The un-natural history of an adolescent with combined congenital and acquired heart disease.

This study describes the un-natural history of a 16-year-old patient, presenting with a critical bicuspid aortic valve stenosis, who was initially treated in the neonatal period and later with a valvuloplasty. This focused the attention on palliative interventions that, in young adulthood or middle age, are usually related to several complications, until heart transplantation. The other important aspect of this case is the presence of a coronary atherosclerotic plaque producing a significant obstruction, in the setting of haemodynamic acute postoperative failure caused by the sudden aortic valve laceration and insufficiency. This favoured the transmural myocardial antero-septal evolution of the myocardial ischaemic-reperfusion damage. This case is peculiar in that it presents two unrelated entities in their natural history. The coronary lesion was an unexpected finding in an adolescent with congenital heart disease. The severity of the coronary lesion became haemodynamically significant as a combination of the hypoperfusion due to the massive aortic valve regurgitation following the acute failure of the aortic valve plasty and the vasoconstriction of the eccentric speared segment. Once again, the complete understanding of grown-up patients with congenital hart disease is mandatory together with the point that a close collaboration of a multidisciplinary team is essential for appropriate operative timing and planning the most suitable treatment option. Acquired heart diseases can rarely present in association in this group of patients and need to be taken into account.

Ascending aorta diameters measured by echocardiography using both leading edge-to-leading edge and inner edge-to-inner edge conventions in healthy volunteers.

AIMS: Reference ranges of ascending aorta diameters (AAoD) for two-dimensional echocardiography (2DE) using inner edge (IE) convention are lacking, preventing the comparison of AAoD measurements by 2DE with those obtained by other imaging modalities. METHODS AND RESULTS: We used harmonic imaging 2DE to prospectively study 218 healthy volunteers (56% women, 42 ± 15 years, 18-80 years). Measurements were performed at the level of aortic root (AoR), sinotubular junction (STJ), and proximal tubular portion (TAo, 1 cm from the STJ) using both leading edge (LE) and IE conventions at end-diastole and end-systole. Feasibility of AAoD measurements between end-diastole and end-systole was similar at AoR and STJ levels, but it was significantly different at TAo level (82 vs. 96%, respectively, P < 0.0001). Ascending aorta diameters indexed to height were larger in men than in women (P < 0.0001). After adjusting for the effect of gender, only age and body surface area (BSA) were independent predictors of AAoD at multivariable analysis. Average end-diastolic AoR, STJ, and TAo diameters measured using IE convention were similar between genders (17 ± 2, 15 ± 2, and 15 ± 2 mm/m(2), respectively). Corresponding AAoD measured using the LE convention were 18 ± 2, 16 ± 2, and 17 ± 4 mm/m(2), respectively. On average, the end-systolic AAoD measured using LE were 2 mm larger than those performed using IE or at end-diastole. Mean aortic wall thickness was 2.4 ± 0.8 mm. CONCLUSION: End-diastolic AAoD measured using IE were significantly smaller than those obtained either using LE convention or at end-systole. Gender-specific reference values for AAoD indexed for BSA should be used to identify ascending aorta pathology.

Right atrial size and function assessed with three-dimensional and speckle-tracking echocardiography in 200 healthy volunteers.

