Mariano Pego

MicroRNA-424(322) as a new marker of disease progression in pulmonary arterial hypertension and its role in right ventricular hypertrophy by targeting SMURF1.

Aims MicroRNAs (miRNAs) have been implicated in the pathogenesis of pulmonary hypertension (PH), a multifactorial and progressive condition associated with an increased afterload of the right ventricle leading to heart failure and death. The main aim of this study was to correlate the levels of miR-424(322) with the severity and prognosis of PH and with right ventricle hypertrophy progression. Additionally, we intended to evaluate the mechanisms and signalling pathways whereby miR-424(322) secreted by pulmonary arterial endothelial cells (PAECs) impacts cardiomyocytes. Methods and results Using quantitative real-time PCR, we showed that the levels of circulating miR-424(322) are higher in PH patients when compared with healthy subjects. Moreover, we found that miR-424(322) levels correlated with more severe symptoms and haemodynamics. In the subgroup of Eisenmenger syndrome patients, miR-424(322) displayed independent prognostic value. Furthermore, we demonstrated that miR-424(322) targets SMURF1, through which it sustains bone morphogenetic protein receptor 2 signalling. Moreover, we showed that hypoxia induces the secretion of miR-424(322) by PAECs, which after being taken up by cardiomyocytes leads to down-regulation of SMURF1. In the monocrotaline rat model of PH, we found an association between circulating miR-424(322) levels and the stage of right ventricle hypertrophy, as well as an inverse correlation between miR-424(322) and SMURF1 levels in the hypertrophied right ventricle. Conclusions This study shows that miR-424(322) has diagnostic and prognostic value in PH patients, correlating with markers of disease severity. Additionally, miR-424(322) can target proteins with a direct effect on heart function, suggesting that this miRNA can act as a messenger linking pulmonary vascular disease and right ventricle hypertrophy.

Renal artery aneurysm: An endovascular treatment for a rare cause of hypertension

Renal artery aneurysms are a rare cause of secondary hypertension. Endovascular treatment with a polytetrafluoroethylene (PTFE)-coated stent can exclude aneurysms and treat hypertension. We report the case of a 23-year-old man with hypertension diagnosed three years earlier and in whom renal angiography revealed three aneurysms involving the right renal artery. A covered stent was implanted, resulting in successful exclusion of the aneurysm. Ten months after the procedure the patient is asymptomatic and with normal blood pressure without antihypertensive therapy.

Real-world, long-term survival of incident patients with pulmonary arterial hypertension

BACKGROUND Pulmonary arterial hypertension (PAH) is a progressive, fatal disease. Long-term outcomes data are scarce in Portugal. We aimed to estimate survival of newly diagnosed PAH at a Portuguese referral center in the modern management era. METHODS Between January 2009 and November 2015 all incident PAH cases were consecutively enrolled in a prospective cohort study. Sixty-five patients were followed up for a median of 3.1 [interquartile range 1.7-5.4] years. Kaplan-Meier survival analysis was used to estimate 1-, 3-, and 5-year survival and to compare it with a historical PAH survival estimated from the NIH cohort. RESULTS Mean age was 48±19 years with female preponderance (68%). The most common PAH subgroup was congenital heart disease (PAH-CHD) (n=31; 48%), followed by connective tissue disease (PAH-CTD) (n=16; 25%), idiopathic (IPAH) (n=8; 12%) and hereditary (HPAP) (n=1; 1.5%). BNP values (hazard ratio [HR] 2.07; 95%CI 1.34-3.22; P=0.001) and male gender [HR 4.34 (1.44-13.09); P=0.009] were predictors of death. Survival rates at 1-, 3- and 5-years were 95%, 77% and 71%. Survival was not statistically different between PAH etiologies (Log-rank P=0.7). However, PAH-CHD was associated with a decreased risk of the combined endpoint of all-cause mortality and admission for decompensated heart failure [HR 0.36 (0.15-0.85); P=0.02]. We found a non-significant numerically higher survival of incident IPAH, HPAH and DPAH patients in comparison with the historical NIH cohort. CONCLUSIONS In this cohort of incident PAH patients, PAH-CHD patients had better overall prognosis. Higher BNP values and male gender were associated with higher mortality.

