Paradoxical sinus deceleration during dobutamine stress echocardiography: case series and review of the literature.

Background: Dobutamine stress echocardiography is an established diagnostic modality for assessing myocardial ischaemia in patients with known or suspected coronary artery disease. Dobutamine infusion causes dose-dependent increase in heart rate and contractility. However, in some cases, it induces paradoxical sinus deceleration, whose underlying mechanism and clinical significance are not fully understood. Case summary: We present episodes of paradoxical sinus deceleration observed during dobutamine stress echocardiography in six (four males and two females) patients and described its patterns of occurrence and clinical and echocardiographic characteristics. Discussion: Paradoxical sinus deceleration occurred mostly at maximal dobutamine infusion was accompanied with a decline in blood pressure and resolved spontaneously following cessation of dobutamine infusion. Individuals experiencing paradoxical sinus deceleration had in common abnormal left ventricle geometry but differed with regard to age, sex, and cardiometabolic risk factors.

Diastolic function deterioration in type 2 diabetes mellitus: predictive factors over a 3-year follow-up.

Aims: Diastolic dysfunction is frequent in patients with type 2 diabetes mellitus (DM2) and associated with a poor prognosis. This study aimed to describe diastolic function changes over time in DM2 patients and to identify predictive factors of diastolic function deterioration. Methods and results: Diastolic function was assessed by echocardiography according to the EACVI/ASE recommendations at baseline and 3-year follow-up in a prospective cohort of 310 DM2 patients without overt heart disease. Predictors of diastolic function deterioration were identified using logistic regression analysis. During the 3-year follow-up, prevalence of diastolic dysfunction increased from 49% to 67% (P = 0.001). Only 32% of the patients had a normal diastolic function both at baseline and 3 years and 27% of the patients presented diastolic function deterioration. At multivariable analysis, age (OR = 1.05 [1.01-1.09], P < 0.01), retinopathy (OR = 2.00 [1.10-3.63], P = 0.02), and increase in systolic blood pressure during follow-up (OR = 1.03 [1.01-1.04], P < 0.01) were predictive of diastolic function deterioration. Conclusion: Age, retinopathy, and increase in blood pressure over time are associated with an increased risk of diastolic function deterioration in DM2 patients. The presence of these co-factors might help to early identify patients at risk of heart failure.

Long-Term Dose-Dependent Agalsidase Effects on Kidney Histology in Fabry Disease.

BACKGROUND AND OBJECTIVES: Dose-dependent clearing of podocyte globotriaosylceramide has previously been shown in patients with classic Fabry disease treated with enzyme replacement. Our study evaluates the dose-dependent effects of agalsidase therapy in serial kidney biopsies of patients treated for up to 14 years. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Twenty patients with classic Fabry disease (12 men) started enzyme replacement therapy at a median age of 21 (range =7-62) years old. Agalsidase-α or -ß was prescribed for a median of 9.4 (range =5-14) years. The lower fixed dose group received agalsidase 0.2 mg/kg every other week throughout the follow-up period. The higher dose group received a range of agalsidase doses (0.2-1.0 mg/kg every other week). Dose changes were made due to disease progression, suboptimal effect, or agalsidase-ß shortage. Serial kidney biopsies were performed along with clinical assessment and biomarkers and scored according to recommendations from the International Study Group of Fabry Nephropathy. RESULTS: No statistical differences were found in baseline or final GFR or albuminuria. Kidney biopsies showed significant reduction of podocyte globotriaosylceramide in both the lower fixed dose group (-1.39 [SD=1.04]; P=0.004) and the higher dose group (-3.16 [SD=2.39]; P=0.002). Podocyte globotriaosylceramide (Gb3) reduction correlated with cumulative agalsidase dose (r=0.69; P=0.001). Arterial/arteriolar intima Gb3 cleared significantly in the higher dose group, all seven patients with baseline intimal Gb3 cleared the intima, one patient gained intimal Gb3 inclusions (P=0.03), and medial Gb3 did not change statistically in either group. Residual plasma globotriaosylsphingosine levels remained higher in the lower fixed dose group (20.1 nmol/L [SD=11.9]) compared with the higher dose group (10.4 nmol/L [SD=8.4]) and correlated with cumulative agalsidase dose in men (r=0.71; P=0.01). CONCLUSIONS: Reduction of podocyte globotriaosylceramide was found in patients with classic Fabry disease treated with long-term agalsidase on different dosing regimens, correlating with cumulative dose. Limited clearing of arterial/arteriolar globotriaosylceramide raises concerns regarding long-term vascular effects of current therapy. Residual plasma globotriaosylsphingosine correlated with cumulative dose in men.

