Corrigendum to: 2014 ESC Guidelines on the diagnosis and treatment of aortic diseases.

Corrigendum to: 2014 ESC Guidelines on the diagnosis and treatment of aortic diseases [Eur Heart Journal (2014) 35, 2873­2926,doi:10.1093/eurheartj/ehu281]. In Table 3, the radiation for MRI is "0" and not "-". The corrected table is shown below.

Pulmonary arterial hypertension-related myopathy: an overview of current data and future perspectives.

BACKGROUND AND AIM: Exercise intolerance is one of the key features of pulmonary arterial hypertension (PAH). The main determinants of exercise impairment include hypoxemia, reduced right ventricular output, perfusion/ventilation mismatch, and weakness of skeletal and breathing muscles. The aim of the current review is to describe the findings in the existing literature about respiratory and muscle dysfunction in PAH. Animal and clinical studies regarding both respiratory and peripheral skeletal muscles and the effect of exercise training on muscle function in PAH patients are analyzed. DATA SYNTHESIS: PAH myopathy is characterized by reduced skeletal muscle mass, reduced volitional and non-volitional contractility, reduced generated force, a fiber switch from type I to type II, increased protein degradation through ubiquitin-proteasome system (UPS) activation, reduced mitochondrial functioning, and impaired activation-contractility coupling. Increased inflammatory response, impaired anabolic signaling, hypoxemia, and abnormalities of mitochondrial function are involved in the pathophysiology of this process. Exercise training has been shown to improve exercise capacity, peak oxygen uptake, quality of life, and possibly clinical outcomes of PAH patients. CONCLUSIONS: The skeletal muscles of PAH patients show a wide spectrum of cellular abnormalities that finally culminate in muscle atrophy and reduced contractility. Exercise training improves muscle function and bears a positive impact on the clinical outcomes of PAH patients.

Physiologic and pathophysiologic changes in the right heart in highly trained athletes.

Exercise causes changes in the heart in response to the hemodynamic demands of increased systemic and pulmonary requirements during exercise. Understanding these adaptations is of great importance, since they may overlap with those caused by pathological conditions. Initial descriptions of athlete's heart focused mainly on chronic adaptation of the left heart to training. In recent years, the substantial structural and functional adaptations of the right heart have been documented, highlighting the complex interplay with left heart. Moreover, there is evolving evidence of acute and chronic cardiac damage, mainly involving the right heart, which may predispose subjects to atrial and ventricular arrhythmias, configuring an exercise-induced cardiomyopathy. The aim of this article is to review the current knowledge on the physiologic and pathophysiologic changes in the right heart in highly trained athletes.

Diagnosis of acute aortic syndromes : imaging and beyond.

Acute aortic syndromes are fatal medical conditions including classic acute aortic dissection, intramural hematoma, and penetrating atherosclerotic ulcer. Given the nonspecific symptoms and signs, a high clinical index of suspicion followed by an imaging study, namely transesophageal echocardiography, computed tomography, and magnetic resonance imaging (sensitivity 98-100% and specificity 95-100%), is a conditio sine qua non for prompt diagnosis of acute aortic syndromes. This article provides an overview of established and emerging approaches for the assessment of acute aortic syndromes, with focus on imaging and biomarkers. In this regard, D-dimer levels (cut-off: 500 ng/ml) may be useful to rule out aortic dissection, if used within the first 24 h after symptom onset.

Acute aortic syndromes.

Acute aortic syndromes (AAS) comprise a group of potentially lethal conditions that require prompt recognition, diagnosis as well as acute medical stabilization and surgical intervention. The purpose of this article is to review the relevant variants of AAS presentation, as well as diagnostic and management issues, including adequate long-term medical therapy and follow-up imaging. In this context, the American College of Cardiology and the American Heart Association recently published guidelines on the management of thoracic aortic disease, drawing greater attention to these processes.

Exercise stress echocardiography for the study of the pulmonary circulation.

