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Aspirin and P2Y12 receptor antagonists are widely used across the spectrum of cardiovascular and cerebrovascular diseases. Gastrointestinal complications, including ulcer and bleeding, are relatively common during antiplatelet treatment and, therefore, concomitant proton pump inhibitor (PPI) treatment is often prescribed. However, potential increased risk of cardiovascular events has been suggested for PPIs, and, in recent years, it has been discussed whether these drugs may reduce the cardiovascular protection by aspirin and, even more so, clopidogrel. Indeed, pharmacodynamic and pharmacokinetic studies suggested an interaction through hepatic CYP2C19 between PPIs and clopidogrel, which could translate into clinical inefficacy, leading to higher rates of cardiovascular events. The FDA and the EMA sent a warning in 2010 discouraging the concomitant use of clopidogrel with omeprazole or esomeprazole. In addition, whether the use of PPIs may affect the clinical efficacy of the new P2Y12 receptor antagonists, ticagrelor and prasugrel, remains less known. According to current guidelines, PPIs in combination with antiplatelet treatment are recommended in patients with risk factors for gastrointestinal bleeding, including advanced age, concurrent use of anticoagulants, steroids or non-steroidal anti-inflammatory drugs, and Helicobacter pylori infection. Like vitamin K antagonists (VKAs), DOACs can determine gastrointestinal bleeding. Results from both randomized clinical trials and observational studies suggest that high-dose dabigatran (150 mg bid), rivaroxaban and high-dose edoxaban (60 mg daily) are associated with a higher risk of GI bleeding as compared with apixaban and warfarin. In patients taking oral anticoagulant with GI risk factor, PPI could be recommended, even if usefulness of PPIs in these patients deserves further data. Helicobacter pylori should always be searched, and treated, in patients with history of peptic ulcer disease (with or without complication). Given the large number of patients treated with antithrombotic drugs and PPIs, even a minor reduction of platelet inhibition or anticoagulant effect potentially carries a considerable clinical impact. The present joint statement by ANMCO and AIGO summarizes the current knowledge regarding the widespread use of platelet inhibitors, anticoagulants, and PPIs in combination. Moreover, it outlines evidence supporting or opposing drug interactions between these drugs and discusses consequent clinical implications.

Background and aims Low potassium intake, in addition to high sodium, has been associated with higher risk of hypertension and CVD. The Study assessed habitual potassium intake and sodium/potassium ratio of the Italian adult population from 2008 to 2012 to 2018–2019 based on 24-h urine collection, in the framework of the CUORE Project/MINISAL-GIRCSI/MENO SALE PIU’ SALUTE national surveys. Methods and results Data were from cross-sectional surveys of randomly selected age-and-sex stratified samples of resident persons aged 35–74 years in 10 (out of 20) Italian regions. Urinary electrolyte and creatinine measurements were performed in a central laboratory. Analyses considered 942 men and 916 women, examined in 2008–2012, and 967 men and 1010 women, examined in 2018–2019. In 2008–2012, the age-standardized mean of potassium intake (urinary potassium accounts for 70% of potassium intake) was 3147 mg (95% CI 3086–3208) in men and 2784 mg (2727–2841) in women, whereas in 2018–2019, it was 3043 mg (2968–3118) and 2561 mg (2508–2614) respectively. In 2008–2012, age-adjusted prevalence of persons with an adequate potassium intake (i.e. ≥ 3510 mg/day) was 31% (95% CI 28–34%) for men and 18% (16–21%) for women; in 2018–2019, it was 26% (23–29%) and 12% (10–14%) respectively. The sodium/potassium ratio significantly decreased both in men and women. Conclusions The average daily potassium intake of the Italian general adult population remains lower than the WHO and EFSA recommended level. These results suggest the need of a revision to strengthen initiatives for the promotion of an adequate potassium intake at the population level.

