Balloon Pulmonary Angioplasty in Patients with Chronic Thromboembolic Pulmonary Hypertension in Greece: Data from the Hellenic Pulmonary Hypertension Registry.

Balloon pulmonary angioplasty (BPA) is a novel and promising treatment option for patients with chronic thromboembolic pulmonary hypertension (CTEPH) who are ineligible for pulmonary endarterectomy (PEA) and for those with persistent or recurrent pulmonary hypertension after PEA. We present the results of BPA procedures in CTEPH patients included in the Greek Pulmonary Hypertension Registry, evaluating the real-life efficacy and safety. We analyzed data from 180 BPA procedures (2−17/patient, mean 8 ± 4/patient, 1248 dilated vessels, 0−18/session). Significant improvements were observed in mean pulmonary arterial pressure (a reduction by 44%, p < 0.001), pulmonary vascular resistance (reduction by 60%, p < 0.001), and NT-proBNP (decrease by >70%, p: 0.003), while cardiac index improved modestly (9% increase, p = 0.143). We had 37 BPA-related non-fatal complications (20.6% in all interventions), predominantly including hemoptysis. Overall survival was 91%, 75% and 62% at 3, 4 and 5 years, respectively. Therefore, BPA may be a promising therapeutic option in patients with CTEPH in Greece.

Epidemiology and Management of Chronic Thromboembolic Pulmonary Hypertension in Greece. Real-World Data from the Hellenic Pulmonary Hypertension Registry (HOPE).

Chronic Thromboembolic Pulmonary Hypertension (CTEPH) is a rare disease with poor prognosis if left untreated, characterized by pulmonary vascular bed obstruction due to unresolving thromboembolic material. The Hellenic pulmonary hypertension registry (HOPE) was launched in Greece in early 2015 and enrolls patients from all pulmonary hypertension subgroups in Greece. In total, 98 patients with CTEPH were enrolled from January 2015 until November 2019. Of these patients, 55.1% represented incident population, 50% were classified in the World Health Organization functional class II and 49% had a history of acute pulmonary embolism. The median values of pulmonary vascular resistance (PVR) and cardiac index were 7.4 (4.8) WU and 2.4 (1.0) L/min/m2, respectively, the mean diffusing capacity for carbon monoxide was 74.8 ± 20.6%, the median 6-minute walk distance was 347 (220) meters and the median value of N Terminal-pro brain natriuretic peptide was 506.0 (1450.0) pg/mL. In total, 60.2% of the patients were under pulmonary arterial hypertension-targeted therapy at the time of enrolment; specifically, riociguat was received by 35.7% of the patients and combination therapy was the preferred strategy for 16% of the patients. In total, 74 patients were evaluated for pulmonary endarterectomy (PEA), 34 (45.9%) were assessed as operable but only 23 of those (31.1%) finally underwent PEA. The remaining 40 patients were ineligible for PEA according to the operability assessment and 13 (17.6%) of them underwent balloon pulmonary angioplasty. The age of the non-operable patients was significantly higher than the operable patients (p < 0.001), while there was no significant difference with regard to the history of coagulopathies between the operable and non-operable patients (p = 0.33).

Echocardiography in Pulmonary Arterial Hypertension: Is It Time to Reconsider Its Prognostic Utility?

Pulmonary arterial hypertension (PAH) is characterized by an insult in the pulmonary vasculature, with subsequent right ventricular (RV) adaptation to the increased afterload that ultimately leads to RV failure. The awareness of the importance of RV function in PAH has increased considerably because right heart failure is the predominant cause of death in PAH patients. Given its wide availability and reduced cost, echocardiography is of paramount importance in the evaluation of the right heart in PAH. Several echocardiographic parameters have been shown to have prognostic implications in PAH; however, the role of echocardiography in the risk assessment of the PAH patient is limited under the current guidelines. This review discusses the echocardiographic evaluation of the RV in PAH and during therapy, and its prognostic implications, as well as the potential significant role of repeated echocardiographic assessment in the follow-up of patients with PAH.

