Global longitudinal strain assessment of cardiac function and extravascular lung water formation after diving using semi-closed circuit rebreather.

PURPOSE: The aim of the present investigation is to study the relationship of ventricular global longitudinal strain (GLS) and ultrasound lung comets (ULC) formation to establish a link between extravascular pulmonary water formation and cardiac contractile dysfunction. METHODS: This is a prospective observational study including 14 active military divers. The subjects performed two sea dives of 120 min each with a semi-closed SCUBA circuit at 10 m depth. Divers were examined at baseline, 15 min (D1) and 60 min (D2) after diving. The evaluation included pulmonary and cardiac echography (including speckle tracking techniques). Blood samples were drawn at baseline and after diving, assessing hs-TnT and Endothelin-1. RESULTS: ULC were detected in 9 (64.2%) and 8 (57.1%) of the subjects after D1 and D2 respectively. No differences were found in right and left ventricular GLS after both immersions (RV: Baseline: - 17.9 4.9 vs. D1: - 17.2 6.5 and D2: - 16.7 5.8 s-1; p = 0.757 and p = 0.529; LV: Baseline: - 17.0 2.3 vs. D1: - 17.4 2.1 and D2: - 16.9 2.2 s-1; p = 0.546 and p = 0.783). However, a decrease in atrial longitudinal strain parameters have been detected after diving (RA: Baseline: 35.5 9.2 vs. D1: 30.3 12.8 and D2: 30.7 13.0 s-1; p = 0.088 and p = 0.063; LA: Baseline: 39.0 10.0 vs. D1: 31.6 6.1 and D2: 32.4 10.6 s-1; p = 0.019 and p = 0.054). CONCLUSION: In the present study, no ventricular contractile dysfunction was observed. However, increase pulmonary vasoconstriction markers were present after diving.

Influence of aortic regurgitation after TAVI on left ventricular filling pattern.

BACKGROUND: Paravalvular aortic regurgitation after transcatheter aortic valve implantation is associated with a hemodynamic deterioration and a poor outcome. We aim to determine the early hemodynamic effect of paravalvular aortic regurgitation in relation with the change in the left ventricle filling pattern and to assess their clinical outcome. MATERIAL AND METHODS: Eighty-two consecutive patients referred for transcatheter aortic valve implantation were included. Patients were classified according to the change in the left ventricular filling pattern, and significant paravalvular aortic regurgitation (grade ≥ 2) was reported. Follow-up and incidence of death and hospitalization for heart failure were reported. RESULTS: Sixteen patients (19·5%) presented a worsening of left ventricular filling pattern. The incidence of significant paravalvular aortic regurgitation was higher in the group with a worsening of left ventricular filling pattern (56·3% vs. 19·7%; P = 0·009). In the multivariate analysis, the only variable significantly associated with the worsening of left ventricular filling pattern was the significant paravalvular aortic regurgitation (OR 4·84; 95% CI 1·23 - 19·1; P = 0·024). During the follow-up (642·5 days), there was a higher incidence of the endpoint of death or hospitalization for heart failure in the group with a worsening of left ventricular filling pattern (62·5% vs. 31·8%; P = 0·042) and a lower event-free survival rate (long rank test = 0·013). CONCLUSIONS: The presence of a significant paravalvular aortic regurgitation is associated with a worsening in parameters of diastolic function. This finding should alert the cardiologist as patients with a worsening of left ventricular filling pattern present a higher incidence of paravalvular aortic regurgitation and a less favourable outcome.

