Characterizing diabetic cardiomyopathy: baseline results from the ARISE-HF trial.

BACKGROUND: Diabetic cardiomyopathy (DbCM) is a form of Stage B heart failure (HF) at high risk for progression to overt disease. Using baseline characteristics of study participants from the Aldose Reductase Inhibition for Stabilization of Exercise Capacity in Heart Failure (ARISE-HF) Trial we sought to characterize clinical characteristics of individuals with findings consistent with DbCM. METHODS: Among study participants meeting inclusion criteria, clinical characteristics, laboratory testing, imaging, Kansas City Cardiomyopathy Questionnaire (KCCQ), Physical Activity Scale of the Elderly (PASE) and cardiopulmonary exercise testing (CPET) results were tabulated. Cluster phenogroups were identified. RESULTS: Among 691 study participants (mean age 67.4 years; 50% were female), mean duration of type 2 diabetes mellitus (T2DM) was 14.5 years. The median (Q1, Q3) N-terminal pro-B type natriuretic peptide and high sensitivity cardiac troponin T were 71 (35, 135) ng/L and 9 [6, 12] ng/L. The most common echocardiographic abnormalities were reduced global longitudinal strain in 25.3% and impaired diastolic relaxation in 17.7%. Despite rather well-preserved KCCQ scores the average PASE score was markedly impaired at 155 accompanied by an average maximal oxygen consumption of 15.7 mL/Kg/minute on CPET. In K-means clustering, 4 phenogroups were identified including a higher-risk group with more advanced age, greater elevation of cardiac biomarkers, and more prevalent evidence for diastolic dysfunction and left ventricular hypertrophy. CONCLUSIONS: Baseline data from the ARISE-HF Trial provide clinical characterization of individuals with T2DM and features of stage B HF, and may help clarify the diagnosis of DbCM. TRIAL REGISTRATION: ARISE-HF, NCT04083339.

Rationale and design of the Aldose Reductase Inhibition for Stabilization of Exercise Capacity in Heart Failure Trial (ARISE-HF) in patients with high-risk diabetic cardiomyopathy.

BACKGROUND: Diabetic cardiomyopathy (DbCM) is a specific form of heart muscle disease that may result in substantial morbidity and mortality in individuals with type 2 diabetes mellitus (T2DM). Hyperactivation of the polyol pathway is one of the primary mechanisms in the pathogenesis of diabetic complications, including development of DbCM. There is an unmet need for therapies targeting the underlying metabolic abnormalities that drive this form of Stage B heart failure (HF). METHODS: Aldose reductase (AR) catalyzes the first and rate-limiting step in the polyol pathway, and AR inhibition has been shown to reduce diabetic complications, including DbCM in animal models and in patients with DbCM. Previous AR inhibitors (ARIs) were limited by poor specificity resulting in unacceptable tolerability and safety profile. AT-001 is a novel investigational highly specific ARI with higher binding affinity and greater selectivity than previously studied ARIs. ARISE-HF (NCT04083339) is an ongoing Phase 3 randomized, placebo-controlled, double blind, global clinical study to investigate the efficacy of AT-001 (1000 mg twice daily [BID] and 1500 mg BID) in 675 T2DM patients with DbCM at high risk of progression to overt HF. ARISE-HF assesses the ability of AT-001 to improve or prevent decline in exercise capacity as measured by functional capacity (changes in peak oxygen uptake [peak VO2]) over 15 (and possibly 27) months of treatment. Additional endpoints include percentage of patients progressing to overt HF, health status metrics, echocardiographic measurements, and changes in cardiacbiomarkers. RESULTS: The ARISE-HF Trial is fully enrolled. CONCLUSIONS: This report describes the rationale and study design of ARISE-HF.

Derivation and Validation of a Clinical Score for Predicting Postoperative Atrial Fibrillation in Noncardiac Elective Surgery (the HART Score).