Reduced global longitudinal strain at rest and inadequate blood pressure response during exercise treadmill testing in male heterozygous familial hypercholesterolemia patients.

BACKGROUND: Heterozygous familial hypercholesterolemia (heFH) is a genetic disorder leading to premature coronary artery disease (CAD). We hypothesized that the subclinical pathophysiologic consequences of hypercholesterolemia may be detected before the occurrence of clinically overt CAD by stress testing and myocardial strain imaging. PATIENTS-METHODS: We evaluated the treadmill tests (ETTs) of 46 heFH men without known arterial hypertension/diabetes mellitus/vasculopathy like CAD and of 39 healthy men matched for age, baseline systolic/diastolic blood pressure (BP) and heart rate (HR), using Bruce protocol. Global longitudinal strain (GLS) of the left ventricle (LV) additionally to ejection fraction was obtained. RESULTS: heFH men reached a significantly higher peak systolic and diastolic BP compared to controls (p = 0.002 and p < 0.001, respectively). Mean rate pressure product was significantly higher in heFH patients (p = 0.038). Both duration of the ETT and workload in metabolic equivalents was lower in the heFH group (p < 0.001 and p < 0.001, respectively). Baseline to peak rise of systolic and diastolic BP in heFH men was higher (p = 0.008 and p < 0.001 for systolic and diastolic BP, respectively). Furthermore, heFH men had higher rise of HR from baseline to peak, compared to controls; (p = 0.047). GLS in heHF men was slightly decreased (p = 0.014), although the ejection fraction was similar in both groups. CONCLUSION: heFH men have a higher rise in systolic/diastolic BP during ETT, which may reflect early, preclinical hypertension. Furthermore, slight impairment of LV GLS is present, despite the absence of apparent myocardial dysfunction in conventional 2D echocardiography.

Echocardiographic reference ranges for normal left ventricular layer-specific strain: results from the EACVI NORRE study.

AIMS: To obtain the normal range for 2D echocardiographic (2DE) measurements of left ventricular (LV) layer-specific strain from a large group of healthy volunteers of both genders over a wide range of ages. METHODS AND RESULTS: A total of 287 (109 men, mean age: 46 ± 14 years) healthy subjects were enrolled at 22 collaborating institutions of the EACVI Normal Reference Ranges for Echocardiography (NORRE) study. Layer-specific strain was analysed from the apical two-, three-, and four-chamber views using 2DE software. The lowest values of layer-specific strain calculated as ±1.96 standard deviations from the mean were -15.0% in men and -15.6% in women for epicardial strain, -16.8% and -17.7% for mid-myocardial strain, and -18.7% and -19.9% for endocardial strain, respectively. Basal-epicardial and mid-myocardial strain decreased with age in women (epicardial; P = 0.008, mid-myocardial; P = 0.003) and correlated with age (epicardial; r = -0.20, P = 0.007, mid-myocardial; r = -0.21, P = 0.006, endocardial; r = -0.23, P = 0.002), whereas apical-epicardial, mid-myocardial strain increased with the age in women (epicardial; P = 0.006, mid-myocardial; P = 0.03) and correlated with age (epicardial; r = 0.16, P = 0.04). End/Epi ratio at the apex was higher than at the middle and basal levels of LV in men (apex; 1.6 ± 0.2, middle; 1.2 ± 0.1, base 1.1 ± 0.1) and women (apex; 1.6 ± 0.1, middle; 1.1 ± 0.1, base 1.2 ± 0.1). CONCLUSION: The NORRE study provides useful 2DE reference ranges for novel indices of layer-specific strain.

Correlation between non-invasive myocardial work indices and main parameters of systolic and diastolic function: results from the EACVI NORRE study.