AIMS: Right atrial (RA) size predicts the outcome in some pathological conditions but reference values for RA volumes and myocardial function remain to be defined. Thus, we used two-dimensional speckle-tracking echocardiography (2D-STE) and three-dimensional echocardiography (3DE) to define normative reference values of RA volumes and function. METHODS AND RESULTS: Two hundreds healthy volunteers (43 ± 15 years, range 18-75; 44% men) underwent two-dimensional echocardiography (2DE) to obtain RA volumes and longitudinal strain (LS) of RA wall using 2D-STE, and 3DE to measure maximal (Vmax), minimal, and preA volumes to calculate total, passive, and active emptying volumes (TotEV, PassEV, and ActEV) and emptying fractions (TotEF, PassEF, and ActEF). Three-dimensional echocardiography volumes (Vmax, 52 ± 15 mL vs. 41 ± 14 mL), EVs (TotEV, 33 ± 10 mL vs. 24 ± 9 mL), and EFs (TotEF, 63 ± 9 vs. 58 ± 9%) were larger than 2DE ones (all P < 0.0001). Indexed 3D volumes were significantly larger in men than in women. RA TotEF correlated with total LS (r = 0.24, P = 0.025) and PassEF with positive LS (LSpos; r = 0.34, P < 0.0001). Ageing was associated with a decrease in passive (LSpos, r = -041; PassEV, r = -0.26; PassEF, r = -0.38; all P < 0.0001) and an increase in active RA function (negative LS, r = 0.34; ActEV, r = 0.25; all P < 0.0001; and ActEF, r = 0.15; P = 0.035) in order to maintain TotEV (r = -0.14, P = 0.05). CONCLUSION: Our study provides normative values for RA volumes and function measured by 3DE and 2D-STE in a relatively large cohort of healthy subjects with a wide age range. These data will help clinicians to identify RA remodelling and dysfunction.

R25C mutation in the NKX2.5 gene in Italian patients affected with non-syndromic and syndromic congenital heart disease.

AIMS: Heterozygous mutations in the transcription factor Nkx2.5 indicate a genetic cause for congenital heart diseases (CHDs) in human beings. The present study aimed to assess the prevalence of NKX2.5 mutations in Italian patients with sporadic non-syndromic and syndromic CHD, as well as to appraise any genotype-phenotype correlations. METHODS: One hundred Italian patients affected with CHD (90 had sporadic non-syndromic CHD and 10 had syndromic CHD) were screened for NKX2.5 mutations. The coding region and flanking regions involved in gene splicing of the CSX/NKX2.5 gene were amplified from genomic DNA by PCR, and mutational analysis was performed using denaturing high performance liquid chromatography and DNA sequencing. RESULTS: One previously reported NKX2.5 mutation (c.73C>T, p.R25C) was identified in two of the 100 CHD patients (2%). We have detected the p.R25C alteration in a woman showing aneurysm of the membranous septum, aortic coarctation and bicuspid aortic valve, that was a different phenotype from those previously reported, and for the first time in a patient with syndromic CHD with Down's syndrome (posterior ventricular septal defect, atrial septal defect, left superior cava vein ' sinus, and patent ductus arteriosus). CONCLUSION: Our results confirm that NKX2.5 mutations are not a common cause of CHD; furthermore, the p.R25C variation may increase susceptibility to development of CHD in patients with and without chromosomal abnormalities.

Comprehensive analysis of left ventricular geometry and function by three-dimensional echocardiography in healthy adults.

BACKGROUND: Recent European Association of Echocardiography and American Society of Echocardiography guidelines on three-dimensional echocardiography state that normal values of left ventricular (LV) parameters for age and body size remain to be established. METHODS: In 226 consecutive healthy subjects (125 women; age range, 18-76 years), comprehensive three-dimensional echocardiographic analyses of LV parameters were performed, and values were compared with those obtained by conventional echocardiography. RESULTS: Upper reference values (mean+ 2 SDs) for three-dimensional LV end-diastolic and end-systolic volumes were 85 and 34 mL/m(2) in men and 72 and 28 mL/m(2) in women, respectively. Indexing LV volumes to body surface area did not eliminate gender differences. Lower reference values (mean - 2 SDs) for ejection fraction were 54% in men and 57% in women and for stroke volume were 25 and 24 mL/m(2), respectively. Upper reference values for LV mass were 97 g/m(2) in men and 90 g/m(2) in women and for end-diastolic sphericity index were 0.49 and 0.48, respectively. Significant age dependency of LV parameters was identified and reported across age groups. Three-dimensional echocardiographic LV volumes were larger, ejection fraction was similar, and LV stroke volume and mass were significantly smaller in comparison with the corresponding values obtained by conventional echocardiography. CONCLUSIONS: The investigators report a comprehensive analysis of LV geometry and function using three-dimensional echocardiography in a relatively large cohort of healthy Caucasian subjects with a wide age range. These may serve to establish age-specific and gender-specific reference ranges, which are crucial for the routine implementation of three-dimensional echocardiography to detect LV remodeling and dysfunction in clinical practice.

