Savvas Toumanidis

Impact of Obesity on 24-Hour Ambulatory Blood Pressure and Hypertension

The purpose of the present study was to determine the relationship between body mass index (BMI) and parameters derived from 24-hour ambulatory blood pressure monitoring including mean 24-hour daytime and nighttime systolic and diastolic blood pressures, 24-hour daytime and nighttime pulse pressure, mean 24-hour daytime and nighttime heart rate, dipping and nondipping status. 3216 outpatient subjects who visited our hypertension center and were never treated with antihypertensive medication underwent 24-hour blood pressure monitoring. BMI was significantly correlated with clinic systolic and diastolic blood pressures. Significant correlations were also found between BMI and mean 24-hour daytime and nighttime systolic blood pressure, 24-hour daytime and nighttime pulse pressure, and mean 24-hour daytime and nighttime heart rate. In multivariate regression analysis, clinic systolic, diastolic blood pressure, mean 24-hour systolic blood pressure, 24-hour pulse pressure, and high-density lipoprotein were independently correlated with BMI. The incidence of white coat hypertension was higher in overweight and obese patients than in normal weight subjects. Confirmed ambulatory blood pressure hypertension was also found to be higher in overweight and obese individuals compared with normal weight subjects. Our data also highlight the higher incidence of nondipping status in obesity. These findings suggest that obese patients had increased ambulatory blood pressure parameters and altered circadian blood pressure rhythm with increased prevalence of nondipping status.

Treatment of light chain (AL) amyloidosis with the combination of bortezomib and dexamethasone

Background and Objectives High-dose melphalan and autologous stem cell transplantation is currently the treatment of choice for selected patients with AL amyloidosis; however, new treatments are needed for patients who are ineligible for or relapse after this procedure. Bortezomib is a proteasome inhibitor with proven activity in multiple myeloma, and the addition of dexamethasone results in superior outcome. We evaluated the activity and feasibility of the combination of bortezomib and dexamethasone (BD) in patients with AL amyloidosis. Design and Methods Consecutive patients with histologically proven, symptomatic AL amyloidosis were treated with BD. Results Eighteen patients, including seven who had relapsed or progressed after previous therapies were treated with BD. Eleven (61%) patients had two or more organs involved; kidneys and heart were affected in 14 and 15 patients, respectively. The majority of patients had impaired performance status and high brain natriuretic peptide values; serum creatinine was elevated in six patients. Among evaluable patients, 94% had a hematologic response and 44% a hematologic complete response, including all five patients who had not responded to prior high dose dexamethasone-based treatment and one patient under dialysis. Five patients (28%) had a response in at least one affected organ. Hematologic responses were rapid (median 0.9 months) and median time to organ response was 4 months. Neurotoxicity, fatigue, peripheral edema, constipation and exacerbation of postural hypotension were manageable although necessitated dose adjustment or treatment discontinuation in 11 patients. Interpretation and Conclusions The combination of BD is feasible in patients with AL amyloidosis. Patients achieve a rapid hematologic response and toxicity can be managed with close follow-up and appropriate dose adjustment. This treatment may be a valid option for patients with severe heart or kidney impairment.

Target Organ Damage in “White Coat Hypertension” and “Masked Hypertension”

BACKGROUND In this study we investigated (i) the prevalence of white coat hypertension (WCH) and masked hypertension (MH) in patients who had never been treated earlier with antihypertensive medication, and (ii) the association of these conditions with target organ damage. METHODS A total of 1,535 consecutive patients underwent office blood pressure (BP) measurements, 24-h ambulatory BP monitoring (ABPM), echocardiography, and ultrasonography of the carotid arteries. Subjects who showed normotension or hypertension on the basis of both office and ambulatory BP (ABP) measurement were characterized as having confirmed normotension or confirmed hypertension, respectively. WCH was defined as office hypertension with ambulatory normotension, and MH as office normotension with ambulatory hypertension. RESULTS WCH was found in 17.9% and MH in 14.5% of the subjects. The prevalence of WCH was significantly higher in subjects with obesity, while the prevalence of MH was significantly higher in normal-weight subjects. The confirmed hypertensive subjects as well as the masked hypertensive subjects had significantly higher left ventricular mass (LVM) (corrected for body surface area) and carotid intima media thickness (cIMT) than the confirmed normotensive subjects did (108.9 +/- 30.6, 107.1 +/- 29.1 vs. 101.4 +/- 29.9 g/m(2) and 0.68 +/- 0.16, 0.68 +/- 0.21 vs. 0.63 +/- 0.15 mm, respectively, P < 0.005). White coat hypertensive subjects did not have a significantly higher LVM index than confirmed normotensive subjects (101.5 +/- 25.9 vs. 101.4 +/- 29.9 g/m(2)); they tended to have higher cIMT than the confirmed normotensive subjects, but the difference was not statistically significant (0.67 +/- 0.15 vs. 0.63 +/- 0.15 mm). CONCLUSIONS WCH and MH are common conditions in patients who visit hypertension outpatient clinics. Confirmed hypertension and MH are accompanied by increased LVM index and cIMT, even after adjusting for other risk factors.

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.