TWEAK and NT-proBNP levels predict exercise capacity in hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is characterized by inappropriate hypertrophy, myocyte disarray and increased interstitial fibrosis. The tumour necrosis factor-like weak inducer of apoptosis (TWEAK) is a cell surface cytokine with biological activities including stimulation of cell growth, induction of inflammatory cytokines and stimulation of apoptosis. There are controversial data about the potential role of TWEAK in different cardiovascular pathologies. NT-proBNP is an established biomarker of myocardial wall stress, associated with poor functional class in HCM. We hypothesized that effort capacity in patients with HCM could be related to serum levels of these biomarkers. MATERIALS AND METHODS: We included 40 haemodynamic stable HCM patients and 53 healthy controls with similar sex and age. We studied exercise capacity by maximal oxygen consumption in a limited treadmill exercise test. TWEAK and NT-proBNP were assayed by ELISA method and automated Elecsys® platform, respectively. We obtained 46 samples of myocardial tissues by septal myectomy in patients with HCM and evaluated myocardial fibrosis, immunoreaction with TWEAK antibody and apoptosis with TUNEL assay. RESULTS: We found raised TWEAK and NT-proBNP serum levels in patients when compared with control levels (both P < 0.001). In a multivariate analysis, TWEAK and NT-proBNP levels, as well as sex, remained independently associated with the effort capacity (all P < 0.05). We found an association between immunoreaction degree and the degree of myocardial fibrosis (P = 0.021), as well as apoptosis (P = 0.002) in the tissue samples from patients undergoing septal myectomy. CONCLUSIONS: TWEAK and NT-proBNP levels are biomarkers of disease severity independently associated with the effort capacity in patients with HCM.

Aortic valve stenosis planimetry by means of three-dimensional transesophageal echocardiography in the real clinical setting: feasibility, reliability and systematic deviations.

AIMS: To assess the feasibility and reliability of aortic valve area (AVA) planimetry by means of three-dimensional transesophageal echocardiography (3DTEE) as compared with the transthoracic echocardiogram (TTE) calculation of AVA, to determine the systematic deviations between measurements, and to describe the distribution of mean systolic in relation with 3DTEE anatomical AVA. METHODS AND RESULTS: Three hundred seven patients with aortic valve stenosis (AVS) underwent both TTE and 3DTEE for AVA measurement by means of the continuity equation and direct anatomical planimetry, respectively. AVA planimetry was achieved in 282 (91.9%) of patients. Severity of the aortic valve calcification was independently associated with a poorer performance of planimetry. Intraclass correlation coefficient yielded a 0.848 (95% CI: 0.807-0.879) value. 3DTEE rendered a mild constant underestimation of AVA in comparison with TTE. Severe aortic stenosis according to the area criterion (<1 cm(2) ) despite mean systolic gradient below 40 mm Hg was detected in 37.6% of the study population, and in 33.7% of the subset of patients with preserved left ventricular ejection fraction. CONCLUSIONS: Reliability of AVA planimetry by 3DTEE in comparison with the calculation by TTE is good, but 3DTEE underestimates slightly the measurement. Feasibility of the technique is good but independently affected by valvular calcification. Inconsistent classification of AVS severity as graded by AVA or mean systolic gradient is observed in the overall population and in patients with preserved systolic function.

Invasive management of significant tricuspid regurgitation in clinical practice.

BACKGROUND: Tricuspid regurgitation (TR) is a prevalent condition inside valvular heart disease (VHD) with relevant prognosis implications. However, concordance between real management in clinical practice and invasive treatment recommendations of European Society of Cardiology (ESC) guidelines is unknown. METHODS: A substudy of ESC VHD II survey was performed to evaluate the real treatment of TR compared to the clinical ESC guidelines recommendations published in 2012, 2017 and 2021 was performed. TR cases with surgical indication were divided in 3 groups: 1: severe isolated TR without previous left VHD; 2: moderate/severe TR and concomitant severe left VHD; 3: severe TR plus previous left VHD surgery. RESULTS: Of 902 patients assessed, 123 had significant TR. Fifty (41%) cases demonstrated ESC guidelines 2012-2017 Class I or IIa recommendations for invasive treatment: 9(18%) of group 1, 37(74%) of group 2 and 4(8%) of group 3. Surgery was performed in 24 patients (48%); 1 in group 1(4%), 22 in group 2(92%) and 1 in group 3(4%). Overall concordance was 48% (group 1: 11%; group 2: 59%; group 3: 25%). Regarding the 2021 ESC guidelines only one patient changed groups with an overall concordance of 47% (group 1: 10%; group 2: 59%; group 3: 25%). CONCLUSION: Concordance between 2012, 2017 and 2021 ESC guidelines recommendations and clinical practice for TR surgical intervention is low, especially in those without concomitant severe left VHD. These results suggest the need to improve further guideline implementation and alternative treatments, such as percutaneous, which could resolve potential discrepancies in those clinical scenarios.