Structured abstract Background The management of atrial fibrillation (AF) has changed with the introduction of direct anticoagulants (DOACs) and new techniques such as catheter ablation. An update collection of data from “real world” AF patients followed by cardiologists is useful to obtain information on both management, outcomes and guideline adherence in clinical practice. Methods Follow-up information on survival, embolic and bleeding events and hospital readmission, persistence of oral anticoagulant (OAC) therapy was collected in 84 centers participating to the BLITZ-AF study. Results Patients were followed for a median of 366 days (IQR: 356–378) and vital status was available for 2159 patients. Mortality was 9.2%. Heart failure was the most common cardiovascular cause of death (70%) followed by arrhythmias (6.7%), acute coronary syndrome (5.0%) and ischemic stroke (2.5%). During follow-up 18.1% of the patients were readmitted, mainly (81.3%) for cardiovascular causes. Patients on OAC were 83.4%, 9.1% were on antiplatelets and 7.5% did not receive antithrombotic therapy. The use of DOACs increased from 42.1% to 46.4% during the follow-up, OAC discontinuation occurred in 9.1%. AF recurrences occurred in 23.4% of the patients discharged in sinus rhythm. Rate control strategy was adopted in 55.9% and beta-blockers were the most used drugs (81.9%). Amiodarone (22%) and flecainide (9.7%) were the most frequent used antiahrrythmic drugs. Conclusions The follow-up of the BLITZ-AF study provide an up to date picture of the clinical course of patients with AF, who appear frequently affected by heart failure and severe comorbidities which might have led to the high mortality rate.

Patients with non ST-segment elevation acute coronary syndromes (NSTE-ACS) and peripheral arterial disease (PAD) present a worse prognosis compared to those without PAD. We sought to describe contemporary trends of in-hospital management and outcome of patients admitted for NSTE-ACS with associated PAD.We analyzed data from 6 Italian nationwide registries, conducted between 2001 and 2014, including consecutive NSTE-ACS patients.Out of 15,867 patients with NSTE-ACS enrolled in the 6 registries, 2226 (14.0%) had a history of PAD. As compared to non-PAD patients, those with PAD had significantly more risk factors and comorbidities (all p 0.0001) that increased over time. Patients with PAD underwent less frequently coronary angiography (72.0% vs 79.2%, p 0.0001) and percutaneous coronary intervention (PCI, 42.9% vs 51.8%, p 0.0001), compared to patients without PAD. Over the years, a progressive and similar increase occurred in the rates of invasive procedures both in patients with and without PAD (both p for trend0.0001). The crude in-hospital mortality rate did not significantly change over time (p for trend = 0.83). However, as compared to 2001, the risk of death was significantly lower in all other studies performed at different times, after adjustment for multiple comorbidities.. At multivariable analysis, PAD on admission was an independent predictor of in-hospital mortality [odds ratio (OR): 1.75; 95% confidence intervals (CI): 1.35-2.27; p 0.0001].Over the 14 years of observation, patients with PAD and NSTE-ACS exhibited worsening baseline characteristics and a progressive increase in invasive procedures. Whereas crude in-hospital mortality did not change over time, we observed a significant reduction in comorbidity-adjusted mortality, as compared to 2001.

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.

Even though vitamin K antagonists (VKAs) have been employed for >50 years, there is still some uncertainty about the best strategy to reverse anticoagulation due to VKAs in cases of major bleeding. Furthermore, there is also scarce evidence about the most appropriate way to treat serious bleeding associated with non-vitamin K antagonist oral anticoagulants. This review analyses the main advantages and disadvantages of the various forthcoming therapeutic options to restore a normal coagulation status in anticoagulated patients with ongoing serious bleeding. It discusses the role of fresh frozen plasma, prothrombin complex concentrates and recombinant factor VII activated. Moreover, we report updated evidence on antidotes currently available or in development. Finally, this article proposes a comprehensive algorithm that summarizes major bleeding management during treatment with oral anticoagulants.

In the last decade, the introduction of non-vitamin K antagonist oral anticoagulants (NOACs) in clinical practice has changed the therapeutic landscape in the prevention of thromboembolic events. Although NOACs compared to vitamin K antagonists (VKAs) have demonstrated a similar or slightly lower rate of major bleeding and a lower rate of intracranial or fatal bleeding, hemorrhaging still represents the main adverse effect of anticoagulant treatment. This review reports data on the rates of major bleeding with old and new oral anticoagulants. It analyses laboratory tests that can be used to assess the intensity of anticoagulation in patients treated with oral anticoagulants and discusses general measures to implement in managing major bleeding.