Comparison of three different regimens of intermittent inotrope infusions for end stage heart failure

AIMS Inotrope treatment is often necessary in refractory to optimal management end stage heart failure, when signs of end-organ hypoperfusion appear. The effect of specific inotropes on patient outcome remains controversial. The aim of the study was to compare the effect of levosimendan versus dobutamine, alone or in combination with levosimendan, on the outcome of end-stage heart failure patients, requiring inotropic therapy. METHODS AND RESULTS We studied 63 patients in NYHA class IV, refractory to optimal medical therapy, recently hospitalized for cardiac decompensation and stabilized by an intravenous inotrope. They were randomly assigned to intermittent infusions of either a) dobutamine, 10mg/kg/min, versus b) levosimendan, 0.3mg/kg/min, versus c) dobutamine, 10mg/kg/min+levosimendan 0.2 mg/kg/min, each administered weekly, for 6h, over a 6-month period. All patients received amiodarone, 400 mg/day, to suppress the proarrhythmic effects of the inotropes. Baseline characteristics of the 3 groups were similar. At 6 months, survival free from death or urgent left ventricular device implantation was 80% in the levosimendan, 48% in the dobutamine (P=0.037 versus levosimendan), and 43% in the levosimendan+dobutamine (P=0.009 versus levosimendan) group. At 3months, NYHA class improved significantly in all 3 groups, whereas pulmonary capillary wedge pressure decreased (27 ± 4 to 19 ± 8 mmHg, P=0.008) and cardiac index increased (1.5 ± 0.3 to 2.1 ± 0.3 l/min/m(2), P=0.002) significantly only in patients assigned to levosimendan. CONCLUSIONS In patients with refractory end-stage heart failure, intermittent administration of levosimendan conferred survival and hemodynamic benefits in comparison to a regimen of intermittent infusions of dobutamine, alone or in combination with levosimendan.

Effect of 24-hour blood pressure and heart rate variations on left ventricular hypertrophy and dilatation in essential hypertension

This study correlates variables derived from blood pressure (BP) and heart rate (HR) monitoring with the degree of left ventricular structural changes in essential hypertension. Forty patients with mild-to-moderate hypertension according to World Health Organization criteria underwent 24-hour ambulatory monitoring. Echocardiographic (posterior wall and interventricular septum thickness, left ventricular mass) or ECG (SV1 + RV5) indices of hypertrophy were significantly (p less than 0.01) correlated (positive correlations) with derivatives of BP monitoring (mean systolic and diastolic BP values) but not with HR derivatives. Echocardiographic indices of dilatation (left ventricular end-diastolic volume and diameter) were significantly (p less than 0.01 to less than 0.001) correlated (negative correlations) with derivatives of HR monitoring (mean HR values, mainly during the night) but not with BP derivatives. It is concluded that in essential hypertension, left ventricular hypertrophy depends on mean 24-hour systolic and diastolic BP values, whereas left ventricular dilatation appears to be more prominent in patients with bradycardia mainly during the night.

Obesity and daytime pulse pressure are predictors of left ventricular hypertrophy in true normotensive individuals.

Objective To investigate predictors of left ventricular mass corrected for height2.7 (LVMI) and left ventricular hypertrophy in patients who were found to be normotensive with both office and 24-h ambulatory blood pressure (BP) measurements. Methods A total of 805 consecutive patients were analyzed. All patients underwent office BP measurements, 24-h ambulatory BP monitoring, laboratory measurements for cardiovascular risk factors and echocardiography. Individuals with both office and ambulatory normotension were characterized as true normotensive. Results LVMI was found to be 34.5 ± 10.9 g/m2.7 in normal-weight patients and 48.7 ± 13.0 g/m2.7 in obese patients (P < 0.0001). LVMI was found to be 41.7 ± 10 g/m2.7 in overweight patients, significantly lower than the values of obese patients (P < 0.005) and higher than the values of normal-weight patients (P < 0.001). These results remained significant even after adjustment for age, sex, daytime and nighttime SBP, daytime and nighttime DBP, daytime and nighttime BP variability and daytime and nighttime pulse pressure (PP). In a multivariate analysis model, in which LVMI was the dependent variable and office SBP, office DBP, daytime and nighttime SBP and DBP, daytime and nighttime PPs and variabilities, day–night SBP ratio, fasting serum glucose, triglycerides, total cholesterol, age and BMI were inserted as independent variables with weighted least squares regression by sex, the predictors of LVMI were age, BMI and daytime PP (r2 = 0.31). Left ventricular hypertrophy was 17.67 times more likely in obese patients as compared with normal-weight true normotensive individuals. Conclusion Obesity may represent a significant cardiovascular risk factor even in normotensive individuals. Other predictors of LVMI were ageing and daytime PP.

White-coat effect in normotension and hypertension.

ObjectivesThe 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. MethodsA 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. ResultsA 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). ConclusionsThe 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.

Ortner's Syndrome: A Multifactorial Cardiovocal Syndrome

Sotiris C. Plastiras, MD; Constantinos Pamboucas, MD; Tsila Zafiriou, MD; Nikolaos Lazaris, MD; Savvas Toumanidis, MD Department of Clinical Therapeutics, University of Athens Medical School Alexandra Hospital Athens, Greece Address for correspondence: Sotiris C. Plastiras, MD Department of Clinical Therapeutics University of Athens Medical School ‘‘Alexandra Hospital’’ Athens, Greece Vasilisis Sofias & Lourou St, 11528 splastiras@panafonet.gr

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.Am. J. Hematol. 90:E60–E65, 2015.