Search

Idiopathic pulmonary fibrosis (IPF) is a specific form of chronic, progressive, fibrosing interstitial pneumonia of unknown cause that leads to respiratory failure and death within few years of diagnosis. Pulmonary hypertension (PH) is a common complication in IPF, where it is strongly associated with increased morbidity and mortality. Patients with IPF and PH have particularly poor prognosis, despite current best medical therapies and the anti-fibrotic therapy with pirfenidone or nintedanib. The aim of our study was to assess the clinical and prognostic impact of PH in patients affected by IPF, already treated with pirfenidone or nintedanib. Seventy-four consecutive outpatients with a diagnosis of IPF, in therapy with pirfenidone or nintedanib, were prospectively enrolled in the study. All patients underwent pulmonary and cardiology assessment by clinical exam, spirometry, DLCO test, chest CT, 6MWT and echocardiography performed by a cardiologist experienced in PH in an ambulatory setting under resting conditions. GAP index has been determinate for all patients. During follow-up, all patients were evaluated every 6 months, or less if necessary. Data about mortality were then collected in a 3-year follow-up. Of the seventy-four patients enrolled, 38 were treated with pirfenidone and 36 with nintedanib. The two groups were comparable for age, gender, FVC, DLCO and PAPS. The patients were also divided in four groups, based on presence of mild/moderate/severe PH by echocardiography at baseline. Significant differences were found for DLCO and the GAP index. Severity of PH was significantly associated with a reduction of DLCO and with an increased GAP index. Survival was directly correlated with 6MWT (R = 0.48), DLCO (R = 0.29, p

Purpose The use of sodium-glucose-cotransporter-type-2 inhibitors (SGLT2i) was associated in previous studies with an improved vascular function in non-human experimental models. We therefore sought to evaluate possible changes in endothelial function assessed by flow-mediated dilation (FMD) in patients with chronic heart failure (CHF) and type-2 diabetes mellitus (T2DM), switching from other oral hypoglycemic agents to SGLT2i in an observational study. Methods Twenty-two consecutive outpatients with CHF and T2DM were enrolled after switching to SGLT2i therapy, and compared with 23 consecutive controls from the same registry comparable for principal clinical characteristics. In all patients, endothelial function was assessed by FMD at baseline and after 3 months of follow-up. Results Three months of therapy with SGLT2i were associated with a statistically significant improvement in endothelial function (19.0 ± 5.7% vs 8.5 ± 4.1%, p p Conclusions Switch to SGLT2i in patients with CHF and T2DM was associated in an observational non-randomized study with an improved endothelial function.

Background Despite the use of optimal medical therapy, HFrEF remains a leading cause of morbidity, mortality and health care costs. The introduction of angiotensin receptor/neprilysin inhibitors (ARNIs) had a revolutionary impact on the treatment of patients with heart failure and reduced left ventricular ejection fraction (HFrEF). Methods The aim of the study was to monitor over time the perceived quality of life, the physical performance, the trend of BNP and NT-ProBNP and the NYHA functional class in patients with HFrEF during treatment with sacubitril/valsartan. We enrolled 37 patients (63 ± 10 years old, 76% men) who underwent a total of one year follow-up. All patients underwent clinical evaluation, 6MWT, blood analysis (in particular NT-pro-BNP and BNP, renal function test); Kansas City Cardiomyopathy Questionnaire (KCCQ) and the NYHA functional class assessment were also performed, at the beginning of the study and after 3, 6 and 12 months of therapy. Results We observed at each follow-up a significant improvement of KCCQ score, 6MWT, NTProBNP, BNP and of NYHA class. However, analyzing the Δ % of variation of each single parameter, the improvement was not uniform in time. We also observed that only 37% of patients tolerated the full recommended dose of sacubitril/valsartan (97/103 mg b.i.d.); of the remaining, 40% tolerated the intermediate dose (49/51 mg b.i.d.) and 23% the minimum (24/26 md b.i.d.). Conclusions Sacubitril/valsartan therapy improves significantly quality of life, physical effort resistance, BNP and NT-ProBNP and NYHA functional class in patients with HFrEF. Although not all the patients tolerated the maximum recommended dose, the beneficial effects were significant even at lower doses.

Left ventricular (LV) remodelling is a major mechanism underlying disease progression in patients with heart failure (HF) with reduced ejection fraction (EF). Previous studies that LVEF improvement and reverse remodelling can be achieved after therapy with Sacubitril/Valsartan in real-world settings. Therefore, we sought to investigate possible predictors of LV remodelling, in particular echocardiographic parameters derived by Tissue Doppler Imaging.Patients with chronic HF, LV dysfunction (EF35%), NYHA class II-III were followed up between September 2016 and January 2019. All patients underwent clinical and echocardiography follow up at baseline and after 12 months of therapy with sacubitril/valsartan.Fifty-four consecutive outpatients were enrolled in the study. At follow-up visit LVEF (38 ± 9 vs. 30 ± 5%,Treatment with sacubitril/valsartan in patients with systolic dysfunction is associated with an improvement in LVEF in a real world scenario. Smaller LV volumes are associated with better reverse LV remodelling.

Despite recent advances in chronic heart failure (HF) therapy, the prognosis of HF patients remains poor, with high rates of HF rehospitalizations and death in the early months after discharge. This emphasizes the need for incorporating novel HF drugs, beyond the current approach (that of modulating the neurohumoral response). Recently, new antidiabetic oral medications (sodium-glucose cotransporter 2 inhibitors (SGLT2i)) have been shown to improve prognosis in diabetic patients with previous cardiovascular (CV) events or high CV risk profile. Data from DAPA-HF study showed that dapaglifozin is associated with a significant reduction in mortality and HF hospitalization as compared with placebo regardless of diabetes status. Recently, results from EMPEROR-Reduced HF trial were consistent with DAPA-HF trial findings, showing significant beneficial effect associated with empagliflozin use in a high-risk HF population with markedly reduced ejection fraction. Results from the HF with preserved ejection fraction trials using these same agents are eagerly awaited. This review summarizes the evidence for the use of gliflozins in HF treatment.

Rationale: An initial oral combination of drugs is being recommended in pulmonary arterial hypertension (PAH), but the effects of this approach on risk reduction and pulmonary vascular resistance (PVR) are not known.Objectives: To test the hypothesis that a low-risk status would be determined by the reduction of PVR in patients with PAH treated upfront with a combination of oral drugs.Methods: The study enrolled 181 treatment-naive patients with PAH (81% idiopathic) with a follow-up right heart catheterization at 6 months (interquartile range, 144-363 d) after the initial combination of endothelin receptor antagonist + phosphodiesterase-5 inhibitor drugs and clinical evaluation and risk assessments by European guidelines and Registry to Evaluate Early and Long-Term PAH Disease Management scores.Measurements and Main Results: Initial combination therapy improved functional class and 6-minute-walk distance and decreased PVR by an average of 35% (median, 40%). One-third of the patients had a decrease in PVR

Heart failure is a complex syndrome affecting several organs including kidney, lungs, liver, brain muscles and sympathetic system. Each of these organs might contribute to its severity and prognosis. The prognosis assessment is critical for a correct heart failure management. It has already been demonstrated that a single parameter is weaker for prognosis than different parameters combined. The Metabolic Exercise test data combined with Cardiac and Kidney Indexes (MECKI) score has been built and validated for heart failure with reduced ejection fraction (HFrEF) patients by considering cardiopulmonary exercise test data combined with clinical, laboratory and echocardiographic measurements. The betablockers treatment is a milestone in the HFrEF management. In the MECKI score database, the association of betablockers treatment with outcome has been investigated in different settings.