Contact pathway in surgical and transcatheter aortic valve replacement.

Background: Aortic valve replacement is the gold standard treatment for severe symptomatic aortic stenosis, but thrombosis of bioprosthetic valves (PVT) remains a concern. Objective: To analyze the factors involved in the contact pathway during aortic valve replacement and to assess their impact on the development of thromboembolic complications. Methods: The study was conducted in 232 consecutive patients who underwent: transcatheter aortic valve replacement (TAVR, N = 155), and surgical valve replacement (SAVR, N = 77) (MUVITAVI project). Demographic and clinical data, outcomes including a combined end point (CEP) of thrombotic events, and imaging controls were recruited. Samples were collected 24 h before and 48 h after valve replacement. FXII, FXI and (pre)kallikrein were evaluated by Western Blot and specific ELISA with nanobodies. Results: The CEP of thrombotic events was reached by 19 patients: 13 patients presented systemic embolic events and 6 patients subclinical PVT. Valve replacement did not cause FXII activation or generation of kallikrein. There was a significant reduction of FXI levels associated with the procedure, which was statistically more pronounced in SAVR than in TAVR. Cases with reductions of FXI below 80% of basal values had a lower incidence of embolic events during the procedure than patients in whom FXI increased above 150%: 2.7 vs. 16.7%; p: 0.04. Conclusion: TAVR or SAVR did not significantly activate the contact pathway. A significant reduction of FXI, was observed, particularly in SAVR, associated with lower incidence of thrombotic events. These results encourage evaluating the usefulness and safety of FXI-directed antithrombotic treatments in these patients.

Serum levels of high-sensitivity troponin T: a novel marker for cardiac remodeling in hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is characterized by inappropriate hypertrophy, small-vessel coronary artery disease, myocyte disarray, and increased interstitial fibrosis. High-sensitivity troponin T (hs-TnT) could be a reliable indicator of myocardial remodeling, a proposed prognostic marker in HCM. Therefore we hypothesized that increased hs-TnT levels are related to different variables associated with myocardial remodeling, such as the presence of fibrosis assessed with cardiac magnetic resonance imaging (MRI). METHODS AND RESULTS: We included 95 hemodynamically stable HCM patients, 72 male, aged 45.7 ± 14.2 years, and 45 healthy control subjects with similar age and gender. A complete history and clinical examination was performed, including 12-lead electrocardiogram (ECG), echocardiography, 24-hour ECG-Holter monitoring, symptom-limited treadmill exercise test, and late gadolinium enhancement in cardiac MRI. Risk factors for sudden death were evaluated. A blinded cardiac MRI was performed with late gadolinium enhancement study. Serum hs-TnT levels were assayed. A high proportion (42%) of hemodynamically stable patients studied showed increased levels of hs-TnT. The hs-TnT levels were raised in patients with severe dyspnea: New York Heart Association (NYHA) functional class ≥3 (P = .020), outflow obstruction (P = .013), systolic dysfunction (P = .037), abnormal blood pressure response (P = .036), and presence of gadolinium enhancement (P = .021). The hs-TnT levels correlated positively with the maximum left ventricular wall thickness (r = 0.47; P < .001), left atrial diameter (r = 0.36, P = .014), and outflow gradient (r = 0.28; P = .008). CONCLUSIONS: A high proportion of hemodynamically stable patients show increased levels of hs-TnT. We observed that raised hs-TnT serum levels are associated with different conditions related to the severity of the disease.