Exercise stress tests have been used for the diagnosis of pulmonary hypertension, but with variable protocols and uncertain limits of normal. The pulmonary haemodynamic response to progressively increased workload and recovery was investigated by Doppler echocardiography in 25 healthy volunteers aged 19-62 yrs (mean 36 yrs). Mean pulmonary artery pressure ((Ppa)) was estimated from the maximum velocity of tricuspid regurgitation. Cardiac output (Q) was calculated from the aortic velocity-time integral. Slopes and extrapolated pressure intercepts of (Ppa)-Q plots were calculated after using the adjustment of Poon for individual variability. A pulmonary vascular distensibility alpha was calculated from each (Ppa)-Q plot to estimate compliance. (Ppa) increased from 14+/-3 mmHg to 30+/-7 mmHg, and decreased to 19+/-4 mmHg after 5 min recovery. The slope of (Ppa)-Q was 1.37+/-0.65 mmHg x min(-1) x L(-1) with an extrapolated pressure intercept of 8.2+/-3.6 mmHg and an alpha of 0.017+/-0.018 mmHg(-1). These results agree with those of previous invasive studies. Multipoint (pa)-Q plots were well described by a linear approximation, from which resistance can be calulated. We conclude that exercise echocardiography of the pulmonary circulation is feasible and provides realistic resistance and compliance estimations. Measurements during recovery are unreliable because of rapid return to baseline.

Multiple hormonal and metabolic deficiency syndrome in chronic heart failure: rationale, design, and demographic characteristics of the T.O.S.CA. Registry.

Recent evidence supports the concept that progression of chronic heart failure (CHF) depends upon an imbalance of catabolic forces over the anabolic drive. In this regard, multiple hormonal deficiency syndrome (MHDS) significantly has impacts upon CHF progression, and is associated with a worse clinical status and increased mortality. The T.O.S.CA. (Trattamento Ormonale nello Scompenso CArdiaco; Hormone Therapy in Heart Failure) Registry (clinicaltrial.gov = NCT02335801) tests the hypothesis that anabolic deficiencies reduce survival in a large population of mild-to-moderate CHF patients. The T.O.S.CA. Registry is a prospective multicenter observational study coordinated by "Federico II" University of Naples, and involves 19 centers situated throughout Italy. Thyroid hormones, insulin-like growth factor-1, total testosterone, dehydroepiandrosterone , and insulin are measured at baseline and every year for a patient-average follow-up of 3 years. Subjects with CHF are divided into two groups: patients with one or no anabolic deficiency, and patients with two or more anabolic deficiencies at baseline. The primary endpoint is the composite of all-cause mortality and cardiovascular hospitalization. Secondary endpoints include the composite of all-cause mortality and hospitalization, the composite of cardiovascular mortality and cardiovascular hospitalization, and change of VO2 peak. Patient enrollment started in April 2013, and was completed in July 2017. Demographics and main clinical characteristics of enrolled patients are provided in this article. Detailed cross-sectional results will be available in late 2018. The T.O.S.CA. Registry represents the most robust prospective observational trial on MHDS in the field of CHF. The study findings will advance our knowledge with regard to the intimate mechanisms of CHF progression and hopefully pave the way for future randomized clinical trials of single or multiple hormonal replacement therapies in CHF.

Acute aortic dissection in the young: clinical series.

Acute aortic dissection (AAD) is an uncommon lethal cardiovascular emergency demanding prompt diagnosis and aggressive therapeutic intervention. Although it usually affects males over 60 years of age, it may also occur in young adults with specific risk factors such as Marfan syndrome, bicuspid aortic valve and larger aortic dimensions. Moreover, it should be underlined that it is frequently associated with unusual presentation and that the mortality risk is similar to older AAD patients. Thus ''a call to arms'' of the medical community is needed to better understand the spectrum of acute aortic syndromes and to define appropriate diagnostic and therapeutic pathways. We report a series of 6 young patients with type A - AAD referred over the past years at our institute.

P1007Aortic root diameters and aortic regurgitation in hypertensive patients and normal subjects.