BACKGROUND: Upfront combination therapy with ambrisentan and tadalafil has been reported to improve the condition of patients with pulmonary arterial hypertension (PAH) more than with either drug alone. However, little is known about the long-term associated changes in hemodynamics and risk assessment scores. METHODS: This was a multicenter, retrospective analysis of clinical data in 106 patients with newly diagnosed PAH. Clinical evaluations, including demographics, medical history, World Health Organization (WHO) functional class (FC) and 6-minute walk distance (6MWD), right heart catheterization, and Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL) risk score 2.0, were assessed over 48 months of ambrisentan‒tadalafil therapy. RESULTS: At baseline, 9 patients (9%) showed a low (8) REVEAL risk score. At a median follow-up of 2 years, 45 patients (43%) showed a low, 47 patients (44%) showed an intermediate, and 14 patients (13%) showed a high REVEAL score, along with improvements in WHO FC, 6MWD and a decrease in mean pulmonary artery pressure and N-terminal pro brain natriuretic peptide (all p < 0.001). Pulmonary vascular resistance (PVR) decreased by 37% from 11.5 ± 6.5 to 7.2 ± 4.1 Wood units (p < 0.001). A total of 61 patients (57%) remained in intermediate-risk or high-risk categories. Low-risk patients had either a decrease in PVR of >50% or a stroke volume within the limits of normal. CONCLUSIONS: Initial combination therapy with ambrisentan and tadalafil in PAH improves the REVEAL risk score in proportion to decreased PVR and preserved stroke volume but still insufficiently so in approximately 50% of the patients.

Renin-angiotensin-aldosterone system (RAAS) inhibition is a mainstay of the pharmacological treatment of heart failure with reduced ejection fraction (HFrEF). In the last years RAAS blockade has been improved by the introduction of the Angiotensin Receptor-Neprilysin Inhibitor (ARNI) sacubitril/valsartan, that combines RAAS inhibition with the block of neprilysin, boosting the positive effects of natriuretic peptides. The PARADIGM-HF trial demonstrated a significant advantage of sacubitril/valsartan over enalapril on the reduction of cardiovascular (CV) mortality and heart failure hospitalizations rates. Then, several randomized clinical trials and observational studies investigated its role in different clinical settings and its efficacy has been fully recognized in the most recent HFrEF European and USA guidelines. The effects of sacubitril/valsartan on major CV outcomes are associated with reduction of NT-proBNP levels and reverse cardiac remodeling and mitral regurgitation, recognized as one of the mechanistic effects of the drug explaining the favorable prognostic effects. A careful evaluation of patients' clinical profile is relevant to implement the use of ARNI in the clinical practice and to obtain the maximal treatment efficacy. The present Position Paper reports the opinion of the Italian Society of Cardiology on the optimal blockade of the RAAS system in HF patients with the aim of fostering widespread implementation of scientific evidence and practice guidelines in the medical community.

BACKGROUND Right heart catheterization (RHC) is recommended by guidelines for the diagnosis of pulmonary hypertension, the definition of hemodynamic impairment and responsiveness to drug therapy. However, RHC is an invasive test with associated risk of complications. Noninvasive echocardiographic tools, possibly predictive of pulmonary hypertension at RHC, could be therefore extremely useful. METHODS Sixty-four consecutive patients with suspected pulmonary hypertension were enrolled in the study and assessed by echocardiography and RHC. Diagnosis of pulmonary hypertension was based on mean pulmonary artery pressure (≥25 mmHg) at RHC. RESULTS Of 64 consecutive patients enrolled, 77% were diagnosed as having pulmonary hypertension after RHC. On the basis of significant differences between patients with pulmonary hypertension at RHC and those without on echocardiographic assessment, a multiple logistic regression model was constructed to predict the presence of pulmonary hypertension at RHC. The score was calculated using right atrium and ventricular diastolic area, tricuspid regurgitation Vmax, tricuspid regurgitation severity degree and left ventricular ejection fraction. The score area under the curve was therefore 0.786 (P = 0.0001), higher than for tricuspid regurgitation Vmax (P = 0.06). A score value more than 57 was associated with a 93% sensitivity, a 67% specificity, a 91% positive predictive power, a 73% negative predictive power, and an odds ratio 27 (P

Background Sacubitril/valsartan changed the treatment of heart failure with reduced ejection fraction (HFrEF), due to the positive effects morbidity and mortality partly mediated by left ventricular reverse remodeling (LVRR). The aim of this multicenter study was to identify echocardiographic predictors of LVRR after sacubitril/valsartan administration. Methods Patients with HFrEF requiring therapy with sacubitril/valsartan from 13 Italian centers were included. Echocardiographic indexes including speckle tracking echocardiography (STE) were used to predict LVRR (defined as LV end-systolic volume reduction and ejection fraction [LVEF] improvement >10% at follow-up) at 6 months follow-up as the primary endpoint. Changes in symptoms (NYHA class) and neurohormonal activations (N-terminal-pro-brain natriuretic peptide [NTproBNP]) were also evaluated as secondary endpoints. Patients with poor acoustic windows and missing data were excluded. Results The final population consisted of 341 patients (mean age: 65±10 years; 18% female, median LVEF 30% [interquartile range:25; 34]. At 6 months follow-up, cardiac dimensions and function, including left heart STE parameters, improved (Table 1). Moreover, 82 (24%) patients showed early complete response (LVRR and LVEF ≥35%), 55 (16%) early incomplete response (LVRR and LVEF −9.3% showed a good accuracy in predicting LV RR (Figure 1). LA strain was the best predictor of positive changes in NYHA class and NT-proBNP (all p Conclusions STE parameters at baseline could be useful to predict LVRR and early clinical response to sacubitril-valsartan, and thus could be used as a guide for treatment in patients with HFrEF. Funding Acknowledgement Type of funding sources: None. Table 1Figure 1

BACKGROUND Observational studies have demonstrated that treatment with sacubitril/valsartan may improve left ventricular (LV) systolic and diastolic function in subjects with reduced LV ejection fraction (LVEF) in real-world studies. Subjects with heart failure and reduced EF (HFrEF), however, are also characterized by an impaired right ventricular (RV) function. We therefore aimed to evaluate whether also RV function may improve after S/V therapy and possible predictors of RV improvement could be identified at echocardiography and tissue Doppler imaging. METHODS Fifty consecutive patients (67 ± 8 years, LVEF 28 ± 6%, male 86%) with chronic HFrEF and NYHA class II-III were followed up for 6 months after therapy with S/V. LV&RV function was assessed at baseline and after 6 months of therapy. RESULTS After 6-month therapy with S/V a significant improvement was shown in the following echocardiography parameters assessing RV function: PAsP (31 ± 11 vs. 35 ± 10 mmHg, p

