Showing papers in "European Heart Journal Supplements in 2016"

Outline of the report on cardiovascular diseases in China, 2014.

Abstract: The risk factors for cardiovascular diseases (CVDs) are more prevalent in the Chinese population, and therefore, increase the incidence of CVD. In general, CVD morbidity and mortality will remain an upward trend in the next 10 years. Cardiovascular disease is the leading cause of death in China, which accounts for >40% of deaths from any cause. The burden of CVD is substantial and has become an important public health issue. Measures for the prevention and treatment of CVD in China should be further enforced without delay. Since 2005, the National Center for Cardiovascular Diseases has organized experts of cardiology, neurology, nephrology, diabetes, epidemiology, community health, health economics, biostatistics, and other related fields to compile the annual Report on Cardiovascular Diseases in China. The report aims to provide a timely review of the trend of the epidemic of CVD and to assess the progress of prevention and control of CVD. We present an abstract from the Report on Cardiovascular Diseases in China (2014), including trends in CVD, morbidity and mortality of major CVD, up-to-date assessment of risk factors, as well as health resources for CVD, and a profile of medical expenditure, with the aim of providing evidence for decision making in CVD prevention and control programmes in China, and of delivering the most authoritative information on CVD prevention and control for all citizens.

Current practice in identifying and treating cardiovascular risk, with a focus on residual risk associated with atherogenic dyslipidaemia

Abstract: A panel of European experts on lipids and cardiovascular disease discussed clinical approaches to managing cardiovascular risk in clinical practice, including residual cardiovascular risk associated with lipid abnormalities, such as atherogenic dyslipidaemia (AD). A simplified definition of AD was proposed to enhance understanding of this condition, its prevalence, and its impact on cardiovascular risk. Atherogenic dyslipidaemia can be defined by high fasting triglyceride levels (≥2.3 mmol/L) and low high-density lipoprotein cholesterol (HDL-c) levels (≤1.0 and ≤1.3 mmol/L in men and women, respectively) in statin-treated patients at high cardiovascular risk. The use of a single marker for the diagnosis and treatment of AD, such as non-HDL-c, was advocated. Interventions including lifestyle optimization and low-density lipoprotein (LDL)-lowering therapy with statins (±ezetimibe) are implemented by all experts. Treatment of residual AD can be performed with the addition of fenofibrate, since it can improve the complete lipoprotein profile and reduce the risk of cardiovascular events in patients with AD. Specific clinical scenarios in which fenofibrate may be prescribed are discussed, and include patients with very high triglycerides (≥5.6 mmol/L), patients who are intolerant or resistant to statins, and patients with AD and at high cardiovascular risk. The fenofibrate–statin combination was considered by the experts to benefit from a favourable benefit–risk profile. Cardiovascular experts adopt a multifaceted approach to the prevention of atherosclerotic cardiovascular disease, with lifestyle optimization, LDL-lowering therapy, and treatment of AD with fenofibrate routinely used to help reduce a patient's overall cardiovascular risk.

Understanding acute heart failure: pathophysiology and diagnosis

Abstract: Acute heart failure (AHF) is a relevant public health problem causing the majority of unplanned hospital admissions in patients aged of 65 years or more. AHF was historically described as a pump failure causing downstream hypoperfusion and upstream congestion. During the last decades a more complex network of interactions has been added to the simplistic haemodynamic model for explaining the pathophysiology of AHF. In addition, AHF is not a specific disease but the shared clinical presentation of different, heterogeneous cardiac abnormalities. Persistence of poor outcomes in AHF might be related to the paucity of improvements in the acute management of those patients. Indeed, acute treatment of AHF still mainly consists of intravenous diuretics and/or vasodilators, tailored according to the initial haemodynamic status with little regard to the underlying pathophysiological particularities. Therefore, there is an unmet need for increased individualization of AHF treatment according to the predominant underlying pathophysiological mechanisms to, hopefully, improve patient's outcome. In this article we review current knowledge on pathophysiology and initial diagnosis of AHF.

