Background Right ventricular dysfunction (RVD) is associated with poor cardiovascular outcome. The renin–angiotensin–aldosterone system is involved in alterations of the left ventricular geometry and function. Detrimental effects of the renin–angiotensin–aldosterone system on the right ventricular function are being postulated, but data supporting this assumption are still lacking. The aim of the study was to assess the impact of hyperreninemia, hyperaldosteronism or their combination on right ventricular function in hypertensive individuals. Methods Plasma renin activity (PRA) and plasma aldosterone concentrations (PACs) were measured in 116 hypertensive patients, divided as follows: normal PRA and PAC (n = 38); high PRA and normal PAC (hypereninemia) (n = 26); normal PRA and high PAC (hyperaldosternism) (n = 27); high PRA and PAC (HRA) (n = 25). Echocardiographic evaluation of the left and right ventricles (RV), including tissue Doppler imaging, was performed. RVD was identified by tissue Doppler Imaging-derived Myocardial Performance Index, calculated with a multisegmental approach. Results Indices of the right ventricular structure and function, as well as the prevalence of RVD, were higher in hyperreninemia and hyperaldosternism groups as compared with the normal group, and a further increase was observed in the HRA patients. Regression models showed a similar risk of RVD in the hyperreninemia and hyperaldosternism patients, regardless of systemic and pulmonary pressure, as well as left ventricular dysfunction. Notably, patients with both hyperreninemia and hyperaldosternism exhibited the strongest association with RVD as compared with patients with only hyperreninemia or hyperaldosternism. Conclusions Isolated hyperreninemia or hyperaldosternism determines a similar impairment of the right ventricular function, whereas their combination is further detrimental. Renin and aldosterone may represent early biomarkers of right ventricular dysfunction in hypertension.

Objectives: An increased dispersion of myocardial repolarization represents one of the mechanisms underlying the arrhythmic risk in hypertrophic cardiomyopathy (HCM). We investigated spatial myocardial repolarization dispersion indices in HCM patients with nonsustained ventricular tachycardia (NSVT) and, contextually, their main clinical determinants. Methods: Fifty-two well-matched HCM outpatients were categorized into two groups according to the presence or the absence of NSVT at 24-hour Holter electrocardiogram (ECG) monitoring. Each patient underwent a clinical examination, including Doppler echocardiogram integrated with tissue Doppler imaging, cardiac magnetic resonance, and 12-lead surface ECG to calculate the dispersion for the following intervals: QRS, Q-Tend (QTe), Q-Tpeak, Tpeak-Tend (TpTe), J-Tpeak, and J-Tend. Results: The NSVT group showed only QTe dispersion and TpTe dispersion values to be significantly higher than their counterparts. NSVT occurrence was independently predicted by late gadolinium enhancement presence (p = 0.021) and QTe Bazett dispersion (p = 0.030), the latter strongly associated with the myocardial performance index (MPI) obtained at the basal segment of the interventricular septum (p = 0.0004). Conclusion: Our data support QTe dispersion as an easy and noninvasive tool for identifying HCM patients with NSVT propensity. The strong relationship between QTe dispersion and MPI allows us to hypothesize an intriguing link between electrical instability and confined myocardial areas of systodiastolic dysfunction.

BACKGROUND Growing evidence suggests that late gadolinium enhancement (LGE) at cardiac magnetic resonance (CMR) is an additive marker of disease severity, and possibly of arrhythmic risk, in hypertrophic cardiomyopathy (HCM). We investigated the possible relationship between LGE and markers of myocardial repolarization dispersion in HCM. METHODS AND RESULTS Eighty-five HCM outpatients underwent CMR and short-period electrocardiogram analysis to calculate the temporal myocardial repolarization dispersion through the QT variance normalized for QT mean (QTVN) and the QT variability index (QTVI). The QT dispersion in the spatial domain was also obtained. Patients with LGE (62%) had higher left atrial volume, maximum wall thickness, and left ventricular mass (P<0.0001), as well as a greater prevalence of non-sustained ventricular tachycardia (P<0.0001) and hypotensive blood pressure response (P=0.044). Both QTVN and QTVI were higher in the group with LGE (P<0.0001). At multivariate analysis, using QTVI as the dependent variable, %LGE (P<0.0001), age (P<0.0001), left ventricular outflow obstruction (P=0.038), and sudden cardiac death risk factor burden (P=0.020) reached statistical significance. Otherwise, only %LGE (P=0.005) and left ventricular mass index (P=0.015) remained associated with QTVN. CONCLUSIONS Temporal myocardial repolarization dispersion correlates with LGE extent. Whether these variables could be useful in HCM clinical management warrants confirmation by larger prospective studies.