Aims: Exercise oscillatory ventilation (EOV) is a pivotal cardiopulmonary exercise test parameter for the prognostic evaluation of patients with chronic heart failure (HF). It has been described in patients with HF with reduced ejection fraction (50%, HFpEF), but no data are available for patients with HF with mid-range ejection fraction (40–49%, HFmrEF). The aim of the study was to evaluate the prognostic role of EOV in HFmrEF patients. Methods and results: We analysed 1239 patients with HFmrEF and 4482 patients with HFrEF, enrolled in the MECKI score database, with a 2-year follow-up. The study endpoint was the composite of cardiovascular death, urgent heart transplant, and ventricular assist device implantation. We identified EOV in 968 cases (16% and 17% of cases in HFmrEF and HFrEF,. respectively). HFrEF EOV+ patients were significantly older, and their parameters suggested a more severe HF than HFrEF EOV− patients. A similar behaviour was found in HFmrEF EOV+ vs. EOV− patients. Kaplan–Meier analysis, irrespective of ejection fraction, showed that EOV is associated with a worse survival, and that patients with HFrEF and HFmrEF EOV+ had a significantly worse outcome than the EOV− of the same ejection fraction groups. EOV-associated survival differences in HFmrEF patients started after 18 months of follow-up. Conclusion: Exercise oscillatory ventilation has a similar prevalence and ominous prognostic value in both HFmrEF and HFrEF patients, indicating a group of patients in need of a more intensive follow-up and a more aggressive therapy. In HFmrEF, the survival curves between EOV+ and EOV− patients diverged only after 18 months.

Aims: Exercise-derived parameters, specifically peak exercise oxygen uptake (peak VO2) and minute ventilation/carbon dioxide relationship slope (VE/VCO2 slope), have a pivotal prognostic value in heart failure (HF). It is unknown how the prognostic threshold of peak VO2 and VE/VCO2 slope has changed over the last 20 years in parallel with HF prognosis improvement. Methods and results: Data from 6083 HF patients (81% male, age 61 ± 13 years), enrolled in the MECKI score database between 1993 and 2015, were retrospectively analysed. By enrolment year, four groups were generated: group 1 1993–2000 (n = 440), group 2 2001–2005 (n = 1288), group 3 2006–2010 (n = 2368), and group 4 2011–2015 (n = 1987). We compared the 10-year survival of groups and analysed how the overall risk (cardiovascular death, urgent heart transplantation, or left ventricular assist device implantation) changed over time according to peak VO2 and VE/VCO2 slope and to major clinical and therapeutic variables. At 10 years, a progressively higher survival from group 1 to group 3 was observed, with no further improvement afterwards. A 20% risk for peak VO2 15 mL/min/kg (95% confidence interval 16–13), 9 (11–8), 4 (4–2) and 5 (7–4) was observed in group 1, 2, 3, and 4, respectively, while the VE/VCO2 slope value for a 20% risk was 32 (37–29), 47 (51–43), 59 (64–55), and 57 (63–52), respectively. Conclusions: Heart failure prognosis improved over time up to 2010 in a HF population followed by experienced centres. The peak VO2 and VE/VCO2 slope cut-offs identifying a definite risk progressively decreased and increased over time, respectively. The prognostic threshold of peak VO2 and VE/VCO2 slope must be updated whenever HF prognosis improves.

The usefulness of β-blockers in heart failure (HF) patients with permanent atrial fibrillation (AF) has been questioned. Background: The usefulness of β-blockers in heart failure (HF) patients with permanent atrial fibrillation (AF) has been questioned. Methods and results: We analyzed data from HF patients (958 patients (801 males, 84%, age 67 ± 11 years)) with AF enrolled in the MECKI score database. We evaluated prognosis (composite of cardiovascular death, urgent heart transplant, or left ventricular assist device) of patients receiving β-blockers (n = 777, 81%) vs. those not treated with β-blockers (n = 181, 19%). We also analyzed the role β1-selectivity and the role of daily β-blocker dose. To account for different HF severity, Kaplan-Meier survival curves were normalized for relevant confounding factors and for treatment strategies. Dose was available in 629 patients. Median follow-up was 1312 (577–2304) days in the entire population, 1203 (614–2420) and 1325 (569–2300) days in patients not receiving and receiving β-blockers. 224 (23%, 54/1000 events/year), 163 (21%, 79/1000 events/year), and 61 (34%, 49/1000 events/year) events were recorded, respectively. At 10-year patients treated with β-blockers had a better outcome (HR 0.447, p < 0.01) with no effects as regards β1selective drugs (53%) vs. β1-β2 blockers (47%). Survival improved in parallel with β-blocker dose increase (HR 0.296, 0.496, 0.490 for the high, medium, and low dose vs. no β-blockers, p < 0.0001). Conclusion: HF patients with AF taking a β-blocker have a better outcome (with a survival improvement in parallel with daily dose but no differences as regards β1 selectivity) but this does not mean that β-blockers improve outcomes in these patients as we cannot control for all the potential confounders associated with β-blocker use.

Patients affected by heart failure with reduced ejection fraction (HFrEF) receive clinical and functional beneficial effects from treatment with sacubitril/valsartan. However previous studies have shown that patients with an implantable cardioverter defibrillator (ICD) could obtain even greater benefit, but only make up a only a small proportion of patients. In the current study we evaluated the effect of sacubitril/valsartan in patients with an ICD. Thirty-five outpatients with HFrEF (aged 60 ± 11 years, 28 were males), on optimal medical therapy were studied. All patients received an ICD at least 6 months before enrollment or were non-responders to ICD plus resynchronization (CRT-D). An open-label sacubitril/valsartan treatment was established at the maximum tolerated dose. Clinical assessment, 6-min walk test (6MWT) and echocardiography, were performed during follow-up at 90, 180, and 360 days. Quality of life score and perceived fatigue on exercise were assessed. Clinical conditions dramatically improved in most patients, especially within the first 6 months of therapy (76 % were in NYHA-I and 24 % in NYHA-II at the end of study vs 71 % NYHA-II and 29 % NYHA III at enrollment, p < 0.001). Quality of life and exercise performance significantly improved according to N-terminal pro-brain natriuretic peptide (NT-proBNP) serum levels lowering. Walking distance at 6MWT increased from 274 ± 97 to 389 ± 53 m and walking speed from 0.74 ± 0.27 to 1.07 ± 0.15 m/s (p < 0.001), while oxygen saturation did not differ significantly (from 90 ± 1 % to 91 ± 2 %). More gradual was left ventricular reverse remodeling. Ejection fraction improved mildly (+ 5 points %, p < 0.001). Global longitudinal strain and diastolic function were also assessed over time. Sacubitril/valsartan therapy for HFrEF may lead to significant clinical and functional improvements even in patients with ICD at greater arrhythmic risk. Clinical improvement is obtained within the first 6 months of treatment while reverse remodeling needs more time.

The authors regret that the Author Dr. Bussotti Maurizio appears with the following affiliation: Unità Operativa Cardiologia Riabilitativa, Multimedica IRCCS, Milano, Italy. But that was a mistake, the right affiliation of Dr. Bussotti Maurizio is instead: Department of Cardiology, Istituti Clinici Scientifici Maugeri IRCCS, Milano, Italy. The authors kindly ask you to correct this affiliation also with all abstracting partners as PubMed. The authors would like to apologise for any inconvenience caused. DOI of original article: .