Postoperative atrial fibrillation (POAF) represents the most frequent cardiac arrhythmia in the surgical setting. It affects almost 3% of all patients over 45 years old who underwent noncardiovascular surgery and is associated with a higher risk of stroke, heart failure, myocardial infarction, and cardiac arrest. The study aimed to assess independent predictors of POAF and derive and validate a score for risk prediction in clinical practice. This was a retrospective cohort study including all consecutive candidates to all types of noncardiac elective surgery attending a cardiological preoperative assessment from 2016 to 2019. Exclusion criteria were a previous diagnosis of AF and the cancelation of the planned surgery. A total of 2,048 patients were enrolled (1350 men, aged 72 ± 12 years). A total of 44 patients experienced POAF (2.1%) - median 3 days (first to third quartile 2 to 4 days). Age (odds ratio [OR] 1.03 for each year, 95% confidence interval [CI] 1.01 to 1.07), hypertension (OR 3.43, 95% CI 1.22 to 9.63), thyroid dysfunction (OR 2.47, 95% CI 1.22 to 5.01), and intermediate or high-risk surgery (OR 18.28, 95% CI 2.51 to 33.09) resulted as independent predictors of POAF (all p <0.05). The Hypertension, Age, surgery Risk, and Thyroid dysfunction score (OR 2.59 for each point, 95% CI 1.79 to 3.75, p <0.001) was then created based on those 4 items. A cut-off score ≥6 had a 70% sensitivity and a 72% specificity in detecting POAF (area under the curve 0.76). Bootstrapping for internal validation confirmed the overall results (area under the curve 0.72). In conclusion, POAF complicates around 2% of all noncardiac surgery. A 4-item risk score, such as the Hypertension, Age, surgery Risk, and Thyroid dysfunction score, could be effective in implementing POAF screening and improving management.

Sports Activity and Arrhythmic Risk in Cardiomyopathies and Channelopathies: A Critical Review of European Guidelines on Sports Cardiology in Patients with Cardiovascular Diseases.

The prediction and prevention of sudden cardiac death is the philosopher's stone of clinical cardiac electrophysiology. Sports can act as triggers of fatal arrhythmias and therefore it is essential to promptly frame the athlete at risk and to carefully evaluate the suitability for both competitive and recreational sports activity. A history of syncope or palpitations, the presence of premature ventricular complexes or more complex arrhythmias, a reduced left ventricular systolic function, or the presence of known or familiar heart disease should prompt a thorough evaluation with second level examinations. In this regard, cardiac magnetic resonance and electrophysiological study play important roles in the diagnostic work-up. The role of genetics is increasing both in cardiomyopathies and in channelopathies, and a careful evaluation must be focused on genotype positive/phenotype negative subjects. In addition to being a trigger for fatal arrhythmias in certain cardiomyopathies, sports also play a role in the progression of the disease itself, especially in the case arrhythmogenic right ventricular cardiomyopathy. In this paper, we review the latest European guidelines on sport cardiology in patients with cardiovascular diseases, focusing on arrhythmic risk stratification and the management of cardiomyopathies and channelopathies.

Prognostic value of the chest X-ray in patients hospitalised for heart failure.

BACKGROUND: Patients admitted to hospital with heart failure will have had a chest X-ray (CXR), but little is known about their prognostic significance. We aimed to report the prevalence and prognostic value of the initial chest radiograph findings in patients admitted to hospital with heart failure (acute heart failure, AHF). METHODS: The erect CXRs of all patients admitted with AHF between October 2012 and November 2016 were reviewed for pulmonary venous congestion, Kerley B lines, pleural effusions and alveolar oedema. Film projection (whether anterior-posterior [AP] or posterior-anterior [PA]) and cardiothoracic ratio (CTR) were also recorded. TRIAL REGISTRATION: ISRCTN96643197 RESULTS: Of 1145 patients enrolled, 975 [median (interquartile range) age 77 (68-83) years, 61% with moderate, or worse, left ventricular systolic dysfunction, and median NT-proBNP 5047 (2337-10,945) ng/l] had an adequate initial radiograph, of which 691 (71%) were AP. The median CTR was 0.57 (IQR 0.53-0.61) in PA films and 0.60 (0.55-0.64) in AP films. Pulmonary venous congestion was present in 756 (78%) of films, Kerley B lines in 688 (71%), pleural effusions in 649 (67%) and alveolar oedema in 622 (64%). A CXR score was constructed using the above features. Increasing score was associated with increasing age, urea, NT-proBNP, and decreasing systolic blood pressure, haemoglobin and albumin; and with all-cause mortality on multivariable analysis (hazard ratio 1.10, 95% confidence intervals 1.07-1.13, p < 0.001). CONCLUSIONS: Radiographic evidence of congestion on a CXR is very common in patients with AHF and is associated with other clinical measures of worse prognosis. Signs of heart failure are highly prevalent in patients presenting to hospital with acute heart failure and when combined into a chest x-ray score, relate to a worse long term risk of death.