Background: Right ventricular dysfunction (RVD) is a major predictor of cardiovascular mortality. Inadequate suppression of the reninangiotensin-aldosterone system (RAAS) after postural manoeuvres favours alterations of left ventricular (LV) function. The effects of RAAS dysregulation on RV performance remain elusive. The present study investigated RV function in hypertensive patients with or without altered RAAS activation.Methods: Plasma renin activity (PRA) and plasma aldosterone concentration (PAC) were measured in 104 newly diagnosed hypertensive patients after both supine and upright positioning to assess dynamic changes of RAAS induced by antigravitational stress. Twenty-four-hour ambulatory blood pressure monitoring and echocardiographic evaluation of the right ventricle including tissue Doppler imaging (TDI) were performed. Patients were divided as follows: (1) normal PRA and PAC (N group [n = 58]), (2) suppressible RAAS after supine positioning (SR group [n = 24]), and (3), nonsuppressible RAAS (NSR group [n = 22]). RVD was identified by the TDI-derived myocardial performance index (MPI) calculated with a multisegmental approach.Results: Patients in the NSR group had reduced indices of RV function compared with patients in the N and SR groups. MPI of the right ventricle as well as prevalence of RVD were also significantly higher in the NSR group. Regression models showed that inadequate RAAS suppression was independently associated with RVD, regardless of blood pressure values and LV dysfunction (LVD).Conclusions: Patients without supine normalization of RAAS display a significant impairment of RV function. Our findings suggest that a dynamic RAAS evaluation may help to identify hypertensive patients at higher risk of RVD.

Metabolic syndrome (MetS) and type 2 diabetes (T2DM) have been associated with an impairment of left (LV) and right ventricular (RV) function as well as an increased risk of heart failure (HF). However, it remains unclear whether these clinical entities or their associations promote a similar derangement of biventricular function. Overall, 345 patients without overt cardiovascular disease consecutively underwent routine blood chemistry including high-sensitivity C reactive protein (hs-CRP) and echocardiographical examination with conventional and tissue Doppler imaging (TDI) of both ventricles. According to the ATP III criteria and fasting glucose levels, the study population was stratified into four groups: (1) healthy controls (n=120); (2) MetS without T2DM (n=84); (3) T2DM without MetS (n=49); and (4) MetS+T2DM (n=92). The Myocardial performance index (MPI) of the RV and LV was obtained with a multi-segmental approach using TDI. Patients with MetS and T2DM exhibited a similar impairment of biventricular function compared with healthy controls, whereas a further decline was observed in patients having both MetS and T2DM. In addition to MetS markers, hs-CRP exhibited the strongest association with the MPI of both ventricles. Regression analyses indicated that individual MetS markers were inferior to MetS in identifying subtle cardiac dysfunction. Independent associations of MetS and T2DM with biventricular dysfunction were comparable, and the coexistence of MetS and T2DM exhibited the highest risk for biventricular dysfunction. Our findings emphasize the importance of MetS as an equivalent of T2DM and support a synergic effect of these clinical conditions on cardiac organ damage requiring more aggressive therapeutic strategies to prevent HF.

AIMS:Occurrence of heart failure during dialysis treatment is associated with high mortality. However, mechanisms underlying left ventricular dysfunction (LVD) in these patients are still elusive. In patients undergoing haemodialysis, arteriovenous fistula (AVF) is associated with right ventricular dysfunction (RVD) and a further impairment is observed when AVF is brachial rather than radial. However, it is not known whether AVF-induced RVD is associated with an impaired left ventricular function. We studied the relation between right and left ventricular function in 120 patients undergoing either haemodialysis or peritoneal dialysis and 100 healthy age-matched controls. METHODS:Echocardiography including tissue Doppler imaging (TDI) was performed for both ventricles. Average myocardial performance index (MPI) of the right ventricle (RV MPI) was obtained with a multisegmental approach by using TDI. RESULTS:RVD was higher in haemodialysis than peritoneal dialysis patients and a further increase was observed in haemodialysis patients with brachial access. Interestingly, RV MPI inversely correlated with indices of both left ventricular contraction and relaxation and the association was even stronger in haemodialysis patients, particularly in those with brachial AVF. Of note, dialysis patients in the upper tertile of RV MPI showed the larger impairment of left ventricular function. Regression analyses showed that RV MPI was independently associated with reduced left ventricular function. By contrast, LVD did not significantly affect right ventricular performance in this setting. CONCLUSION:AVF-induced RVD may contribute to LVD in dialysis patients. AVF plays a pivotal role in triggering LVD via right-to-left ventricular interdependence.