Background In pulmonary arterial hypertension (PAH) upfront oral therapy represents the standard of care for naive patients at low and intermediate risk. However little is known about associated changes in risk assessment and prediction of low risk status achievement. Purpose To evaluate determinants of PVR reduction in patients treated with upfront oral therapy and to create a score to predict PVR reduction after upfront oral treatment and compared its additive value on top of the European and REVEAL scoring system in predicting treatment response. Methods One-hundred-eighty-one consecutive naive PAH patients treated with upfront therapy at 11 italian centers were retrospectively evaluated. Evaluation included clinical, hemodynamic and simple echocardiographic parameters, together with European and REVEAL 2.0 risk scores. Results At the time of diagnosis, the majority of the patients was idiopathic PAH (80.6%), female (66.3%), at intermediate risk, 71.8% and 55.2%, respectively, according to the European (average method) and the REVEAL 2.0 risk scores. Ambrisentan-Tadalafil was the most frequent combination used (62%). The median PVR reduction obtained after 180 days (IQR 79–394) was −40.4% (IQR −25.8; −45.3). Age ≥60 years, male-sex, baseline mPAP 48 mmHg associated with low CI (1 associated with low TAPSE ( At second evaluation 78 (43.1%) patients achieved or remained at European-derived low risk status, while 63 (34.8%) considering the REVEAL 2.0 score. Multivariate analysis for the prediction of treatment failure, defined as the absence of low-risk status at follow-up, demonstrated the incremental prognostic power of the models incorporating the treatment response score (≥3) on top of the European and REVEAL 2.0 scores, improving risk discrimination by 63.2% (IDI index 0.056) and 36.8% (IDI index 0.080), respectively. Conclusions A significant proportion of PAH patients treated with upfront oral combination are not able to achieve a low-risk status. The treatment response score helps clinicians in predicting treatment failure at the time of diagnosis. Funding Acknowledgement Type of funding source: None

Background: Dual antiplatelet therapy and anticoagulants may be required in the case of coexistence of coronary artery disease and atrial fibrillation (AF) undergoing (PCI), with associated increased bleeding rates. The introduction of direct oral anticoagulants (DOACs), however, significantly reduced the incidence of bleeding complications in this clinical setting of patients. We therefore sought to assess whether the recent publication of the AUGUSTUS and ENTRUST-AF PCI studies significantly impacted current evidence on the use of DOACs in AF patients treated with PCI. Methods: We performed a meta-analysis of randomized controlled studies enrolling patients with nonvalvular AF undergoing PCI. We assessed pooled estimates of risk ratios (RRs) and 95%CIs for any bleeding (AB), cardiovascular events (CVE), and death at follow-up: 12,542 patients have been included in the analysis. We particularly analyzed data comparing dual anti-thrombotic therapy (DOAC plus single anti-platelet therapy) with triple (DOAC plus dual anti-platelet therapy). Results: When compared with patients receiving standard triple therapy with warfarin, patients receiving DOACs had a significantly lower risk of AB (RR 0.65; 95% CI, 0.61–0.70, p

Chronic heart failure (CHF) is characterized by higher rates of atrial fibrillation (AF) and endothelial dysfunction (ED). First line anticoagulant therapy in AF is represented by direct oral anticoagulants (DOACs); several patients, however, are still treated with vitamin-K inhibitors. The use of DOACs is associated in previous studies with an improved vascular function. We therefore sought to evaluate possible changes in endothelial function assessed by flow-mediated dilation (FMD) in patients with CHF and AF shifting from warfarin to DOACs.Forty-three consecutive outpatients were enrolled in the study. FMD was assessed at baseline and after 4 months. Patients were compared according to AC therapy.After the first measurement of FMD, 18 patients "switched" to DOACs because of poor compliance to warfarin therapy or time in therapeutic range, 19 patients continued to use DOACs, 6 warfarin. "Switched" patients to DOACs therapy showed an improved FMD (19.0 ± 6.6% vs 3.8 ± 1.3%, p 0.0001); C-reactive protein (CRP) levels decreased in "switched" patients from 1.4 ± 0.5 to 1.0 ± 0.7 mg/dl (p 0.05). FMD and CRP changes were not significant in patients who did not changed anticoagulant therapy. In switched patients, changes in CRP levels were proportional to FMD changes (r = -0.50, p 0.05). Shifting from warfarin to DOACs was significantly correlated to improved FMD levels even at multivariable analysis (p 0.05).Switch from warfarin to DOACs in patents with CHF and AF was associated in an observational non randomized study with an improved endothelial function. Changes in FMD values were related to changes in CRP levels.

Introduction Several systemic conditions, inflammatory disease, infections and alcoholism, may affect both the heart and the liver. Common conditions, such as the non-alcoholic fatty liver disease (NAFLD), may increase the risk of cardiac dysfunction. Patients with acute decompensated HF (ADHF) may develop acute ischemic hepatitis and, chronic HF patients may develop congestive hepatopathy (CH). Evidence acquisition Laboratory anomalies of hepatic function may predict the outcome of patients with advanced HF and the evaluation of both cardiac and hepatic function is very important in the management of these patients. In clinically apparent ischemic hepatitis more than 90% of patients have some right-sided HF. There are systemic disorders characterized by the accumulation of metals or by metabolism defects that may affect primarily the liver but also the heart leading to symptomatic hypertrophic cardiomyopathy (HCM). Evidence synthesis Abnormal LFTs indicate the mechanism of liver injury: liver congestion or liver ischemia. In AHF, it's important an adequate evaluation of heart and liver function in order to choose the treatment in order to ensure stable hemodynamic as well as optimal liver function. Conclusions Measurements of LFTs should be recommended in the early phase of ADHF management. Physicians with interest in HF should be trained in the evaluation of LFTs. It's very important for cardiologists to know the systemic diseases affecting both heart and liver and the first imaging or laboratory findings useful for a diagnosis. it is very important for internists, nephrologists, cardiologists, primary physicians and any physicians with interest in treating HF to recognize such signs and symptoms belong to rare diseases and liver diseases that could be mistaken for HF.

Catheter ablation (CA) of atrial fibrillation (AF) is an important rhythm control strategy for patients with drug-refractory AF. We aimed to perform an updated meta-analysis of direct oral anticoagulants (DOACs) vs vitamin K antagonists (VKAs) as uninterrupted anticoagulation in patients undergoing AF ablation to assess safety and efficacy of DOAC, after the publication of recent data on edoxaban in CA of AF. We performed a meta-analysis of RCTs enrolling patients undergoing AF ablation. We assessed Mantel-Haenszel pooled estimates of risk ratios (RRs) and 95% CIs for thromboembolic events, major bleeding (MB), and non-major bleeding (NMB). A total of 2118 patients have been included in the analysis. Compared with patients receiving VKA, patients receiving DOACs had a lower, although non-significant, risk of thromboembolic events (RR, 0.40; 95% CI, 0.09–1.76; P = 0.23). MB rates in patients treated with DOACs were statistically significantly lower than VKA (RR, 0.61; 95% CI, 0.39–0.93, P = 0.02). The incidence of NMB was not significantly different (RR, 0.98; 95% CI, 0.83–1.57, p n.s.). In a meta-analysis of RCTs, an uninterrupted DOACs strategy for CA of AF appears to be superior to uninterrupted VKA in terms of safety; a non-significant trend favoring DOACs in terms of efficacy is also evident.

