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Aims This study aimed to evaluate a novel echocardiographic algorithm for quantitative estimation of pulmonary artery wedge pressure (PAWP) and pulmonary vascular resistance (PVR) in patients with heart failure and pulmonary hypertension (PH) scheduled to right heart catheterization (RHC). Methods and results In this monocentric study, 795 consecutive patients (427 men; age 68.4 ± 12.1 years) undergoing echocardiography and RHC were evaluated. Multiple regression analysis was performed to identify echocardiographic predictors of PAWP and PVR measured by RHC in the derivation group (the first 200 patients). The diagnostic accuracy of the model was then tested in the validation group (the remaining 595 patients). PH was confirmed by RHC in 507 (63.8%) patients, with 192 (24.2%) cases of precapillary PH, 248 (31.2%) of postcapillary PH, and 67 (8.4%) of combined PH. At regression analysis, tricuspid regurgitation maximal velocity, mitral E/e′ ratio, left ventricular ejection fraction, right ventricular fractional area change, inferior vena cava diameter, and left atrial volume index were included in the model (R = 0.8, P

Evidence of sympathetic and renin-angiotensin-aldosterone system activation provided a rationale for neurohormonal antagonism in heart failure with reduced ejection fraction (HFrEF), while no data are available in patients with milder degree of systolic dysfunction. We aimed to investigate neurohormonal function in HF with preserved and mid-range EF (HFpEF/HFmrEF).Three cohorts (n = 189/each) of stable HFpEF, HFmrEF and HFrEF patients were selected (median age 70, 67 and 67 years; male 56%, 73% and 74%, respectively). Patients received a baseline clinical assessment including plasma renin activity (PRA), aldosterone, catecholamines, and N-terminal fraction of pro-B-type natriuretic peptide (NT-proBNP) assays, and were followed-up for all-cause death.Neuroendocrine profile was similar between HFpEF and HFmrEF, while all neurohormones except epinephrine were higher in HFrEF than in HFmrEF (NT-proBNP 2332 ng/L, IQR 995-5666 vs 575 ng/L, 205-1714; PRA 1.7 ng/mL/h, 0.4-5.6 vs 0.6 ng/mL/h, 0.2-2.6; aldosterone 153 ng/L, 85-246 vs 113 ng/L, 72-177; norepinephrine 517 ng/L, 343-844 vs 430 ng/L, 259-624; all p 0.001, epinephrine 31 ng/L, 10-63 vs 25 ng/L, 10-44; p = 0.319). These findings were unrelated to treatment heterogeneity. Ten percent of HFpEF patients had elevated PRA, aldosterone and norepinephrine vs. 8% in HFmrEF and 21% in HFrEF. During a 5-year follow-up, survival decreased with the number of neurohormones elevated (HFpEF: log-rank 7.8, p = 0.048; HFmrEF: log-rank 11.8, p = 0.008; HFrEF: log-rank 8.1, p = 0.044).Neurohormonal activation is present only in a subset of patients with HFpEF and HFmrEF, and may hold clinical significance. Neurohormonal antagonism may be useful in selected HFpEF/HFmrEF population.

Neurohormonal activation has never been investigated in patients with cardiac amyloidosis (CA). Forty-seven patients with amyloid light-chain (AL)-CA and 61 with transthyretin (ATTR)-CA were matched to non-amyloidotic heart failure (HF) patients based on age, sex, left ventricular ejection fraction ranges, renal function and HF therapies. N-terminal pro-B-type natriuretic peptide (NT-proBNP), norepinephrine and renin were dosed. The primary and secondary endpoints were 1-year cardiovascular death or HF hospitalisation, and 5-year cardiovascular death, respectively. Patients with AL-CA had a 10-fold higher NT-proBNP than HF patients (6548 ng/L [2059���15,097] vs. 692 [243���2241], p p = 0.047). Patients with ATTR-CA had higher NT-proBNP (3984 ng/L [2275���9505] vs. 1751 [470���4768], p = 0.006), norepinephrine (552 ng/L [344���855] vs. 441 [323���601], p = 0.020), and renin (14 mU/L [8���80] vs. 10 [4���34], p = 0.017). Patients with AL- or ATTR-CA had more often 2 or 3 neurohormones above the corresponding upper reference limits than matched HF patients. NT-proBNP and aldosterone were univariate predictors of the primary endpoint in patients with ATTR-CA, but not in matched controls. NT-proBNP and renin predicted the secondary endpoint in patients with AL-CA, but not in matched controls. Patients with CA display a neurohormonal activation, with some prognostic significance.