BACKGROUND: Extensive evidence exists about the prognostic role of systolic blood pressure (SBP) reduction ≤140mmHg. Recently, the SPRINT trial successfully tested the strategy of lowering SBP

To describe the clinical characteristics, contemporary trends of in-hospital management and outcome of patients admitted for an acute coronary syndrome (ACS) with associated atrial fibrillation (AF).We analyzed data from four Italian nationwide prospective registries, conducted between 2001 and 2014, including consecutive ACS patients.Out of 16,803 ACS patients, 1019 (6.1%) presented with concomitant AF: 668 with non-ST elevation (NSTE)-ACS and 351 with ST-elevation myocardial infarction (STEMI). As compared to no-AF patients, those with AF were older and had significantly more prior cardiac events and comorbidities (all p0.005). A progressive increase occurred over time in the rates of coronary angiography and percutaneous coronary intervention, both in NSTE-ACS (p for trend=0.0002 and 0.0008, respectively) and STEMI patients with AF at admission (both p for trend0.0001), with trends similar to those observed in non-AF patients. Among STEMI patients, in-hospital mortality decreased by 50% in those without AF (7.5% in 2001 to 3.3% in 2014, p0.0001), with a similar decrease in those with AF (20% vs 10.7%, p=0.20), even though not statistically significant. At multivariable analysis, AF on admission was not an independent predictor of in-hospital mortality [odds ratio (OR): 0.82; 95% confidence intervals (CI): 0.52-1.30; p=0.41 for NSTE-ACS, and OR: 1.07; 95% CI: 0.73-1.57; p=0.74 for STEMI].Over the last 14years, the in-hospital management of ACS patients with AF has significantly improved as for patients without AF, with comparable effect in terms of outcome.

Background Speckle-tracking echocardiography allows early detection of subclinical left ventricular systolic dysfunction (LVSD) in patients with rheumatoid arthritis (RA). In this prospective study, we assessed the prevalence and the prognostic role of subclinical LVSD detected by speckle-tracking echocardiography in RA patients. Methods Two-dimensional global longitudinal strain (GLS) and global circumferential strain (GCS) were measured in 209 RA patients without overt cardiac disease. LVSD was defined as low GLS (> −16.0%), low GCS (> −17.8%), or both. The primary end point was all-causes hospitalization; the coprimary end point was hospitalization for cardiovascular causes. Results The study population had a mean age of 58 ± 11 years; 67% were female, 52% had hypertension, and the RA duration was 14 ± 10 years. Low GLS was detected in 51 patients (24%), low GCS in 42 patients (20%), and combined low GLS and GCS in 18 patients (9%). During a median follow-up time of 16 months (range, 10–21 months), a primary end point occurred in 50 patients (24%), and 25 patients were hospitalized for a cardiovascular event. Multiple Cox regression analyses revealed that combined low GLS and GCS was independently associated with the end point defined as all-causes hospitalization together with higher aortic stiffness. Examined individually, neither low GCS nor low GLS showed an independent association with this typology of clinical outcome. Conversely, both low GCS and low GLS (examined individually or as combined low GLS and GCS) emerged as strong independent prognosticators of cardiovascular events. Conclusions Subclinical LVSD defined as low GLS, GCS, or both is common in RA patients without overt cardiac disease and provides additional prognostic information in these individuals.

Objectives The aim of this study was to assess the relationship between gait speed and the risk for death and/or hospital admission in older patients with heart failure (HF). Background Gait speed is a reliable single marker of frailty in older people and can predict falls, disability, hospital admissions, and mortality. Methods In total, 331 community-living patients ≥70 years of age (mean age 78 ± 6 years, 43% women, mean ejection fraction 35 ± 11%, mean New York Heart Association functional class 2.7 ± 0.6) in stable condition and receiving optimized therapy for chronic HF were prospectively enrolled and followed for 1 year. Gait speed was measured at the usual pace over 4 m, and cutoffs were defined by tertiles: ≤0.65, 0.66 to 0.99, and ≥1.0 m/s. Results There was a significant association between gait speed tertiles and 1-year mortality: 38.3%, 21.9%, and 9.1% (p Conclusions Gait speed is independently associated with death, hospitalization for HF, and all-cause hospitalization and improves risk stratification in older patients with HF evaluated using the Cardiac and Comorbid Conditions Heart Failure score. Assessment of frailty using gait speed is simple and should be part of the clinical evaluation process.

