A functional supervised learning approach to the study of blood pressure data.

In this work, a functional supervised learning scheme is proposed for the classification of subjects into normotensive and hypertensive groups, using solely the 24-hour blood pressure data, relying on the concepts of Fréchet mean and Fréchet variance for appropriate deformable functional models for the blood pressure data. The schemes are trained on real clinical data, and their performance was assessed and found to be very satisfactory.

Long-term outcomes of primary systemic light chain (AL) amyloidosis in patients treated upfront with bortezomib or lenalidomide and the importance of risk adapted strategies.

Bortezomib and lenalidomide are increasingly used in patients with AL amyloidosis, but long term data on their use as primary therapy in AL amyloidosis are lacking while early mortality remains significant. Thus, we analyzed the long term outcomes of 85 consecutive unselected patients, which received primary therapy with bortezomib or lenalidomide and we prospectively evaluated a risk adapted strategy based on bortezomib/dexamethasone to reduce early mortality. Twenty-six patients received full-dose bortezomib/dexamethasone, 36 patients lenalidomide with oral cyclophosphamide and low-dose dexamethasone and 23 patients received bortezomib/dexamethasone at a dose and schedule adjusted to the risk of early death. On intent to treat, 67% of patients achieved a hematologic response (24% hemCRs) and 34% an organ response; both were more frequent with bortezomib. An early death occurred in 20%: in 36% of those treated with full-dose bortezomib/dexamethasone, in 22% of lenalidomide-treated patients but only in 4.5% of patients treated with risk-adapted bortezomib/dexamethasone. Activity of full vs. adjusted dose bortezomib/dexamethasone was similar; twice weekly vs. weekly administration of bortezomib also had similar activity. After a median follow up of 57 months, median survival is 47 months and is similar for patients treated with bortezomib vs. lenalidomide-based regimens. However, risk adjusted-bortezomib/dexamethasone was associated with improved 1-year survival vs. full-dose bortezomib/dexamethasone or lenalidomide-based therapy (81% vs. 56% vs. 53%, respectively). In conclusion, risk-adapted bortezomib/dexamethasone may reduce early mortality and preserve activity while long term follow up indicates that remissions obtained with lenalidomide or bortezomib may be durable, even without consolidation with alkylators.

Value of apical circumferential strain in the early post-myocardial infarction period for prediction of left ventricular remodeling.

BACKGROUND: Left ventricular (LV) remodeling after acute myocardial infarction (AMI) is related to increased morbidity and mortality. The aim of the present study was to examine whether LV deformational and torsional parameters can predict LV remodeling in patients with AMI. METHODS: Forty-two patients (age 57 ± 14 years) presenting with an anterior ST-elevation AMI and treated with primary percutaneous transluminal coronary angioplasty (PTCA) were included in the study. Four days post MI, LV ejection fraction (EF), LV torsion, longitudinal (4-, 3- & 2-chamber) and circumferential strain of the LV apex were evaluated by conventional and speckle-tracking echocardiography. The echocardiographic study was repeated at 3 months post-AMI and patients with LV remodeling, i.e. an increase >15% in LV end-systolic volume (LVESV), were identified. RESULTS: The 13 patients with LV remodeling had significantly more impaired apical circumferential strain (-7.3 ± 2.2% vs. -18.9 ± 5.2%, p=0.001), EF (42 ± 7% vs. 48.9 ± 6%, p=0.005), LV apical rotation (6.8 ± 4.8° vs. 11.1 ± 4.0°, p=0.027), and LV global longitudinal strain (-9.7 ± 1.9% vs. -12.9 ± 2.9%, p=0.03) on the 4th day post-AMI, in comparison to those without LV remodeling. Apical circumferential strain on the 4th day post-AMI showed the strongest correlation with the LVESV 3 months post-AMI (r=0.76, p=0.001), compared to EF (r=-0.60, p=0.001), global longitudinal strain (r=0.56, p=0.001), and LV apical rotation (r=-0.53, p=0.001). Furthermore, apical circumferential strain demonstrated the highest diagnostic accuracy: area under the receiver operating characteristic (ROC) curve 0.98, with sensitivity 100% and specificity 96% for prediction of LV remodeling, using a cutoff value <-11.0%. CONCLUSION: In patients with anterior AMI, LV apical circumferential strain in the early post-MI period constitutes a significant prognostic factor for LV remodeling at 3 months. Assessment of this parameter may identify patients at high risk for heart failure development.