Amyloidosis is a systemic disorder characterized by extracellular deposition of insoluble fibrils. The most common forms are amyloid light chain and amyloid transthyretin (ATTR) amyloidoses. Cardiac involvement may be found in both these forms, and is an important cause of morbidity and mortality. The clinical presentation of cardiac amyloidosis (CA) may be represented by congestive heart failure (HF), possibly progressing to end-stage HF, as well as atrial fibrillation with possible thromboembolic events, and also conduction disturbances related to amyloid infiltration of conduction fibres. Beyond therapies targeting the blood dyscrasia or the ATTR amyloidogenic cascade, a careful choice of drug therapies, need for device implantation, and possibly treatments for advanced HF is then warranted. In the present review, we try to provide a useful guide to clinicians treating patients with CA by enucleating 10 main questions and answering them based on the evidence available as well as expert opinion and our clinical experience.

Aim Several studies suggest that the N-terminal fragment of pro-brain natriuretic peptide levels are quite different in wild-type transthyretin (TTR)-related amyloidosis (ATTRwt) and mutated TTR-related amyloidosis (ATTRm) compared with immunoglobulin light-chain cardiac amyloidosis. Our aim was to test this hypothesis in a cohort of patients with different types of cardiac amyloidosis. Patients and methods Seventy patients with ATTRwt, ATTRm, and light-chain cardiac amyloidosis matched for left ventricular (LV) mass index were studied by standard echocardiography, tissue Doppler imaging, and plasmatic cardiac biomarkers. Results Despite similar LV mass and renal function, patients with ATTR cardiac amyloidosis showed lower levels of N-terminal fragment of pro-brain natriuretic peptide than do light-chain amyloidosis ones, especially when expressed as a function of LV mass index. Conclusion Amyloidogenic light-chain-derived fibrils induce more severe myocardial dysfunction in light-chain amyloidosis than in ATTR, despite similar myocardial infiltration. Thus, the degree of cardiac dysfunction may be related not only to the amount of amyloid deposited, but also to qualitative differences among fibrils.

Objectives This study aimed to investigate the accuracy of a broad range of echocardiographic variables to develop multiparametric scores to diagnose CA in patients with proven light chain (AL) amyloidosis or those with increased heart wall thickness who had amyloid was suspected. We also aimed to further characterize the structural and functional changes associated with amyloid infiltration. Background Cardiac amyloidosis (CA) is a serious but increasingly treatable cause of heart failure. Diagnosis is challenging and frequently unclear at echocardiography, which remains the most often used imaging tool. Methods We studied 1,187 consecutive patients evaluated at 3 referral centers for CA and analyzed morphological, functional, and strain-derived echocardiogram parameters with the aim of developing a score-based diagnostic algorithm. Cardiac amyloid burden was quantified by using extracellular volume measurements at cardiac magnetic resonance. Results A total of 332 patients were diagnosed with AL amyloidosis and 339 patients with transthyretin CA. Concentric remodeling and strain-derived parameters displayed the best diagnostic performance. A multivariable logistic regression model incorporating relative wall thickness, E wave/e′ wave ratio, longitudinal strain, and tricuspid annular plane systolic excursion had the greatest diagnostic performance in AL amyloidosis (area under the curve: 0.90; 95% confidence interval: 0.87 to 0.92), whereas the addition of septal apical–to–base ratio yielded the best diagnostic accuracy in the increased heart wall thickness group (area under the curve: 0.80; 95% confidence interval: 0.85 to 0.90). Conclusions Specific functional and structural parameters characterize different burdens of CA deposition with different diagnostic performances and enable the definition of 2 scores that are sensitive and specific tools with which diagnose or exclude CA.