The association of hypertension with asymptomatic cardiovascular organ damage in rheumatoid arthritis.

BACKGROUND: The association of hypertension with asymptomatic cardiovascular organ damage in patients with rheumatoid arthritis (RA) has been little studied by echocardiography. METHODS: Echocardiography was done in 134 RA patients and 102 healthy controls. Left ventricular (LV) geometry was considered abnormal if LV mass index or relative wall thickness was increased. LV diastolic dysfunction was considered present if septal early diastolic tissue velocity <8 cm/s. Systemic arterial compliance (SAC) was assessed from stroke volume index/pulse pressure ratio. RESULTS: The hypertensive RA patients (n = 72) had higher inflammatory activity, older age and more diabetes than the normotensive RA patients (n = 62) (all p < 0.05). Rates of abnormal LV geometry, LV diastolic dysfunction and lower SAC were higher among the hypertensive RA patients (p < 0.05), but similar between normotensive RA patients and controls. Hypertension was associated with a 3-fold higher prevalence both for abnormal LV geometry (odds ratio 2.89 [95% confidence interval 1.09-7.63], p = 0.03) and for diastolic LV dysfunction (odds ratio 2.92 [95% confidence interval 1.14-7.46], p = 0.03) as well as lower SAC (ß = 0.31, p = 0.001) independent of age, gender, diabetes and inflammatory activity measured by erythrocyte sedimentation rate. CONCLUSION: The presence of asymptomatic cardiovascular organ damage in RA patients is closely associated with hypertension independent of inflammatory activity.

Myocardial function in aortic stenosis--insights from radial multilayer Doppler strain.

BACKGROUND: Left ventricular (LV) radial tissue Doppler imaging (TDI) strain increases gradually from the subepicardial to the subendocardial layer in healthy individuals. A speckle tracking echocardiography study suggested this gradient to be reduced in parallel with increasing aortic stenosis (AS) severity. METHODS: We used TDI strain in 84 patients with AS (mean age 73 ± 10 years, 56% hypertensive) for superior assessment of layer strain. 38 patients had non-severe and 46 severe AS by aortic valve area corrected for pressure recovery. Peak systolic radial TDI strain was measured in the subendocardial, mid-myocardial and subepicardial layers of the basal inferior LV wall, each within a region of interest of 2 × 6 mm (strain length 2 mm). RESULTS: Radial strain was lower in the subepicardial layer (33.4 ± 38.6%) compared to the mid-myocardial and subendocardial layers (50.3 ± 37.3% and 53.0 ± 40.0%, respectively, both p < 0.001 vs. subepicardial). In the subendo- and midmyocardium, radial strain was lower in patients with severe AS compared to those with non-severe AS (p < 0.05). In multivariate regression analyses including age, heart rate, inferior wall thickness, hypertension, and AS severity, radial strain in the mid-myocardium was primarily attenuated by presence of hypertension (ß = -0.23) and AS severity (ß = -0.26, both p < 0.05), while radial strain in the subendocardium was significantly influenced by AS severity only (ß = -0.35, p < 0.01). CONCLUSIONS: In AS, both the AS severity and concomitant hypertension attenuate radial TDI strain in the inferior LV wall. The subendocardial radial strain is mainly influenced by AS severity, while midmyocardial radial strain is attenuated by both hypertension and AS severity.

Disease activity and left ventricular structure in patients with rheumatoid arthritis.

OBJECTIVE: Increased left ventricular (LV) wall thickness/internal diameter ratio (relative wall thickness) was recently reported in RA patients. The aim of this study was to assess the association between LV relative wall thickness and RA disease activity. METHODS: Clinical and echocardiographic data from 129 RA patients without established cardiovascular disease and 102 controls were used. RA disease activity was assessed by different composite scores and active RA defined by the Simplified Disease Activity Index (SDAI) level exceeding the cut-off for remission (SDAI >3.3). RESULTS: The RA patients were on average 61.3 years old, 77% were women and 67% had active RA (SDAI >3.3). Patients with active RA had greater LV relative wall thickness and included more patients with treated hypertension (all P < 0.05), but had LV mass index and blood pressure comparable to patients in remission. Having active RA by the SDAI score (ß = 0.20, P = 0.008) was also independently associated with greater LV relative wall thickness after adjusting for systolic blood pressure, wall stress, age and sex in a multivariate model. This association was robust also in secondary models including other disease activity composite scores such as the Clinical Disease Activity Index and 28-joint DAS. CONCLUSION: Among RA patients, higher disease activity was independently associated with greater LV relative wall thickness, reflecting subclinical heart disease. The findings point to the importance of disease activity control in RA patients to prevent progression to clinical heart disease.