Apical rotation as an early indicator of left ventricular systolic dysfunction in acute anterior myocardial infarction: experimental study.

INTRODUCTION: The aim of this study was to determine whether left ventricular (LV) apical rotation assessed by speckle tracking echocardiography (STE) can predict global LV systolic dysfunction after acute anterior myocardial infarction (AMI). METHODS: STE analysis was applied to LV short-axis images at the basal and apical levels in 21 open-chest pigs, before and after left anterior descending coronary artery ligation. LV radial and circumferential strain and strain rate, apical and basal rotation, and LV torsion were recorded. RESULTS: LV apical rotation (3.68 ± 1.73° pre-AMI vs. 2.19 ± 1.64° post-AMI, p<0.009), peak systolic rotation rate, and radial and circumferential strain as well as strain rate decreased significantly 30 min postAMI. The LV global torsion decreased significantly. Strain and rotational changes of the LV apex were primarily correlated with ejection fraction (EF), but those of the LV base were not. EF had a significant correlation with the global LV twist (r=0.31, p<0.05). On multivariate linear regression analysis, fractional shortening of the long-axis (FSL) (b=0.58, p<0.001), rotation of the LV apex (b=0.32, p<0.006) and LV dp/dtmax (b=0.26, p<0.02) were independently related with EF. On analysis, of the receiver operating characteristic curve, the area under the curve for apical rotation was 0.765, p<0.006; the best cutoff value of 2.92° had sensitivity 80% and specificity 71% in predicting EF<40%. CONCLUSION: Apical rotation assessed by STE is a potential noninvasive early indicator of global LV systolic dysfunction in AMI and has a satisfactory association with LVEF. Its assessment could be valuable in clinical and research cardiology.

Brain edema formation is associated with the time rate of blood pressure variation in acute stroke patients.

OBJECTIVES: Both brain edema and increased blood pressure (BP) variability are associated with poor outcome after stroke. The aim of the present study was to evaluate a possible association between edema formation and a relatively new index of BP variability defined as time rate (TR) of BP variation. PATIENTS AND METHODS: A total of 128 first-ever acute stroke patients underwent 24-h ambulatory BP monitoring within 24 h from onset of stroke. All patients were imaged with computed tomography scan on admission and after 5 days to determine the presence of brain edema. The TR of BP variation was defined as the first derivative of the BP values against time. Known risk factors and neurological severity on admission were documented. RESULTS: The 24-h TR of systolic BP variation was significantly higher (P<0.001) in stroke patients with brain edema (0.69±0.15 mmHg/min) compared with those without edema (0.57±0.12 mmHg/min). The multivariate logistic regression model showed that a 0.1 mmHg/min increase in the TR of 24-h systolic BP variation was associated with a 13.9% increased probability of the presence of brain edema (odds ratio=1.139, 95% confidence interval: 1.058-1.225, P<0.001), after adjusting for history of diabetes mellitus, hypercholesterolemia, type of stroke, neurological deficit, and 24-h systolic BP. CONCLUSION: Increased values of 24-h TR of systolic BP variation are associated independently with formation of edema in acute stroke patients.

Thyroid hormone and recovery of cardiac function in patients with acute myocardial infarction: a strong association?