PURPOSE: : The association between aortic root diameters and aortic regurgitation in hypertension (HT) is disputed with lack of understanding of the underline mehanisms lT. We investigate the relationship between aortic root diameters and aortic regurgitation in newly diagnosed and never treated hypertensive patients and in a group healthy subjects. METHOD: Participants were 175 hypertensives (42 F and 133 M) and 305 normotensives (134 F, 168 M) age matched (mean age 52.4±13 vs 52.6 ±15.2 years). Antropometric, office blood pressure (BP) measurements, a comprehensive echocardiography and local carotid stiffness study were performed. Aortic measures for annulus, sinuses of Valsalva, sinotubular junction and ascending aorta were taken in late diastole according to the leading edge method. The sinotubular junction/annulus ratio was calculated. RESULTS: Hypertensive patients had significantly higher body surface area (BSA), systolic (SBP) and diastolic pressure (DBP), mean arterial pressure (MAP) and pulse?pressure (PP) (p<0.0001) than normotensives. Annulus and sinotubular junction diameters, indexed by BSA and after adjustment for gender, MAP, heart rate?(HR), were significantly higher in normotensives than hypertensives. Considering subjects with aortic regurgitation (trivial or mild) we found a higher prevalence in?hypertensives (25.7 % vs 10.2%, p<0.0001). Moreover in hypertensives we found no difference in aortic diameters between patients with or without aortic regurgitation?but ascending aorta /BSA (p=0.002) whereas in healthy subjects aortic regurgitation was associated with larger aortic root diameters included sinotubular junction/annulus ratio (table 1). In the logistic regression analysis, aortic regurgitation was associated with age, gender, BP parameters, one point carotid stiffness parameters. CONCLUSIONS: Hypertensive patients had smaller indexed aortic root dimensions than normal subjects but they had heigher prevalence of trivial-mild aortic regurgitation in contrast to normotensives who had aortic regurgitation combined with larger aortic diameters.

The Tosca Registry: An Ongoing, Observational, Multicenter Registry for Chronic Heart Failure.

The ageing of the population in western countries, the continuous increase of the prevalence of chronic diseases, the frequent coexistence of several morbid conditions (comorbidity) requires health professionals and Institutions to face difficult challenges, including increasing costs, need for more effective and sustainable therapies, and organizational issues. The European Innovation Partnership on Active and Healthy Ageing aims at enabling European citizens to lead healthy, active and independent lives while ageing. We herein discuss some key concepts bearing a special significance in the light of the Partnership aims, and present research and educational projects active in our local environment. Among these, the multicentre project TOSCA (Trattamento Ormonale nello Scompenso CArdiaco) that, although primarily focused on the understanding of the interactions between hormones and chronic heart failure (CHF), is also aimed at developing more effective models of clinical care. We provide the scientific background and current stage of the project. In the context of a growing complexity of the patients' clinical management, the polipharmacy is a new arising challenge for clinicians, bearing direct economic, organizational and clinical implications. A better understanding, characterization and management of this issue represent an additional target of the TOSCA network.

Range of tricuspid regurgitation velocity at rest and during exercise in normal adult men: implications for the diagnosis of pulmonary hypertension.

OBJECTIVES: The aim of this study was to explore the full range of tricuspid valve regurgitation velocity (TRV) at rest and with exercise in disease free individuals. Additionally we examined the relationship of stroke volume (SV), cardiac output (CO) and TRV to exercise capacity. BACKGROUND: Doppler evaluation of TRV can be used to estimate pulmonary artery systolic pressure (PASP). Most studies have assumed TRV < or = 2.5 m/s as the upper limits of normal. The full range of TRV with exercise has been incompletely defined. METHODS: Highly conditioned athletes (n = 26) and healthy, active, young male volunteers (n = 14) underwent standardized recumbent bicycle exercise. Exercise parameters included: TRV, SV, CO, systolic (SBP) and diastolic (DBP) systemic blood pressure. RESULTS: Tricuspid valve regurgitation, SV, HR and CO were significantly higher in athletes than in nonathletes over all workloads, including rest. Systolic blood pressure and DBP did not show significant differences between the two groups. CONCLUSIONS: This study defines the upper physiologic limits of TRV at rest and during exercise in normals and provides a noninvasive standard for the diagnosis of pulmonary hypertension.

Secondary pulmonary hypertension--diagnosis and management.