The increasing number of patients with heart failure HF and comorbidities is due to aging population and increase of life expectancy of patients with cardiovascular disease. Encouraging results derived by recent trials may suggest some comorbidities as new targets for new drugs, highlighting the need for a better understanding of the comorbidities’ effects in HF patients and the need of a multidisciplinary approach for the management of chronic HF with comorbidities. We report a brief review about main cardiovascular and non-cardiovascular comorbidities in HF patients in order to update physicians and researchers engaged in the HF research or in “fight against heart failure.”

Background Heart failure with midrange ejection fraction (HFmrEF) represents a heterogeneous category where phenotype, as well as prognostic assessment, remains debated. The present study explores a specific HFmrEF subset, namely those who recovered from a reduced EF (rec-HFmrEF) and, particularly, it focuses on the possible additive prognostic role of cardiopulmonary exercise testing. Methods and Results We analyzed data from 4535 patients with HFrEF and 1176 patients with rec-HFmrEF from the Metabolic Exercise combined with Cardiac and Kidney Indexes database. The end point was cardiovascular death at 5 years. The median follow-up was 1343 days (25th–75th range 627–2403 days). Cardiovascular death occurred in 552 HFrEF and 61 rec-HFmrEF patients. The multivariate analysis confirmed an independent role of the MECKI score's variables in HFrEF (C-index = 0.744) whereas, in the rec-HFmrEF group, only age and peak oxygen uptake (pVO2) remained associated to the end point (C-index = 0.745). A peak oxygen uptake of ≤55% of predicted and a ventilatory efficiency of ≥31 resulted as the most accurate cut-off values in the outcome prediction. Conclusions: Present data support the cardiopulmonary exercise test and, particularly, the peak oxygen uptake, as a useful tool in the rec-HFmrEF prognostic assessment. A peak VO2 of ≤55% predicted and ventilatory efficiency of ≥31 might help to identify a high-risk rec-HFmrEF subgroup.

Background: Hyperuricemia prognostic impact on clinical outcomes in chronic heart failure (HF) patients has been investigated with inconclusive results. Objectives: Aim of the study was to evaluate the prognostic impact of serum uric acid (SUA) on long-term clinical outcomes in HF. Methods: An analysis of MECKI (Metabolic Exercise Cardiac Kidney Index) database, with median follow-up of 3.4 years. Results: Relation between SUA and all-cause/ cardiovascular (CV) deaths have been analysed in 4,577 patients (3,688 males, age 62.7 ± 12.9 years), with reduced ejection fraction HF (35 ± 11%), peakVO2 1151 ± 440 ml/min; NYHA class I-II (72.6%), III-IV (27.4%). SUA was associated with increased total and CV mortality (HR 1.120 and HR 1.128, respectively p < 0.0001), also after adjustment for peakVO2, VE/VCO2 slope, diuretic use and MECKI score. SUA was significantly associated with CV mortality only in NYHA class I-II (HR 1.17, p < 0.0001) while there was no association in class III-IV (HR 1.03, p = NS). No prognostic added values of SUA with respect to the MECKI score was observed at the ROC analysis. Conclusions: SUA is confirmed to be associated with increased mortality, but in less severe HF only. However SUA did not show additional prognostic power to the MECKI score

The right ventricle has become increasingly studied in cardiovascular research. In this article, we describe specific pathophysiological characteristics of the right ventricle, with special focus on functional and molecular modifications as well as therapeutic strategies in right ventricular dysfunction, underlining the differences with the left ventricle. Then we analyze the main imaging modalities to assess right ventricular function in different clinical settings. Finally, we acknowledge main therapeutic advances for treatment of right heart diseases.

Pulmonary arterial hypertension, a disease largely neglected until a few decades ago, is presently the object of intense studies by several research teams. Despite considerable progress, pulmonary arterial hypertension remains a major clinical problem, because it is not always easy to diagnose, treat, and prevent. The disease was considered incurable until the late 1990s, when Epoprostenol was introduced as the first tool against this illness. More recently, therapy for pulmonary arterial hypertension gained momentum after publication of the SERAPHIN and AMBITION trials, which also highlighted the importance of upfront therapy. This review also focuses on recent substudies from these trials and progress in drugs targeting the endothelin pathway. Future perspectives with regard to endothelin-receptor antagonists are also discussed.

Background In idiopathic pulmonary arterial hypertension (IPAH) treatment goals include improving right ventricular (RV) function, hemodynamics and symptoms to move patients to a low-risk category for adverse clinical outcomes. No data are available on the effect of upfront combination therapy on RV improvement as compared with monotherapy. The aim of this study was to evaluate echocardiographic RV morphology and function in patients affected by IPAH and treated with different strategies. Methods Sixty-nine consecutive, treatment-naive IPAH patients treated with first-line upfront combination therapy at 10 centers were retrospectively evaluated and compared with 2 matched cohorts treated with monotherapy after short-term follow-up. Evaluation included clinical, hemodynamic and echocardiographic parameters. Results At 155 ± 65 days after baseline evaluation, patients in the oral+prostanoid group (Group 1) had the most clinical and hemodynamic improvement compared with the double oral group (Group 2), the oral monotherapy group (Group 3) and the prostanoid monotherapy group (Group 4). The more extensive reduction of pulmonary vascular resistance in Groups 1, 2 and 4 was associated with significant improvement in all RV echocardiographic parameters compared with Group 3. Considering the number of patients who reached the target goals suggested by established guidelines, 8 of 27 (29.6%) and 7 of 42 (16.7%) patients in Groups 1 and 2, respectively, achieved low-risk status, as compared with 2 of 69 (2.8%) and 6 of 27 (22.2%) in Groups 3 and 4, respectively. Conclusions In advanced treatment-naive IPAH patients, an upfront combination therapy strategy seems to significantly improve hemodynamics and RV morphology and function compared with oral monotherapy. The most significant results seem to be achieved with prostanoids plus oral drug, whereas the use of the double oral combination and prostanoids as monotherapy seem to produce similar results.