The bumpy road to drug development for acute heart failure

Abstract: The prevalence of heart failure (HF) continues to grow, in large part attributed to the aging population. Parallel to this trend is the increasing burden of hospitalization for worsening HF, which accounts for the majority of the very high societal burden of costs of care for these patients. These hospitalizations represent a change in the trajectory of the disease process and are associated with a significantly higher risk of adverse outcomes, a trend that has not changed over the past two decades. Although short-term readmissions are due to haemodynamic congestion, long-term prognosis and mortality are the result of the continuous deterioration of cardiac substrate, worsening of comorbidities, and progression of HF. Thus, when planning a new therapeutic intervention in acute HF, it is essential to have insight into the mechanism and temporal distribution of adverse outcomes. Furthermore, as acute HF patients die or are readmitted due to multiple reasons it is important to match the mechanism of action of the intervention to the mechanism of the adverse event. Despite many clinical trials to date in these patients, there currently is not a single agent that is known to improve post-discharge mortality risk in these patients. A variety of reasons have been offered to account for the lack of success in these clinical trials. A careful review of these previous experiences offers some significant insights into lessons learned and provides guidance for future novel intervention development for this growing patient population.

Heart failure: an historical perspective

Abstract: The story of heart failure (HF) traces a path from the oldest records of human healing practices several millennia ago, winding through various changing models of physiology, sickness and health. It passes through today’s landscape of neurohormonal modulation, device therapy, and assist devices, towards a future of therapies, some in development today, some as-yet unimagined, based on pathophysiological insights yet to come. This review attempts to follow the path and notes the traces left by earlier travellers, as well as the therapeutic improvements made possible by the developments in our understanding of HF that followed from their successes and failures. As we focus on pathophysiology, transplantation and mechanical assist devices will be treated more cursorily. Likewise, as this is a history of the development of modern (sometimes ‘Western’ although more properly ‘global’ or ‘scientific’) medicine, alternative therapies are not discussed in this paper.

Practical multidisciplinary approaches to heart failure management for improved patient outcome

Abstract: Heart failure (HF) affects millions of people worldwide. Many patients experience repeated hospital admissions and a poor quality of life, and many die prematurely. The period following discharge from hospital is recognized as a particularly vulnerable time. Effective HF multidisciplinary teams are now recommended in HF guidelines and can improve outcomes, alleviate suffering, and make the overall experience of HF better for patients and their families. Yet audit of HF services reports inadequate levels of adherence with these recommendations and wide variation across countries and regions. This article aims to summarize the key elements necessary for high-quality multidisciplinary care to be provided for all patients, throughout the HF trajectory, from acute hospital admission to long-term follow-up. It also discusses practical approaches to improve communication between the acute hospital and community healthcare teams. These will need to be adapted depending on local needs and resources. These include HF management programmes, structured discharge planning, medicines reconciliation, nurse-led ‘in-reach’ and ‘out-reach’ approaches, and long-term follow-up and monitoring. The importance of involving patients and their families in discharge planning and empowering and educating them in self-care is also discussed. The overall goal is to develop strong multidisciplinary teams that improve patient outcomes, and ensure seamless care is offered to all patients.

Surgical ventricular reconstruction for ischaemic heart failure: state of the art

Abstract: Patients with ischaemic cardiomyopathy and left ventricular (LV) systolic dysfunction represent the highest-risk population with heart failure (HF). The cornerstone of treatment remains guideline-driven medical therapy, which is associated with significant improvement in survival and quality of life. The most commonly considered surgical interventions are coronary artery bypass graft surgery, at times combined with surgical ventricular reconstruction (SVR) and surgery for mitral valve regurgitation. Surgical ventricular reconstruction has been introduced as an optional therapeutic strategy aimed to reduce LV volumes through the exclusion of the scar tissue, thereby restoring the physiological volume and shape and improving cardiac function and clinical status. This review will briefly discuss the rationale to surgically reverse LV remodelling, the technique, and the indications, to the best of our knowledge, coming from the Center with the largest worldwide experience. The evolving data on the role of SVR for the treatment of ischaemic HF will be addressed as well.

Switching between ticagrelor and clopidogrel in patients who underwent percutaneous coronary intervention: insight into contemporary practice in Chinese patients.

