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Background Prognosis of Takotsubo syndrome (TTS) remains controversial due to scarcity of available data. Additionally, the effect of the triggering factors remains elusive. Objectives This study compared prognosis between TTS and acute coronary syndrome (ACS) patients and investigated short- and long-term outcomes in TTS based on different triggers. Methods Patients with TTS were enrolled from the International Takotsubo Registry. Long-term mortality of patients with TTS was compared to an age- and sex-matched cohort of patients with ACS. In addition, short- and long-term outcomes were compared between different groups according to triggering conditions. Results Overall, TTS patients had a comparable long-term mortality risk with ACS patients. Of 1,613 TTS patients, an emotional trigger was detected in 485 patients (30%). Of 630 patients (39%) related to physical triggers, 98 patients (6%) had acute neurologic disorders, while in the other 532 patients (33%), physical activities, medical conditions, or procedures were the triggering conditions. The remaining 498 patients (31%) had no identifiable trigger. TTS patients related to physical stress showed higher mortality rates than ACS patients during long-term follow-up, whereas patients related to emotional stress had better outcomes compared with ACS patients. Conclusions Overall, TTS patients had long-term outcomes comparable to age- and sex-matched ACS patients. Also, we demonstrated that TTS can either be benign or a life-threating condition depending on the inciting stress factor. We propose a new classification based on triggers, which can serve as a clinical tool to predict short- and long-term outcomes of TTS. (International Takotsubo Registry [InterTAK Registry]; NCT01947621)

Cardiac magnetic resonance myocardial feature tracking (CMR-FT) derived global strain assessments provide incremental prognostic information in patients following acute myocardial infarction (AMI). Functional analyses of the remote myocardium (RM) are scarce and whether they provide an additional

Diabetes mellitus is associated with significant morbidity and mortality. The lifetime glycemic exposure (usually much longer in type 1 than in type 2 diabetes mellitus) is integral in the development of comorbidities. The title of a recent paper read, “Heart failure: a cardiovascular outcome in

Objectives We sought to determine whether structured exercise training (ET) improves maximal exercise capacity, left ventricular diastolic function, and quality of life (QoL) in patients with heart failure with preserved ejection fraction (HFpEF). Background Nearly one-half of patients with heart failure experience HFpEF, but effective therapeutic strategies are sparse. Methods A total of 64 patients (age 65 ± 7 years, 56% female) with HFpEF were prospectively randomized (2:1) to supervised endurance/resistance training in addition to usual care (ET, n = 44) or to usual care alone (UC) (n = 20). The primary endpoint was the change in peak Vo2 after 3 months. Secondary endpoints included effects on cardiac structure, diastolic function, and QoL. Results Peak Vo2 increased (16.1 ± 4.9 ml/min/kg to 18.7 ± 5.4 ml/min/kg; p Conclusions Exercise training improves exercise capacity and physical dimensions of QoL in HFpEF. This benefit is associated with atrial reverse remodeling and improved left ventricular diastolic function. (Exercise Training in Diastolic Heart Failure–Pilot Study: A Prospective, Randomised, Controlled Study to Determine the Effects of Physical Training on Exercise Capacity and Quality of Life [Ex-DHF-P]; ISRCTN42524037)

Objectives: We investigated changes in Na+currents (INa) in permanent (or chronic) atrial fibrillation (AF) and the effects of INainhibition using ranolazine (Ran) on arrhythmias and contractility ...

