HIV-associated pulmonary arterial hypertension: from bedside to the future.

Pulmonary arterial hypertension (PAH) is a life-threatening complication of HIV infection. The prevalence of HIV-associated PAH (HIV-PAH) seems not to be changed over time, regardless of the introduction of highly active antiretroviral therapy (HAART). In comparison with the incidence of idiopathic PAH in the general population (1-2 per million), HIV-infected patients have a 2500-fold increased risk of developing PAH. HIV-PAH treatment is similar to that for all PAH conditions and includes lifestyle changes, general treatments and specific treatments.

Inflammatory activation and carbohydrate antigen-125 levels in subjects with atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) might be associated with an inflammatory activation and reduced left ventricular (LV) function. Less is known with regard to newly introduced markers of LV dysfunction such as carbohydrate antigen-125 (CA-125) in subjects with AF. The aim of this study was therefore to assess possible associations between AF, inflammatory markers and CA-125. METHODS AND RESULTS: Forty-eight consecutive patients with AF and 58 control patients in sinus rhythm were enrolled in this study. Patients with acute heart failure, chronic inflammatory or neoplastic disease were excluded from the study. Circulating levels of hs-C-reactive protein (CRP), interleukin-8 (IL-8), IL-6, soluble IL-2 receptor (sIL-2r), TNF-α and CA-125 were assessed; all patients underwent clinical examination with NYHA class assessment and echocardiography. Patients with AF were characterised by higher levels of IL-8 (180 ± 266 vs. 39 ± 43 pg/mL, P < 0·001), sIL-2r (987 ± 1045 vs. 680 ± 336 U/mL, P < 0·05) and TNF-α (26 ± 25 vs. 9 ± 4 pg/mL, P < 0·001). Patients with AF duration < 6 months had higher levels of CRP (54 ± 73 vs. 12 ± 14 mg/dL, P < 0·05) and IL-8 (251 ± 225 vs. 99 ± 123 pg/mL, P < 0·05) when compared with AF duration > 6 months. CA-125 levels were not statistically different if comparing subjects with AF with controls and AF > 6 months with AF < 6 months. Among patients with AF, CA-125 levels were significantly related to NYHA class, (r = 0·33, P < 0·05) as well as IL-6 levels (r = 0·31, P < 0·05). Results remained statistically significant even after multivariable correction for age, gender and LV ejection fraction. RESULTS AND CONCLUSION: AF is characterised by an inflammatory activation. Impaired functional class in AF subjects might be associated with increased CA-125 levels and higher inflammatory markers.

Early onset of coronary heart disease in a young woman with familial hypercholesterolemia: coronary findings and effect of short term treatment with high dose atorvastatin.

We describe the case of a 22-year old woman affected by familial hypercholesterolemia, referred for chest pain and treated with angioplasty of left anterior descending coronary artery. Marked systemic inflammation associated with acute coronary syndrome was reduced by 1-month therapy with high dose atorvastatin.

Multiprofessional and intrahospital experience for diagnosis and treatment of pulmonary arterial hypertension.

BACKGROUND: Referral centres for pulmonary hypertension will provide care by a multiprofessional team, which should as a minimum comprise: consultant physicians with a special interest in PH, clinical nurse specialist, radiologist, cardiologist with expertise in echocardiography. AIMS: this study sought to determine whether the experience of the establishment of a clinic for pulmonary arterial hypertension, initially created only for the treatment and diagnosis of heart failure, may be considered positive. METHODS: From 1 July 2008 to January 1, 2012 we evaluated 80 patients in our ambulatory dedicated to the diagnosis and treatment of PAH. All patients were performed to clinical evaluation, ECG, and echocardiography with estimation of the sPAP. Then we evaluated the functional capacity through cardiopulmonary exercise testing or six minute walking test (6MWT). RHC was required to confirm the diagnosis of pulmonary arterial hypertension. RESULTS: 80 patients (mean age: 50.9 +/- 18.68 years, 31 males) were evaluated in our center; the largest groups subjected to screening were thalassemia (21 subjects), rheumatologic patients (18 patients), respirators, suspected of "out-of Proportion" (12 patients) and 4 patients with OSAS. 8 adult congenital heart patients. A diagnosis of PAH after right heart catheterization was possible in 25 cases. In particular, among patients with pulmonary arterial hypertension, 8 had a rheumatic etiology (systemic sclerosis), 2 post-thromboembolic disease, 5 patients had congenital heart disease, 1 patient with HIV infection, 1 patient with thalassemia major, 1 chronic lymphocytic leukemia and 1 with myelodysplasia. CONCLUSIONS: The initial experience of our center and network within our hospital may be considered positive, because it permitted to patients easy access to hospital services, to undertake a comprehensive prognostic stratification and to recognize the early signs of worsening in subsequent tests.