Real-time three-dimensional transoesophageal echocardiography in the assessment of aortic valve stenosis.

AIMS: To determine the feasibility of real-time three-dimensional transoesophageal echocardiography (3D-TOE) in the evaluation of aortic valve stenosis, to study its reliability, and to test the concordance of this new method when compared with transthoracic two-dimensional echocardiography (2D-TTE) as the diagnostic standard. METHODS AND RESULTS: Fifty-nine consecutive patients with moderate-to-severe aortic valve stenosis were assessed by means of 2D-TTE and 3D-TOE by independent blinded observers. Aortic valve planimetry was possible in 94.9% of patients. Inter-observer intraclass correlation coefficients (ICC) were 0.892 (CI 95% 0.818-0.936; P < 0.001), and 0.871 (CI 95% 0.780-0.925; P < 0.001) for 2D-TTE and 3D-TOE, respectively. Bland-Altman plot showed a mean difference in aortic valve area (AVA) of 0.040 cm(2), with 2D-TTE yielding larger values than 3D-TOE. ICC of both methods was 0.724 (CI 95% 0.530-0.839; P < 0.001). CONCLUSION: Assessment of AVA by means of 3D-TOE is feasible in most patients with aortic valve stenosis. Reliability of the measurement is good. However, there is some disagreement with standard 2D-TTE that needs further investigation.

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.

Galectin-3 and ß-trace protein concentrations are higher in clinically unaffected patients with Fabry disease.

Current therapies have not shown benefit in organ damage reversal in Fabry disease (FD), but biomarkers could help risk stratification and prognosis. We investigated if several biomarkers of cardiac fibrosis, cardiac wall stress, myocardial injury, renal function and inflammation, are associated with early cardiac affectation in FD patients. We included FD patients from four cardiology outpatient clinics of southeastern Spain. At inclusion, Galectin-3 (Gal-3), N-terminal proB-type natriuretic peptide, high sensitivity troponin T (hsTnT), ß-trace protein (BTP) and interleukin-6 concentrations were measured. The relation of biomarkers concentrations with clinical features, cardiac involvement and organ affectation according to the Mainz Severity Score Index (MSSI) was investigated. 44 FD patients (n = 21 affected and n = 23 unaffected) were compared to age and sex-respectively matched healthy controls. Significant differences in biomarkers' concentration between FD groups were observed. Importantly, Gal-3 and BTP levels were higher in unaffected patients when compared with age and sex-matched healthy controls (both p < 0.05). All the biomarkers correlated with clinical features. When cut-off values for clinical affectation (measured as MSSI ≥ 20) were established, only hsTnT (OR 30.69, 95% CI 2.70-348.42) and male sex (OR 8.17, 95% CI 1.16-57.75) were independently associated with cardiac damage by multivariate regression analysis. Gal-3 and BTP levels are increased in unaffected FD patients compared to healthy controls. This suggests that these biomarkers could be useful for the early detection of cardiac affectation in FD patients. On the other hand, hsTnT and male sex are independent risk factors for established clinical cardiac damage in FD.

Prognosis of Patients With Severe Aortic Stenosis After the Decision to Perform an Intervention.