The aim of the study was to assess the clinical and prognostic impact of early functional mitral regurgitation (FMR) improvement on the outcome of patients with idiopathic dilated cardiomyopathy (IDC). The prevalence and prognostic role of FMR improvement, particularly at early follow-up, in patients with IDC are still unclear. From 1988 to 2009, we enrolled 470 patients with IDC with available FMR data at baseline and after 6 ± 2 months. According to the evolution of FMR, patients were classified into 3 groups: stable absent-mild FMR, early FMR improvement (downgrading from moderate-severe to absent-mild), and persistence/early development of moderate-severe FMR. At baseline, 177 of 470 patients (38%) had moderate-severe FMR. Patients with early FMR improvement had significantly better survival rate-free from heart transplant with respect to those with persistence/early development of moderate-severe FMR (93%, 81%, and 66% vs 91%, 64%, and 52% at 1, 6, and 12 years, respectively; p = 0.044). At 6-month follow-up multivariate analysis, FMR improvement was associated with better prognosis (hazard ratio 0.78, 95% confidence interval [CI] 0.64 to 0.96, p = 0.02); the other independent predictors were male gender, heart failure duration, and early re-evaluation of the New York Heart Association class and left ventricle systolic function. This model provided more accurate risk stratification compared with the baseline model (Net Reclassification Index 80% at 12 months and 41% at 72 months). In conclusion, in a large cohort of patients with IDC receiving optimal medical treatment, early improvement of FMR was frequent (53%) and emerged as a favorable independent prognostic factor with an incremental short- and long-term power compared with the baseline evaluation.

BACKGROUND: In the recent Italian Network on Heart Failure (IN-HF) Outcome registry, including 1,855 patients with acute heart failure (AHF), were viewed the use of inotropes and their prognostic implication onin-hospital and 12-month mortality. METHODS: IN-HF Outcome is aprospective, multicenter, observational, study involving 61 Italian cardiology centers. AHF patients have been enrolled over a 2-year period and followed-up for 1 year. Inotropes were used in 360 patients (19.4%). RESULTS: Patients who received inotropes had a more severe clinical and hemodynamic profile than those who did not and exhibited a significantly higher rate of in-hospital (21.4% vs 2.7%, p < 0.01) and 1-year (50.6% vs 17.7%, p < 0.01) mortality. At entry, systolic blood pressure (SBP) was < 110 mm Hg in 58%, 111 to 130 mm Hg in 24.5%, and > 130 mm Hg in 17.5%. Multivariable analyses showed use of inotropes was the strongest predictor of all-cause death. These data were confirmed by propensity score analyses. According to SBP at entry, the 2 groups with SBP > 110 mm Hg who took inotropes, despite a more favorable clinical profile, exhibited a similar worse prognosis, particularly at 1 year: 56.3% (≤ 110 mmHg), 43.7% (111-130 mm Hg), and 40.3% (4130 mm Hg) vs 17.7%. CONCLUSIONS: Inotropes were used in nearly 20% of the patient admitted for AHF, and this treatment was associated with a short-term to medium-term poor prognosis. An inappropriate use of inotropes in patients with normal to high SBP, and presumably preserved cardiac output, may have significantly contributed to affect the all-group outcome.

Background Chronic renal dysfunction (RD) frequently coexists with heart failure (HF) and influences outcome. Patients with acute HF (AHF) and severe RD are frequently excluded in the trials. We characterized these subjects and assessed incidence and predictors of in-hospital and one-year mortalities. Methods We selected the 455 patients included in the "IN-HF Outcome" Italian registry belonging to the lowest quartile of estimated glomerular filtration rate (eGFR < 40 ml/min/1.73 m2). Results Mean eGFR at entry in severe RD patients was 28 ± 9 ml/min/1.73 m2. Compared to 1368 patients with more preserved eGFR, they were older, with more co-morbidities and more frequently ischemic etiology of HF. In-hospital and one-year all-cause mortality rates were 14% and 44% respectively, twice higher than the entire population. Predictors of in-hospital mortality were an abnormal status of consciousness, older age, hyponatremia, lower systolic blood pressure and eGFR. The same conditions (except eGFR) predicted one-year mortality together with the absence of diabetes and no treatment with beta-blockers or diuretics. Conclusions In patients with AHF and severe RD, in-hospital and one-year all-cause mortality rates are very high. Independent predictors such as older age, and signs of hypoperfusion and hyponatremia may be identified but preventing and reversing RD remain the key targets for the clinical management of these patients.