AIMS: The present study sought to evaluate the correlation between indices of non-invasive myocardial work (MW) and left ventricle (LV) size, traditional and advanced parameters of LV systolic and diastolic function by 2D echocardiography (2DE). METHODS AND RESULTS: A total of 226 (85 men, mean age: 45 ± 13 years) healthy subjects were enrolled at 22 collaborating institutions of the Normal Reference Ranges for Echocardiography (NORRE) study. Global work index (GWI), global constructive work (GCW), global work waste (GWW), and global work efficiency (GWE) were estimated from LV pressure-strain loops using custom software. Peak LV pressure was estimated non-invasively from brachial artery cuff pressure. LV size, parameters of systolic and diastolic function and ventricular-arterial coupling were measured by echocardiography. As advanced indices of myocardial performance, global longitudinal strain (GLS), global circumferential strain (GCS), and global radial strain (GRS) were obtained. On multivariable analysis, GWI was significantly correlated with GLS (standardized beta-coefficient = -0.23, P < 0.001), ejection fraction (EF) (standardized beta-coefficient = 0.15, P = 0.02), systolic blood pressure (SBP) (standardized beta-coefficient = 0.56, P < 0.001) and GRS (standardized beta-coefficient = 0.19, P = 0.004), while GCW was correlated with GLS (standardized beta-coefficient = -0.55, P < 0.001), SBP (standardized beta-coefficient = 0.71, P < 0.001), GRS (standardized beta-coefficient = 0.11, P = 0.02), and GCS (standardized beta-coefficient = -0.10, P = 0.01). GWE was directly correlated with EF and inversely correlated with Tei index (standardized beta-coefficient = 0.18, P = 0.009 and standardized beta-coefficient = -0.20, P = 0.004, respectively), the opposite occurred for GWW (standardized beta-coefficient =--0.14, P = 0.03 and standardized beta-coefficient = 0.17, P = 0.01, respectively). CONCLUSION: The non-invasive MW indices show a good correlation with traditional 2DE parameters of myocardial systolic function and myocardial strain.

Improving Survival in Patients with Pulmonary Arterial Hypertension: Focus on Intravenous Epoprostenol.

Pulmonary arterial hypertension represents a devastating disease, causing progressive increase of pulmonary vascular resistance leading to right ventricular dysfunction and death. Therapeutic management has rapidly advanced in recent years due to improved understanding of pathophysiology and new drugs have been developed; however, survival remains poor. Oral agents as phosphodiesterase type V inhibitors, the soluble guanylyl cyclase stimulator riociguat, the prostacyclin receptor agonist selexipag and the endothelin receptor antagonists have each achieved evidence-based validation and are recommended for pulmonary arterial hypertension. Initial oral monotherapy or combination therapy is recommended for patients with low or intermediate risk according to each patient's risk stratification. Intravenous epoprostenol is a synthetic prostacyclin and the first drug approved for the disease. Although it represents the only treatment shown to reduce mortality, it is underused. Survival rates for patients treated with oral combination drug therapies are lower than those for patients treated with initial combination therapies including intravenous epoprostenol. This raises the interesting question of whether intermediate risk pulmonary arterial hypertension patients should be routinely introduced to therapies including intravenous epoprostenol rather than combination oral therapies.

Pulmonary arterial hypertension associated with interferon-beta treatment for multiple sclerosis. Case report and literature review.

Drug-Induced Pulmonary Arterial Hypertension (PAH) represents a well-known entity, predominantly related to anorexigens. Interferon-ß (IFN) is considered to be a drug with a possible risk of inducing PAH. We report a patient with Multiple Sclerosis treated with IFN-ß who diagnosed with PAH and her course of disease under specific PAH drug therapy. A review of the literature in IFN-ß-induced PAH is provided.

Echocardiographic reference ranges for normal non-invasive myocardial work indices: results from the EACVI NORRE study.

AIMS: To obtain the normal ranges for 2D echocardiographic (2DE) indices of myocardial work (MW) from a large group of healthy volunteers over a wide range of ages and gender. METHODS AND RESULTS: A total of 226 (85 men, mean age: 45 ± 13 years) healthy subjects were enrolled at 22 collaborating institutions of the Normal Reference Ranges for Echocardiography (NORRE) study. Global work index (GWI), global constructive work (GCW), global work waste (GWW), and global work efficiency (GWE) were estimated from left ventricle (LV) pressure-strain loops. Peak LV systolic pressure was non-invasively derived from brachial artery cuff pressure. The lowest values of MW indices in men and women were 1270 mmHg% and 1310 mmHg% for GWI, 1650 mmHg% and 1544 mmHg% for GCW, and 90% and 91% for GWE, respectively. The highest value for GWW was 238 mmHg% in men and 239 mmHg% in women. Men had significant lower values of GWE and higher values of GWW. GWI and GCW significantly increased with age in women. CONCLUSION: The NORRE study provides useful 2DE reference ranges for novel indices of non-invasive MW.