Abstract: Ticagrelor has been proved to be more effective than clopidogrel; however, little is known about the switching between ticagrelor and clopidogrel in real-world clinical practice. We assessed the prevalence, related factors, dose bridging, compliance, and short-term outcomes of in-hospital switching between ticagrelor and clopidogrel in consecutively recruited patients treated by ticagrelor after percutaneous coronary intervention (PCI). A total of 417 eligible patients administrated with ticagrelor in-hospital after PCI were recruited. Switching between ticagrelor and clopidogrel occurred in 362 (86.8%) patients, with 318 (76.3%) from clopidogrel to ticagrelor occurring mainly after PCI and 44 (10.6%) from ticagrelor to clopidogrel primarily at discharge. History of cerebrovascular disease, final diagnosis of acute coronary syndrome, left main disease, ostial lesion, co-administration with warfarin, CYP2C19 loss-of-function alleles’ carriage status, and ticagrelor-related dyspnoea emerged as related factors for the switching between clopidogrel and ticagrelor. Dose bridging between clopidogrel loading dose and ticagrelor maintenance dose (MD) was more frequent in patients switching from clopidogrel to ticagrelor, while the bridging between ticagrelor MD and clopidogrel MD was more likely to occur in patients switched from ticagrelor to clopidogrel. At 6 month follow-up, poor compliance was observed in patients from clopidogrel to ticagrelor (64.8%) or treated only by ticagrelor (50.9%), but perfect compliance in patients from ticagrelor to clopidogrel (100%). After excluding the cases with incompliance, patients switching from ticagrelor to clopidogrel had a relatively lower bleeding risk in comparison with patients with constant ticagrelor treatment and those switching from clopidogrel to ticagrelor (29.5% vs. 50.0% vs. 46.6%, adjusted P = 0.02). In-hospital switching between ticagrelor and clopidogrel is frequent in patients undergoing PCI. In comparison with constant ticagrelor treatment, switching from clopidogrel to ticagrelor in ischaemic high-risk patients confers similar antiplatelet efficacy and safety, while switching from ticagrelor to clopidogrel in ischaemic low-risk patients relates to lower hazard for bleeding events.

Novel cardiac magnetic resonance biomarkers: Native T1 and extracellular volume myocardial mapping

Abstract: Cardiac magnetic resonance (CMR) is a non-invasive diagnostic tool playing a key role in the assessment of cardiac morphology and function as well as in tissue characterization. Late gadolinium enhancement is a fundamental CMR technique for detecting focal or regional abnormalities such as scar tissue, replacement fibrosis, or inflammation using qualitative, semi-quantitative, or quantitative methods, but not allowing for evaluating the whole myocardium in the presence of diffuse disease. The novel T1 mapping approach permits a quantitative assessment of the entire myocardium providing a voxel-by-voxel map of native T1 relaxation time, obtained before the intravenous administration of gadolinium-based contrast material. Combining T1 data obtained before and after contrast injection, it is also possible to calculate the voxel-by-voxel extracellular volume (ECV), resulting in another myocardial parametric map. This article describes technical challenges and clinical perspectives of these two novel CMR biomarkers: myocardial native T1 and ECV mapping.

The care for adults with congenital heart disease: organization and function of a grown-up congenital heart disease unit

Abstract: Thanks to the improvement of surgical and interventional cardiac procedures, the majority of children with congenital heart defects (CHD) can now be expected to reach adulthood. The number of adults with congenital heart disease (ACHD) will inevitably increase, and recent data affirm that in Europe, we are actually faced with an estimated patient population of 2.3 million. These patients, particularly the adults with moderate and highly complex CHD, can be very difficult to manage, and should be treated in few experienced and specialized ‘grown-up congenital heart disease’ (GUCH) units, concentrating resources, patients, funding, and professional experiences. On 2000, we created a GUCH unit in our hospital that rapidly became a referral centre in Italy for number and complexity of patients treated. The present study is a presentation of how is organized our GUCH unit and a brief overview of our more recent experience with ACHD patients.

International cooperation in healthcare: model of IRCCS Policlinico San Donato and Bambini Cardiopatici nel Mondo Association for congenital heart diseases.

Abstract: Cooperation activity in training programmes promoted by IRCCS Policlinico San Donato and Bambini Cardiopatici nel Mondo Association is a model of cooperation between people as an alternative intervention in promoting the right to healthcare, especially offering programmes of training and medical care on cardiovascular and congenital heart disease. This new strategy, implemented in several developing countries, has absolutely contributed to the improvement of the medical services concerning the diagnostic and surgical approach in the treatment of paediatric and adult cardiovascular disease. To strengthen this kind of activity, both IRCCS Policlinico San Donato and Bambini Cardiopatici nel Mondo have introduced a global perspective aiming at the realization of surgical missions ‘in situ’, building new cardiac surgery units in collaboration with the local partners, which are mainly university hospitals. They, furthermore, support financially the scholarship and accommodation in favour of medical and paramedical staff.