Aims To compare the effects of two thrombus aspiration devices, the manual catheter Export® and the more complex and expensive mechanical Angiojet®, on several indices of reperfusion in acute ST-elevation myocardial infarction (STEMI). Methods and results Clinical, hemodynamic and procedural characteristics of 185 STEMI patients, randomized to treatment with Export (n=95) or Angiojet (n=90) during primary percutaneous coronary intervention (PPCI) were analyzed. The primary endpoint was ST-segment elevation reduction 90min after culprit vessel re-opening. Secondary endpoints included variations in some angiographic parameters (TIMI Flow, TIMI Frame Count and Myocardial Blush Grade) and Infarct Size and Severity at myocardial scintigraphy. A significant reduction in ST-elevation was observed in both groups after PPCI without significant differences between the two groups. No significant difference between Angiojet vs. Export was observed in ST-segment resolution >50% and ≥70%, in TIMI Flow, TIMI Frame Count and Myocardial Blush Grade before vs. after PPCI and in Infarct Size and Severity. Conclusions PPCI with thrombus aspiration was effective in both groups of patients, without differences in myocardial reperfusion and necrosis indices. These results could support the routine use of manual devices during PPCI, reserving the more expensive Angiojet in case of manual device failure and persistent or massive intracoronary thrombosis, with favorable implications in terms of cost containment.

Background Few data are so far available on the relation between increased glucose values and insulin resistance and mortality at short-term in patients with acute heart failure (AHF). Methods The present investigation, performed in 409 consecutive patients with AHF complicating acute coronary syndrome (ACS), was aimed at assessing the prognostic role of admission glycaemia and acute insulin resistance (as indicated by the Homeostatic Model Assessment - HOMA index) for death during Intensive Cardiac Care (ICCU) stay. Admission glucose tertiles were considered. Results In our series, diabetic patients accounted for the 33%. Patients in the third glucose tertiles exhibited the lowest LVEF (both on admission and at discharge), a higher use of mechanical ventilation, intra-aortic balloon pump and inotropic drugs and the highest in-ICCU mortality rate. In the overall population, hyperglycaemic patients (both diabetic and non diabetic) were 227 (227/409, 55.5%). Admission glycaemia was an independent predictor of in-ICCU mortality, together with admission LVEF and eGFR, while acute insulin resistance (as indicated by HOMA-index) was not associated with early death. The presence of admission hyperglycaemia in non-diabetic patients was independently associated with in-ICCU death while hyperglycaemia in diabetic patients was not. Conclusions According to our results, hyperglycaemia is a common finding in patients with ACS complicated by AHF and it is an independent predictor of early death. Non-diabetic patients with hyperglycaemia are the subgroup with the highest risk of early death.

Patients' response to dual antiplatelet therapy (DAPT) is subject to variations and its monitoring allows to individualize this therapy. In this study, we evaluated if a strategy of tailored DAPT after platelet function testing could reduce high on-treatment platelet reactivity (HPR) and improve outcome of patients treated with stent implantation. In 257 patients undergoing percutaneous angioplasty, platelet function was measured by light transmittance aggregometry (LTA) using 10 µM/L adenosine-diphosphate (ADP) and 1 mM arachidonic acid (AA) as agonists. Patients with HPR by ADP (≥70%) were switched to double-dose clopidogrel, ticlopidine, prasugrel or ticagrelor; in patients with HPR by AA (≥20%) acetylsalicylic acid dose was increased if not contraindicated. Platelet function analysis was repeated 48 hours after therapy variation. At 20-month follow-up major adverse cardiovascular events (MACE) and bleedings were assessed. HPR was detected in 97/257 (37.7%) patients: 69/257 (26.8%) had HPR by ADP and 71/257 (27.6%) had HPR by AA. In patients with HPR by ADP or by AA, tailored DAPT determined a significant reduction in residual platelet reactivity. No significant difference in MACE or bleeding occurrence was documented in HPR patients treated with tailored DAPT vs. those without HPR. HPR patients treated with tailored DAPT had significant lower follow-up MACE and deaths vs. 139 HPR patients not switched, even after propensity score analysis. These results suggest that a DAPT tailored on platelet testing can improve antiplatelet response in HPR patients, possibly reducing their thrombotic events to a level similar to non-HPR patients, without increasing the risk of bleeding.