From cell to heart: the impact of the cell organelles dysfunction on heart disease.

: Cellular morphology reflects biologic behavior and activity of the tissue and of the organ also reflects the genetic and molecular biology of the cells themselves. This intermediary position places examination of the cell in a key role to our understanding of the innumerable processes that affect this closely knit chain, from molecules to host. A large volume of the cell is occupied by organelles that come in a variety of shapes and sizes. Organelles are dynamic to maintain homeostasis and adjust to the various functions of the cell. The cardiovascular system is metabolically very active and is therefore particularly vulnerable to defects of the cellular substructures, such as the mitochondrial respiratory chain. Given the functional complexity of the cardiovascular system, it is not surprising that defects in cell organelles produce diverse clinical manifestations. Organelle dysfunction is being recognized as the basis of a wide variety of heart diseases. In this review, the authors discuss the relationship between organelle structure and function in myocardial cells and how these organelles have been linked to the cardiovascular diseases.

Echocardiographic reference ranges for normal left atrial function parameters: results from the EACVI NORRE study.

Aims: To obtain the normal ranges for echocardiographic measurements of left atrial (LA) function from a large group of healthy volunteers accounting for age and gender. Methods and results: A total of 371 (median age 45 years) healthy subjects were enrolled at 22 collaborating institutions collaborating in the Normal Reference Ranges for Echocardiography (NORRE) study of the European Association of Cardiovascular Imaging (EACVI). Left atrial data sets were analysed with a vendor-independent software (VIS) package allowing homogeneous measurements irrespective of the echocardiographic equipment used to acquire data sets. The lowest expected values of LA function were 26.1%, 48.7%, and 41.4% for left atrial strain (LAS), 2D left atrial emptying fraction (LAEF), and 3D LAEF (reservoir function); 7.7%, 24.2%, and -0.53/s for LAS-active, LAEF-active, and LA strain rate during LA contraction (SRa) (pump function) and 12.0% and 21.6% for LAS-passive and LAEF-passive (conduit function). Left atrial reservoir and conduit function were decreased with age while pump function was increased. All indices of reservoir function and all LA strains had no difference in both gender and vendor. However, inter-vendor differences were observed in LA SRa despite the use of VIS. Conclusion: The NORRE study provides contemporary, applicable echocardiographic reference ranges for LA function. Our data highlight the importance of age-specific reference values for LA functions.

Echocardiographic reference ranges for normal left ventricular 2D strain: results from the EACVI NORRE study.

AIMS: To obtain the normal ranges for 2D echocardiographic (2DE) measurements of left ventricular (LV) strain from a large group of healthy volunteers accounting for age and gender. METHODS AND RESULTS: A total of 549 (mean age: 45.6 ± 13.3 years) healthy subjects were enrolled at 22 collaborating institutions of the Normal Reference Ranges for Echocardiography (NORRE) study. 2DE data sets have been analysed with a vendor-independent software package allowing homogeneous measurements irrespective of the echocardiographic equipment used to acquire the data sets. The lowest expected values of LV strains and twist calculated as ± 1.96 standard deviations from the mean were -16.7% in men and -17.8% in women for longitudinal strain, -22.3% and -23.6% for circumferential strain, 20.6% and 21.5% for radial strain, and 2.2 degrees and 1.9 degrees for twist, respectively. In multivariable analysis, longitudinal strain decreased with age whereas the opposite occurred with circumferential and radial strain. Male gender was associated with lower strain for longitudinal, circumferential, and radial strain. Inter-vendor differences were observed for circumferential and radial strain despite the use of vendor-independent software. Importantly, no intervendor differences were noted in longitudinal strain. CONCLUSION: The NORRE study provides contemporary, applicable 2D echocardiographic reference ranges for LV longitudinal, radial, and circumferential strain. Our data highlight the importance of age- and gender-specific reference values for LV strain.

