Do the Different Types of Pulmonary Hypertension Cause the Same Effect on Right Heart and Serum Asymmetrical Dimethylarginine Levels in Female Patients?

ABSTRACT Objective: Right-heart function is a major determinant of clinical outcome in patients with elevated pulmonary artery pressure due to pulmonary venous hypertension (PVH) and pulmonary arterial hypertension (PAH). Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase. This study aimed to evaluate if different types of pulmonary hypertension (PH) would cause the same effect on right-heart functions and serum ADMA levels in female patients. Methods: This study included patients with PAH as group I, patients with PVH due to mitral stenosis (mitral valve area ≤ 1.5 cm2, without any additional valve or left-heart disease and systolic pulmonary artery pressure ≥ 50 mmHg in transthoracic echocardiography) as group II, and healthy control subjects as group III. Transthorasic echocardiographic evaluations for right-heart functions were performed according to the guidelines of the American Society of Echocardiography. Venous blood samples were collected, and the serum ADMA concentrations were obtained with the ELISA kit (DRG® International Inc., Springfield, NJ, USA). Results: Patients in groups I and II had higher ADMA levels than healthy control subjects. Right-atrium area and dimensions, right-ventricular (RV) volumes, grade of tricuspid regurgitation, systolic pulmonary arterial pressure, RV wall thickness, and RV outflow tract diameters were significantly higher in group I patients than in group II patients. Right-ventricular myocardial performance index was lower, and RV fractional area change and tricuspid valve systolic tissue Doppler velocity were higher in group II patients than in group I patients. Conclusion: This study demonstrated that both PAH and PVH caused increase in right-heart dimensions and impairment in right-heart functions.

Combination Therapy in Pulmonary Arterial Hypertension: Single Centre Long-term Experience.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a progressive disease of the pulmonary vascular bed and causes right heart failure and death. Combination therapy which targets three different pathways is necessary due to the progressive nature of the disease. In patients with PAH, there are two approaches in combination therapy: "first-line up-front" and "sequential add-on" treatment. In "firstline up-front" treatment, patients receive double or triple drug therapy from the start. In the "sequential add-on" approach, a single drug is initially started and then according to the patient's requirements, a second or third drug is added. There is insufficient evidence about the efficiency and safety of treatment approaches. In this study, we aimed to evaluate the treatment approach in patients with PAH at a tertiary centre. METHODS: Pulmonary arterial hypertension was diagnosed according to clinical, echocardiographic and right heart catheterization findings. The patients received bosentan, sildenafil and iloprost treatment in accordance with guidelines recommendations. Clinical worsening in patients was defined as death, requirement of hospitalization for PAH, a 15% decline in the six-minute walk test (6MWT) distance, deterioration in functional capacity, and symptoms and findings of right heart failure. RESULTS: At the end of the follow-up period, clinical and echocardiographic findings, brain natriuretic peptide (BNP) levels and oxygen saturation were similar between patients who completed the study with monotherapy and with combination therapy. The follow-up period was significantly longer in patients who required combination treatment. Two patients (6.9%) died and four patients (13.8%) were hospitalized due to recurrent symptoms and findings of right heart failure. At the end of follow-up, 10 patients (34.5%) completed the study with a single drug, 15 patients (51.7%) with two drugs and four patients (13.8%) with three drugs. CONCLUSION: In this study, combination therapy was given to patients as "sequential add-on therapy". At the end of the follow-up period, monotherapy was sufficient in 34.5% of patients of the study group and in eight patients, sildenafil or prostaglandin analogues were added; a total of 15 patients (48.4%) completed the study under dual therapy. Four patients (12.9%) received combination therapy with three drugs.

Independent relationship of serum uric acid levels with leukocytes and coronary atherosclerotic burden.