Amyloidosis prognosis is often related to the onset of heart failure and a worsening that is concomitant with kidney-liver dysfunction; thus the Model for End-stage Liver disease (MELD) may be an ideal instrument to summarize renal-liver function. Our aim has been to test the MELD score as a prognostic tool in amyloidosis. We evaluated 128 patients, 46 with TTR-related amyloidosis and 82 with AL amyloidosis. All patients had a complete clinical and echocardiography evaluation; overall biohumoral assessment included troponin I, NT-proBNP, creatinine, total bilirubin and INR ratio. The study population was dichotomized at the 12 cut-off level of MELD scores; those with MELD score >12 had a lower survival compared to controls in the study cohort (40.7 vs 66.3 %; p = 0.006). Either as a continuous and dichotomized variable, MELD shows its independent prognostic value at multivariable analysis (HR = 1.199, 95 % CI 1.082-1.329; HR = 2.707, 95 % CI 1.075-6.817, respectively). MELD shows a lower prognostic sensitivity/specificity ratio than troponin I and NT-proBNP in the whole study population and AL subgroup, while in TTR patients MELD has a higher sensitivity/specificity ratio compared to troponin and NT-proBNP (ROC analysis-AUC: 0.853 vs 0.726 vs 0.659). MELD is able to predict prognosis in amyloidosis. A MELD score >12 selects a subgroup of patients with a higher risk of death. The predictive accuracy seems to be more evident in TTR patients in whom currently no effective scoring systems have been validated.

INTRODUCTION The rehospitalization rate for decompensated heart failure (HF) is high and can be ascribed also to a suboptimal decongestion before discharge. Congestion can be treated with diuretics or continuous renal replacement therapy (CRRT). Aim of this study was to evaluate if diuretics and CRRT, used in agreement to international guidelines, may have a dissimilar decongestion ability in patients with decompensated HF with different baseline characteristics. METHODS In 88 patients with HF (NYHA class Ill-IV) we evaluated the effect of CRRT (n = 46) and intravenous diuretics (n = 42) on clinical and instrumental signs of congestion. A clinical score was obtained as the sum of signs and symptoms of HF to estimate the severity of each patient's clinical condition.The choice of diuretics or CRRT was guided by renal impairment or diuretics' resistance. RESULTS A significant reduction in clinical HF score was observed in the CRRT group at discharge vs admission (1.3 +/- 1.9 vs 5.7 +/- 2.3, P < 0.001) and in the diuretic group (1.8 +/- 1.4 vs 3.7 +/- 1.6, P < 0.001), while a significant reduction in radiographic signs of pulmonary congestion, pleural effusion, echocardiographic systolic arterial pulmonary pressure (43.41 +/- 13.6 vs 50.5 +/- 20.2 mmHg, P < 0.005) and NT-proBNP (6,676 vs 15,492 pg/ml, P < 0.05) were observed only in CRRT patients. Moreover, also urine output significantly increased only in CRRT patients (1.8 +/- 0.8 vs 0.9 +/- 0.6 ml/h/kg, P < 0.001). CONCLUSIONS CRRT and diuretics showed an equivalent ability in relieving clinical signs and symptoms of HF but only CRRT was able to significantly improve several instrumental and biohumoral indicators of congestion.