fraction. Rev Esp Cardiol 2013;66:261–8. [9] Herrmann HC, Pibarot P, Hueter I, et al. Predictors of mortality and outcomes of therapy in low-flow severe aortic stenosis: a Placement of Aortic Transcatheter Valves (PARTNER) Trial analysis. Circulation 2013;127:2316–26. [10] Ozkan A, Hachamovitch R, Kapadia SR, Tuzcu EM,Marwick TH. Impact of aortic valve replacement on outcome of symptomatic patients with severe aortic stenosis with low gradient and preserved left ventricular ejection fraction. Circulation 2013;128(6):622–31.

Aims Type 2 diabetes mellitus (DM) is associated with higher risk of heart failure. Over the last three decades several studies demonstrated the presence of asymptomatic systolic and/or diastolic left ventricular (LV) dysfunction (asymLVD) in patients with normal LV ejection fraction (LVEF). Purpose of our study was to assess the prevalence and factors associated with asymLVD in DM patients by echocardiographic indexes more sensitive than LVEF and transmitral flow detected by pulsed Doppler. Methods 386 DM patients without overt cardiac disease were enrolled from January to October 2011. Stress-corrected midwall shortening (sc-MS) and mitral annular peak systolic velocity ( S ′) were considered as indexes of systolic function of circumferential and longitudinal myocardial fibers, respectively. Early diastolic velocity of transmitral flow was divided by early diastolic Tissue Doppler velocity of mitral annulus for identifying diastolic LVD. Results asymLVD was detected in 262 patients (68%). 106 (27%) had isolated systolic asymLVD, 61 (16%) isolated diastolic asymLVD; in 95 (25%) systolic and diastolic asymLVD coexisted. Patients with asymLVD were older, had lower glomerular filtration rate, higher levels of glycated hemoglobin, C reactive protein, LV mass, relative wall thickness and prevalence of valve calcifications. Older age (HR 1.1 [1.02–1.18], p = 0.01), aortic valve calcifications (HR 6.3 [1.31–30.31], p = 0.02), LV concentric geometry defined as relative wall thickness ≥0.43 (HR 15.44 [2.96–80.44], p = 0.001) were independent predictors of asymLVD at multivariate analysis. Conclusions Using suitable echocardiographic indexes, asymLVD is detectable in two/third of DM patients without overt cardiac disease and is predicted by older age, cardiac valve calcifications and LV concentric remodeling.

Aims Left ventricular dysfunction (LVD) in type 2 diabetes mellitus (DM) (DYDA) study is a prospective investigation enrolling 960 with DM without overt cardiac disease. At baseline, a high prevalence of LVD was detected by analysing midwall shortening. We report here the incidence of clinical events in DYDA patients after 2-year follow-up and the frequency of LVD detected at baseline and 2-year evaluation. Methods Systolic LVD was defined as midwall shortening ≤15%, diastolic LVD as any condition different from “normal diastolic function” identified as E/A ratio on Doppler mitral flow between 0.75 and 1.5 and deceleration time of E wave >140 ms. Major outcome was a composite of major events, including all-causes death and hospital admissions. Results During the study period, any systolic/diastolic LVD was found in 616 of 699 patients (88.1%) in whom LVD function could be measured at baseline or at 2 years. Older age and high HbA1c predicted the occurrence of LVD. During the follow-up 15 patients died (1.6%), 3 for cardiovascular causes, 139 were hospitalized (14.5%, 43 of them for cardiovascular causes, 20 for a new cancer). Conclusions During a 2-year follow-up any LVD is detectable in a large majority of patients with DM without overt cardiac disease. Older age and higher HbA1c predict LVD. All-cause death or hospitalization occurred in 15% of patients, cardiovascular cause was uncommon. Independent predictors of events were older age, pathologic lipid profile, high HbA1c, claudicatio and repaglinide therapy. Echo-assessed LVD at baseline was not prognosticator of events.