BACKGROUND AND AIM: Epidemiological studies have shown that increased serum uric acid (SUA) level is associated with coronary artery disease (CAD). Leukocytes have been shown to play an important role in the atherosclerotic process. The aim of the study was to investigate whether there is any relationship among SUA, leukocyte counts and coronary atherosclerotic burden in patients who are suspected of having CAD. METHOD AND RESULTS: We enrolled 690 eligible patients who had undergone coronary angiography between October 2005 and June 2006 in a consecutive manner. The relationship of SUA with total and differential leukocyte counts and CAD was investigated. Serum uric acid levels (5.57+/-1.64 vs 4.63+/-1.27 mg/dl, p<0.001) and leukocytes were higher in patients with CAD than those with normal coronary arteries (NCA). When we divided the patients into four groups according to the quartiles of SUA, we found that the monocyte count was prominently related with SUA (478+/-165, 553+/-177, 565+/-199 and 607+/-229 mm(-)(3), Q1-Q4, p<0.001). In multivariate analysis, SUA was an independent predictor of CAD (OR, 1.270; 95% CI, 1.087-1.484, p=0.003). When we performed multiple linear regression analyses to determine the independent predictors of inflammatory cells in blood, we found a strong, positive and independent relationship between SUA with neutrophils (beta+/-SE: 206+/-60, p=0.001) and monocytes (beta+/-SE: 35+/-7, p<0.001). CONCLUSION: Our study results demonstrated that neutrophils and monocytes which play an important role in inflammation and atherosclerosis were independently related with SUA. This finding suggests an important epidemiologic relation and may provide a possible causative mechanism of SUA in atherosclerotic process.

Myocardial infarction in the young.

An increasing number of patients under 40 years of age are being hospitalized with the diagnosis of acute myocardial infarction. This is partly due to the increased prevalance of risk factors for atherosclerosis in the younger age group; especially increased incidence of impaired fasting glucose, high triglyceride, low high-density lipoprotein levels and increased waist to hip ratio. However, non-atherosclerotic coronary artery disease or hypercoagulability should also be investigated or at least suspected in the younger patients. The pathophysiology of different clinical conditions and disease states which cause acute coronary syndromes in the young patients are reviewed, and the diagnostic modalities and therapatic options for these conditions are briefly discussed by searching for "premature atherosclerosis", "hypercoagulable states", "risk factors for atherosclerosis in youth", "novel risk factors for atherosclerosis", "non-atherosclerotic coronary artery diseases" in PubMed.

Successful switch from inhaler iloprost to treatment in a patient who initially presented with pulmonary arterial hypertension and diagnosed as SLE.

BACKGROUND: SLE-induced Pulmonary Arterial Hypertension increases morbidity and mortality. Vasoconstruction, thrombosis, inflammation are the mostly proposed factors in PAH. Time until PAH develops is variable in patients with SLE. It has been shown that vasoactive agents improve symptoms and clinical findings in patients with SLE-induced-PAH. METHODOLOGY: The case note of the patient with with pulmonary arterial hypertension and SLE was retrieved and reviewed, and literature search was done. We reported a patient whose initially symptoms and clinical findings were consistent with idiopathic PAH and then had been diagnosed as SLE. RESULT: The patient tolerated the switch treatment from inhaler Iloprost from oral Bosentan well. Her symptoms, clinical findings and 6 minutes walking distance improved with treatment. CONCLUSION: Vasodilator treatment appears to be beneficial in patients with SLE-associated PAH and switch therapy also seems to be well tolerated. Additionally, in connective tissue diseases it must be kept in mind that PAH might be the presenting symptom.

Cardiac systolic function in patients receiving hematopoetic stem cell transplantation: risk factors for posttransplantation cardiac toxicity.

One hundred eleven patients who received 125 hematopoetic stem cell transplantations (HSCT) with myeloablative conditioning regimens were retrospectively evaluated for the development of cardiac toxicity (CT). The aims of this study were to assess the frequency of cardiac complications in patients receiving HSCT and to investigate the value of pretransplantation variables to predict posttransplantation CT. Severe grade III-IV CT was not observed in this cohort, in whom pretransplantation eligibility criteria excluded the patients with a left ventricular ejection fraction (LVEF) of 50% or less. Grade I-II CT was seen in 13.4% patients. Patients with a history of previous mediastinal radiotherapy, high doses of anthracycyclines, and a longer interval between diagnosis and treatment were found to have higher risk of developing CT. Pretransplantation ferritin levels and the type of HSCT did not seem to have an effect on posttransplantation cardiac complications. Our results indicated that CT was managable in patients with a LVEF of at least 50%.