Myocardial Infarction Without Obstructive Coronary Artery Disease (MINOCA): A Practical Guide for Clinicians.

Myocardial infarction without obstructive coronary artery disease (MINOCA) is defined by the evidence of spontaneous acute myocardial infarction (MI) and angiographic exclusion of coronary stenoses ≥50% in any potential infarct related artery, after having ruled out other clinically overt causes for the acute presentation. The introduction of this new concept was meant to encourage discovery of putative pathophysiological mechanisms and development of specific therapeutic measures. In recent years, we have witnessed significant advances in the fields of epidemiology, pathophysiology, diagnosis, prognosis estimation and therapeutics of MINOCA. So far, however, the definition of MINOCA has been rather heterogeneous since specific cardiac conditions such as myocarditis and Takotsubo syndrome have often been included, generating conflicting results. In this review, we summarize the current state-of-the-art in the expanding MINOCA field and propose a comprehensive stepwise approach for the rational diagnostic assessment of these challenging patients. Our aim is to provide clinicians with an "Ariadne's thread" according to the recent fourth universal definition of MI in order to not get lost in MINOCA's labyrinth.

High-sensitivity C-reactive protein in chronic heart failure: patient characteristics, phenotypes, and mode of death.

AIMS: Plasma concentrations of high-sensitivity C-reactive protein (hsCRP) are often raised in chronic heart failure (CHF) and might indicate inflammatory processes that could be a therapeutic target. We aimed to study the associations between hsCRP, mode and cause of death in patients with CHF. METHODS AND RESULTS: We enrolled 4423 patients referred to a heart failure clinic serving a local population. CHF was defined as relevant symptoms or signs with either a reduced left ventricular ejection fraction <40% or raised plasma concentrations of amino-terminal pro-B type natriuretic peptide (NT-proBNP >125 pg/mL). The median [interquartile range (IQR)] plasma hsCRP for patients diagnosed with CHF (n = 3756) was 3.9 (1.6-8.5) mg/L and 2.7 (1.3-5.1) mg/L for those who were not (n = 667; P < 0.001). Patients with hsCRP ≥10 mg/L (N = 809; 22%) were older and more congested than those with hsCRP <2 mg/L (N = 1117, 30%). During a median follow-up of 53 (IQR 28-93) months, 1784 (48%) patients with CHF died. Higher plasma hsCRP was associated with greater mortality, independent of age, symptom severity, creatinine, and NT-proBNP. Comparing a hsCRP ≥10 mg/L to <2 mg/L, the hazard ratio for all-cause mortality was 2.49 (95% confidence interval 2.19-2.84; P < 0.001), for cardiovascular (CV) mortality was 2.26 (1.91-2.68; P < 0.001), and for non-CV mortality was 2.96 (2.40-3.65; P < 0.001). CONCLUSION: In patients with CHF, a raised plasma hsCRP is associated with more congestion and a worse prognosis. The proportion of deaths that are non-CV also increases with higher hsCRP.

Prevalence and Incidence of Atrial Fibrillation in Ambulatory Patients With Heart Failure.