Background: Prognostic stratification in heart failure (HF) is crucial to guide clinical management and treatment decision-making. Currently available models to predict HF outcome have multiple limitations. We developed a simple risk stratification model, based on routinely available clinical information including comorbidities, the Cardiac and Comorbid Conditions HF (3C-HF) Score, to predict all-cause 1-year mortality in HF patients. Methods: We recruited in a cohort study 6274 consecutive HF patients at 24 Cardiology and Internal Medicine Units in Europe. 2016 subjects formed the derivation cohort and 4258 the validation cohort. We entered information on cardiac and comorbid candidate prognostic predictors in a multivariable model to predict 1-year outcome. Results: Median age was 69 years, 35.8% were female, 20.6% had a normal ejection fraction, and 65% had at least one comorbidity. During 5861 person-years follow-up, 12.1% of the patients met the study end-point of all-cause death (n = 750) or urgent transplantation (n = 9). The variables that contributed to outcome prediction, listed in decreasing discriminating ability, were: New York Heart Association class III-IV, left ventricular ejection fraction < 20%, no beta-blocker, no renin-angiotensin system inhibitor, severe valve heart disease, atrial fibrillation, diabetes with micro or macroangiopathy, renal dysfunction, anemia, hypertension and older age. The C statistic for 1-year all-cause mortality was 0.87 for the derivation and 0.82 for the validation cohort. Conclusions: The 3C-HF score, based on easy-to-obtain cardiac and comorbid conditions and applicable to the 1-year time span, represents a simple and valuable tool to improve the prognostic stratification of HF patients in daily practice.

Cardiac Calcification at Transthoracic EchocardiographyPredicts Stress EchoResults: a Multicentre StudyNicola Gaibazzi, Rosa Sicari, Eustachio Agricola, Giovanni Cioffi, CarmineMazzone, Lisa Albertini, Giacomo Faden, Sabrina Molinaro, DamianoRegazzoli, Andrea Di Lenarda,Pompilio FaggianoPII: S0167-5273(14)00666-4DOI: doi: 10.1016/j.ijcard.2014.04.007Reference: IJCA 17908To appear in

Objectives We explored whether vascular protection by carvedilol could contribute to its superior effects in the treatment of heart failure (HF) compared with metoprolol tartrate in the COMET (Carvedilol Or Metoprolol European Trial) study. Background Full adrenergic blockade by carvedilol and additional (e.g., antioxidative) properties may lead to vascular protection relative to beta-1 blockade alone, and contribute to its efficacy in HF treatment. Methods Three thousand twenty-nine patients with HF due to ischemic (51%) or idiopathic cardiomyopathy (44%) were randomized double-blind to carvedilol (n = 1,511) or metoprolol (n = 1,518) and followed for 58 months. Vascular end points were cardiovascular death, stroke, stroke death, myocardial infarction (MI), and unstable angina. Results The effect of carvedilol on cardiovascular death improved consistently in subgroups with prespecified baseline variables. Myocardial infarctions were reported in 69 carvedilol and 94 metoprolol patients (hazard ratio [HR] 0.71, 95% confidence interval [CI] 0.52 to 0.97, p = 0.03). Cardiovascular death or nonfatal MI combined were reduced by 19% in carvedilol (HR 0.81, 95% CI 0.72 to 0.92, p = 0.0009 vs. metoprolol). Unstable angina was reported as an adverse event in 56 carvedilol and in 77 metoprolol patients (HR 0.71, 95% CI 0.501 to 0.998, p = 0.049). A stroke occurred in 65 carvedilol and 80 metoprolol patients (HR 0.79, 95% CI 0.57 to 1.10). Stroke or MI combined occurred in 130 carvedilol and 168 metoprolol patients (HR 0.75, 95% CI 0.60 to 0.95, p = 0.015), and fatal MI or fatal stroke occurred in 34 carvedilol and in 72 metoprolol patients (HR 0.46, 95% CI 0.31 to 0.69, p = 0.0002). Death after a nonfatal MI or stroke occurred in 61 of 124 carvedilol and in 106 of 160 metoprolol patients (HR 0.66, 95% CI 0.48 to 0.90, p = 0.0086). Conclusions Carvedilol improves vascular outcomes better than metoprolol. These results suggest a ubiquitous protective effect of carvedilol against major vascular events.