INTRODUCTION AND OBJECTIVES: Current therapeutic options for severe aortic stenosis (AS) include transcatheter aortic valve implantation (TAVI) and surgical aortic valve replacement (SAVR). Our aim was to describe the prognosis of patients with severe AS after the decision to perform an intervention, to study the variables influencing their prognosis, and to describe the determinants of waiting time > 2 months. METHODS: Subanalysis of the IDEAS (Influence of the Severe Aortic Stenosis Diagnosis) registry in patients indicated for TAVI or SAVR. RESULTS: Of 726 patients with severe AS diagnosed in January 2014, the decision to perform an intervention was made in 300, who were included in the present study. The mean age was 74.0 ± 9.7 years. A total of 258 (86.0%) underwent an intervention: 59 TAVI and 199 SAVR. At the end of the year, 42 patients (14.0%) with an indication for an intervention did not receive it, either because they remained on the waiting list (34 patients) or died while waiting for the procedure (8 patients). Of the patients who died while on the waiting list, half did so in the first 100 days. The mean waiting time was 2.9 ± 1.6 for TAVI and 3.5 ± 0.2 months for SAVR (P = .03). The independent predictors of mortality were male sex (HR, 2.6; 95%CI, 1.1-6.0), moderate-severe mitral regurgitation (HR, 2.6; 95%CI, 1.5-4.5), reduced mobility (HR, 4.6; 95%CI, 1.7-12.6), and nonintervention (HR, 2.3; 95%CI, 1.02-5.03). CONCLUSIONS: Patients with severe aortic stenosis awaiting therapeutic procedures have a high mortality risk. Some clinical indicators predict a worse prognosis and suggest the need for early intervention.

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.

Matrix metalloproteinases and tissue remodeling in hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is defined by the presence of unexplained left ventricular hypertrophy, myocyte disarray, and interstitial fibrosis. An increase in extracellular matrix produces interstitial fibrosis, by raised amounts of collagen type I/III. Regions of myocardial late gadolinium enhancement by cardiac magnetic resonance (CMR) represented increased myocardial collagen. Regarding the role of matrix metalloproteinases (MMPs) in myocardial remodeling and subsequent fibrosis, the aim of our study was to explore the relation between MMP system and myocardial late gadolinium enhancement by CMR (as expression of image-documented fibrosis) and N-terminal pro-brain natriuretic peptide (NT-proBNP) (as a marker of cardiac overload) in HCM. METHODS: We included 67 HCM patients (44 men aged 49 +/- 14 years) and were compared to 58 controls with similar age and sex. Risk factors for sudden death were recorded. A blinded CMR was performed with gadolinium. Matrix metalloproteinase 1, MMP-2, and MMP-9 plasma levels were assayed by enzyme-linked immunosorbent assay. Serum samples were used for measurement of NT-proBNP. RESULTS: In patients, >50% of MMP-1 values were below the lowest limit of detection of the technique. Raised levels of MMP-2, MMP-9, and NT-proBNP were observed in HCM patients (all P < .01). Matrix metalloproteinase 2 was associated with dyspnea (P = .049) and correlated with MMP-9 (r = 0.28, P = .025) and NT-proBNP (r = 0.39, P = .001). Matrix metalloproteinase 9 was associated with the presence of gadolinium enhancement in CMR (P = .001) and correlated with NT-proBNP (r = 0.52, P < .001). NT-proBNP was also associated with gadolinium enhancement (P = .006). Both MMP-2 and MMP-9 correlated negatively with exercise capacity (metabolic equivalent units), (r = -0.36 and r = -0.42 respectively, both P < .01). On multivariate analysis (adjusted by sudden death risk factors and echocardiographic markers), only MMP-9 was associated with fibrosis (P = .011). CONCLUSIONS: Matrix metalloproteinase 9 is independently associated with gadolinium enhancement on CMR in patients with hypertrophic cardiomyopathy, suggesting that the MMP system has an important role in cardiac remodeling and fibrosis in this condition.