Objectives The purpose of this study was to examine the impact of obesity and weight loss on the angiogenic and regenerative capacity of endothelial progenitor cells (EPCs). Background EPCs participate in angiogenesis and tissue repair. Several cardiovascular risk factors are associated with EPC dysfunction. Methods Early outgrowth EPCs were isolated from 49 obese (age 42 ± 14 years; body mass index 42 ± 7 kg/m2) normoglycemic participants in a professional weight reduction program and compared with those from 49 age-matched lean controls. EPC function was tested both in vitro and in vivo. Results EPCs expanded from the obese possessed reduced adhesive, migratory, and angiogenic capacity, and mice treated with obese EPCs exhibited reduced EPC homing in ischemic hind limbs in vivo. EPCs from the obese subjects failed to respond to conditioned medium of lean controls or to potent angiogenic factors such as vascular endothelial growth factor. Although no differences existed between lean and obese EPCs regarding the surface expression of vascular endothelial growth factor or chemokine receptors, basal p38 mitogen-activated protein kinase (MAPK) phosphorylation was elevated in obese EPCs (3.7 ± 2.1-fold increase; p = 0.006). These cells also showed reduced secretion of the angiogenic chemokines interleukin-8 (p = 0.047) and monocyte chemoattractant protein-1 (p = 0.012). By inhibiting p38 MAPK, we could restore chemokine levels to those of lean control EPCs and also improve the angiogenic properties of obese EPCs. Accordingly, 6-month follow-up of 26 obese persons who achieved significant weight reduction revealed normalization of p38 MAPK phosphorylation levels and improved EPC function. Conclusions Obesity is associated with a reversible functional impairment of EPCs. This involves reduced secretion of angiogenic chemokines and increased basal phosphorylation of signaling molecules, notably p38 MAPK.

ObjectivesThis study was designed to investigate whether nicotinamide adenine dinucleotide 3-phosphate (reduced form) (NADPH) oxidase is expressed in the human heart and whether it contributes to reactive oxygen species (ROS) production in heart failure.BackgroundA phagocyte-type NADPH oxidase complex is a major source of ROS in the vasculature and is implicated in the pathophysiology of hypertension and atherosclerosis. An increase in myocardial oxidative stress due to excessive production of ROS may be involved in the pathophysiology of congestive heart failure. Recent studies have suggested an important role for myocardial NADPH oxidase in experimental models of cardiac disease. However, it is unknown whether NADPH oxidase is expressed in the human myocardium or if it has any role in human heart failure.MethodsMyocardium of explanted nonfailing (n = 9) and end-stage failing (n = 13) hearts was studied for the expression of NADPH oxidase subunits and oxidase activity.ResultsThe NADPH oxidase subunits p22phox, gp91phox, p67phox, and p47phoxwere all expressed at messenger ribonucleic acid and protein level in cardiomyocytes of both nonfailing and failing hearts. NADPH oxidase activity was significantly increased in end-stage failing versus nonfailing myocardium (5.86 ± 0.41 vs. 3.72 ± 0.39 arbitrary units; p < 0.01). The overall level of oxidase subunit expression was unaltered in failing compared with nonfailing hearts. However, there was increased translocation of the regulatory subunit, p47phox, to myocyte membranes in failing myocardium.ConclusionsThis is the first report of the presence of NADPH oxidase in human myocardium. The increase in NADPH oxidase activity in the failing heart may be important in the pathophysiology of cardiac dysfunction by contributing to increased oxidative stress.

Background: Current guidelines advise the use of echocardiography to non-invasively estimate the likelihood of pulmonary hypertension (PH) in patients. The maximal tricuspid regurgitation velocity (TRVmax) is recommended as the main parameter to use in assessing the echocardiographic probability of

OBJECTIVESWe sought to define the therapeutic dose range of levosimendan in patients with New York Heart Association class II-IV heart failure of ischemic origin.BACKGROUNDLevosimendan is a calcium sensitizer for treatment of acute decompensated heart failure.METHODSA double-blind, placebo-controlled, randomized, multicenter, parallel-group study included 151 adult patients. Levosimendan was given as a 10-min intravenous bolus of 3, 6, 12, 24 or 36 μg/kg, followed by a 24-h infusion of 0.05, 0.1, 0.2, 0.4 or 0.6 μg/kg/min, respectively. Dobutamine, for comparative purposes, was given as an open-label infusion (6 μg/kg/min). The primary efficacy variable was the proportion of patients achieving in each treatment group at least one of the following: 1) a ≥15% increase in stroke volume (SV) at 23 h to 24 h; 2) a ≥25% decrease in pulmonary capillary wedge pressure (PCWP) (and ≥4 mm Hg) at 23 h to 24 h; 3) a ≥40% increase in cardiac output (CO) (with change in heart rate [HR]