Heart failure (HF) and atrial fibrillation (AF) commonly co-exist. We aimed to determine the prevalence and incidence of AF in ambulatory patients with HF. HF was defined by the presence of symptoms or signs supported by objective evidence of cardiac dysfunction: either a left ventricular ejection fraction (LVEF) ≤45% (HF and a reduced ejection fraction, HFrEF), or LVEF >45% and a raised plasma concentration of amino-terminal pro-B type natriuretic peptide (NT-proBNP >220 ng/L; HFpEF). Of 3,570 patients with HF, 1,164 were in AF at baseline (33%), with a higher prevalence among patients with HFpEF compared with HFrEF (40% vs 26%, respectively, p <0.001). Compared with patients with HF in sinus rhythm, those in AF were older, had more severe symptoms and higher NT-proBNP, worse renal function, and were more likely to receive loop diuretics, despite having a higher LVEF. Of those in sinus rhythm, 1,372 patients had HFrEF and 1,034 had HFpEF. The incidence of AF at 1 year (3.0%) was similar for each phenotype (p = 0.73). Increasing age, male gender, history of paroxysmal AF, and higher plasma concentrations of NT-proBNP were independent predictors of incident AF during a median follow-up of 1,574 (interquartile range: 749 to 2,821) days; the predictors were similar for each phenotype. In conclusion, the prevalence of AF is high, especially in patients with HFpEF, but its incidence is modest. This may be because their onset is near simultaneous with the development of AF precipitating the onset of HF.

Tachycardiomyopathy in Patients without Underlying Structural Heart Disease.

Tachycardiomyopathy (TCM) is an underestimated cause of reversible left ventricle dysfunction. The aim of this study was to identify the predictors of recurrence and incidence of major cardiovascular events in TCM patients without underlying structural heart disease (pure TCM). The prospective, observational study enrolled all consecutive pure TCM patients. The diagnosis was suspected in patients admitted for heart failure (HF) with a reduced ejection fraction and concomitant persistent arrhythmia. Pure TCM was confirmed after the clinical and echocardiographic recovery during follow-up. From 107 pure TCM patients (9% of all HF admission, the median follow-up 22.6 months), 17 recurred, 51 were hospitalized for cardiovascular reasons, two suffered from thromboembolic events and one died. The diagnosis of obstructive sleep apnoea syndrome (OSAS, hazard ratio (HR) 5.44), brain natriuretic peptide on admission (HR 1.01 for each pg/mL) and the heart rate at discharge (HR 1.05 for each bpm) were all independent predictors of TCM recurrence. The left ventricular ejection fraction at discharge (HR 0.96 for each%) and the heart rate at discharge (HR 1.02 for each bpm) resulted as independent predictors of cardiovascular-related hospitalization. Pure TCM is more common than previously thought and associated with a good long-term survival but recurrences and hospitalizations are frequent. Reversing OSAS and controlling the heart rate could prevent TCM-related complications.

Prevalence, pattern and clinical relevance of ultrasound indices of congestion in outpatients with heart failure.

AIMS: Even if treatment controls symptoms, patients with heart failure may still be congested. We aimed at assessing the prevalence and clinical relevance of congestion in outpatients with chronic heart failure. METHODS AND RESULTS: We recorded clinical and ultrasound [lung B-lines; inferior vena cava (IVC) diameter; internal jugular vein diameter before and after a Valsalva manoeuvre (JVD ratio)] features of congestion in heart failure patients during a routine check-up. Of 342 patients who attended, predominantly in New York Heart Association class I or II (n = 257; 75%), 242 (71%) had at least one feature of congestion, either clinical (n = 139; 41%) or by ultrasound (n = 199; 58%). Amongst patients (n = 203, 59%) clinically free of congestion, 31 (15%) had ≥ 14 B-lines, 57 (29%) had a dilated IVC (> 2.0 cm), 38 (20%) had an abnormal JVD ratio (< 4), 87 (43%) had at least one of these, and 27 (13%) had two or more. During a median follow-up of 234 (interquartile range 136-351) days, 60 patients (18%) died or were hospitalized for heart failure. In univariable analysis, each clinical and ultrasound measure of congestion was associated with increased risk but, in multivariable models, only higher N-terminal pro-B-type natriuretic peptide and IVC, and lower JVD ratio, were associated with the composite outcome. CONCLUSIONS: Many patients with chronic heart failure with few symptoms have objective evidence of congestion and this is associated with an adverse prognosis. Whether using these measures of congestion to guide management improves outcomes requires investigation.