OBJECTIVE: This study investigated whether changes in thyroid hormone (TH) in plasma are associated with the recovery of cardiac function in patients with acute myocardial infarction (AMI). Previous experimental studies have provided evidence of potential implication of TH signaling in post-ischemic recovery of cardiac function. METHODS: A total of 47 patients with AMI and early reperfusion therapy were included in this study. Myocardial injury was analyzed by peak creatinine kinase-MB (CKMB) and cardiac function was assessed by echocardiographic left ventricular ejection fraction (LVEF%). Recovery of function (ΔEF%) was estimated as the difference of LVEF% between 48  h and 6 months (6  mo) after AMI. Total triiodothyronine (T(3)), thyroxine (T(4)), and TSH were measured in plasma at different time points (24  h, 48  h, 5  d, and 6  mo). RESULTS: A significant correlation between LVEF% and T(3) (r=0.5, P=0.0004) was found early after AMI (48  h), whereas no correlation was observed between CKMB and T(3) (r=-0.04, P=0.81). A strong correlation was found between ΔEF% and total T(3) (r=0.64, P=10(-6)) at 6  mo after AMI. Furthermore, multivariate regression analysis revealed that T(3) at 6  mo (r=0.64, r(2)=0.41, P=10(-6)) was an independent determinant of ΔEF%. CONCLUSION: Changes in T(3) levels in plasma are closely correlated with the early and late recovery of cardiac function after AMI. T(3) levels at 6  mo appear to be an independent predictor of late functional recovery.

Is left ventricular dysfunction reversed after treatment of active acromegaly?

It has been suggested that control of GH and IGF excess can arrest the progression of cardiovascular abnormalities and normalize cardiac performance. The aim of the present study was to investigate the reversibility of acromegalic cardiomyopathy in patients with active and inactive disease and to evaluate the effect of the inactivity of the disease on left ventricular (LV) diastolic dysfunction, irrespective of the applied treatment. The patient population consisted of 55 patients who were studied in the active and/or inactive phase. A complete M-mode, two-dimensional and color-flow Doppler echocardiographic examination was performed. LV mass index and posterior wall index were significantly lower in patients with inactive acromegaly compared to those with active disease (P < 0.03 respectively). Diastolic dysfunction was improved in patients with inactive compared to those with active disease (E/A ratio P < 0.009). IGF was positively correlated with LV mass index (r = 0.28, P < 0.02). Multivariate linear regression analysis showed that in active patients the E/A ratio was independently related to age (ß = -0.674, P < 0.001) and GH (ß = 0.282, P < 0.03), whereas in inactive patients none of the parameters were related significantly with the E/A ratio. In a subgroup of 15 patients who were studied in both the active and inactive phase of the disease, the reduction in GH levels was correlated positively with the reduction in LV mass index (r = 0.89, P < 0.0001) and negatively with the improvement in E/A ratio (r = -0.74, P < 0.001). In conclusion, the results of the present study indicate an improvement of left ventricular diastolic function and a significant improvement of cardiac hypertrophy in patients with inactive acromegaly and normal systolic cardiac function compared to those with active disease.

Myocardial performance index suggests optimal fluid loss during hemodialysis.

BACKGROUND: Patients on long-term maintenance hemodialysis (HD) are at high risk of developing cardiovascular disease and suffering various cardiovascular complications during HD. HYPOTHESIS: The purpose of this study was to evaluate the influence of changing loading conditions on the myocardial performance index (MPI) in patients on long-term HD and to specify an optimal level of fluid loss during HD that would maintain stable global cardiac function. METHODS: The study consisted of 52 patients with end-stage renal failure (ESRF), mean age 56±11.7 y, range: 25-80 y, on regular HD. For each patient a complete echocardiographic-Doppler examination was performed before and after HD. Systolic and diastolic parameters of left ventricular function were measured, and the myocardial performance index (MPI) was calculated. RESULTS: The MPI was significantly prolonged after HD (0.47±0.15 before HD versus 0.59±0.16 after HD, p < 0.001). Mean change in body weight during HD was 2.1±0.86 kg. The MPI did not change significantly in patients with intradialytic weight loss up to 1.75 kg. CONCLUSIONS: The MPI value seems to be independent of acute preload changes only when fluid loss is less than 1.75 kg. A 1.75-kg fluid loss during HD seems to be the optimal goal. In ESRF patients on HD, the MPI seems to be a good indicator of global left ventricular function and potentially a valuable aid in the effort to maintain optimal fluid balance.