AIMS Mineralocorticoid receptor antagonists (MRAs) have been demonstrated to improve outcomes in reduced ejection fraction heart failure (HFrEF) patients. However, MRAs added to conventional treatment may lead to worsening of renal function and hyperkalaemia. We investigated, in a population-based analysis, the long-term effects of MRA treatment in HFrEF patients. METHODS AND RESULTS We analysed data of 6046 patients included in the Metabolic Exercise Cardiac Kidney Index score dataset. Analysis was performed in patients treated (n = 3163) and not treated (n = 2883) with MRA. The study endpoint was a composite of cardiovascular death, urgent heart transplantation, or left ventricular assist device implantation. Ten years' survival was analysed through Kaplan-Meier, compared by log-rank test and propensity score matching. At 10 years' follow-up, the MRA-untreated group had a significantly lower number of events than the MRA-treated group (P

In their clinical practice, physicians can face heart diseases (chronic or acute heart failure) affecting the liver and liver diseases affecting the heart. Systemic diseases can also affect both heart and liver. Therefore, it is crucial in clinical practice to identify complex interactions between heart and liver, in order to provide the best treatment for both. In this review, we sought to summarize principal evidence explaining the mechanisms and supporting the existence of this complicate cross-talk between heart and liver. Hepatic involvement after heart failure, its pathophysiology, clinical presentation (congestive and ischemic hepatopathy), laboratory and echocardiographic prognostic markers are discussed; likewise, hepatic diseases influencing cardiac function (cirrhotic cardiomyopathy). Several clinical conditions (congenital, metabolic and infectious causes) possibly affecting simultaneously liver and heart have been also discussed. Cardiovascular drug therapy may present important side effects on the liver and hepato-biliary drug therapy on heart and vessels; post-transplantation immunosuppressive drugs may show reciprocal cardio-hepatotoxicity. A heart-liver axis is drafted by inflammatory reactants from the heart and the liver, and liver acts a source of energy substrates for the heart.

Aims Risk stratification in heart failure (HF) is crucial for clinical and therapeutic management. A multiparametric approach is the best method to stratify prognosis. In 2012, the Metabolic Exercise test data combined with Cardiac and Kidney Indexes (MECKI) score was proposed to assess the risk of cardiovascular mortality and urgent heart transplantation. The aim of the present study was to compare the prognostic accuracy of MECKI score to that of HF Survival Score (HFSS) and Seattle HF Model (SHFM) in a large, multicentre cohort of HF patients with reduced ejection fraction. Methods and results We collected data on 6112 HF patients and compared the prognostic accuracy of MECKI score, HFSS, and SHFM at 2- and 4-year follow-up for the combined endpoint of cardiovascular death, urgent cardiac transplantation, or ventricular assist device implantation. Patients were followed up for a median of 3.67 years, and 931 cardiovascular deaths, 160 urgent heart transplantations, and 12 ventricular assist device implantations were recorded. At 2-year follow-up, the prognostic accuracy of MECKI score was significantly superior [area under the curve (AUC) 0.781] to that of SHFM (AUC 0.739) and HFSS (AUC 0.723), and this relationship was also confirmed at 4 years (AUC 0.764, 0.725, and 0.720, respectively). Conclusion In this cohort, the prognostic accuracy of the MECKI score was superior to that of HFSS and SHFM at 2- and 4-year follow-up in HF patients in stable clinical condition. The MECKI score may be useful to improve resource allocation and patient outcome, but prospective evaluation is needed.

Aims: The use of β-blockers represents a milestone in the treatment of heart failure with reduced ejection fraction (HFrEF). Few studies have compared β-blockers in HFrEF, and there is little data on the effects of different doses. The present study aimed to investigate in a large database of HFrEF patients (MECKI score database) the association of β-blocker treatment with a composite outcome of cardiovascular death, urgent heart transplantation or left ventricular assist device implantation, addressing the role of β-selectivity and dosage regimens. Methods and results: In 5242 HFrEF patients, we investigated the role of: (i) β-blocker treatment vs. non-β-blocker treatment, (ii) β1-/β2-receptor-blockers vs. β1-selective blockers, and (iii) daily β-blocker dose. Patients were followed for 3.58 years, and 1101 events (18.3%) were observed; 4435 patients (86.8%) were on β-blockers, while 807 (13.2%) were not. At 5 years, β-blocker-patients showed a better outcome than non-β-blocker-subjects [hazard ratio (HR) 0.48, P 2 5 mg carvedilol equivalent daily dose, n = 1005) patients than in both medium dose (12.5–25 mg, n = 1431) and low dose (

We report the case of 63-year-old man, complaining of dyspnea and with abnormal systolic motion of the interventricular septum at echocardiography, referred for coronary angiography and suspect coronary artery disease. In the presence of normal coronary angio, a specific work-up showed chronic thromboembolic pulmonary hypertension requiring pulmonary endarterectomy. The case highlights the need for a global cardiovascular and imaging approach in presence of poorly specific symptoms and signs of coronary artery disease.

BackgroundCardiopulmonary exercise testing allows the assessment of integrative cardiopulmonary response to exercise.AimsThe aim of the study was to better understand the exercise physiology in pulmonary arterial hypertension related to adult congenital heart disease compared to non-adult congenital heart disease patients by means of cardiopulmonary exercise testing parameters.MethodsThe present is a multicentre retrospective study which includes pulmonary hypertension group 1 and group 4 patients. All subjects underwent full clinical and instrumental evaluation, including cardiopulmonary exercise testing and right heart catheterization.ResultsOne hundred and sixty-seven pulmonary hypertension patients (93 women and 74 men, 57 adult congenital heart disease and 110 non-adult congenital heart disease) were enrolled. Adult congenital heart disease patients had higher pulmonary pressure (mean pulmonary arterial pressure: 59.8 ± 19.5 mmHg vs 44.6 ± 16.5 mmHg, p ConclusionsIn pulmonary arterial hypertension-adult congenital heart disease patients, pulmonary pressure and ventilation/carbon dioxide elimination slope are higher compared to non-adult congenital heart disease pulmonary hypertension patients, while pulmonary blood flow and peak oxygen uptake are lower. After matching patients for gender and peak oxygen uptake, pulmonary pressure and ventilation/carbon dioxide elimination remain higher in adult congenital heart disease patients suggesting that the long-term adaptation to high pulmonary pressure, hypoxia and low pulmonary blood flow, as well as a persisting shunt has, at least partially, preserved exercise performance of pulmonary arterial hypertension-adult congenital heart disease patients.

Aims Obesity has been found to be protective in heart failure (HF), a finding leading to the concept of an obesity paradox. We hypothesized that a preserved cardiorespiratory fitness in obese HF patients may affect the relationship between survival and body mass index (BMI) and explain the obesity paradox in HF. Methods and results A total of 4623 systolic HF patients (LVEF 31.5 ± 9.5%, BMI 26.2 ± 3.6 kg/m2) were recruited and prospectively followed in 24 Italian HF centres belonging to the MECKI Score Research Group. Besides full clinical examination, patients underwent maximal cardiopulmonary exercise test at study enrolment. Median follow-up was 1113 (553–1803) days. The study population was divided according to BMI ( 30 to ≤35 kg/m2) and predicted peak oxygen consumption (peak VO2, 80%). Study endpoints were all-cause and cardiovascular deaths including urgent cardiac transplant. All-cause and cardiovascular deaths occurred in 951 (28.6%, 57.4 per person-years) and 802 cases (17.4%, 48.4 per 1000 person-years), respectively. In the high BMI groups, several prognostic parameters presented better values [LVEF, peak VO2, ventilation/carbon dioxide slope, renal function, and haemoglobin (P < 0.01)] compared with the lower BMI groups. Both BMI and peak VO2 were significant positive predictors of longer survival: both higher BMI and peak VO2 groups showed lower mortality (P < 0.001). At multivariable analysis and using a matching procedure (age, gender, LVEF, and peak VO2), the protective role of BMI disappeared. Conclusion Exercise tolerance affects the relationship between BMI and survival. Cardiorespiratory fitness mitigates the obesity paradox observed in HF patients.