Relationship between N-terminal pro-B type natriuretic peptide and extensive echocardiographic parameters in mild to moderate aortic stenosis.

CONTEXT: The N-terminal pro-B type natriuretic peptide levels (NT pro-BNP) are increased in cases of volume or pressure overload. AIMS: To examine NT pro-BNP levels and enclose whether any relationship is present between the levels of NT pro-BNP and extensive echocardiographic parameters in asymptomatic patients with mild to moderate aortic stenosis (AS). SETTINGS AND DESIGN: A cross-sectional study about the NT pro-BNP levels was conducted in 37 asymptomatic AS patients and compared with 40 controls. METHODS: Patients < 70 years old with mild to moderate AS with a peak transaortic gradient > 20 mm Hg in transthoracic echocardiogram were included in our study. Extensive echocardiographic parameters and NT pro-BNP levels were obtained from these patients and these indices were compared with the control population selected from the patients who had similar clinical characteristics with the AS patients. STATISTICAL ANALYSIS: NT-proBNP values were found to be distribution free. Spearman correlation coefficient was used for correlation analysis. Mean values were compared by the Kruskal-Wallis test. RESULTS: The NT pro-BNP levels were increased in patients with AS (median; interquartiles range: 686 [449-855] pg/mL vs. 140 [116-150] pg/mL, P < 0.001). Among patients with AS, when correlation analysis was performed mean transaortic gradient, aortic valve area index, myocardial performance index, E(m)/A(m) ratio, left-ventricular mass index (LVMI) and E/E(m) ratio had correlations (r=0.38, P = 0.026; r=-0.46, P =0.008; r=0.19, P =0,049; r=-0.22, P =0.04, r=0.49, P =0.003 and r=0.53, P <0.001 respectively) with plasma NT pro-BNP levels. The LVMI (r = 0.49, P = 0.003) and E/E(m) ratio (r = 0.53 P < 0.001) have the strongest correlations when compared to other parameters. CONCLUSION: Plasma NT pro-BNP levels are increased in even asymptomatic patients with AS and correlated with several echocardiographic parameters related to severity of AS and degree of diastolic dysfunction. As a result, NT pro-BNP levels may be used in the follow-up of asymptomatic patients having mild to moderate AS.

Myocardial indium-111-antimyosin uptake in essential hypertension.

AIM: Evaluation of myocardial uptake of (111)In-anti-myosin antibodies in patients with essential hypertension for the verification of our hypothesis that it may increase in stage 1 in the left ventricle as a result of myocardial damage. PATIENTS, METHODS: Twelve men (mean age: 59+/-2.4 years) suffering from angina like symptoms and essential hypertension in clinical stage 1 according to the JNC-VI criteria were included into the study. These patients showed normal perfusion as revealed by thallium-201 myocardial study and coronary angiography. Left ventricular mass index was determined in echocardiography. Planar antimyosin images were obtained 48 h after the intravenous injection of the tracer. Heart to lung ratios were calculated as a parameter of myocardial tracer uptake using appropriate region of interests; values>1.52 were considered as abnormal. RESULTS: We observed increased anti-myosin uptake (mean: 1.71+/-0.12) consistent with myocardial damage in 11 of 12 patients. Nine of 12 patients had a left ventricular hypertrophy with left ventricular mass index values (mean: 131 g/m(2)+/-9.48) above 115 g/m(2). Heart to lung ratio was correlated significantly to left ventricular mass index (r = 0.902, p<0.001) and duration of hypertension (r = 0.948, p<0.001). CONCLUSION: Our results suggest that (111)In-antimyosin imaging may indicate myocyte damage in early phases of hypertensive heart disease.

Behcet's disease with a large and free right atrial thrombus.

We present a case of a 27-year-old male patient with Behcet's disease who presented with dyspnoea and haemoptysis in whom further investigation revealed a large and free right atrial thrombus and pulmonary thromboembolism. Considering the absence of haemodynamic compromise and the risk of recurrence after surgical treatment for cardiac thrombus, we preferred medical management which consisted of immunosuppression and anticoagulation. On a follow-up period of 12 months we observed complete dissolution of the thrombus and dramatic improvement of clinical status.

Direct stenting in angiographically apparent thrombus-containing lesions.