Objectives This study was designed to investigate the loss of well-being, in terms of life-years, overall and in patients randomized to metoprolol versus carvedilol in the Carvedilol Or Metoprolol European Trial (COMET). Background The ultimate objectives of treating patients with heart failure are to relieve suffering and prolong life. Although the effect of treatment on mortality is usually described in trials, the effects on patient well-being throughout the trials’ courses are rarely reported. Methods A total of 3,029 patients randomized in the COMET study were included in the analysis. “Patient journey” was calculated by adjusting days alive and out of hospital over four years using a five-point score completed by the patient every four months, adjusted according to the need for intensification of diuretic therapy. Scores ranged from 0% (dead or hospitalized) to 100% (feeling very well). Results Over 48 months, 17% of all days were lost through death, 1% through hospitalization, 23% through impaired well-being, and 2% through the need for intensified therapy. Compared with metoprolol, carvedilol was associated with fewer days lost to death, with no increase in days lost due to impaired well-being or days in hospital. The “patient journey” score improved from a mean of 54.8% (SD 26.0) to 57.4% (SD 26.3%) (p Conclusions Despite treatment with beta-blockers, heart failure remains associated with a marked reduction in well-being and survival. Loss of quality-adjusted life-years through death and poor well-being seemed of similar magnitude over four years, and both were much larger than the loss that could be attributed to hospitalization.

Summary Backgroundblockers reduce mortality in patients who have chronic heart failure, systolic dysfunction, and are on background treatment with diuretics and angiotensin-converting enzyme inhibitors. We aimed to compare the effects of carvedilol and metoprolol on clinical outcome. Methods In a multicentre, double-blind, and randomised parallel group trial, we assigned 1511 patients with chronic heart failure to treatment with carvedilol (target dose 25 mg twice daily) and 1518 to metoprolol (metoprolol tartrate, target dose 50 mg twice daily). Patients were required to have chronic heart failure (NYHA II-IV), previous admission for a cardio- vascular reason, an ejection fraction of less than 0·35, and to have been treated optimally with diuretics and angiotensin- converting enzyme inhibitors unless not tolerated. The primary endpoints were all-cause mortality and the composite endpoint of all-cause mortality or all-cause admission. Analysis was done by intention to treat. Findings The mean study duration was 58 months (SD 6). The mean ejection fraction was 0·26 (0·07) and the mean age 62 years (11). The all-cause mortality was 34% (512 of 1511) for carvedilol and 40% (600 of 1518) for metoprolol (hazard ratio 0·83 (95% CI 0·74-0·93), p=0·0017). The reduction of all- cause mortality was consistent across predefined subgroups. The composite endpoint of mortality or all-cause admission occurred in 1116 (74%) of 1511 on carvedilol and in 1160 (76%) of 1518 on metoprolol (0·94 (0·86-1·02), p=0·122). Incidence of side-effects and drug withdrawals did not differ by much between the two study groups. Interpretation Our results suggest that carvedilol extends survival compared with metoprolol.

β-Blockers reduce mortality in patients with congestive heart failure and a proposed mechanism has been changes of autonomic tone. Heart rate variability is a non-invasive tool to estimate cardiac autonomic tone. The aim was to study changes of heart rate variability in patients with congestive heart failure on placebo, on the β 1 -selective antagonist metoprolol or 24 h after metoprolol withdrawal. Forty-five patients with congestive heart failure were studied with Holter recordings. Heart rate variability measurements were performed before, after 6–12 months of treatment with 150 mg metoprolol/placebo, or 24 h after discontinued metoprolol. After treatment, patients on β-blockade had a significantly longer mean RR interval and changes of heart rate variability, suggesting elevated vagal tone. Patients monitored in the rebound phase of β-blocker withdrawal had a significant vagal reduction to the level of the placebo group. There was also a nonsignificant trend towards increased sympathetic tone (LF/HF over 24 h), compared with the β-blockade group. Heart rate variability indicates an elevated vagal tone during treatment with metoprolol but β-blockade withdrawal shifts the autonomic balance towards lower vagal and higher sympathetic tone within 24 h. These results could imply a potential risk when abruptly discontinuing β-blockade medication in these patients.