Percutaneous coronary intervention (PCI) requires the use of iodinated contrast medium and consequently poses the risk of contrast-induced nephropathy (CIN), which can negatively impact on outcome. Patients with chronic kidney disease (CKD) are at particularly high risk of CIN. In this study, we investigated the role of continuous renal replacement therapy (CRRT) performed before and after versus only after PCI in patients with CKD.We studied 46 consecutive patients with CKD (mean creatinine2 mg/dL) submitted to PCI: 21 (mean creatinine 2.7 ± 1.6 mg/dL) treated with CRRT only after PCI (CRRTpost) and 25 (mean creatinine 3.0 ± 1.3 mg/dL) with CRRT before and after PCI (CRRTpre-post). CRRT was performed with hemofiltration (creatinine3 mg/dL) or hemodiafiltration (creatinine3 mg/dL), initiated 6-8 hours before PCI and re-started immediately post PCI for 18-24 hours.Creatinine showed a greater reduction in CRRTpre-post (2.4 ± 1.0 vs. 3.0 ± 1.3 mg/dL; P=.002) with respect to CRRTpost (2.6 ± 1.3 vs 2.7 ± 1.6 mg/dL; P=.667). At median 14.7-month follow-up, CKD worsened in 3 patients (12%) of CRRTpre-post and in 9 (43%) of CRRTpost (P=.042). Kaplan-Meier analysis at 18 months showed a significantly higher overall mortality in patients treated with CRRTpre-post vs. CRRTpost (P=.041), which became even more significant during the entire follow-up period (P=.026) and an increase in cardiovascular deaths (5 vs. 0, respectively).Our results suggest that in CKD patients undergoing PCI, CRRT performed before and after is more effective in preventing a further deterioration of renal function and is associated with an improved long-term outcome when compared to CRRT performed only after.

A pivotal role in treating decompensated heart failure (HF) is played by inotropes and calcium sensitizers such as levosimendan. In this study, the authors evaluated whether levosimendan could determine further clinical and hemodynamic benefits in 31 HF patients (New York Heart Association [NYHA] class III or IV), after successful treatment with diuretics (n=15) or ultrafiltration (n=16). Systolic, diastolic, dicrotic, and mean arterial pressures; systemic vascular resistance (SVR); some classic hemodynamic variables (cardiac output [CO], stroke volume [SV], dP/dt(max) ); and indices of cardiovascular system performance (cardiac cycle efficiency [CCE], cardiac power output) have been assessed by the pressure recording analytical method (PRAM), a minimally invasive monitoring system, before levosimendan infusion, at the end of treatment (EoT), and 36 hours after EoT (post-36). A significant increase in CCE, CO, SV, and dP/dt(max) and a significant decrease in diastolic and dicrotic arterial pressures and in SVR have been observed at EoT and at post-36. After the addition of levosimendan, a further reduction in signs and symptoms of HF and NYHA class was observed. Five patients showed an opposite trend of several hemodynamic parameters without any significant clinical improvement (nonresponders). In conclusion, most HF patients treated with diuretics or ultrafiltration receive additional clinical and hemodynamic benefits from levosimendan. The characterization of nonresponders could help in optimizing its use.

In non-ST-elevation acute coronary syndromes (ACS), an early invasive strategy is recommended for middle/high-risk patients; however, the optimal timing for coronary angiography is still debated. The aim of this study was to evaluate the prognostic implications of the time of angiography in ACS patients treated in accord with an early invasive strategy. We analyzed the relationship between the time of angiography and outcomes at follow-up in 517 ACS patients, of whom 482 were revascularized with percutaneous coronary intervention (PCI) (86.9%) or coronary artery by-pass graft (13.1%). We also evaluated the influence of clinical, biohumoral and angiographic variables on the patients' outcomes at follow-up. Among patients submitted to angiography at different time intervals from both hospital admission and symptom onset, significant differences neither in mortality nor in cardiac ischemic events at follow-up were observed. At univariate analysis, complete versus partial revascularization, longer hospital stay, higher TIMI risk score, diabetes mellitus, higher discharge creatinine and admission anemia were associated with mortality and cardiac ischemic events at follow-up; a lower left ventricular ejection fraction was associated with mortality; higher peak troponin I and previous PCI were associated with cardiac ischemic events at follow-up. At multivariate analysis longer hospital stay, higher discharge creatinine levels, and previous PCI were independent predictors of cardiac ischemic events at follow-up. Our evaluation in ACS patients treated with an early invasive strategy does not support the concept that angiography should be performed as soon as possible after symptom onset or hospital admission. Rather, an unfavorable long-term outcome is influenced principally by the clinical complexity of patients.