Real-time three-dimensional echocardiography in evaluating Libman-Sacks vegetations.

Libman-Sacks endocarditis, characterized by sterile fibrofibrinous vegetations that have the potential to develop anywhere on the endocardial surface, was originally reported in 1924. The mitral valve is most commonly affected, followed by the aortic valve, whereas tricuspid and pulmonary valves are seldom involved. Libman-Sacks vegetations can be found in approximately 1 of 10 patients with systemic lupus erythematosus by transoesophageal echocardiography (TTE), and they are variably associated with lupus duration, disease activity, anticardiolipin antibodies, and antiphospholipid syndrome manifestations. The capability to perform real-time 3D (RT3D) imaging in the evaluation of Libman-Sacks vegetation size may strengthen the already established role of transthoracic echocardiogram and TTE. The exact estimation of vegetation size may influence therapeutic interventions. Therefore, we are trying to highlight the role of RT3D echocardiography in assessing vegetation size in a patient with Libman-Sacks endocarditis.

Transesophageal atrial pacing stress echocardiography: difficulties in the performance and the interpretation of the test.

INTRODUCTION: Transesophageal atrial pacing stress echocardiography (TEAPSE) has been proposed as an alternative stress echo test in selected patients with known or suspected coronary artery disease. The purpose of this study was to determine: (1) whether TEAPSE could serve as a suitable provocative stress test in patients with stroke and (2) to investigate whether the pseudohypertrophy during TEAPSE that has been observed in experimental studies is also seen in the clinical setting. METHODS: TEAPSE at increasing heart rates was performed in 29 patients with stroke. The end-diastolic and end-systolic left ventricular (LV) wall/cavity circumferential area was traced and the ratio was calculated at each pacing stage, as well as the percent systolic thickening. RESULTS: A progressive increase in LV wall thickness was noted at high TEAPSE rates (from 1.31 +/- 0.21 mm at baseline to 1.47 +/- 0.27 mm at +50 beats/min of TEAPSE, p<0.05). The ratio wall/cavity area increased significantly at end diastole (from 1.65 +/- 0.36 at baseline to 2.12 +/- 0.49 at +50 beats/min, p<0.05). Percent systolic thickening was inversely correlated with the increase in wall thickness (r=-0.30, p<0.004) and the ratio wall/cavity area in diastole (r=-0.41, p<0.001). Feasibility of TEAPSE was 52% (15 of the 29 patients). CONCLUSIONS: The occurrence of pseudohypertrophy during TEAPSE in conjunction with the low feasibility rate makes the performance and the interpretation of the test problematic. Therefore, other modalities of stress echocardiography should be considered for routine clinical use and TEAPSE could be applied in specific circumstances when other modalities are either contraindicated or unavailable.

Ability of ambulatory blood pressure monitoring and myocardial/carotid ultrasound to predict the location and the severity of coronary artery lesions in normotensive patients: a clinical study.

Pulse pressure has been recognized as a marker of cardiovascular disease in normotensives. Moreover, internal carotid artery intima-media thickness (IMT) has been proposed to reflect coronary artery lesions. The aim of the present study was to evaluate the predictive value of other parameters derived from ambulatory blood pressure monitoring (ABPM), myocardial ultrasound, and carotid ultrasound to predict the location and the severity of coronary artery disease in normotensives. One hundred and thirteen patients with suspected coronary artery disease underwent coronary angiography, 24-h ABPM and myocardial/carotid ultrasound. Multivariate analysis was applied and equations were extrapolated based on independent variables derived from ABPM and ultrasound. The Gensini score was independently correlated with male gender, pulse pressure, average heart rate for both 24-h (p=0.001) and night (p=0.006) values, as well as percentage of high systolic blood pressure (BP), average diastolic BP, average mean BP, and heart rate concerning daily mesurements (p=0.001). Moreover, the Gensini score was independently correlated with end-systolic volume, posterior wall thickness during systole and intraventricular septum thickness during diastole, along with male gender and age (p=0.001), as well as mean internal and right common carotid artery IMT (p=0.002). Similar mathematical formulas have been calculated separately for the coronary arteries and their main branches. In conclusion, the location and the severity of coronary disease can be effectively evaluated by ABPM and myocardial/carotid ultrasound in normotensives. This approach could be useful for determining atypical patients at risk and/or for treating patients with suspected coronary disease who refuse coronary angiography.