Longitudinal myocardial strain alteration is associated with left ventricular remodeling in asymptomatic patients with type 2 diabetes mellitus.

BACKGROUND: In normal subjects, left ventricular (LV) dimensions have been shown to decrease over time, while wall thickness is increasing. The aim of this study was to investigate LV remodeling in a cohort of patients with type 2 diabetes mellitus during a 3-year follow-up period and its potential association with decreased longitudinal systolic strain (εL). METHODS: One hundred seventy-two patients with type 2 diabetes without overt heart disease were prospectively enrolled and underwent echocardiography with speckle-tracking imaging to assess global LV εL at baseline and at 3 years. The associations between alteration in εL (defined as |εL| < 18%), LV geometry at baseline, and LV remodeling over time were evaluated. RESULTS: Among the 172 enrolled patients, 154 completed 3-year follow-up. At baseline, patients with εL alteration had higher LV end-systolic volumes (28 ± 11 vs 23 ± 9 mL, P < .001) and relative wall thicknesses (RWT; 0.44 ± 0.06 vs 0.40 ± 0.07, P = .008) compared with those with normal εL. At 3-year follow-up, RWTs remained stable in both groups. LV volumes significantly decreased in patients with normal εL but not in patients with εL alteration. Multivariate analysis showed that εL alteration was independently associated with LV end-systolic volume (ß = 5.0, P = .006) and RWT (ß = 0.03, P = .03) at baseline and with changes in both LV end-diastolic volume (ß = 19.1, P = .001) and LV end-systolic volume (ß = 2.6, P = .047) over 3 years. CONCLUSIONS: In patients with type 2 diabetes, εL alteration was associated with higher RWT and LV volumes and with the absence of decreases in LV volumes over time, which might be an early sign of adverse LV remodeling.

Acute obstruction by Pannus in patients with aortic medtronic-hall valves: 30 years of experience.

BACKGROUND: Acute dysfunction of mechanical aortic valve prostheses is a life-threatening adverse event. Pannus overgrowth, which is fibroelastic hyperplasia originating from the periannular area, is one cause of dysfunction. The aim of this study was to determine the annual incidence of readmittance resulting from acute obstruction caused by pannus during 30 years of observation in patients with Medtronic-Hall aortic valve prostheses and to analyze the risk factors associated with pannus development. METHODS: From 1982 to 2004, 1,187 patients in our department underwent aortic valve replacement with Medtronic-Hall mechanical monoleaflet valve prostheses. As of December 31, 2012, 27 of these patients (2.3%) had presented with acute valve dysfunction caused by pannus obstruction. RESULTS: The annual incidence of pannus was 0.7 per 1,000. The median time from the primary operation to prosthetic dysfunction was 11.1 years (range, 1.2 to 26.8 years). Of the 20 patients who underwent reoperation, 2 died. Seven patients died before reoperation. Women had a higher risk for the development of obstructing pannus, and patients with pannus obstruction were younger. Valve size was not an independent risk factor. CONCLUSIONS: Women and younger patients are at higher risk for pannus development. When acute dysfunction by pannus is suspected in a mechanical aortic valve, an immediate echocardiogram and an emergency aortic valve replacement should be carried out because of the potential of a fatal outcome.

Left atrial systolic force in asymptomatic aortic stenosis.

BACKGROUND: There is a limited knowledge about left atrial (LA) systolic force (LASF) and its key determinants in patients with asymptomatic mild-moderate aortic stenosis (AS). METHODS: We used baseline clinic and echocardiographic data from 1,566 patients recruited in the simvastatin ezetimibe in aortic stenosis study evaluating the effect of placebo-controlled combined simvastatin and ezetimibe treatment in asymptomatic AS. The LASF was calculated by Manning's method. Low and high LASF were defined as <5th and >95th percentile of the distribution within the study population, respectively. RESULTS: Mean LASF in the total study population was 21±14 kdynes/cm2. The determinants of LASF were higher age, heart rate, body mass index, systolic blood pressure, left ventricular (LV) mass, mitral peak early velocity, maximal LA volume, and longer mitral deceleration time (multiple R2=0.37, P<0.01). High LASF (78 patients) was characterized by abnormal LV relaxation in 90% of the cases. Low LASF (82 patients) was associated with restrictive LV filling pattern, absence of abnormal relaxation pattern, smaller maximal LA volume, and lower body mass index. In 40% of the patients with low LASF, estimated LV filling pressures were normal and the reduced LA force was explainable by an intrinsic systolic LA dysfunction. CONCLUSIONS: In patients with asymptomatic AS, LASF was closely related to filling pressure. Higher LASF invariably signifies the maximal LA effort to keep near normal LV filling pressure; lower LASF belongs to a heterogeneous group of patients in which it is much more difficult to depict who have low LA preload or who have intrinsic systolic LA dysfunction.