Clinical and prognostic relationships of pulmonary artery to aorta diameter ratio in patients with heart failure: a cardiac magnetic resonance imaging study.

BACKGROUND: The pulmonary artery (PA) distends as pressure increases. HYPOTHESIS: The ratio of PA to aortic (Ao) diameter may be an indicator of pulmonary hypertension and consequently carry prognostic information in patients with chronic heart failure (HF). METHODS: Patients with chronic HF and control subjects undergoing cardiac magnetic resonance imaging were evaluated. The main PA diameter and the transverse axial Ao diameter at the level of bifurcation of the main PA were measured. The maximum diameter of both vessels was measured throughout the cardiac cycle and the PA/Ao ratio was calculated. RESULTS: A total of 384 patients (mean age, 69 years; mean left ventricular ejection fraction, 40%; median NT-proBNP, 1010 ng/L [interquartile range, 448-2262 ng/L]) and 38 controls were included. Controls and patients with chronic HF had similar maximum Ao and PA diameters and PA/Ao ratio. During a median follow-up of 1759 days (interquartile range, 998-2269 days), 181 patients with HF were hospitalized for HF or died. Neither PA diameter nor PA/Ao ratio predicted outcome in univariable analysis. In a multivariable model, only age and NT-proBNP were independent predictors of adverse events. CONCLUSIONS: The PA/Ao ratio is not a useful method to stratify prognosis in patients with HF.

Is Swimming Safe in Heart Failure? A Systematic Review.

It is not clear whether swimming is safe in patients with chronic heart failure. Ten studies examining the hemodynamic effects of acute water immersion (WI) (155 patients; average age 60 years; 86% male; mean left ventricular ejection fraction (LVEF) 29%) and 6 randomized controlled trials of rehabilitation comparing swimming with either medical treatment only (n = 3) or cycling (n = 1) or aerobic exercise (n = 2), (136 patients, average age 59 years; 84% male, mean LVEF 31%) were considered. In 7 studies of warm WI (30-35°C): heart rate (HR) fell (2% to -15%), and both cardiac output (CO) (7-37%) and stroke volume (SV) increased (13-41%). In 1 study of hot WI (41°C), systemic vascular resistance (SVR) fell (41%) and HR increased (33%). In 2 studies of cold WI (12-22°C), there were no consistent effects on HR and CO. Compared with medical management, swimming led to a greater increase in peak VO2 (7-14%) and 6 minute walk test (6MWT) (7-13%). Compared with cycle training, combined swimming and cycle training led to a greater reduction in resting HR (16%), a greater increase in resting SV (23%) and SVR (15%), but no changes in resting CO and a lesser increase in peak VO2 (6%). Compared with aerobic training, combined swimming and aerobic training lead to a reduction in resting HR (19%) and SVR (54%) and a greater increase in SV (34%), resting CO (28%), LVEF (9%), and 6MWT (70%). Although swimming appears to be safe, the studies conducted have been small, very heterogeneous, and inconclusive.

Non-invasive measurement of right atrial pressure by near-infrared spectroscopy: preliminary experience. A report from the SICA-HF study.

AIMS: To assess the clinical value of measuring right atrial pressure (RAP) using near-infrared spectroscopy (NIRS) in patients with chronic heart failure (CHF). METHODS AND RESULTS: RAP was measured non-invasively using NIRS over the external jugular vein (Venus 1000, Mespere LifeSciences, Canada) in ambulatory patients with CHF enrolled in the Studies Investigating Co-morbidities Aggravating Heart Failure (SICA-HF) programme. Comparing 243 patients with CHF (mean age 71 years; mean left ventricular ejection fraction (LVEF) 45%, median NT-proBNP 788 ng/L) to 49 controls (NT-proBNP ≤125 ng/L), RAP was 7 [interquartile range (IQR) 4-11] mmHg vs. 4 (IQR 3-8) mmHg (P < 0.001). Those with RAP ≥10 mmHg (n = 75) were older, had more severe clinical congestion and renal dysfunction, higher plasma NT-proBNP, larger left atrial volume, higher systolic pulmonary pressure and were more often in atrial fibrillation but their LVEF was similar to patients with lower RAP. During a median follow-up of 595 (IQR: 492-714) days, 49 patients (20%) died or were hospitalized for worsening CHF. Compared with patients with RAP ≤5 mmHg, those with RAP ≥10 mmHg had a greater risk of an event (hazard ratio 2.38, 95% confidence interval 1.19-4.75, P = 0.014). RAP measured by NIRS predicted outcome, competing with NT-proBNP in multivariable models. CONCLUSIONS: Measuring RAP using NIRS identifies ambulatory patients with CHF who have more severe congestion and a worse outcome. The device might be a useful objective method of monitoring RAP, especially for those inexperienced in eliciting physical signs or when measurement of natriuretic peptides is not immediately available.