Effect of dobutamine on left ventricular functional geometry after acute myocardial infarction: experimental study.

INTRODUCTION: Acute myocardial infarction causes left ventricular (LV) remodelling, which forms the substrate for its early and late complications. The aim of this experimental study was to evaluate the acute changes in LV functional geometry after acute myocardial infarction using echocardiography and to investigate the effect of continuous intravenous dobutamine administration on those changes. METHODS: In 22 pigs acute myocardial infarction was induced by ligation of the anterior descending branch of the left coronary artery. In 11 animals dobutamine was administered at a rate of 5 microg/kg/min (Group B), while the remainder (Group A) served as controls. Before infarction and 5, 15, 45 and 75 minutes after, the fractional shortening of the long (FSL) and short (FSS) axes of the LV were measured echocardiographically and the ejection fraction (EF) was calculated. RESULTS: In Group A FSL and EF reduced significantly after infarction (p < 0.0001), while FSS increased significantly (p < 0.05). In Group B FSL and EF reduced significantly 5 minutes after infarction and then returned progressively to normal values after 15 min (EF) and 45 min (FSL). FSS did not change significantly during 75 minutes after infarction. CONCLUSIONS: Dobutamine, administered at a rate of 5 microg/kg/min during acute experimental anterior myocardial infarction, before the appearance of early complications, may prevent the acute, unfavourable remodelling of the LV, as manifested by a decrease in FSL and EF and a compensatory increase in FSS.

Carotid artery intima-media thickness could predict the presence of coronary artery lesions.

The purpose of the present study was to examine whether intima-media thickness (IMT) predicts the presence of the coronary artery lesions independent of other risk factors including clinic blood pressure (BP), parameters of 24-h ambulatory BP monitoring, body mass index, serum cholesterol, and glucose levels. The study population consisted of 390 consecutive subjects who had recently undergone coronary arteriography; 51 subjects with no measurable lesions in their coronary arteries (control group) and 339 subjects with coronary artery lesions (coronary artery disease [CAD] group). Mean IMT of the common carotid artery (MCCA) and internal carotid artery (MICA) were significantly higher in subjects with CAD compare control subjects (P < .0001). Carotid IMT could predict the presence of coronary artery lesions independently of clinic or ambulatory BP values, BMI, serum cholesterol, and glucose levels (P < .01). Carotid IMT predicted the presence of significant coronary artery lesions with cutoff values 0.85 and 0.80 for MICA and MCCA, respectively. The IMT could be a clinical useful test for the presence of significant coronary artery lesions.

Evaluation of myocardial performance index to predict mild rejection in cardiac transplantation.

BACKGROUND: Early diagnosis of heart transplant rejection is mandatory, since even mild rejection can rapidly progress to more severe rejection. Noninvasive diagnosis of heart transplant rejection still remains a challenge. HYPOTHESIS: The purpose of the study was to determine a possible association between myocardial performance index (MPI) and biopsy score of the heart transplant. METHODS: This is a retrospective cohort analysis of 99 complete Doppler echocardiographic studies from 24 consecutive patients (23 men) performed within 24 h of endomyocardial biopsy. Mean age of the cohort was 50 +/- 9 years and mean time from transplantation was 19 +/- 21 months (1-81). All patients were in sinus rhythm. Myocardial performance index was calculated as the ratio of isovolumic contraction time plus isovolumic relaxation time divided by ejection time. Left ventricular dimensions, left ventricular mass, ejection fraction, and a number of Doppler indices (E-point velocity, A-point velocity, deceleration time, and deceleration slope) were also measured. The International Society for Heart and Lung Transplantation (ISHLT) grading system was used for the classification of endomyocardial biopsies. RESULTS: Myocardial performance index was significantly prolonged (0.60 +/- 0.13, 0.68 +/- 0.08, 0.75 +/- 0.20, in biopsy scores 0, IA, and IB, respectively; p<0.001). Isovolumic contraction time was significantly prolonged; isovolumic relaxation time was not significantly changed. Ejection time and deceleration time were significantly shortened. Multivariate stepwise regression analysis revealed that MPI and deceleration time were the only independent predictors of biopsy score (r=0.48, F=10.53, p<0.0001). CONCLUSION: Myocardial performance index seems to be a useful adjunct in the follow-up of cardiac transplant patients. These preliminary data suggest that a larger study may be indicated to clarify the relevance of myocardial performance index.