Secondary pulmonary hypertension (SPHtn) is generally attributable to abnormalities in structure or function of the heart or lung parenchyma. While often defined as a physiologic parameter, pulmonary hypertension (PHtn) can be a major contributor to death and disability in cardiopulmonary diseases. Both detection and management are a challenge. We will review the pathophysiology, diagnostic tools, and treatment strategies in SPHtn with an emphasis on cor pulmonale associated with chronic obstructive pulmonary disease (COPD), pulmonary vasculopathies, and pulmonary embolus. The pathophysiology and common etiologies of SPHtn can be divided into three major categories: (1) elevated pulmonary venous pressure (LV failure and mitral valve disease), (2) pulmonary vascular occlusive disease with or without pulmonary parenchymal disease (pulmonary emboli, COPD, connective tissue diseases), and (3) hypoxemia (sleep apnea). The echo-Doppler is a simple cost-effective tool for detecting PHtn, evaluating right ventricular function, and distinguishing common etiologies such as abnormal systolic and diastolic left ventricular function and mitral valve disease. The ventilation-perfusion radionuclide scan can be used to exclude thromboembolic PHtn, but a helical computer tomography with contrast or pulmonary angiography are necessary to distinguish patients that may benefit from a pulmonary thromboendarterectomy. The six minute walk oxygen saturation test is useful as a quantitative measure of functional capacity, prognosis, response to therapy, and oxygen requirement. Treatment strategies in cor pulmonale are tailored to the specific diagnosis, but generally include proper nutrition, exercise, oxygen supplementation, medications such as digoxin, diuretics, anti-coagulation, and pulmonary vasodilator therapy in selected patients.

A novel miR-371a-5p-mediated pathway, leading to BAG3 upregulation in cardiomyocytes in response to epinephrine, is lost in Takotsubo cardiomyopathy.

Molecular mechanisms protecting cardiomyocytes from stress-induced death, including tension stress, are essential for cardiac physiology and defects in these protective mechanisms can result in pathological alterations. Bcl2-associated athanogene 3 (BAG3) is expressed in cardiomyocytes and is a component of the chaperone-assisted autophagy pathway, essential for homeostasis of mechanically altered cells. BAG3 ablation in mice results in a lethal cardiomyopathy soon after birth and mutations of this gene have been associated with different cardiomyopathies including stress-induced Takotsubo cardiomyopathy (TTC). The pathogenic mechanism leading to TTC has not been defined, but it has been suggested that the heart can be damaged by excessive epinephrine (epi) spillover in the absence of a protective mechanism. The aim of this study was to provide more evidence for a role of BAG3 in the pathogenesis of TTC. Therefore, we sequenced BAG3 gene in 70 TTC patients and in 81 healthy donors with the absence of evaluable cardiovascular disease. Mutations and polymorphisms detected in the BAG3 gene included a frequent nucleotide change g2252c in the BAG3 3'-untranslated region (3'-UTR) of Takotsubo patients (P<0.05), resulting in loss of binding of microRNA-371a-5p (miR-371a-5p) as evidenced by dual-luciferase reporter assays and argonaute RNA-induced silencing complex catalytic component 2/pull-down assays. Moreover, we describe a novel signaling pathway in cardiomyocytes that leads to BAG3 upregulation on exposure to epi through an ERK-dependent upregulation of miR-371a-5p. In conclusion, the presence of a g2252c polymorphism in the BAG3 3'-UTR determines loss of miR-371a-5p binding and results in an altered response to epi, potentially representing a new molecular mechanism that contributes to TTC pathogenesis.

Echocardiographic predictors of an adverse response to a nifedipine trial in primary pulmonary hypertension: diminished left ventricular size and leftward ventricular septal bowing.