The presence of remodeled and mixed atherosclerotic plaques at coronary ct angiography predicts major cardiac adverse events - The CAFÉ-PIE Study.

BACKGROUND: It is still unclear how to exploit information made available by coronary computed tomography angiography (CCTA) on coronary artery disease (CAD) features in order to better predicting major adverse cardiac events (MACEs). Aim of this study was to validate the prognostic role of a comprehensive and simplified CT-derived score in patients evaluated for suspected CAD. METHODS: A prospective registry included 477 consecutive symptomatic patients without known CAD who underwent clinically-indicated CCTA. All patients were followed-up for MACE occurrence for a period of 49±15-month. RESULTS: The mean CT Score was 10.5±10.8, with a MACE rate of 11.3%. There was a stepwise relationship between MACE rate during follow-up and CT Score values. MACEs were 1.9% in patients with CT Score<10 (reference group), 16.6% in those with CT Score 10-20 (OR 9.9, 95% C.I. 3.5-27.8 vs. reference group, p<0.001), 24.5% in those with CT Score 21-30 (OR 16.6, 95% C.I. 6.1-45.0 vs. reference group, p<0.001), and 47.4% in those with CT Score>30 (OR 46.1, 95% C.I. 13.0-162.9 vs. reference group, p<0.001) (p for trend <0.001). At ROC curve analysis, CT Score was the best predictor of MACE (AUC: 0.81, CI 95%: 0.78-0.84) as compared to Diamond and Forrester score (p<0.001), segment stenosis score (p<0.05) and segment involved score (p<.0.01). CONCLUSIONS: The use of an integrated score obtained with CCTA and based on the presence of remodeled and mixed atherosclerotic coronary plaques may improve MACE prediction in symptomatic patients at intermediate risk outweighing that provided by standard clinical and CCTA scores.

Carotid intima media thickness and coronary atherosclerosis linkage in symptomatic intermediate risk patients evaluated by coronary computed tomography angiography.

BACKGROUND: There is a growing evidence that carotid intima media thickness (CIMT) is associated with coronary artery disease (CAD) and it should be used as a predictor of atherosclerotic burden of coronary arteries. However, these studies have been performed by using invasive coronary angiography (ICA) and in high-risk patients for CAD. The purpose of this study was to evaluate the correlation between CIMT by ultrasound and coronary atherosclerosis in symptomatic intermediate risk patients by coronary computed tomography angiography (CCTA). METHODS: We enrolled 204 consecutive symptomatic patients (mean age: 61±10; men: 118) and intermediate risk for CAD. All patients underwent CIMT ultrasound evaluation and CCTA. Coronary artery calcium score (CACS), characteristics of plaques, severity of CAD, segment involvement score (SIS) and Gensini's score were assessed and compared with CIMT values. RESULTS: CIMT has been proved as an independent predictor of a number of coronary artery plaques, overall number of mixed and remodeled plaques, presence of obstructive CAD, high SIS and Gensini's score (HR 1.2, CI 1.05-1.42, p 0.01; HR 1.2, CI 1.01-1.41, p 0.03; HR 9.0, CI 1.37-59.7, p 0.02; HR 21.0, CI 2.40-184, p<0.01; HR 1.2, CI 1.08-1.42, p<0.01; HR 1.2, CI 1.08-1.42, p<0.01, respectively). A cut-off value>1.3 was associated with a better positive and negative predictive value (100% and 69%) to predict the combined endpoint of presence and mixed and/or remodeled coronary artery plaques. CONCLUSIONS: CIMT is an independent predictor of coronary atherosclerotic burden as detected by CCTA in symptomatic intermediate risk patients.