Point-of-care haemostasis and coagulation monitoring in cardiac surgery at IRCCS Policlinico San Donato.

Abstract: A rational management of perioperative and postoperative bleeding in modern cardiac surgery requires a thorough application of point-of-care (POC) monitoring in order to prevent and readily treat alterations of the haemostatic process. Preoperative platelet dysfunction, residual heparin after extracorporeal circulation, coagulation factors, and/or fibrinogen deficiency could be ruled out and specifically addressed with an appropriate treatment. Our approach includes preoperative platelet function testing of patients administered with thienopyridines or ticagrelor within 7–10 days before planned surgery and platelet function testing-based surgery timing. In the case of postoperative bleeding, residual heparin is tested and additional protamine is eventually administered. Simultaneously, an overall activity of coagulation factors (except fibrinogen) is assessed and, if significantly reduced, correction with prothrombotic complex concentrate is considered. If fibrinogen deficiency is suspected, a specific test is run, and in the case of severe reduction, the deficiency is compensated by fibrinogen concentrate or appropriate volume of fresh-frozen plasma. If both coagulation factors and fibrinogen activity are reduced, fibrinogen is usually considered for correction as first line, followed by prothrombin complex concentrate in the case of further bleeding. It is our clinical practice not to test nor to treat patients until postoperative bleeding appears clinically relevant. At IRCCS Policlinico San Donato, we firmly believe in the importance of the POC-based strategy for haemostatic treatment and constantly update our knowledge through research projects targeted in answering clinically relevant questions.

Effect of intravenous l-carnitine in Chinese patients with chronic heart failure

Abstract: Chronic heart failure (CHF) may be associated with an energy deficit in cardiac muscle. As levo-carnitine (LC) is involved in the production of myocardial energy, it is hypothesized that LC supplementation may ameliorate CHF symptoms. This multicentre, randomized, double-blind, and placebo-controlled study included 265 patients with CHF. Patients were randomized to receive either LC or placebo, twice a day. Endpoints were measured after 7 days of treatment. Primary endpoint was a reduction of at least one NYHA class. Secondary endpoints were changes in 6-min walk distance (6-MWD) compared with baseline, either alone or in combination with NYHA class decrease, left ventricular ejection fraction, and NT-proBNP level, together with adverse events. The primary endpoint was reached in 60.9% of patients treated with LC, compared with only 44.7% of the placebo group ( P = 0.012). Among the secondary endpoints, 6-MWD, alone or in combination with NYHA class, improved significantly in the LC group compared with placebo ( P = 0.0497 and P = 0.003, respectively). l-Carnitine was well tolerated. The lowest baseline values of plasma-free carnitine were observed in patients with NYHA classes III and IV where the effect of LC supplementation was greatest ( P = 0.002). Treatment with LC significantly improved CHF symptoms in Chinese patients, probably by correcting a status of carnitine insufficiency.

Residual cardiovascular risk

Abstract: Residual cardiovascular risk is often associated with lipid abnormalities, such as atherogenic dyslipidaemia (AD). Dyslipidaemias are one of the determinants of the risk of developing atherosclerotic cardiovascular disease. In addition to low-density lipoprotein (LDL) particles, which are the most atherogenic lipoproteins, other apolipoprotein B-containing lipoproteins [e.g. triglyceride (TG)-rich lipoproteins and their remnants] contribute to intimal cholesterol deposition and to the development of atherosclerosis. Lipoprotein size is a key determinant of atherogenesis, with remnants being able to penetrate the arterial intima and bind to and be retained by connective matrix tissue, thus directly contributing to plaque formation and progression. This is particularly …

microRNAs in ischaemic cardiovascular diseases.