What proportion of patients with chronic heart failure are eligible for sacubitril-valsartan?

AIMS: The PARADIGM-HF trial showed that sacubitril-valsartan, an ARB-neprilysin inhibitor, is more effective than enalapril for some patients with heart failure (HF). It is uncertain what proportion of patients with HF would be eligible for sacubitril-valsartan in clinical practice. METHODS AND RESULTS: Between 2001 and 2014, 6131 patients consecutively referred to a community HF clinic with suspected HF were assessed. The criteria required to enter the randomized phase of PARADIGM-HF, including symptoms, NT-proBNP, and current treatment with or without target doses of ACE inhibitors or ARBs, were applied to identify the proportion of patients eligible for sacubitril-valsartan. Recognizing the diversity of clinical opinion and guideline recommendations concerning this issue, entry criteria were applied singly and in combination. Of 1396 patients with reduced left ventricular ejection fraction (≤40%, HFrEF) and contemporary measurement of NT-proBNP, 379 were on target doses of an ACE inhibitor or ARB at their initial visit and, of these, 172 (45%) fulfilled the key entry criteria for the PARADIGM-HF trial. Lack of symptoms (32%) and NT-proBNP <600 ng/L (49%) were common reasons for failure to fulfil criteria. A further 122 patients became eligible during follow-up (n = 294, 21%). However, if background medication and doses were ignored, then 701 (50%) were eligible initially and a further 137 became eligible during follow-up. CONCLUSIONS: Of patients with HFrEF referred to a clinic such as ours, only 21% fulfilled the PARADIGM-HF randomization criteria, on which the ESC Guidelines are based; this proportion rises to 60% if background medication is ignored.

Takotsubo syndrome in the paediatric population: a case report and a systematic review.

We describe the case of a takotsubo syndrome in a 12-year-old male patient following an acute intracranial haemorrhage, which had a favourable outcome. We also performed a systematic review of published case reports in patients younger than 18 years. Although takotsubo syndrome is common in postmenopausal women, in the paediatric population it equally affects both sexes. Compared with adults, paediatric patients more commonly present with heart failure symptoms or loss of consciousness. A higher proportion of paediatric patients have ST segment depression on ECG. Moreover, in younger patients, a high proportion has nonapical anatomical variants and more severe left ventricular impairment. The increase in troponin and the decrease in left ventricular ejection fraction, the prevalence of neurological or psychological disorders, and in-hospital outcome are similar between adults and children.

Cardiac Dysfunction, Congestion and Loop Diuretics: their Relationship to Prognosis in Heart Failure.

