, left atrial volume index, and mitral E/A, was developed and validated in derivation (n = 90) and validation (n = 93) subgroups. Both invasive PADP (r = .92, P < .001) and e-PADP (r = .72, P < .001) correlated closely with PAWP, and e-PADP predicted PAWP (AUC: 0.85, CI: 0.79-0.91) with a 94% positive predictive value (PPV) and a 55% negative predictive value (NPV), after exclusion of five patients with precapillary pulmonary hypertension. The e-PADP-based algorithm predicted PAWP with higher accuracy (PPV = 94%; NPV = 67%; accuracy = 85%; kappa: 0.65, P < .001) than the ASE-EACVI 2016 recommendations (PPV = 97%; NPV = 47%; accuracy = 68% undetermined = 18.9%; kappa: 0.15, P < .001). CONCLUSIONS: An algorithm based on noninvasively e-PADP can accurately predict increased PAWP in patients with cardiac disease and reduced or preserved LV EF.

Similar predictive value of six-minute walking distance and B-type natriuretic peptide in heart failure with reduced to mid-range ejection fraction.

The prognostic insights of heart failure (HF) with mid-range (40-49%) ejection fraction (HFmrEF) are not fully elucidated. We investigated whether the six-minutes walking test (6MWT) and brain natriuretic peptide (BNP) are predictive of outcome across the spectrum of LV systolic dysfunction and whether the HFmrEF cut-off impacts the risk stratification abilities of these tests. We studied 538 outpatients, aged 70±12 years, 28% females, with stable chronic HF and EF<50%, 349 with HFmrEF and 189 with HFrEF. End-points were all-cause and cardiac death. HFrEF patients were more often male, with ischemic etiology, severe symptoms, higher BNP levels, and cardiac mortality than HFmrEF subjects. During 32 (15-46) months follow-up, 123 (23%) patients died, 95 (18%) for cardiac causes. Cut-offs of 125 pg/ml for BNP and 360 meters for 6MWT distance were associated with lower all-cause (10% vs 38%, p<0.001 and 10% vs 26%, p<0.001, respectively) and cardiac mortality (6% vs 36%, p<0.001 and 8% vs 23%, p<0.001, respectively). BNP (HR 2.144, 95%CI, 1.403-3.276) and 6MWT walked distance (HR 1.923, 95%CI, 1.195-3.096) independently predicted outcome, after adjustment for age, gender, obesity, kidney dysfunction, ischemic etiology, NYHA class, unlike the 40% LVEF threshold. Model discrimination and survival differences were significant across LVEF strata. Higher BNP levels and shorter walked distance combined identified patients (26% overall) at particularly poor prognosis in both phenotype groups. Despite differences between HFmrEF and HFrEF patients in clinical and biomarker profile, BNP levels and 6MWT walked distance retain prognostic value over the entire spectrum of LV systolic dysfunction.

Additive Value of Biomarkers and Echocardiography to Stratify the Risk of Death in Heart Failure Patients with Reduced Ejection Fraction.

BACKGROUND: Risk stratification is a crucial issue in heart failure. Clinicians seek useful tools to tailor therapies according to patient risk. METHODS: A prospective, observational, multicenter study on stable chronic heart failure outpatients with reduced left ventricular ejection fraction (HFrEF). Baseline demographics, blood, natriuretic peptides (NPs), high-sensitivity troponin I (hsTnI), and echocardiographic data, including the ratio between tricuspid annular plane excursion and systolic pulmonary artery pressure (TAPSE/PASP), were collected. Association with death for any cause was analyzed. RESULTS: Four hundred thirty-one (431) consecutive patients were enrolled in the study. Fifty deaths occurred over a median follow-up of 32 months. On the multivariable Cox model analysis, TAPSE/PASP ratio, number of biomarkers above the threshold values, and gender were independent predictors of death. Both the TAPSE/PASP ratio ≥0.36 and TAPSE/PASP unavailable groups had a three-fold decrease in risk of death in comparison to the TAPSE/PASP ratio <0.36 group. The risk of death increased linearly by 1.6 for each additional positive biomarker and by almost two for women compared with men. CONCLUSIONS: In a HFrEF outpatient cohort, the evaluation of plasma levels of both NPs and hsTnI can contribute significantly to identifying patients who have a worse prognosis, in addition to the echocardiographic assessment of right ventricular-arterial coupling.

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.

Interactive role of diastolic dysfunction and ventricular remodeling in asymptomatic subjects at increased risk of heart failure.

Diastolic dysfunction (DD) and left ventricular remodeling (LVR) characterize patients at risk for heart failure (HF). To assess the prognostic impact of different diastolic function algorithms and a complex LVR classification (CRC) in asymptomatic subjects with preserved ejection fraction (EF) at risk for HF. We analyzed 1923 asymptomatic patients (male 43%; age 57, 33-76 years) with at least one cardiovascular risk factor and preserved (> 50%) EF. We used three algorithms for LV diastolic function assessment (Paulus et al. in Eur Heart J 28(20):2539-2550, 2007; Nagueh et al. in J Am Soc Echocardiogr 22(2):107-133, 2009, Eur Heart J Cardiovasc Imaging 17(12):1321-1360, 2016), and two algorithms for LVR (classic and CRC). We considered a composite end-point: cardiac death and hospitalization for HF. The highest presence of DD was diagnosed by Nagueh 2009 (211, 11%), while the prevalence according to Nagueh 2016 (63 patients, 3.2%) turned out to be the lowest (p < 0.001 vs the other algorithms). According to CRC, 780 (48.6%) patients had normal or physiologic hypertrophy, 298 (15.5%) concentric remodeling, 85 (4.4%) eccentric remodeling, 294 (15.3%) concentric hypertrophy, 39 (2%) mixed hypertrophy, 80 (4.1%) dilated hypertrophy, 73 (3.7%) eccentric hypertrophy and 294 (15.3%) were unclassifiable. After 39-month follow-up (261 events, 13.6%), Cox-regression (adjusted for age, gender, history of stable ischemic heart disease, classic remodeling classification) identified CRC (p = 0.01) and Nagueh 2016 (p < 0.001) as independent predictors of end-point. The coexistence of an adverse LVR by CRC and DD by Nagueh 2016 was associated with the worst prognosis. A concurrent structural (CRC) and functional (Nagueh Op. Cit) analysis improves prognostic stratification in asymptomatic subjects at risk for HF with preserved EF.