Francesco Solbiati

Effects of dual blockade of Renin-Angiotensin system on concentric left ventricular hypertrophy in essential hypertension: a randomized, controlled pilot study.

BACKGROUND The renin-angiotensin system (RAS) plays a major role in promoting left ventricular (LV) remodeling in essential hypertension. We designed a controlled, randomized pilot study aimed to test the hypothesis that the dual RAS blockade with angiotensin-converting enzyme (ACE) inhibitor (ACEi) + angiotensin II receptor blocker (ARB) can be more effective in decreasing LV hypertrophy and improving diastolic function than a largely employed association such as ACEi + calcium-antagonist (Ca-A). METHODS Twenty-four never-treated hypertensive patients with LV concentric hypertrophy were randomized to ramipril + candesartan or ramipril + lercanidipine. Before and after the 6-month treatment they underwent a 24-h blood pressure (BP) monitoring and echocardiographic examination. RESULTS At baseline, age, body mass index (BMI), 24-h BP, and LV morpho-functional parameters were similar between the two groups. The 6-month treatment induced in both groups a significant decrease of 24-h BP, septal and posterior wall thickness, and LV mass index (LVMi) (ACEi + ARB 155 +/- 19 to 122 +/- 17 g/m(2), P < 0.0001; ACEi + Ca-A 146 +/- 18 to 127 +/- 20 g/m(2), P < 0.0001). Systolic function remained unchanged; LV diastolic parameters increased significantly in both groups. The extent of 24-h BP decrease was similar between the two groups (-13.3/16.3% vs. -12.3/15.8%, P = 0.63/P = 0.71), whereas the decrease of LV mass (-22% vs. -12.8%, P < 0.005) and the improvement of diastolic function were greater in ACEi + ARB group. CONCLUSIONS In comparison with ACEi + Ca-A, ACEi + ARB treatment showed a greater antiremodeling effect, that can be reasonably ascribed to a BP-independent effect of the dual RAS blockade.

JAK2-V617F mutation and Philadelphia positive chronic myeloid leukemia.

JAK2 is a tyrosine kinase that plays an important role in the signaling pathways of many hematopoietic growth factor receptors. A single acquired point mutation – V617F – in JAK2 occurs in the great majority of patients with polycythemia vera (PV) and approximately half of the patients with idiopathic myelofibrosis (IMF) or essential thrombocythemia (ET). In contrast, the JAK2-V617F mutation is only rarely found in chronic myeloid leukemia (CML) but, recently, some authors have reported the coexistence of JAK2V617F and BCR/ABL+ in CML patients expressing the p210 BCR–ABL oncoprotein. Here, we report a CML patient with the expression of p210/b2a2 type BCR–ABL transcript and JAK2V617F mutation.

OSA, metabolic syndrome and CPAP: Effect on cardiac remodeling in subjects with abdominal obesity

BACKGROUND We evaluated whether obstructive sleep apnoea (OSA) and continuous positive airway pressure (CPAP) treatment influence left ventricular (LV) remodelling independently of abdominal obesity and metabolic syndrome (MetS). METHODS Cardiorespiratory examination, 24-h BP monitoring and echocardiogram were performed in overweight/obese patients with increased abdominal adiposity and symptoms suggesting OSA : OSA/MetS (n.50), OSA/noMetS (n.22), noOSA/MetS (n.29), noOSA/noMets (n.16). The evaluation was repeated in 41 patients after ≥18 months of CPAP. RESULTS Despite similar age, gender, BMI and 24-h BP, the 2 groups with MetS had greater LV remodelling (LV hypertrophy and diastolic dysfunction) than the 2 groups without MetS. From multiple regression analysis independent determinants for LV mass were MetS, 24-h systolic BP and age, for LV diastolic function were LV mass index, MetS and age. After CPAP, the 20 patients with decreased body weight showed diastolic BP decrease, LV hypertrophy regression and diastolic function improvement, whereas, despite similar respiratory improvement, BP and LV parameters were unchanged in the 21 patients with body weight unchanged/increased. CONCLUSION In patients with increased abdominal adiposity, LV remodelling is not associated to OSA per se; chronic CPAP treatment does not influence LV remodelling whose regression is mainly linked to body weight decrease.