Gender differences and role of pregnancy in the history of post-surgical women affected by tetralogy of Fallot.

BACKGROUND: The aim of this study was to describe gender differences in patients operated on for TOF and to define the impact of pregnancy in late post-surgical follow-up in women. METHODS: In this research, we studied 145 patients after correction of TOF: 66 male, 79 women, 41 of which reported history of 68 pregnancies, means age 37±10 years, age at operation 7±8 years, mean duration of post-surgical follow-up 30±7 years. Selected variables were compared according to sex and according to history of pregnancy with statistical tests. RESULTS: Men had more severe hemodynamic impairment and a higher number of cardiac reoperations than females. 41% of patients had at least one complication during pregnancy; there were 16 (67%) abortions and 39 (74%) Caesarian delivers; the recurrence of congenital heart defect was 10%. After pregnancy, there was a shift from first to second functional class: unique pregnancy determined no differences in term of morpho-functional ventricular features compared to nulliparous, but they complained fatigue and palpitation and echocardiographyc dysfunction. Left ventricular dysfunction and QRS duration at ECG were independent predictors of ventricular arrhythmias in all patients. CONCLUSIONS: There were no gender-specific differences in patients operated on for TOF using ventriculotomy. Pregnancy is an event in these patients at risk for the newborn, in terms of miscarriage, prematurity, and recurrence of birth defects, and for the mother in terms of ventricular dysfunction and electrical instability. At least a single pregnancy does not appear to significantly modify the natural history of post-surgical patients operated on for TOF.

A new view on congenital heart disease: clinical burden prevision of changing patients.

The introduction and diffusion of cross-sectional echocardiography at the end of 1970s significantly improved case ascertainment and allowed the identification of congenital heart defects with a significant increase of mild forms. However, the prevalence of severe congenital heart disease (CHD), which represented 11.7% of overall cardiovascular malformations, remained quite stable (less than 1 per 1000 live births). In past decades, a new population of adults with CHD emerged who need specialized care in centres with trained and experienced professional staff with a different level of expertise. Clinical implications of this new scenario are discussed in this article.

Mental stress and ischemic heart disease: evolving awareness of a complex association.

The connection between cardiovascular disease and psychosocial risk factors has been the subject of an ever-growing body of literature over the last 50 years. Studies on the role of negative emotions, personality traits, chronic stress and social determinants have brought to light their possible role in triggering acute coronary syndromes, although further studies are required to clarify controversial results regarding the association between cardiovascular risk and important psychological problems such as depression and anxiety. The recognition of the role of emotional events in acute coronary syndromes paved the way for provocation experiments, aimed at inducing mental stress in a controlled setting and then documenting reversible impairment of myocardial perfusion, depolarization anomalies and arrhythmias. This ultimately led to the formalization of the concept of mental stress-induced myocardial ischemia. Accumulating evidence on the mechanistic bases of such phenomena outline a wide range of central and peripheral physiological changes associated with emotions and behaviors, whose effects are exerted on the cardiovascular system, sympathetic nervous system and the hypothalamus-hypophysis neuroendocrine axis. This article outlines the main steps in the identification of psychological aspects as cardiovascular risk factors and emphasizes the relevance of emotional stress as a trigger of acute cardiovascular events. Finally, a description is provided of the pathophysiological mechanisms behind mental stress-induced myocardial ischemia and pathways connecting the heart and brain.