Abstract: microRNAs (miRNAs) are non-coding RNA molecules that modulate the stability and/or the translational efficiency of specific messenger RNAs. They have been shown to play a regulatory role in most biological processes and their expression is disrupted in many cardiovascular diseases. This review describes studies performed at Policlinico San Donato-IRCCS in cell cultures, animal models, and patients, showing a penetrant role of miRNAs in cell response to hypoxia and in ischaemic cardiovascular diseases. These experiments indicate miRNA as an emerging class of therapeutic targets.

Modern ECMO: why an ECMO programme in a tertiary care hospital.

Abstract: Extracorporeal Membrane Oxygenation (ECMO) represents a useful tool to support the lungs and the heart when all conventional therapies failed and the patients are at risk of death. While the Extracorporeal Life Support Organization (ELSO) collects data from different institutions that joined the Registry and reports overall outcome, individual centres often collide with results below expectations, either in adults and in paediatric population. Some authors suggest that poor outcomes could be overcome with a programme dedicated to ECMO, with specialized professionals adequately trained on ECMO and with a consistent number of procedures. In 2012, The IRCCS PSD ECMO Programme was instituted with the specific aim of achieving better results than hitherto obtained. After only 1 year of activity, the results justified the programme, with a better survival rate for each group investigated, particularly in adults, but surprisingly in paediatrics too, where the results were better than what reported by ELSO. Although the number of patients treated with ECMO is still growing up, the effects of the ECMO programme continue to exert a positive action on outcome even now. The present article reports data on survival, blood loss, and blood consumption during ECMO in the last few years at our institution.

Benefits of once-daily dosing with non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation.

Abstract: Atrial fibrillation (AF) is the most prevalent clinically relevant arrhythmia, affecting millions of individuals in Europe and the USA. Atrial fibrillation increases the risk of stroke; the long-term standard of care for prevention of AF-related stroke is anticoagulation. The use of anticoagulants should be based on the absolute risks of stroke and bleeding and the relative benefit-risk profile of the individual patient. Treatment options include vitamin K antagonists (VKAs) such as warfarin, whose use is long-established but associated with drawbacks, including regular coagulation monitoring requirements and many food and drug interactions. The non-VKA oral anticoagulants are gaining widespread use as alternatives to VKAs, and are supported in treatment guidelines for patients with AF at moderate to high risk of stroke. Adherence to medication is important for the long-term efficacy of any therapy; however, relatively low levels of medication adherence are to be expected in 'real-world' AF patients compared with clinical trials. Experience across several therapy areas, including cardiovascular disease, shows that poor adherence to chronic medication is common. However, simple dosing schedules may be advantageous in this respect, and because long-term outcomes in AF are likely to be influenced by adherence, once-daily dosing has the potential to improve rates of stroke prevention in patients with AF.

A survey of national cardiology workforce in China

Abstract: Cardiologists provided specialized care for patients with various cardiac conditions. The qualification system of subspecialty as cardiologist is well established in developed countries. However, there is no standardized national training programmes and common board certification for cardiovascular professionals in China. We launched a survey of national cardiology workforce to assess general characteristics of cardiovascular care providers in China. This survey includes licensed physicians who are currently working as cardiovascular care givers in tertiary or secondary hospitals in mainland China (Taiwan, Hongkong, and Macau were not included). A total of 25 240 physicians from 31 provinces responded to survey, achieving an estimated response rate at 76.5%. Data on demographic information, work characteristics, educational background, and professional skills of the physicians were collected. Results showed that cardiologist to population ratio is 1.9 per 100 000 and the number of cardiologist per 100 000 population over age of 65 is 21.3. Average age of respondents is 38.22 ± 8.19 and average time of medical practice after receiving medical certification is 12.1 ± 8.5 years. By gender and educational background, 58.5% of subjects are male and 33.3% had postgraduate degree. 25.9% of surveyed cardiologists were actively practicing interventional cardiology, but only 39.4% of them were licensed with interventional cardiology certification. Proportion of cardiologists worked on cardiac pacing, ablation of arrhythmia, and interventional treatment of congenital heart disease is 24.2, 14.1, and 9%, respectively, accordingly only 17.4, 36.5, and 25.6% of them had received specialty certifications. Physicians in eastern and middle regions had better educational background and training opportunities than those in western regions. This current survey is the most comprehensive investigation on cardiology workforce in China. The comparative study indicated a scarcity of cardiologists in China. This survey also helps greatly to guide authorities on decision making to improve training and specialty certification system of Cardiologist in China.