Pulse pressure and left ventricular diastolic dysfunction in hypertensive patients.

BACKGROUND: Impaired left ventricular diastolic function is a common finding in essential hypertension. METHODS: In order to investigate possible relationships between flow velocity through the mitral valve (E/A; index of left ventricular diastolic function) and 24-hour blood pressure and heart rate variations, 198 patients with mild to moderate essential hypertension were studied by Doppler echocardiography and ambulatory blood pressure monitoring. They were divided according to age into group 1 (n = 88, age 40-54 years) and group 2 (n = 110, age 55-79 years). Each group was divided into subgroups with (1a, 2a) or without (1b, 2b) left ventricular hypertrophy according to the end-diastolic posterior wall thickness and/or the interventricular septum thickness. RESULTS: In a multivariate stepwise regression analysis, age (beta = -0.25, p < 0.0001), posterior wall thickness (beta = -0.31, p < 0.0057) and mean heart rate during the day (beta = -0.34, p < 0.0284) were the independent predictors of E/A in the pooled population. In group 1a (young subjects with left ventricular hypertrophy), mean systolic blood pressure during the night (beta = -0.33, p < 0.041) was the only independent predictor of E/A. In the elderly group without left ventricular hypertrophy (group 2b), the mean heart rate during the day (beta = -0.44, p < 0.0000) and mean pulse pressure during the night (beta = -0.60, p < 0.0007) were the independent predictors of E/A. CONCLUSIONS: The new finding provided by this study is that in elderly hypertensive patients without left ventricular hypertrophy, a large pulse pressure at night may serve as an independent predictor of abnormal left ventricular diastolic filling.

White-coat effect in normotension and hypertension.

OBJECTIVES: The difference between clinic and daytime ambulatory blood pressure is referred to as the white-coat effect. In this study, we investigated (i) the magnitude of the white-coat effect in subjects with different daytime ambulatory blood pressure levels, and (ii) the association of the white-coat effect with left ventricular mass. METHODS: A total of 1581 subjects underwent clinic blood pressure readings, 24-h ambulatory blood pressure monitoring and left ventricular echocardiographic assessment. Their mean daytime systolic blood pressure varied from 88.0 to 208.9 mmHg and their mean daytime diastolic blood pressure from 40.3 to 133.0 mmHg. RESULTS: A negative correlation was found between the systolic or diastolic white-coat effect and the systolic or diastolic daytime ambulatory blood pressure (r = -0.22, P < 0.000 and r = -0.50, P < 0.000, respectively). Left ventricular mass significantly correlated with ambulatory blood pressure (P < 0.001), but there was no association between left ventricular mass and clinic blood pressure or white-coat effect. Furthermore, the white-coat effect was reversed at the highest level of systolic or diastolic daytime ambulatory blood pressure (systolic over 170 mmHg or diastolic over 100 mmHg) when systolic or diastolic daytime ambulatory blood pressure was higher than systolic or diastolic clinic blood pressure (ambulatory blood pressure hypertension). CONCLUSIONS: The white-coat effect shows an inverse association with daytime ambulatory blood pressure level (systolic or diastolic), being significantly more prominent for levels below 140/80 mmHg for systolic/diastolic daytime ambulatory blood pressure and reversed with daytime ambulatory blood pressure levels above 170/100 mmHg.