Inadequate suppression of renin–angiotensin–aldosterone system (RAAS) following postural maneuvers may have detrimental effects on cardiac structure and function. In this study, we aimed to appraise the clinical significance of this phenomenon by assessing its relation with inappropriate ventricular mass (ILVM), an adverse phenotype of LV remodeling and dysfunction.

The well known atheroprotective effects of high density lipoprotein cholesterol (HDL) are based on reverse cholesterol transport as well as anti-inflammatory properties [1,2]. Primary prevention studies have confirmed that HDL levels are strongly associated with reduced cardiovascular events [3]. However, recent evidence supports the notion that HDL functionality may be impaired under certain conditions [4,5]. Ansell and colleagues reported that HDL isolated from subjects with coronary artery disease (CAD) had less antiinflammatory activity than HDL derived from healthy controls, thus providing the first evidence that HDL may be dysfunctional in this setting [6]. Interestingly, in CAD patients HDL has shown to be even proinflammatory, thus increasing monocyte chemiotaxis, reactive oxygen species production, endothelial dysfunction and cellular apoptosis [6,7]. Hence, HDL may not be protective in secondary prevention of coronary artery disease. This issue needs to be rapidly clarified since therapies that raise HDL levels are being investigated for the treatment of CAD patients [8,9]. In the present study we sought to determine whether higher HDL levels maintain their protective effects also in patients with CAD. From March 2006 to April 2009 we consecutively enrolled 184 patients with a first manifestation of CAD (mean age 62±10 years, male/female ratio 3:1). All patients taking lipid-lowering agents or other cardiovascular medications at admission were excluded from the study. Moreover, patients with relevant comorbidities (renal failure, COPD, infective or inflammatory diseases, autoimmune disorders, cancer) were also not considered. All subjects underwent coronary angiography and routine blood chemistry including high sensitivity C-reactive protein (hs-CRP) and lipid profile comprehensive of ApoB-100 and ApoA1 determination. The study was approved by our Institute Committee and all patients signed an informed consent. The study population was divided into groups with higher (N50 for women, N40 formen) and lower HDL levels (≤50 for women, ≤40 for men, Table 1), according to ATPIII criteria [10]. Groups did not significantly differ for demographic and antropometric characteristics as well as for the prevalence of cardiovascular risk factors and left ventricular ejection fraction (EF). Serum creatinine, fasting plasma glucose, uric acid and Pro-BNP were similar in the two groups. HDL and ApoA1 were significantly different but the groups did not differ with regard to LDL and ApoB-100 levels (Table 1). Patients with high HDL had significantly lower triglycerides and hs-CRP values (Table 1). Notably, statin treatment and dose were similar between the two groups (Table 2). Cardiovascular end-points were assessed by clinic visits and programmed phone contacts up to 3 years after the first admission. Determinations of lipid fractions were performed both at baseline and follow-up. No significant changes in HDL levels were observed during follow-up either in patients with high or low HDL (Fig. 1A,B). Major adverse cardiovascular events (MACE) consisted of: (1) mortality for all causes; (2) myocardial infarction (MI); (3) revascularization by percutaneous coronary intervention or by-pass surgery; (4) cerebrovascular events including transient ischemic attack and stroke. Data analysis was performed with SPSS 13.0 software package (SPSS Inc., Chicago). Numerical data are reported as