Variables associated with contrast-enhanced cardiovascular magnetic resonance in hypertrophic cardiomyopathy: clinical implications.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) shows increased myocardial collagen and disarray. Late gadolinium enhancement in cardiovascular magnetic resonance (CMR) is observed in regions of increased myocardial collagen. The extent of late gadolinium enhancement has been associated with higher prevalence of risk factors of sudden death. The aim of the present study was to describe the clinical characteristics and the presence of risk factors for sudden death in a series of patients from 2 referral centers for HCM in relation to late gadolinium enhancement in CMR. METHODS AND RESULTS: A total of 120 patients (47 +/- 16 years) were included. All patients fulfilled conventional criteria for HCM. A complete history and clinical examination were performed. Risk factors for sudden death were evaluated. A blinded CMR was performed with late gadolinium enhancement in the left ventricular short-axis orientation. NT pro B-type natriuretic protein (BNP) and C-reactive protein were determined in serum samples. A total of 83 patients (69%) showed late gadolinium enhancement. These patients had higher maximal left ventricular wall thickness (22 +/- 5 versus 17 +/- 3 mm, P < .001), showed more frequently obstruction (42% versus 16%, P = .006), nonsustained ventricular tachycardia (38% versus 8%, P = .001), worse exercise capacity (8 +/- 4 versus 10 +/- 4 METs, P = .003) and increased levels of NT BNP (656 [300-1948] versus 290 [122-948] pg/mL, P = .020). On multivariate analysis, maximal left ventricular wall thickness (P < .001) and nonsustained ventricular tachycardia (P = .011) remained associated with gadolinium-enhanced imaging. Number of risk factors for sudden death was associated with late gadolinium enhancement (OR 2.18, 95%CI 1.45-3.20, P < .001). CONCLUSIONS: Late gadolinium enhancement in CMR is a common finding in HCM. Increased maximal left ventricular wall thickness and nonsustained ventricular tachycardia are associated with late gadolinium enhancement. Associations with risk factors for sudden death and functional status are observed.

Systolic aortic regurgitation.

Aortic regurgitation is normally a diastolic phenomenon. Echocardiographic images of systolic aortic regurgitation in a patient with atrial fibrillation and heart failure are presented, and haemodynamic interpretation is provided.

Transient global amnesia after dobutamine--atropine stress echocardiography.

Dobutamine-atropine stress echocardiography is a useful and relatively safe test for coronary artery disease assessment. However, possible complications should be recognized. We describe a case of transient global amnesia in a woman who underwent a standard-protocol dobutamine-atropine stress echocardiogram for coronary ischaemia detection, after having complained about chest pain. The test was not positive for coronary ischaemia, but a typical picture of transient global amnesia ensued. Symptoms shortly resolved spontaneously. Neurological work up was negative for organic disease. Transient global amnesia is a neurological syndrome of unknown origin and good prognosis. Dobutamine-atropine stress echocardiography can be added to the described precipitants of transient global amnesia. This neurological syndrome should be taken into account as a possible complication of dobutamine-atropine stress echocardiography.

Factors Influencing the Phenotypic Expression of Hypertrophic Cardiomyopathy in Genetic Carriers.

INTRODUCTION AND OBJECTIVES: Hypertrophic cardiomyopathy (HCM) is a disorder with variable expression. It is mainly caused by mutations in sarcomeric genes but the phenotype could be modulated by other factors. The aim of this study was to determine whether factors such as sex, systemic hypertension, or physical activity are modifiers of disease severity and to establish their role in age-related penetrance of HCM. METHODS: We evaluated 272 individuals (mean age 49 ± 17 years, 57% males) from 72 families with causative mutations. The relationship between sex, hypertension, physical activity, and left ventricular hypertrophy was studied. RESULTS: The proportion of affected individuals increased with age. Men developed the disease 12.5 years earlier than women (adjusted median, 95%CI, -17.52 to -6.48; P < .001). Hypertensive patients were diagnosed with HCM later (10.8 years of delay) than normotensive patients (adjusted median, 95%CI, 6.28-17.09; P < .001). Individuals who performed physical activity were diagnosed with HCM significantly earlier (7.3 years, adjusted median, 95%CI, -14.49 to -1.51; P = .016). Sex, hypertension, and the degree of physical activity were not significantly associated with the severity of left ventricular hypertrophy. Adjusted survival both free from sudden death and from the combined event were not influenced by any of the exploratory variables. CONCLUSIONS: Men and athletes who are carriers of sarcomeric mutations are diagnosed earlier than women and sedentary individuals. Hypertensive carriers of sarcomeric mutations have a delayed diagnosis. Sex, hypertension, and physical activity are not associated with disease severity in carriers of HCM causative mutations.