The study was designed to evaluate the functional impact of nitric oxide (NO) generation within the myocardium on cardiac contraction in the failing human heart.Heart failure is associated with activation of cytokines and expression of inducible nitric oxide synthase (NOS II), which generates NO from L-arginine. Nitric oxide has been shown to modulate myocardial performance, raising the possibility that cardiac generation of NO by NOS II modulates cardiac contraction in the failing human heart.Left ventricular (LV) tissue of 24 patients with end-stage heart failure was obtained during cardiac transplantation. Gene expression of NOS II and endothelial NO-synthase (NOS III) was quantified by competitive reverse transcription-polymerase chain reaction and compared to tissues of five nonfailing donor hearts. Nitric oxide synthase II activity was determined by citrulline assay and related to changes in force of contraction induced by the beta-adrenergic agonist isoproterenol, NO-donors and/or N-mono-methyl-L-arginine (L-NMMA), an inhibitor of NOS.While NOS III mRNA was reduced in failing hearts, NOS II mRNA was increased in failing LV tissue and correlated with NOS II activity. High NOS II activity was associated with early relaxation and impaired responsiveness to beta-adrenergic stimulation, that is, the inotropic response to isoproterenol in failing hearts was inversely related to NOS II activity (r=0.61, p0.005). Nitric oxide donors or L-NMMA did not affect myocardial performance in failing hearts at baseline. However, L-NMMA enhanced the positive inotropic response to beta-adrenergic stimulation in failing hearts with high NOS II activity. Nitric oxide donors attenuated the isoproterenol-induced increase in force of contraction of failing hearts.Cardiac production of NO by NOS II attenuates the positive inotropic effects of beta-adrenergic stimulation and hastens relaxation in failing human hearts.

We sought to determine whether structured exercise training (ET) improves maximal exercise capacity, left ventricular diastolic function, and quality of life (QoL) in patients with heart failure with preserved ejection fraction (HFpEF).Nearly one-half of patients with heart failure experience HFpEF, but effective therapeutic strategies are sparse.A total of 64 patients (age 65 ± 7 years, 56% female) with HFpEF were prospectively randomized (2:1) to supervised endurance/resistance training in addition to usual care (ET, n = 44) or to usual care alone (UC) (n = 20). The primary endpoint was the change in peak Vo(2) after 3 months. Secondary endpoints included effects on cardiac structure, diastolic function, and QoL.Peak Vo(2) increased (16.1 ± 4.9 ml/min/kg to 18.7 ± 5.4 ml/min/kg; p0.001) with ET and remained unchanged (16.7 ± 4.7 ml/min/kg to 16.0 ± 6.0 ml/min/kg; p = NS) with UC. The mean benefit of ET was 3.3 ml/min/kg (95% confidence interval [CI]: 1.8 to 4.8, p0.001). E/e' (mean difference of changes: -3.2, 95% CI: -4.3 to -2.1, p0.001) and left atrial volume index (milliliters per square meter) decreased with ET and remained unchanged with UC (-4.0, 95% CI: -5.9 to -2.2, p0.001). The physical functioning score (36-Item Short-Form Health Survey) improved with ET and remained unchanged with UC (15, 95% CI: 7 to 24, p0.001). The ET-induced decrease of E/e' was associated with 38% gain in peak Vo(2) and 50% of the improvement in physical functioning score.Exercise training improves exercise capacity and physical dimensions of QoL in HFpEF. This benefit is associated with atrial reverse remodeling and improved left ventricular diastolic function. (Exercise Training in Diastolic Heart Failure-Pilot Study: A Prospective, Randomised, Controlled Study to Determine the Effects of Physical Training on Exercise Capacity and Quality of Life [Ex-DHF-P]; ISRCTN42524037).