Novelty in treatment of pulmonary fibrosis: pulmonary hypertension drugs and others.

Idiopathic pulmonary fibrosis (IPF) is a chronic condition of unknown etiology with deteriorating respiratory function leading to respiratory failure. Corticosteroids, alone or in combination with immunosuppressive drugs such as azathioprine, colchicine, and cyclophosphamide, have been used with limited success. Interferon-gamma-1b showed a significant improvement in pulmonary function only in one study. Pirfenidone, cyclosporine and acetylcysteine may also be of benefit but data from studies are limited. Novel drugs, mainly antifibrotic, anticytokine and immunoregulatory, are currently being investigated in various trial phases. Endothelin receptor antagonists have been shown to have possible beneficial effects in early stages of IPF. However, most recently, the so-called triple combination therapy, anticoagulation therapy and endothelin receptor antagonists, especially ambrisentan, are either harmful or ineffective in IPF and are not recommended. We report a brief review on the present and possible future therapeutic options in IPF.

Heart rate control with oral ivabradine in computed tomography coronary angiography: a randomized comparison of 7.5 mg vs 5 mg regimen.

BACKGROUND: Heart rate (HR) reduction is essential to achieve optimal image quality and diagnostic accuracy with computed tomography coronary angiography (CTCA). Administration of oral ivabradine seems to be more effective than beta-blockade in reducing HR in patients referred for CTCA. METHODS: Two-hundred-fifty-nine consecutive patients referred for CTCA were prospectively enrolled. Patients not receiving beta-blocker at baseline (group 1) and those with beta-blocker therapy (group 2) were enrolled in the study. Each group was randomized into 3 parallel arms with 1:1:1 allocation. Patients who did not receive beta-blocker at baseline: underwent CTCA without beta blocker (n=49), and received ivabradine 5mg (n=48), or 7.5mg ivabradine (n=48). Patients with beta-blocker therapy: continued with the prior beta-blocker without any dose modification (n=38), and received ivabradine 5mg (n=38), or ivabradine 7.5mg (n=38). RESULTS: HR and blood pressure were assessed at admission (T0), immediately before CTCA (T1) and during CTCA (T2). Administration of ivabradine 7.5mg significantly reduced mean relative HR at T1 and T2 (p<0.01), the rate of patients not achieving target HR at T1 (p<0.001) and T2 (p<0.01), and the percentage of patients needing additional IV beta-blockade prior to CTCA (p<0.01). Results remained statistically significant even after correction for age, gender, ejection fraction, risk factors and HR at T0, in a multivariable analysis. CONCLUSIONS: Ivabradine 7.5mg is more effective than ivabradine 5mg in increasing the rate of patients at target HR in patients referred for CTCA.

Subacute inflammatory activation in subjects with acute coronary syndrome and left ventricular dysfunction.

Several lines of evidence indicate that increased inflammatory cytokine levels can be used for risk prediction in patients with acute coronary syndrome (ACS). This study therefore aimed to evaluate correlations between levels of soluble interleukin (IL)-2 receptor (sIL-2r), IL-6, and IL-8 and in-hospital incidence of acute heart failure (AHF) and left ventricular (LV) systolic dysfunction in the subacute phase of ACS. In 48 consecutive patients with ACS, circulating levels of sIL-2r, IL-6, and IL-8 were ascertained 72-96 h after onset of symptoms. Clinical data, LV function, and in-hospital incidence of AHF were also evaluated. IL-8 levels were significantly higher in patients with pulmonary edema (1,829 ± 2,496 vs 456 ± 624 pg/ml, p < 0.05); sIL-2r, IL-6, and IL-8 levels were increased proportionally to Killip class (r = 0.35, p < 0.05; r = 0.48, r = 0.47, p < 0.01) and in patients with LV ejection fraction (LVEF) < 30%. Levels of sIL-2r were inversely related to LVEF in subjects with acute myocardial infarction (r = -0.51, p < 0.05). Soluble IL-2r and IL-8 levels were related to mitral regurgitation severity (r = 0.34, p < 0.05; r = 0.37, p < 0.05). Levels of sIL-2 were proportional to LV end-diastolic diameter (r = 0.49, p < 0.001) and LV end-systolic diameter (r = 0.58, p < 0.001). Number of cytokines with circulating values above upper level of normal was significantly correlated with Killip class and LVEF (r = 0.40, r = -0.38, p < 0.05). sIL-2r, IL-6, and IL-8 are increased in patients with ACS and systolic dysfunction or AHF. These data suggest that inflammatory cytokine activity detectable in peripheral blood may be useful in identifying subjects with a worse clinical course.