Isolated office hypertension: A 3-year follow-up study

The study aimed to evaluate, over a 3‐year period, the progression towards sustained hypertension and left ventricular (LV) changes in patients with isolated office (IO) hypertension (office BP>140 and/or 90 mmHg, daytime BP<130/80 mmHg). After 3 years from the basal evaluation, 38 subjects with basal normal BP and 42 subjects with basal IO hypertension underwent a second 24‐h BP monitoring and echocardiography; 19 patients of the basal IO hypertension group were not revaluated because they had already developed ambulatory hypertension and were on antihypertensive treatment. At the second evaluation, the 38 normotensive subjects had unchanged BP and LV parameters; 25 IO hypertensives have developed sustained hypertension. Considering them together with the 19 patients already treated, 72% of 61 IO hypertensives developed ambulatory hypertension over a 3‐year period. The patients who subsequently developed hypertension differed from the group who did not only for lower basal values of LV diastolic parameters; all the patients with basal LV hypertrophy and/or preclinical diastolic impairment subsequently developed sustained hypertension. In conclusion, IO hypertensive patients show a high rate of progression towards sustained hypertension. Basal LV hypertrophy and/or preclinical diastolic dysfunction were the only markers of a greater risk of becoming hypertensives.

Angiotensin-converting enzyme inhibitors influence left ventricular mass and function independently of the antihypertensive effect.

In our retrospective study, we evaluated whether ACE inhibitors can influence left ventricular (LV) morphofunctional characteristics in essential hypertension independently of the antihypertensive effect. We studied 21 hypertensive patients (group 1) before and after at least 18 months of treatment with ACE inhibitors that did not induce any blood pressure (BP) reduction; as a control group, we evaluated 19 hypertensive patients (group 2) not treated with antihypertensive drugs during the same period. At baseline, the 2 groups, neither one previously treated with antihypertensive drugs, were not significantly different with regard to sex, age, body mass index, 24-hour BP, and heart rate; LV mass index was similar between the groups, whereas LV diastolic indices were significantly lower in group 1. At the second evaluation, body mass index, 24-hour BP, and heart rate were unchanged in both groups; LV mass index was significantly decreased in group 1 and increased in group 2. LV diastolic parameters were significantly improved in group 1, whereas in group 2, diastolic function was significantly deteriorated. In conclusion, our clinical study shows that ACE inhibitors can induce LV hypertrophy regression and improvement of diastolic function also in the absence of any antihypertensive effect.

Acute myeloid leukemia with associated translocation t(15;17) and 11q23/MLL abnormality.

The classification of acute myeloid leukemia (AML) recognizes a subgroup of diseases with recurring genetic abnormalities. Translocation (15;17) is the marker of acute promyelocitic leukemia (APL) and is associated with good prognosis [1]. 11q23/MLL abnormality has been detected in about 4% of AML [2], but never in APL [3]. 11q23/MLL abnormality is related to a previous treatment with topoisomerase inhibitors and also to a monocytic differentiation of blasts [4]. AML with 11q23/MLL has an adverse prognosis, comparable to AML with unfavourable karyotype. In this letter, we describe a case of AML with t(15;17) and t(11;22)(q23;q11.2) abnormalities; as far as we know, this association has not been reported in literature. A 64-year-old woman was admitted to our department because of cytopenia. The patient had no history of myelodysplasia, radiotherapy or chemotherapy, or toxic drug exposure. Clinical examination was negative. Blood cells count showed anaemia (haemoglobin 8.4 g/dL), leucopenia (0.876 10 cells/L) and thrombocytopenia (226 10 cells/L). Myeloid blast cells (8%) were found in peripheral blood smear. Bone marrow examination showed a blastic myeloid infiltration. Blast cells were 35% of nucleated cells and were hypogranular and myeloperossidase positive without similarities to promyelocytic blasts. No Auer’s rod was observed. Blast cells immunophenotype showed strong positivity for CD33, CD13, CD34, CD38 and a moderate expression of CD15 and CD19. HLA-DR, CD10, CD7, CD56 were negative. No morphologic evidence of dyserythropoiesis was detected by bone marrow biopsy. There were no signs of disseminated intravascular coagulation or accelerated fibrinolysis. Cytogenetic analysis revealed the association of t(15;17)(q22;q21) and t(11;22)(q23;q11.2) (WCP 11 and WCP 22 Vysis) abnormalities in all the metaphases analyzed (Figure 1). Reverse transcription polymerase chain reaction (RT-PCR) subsequently confirmed the presence of PML/RARa Bcr1 transcript and fluorescence in situ hybridisation (FISH-painting) confirmed the presence of t(11;22)(q23;q11.2) (Figure 2). Interphase FISH analysis with Vysis LSI MLI Dual Color probe, Break Apart Rearrangement probe showed that MLL gene region (11q23) was involved in the rearrangement (Figure 3). Karyotype and FISHpainting analysis for t(11;22) on lymphocytes were negative, therefore excluding an inherited chromosome translocation. The patient received induction therapy with alltrans-retinoic acid (ATRA) and idarubicin and