Bioresorbable Scaffolds in Cardiac Allograft Vasculopathy—Searching for the Holy Grail

We read with great interest the article by Pighi et al. [1] that presented the Cardiac Allograft Reparative Therapy (CART) study, a prospective multicenter clinical trial to evaluate the performance of the AbsorbTM bioresorbable scaffold (BVS) for treating cardiac allograft vasculopathy (CAV). Determining the best approach to treating CAV—the leading cause of death after heart transplantation—is a serious, yet unmet, need [2]. Introducing BVS into treatment might produce a paradigm shift in focal CAV management. A platform that provides transient arterial support, delivers an antiproliferative drug, and can avoid chronic local inflammatory reactions due to a permanent Bmetallic cage^ is a potentially revolutionary approach to focal CAV. The Absorb BVS is the most studied platform [3]. It is composed of a fully bioresorbable polymeric scaffold with a coating that elutes everolimus, which is an immunosuppressive agent that reduces the incidence and progression of CAV [2]. In our institution, we recently performed routine coronary angiography on a 69-year-old man, who had undergone heart transplantation 3 years earlier. The angiography revealed intermediate stenosis in the mid-segment of the left anterior descending artery (LAD). To assess the physiological impact of the epicardial disease, an invasive LAD coronary flow study was performed and revealed a fractional flow reserve (FFR) of 0.78. Optical coherence tomography (OCT) showed focused concentric intimal hyperplasia (Fig. 1a). After lesion preparation, an Absorb BVS (2.50 × 23 mm) was implanted at the mid-LAD. The post-implant OCT evaluation revealed well-apposed and expanded scaffolds (Fig. 1b). The patient was discharged with dual antiplatelet therapy and optimized immunosuppression treatment. Eleven months later, routine coronary angiography and OCT revealed significant BVS restenosis (Fig. 1c). Revascularization was successfully performed with a paclitaxel-coated balloon (2.50 × 20 mm). What can be said about the role of BVS in the management of CAV? In the presence of focal intimal thickening leading to significant luminal obstruction and a drop in flow reserve, PCI is the intuitive solution, despite the lack of evidence for a survival advantage. BVS appears to be particularly appealing in this setting, providing anatomical and functional vascular restoration with a reduced inflammatory reaction. The feasibility of BVS implantation for treatment of CAV has been demonstrated in some case reports [4], with excellent angiographic results at 6-month [5] and 1-year [6] follow-up. However, our case strengthens the possibility that the restenosis rate might be a major drawback to the use of BVS. Before the promising widespread use of BVS in CAV management becomes a reality, we believe that further investigation is necessary. Therefore, the randomized CART study [1] will be crucial in determining the safety and efficacy of BVS therapy in the cardiac transplant population. Associate Editor Emanuele Barbato oversaw the review of this article

Rest myocardial perfusion imaging: a valuable tool in ED

BACKGROUND Acute chest pain is a frequent cause of emergency department (ED) visits. Rest myocardial perfusion imaging (RMPI) during or immediately after an episode of chest pain can provide diagnostic and prognostic information concerning acute coronary syndromes. AIM Our purpose was to evaluate the RMPI score in risk stratification of chest pain suspected to be of cardiac ischemic origin and negative troponin assessment. METHODS Ninety-six patients without an ongoing myocardial infarction or a history of coronary artery disease and in whom RMPI was performed in the ED because of chest pain suspected to be related with acute myocardial ischemia were included. Follow-up was performed considering the occurrence of death, myocardial infarction, or revascularization in a 12-month period admission. RESULTS Fourteen (14.6%) patients had events. According to survival analysis, the variables related with events were a history of angina (hazard ratio [HR], 4.5; P ≤ .01), an ischemic electrocardiogram (HR, 4.0; P ≤ .01), the abnormal RMPI (HR, 11.4; P ≤ .05), and the RMPI score (HR, 1.1; P ≤ .0001). When the variables of interest were forced into a multivariate model, the χ(2) associated with the model that includes clinical and electrocardiogram information was 16.3 (P ≤ .005) and in the model that also includes RMPI score, it was 23.0 (P ≤ .0005). CONCLUSION In a low- to intermediate-risk group of patients with suspected acute myocardial ischemia, RMPI gives not only diagnostic information but adds prognostic value to the traditional ED risk stratification tools.