A chemical approach to myocardial protection and regeneration

Abstract: The possibility of generating induced pluripotent stem cells from mouse embryonic fibroblasts and human adult fibroblasts has introduced new perspectives for possible therapeutic strategies to repair damaged hearts. However, obtaining large numbers of adult stem cells is still an ongoing challenge, and the safety of genetic reprogramming with lenti- or retro-viruses has several drawbacks not easy to be addressed. Furthermore, the majority of adult stem cell-based clinical trials for heart regeneration have had generally poor and controversial results. Nonetheless, it is now clear that the injected cells activate the growth and differentiation of progenitor cells that are already present in the heart. This is achieved by the release of signalling factors and/or exosomes carrying them. Along this line, chemistry may play a major role in developing new strategies for activating resident stem cells to regenerate the heart. In particular, this review focuses on small molecule approaches for cell reprogramming, cell differentiation, and activation of cell protection.

Comparison of effectiveness of right ventricular mid-septal pacing vs. apical pacing: a randomized-controlled trials

Abstract: The aim of the present study was to compare conventional right ventricular apical pacing (RVAP) with right ventricular mid-septal pacing (RVMSP) in terms of echocardiographic and clinical/biologic features. Ninety-six patients with high-degree atrioventricular block were randomly allocated to RVMSP ( n = 50) and RVAP ( n = 46). Threshold and impedance, echocardiographic left ventricular ejection fraction, ventricular dyssynchrony features, and distance during a 6-min walk test and Minnesota Living with Heart Failure Questionnaire were determined at 6 and 12 months after pacemaker implantation. Serum levels of N-terminal pro-brain natriuretic peptide were measured. At 6 months of follow-up, echocardiographic and clinical/biologic features showed no significant differences between two groups. The RVAP group had more intraventricular dyssynchrony and a trend towards a worse left ventricular ejection fraction compared with the RVMSP at 12 months of follow-up. However, no overt clinical benefits from RVMSP were found. Right ventricular mid-septal pacing was associated with decreased dyssynchrony and better left ventricular ejection fraction compared with the RVAP. Right ventricular mid-septal pacing could represent an alternative pacing site in selected patients to reduce the harmful effects of traditional RVAP.

Water-soluble chitosan regulates vascular remodeling in hypertension via NFATc1.

Abstract: Objective Hypertension is a public health problem in the world, and the disability and mortality rate is extremely high. Its important pathology foundation is vascular remodeling. Water-soluble chitosan (WSC) is the degradation product of chitosan, and have a role to control hypertension. The present study aims to investigate the regulatory effects of WSC on vascular remodeling in hypertension, and further to confirm the roles of nuclear factor c1 of activatied T cells (NFATc1) during this effect. Methods Primary cultured rat abdominal aortic smooth muscle cells were incubated with PBS, AngII, and AngІІ + WSC (0.1 mg/L) for 24 h. MTT and western blot methods were applied to analyzed the cell proliferation and c-myc protein expression, respectively, among all experimental groups. Successfully established spontaneously hypertensive Wistar-kyoto rats (SHR) were divided into two groups randomly: SHR group (n = 30) and SHR + WSC group (n = 30,WSC150 mg/kg/d). Another 15 Wistar-kyoto rats treated with PBS were served as control group. At the end of the experiments, the hemodynamic changes were analyzed using rat tail arterial pressure measuring instrument. H&E staining was performed to observe the morphological changes of abdominal aorta. Furthermore, immunohistochemical method, western blot and real-time quantitative PCR were applied to detected the expression of NAFTc1 protein and mRNA. Results WSC significantly reduced the cell viability in primary cultured rat abdominal aortic smooth muscle cells compare with PBS and AngІІ-treated cells. Compared with PBS group, the enhanced expression level of c-myc protein was observed in AngІІ-treated cells, which was significantly blocked by WSC incubation. Compared with control rats, the abnormally high blood pressure and membrane thickness/lumen diameter ratio of abdominal aorta were noted in SHR model rats, which strongly reduced after WSC administration. Hypertension resulted in an increment on expression of both NFATc1 protein and mRNA in abdominal aorta of Wistar-kyoto rats compared with control groups. Encouragingly, WSC strikingly suppressed the high levels of NFATc1 protein and even mRNA. Conclusion In both cell and animal experiments, we succefully confirmed the regulatory effects of WSC on vascular remodeling in hypertension. Based on the present results, WSC-inhibited vascular remodeling may be related to the modulation on NFATc1 expression. Our experiment provides a solid basis for the clinical application of WSC on hypertension.