We investigated changes in Na(+) currents (I(Na)) in permanent (or chronic) atrial fibrillation (AF) and the effects of I(Na) inhibition using ranolazine (Ran) on arrhythmias and contractility in human atrial myocardium.Electrical remodeling during AF is typically associated with alterations in Ca(2+) and K(+) currents. It remains unclear whether I(Na) is also altered.Right atrial appendages from patients with AF (n = 23) and in sinus rhythm (SR) (n = 79) were studied.Patch-clamp experiments in isolated atrial myocytes showed significantly reduced peak I(Na) density ( approximately 16%) in AF compared with SR, which was accompanied by a 26% lower expression of Nav1.5 (p0.05). In contrast, late I(Na) was significantly increased in myocytes from AF atria by approximately 26%. Ran (10 mumol/l) decreased late I(Na) by approximately 60% (p0.05) in myocytes from patients with AF but only by approximately 18% (p0.05) in myocytes from SR atria. Proarrhythmic activity was elicited in atrial trabeculae exposed to high [Ca(2+)](o) or isoprenaline, which was significantly reversed by Ran (by 83% and 100%, respectively). Increasing pacing rates from 0.5 to 3.0 Hz led to an increase in diastolic tension that could be significantly decreased by Ran in atria from SR and AF patients.Na(+) channels may contribute to arrhythmias and contractile remodeling in AF. Inhibition of I(Na) with Ran had antiarrhythmic effects and improved diastolic function. Thus, inhibition of late I(Na) may be a promising new treatment option for patients with atrial rhythm disturbances and diastolic dysfunction.

Heart failure with preserved ejection fraction (HFpEF) accounts for 50p of all HF patients. Currently, there is no specific treatment for diastolic dysfunction. Ranolazine may improve diastolic function by inhibiting the late Na current. We investigated if ranolazine improved diastolic

OBJECTIVES: We assessed the predictive value of heart-type fatty acid-binding protein (H-FABP) in normotensive patients with acute pulmonary embolism (PE). BACKGROUND: Risk stratification of initially normotensive patients with PE on the basis of right ventricular dysfunction or injury remains controversial. Previous studies investigating biomarkers or imaging modalities included unselected patients, some of whom presented with cardiogenic shock. METHODS: We included 126 consecutive normotensive patients with confirmed PE. Complicated 30-day outcome was defined as death, resuscitation, intubation, or use of catecholamines. Long-term survival was assessed by follow-up clinical examination. RESULTS: During the first 30 days, 9 (7%) patients suffered complications. These patients had higher baseline H-FABP values (median, 11.2 ng/ml [interquartile range: 8.0 to 36.8 ng/ml]) compared with patients with an uncomplicated course (3.4 ng/ml [2.1 to 4.9 ng/ml]; p < 0.001). H-FABP values were above the calculated (by receiver operating characteristic curve analysis) cutoff value of 6 ng/ml in 29 patients. Eight (28%) of them suffered complications versus 1 of 97 patients with low H-FABP (negative predictive value, 99%; p < 0.001). By logistic regression, elevated (> or =6 ng/ml) H-FABP was associated with a 36.6-fold increase in the death or complication risk. The combination of H-FABP with tachycardia was a particularly useful prognostic indicator. H-FABP also predicted long-term mortality over 499 (interquartile range: 204 to 1,166) days (hazard ratio: 3.6; 95% confidence interval: 1.6 to 8.2; p = 0.003). CONCLUSIONS: The H-FABP might be a useful biomarker for risk stratification of normotensive patients with acute PE. peerReviewed

Heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF) are similarly frequent and similarly grim in prognosis in patients presenting with signs of decompensation necessitating hospitalization. Patients presenting with exertional dyspnea are