A multicentre, 12-week study of imidapril and candesartan cilexetil in patients with mild to moderate hypertension using ambulatory blood pressure monitoring.

AbstractBackground: Twenty-four-hour ambulatory blood pressure monitoring (ABPM) provides the most accurate efficacy assessment of an antihypertensive agent throughout a 24-hour dosing interval. The objective of this prospective, randomised, double-blind, parallel-group, multicentre study was to compare the antihypertensive efficacy of imidapril versus candesartan cilexetil using ABPM. Methods: After screening and a single-blind, placebo run-in phase, ambulatory adult patients with mild to moderate hypertension (defined as a mean office sitting diastolic BP [DBP] and systolic BP [SBP], respectively, of 90–109mm Hg and 140–179mm Hg, and a mean ABPM DBP and SBP, respectively, of ≥80mm Hg and ≥125mm Hg) were randomised to once-daily treatment with imidapril or candesartan cilexetil for 12 weeks. ABPM was performed at baseline and at the end of the 12-week treatment period in 112 patients (imidapril group, n = 55; candesartan cilexetil group, n = 57). To achieve the target BP of ≤140/90mm Hg, imidapril was titrated from 5 mg/day to 20 mg/day and candesartan cilexetil was titrated from 4 mg/day to 16 mg/day. Results: Significant (p < 0.001) and similar decreases from baseline in clinic mean DBP and SBP, in mean 24-hour ABPM, DBP and SBP awake and asleep, and in mean BP (MBP) were observed in both treatment groups. In addition, significant and similar reductions in DBP and SBP were observed during the early morning acceleration period in both treatments. The reduction in BP load was higher with imidapril than with candesartan cilexetil: 44.6% versus 34.5% reduction in DBP load and 38.0% versus 32.9% reduction in SBP load, respectively. With respect to the average deviation index expressing a load index, the reduction with imidapril was 41.0% versus 33.6% with candesartan cilexetil. The percentage of DBP dipper patients remained identical before and after treatment in both groups. With regard to SBP, the percentage of dippers increased from 38.2% to 45.5% in the imidapril group and decreased from 54.4% to 42.1% in the candesartan cilexetil group. The incidence of adverse events was similar between the treatment groups and no cases of dry cough were reported. Conclusion: Imidapril in once-daily doses of up to 20mg was shown to be at least as effective as candesartan cilexetil given in once-daily doses of up to 16mg in reducing BP throughout the entire 24-hour dosing interval. Both drugs were well tolerated.

An Alternative Method to Calculate Simplified Projected Aortic Valve Area at Normal Flow Rate

Background Simplified projected aortic valve area (EOAproj) is a valuable echocardiographic parameter in the evaluation of low flow low gradient aortic stenosis (LFLG AS). Its widespread use in clinical practice is hampered by the laborious process of flow rate (Q) calculation. Objetive This study proposes a less burdensome, alternative method of Q calculation to be incorporated in the original formula of EOAproj and measures the agreement between the new proposed method of EOAproj calculation and the original one. Methods Retrospective observational single-institution study that included all consecutive patients with classic LFLG AS that showed a Q variation with dobutamine infusion ≥ |15|% by both calculation methods. Results Twenty-two consecutive patients with classical LFLG AS who underwent dobutamine stress echocardiography were included. Nine patients showed a Q variation with dobutamine infusion calculated by both classical and alternative methods ≥ |15|% and were selected for further statistical analysis. Using the Bland-Altman method to assess agreement we found a systematic bias of 0,037 cm2 (95% CI 0,004 - 0,066), meaning that on average the new method overestimates the EOAproj in 0,037 cm2 compared to the original method. The 95% limits of agreement are narrow (from -0,04 cm2 to 0,12 cm2), meaning that for 95% of individuals, EOAproj calculated by the new method would be between 0,04 cm2 less to 0,12 cm2 more than the EOAproj calculated by the original equation. Conclusion The bias and 95% limits of agreement of the new method are narrow and not clinically relevant, supporting the potential interchangeability of the two methods of EOAproj calculation. As the new method requires less additional measurements, it would be easier to implement in clinical practice, promoting an increase in the use of EOAproj.