Treatment of right ventricular outflow tract dysfunction: a multimodality approach.

Abstract: The right timing to replace the pulmonary valve in a patient with dysfunction of the right ventricular outflow tract is unknown. Both percutaneous pulmonary valve and surgical prosthesis are suitable options. In every patient, the right ventricle (RV) remodels and recovers differently after pulmonary replacement. Therefore, it is difficult to identify the best treatment option and to predict the long-term results. In the last few years, we focused our research on optimizing the characterization of these patients through advanced cardiovascular imaging in order to find possible variables, parameters, and reproducible measurements that can help us in the decision-making process. The aim of the present article is to present our ongoing research lines that focus on the characterization and optimal treatment approach to the dysfunction of the RVOT.

Effect of verapamil in the treatment of type 2 long QT syndrome is not a dose-dependent pattern: a study from bedside to bench, and back

Abstract: Type 2 long QT syndrome (LQT2) is caused by loss-of-function mutations in KCNH2 gene. This study aimed to investigate the efficacy and mechanism of a calcium channel blocker, verapamil, to improve clinical manifestations in LQT2. A 42-year-old woman with a LQT2 phenotype underwent candidate gene screening. Therapeutic effects of verapamil were evaluated by QT-interval measurement and shock count of implantable cardioverter-defibrillator. The electrophysiological effect of verapamil was assessed in a LQT2 model using rabbit ventricular wedge preparations. Direct sequencing of her DNA revealed a heterozygous D609N mutation in KCNH2 . Acute administration of intravenous verapamil (10 mg/h) successfully abolished electrical storm and shortened the corrected QT (QTc) from 671 to 532 ms in the patient. However, long-term use of oral verapamil (240 mg daily) failed to completely prevent the torsades de pointes (TdP) recurrence over a 3-year follow-up period, whereas a low dose of oral verapamil (120 mg daily) totally suppressed the cardiac events in the following 12 months. In in vitro studies, verapamil preferentially abbreviated endocardial action potential duration leading to a reduction in the QT interval and transmural dispersion of repolarization, and suppressed early afterdepolarization. However, high concentration of verapamil caused a significant decrease in both myocardial effective refractory period (ERP) and post-repolarization refractoriness (PRR), which facilitated TdP in the LQT2 model. Our findings indicate a therapeutic role of verapamil in the management of LQT2 patients. However, an inappropriate dose of verapamil may offset beneficial effects by excessively shortening the ERP and PRR to increase the myocardial excitability.

Shorter (≤6 months) vs. longer (≥12 months) dual antiplatelet therapy after second-generation drug-eluting stents implantation: a meta-analysis of randomized controlled trials

Abstract: Optimal duration of dual antiplatelet therapy (DAPT) after second-generation drug-eluting stent (DES) remains unknown. We performed a meta-analysis to evaluate the efficacy and safety of ≤6-month vs. ≥12-month DAPT after implantation of second-generation DES in order to estimate the optimal duration of DAPT. We conducted a literature search for randomized control trials (RCTs) in popular databases including EMBASE, PubMed, the Cochrane Library, and Scopus. Independent investigators abstracted the data on outcomes, characteristics, and qualities of trials included. A fixed-effect model was adopted to pool odds ratios with 95% confidence intervals of the clinical outcomes concerned when I 2 0.05, a random-effect model was applied in other cases. Five published RCTs involving 8407 patients were included in our analysis. There was no significant difference in definite or probable stent thrombosis, myocardial infarction, stroke, target vessel revascularization, all-cause death, and cardiac death between the shorter duration and the longer duration of DAPT. Moreover, no significant difference was observed in the incidences of major bleeding and any bleeding. None of the clinical outcomes differed in patients receiving everolimus-eluting stent or zotarolimus-eluting stent across DAPT groups. Shorter DAPT (≤6 months) after the second-generation DES implantation has no increased risks of adverse cardiac and cerebral events compared with longer DAPT (≥12 months). In addition, longer DAPT does not increase bleeding complications when compared with shorter duration.