BACKGROUND: The clinical course in primary pulmonary hypertension (PPH) is improved by calcium channel blocker therapy in those with a favorable hemodynamic response during a trial of high-dose oral nifedipine. Although trials of nifedipine are performed only in patients who demonstrate pulmonary vasodilator reserve to short-acting agents, this response does not predict the safety of nifedipine treatment, which can result in severe first-dose hypotension and death. STUDY OBJECTIVES: To identify echocardiographic parameters that predict first-dose nifedipine-induced hypotension in patients with PPH. METHODS: The pretrial echocardiograms of 23 consecutive PPH patients (mean age, 42.3 +/- 13 years; 77% female) undergoing evaluation of pulmonary vasodilator reserve with nifedipine were analyzed. Patients were classified as those who suffered first-dose nifedipine hypotension (group 1) and those who did not (group 2). Echocardiographic measures of chamber size and septal geometry in the two groups were compared. RESULTS: Five measures reflecting diminished left ventricular (LV) size and leftward ventricular septal bowing were found to be associated with nifedipine hypotension: LV transverse diameter in systole (LVDs; p = 0.007), LV transverse diameter in diastole (LVDd; p = 0.05), LV area in systole (LVAs; p = 0.009), LV area in diastole (LVAd; p = 0.03), the ratio of RV to LVAs (p = 0. 02), and leftward ventricular septal bowing (p = 0.01). The LV dimensions found to best predict nifedipine-induced hypotension were LVDs < 2.7 cm, LVDd < 4.0 cm, LVAs < 15.5 cm(2), and LVAd < 20.0 cm(2). CONCLUSIONS: Readily available echocardiographic parameters in patients with PPH are predictive of nifedipine-induced hypotension, and can be used to select patients in whom a trial of nifedipine should be avoided.

Dobutamine stress echocardiography for the preoperative evaluation of patients undergoing lung volume reduction surgery.

BACKGROUND: Lung volume reduction surgery has been proposed as a bridge to lung transplantation and as definitive therapy for advanced chronic obstructive lung disease. However, patient selection criteria and optimal preoperative assessment have not been clearly defined. OBJECTIVE: We investigated the feasibility, safety, and value of dobutamine stress echocardiography as a predictor of major early cardiac events in patients who underwent lung volume reduction surgery. METHODS: The study population consisted of 46 patients (21 men and 25 women, mean age 59 +/- 9 years) who underwent dobutamine stress echocardiography (maximum dose 40 microg. kg(-1). min(-1) plus atropine if needed) 180 days or less before lung volume reduction surgery. Adverse cardiac events were prospectively defined and tabulated during hospitalization after the operation and at subsequent outpatient visits. RESULTS: Dobutamine stress echocardiography was interpretable in 45 of 46 (98%) patients. There were no adverse events during testing. The studies revealed normal left ventricular systolic function at rest in all patients and normal right ventricular function in all patients but one. Thirteen patients had right ventricular enlargement. Estimated right ventricular systolic pressure was mildly elevated (>40 mm Hg) in 5 patients. Four patients (9%) had stress tests positive for ischemia. There were no perioperative deaths. Follow-up was available for 44 of 45 patients at a duration of 20.0 +/- 7.0 months. Two major adverse cardiac events occurred in the same patient in whom the results of dobutamine stress echocardiography were positive for ischemia (positive predictive value 25%, 95% confidence interval 0% to 83%; negative predictive value 100%, 95% confidence interval 90 to 100%). CONCLUSION: Despite end-stage chronic obstructive lung disease and poor ultrasound windows, dobutamine stress echocardiography is feasible and safe in patients undergoing evaluation for lung volume reduction surgery. It yields important information on right and left ventricular function and has an excellent negative predictive value for early and late adverse cardiac events.

Aortic dissection with fistula to left atrium: diagnosis by transesophageal echocardiography with successful repair.

The aorta-atria fistula is an infrequent complication of aortic dissection, and it is rarely diagnosed before death. A 41-year-old man who 8 years previously had undergone prosthetic aortic valve replacement had an aortic dissection complicated by aorta-left atrial fistula. This patient had acute left heart failure associated with a systolic and diastolic murmur at the lower left sternal border suggesting an aortic prosthetic malfunction. The cardiac diagnosis was made with transesophageal echocardiography and Doppler color flow imaging; it was notable that the cardiac lesions were not detected by transthoracic echocardiography. On the basis of the echocardiographic findings, the patient underwent successful emergency replacement of the dissecting ascending aorta with closure of the aorta-left atrial fistula. Transesophageal echocardiography is the procedure of choice for defining this abnormality. In this case a prompt surgical repair consisting of replacement of the affected segment of the aorta with the prosthesis and closure of the fistula provided optimum resolution of the clinical situation.