BACKGROUND: Diuretics are the mainstay of treatment for congestion but concerns exist that they adversely affect prognosis. We explored whether the relationship between loop diuretic use and outcome is explained by the underlying severity of congestion amongst patients referred with suspected heart failure. METHOD AND RESULTS: Of 1190 patients, 712 had a left ventricular ejection fraction (LVEF) ≤50 %, 267 had LVEF >50 % with raised plasma NTproBNP (>400 ng/L) and 211 had LVEF >50 % with NTproBNP ≤400 ng/L; respectively, 72 %, 68 % and 37 % of these groups were treated with loop diuretics including 28 %, 29 % and 10 % in doses ≥80 mg furosemide equivalent/day. Compared to patients with cardiac dysfunction (either LVEF ≤50 % or NT-proBNP >400 ng/L) but not taking a loop diuretic, those taking a loop diuretic were older and had more clinical evidence of congestion, renal dysfunction, anaemia and hyponatraemia. During a median follow-up of 934 (IQR: 513-1425) days, 450 patients were hospitalized for HF or died. Patients prescribed loop diuretics had a worse outcome. However, in multi-variable models, clinical, echocardiographic (inferior vena cava diameter), and biochemical (NTproBNP) measures of congestion were strongly associated with an adverse outcome but not the use, or dose, of loop diuretics. CONCLUSIONS: Prescription of loop diuretics identifies patients with more advanced features of heart failure and congestion, which may account for their worse prognosis. Further research is needed to clarify the relationship between loop diuretic agents and outcome; imaging and biochemical measures of congestion might be better guides to diuretic dose than symptoms or clinical signs.

New anthyarrhythmic drugs for atrial fibrillation.

Atrial fibrillation (AF) is a common arrhythmia associated with increased mortality and morbidity. Different studies have shown no significant difference between rhythm and rate control strategies in terms of mortality. Moreover, the use of antiarrhythmic drugs is afflicted by cardiac and extracardiac toxicity and related costs of hospitalization. Nevertheless, some patients require a rhythm-control strategy and new anti-AF agents are being sought. Only few novel agents showed promising results in term of efficacy and safety. Dronedarone and vernakalant are two of these compounds, respectively introduced for the chronic and acute rhythm control of AF. This article will review pharmacology and clinical evidence on the use of dronedarone and vernakalant and will mention currently investigated new antiarrhythmic drugs.

Intravenous vernakalant for the rapid conversion of recent onset atrial fibrillation: systematic review and meta-analysis.

Atrial fibrillation is the most common cardiac arrhythmia and is associated with increased mortality and morbidity. Conversion to sinus rhythm is usually appropriate in patients with acute, symptomatic atrial fibrillation in order to reduce symptoms and prevent complications. Electrical cardioversion is the most used and widespread technique, but requires deep sedation and a fasting state. Pharmacological alternatives are burdened by a delayed onset of action and potential proarrhythmic effects. Therefore, new therapeutic options are being sought. Among those, vernakalant, showed a good efficacy profile and a short onset of action, but with conflicting evidence regarding potential serious adverse events. This drug profile will summarize the pharmacology behind this new drug and review recent evidence in terms of safety and efficacy.

Cardiac resynchronization therapy improves ejection fraction and cardiac remodelling regardless of patients' age.

AIMS: Cardiac resynchronization therapy (CRT) improves symptoms and reduces mortality in heart failure (HF) patients, but little data exist on the efficacy of CRT in the elderly. The aim of our study is to define CRT-related benefits in terms of left ventricular ejection fraction (LVEF) improvement in two subgroups of patients (<75 and ≥75 years old) and test possible differences between these two groups. METHODS AND RESULTS: Single-centre prospective observational study including 65 patients with optimally treated, advanced HF and indication to CRT. All patients were investigated with clinical evaluation, Minnesota Living with Heart Failure Questionnaire (MLHFQ), 12-lead electrocardiogram, and full echocardiographical study before CRT implant and 3 and 12 months after. Left ventricular ejection fraction showed a time-related improvement in the whole population (+10.6% over 12 months) as well as in each subgroup. The magnitude of LVEF improvement was similar in elderly and non-elderly patients (+13.6 vs. +7.9%; P = ns). Left ventricular diameters, pulmonary artery systolic pressure, New York Heart Association class, MLHFQ score, and QRS width all showed a time-related improvement in the whole population as well as in each subgroup. End-diastolic left ventricular diameter remodelling and QRS width reduction were significantly more pronounced in the elderly, whereas other clinical and instrumental secondary endpoints showed a similar improvement between ≥75 and <75 years old patients. There was no significant difference regarding mortality between elderly and non-elderly patients. CONCLUSION: Cardiac resynchronization therapy is as effective in improving LVEF in elderly as in non-elderly patients. Age alone should not be a determinant to restrict resynchronization therapy in HF patients.