Background In hypertrophic cardiomyopathy (HCM), most of the factors associated with the risk of sudden cardiac death (SCD) are also involved in the pathophysiology of exercise limitation. The present multicentre study investigated possible ability of cardiopulmonary exercise test in improving contemporary strategies for SCD risk stratification. Methods A total of 623 consecutive outpatients with HCM, from five tertiary Italian HCM centres, were recruited and prospectively followed, between September 2007 and April 2015. The study composite end point was SCD, aborted SCD and appropriate implantable cardioverter defibrillator (ICD) interventions. Results During a median follow-up of 3.7 years (25th–75th centile: 2.2–5.1 years), 25 patients reached the end point at 5 years (3 SCD, 4 aborted SCD, 18 appropriate ICD interventions). At multivariate analysis, ventilation versus carbon dioxide relation during exercise (VE/VCO 2 slope) remains independently associated to the study end point either when challenged with the 2011 American College of Cardiology Foundation/American Heart Association guidelines-derived score (C index 0.748) or with the 2014 European Society of Cardiology guidelines-derived score (C index 0.750). A VE/VCO 2 slope cut-off value of 31 showed the best accuracy in predicting the SCD end point within the entire HCM study cohort (sensitivity 64%, specificity 72%, area under the curve 0.72). Conclusions Our data suggest that the VE/VCO 2 slope might improve SCD risk stratification, particularly in those HCM categories classified at low-intermediate SCD risk according to contemporary guidelines. There is a need for further larger studies, possibly on independent cohorts, to confirm our preliminary findings.

Background: Several cardiopulmonary exercise test (CPET) parameters (peak VO2, PetCO2 and VE/VCO2) emerged as tools for the prediction of pulmonary arterial hypertension (PAH). Less is known on ventilatory power (VP) in patients with suspect PAH. Aim: To ascertain possible correlations between VP derived at CPET and hemodynamic parameters at right heart catheterization (RHC) indicative of PH. Methods: Forty-seven consecutive outpatients with suspect of PAH were assessed by CPET and RHC; VP was defined as peak SBP divided by the minute ventilation-CO2 production slope at CPET and Diastolic Pressure Gradient (DPG), Trans-pulmonary Pressure Gradient (TPG), mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance (PVR) at RHC were also assessed and compared with VP. Results: VP values were inversely related to mPAP (r −0.427, p 0.003), DPG (r −0.36, p 0.019), TPG (r: −0.43, p 0.004), and PVR (r −0.52, p 0.001). Correlations remained significant even after correction at multivariate analysis for age and gender. VP values below median identified subjects with mPAP ≥ 25 mmHg with an odds ratio of 4.5 (95% confidence interval 1.05–19.36, p

Background: Previous studies and case-series showed improvement in left ventricular (LV) function and reverse remodeling after sacubitril/valsartan therapy in real-world studies. We therefore aimed to evaluate whether also right ventricular (RV) function may improve after sacubitril/valsartan therapy. Methods: Sixty consecutive patients with chronic heart failure and NYHA class II-III were followed up for 12 months after therapy with sacubitril/valsartan. Left and (RV) function was assessed at baseline and after 12 months of therapy. Results: At 12-month control, therapy with sacubitril/valsartan was associated with a significant improvement in a series of echo parameters: LVEF (p

Here we report the identification of two novel mutations in a previously asymptomatic young man who suffered an out-of-hospital sudden cardiac arrest. During following evaluation, diagnosis of early stage dilated cardiomyopathy was established, while electrocardiogram monitoring showed frequent complex ventricular arrhythmias, incomplete right bundle branch block and prolonged QT duration. No reversible causes explaining the clinical presentation were established and an automatic implantable cardioverter defibrillator was therefore implanted. Heterozygous mutations in human protein coding genes NKX2-5 and RBM20 are associated with a wide array of pathological phenotypes some of which are sudden cardiac death, unexplained syncope and either combined or isolated congenital heart diseases such as dilated cardiomyopathy.

We report the case of an incomplete diagnosis of chronic thromboembolic pulmonary hypertension, with relevant prognostic implications, missing the presence of a primary pulmonary artery angiosarcoma. After the late neoplasm diagnosis, the patient, treated for months with riociguat, was considered inoperable and died soon after. This case highlights the need to manage patients with suspected pulmonary arterial hypertension by expert referral centers with specific and multi-professional expertise (heart and thoracic imaging) in order to avoid incomplete or delayed diagnoses.

Pharmacological or electrical cardioversion allows immediate symptoms improvement in the setting of paroxysmal or persistent atrial fibrillation (AF), although the periprocedural risk of systemic embolism should be considered. Recently, there was a great interest on the safety and efficacy of direct oral anticoagulants (DOACs) when used for the cardioversion of non-valvular AF. We performed a random-effects meta-analysis of patients undergoing both electrical and pharmacologic cardioversion for non-valvular AF in the RE-LY, ROCKET-AF, ARISTOTLE, ENGAGE AF-TIMI 48, X-VeRT, ENSURE-AF, and EMANATE trials. We assessed Mantel–Haenszel pooled estimates of risk ratios (RRs) and 95% confidence intervals (CIs) for stroke/systemic embolism (SSE) and major bleeding (MB) at follow-up. A total of 8564 patients have been included in the analysis. When compared with patients receiving vitamin-K antagonists (VKAs), patients receiving DOACs had a lower risk of SSE (RR 0.70, 95% CI 0.33–1.546, P = 0.34), as well as of MB (RR 0.86;,95% CI 0.47–1.58, P = 0.62), although both were non-significant. Funnel plot analysis showed, however, lower RRs with more recent ad hoc studies in comparison with registrational studies, even though statistical significance was not reached. DOACs are as effective and as safe as VKAs for thromboembolic prevention in non-valvular AF in the setting of cardioversion. There are differences, although non-significant, between registrational studies and studies enrolling exclusively patients undergoing cardioversion of AF.

The coexistence of coronary artery disease and atrial fibrillation (AF) in the same individuals raises great concern about the co-treatment with different antithrombotic agents in the case of percutaneous coronary interventions (PCI). The advent of direct oral anticoagulants (DOACs) revolutionised the therapy of AF; less is known, however, about the safety and efficacy of therapy with DOACs in combination with antiplatelet agents after PCI. We performed a meta-analysis of randomized controlled studies enrolling patients with nonvalvular AF undergoing PCI. We assessed Mantel-Haenszel pooled estimates of risk ratios (RRs) and 95% CIs for any bleeding (AB), cardiovascular events (CVE), major bleeding (MB), myocardial infarction (MI), and stent thrombosis (ST) at follow-up: 4849 patients have been included in the analysis. When compared with patients receiving standard triple therapy (vitamin-K antagonists plus double antiplatelet therapy [VKAs plus DAPT]), patients receiving DOACs (rivaroxaban/dabigatran plus either one or two antiplatelet agents) had a statistically significant lower risk of AB (RR, 0.66; 95% CI, 0.59–0.75, p