Myocardial deformation in aortic valve stenosis: relation to left ventricular geometry.

OBJECTIVE: To assess left ventricular (LV) strain and displacement and their relations to LV geometry in patients with aortic stenosis (AS). DESIGN: Cross-sectional echocardiographic study in patients with AS. Peak circumferential, radial and longitudinal strain, and radial, longitudinal and transverse displacement were measured by 2D speckle tracking. Severity of AS was assessed from energy loss index (ELI). LV hypertrophy was present if LV mass/height(2.7) > or =46.7/49.2 g/m(2.7) in women/men and concentric LV geometry if relative wall thickness > or =0.43. LV geometry was assessed from LV mass/height(2.7) and relative wall thickness in combination. Setting Department of Heart Disease, Haukeland University Hospital, Bergen, Norway. PATIENTS: 70 patients with AS (mean age 73+/-10 years, 54% women). INTERVENTIONS: None. Main outcome measures Association of regional and average LV myocardial strain and displacement with LV geometric pattern and degree of AS. RESULTS: Average longitudinal strain was lower in the hypertrophy groups and correlated with higher LV mass index and relative wall thickness, lower stress-corrected mid-wall shortening and smaller ELI (all p<0.05). Average strain and displacement in other directions did not differ between geometric groups. In multivariate regression analysis, lower average longitudinal strain was associated with higher relative wall thickness (beta=0.15), lower ejection fraction (beta=-0.16), systolic blood pressure (beta=-0.16) and energy loss index (beta=-0.20) (all p<0.05) (R(2)=0.72). When relative wall thickness was replaced with LV mass, lower longitudinal strain was also associated with higher LV mass (beta=0.21, p<0.05) (R(2)=0.73). CONCLUSIONS: In patients with AS, lower average longitudinal strain is related to higher LV mass, concentric geometry and more severe AS.

An unusual location of a papillary fibroelastoma.

A 72-year-old woman was hospitalized with recurrent acute coronary syndrome after initial successful treatment of acute ST-elevation myocardial infarction with percutaneous coronary intervention. Echocardiography demonstrated unexpectedly a 9 x 8 mm pendulating structure attached to the anterior, proximal interventricular septum in the left ventricular outflow tract 6 mm beneath the aortic valve annulus. Magnetic resonance imaging of the heart yielded the same findings. The patient underwent coronary artery bypass grafting and tumour excision. The histopathological findings were typical for papillary fibroelastoma (PFE) with a central zone of connective tissue and some elastic fibres without blood vessels and covered by endocardium. PFE is the third most common type of primary cardiac tumours, second to myxoma and lipoma. PFEs are avascular papillomas that predominantly occur on the aortic and mitral valves (90%). However, the present case demonstrates that PFE occasionally can be attached to the ventricular wall endocardium.

Radial deformation by tissue Doppler imaging in multiple myocardial layers.

OBJECTIVES: Measuring strain in multiple myocardial layers using 2-dimensional tissue Doppler imaging may provide valuable diagnostic information about non-transmural disease. However, its feasibility in humans has not been demonstrated previously, and optimal machine settings not defined. DESIGN: From parasternal short axis, zoomed tissue Doppler imaging of the left ventricular inferior wall was obtained in 23 young, healthy humans. Images were recorded with six different machine settings. Velocity, strain rate and strain were measured in two and three layers across the wall. RESULT: For two-layer-measurements, all subendocardial values were significantly higher than the subepicardial ones (p<0.003 for all data sets). Minimal radial and maximal lateral averaging resulted in largest strain differences: 106.4+/-32.6% (mean+/-SD) subendocardially versus 54.2+/-20.1% subepicardially. By similar settings in three layers, strain was 105.7+/-34.5% subendocardially, 81.2+/-26.9% midmyocardially and 48.3+/-26.9% subepicardially (p <0.05). CONCLUSION: We have demonstrated that it is feasible to measure radial velocity, strain rate and strain in up to three individual layers in young healthy humans, and the diagnostic potentials should be tested on patient groups.

Left ventricular long-axis function in treated haemochromatosis.