Background: Some controlled clinical trials showed a beneficial effect of beta-blockers on symptoms, exercise tolerance, and left ventricular function in dilated cardiomyopathy. The purpose of this study was to investigate if there are clinical variables at baseline that could predict a favorable response to long-term metoprolol therapy.

Radial pseudoaneurysm (PA) is a rare complication of the transradial approach for the arterial catheterization.

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Objectives. This study was undertaken to evaluate the frequency of restrictive left ventricular filling pattern in dilated cardiomyopathy, as well as its clinical and hemodynamic correlations and prognostic implications. Background. In dilated cardiomyopathy, as in other heart disease different left ventricular filling patterns were observed on Doppler echocardiography. Some patients showed a “restrictive filling pattern,” similar to that associated with restrictive cardiomyopathy, characterized by predominant E waves and a shortened E deceleration time. Methods. Pulsed Doppler transmitral curves were analyzed in 79 consecutive patients with dilated cardiomyopathy assigned to two study groups according to E deceleration time group 1 (n = 36) had a restrictive left ventricular filling pattern (E deceleration time

To clarify the clinical and prognostic value of the ECG, an ECG review was undertaken in 45 consecutive patients with a histologic diagnosis of active myocarditis (29 men and boys and 16 women and girls; age, 36.8 +/- 15 years; idiopathic myocarditis, 39 cases). In patients (21) with symptoms of recent onset (less than or equal to 1 month) AV block and repolarization abnormalities were the prevailing ECG features at the time of admission, and a pseudoinfarction pattern (Q waves plus ST-segment elevation) frequently heralded a rapidly fatal course ("fulminant myocarditis"). Left atrial enlargement and atrial fibrillation, left ventricular hypertrophy and LBBB, which prevailed in patients who had symptoms for longer periods, corresponded to the most severe degree of left ventricular dysfunction during the initial hemodynamic and echocardiographic evaluation. The overall mortality rate after 58 +/- 24 months from the time of diagnosis was 29%. Abnormal QRS complexes and LBBB were markers of poor survival, independently of initial indexes of left and right ventricular function, both of which indicate an increased propensity for sudden cardiac death.

Dilated cardiomyopathy (DCM) commonly causes heart failure and shows extensive genetic heterogeneity that may be amenable to newly developed next-generation DNA sequencing of the exome. In this study we report the successful use of exome sequencing to identify a pathogenic variant in the TNNT2 gene using segregation analysis in a large DCM family. Exome sequencing was performed on three distant relatives from a large family with a clear DCM phenotype. Missense, nonsense, and splice variants were analyzed for segregation among the three affected family members and confirmed in other relatives by direct sequencing. A c.517T C>T, Arg173Trp TNNT2 variant segregated with all affected family members and was also detected in one additional DCM family in our registry. The inclusion of segregation analysis using distant family members markedly improved the bioinformatics filtering process by removing from consideration variants that were not shared by all affected subjects. Haplotype analysis confirmed that the variant found in both DCM families was located on two distinct haplotypes, supporting the notion of independent mutational events in each family. In conclusion, an exome sequencing strategy that includes segregation analysis using distant affected relatives within a family represents a viable diagnostic strategy in a genetically heterogeneous disease like DCM.

Multivariate analysis was used to analyze the morphometric data of endomyocardial biopsies (area, perimeter and minor diameter) of myocardial cells obtained at light microscopy by a computerized approach with 16 clinical parameters and prognosis in 52 patients with idiopathic dilated cardiomyopathy. The best morphometric parameter was "area" (R2 = 0.47). A positive correlation was found with age (p less than 0.02), interval between first symptoms and diagnosis (p less than 0.02), left ventricular end-diastolic volume (p less than 0.02), cardiac index (p less than 0.05) and echocardiographic end-diastolic diameter (p less than 0.1). A negative correlation was found with prognosis (p less than 0.02), ejection fraction (p less than 0.02), shortening fraction (p less than 0.05), echocardiographic end-systolic diameter (p less than 0.06) and mitral regurgitation presence (p less than 0.1). The parameters that provided no correlation were New York Heart Association class, left ventricular end-diastolic pressure, right atrial pressure, cardiothoracic ratio, presence or absence of heart failure, fever or alcohol intake. These findings suggest that endomyocardial biopsy may provide prognostic information and confirm clinical diagnosis.