Acute pneumopericardium: when echocardiography is not enough

A 46-year-old female with metastasized rectal adenocarcinoma complained of progressive exertional dyspnea. The physical exam was remarkable for low blood pressure (98/54 mmHg) and tachycardia (115 bpm). A severe pericardium effusion with right chambers’ collapse was identified, and the patient was submitted to echocardiography-guided pericardiocentesis by a subxiphoid approach, employing a handheld ultrasound device, with fluoroscopy available. The puncture was undertaken uneventfully, with prompt drainage of serous fluid (500 cc) through a 6Fr pigtail catheter paralleled by pericardial effusion reduction on echo. However, it was impossible to obtain an ultrasound window to visualize the heart at the end of the procedure. Diagnosis: Immediate fluoroscopy showed a pneumopericardium (image and video 1), which explained the imaging finding on transthoracic ultrasound. The air was instantly drained with a 50-cc syringe (video 2). The patient remained asymptomatic and the discharge chest radiography was normal. Pneumopericardium is a rare complication of pericardiocentesis, and we hypothesize that it was due to air leakage to the pericardial drainage system (1). Conservative management is reasonable in hemodinamically stable patients (2); however, we proceeded to aspiration as the catheter was in position. Fluoroscopy was crucial for this clinically inapparent diagnosis.

Pulse pressure can predict mortality in advanced heart failure

INTRODUCTION Pulse pressure (PP) is the difference between systolic and diastolic blood pressure (BP). PP rises markedly after the fifth decade of life. High PP is a risk factor for the development of coronary heart disease and heart failure. The aim of this study was to assess whether PP can be used as a prognostic marker in advanced heart failure. METHODS We retrospectively studied patients in NYHA class III-IV who were hospitalized in a single heart failure unit between January 2003 and August 2012. Demographic characteristics, laboratory tests, and cardiovascular risk factors were recorded. PP was calculated as the difference between systolic and diastolic BP at admission, and the patients were divided into two groups (group 1: PP >40 mmHg and group 2: PP ≤40 mmHg). Median follow-up was 666 ± 50 days for the occurrence of cardiovascular death and heart transplantation. RESULTS During follow-up 914 patients in NYHA class III-IV were hospitalized, 520 in group 1 and 394 in group 2. The most important difference between the groups was in left ventricular dysfunction, which was greater in patients with lower PP. On Kaplan-Meier analysis, group 2 had higher mortality (38 vs. 24 patients, log-rank p=0.002). CONCLUSIONS PP is easily calculated, and enables prediction of cardiovascular death in patients with advanced heart failure.

Heart transplant coronary artery disease: Multimodality approach in percutaneous intervention

Coronary artery disease is the most important cause of late morbidity and mortality after heart transplantation. It is usually an immunologic phenomenon termed cardiac allograft vasculopathy, but can also be the result of donor-transmitted atherosclerosis. Routine surveillance by coronary angiography should be complemented by intracoronary imaging, in order to determine the nature of the coronary lesions, and also by assessment of their functional significance to guide the decision whether to perform percutaneous coronary intervention. We report a case of coronary angiography at five-year follow-up after transplantation, using optical coherence tomography and fractional flow reserve to assess and optimize treatment of coronary disease in this challenging population.