Transient apical ballooning accompanying respiratory infection.

We report the case of a 75-year-old man, referred for worsening dyspnea and fever. The electrocardiography (ECG) showed mild ST-elevation in anterior leads, while cardiac echography severe left ventricular (LV) systolic dysfunction with apical ballooning. Later on, ECG showed negative T-waves and QT-prolongation in the same anterior leads and T-waves positivization during fever peak. Ten days later, LV ejection fraction completely recovered, apical ballooning and fever disappeared. We, therefore, hypothesize that transient apical ballooning found in our patient may have been induced by a respiratory infection, not detectable at seriate blood cultures.

Incremental value and safety of oral ivabradine for heart rate reduction in computed tomography coronary angiography.

BACKGROUND: Heart rate (HR) reduction is essential to achieve optimal image quality and diagnostic accuracy with computed tomography coronary angiography (CTCA). Administration of ivabradine could be an attractive alternative to beta-blockade to reduce HR. METHODS: One-hundred-twenty-three patients referred for CTCA were prospectively enrolled. Patients were divided in two groups depending on the absence or presence of chronic beta-blockade treatment. Within the two groups patients were randomized to either no additional premedication or oral ivabradine for 5 days prior to CTCA. In presence of chronic beta-blockade therapy it was shifted to atenolol 50mg twice a day for 5 days prior to CTCA. HR and blood pressure were assessed at admission (T0), immediately before CTCA (T1) and during CTCA (T2). The target HR was <65 bpm. RESULTS: Ivabradine significantly reduced HR during CTCA. Mean relative HR reduction was 15% for controls, 12% for chronic beta-blockade, 19% for ivabradine and 24% for both chronic beta-blockade and ivabradine at T2 (p for trend <0.001). The rate of patients who reached the target HR at T2 was 83% in controls, 71% with chronic beta-blockade, 97% with ivabradine and 97% with both (p for trend <0.05). The percentage of patients that needed additional IV beta-blockade at T1 decreased from 69% to 40% with ivabradine and 30% with both (p for trend <0.05). CONCLUSIONS: Ivabradine is safe and effective in increasing the rate of patients at target HR and in reducing the need for additional IV beta-blockade in patients referred for CTCA.

Statin therapy blunts inflammatory activation and improves prognosis and left ventricular performance assessed by Tissue Doppler Imaging in subjects with chronic ischemic heart failure: results from the Daunia Heart Failure Registry.

BACKGROUND: A limited number of studies have used Tissue Doppler Imaging (TDI) to evaluate the effect of statin therapy on left ventricular dysfunction in patients with chronic heart failure. In this work, we aimed to determine whether statin administration influenced prognosis, inflammatory activation and myocardial performance evaluated by Tissue Doppler Imaging in subjects enrolled in the Daunia Heart Failure Registry, a local registry of patients with chronic heart failure. METHODS: This study retrospectively analyzed 353 consecutive outpatients with chronic heart failure (mean follow-up 384 days), based on whether statin therapy was used. In all patients, several Tissue Doppler Imaging parameters were measured; circulating levels of interleukin (IL)-6, IL-10 and C-reactive protein were also assayed. RESULTS: Statin administration in 128 subjects with ischemic heart disease was associated with a lower incidence of adverse events (rehospitalization for HF 15% vs. 46%, p<0.001; ventricular arrhythmias 5% vs. 21%, p<0.01; cardiac death 1% vs. 8%, p<0.05), lower circulating levels of IL-6 (p<0.05) and IL-10 (p<0.01), lower rates of chronic heart failure (p<0.001) and better Tissue Doppler Imaging performance (E/E' ratio 12.82 ± 5.42 vs. 19.85 ± 9.14, p<0.001; ET: 260.62 ± 44.16 vs. 227.11 ± 37.58 ms, p<0.05; TP: 176.79 ± 49.93 vs. 136.7 ± 37.78 ms, p<0.05 and St: 352.35 ± 43.17 vs. 310.67 ± 66.46 ± 37.78 ms, p<0.05). CONCLUSIONS: Chronic ischemic heart failure outpatients undergoing statin treatment had fewer readmissions for adverse events, blunted inflammatory activation and improved left ventricular performance assessed by Tissue Doppler Imaging.