Echocardiographic features of primary pulmonary hypertension.

Primary pulmonary hypertension (PPH) is essentially a diagnosis of exclusion and usually is made late because of the nonspecific nature of the early signs and symptoms. Echocardiography is a key screening test in the diagnostic algorithm of patients with suspected PPH. The purpose of this study was to define the echocardiographic Doppler features in patients with PPH at the time of diagnosis. From 1992 to 1997, 51 patients were diagnosed with PPH at our institution. All underwent a standardized transthoracic echocardiographic examination, including a contrast study and transthoracic echocardiographic examination if indicated. Pulmonary artery systolic pressure was calculated from the tricuspid regurgitation jet. The majority of patients had pulmonary artery systolic pressure greater than 60 mm Hg (96%) associated with systolic flattening of the interventricular septum (90%), enlarged right atrium (92%) and ventricle (98%), and reduced right ventricular systolic function (76%). There was an increase in the interventricular septal thickness (>1.2 cm) in 21 (43%) of 49 patients, accompanied by a septal/posterior wall ratio greater than 1.3 in 11 (22%) of 49. Although a reduction in both left ventricular systolic and diastolic volumes was noted, global left ventricular systolic function was preserved in all patients. Mitral E/A ratio was less than 0.7 in 7 (22%) patients studied. Color Doppler revealed moderate to severe tricuspid regurgitation and pulmonic insufficiency in 41 (80%) of 51 and 16 (31%) of 51 of cases, respectively. Pericardial effusion (7 small and 1 moderate) and patent foramen ovale (n = 12) were also frequently detected. At the time of initial diagnosis, PPH is associated with secondary cardiac abnormalities in the majority of patients.

Exercise echocardiography. Principles, methods, and clinical use.

Stress echocardiography is composed of a family of examinations in which various forms of cardiovascular stress are combined with echocardiographic imaging to assist in the diagnosis of coronary artery disease. Exercise cardiography has evolved over the past 20 years into a routinely available clinical tool employed in both university and community hospital settings. This article discusses advantages and disadvantages of using exercise echocardiography.

Reversible pulmonary hypertension in POEMS syndrome--another etiology of triggered pulmonary vasculopathy?

Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes (POEMS) syndrome, a plasma cell dyscrasia associated with pulmonary hypertension, has been treated in the past with anticytokine strategies with a poor outcome. A patient is described who had POEMS syndrome with precapillary pulmonary hypertension and Raynaud's phenomenon, and who responded well to a short course of corticosteroids and long term nifedipine. POEMS syndrome, like anorexigens, cocaine, portal hypertension and human immunodeficiency virus infection, may be another trigger for the pulmonary vascular occlusive process found in primary pulmonary hypertension.

Evaluation of the reproducibility and accuracy of apex beat measurement in the detection of echocardiographic left ventricular dilation.

OBJECTIVE: To develop a standardized method for measuring the width of the apex beat and to determine its precision and accuracy in detecting echocardiographically determined left ventricular dilation. DESIGN: In the reproducibility study, two cardiologists blinded to each other's findings measured the apex beat. To determine accuracy, blind, independent assessment of apex beat measurement was compared with left ventricular enlargement determined by echocardiogram. PATIENTS: One hundred and four patients referred for echocardiogram for a wide variety of suspected cardiac abnormalities. MEASUREMENTS: The apex beat was measured with patients in a 45 degrees left lateral decubitus position; medial and lateral aspects of the impulse and the width were identified using electrocardiographic callipers. Echocardiographic left ventricular dilation was defined as a measure exceeding the 95% prediction limits as determined for the patient's age and body surface area. RESULTS: The intraclass correlation measuring agreement on apex beat size between two cardiologists in 13 patients was 0.95. Of the 104 patients, 57 had a measurable apex beat of whom 50 had a technically adequate echocardiogram. The sensitivity of the measurement, using a cut-point of 40 mm, was 0.48 and the specificity 0.96.