Background: A blunted heart rate (HR) response is associated with an impaired peak oxygen uptake (pVO(2)), a powerful outcome predictor in hypertrophic cardiomyopathy (HCM). The present multicenter study sought to determine the prognostic role for exercise-induced HR response in HCM.Methods: A total of 681 consecutive HCM outpatients on optimized treatment were recruited. The heart failure (HF) end-pointwas death due to HF, cardiac transplantation, NYHA III-IV class progression, HF worsening leading to hospitalization and severe functional deterioration leading to septal reduction. The sudden cardiac death (SCD) end-point included SCD, aborted SCD and appropriate implantable cardioverter defibrillator discharges.Results: During a median follow-up of 4.2 years (25-75th centile: 3.9-5.2), 81 patients reached the HF and 23 the SCD end-point. Covariates with independent effects on the HF end-point were left atrial diameter, left ventricular ejection fraction, maximal left ventricular outflow tract gradient and exercise cardiac power (ECP=pVO(2)*systolic blood pressure) (C-Index= 0.807) whereas the HCM Risk-SCD score and the ECP remained associated with the SCD end-point (C-Index = 0.674). When the VO2-derived variables were not pursued, peak HR (pHR) re-entered in the multivariate HF model (C-Index= 0.777) and, marginally, in the SCD model (C-index= 0.656). A pHR= 70% of the maximum predicted resulted as the best cut-off value in predicting the HF-related events.Conclusions: The cardiopulmonary exercise test is pivotal in the HCM management, however the pHR remains a meaningful alternative parameter. A pHR < 70% identified a HCM population at high risk of HF-related events, thus calling for a reappraisal of the chronotropic incompetence threshold in HCM. (c) 2018 Elsevier B.V. All rights reserved.

Mortality following an admission for acute decompensated heart failure (ADHF) is high and risk stratification in this context remains a challenge. The objective of the present study was to assess whether a simple echocardiographic assessment of pulmonary hypertension (PH) and/or of right ventricular (RV) dysfunction is associated with cardiovascular events in a 1-year follow-up after hospital discharge.The present prospective longitudinal study included 214 patients admitted to hospital with a cardiologist-adjudicated diagnosis of ADHF and a left ventricular ejection fraction (LVEF) at echocardiography 40%. Echocardiography was performed at admission and at discharge and included pulmonary artery systolic pressure (PASP) and RV function as defined by the tricuspid annular plane systolic displacement (TAPSE). The primary end-point was the combination of all-cause mortality and re-hospitalization for worsening heart failure at 1 year after hospital discharge. During an average follow-up period of 230 ± 130 days, 40 patients died and 41 patients underwent re-hospitalization due to ADHF. At multivariate analysis the independent predictors were LVEF, PASP at discharge and creatinine plasma levels (all p 0.001). At ROC analysis the best threshold of PASP to discriminate low-risk from high-risk patients was 40 mm Hg.In ADHF patients with reduced LVEF, PH at discharge is a pivotal prognostic feature to predict morbidity/mortality within the first year after the acute episode.

Initial combination therapy with ambrisentan and tadalafil (upfront therapy) offers clinical benefits in pulmonary arterial hypertension (PAH) and reduces the risk of clinical failure compared with monotherapy in naïve patients. The aim of study is to assess the efficacy of a 12-month upfront therapy with ambrisentan and tadalafil in improving haemodynamics in incident PAH patients.This is a multicentre retrospective analysis of real-world Italian clinical data in 56 patients with newly diagnosed PAH. Clinical evaluations, including demographics, medical history, WHO functional class, 6-min walk distance, and right heart catheterization, were collected from the patients' medical records at baseline and at 12-month follow-up.At baseline, there were 16, 34, and 6 patients in WHO functional class II, III, and IV, respectively. Over a median follow-up of 12 months, 54 (96%) patients were still alive, 6 (11%) of whom received parenteral prostanoids. Ambrisentan-tadalafil combination was associated with significant improvements in WHO functional class (2.2 ± 0.8 vs. 2.8 ± 0.6, P 0.001, improved in 29 patients), exercise capacity (395 ± 123 vs. 353 ± 101 m, P = 0.039), N-terminal probrain natriuretic peptide (528 ± 493 vs. 829 ± 620 pg/ml; P = 0.009), and haemodynamics (right atrial pressure 7 ± 4 vs. 9 ± 5 mmHg, P = 0.02; mean pulmonary artery pressure 45 ± 15 vs. 50 ± 13 mmHg, P = 0.03; cardiac index 3.0 ± 1.0 vs. 2.5 ± 0.9 l/min/m, P = 0.001; pulmonary vascular resistance 8 ± 4 vs. 11 ± 6 Wood units, P = 0.001) compared with baseline.Initial combination therapy with ambrisentan and tadalafil offers clinical benefits and significant haemodynamic improvement in newly diagnosed PAH patients.

Background Tissue Doppler imaging (TDI) is used to improve risk stratification in patients with chronic heart failure (CHF). So far, few studies have used this method to investigate the characteristics of subjects with CHF and Cheyne–Stokes breathing (CSB). The aim of this study was therefore to evaluate whether TDI assessment may predict the presence of CSB in patients with CHF. Materials and methods A total of 41 consecutive patients with CHF enrolled in the Daunia Heart Failure Registry underwent echocardiography assessment and nocturnal polygraphy to evaluate the presence of sleep apnea and CSB. Conventional echocardiography and TDI parameters were calculated. We have also quantified by TDI a combined index (EAS index) of diastolic and systolic performance: E'/(A' × S'). Results Subjects with evidence of CSB (N = 8) were characterized by lower values of A' (5·03 ± 2·64 vs. 7·88 ± 2·64 cm/s, P < 0·01). A' and EAS index values were related to Cheyne–Stokes episode rates (r = −0·49 and 0·52, P < 0·05 and

Tissue Doppler imaging (TDI) may be useful in identifying subjects at higher risk among patients with chronic heart failure (CHF). The clinical role of newly developed TDI parameters, however, still needs to be documented.A total of 287 consecutive patients with CHF enrolled in the Daunia Heart Failure Registry underwent echocardiography assessment and were followed prospectively for a median 255 (204-316) days. Conventional echocardiography and TDI parameters were calculated. We also quantified by TDI a combined index (EAS index) of diastolic and systolic performance E'/(A'xS') and assessed its possible additional prognostic role in combination with 'traditional' parameters such as left ventricular ejection fraction (LVEF) and myocardial performance index (MPI).Subjects readmitted for worsening HF were characterized by higher levels of EAS index (median 0·14 (95% C.I. 0·12-0·21) vs. 0·11 (0·10-0·12, P 0·05)). Increased rates of rehospitalization were found in subjects with EAS indexmedian (0·115) (21% vs. 10%, P 0·05); higher EAS index values predicted the incidence of readmissions for worsening HF during follow-up, even at multivariable analysis. The assessment of EAS index in addition to LVEF and MPI showed an adjunctive prognostic value (log-rank P 0·001 and P 0·05, respectively).EAS index assessed by TDI may be helpful in predicting the risk of rehospitalizations in subjects with CHF. EAS index may represent an independent adjunctive tool for the risk stratification of patients with CHF in addition to 'traditional' tools such as LVEF or MPI.