EACVI appropriateness criteria for the use of transthoracic echocardiography in adults: a report of literature and current practice review.

The European Association for Cardiovascular Imaging (EACVI) has outlined the rationale for setting appropriate use criteria (AUC) in cardiovascular (CV) imaging. Transthoracic echocardiography (TTE) is the most common imaging modality in CV disease and is a central tool in diagnosis, follow-up, management planning and intervention. The purpose of AUC is to inform referrers, both to avoid under-use, which may result in incomplete or incorrect diagnosis and treatment, and also over-use, which may delay correct diagnosis, lead to 'treatment cascade', and wastes resources. The first step in defining AUC for TTE in the adult has been for a panel of experts in echocardiography to review the evidence, guidelines, recommendations, and position papers from the European Society of Cardiology, EACVI and other specialist societies, and current state-of-the-art clinical practice. The attached document summarizes this work, which will be used to under-pin the development of AUC.

3D echocardiographic reference ranges for normal left ventricular volumes and strain: results from the EACVI NORRE study.

AIM: To obtain the normal ranges for 3D echocardiography (3DE) measurement of left ventricular (LV) volumes, function, and strain from a large group of healthy volunteers. METHODS AND RESULTS: A total of 440 (mean age: 45 ± 13 years) out of the 734 healthy subjects enrolled at 22 collaborating institutions of the Normal Reference Ranges for Echocardiography (NORRE) study had good-quality 3DE data sets that have been analysed with a vendor-independent software package allowing homogeneous measurements regardless of the echocardiographic machine used to acquire the data sets. Upper limits of LV end-diastolic and end-systolic volumes were larger in men (97 and 42 mL/m2) than in women (82 and 35 mL/m2; P < 0.0001). Conversely, lower limits of LV ejection fraction were higher in women than in men (51% vs. 50%; P < 0.01). Similarly, all strain components were higher in women than in men. Lower range was -18.6% in men and -19.5% in women for 3D longitudinal strain, -27.0% and -27.6% for 3D circumferential strain, -33.2% and -34.4% for 3D tangential strain and 38.8% and 40.7% for 3D radial strain, respectively. LV volumes decreased with age in both genders (P < 0.0001), whereas LV ejection fraction increased with age only in men. Among 3DE LV strain components, the only one, which did not change with age was longitudinal strain. CONCLUSION: The NORRE study provides applicable 3D echocardiographic reference ranges for LV function assessment. Our data highlight the importance of age- and gender-specific reference values for both LV volumes and strain.

Two-dimensional transthoracic echocardiographic normal reference ranges for proximal aorta dimensions: results from the EACVI NORRE study.

AIMS: To report normal reference ranges for echocardiographic dimensions of the proximal aorta obtained in a large group of healthy volunteers recruited using state-of-the-art cardiac ultrasound equipment, considering different measurement conventions, and taking into account gender, age, and body size of individuals. METHODS AND RESULTS: A total of 704 (mean age: 46.0 ± 13.5 years) healthy volunteers (310 men and 394 women) were prospectively recruited from the collaborating institutions of the Normal Reference Ranges for Echocardiography (NORRE) study. A comprehensive echocardiographic examination was obtained in all subjects following pre-defined protocols. Aortic dimensions were obtained in systole and diastole, following both the leading-edge to leading-edge and the inner-edge to inner-edge conventions. Diameters were measured at four levels: ventricular-arterial junction, sinuses of Valsalva, sino-tubular junction, and proximal tubular ascending aorta. Measures of aortic root in the short-axis view following the orientation of each of the three sinuses were also performed. Men had significantly larger body sizes when compared with women, and showed larger aortic dimensions independently of the measurement method used. Dimensions indexed by height and body surface area are provided, and stratification by age ranges is also displayed. In multivariable analysis, the independent predictors of aortic dimensions were age, gender, and height or body surface area. CONCLUSION: The NORRE study provides normal values of proximal aorta dimensions as assessed by echocardiography. Reference ranges for different anatomical levels using different (i) measurement conventions and (ii) at different times of the cardiac cycle (i.e. mid-systole and end-diastole) are provided. Age, gender, and body size were significant determinants of aortic dimensions.