Carbohydrate antigen-125: additional accuracy in identifying patients at risk of acute heart failure in acute coronary syndrome.

OBJECTIVES: To evaluate levels of carbohydrate antigen-125 (CA-125) in patients with acute coronary syndrome (ACS), with regard to incidence of acute heart failure (AHF) and levels of brain natriuretic peptide (BNP). METHODS: In 47 consecutive patients with ACS, circulating levels of CA-125 and BNP were ascertained in the first 24 h and after 3 days of hospitalization. Left ventricular function and in-hospital incidence of AHF were also evaluated. RESULTS: BNP and CA-125 levels were significantly higher in patients with pulmonary oedema (PO) (564.25+/-500.50 vs. 258.57+/-284.81 pg/ml, P<0.05; 51.78+/-54.71 vs. 13.78+/-12.01 UI/ml, P<0.001) proportionally to Killip class (r=0.44, r=0.47; P<0.01) and were related to LV end-diastolic dimension (r=0.47, P<0.01; r=0.66, P<0.001) and LV ejection fraction (r=-0.63, P<0.001; r=-0.37, P<0.01). CA-125 levels identified patients with PO with higher specificity (97.1 vs. 31.4%), positive predictive value (83.3 vs. 33.3%) and accuracy (83.0 vs. 48.9%) when compared with BNP. CONCLUSION: CA-125 levels are increased in patients with ACS and systolic dysfunction or AHF. Patients with PO are better identified by combined BNP and CA-125 assay rather than by only BNP.

Statin therapy blunts inflammatory activation and improves prognosis and left ventricular performance assessed by Tissue Doppler Imaging in subjects with chronic ischemic heart failure: results from the Daunia Heart Failure Registry

BACKGROUND: A limited number of studies have used Tissue Doppler Imaging (TDI) to evaluate the effect of statin therapy on left ventricular dysfunction in patients with chronic heart failure. In this work, we aimed to determine whether statin administration influenced prognosis, inflammatory activation and myocardial performance evaluated by Tissue Doppler Imaging in subjects enrolled in the Daunia Heart Failure Registry, a local registry of patients with chronic heart failure. METHODS: This study retrospectively analyzed 353 consecutive outpatients with chronic heart failure (mean follow-up 384 days), based on whether statin therapy was used. In all patients, several Tissue Doppler Imaging parameters were measured; circulating levels of interleukin (IL)-6, IL-10 and C-reactive protein were also assayed. RESULTS: Statin administration in 128 subjects with ischemic heart disease was associated with a lower incidence of adverse events (rehospitalization for HF 15 percent vs. 46 percent, p<0.001; ventricular arrhythmias 5 percent vs. 21 percent, p<0.01; cardiac death 1 percent vs. 8 percent, p<0.05), lower circulating levels of IL-6 (p<0.05) and IL-10 (p<0.01), lower rates of chronic heart failure (p<0.001) and better Tissue Doppler Imaging performance (E/E' ratio 12.82 + 5.42 vs. 19.85 + 9.14, p<0.001; ET: 260.62+ 44.16 vs. 227.11 +37.58 ms, p<0.05; TP: 176.79 + 49.93 vs. 136.7 + 37.78 ms, p<0.05 and St: 352.35 + 43.17 vs. 310.67 + 66.46 + 37.78 ms, p<0.05). CONCLUSIONS: Chronic ischemic heart failure outpatients undergoing statin treatment had fewer readmissions for adverse events, blunted inflammatory activation and improved left ventricular performance assessed by Tissue Doppler Imaging.