The data regarding the potential benefits of direct stenting in the setting of angiographically apparent thrombus-containing lesions are scarce. The aim of this study was to evaluate the impact of direct stenting on the angiographic results in the setting of thrombus. We reviewed our institutional interventional database and identified 30 patients who had undergone stenting in the setting of angiographically apparent thrombus-containing lesions (33% unstable angina pectoris, 67% acute myocardial infarction). The majority of patients had a baseline TIMI 2 and 3 flow (80%). Of the 6 patients (20%) who had TIMI 0-1 flow at baseline, four of them achieved a TIMI 2 flow immediately after crossing the lesion with a 0.014 guidewire. Although the remaining 2 patients had TIMI 1 flow, as distal opacification beyond the stenosis was obtained we successfully implanted the stents directly. All stents were successfully implanted without any crossing failure or stent loss. There was no "no re-flow", with a final TIMI 3 flow rate in 93%. In 1 patient with TIMI 2 flow after stenting, TIMI 3 flow was obtained after intracoronary verapamil. In 2 patients (7%, TIMI 2 flow), a final TIMI 3 flow could not be achieved despite intracoronary nitroglycerin and verapamil. There was no stent loss and imprecise stent placement. There were no in-hospital deaths, repeat interventions or coronary artery bypass graft surgeries. However, two patients had undergone mitral valve replacement due to severe mitral regurgitation. Eight patients with recurrent ischemia had control angiography; stents were found to be patent in all 8 patients. Two patients experienced recurrent myocardial infarction (6.6%). Direct stenting strategy in thrombus-containing lesions seems to be a safe and feasible approach in avoiding no re-flow. We believe that benefits observed with direct stenting in this study should be compared to conventional stenting in the same setting with a randomized study.

Stenting of the septal perforator coronary artery.

This report describes the first application of intracoronary stenting to the septal perforator coronary artery in a patient with a totally occluded left anterior descending coronary artery (LAD) and a patent venous graft to the distal LAD. The procedure was successful and resulted in almost complete relief of class III angina. Therefore, diseased large septal perforators may cause angina and be treated effectively by intracoronary stenting in selected cases.

Adjunctive therapies in the cath lab. Subacute stent thrombosis developing twelve days after discontinuation of ticlopidine treatment.

The two structurally related thienopyridines, ticlopidine and clopidogrel in addition to aspirin, have become the standard regimen for prevention of subacute thrombosis (SAT) after coronary stent implantation. Although both regimens are highly effective, ticlopidine suffers from severe hematologic side effects. Recent trials encourage shorter duration of therapy with these agents. However, the optimal duration of antiplatelet therapy after stenting is still not clear. We report a case of SAT developing 12 days after discontinuation of 2 weeks of aspirin plus ticlopidine therapy. We believe that the present data are still not clear regarding the optimum duration of antiplatelet therapy after stenting.

Adjunctive therapies in the cath lab. Intracoronary tirofiban infusion in a case with massive intracoronary thrombus.

By inhibiting platelet aggregation, glycoprotein IIb/IIIa inhibitors prevent arterial occlusion and reduce ischemic complications in the setting of acute ischemic coronary syndromes associated with intracoronary thrombus. There are also accumulating data in the literature regarding the local use of these agents for thrombus dissolution. We report a case with massive right coronary artery thrombus in which the thrombus was successfully dissolved with intracoronary tirofiban infusion. To the best of our knowledge, this is the first case of this kind.

Primary angioplasty and stenting in a patient with primary antiphospholipid syndrome and thrombocytopenia.

Antiphospholipid syndrome is characterized by venous and arterial thrombosis, thrombocytopenia, stroke and, rarely, acute coronary syndromes. However, there are no data available regarding the management of acute myocardial infarction in primary antiphospholipid syndrome with accompanying severe thrombocytopenia and cardiogenic shock. We describe such a case, which was managed by successful primary percutaneous transluminal coronary angioplasty and stent implantation with accompanying immunosuppression therapy.

Pentacuspid aortic valve diagnosed by transoesophageal echocardiography.

Congenital aortic valve anomalies are quite a rare finding in echocardiographic examinations. A case of a 19 year old man with a pentacuspid aortic valve without aortic stenosis and regurgitation, detected by transoesophageal echocardiography, is presented.