Cardiac Dual-source Computed Tomography for the Detection of Left Main Compression Syndrome in Patients with Pulmonary Hyper-tension.

INTRODUCTION: Left Main Compression Syndrome (LMCS) represents an entity described as the extrinsic compression of the left main coronary artery (LMCA) by a dilated pulmonary artery (PA) trunk. We examined the presence of LMCS in patients with pulmonary hypertension (PH) using dual-source computed tomography (DSCT), as a non-invasive diagnostic tool. METHODS: The following parameters were measured: PA trunk diameter (PAD), the distance between PAD and LMCA (LMPA) and the distance between PA and aorta (AoPA). These measurements were related with demographic, echocardiographic, hemodynamic and clinical parameters. Angiography was performed in two patients with LMCS suspected by cardiac computed tomographic angiography. Patients without PH but with angina were examined as controls, using DSCT cardiac angiography to assess the same measurements and to detect the prevalence of coronary artery disease. RESULTS: PA diameter value over 40.00 mm has been associated with PH and LMCS. Furthermore, LMCS did not occur at a distance smaller than 0.50 mm between the PA and the LMCA, and did not correlate with the distance between the PA and the aorta or with cardiac index and NT-proBNP. CONCLUSION: DSCT may represent the initial testing modality in PH patients with dilated PA trunk to exclude LMCS. A periodical rule-out of this rare entity, as assessed by DSCT, in patients with a severely dilated PA seems to be mandatory for PH patients contributing to survival improvement.

Echocardiographic reference ranges for normal cardiac Doppler data: results from the NORRE Study.

AIMS: Reference values for Doppler parameters according to age and gender are recommended for the assessment of heart physiology, specifically for left ventricular (LV) diastolic function. In this study, we report normal reference ranges for Doppler parameters obtained in a large group of healthy volunteers. Echocardiographic data were acquired using state-of-the-art cardiac ultrasound equipment following Doppler acquisition and measurement protocols approved by the European Association of Cardiovascular Imaging. METHODS AND RESULTS: A total of 449 (mean age: 45.8 ± 13.7 years) healthy volunteers (198 men and 251 women) were enrolled at the collaborating institutions of the Normal Reference Ranges for Echocardiography (NORRE) study. A comprehensive echocardiographic examination was obtained from all subjects following predefined protocols. The majority of the Doppler diastolic parameters (e', E/e') as well as right ventricle systolic s' wave velocity were similar in men and women. Left ventricle s' wave velocity was higher in men than in women. E wave and e' were higher in younger subjects and decreased progressively in the older ones. E/e' ratio increased with ageing. Septal e' <8 cm/s was present in 19.7% of the subjects in the 40-60 year group and in 55% of those in the ≥60 year group. However, the cut-off value of average E/e' or lateral E/e' remained <15 or 13, respectively, in the majority of patients. CONCLUSION: The NORRE study provides the reference values for the most useful Doppler parameters in the evaluation of heart physiology. These data highlight the need of using age-specific reference values especially for the diagnosis of LV systolic and diastolic dysfunction and for the estimation of LV filling pressures.

First application of coronary flow reserve measurement for the assessment of left main compression syndrome in pulmonary hypertension.

Left main compression syndrome (LMCS) refers to extrinsic compression of the left main coronary artery because of a dilated pulmonary artery trunk. The condition represents an unusual cause of angina, left ventricular dysfunction, and sudden cardiac death in patients with pulmonary hypertension. We present 2 patients with the syndrome who were followed with serial assessments of coronary flow reserve by transthoracic echocardiography to screen for LMCS-related ischemia.