Once-daily rivaroxaban for long-term stroke prevention in patients with atrial fibrillation.

Abstract: Oral anticoagulation is the long-term standard of care for preventing stroke in patients with atrial fibrillation (AF). However, anticoagulation is associated with an increased risk of bleeding, such that its use should be based on the absolute risks of stroke and bleeding, and the relative benefit–risk profile of the individual patient. Non-vitamin K antagonist oral anticoagulants, including rivaroxaban, are alternatives to vitamin K antagonists such as warfarin in this setting, and are supported in treatment guidelines as the optimal choice for patients with AF at moderate to high risk of stroke. Rivaroxaban can be given in fixed doses without routine coagulation monitoring, and phase III studies have demonstrated its safety profile and efficacy in patients with non-valvular AF, including the elderly and those with co-morbidities. Moreover, rivaroxaban is administered once daily, which has advantages for optimal patient adherence to medication over the long term. The established efficacy and safety profile of rivaroxaban, together with its convenient once-daily dosing schedule, may contribute to improved patient outcomes and lead to sustained benefits for patients with non-valvular AF at risk of stroke.

Effects of levosimendan on calcium transient in norepinephrine-cultured neonatal rat ventricular myocytes

Abstract: This study aimed to explore the changes in calcium transient in the development of heart failure and the effects of levosimendan (LeV) on intracellular calcium dynamics. Cultured neonatal rat ventricular myocytes were divided into four groups: normal, norepinephrine (NE) only (10 µmol/L), NE + LeV1 (0.1 µmol/L), and NE + LeV2 (1 µmol/L). The calcium transients of the myocytes loaded with Fluo-3/AM were observed using a laser scanning confocal microscope. Compared with the control group, the calcium wave in the NE group dispersed, propagated slowly, and exhibited dyssynchrony of Ca2+ release. Norepinephrine accelerated the beating rate of the cultured myocytes, decreased the systolic peak Ca2+, and increased the time to peak (Ttp) and decay time (Tau) of calcium transient. Levosimendan increased the synchrony of calcium transient, and reduced Ttp and Tau. In contrast, LeV did not affect the beating rate and systolic peak Ca2+. Both NE-only- and LeV-treated groups did not affect resting Ca2+ and calcium transient amplitude of the myocytes. The currents from L-type calcium channel currents did not differ among the groups. Both NE and LeV shortened the action potential duration, but the effect of the latter was more serious than that of the former. Western blot results showed that the sarco/endoplasmic reticulum Ca2+-ATPase 2 (SERCA2) expression decreased in the NE group but increased in the LeV groups. The sodium–calcium exchanger 1 (NCX1) expression increased in the NE group but decreased in the LeV groups. Long-term exposure to NE decreased myocardial contractility by reducing the peak Ca2+ of calcium transient and by prolonging and disrupting the conduction of calcium waves. Levosimendan elicits a positive inotropic effect by accelerating the velocity of calcium signal propagation and synchronizing calcium release without increasing calcium influx.

What is on the horizon for improved treatments for acutely decompensated heart failure

Abstract: Patients hospitalized with acutely decompensated heart failure (ADHF) are often critically ill and require immediate treatment to stabilize their haemodynamic status. Despite improving the signs and symptoms of ADHF, currently available therapies have failed to demonstrate improvements in post-discharge outcomes, such as mortality and rehospitalization, and to address the impact of end-organ damage. Furthermore, attempts to develop therapies to treat patients with ADHF over the past 10 to 20 years have been largely unsuccessful, further compounding the problem. Recent evidence supporting a variety of novel therapies, such as serelaxin and natriuretic peptides, may signal a new hope on the horizon for patients with ADHF.

Transcatheter aortic valve replacement-state of the art and a glimpse to the future: 'the Tailored Approach'.

Abstract: Transcatheter aortic valve replacement determined a paradigm shift in the treatment of high-risk patients with severe symptomatic aortic valve stenosis. Notwithstanding the impressive results of the first-generation prostheses, a fast-paced technological evolution is taking place to overcome their limitations, in particular the vascular access damage and the paravalvular leak. Nowadays, with the availability of several different devices, the expert operator can select the right prosthesis for the specific anatomical and clinical situation. As ‘One does not fit all’, the ‘Tailored TAVR Approach’ we describe will conceivably become the future of this therapy.