We recently demonstrated reduced exercise capacity in treated genetic haemochromatosis, in spite of normal radial left ventricular (LV) systolic function assessed by 2-dimensional echocardiography at rest. It remains unknown if haemochromatosis-related impairment of LV long-axis function can be demonstrated also at rest. LV long-axis function was assessed by echocardiography including spectral tissue Doppler of systolic (S') and early (E') diastolic velocities in 105 treated haemochromatosis patients and 50 controls. Patients had higher body mass index, systolic atrioventricular excursion, and smaller LV end-systolic diameter (all P < 0.05). Other conventional echocardiographic variables did not differ. S' was normal in both groups, though significantly higher among the patients (11.1 vs. 9.9 cm/s, P < 0.001). In multiple regression analysis, higher S' was associated with having haemochromatosis, independently of significant contributions from higher atrioventricular excursion and LV length, and lower body mass index and E/E'-ratio (multiple R(2) = 0.44, P < 0.001). E' did not differ between patients and controls. However, in multivariate analysis lower E' was associated with having haemochromatosis independently of significant contributions from higher age and diastolic blood pressure, and lower transmitral E and end-diastolic LV length (multiple R(2) = 0.57, P < 0.001). The long-axis function in the haemochromatosis group was normal. Still haemochromatosis, even in this group of patients treated with regular phlebotomy, influenced both systolic and early diastolic long-axis function, and was associated with higher atrioventricular excursion and S', and with lower E'.

Left ventricular diastolic function in patients with treated haemochromatosis.

OBJECTIVES: We recently demonstrated reduced exercise capacity in phlebotomy treated genetic haemochromatosis in spite of normal systolic function. The present objective was to investigate diastolic function at rest. DESIGN: Diastolic function was echocardiographically assessed in 132 phlebotomy treated genetic haemochromatosis patients and 50 controls. RESULTS: Patients had higher body mass index and heart rate, higher transmitral early (E) (11.2+/-2.6 versus 10.4+/-2.2 cm) and atrial (A) (5.7+/-1.6 versus 5.0+/-1.6) velocity time integrals, pulmonary venous systolic peak velocity (0.58+/-0.12 versus 0.54+/-0.13 m/s) and ratio of E to spectral tissue Doppler E' velocity (6.3+/-1.6 versus 5.6+/-1.4, all p <0.05). Independently of age, heart rate, systolic blood pressure and body weight, having haemochromatosis remained statistically significantly associated with higher E (beta=0.27) and A (beta =0.18) velocity time integrals, pulmonary venous systolic peak velocity (beta =0.21), and E/E'-ratio (beta=0.25) in separate multivariate analyses (all p <0.05). In the youngest age tertile, patients had longer isovolumic relaxation time and lower E' than controls. CONCLUSION: Our findings are compatible with mildly impaired diastolic function in treated haemochromatosis, with delayed relaxation in the younger tertile, and an elevated filling pressure and pseudonormalisation with increasing age.

Reduced exercise capacity in genetic haemochromatosis.

BACKGROUND: Many patients with genetic haemochromatosis complain about fatigue and reduced physical capacity. Exercise capacity, however, has not been evaluated in larger series of haemochromatosis patients treated with repeated phlebotomy. DESIGN AND METHODS: We performed exercise echocardiography in 152 treated haemochromatosis patients (48+/-13 years, 26% women) and 50 healthy blood donors (49+/-13 years, 30% women), who served as controls. Echocardiography was performed at rest and during exercise in a semiupright position on a chair bicycle, starting from 20 W, increasing by 20 W/min. Transmitral early and atrial velocity and isovolumic relaxation time were measured at each step. Ventilatory gas exchange was measured by the breath-to-breath-technique. RESULTS: Compared with healthy controls, haemochromatosis patients were more obese and less trained. More of them smoked, and 17% had a history of cardiovascular or pulmonary disease. Adjusted for training, the left ventricular function and dimensions at rest did not differ between the groups. During exercise the haemochromatosis patients obtained a significantly lower peak oxygen (O2) uptake (28.1 vs. 34.4 ml/kg per min, P<0.001). In a multiple regression analysis haemochromatosis predicted lower peak O2 uptake independently of significant contributions of sex, age, and height, as well as of systolic blood pressure and log-transformed isovolumic relaxation time at peak exercise, whereas no independent association was found with weight or physical activity (multiple R=0.74, P<0.001). Adding genotype, s-ferritin, prevalence of smoking, or history of cardiopulmonary disease among the covariates in subsequent models did not change the results. CONCLUSION: Genetic haemochromatosis, even when treated with regular phlebotomy, is associated with lower exercise capacity independently of other covariates of exercise capacity.