Congestive heart failure is perhaps the most pervasive complication of patients with end-stage renal disease (ESRD), largely exceeding the incidence of acute coronary syndromes [ 1 Mc Cullough P.A. Li S. Jurkovitz C.T. et al. KEEP investigators: chronic kidney disease, prevalence of premature cardiovascular disease, and relationship to short-term mortality. Am Heart J. 2008; 156: 277-283 Abstract Full Text Full Text PDF PubMed Scopus (155) Google Scholar , 2 Trespalacios F.C. Taylor A.J. Agodoa L.Y. Bakris G.L. Abbott K.C. Heart failure as a cause for hospitalization in chronic dialysis patients. Am J Kidney Dis. 2003; 41: 1267-1277 Abstract Full Text Full Text PDF PubMed Scopus (128) Google Scholar ]. Notably, patients complaining new signs and symptoms of heart failure following dialysis treatment display a marked increase in mortality [ [3] Robert N. Foley: clinical epidemiology of cardiac disease in dialysis patients: left ventricular hypertrophy, ischemic heart disease, and cardiac failure. Semin Dial. 2003; 16: 111-117 PubMed Google Scholar ]. Unfortunately, factors precipitating cardiac function during dialysis have not been clearly identified. This leads to significant delays in either diagnosing or preventing the occurrence of biventricular dysfunction and, hence, heart failure in ESRD patients undergoing chronic dialysis. Indeed, a plenty of factors may concur to impair cardiac function in ESRD patients [ [2] Trespalacios F.C. Taylor A.J. Agodoa L.Y. Bakris G.L. Abbott K.C. Heart failure as a cause for hospitalization in chronic dialysis patients. Am J Kidney Dis. 2003; 41: 1267-1277 Abstract Full Text Full Text PDF PubMed Scopus (128) Google Scholar ]. These are mostly represented by traditional risk factors, namely age, gender, hypertension, diabetes, dyslipidemia and “non-traditional” ones, such as uremia, volume overload, anemia, abnormal calcium/phosphate balance and systemic inflammation. Moreover, new evidence supports the concept that dialysis treatment “per se” may impair cardiac function [ [4] Stern A.B. Klemmer P.J. High-output heart failure secondary to arteriovenous fistula. Hemodial Int. 2011; https://doi.org/10.1111/j.1542-4758.2010.00518.x Crossref PubMed Scopus (57) Google Scholar ]. In this regard, the arteriovenous fistula (AVF) in patients undergoing hemodialysis (HD) has been recently associated with an increased risk of pulmonary hypertension, a condition reported as a predictor of mortality in this population [ 5 Yigla M. Fruchter O. Aharonson D. et al. Pulmonary hypertension is an independent predictor of mortality in hemodialysis patients. Kidney Int. 2009; 75: 969-975 Crossref PubMed Scopus (119) Google Scholar , 6 Yigla M. Nakhoul F. Sabag A. et al. Pulmonary hypertension in patients with end-stage renal disease. Chest. 2003; 123: 1577-1582 Crossref PubMed Scopus (242) Google Scholar , 7 Beigi A.A. Sadeghi A.M. Khosravi A.R. Karami M. Masoudpour H. Effects of the arteriovenous fistula on pulmonary artery pressure and cardiac output in patients with chronic renal failure. J Vasc Access. 2009; 10: 160-166 PubMed Google Scholar , 8 Bozbas S.S. Akcay S. Altin C. et al. Pulmonary hypertension in patients with end-stage renal disease undergoing renal transplantation. Transplant Proc. 2009; 41: 2753-2756 Abstract Full Text Full Text PDF PubMed Scopus (54) Google Scholar ]. Indeed, AVF accounts for a prevalence of pulmonary hypertension ranging from 17 to 60% in dialysis patients [ 5 Yigla M. Fruchter O. Aharonson D. et al. Pulmonary hypertension is an independent predictor of mortality in hemodialysis patients. Kidney Int. 2009; 75: 969-975 Crossref PubMed Scopus (119) Google Scholar , 6 Yigla M. Nakhoul F. Sabag A. et al. Pulmonary hypertension in patients with end-stage renal disease. Chest. 2003; 123: 1577-1582 Crossref PubMed Scopus (242) Google Scholar , 7 Beigi A.A. Sadeghi A.M. Khosravi A.R. Karami M. Masoudpour H. Effects of the arteriovenous fistula on pulmonary artery pressure and cardiac output in patients with chronic renal failure. J Vasc Access. 2009; 10: 160-166 PubMed Google Scholar , 8 Bozbas S.S. Akcay S. Altin C. et al. Pulmonary hypertension in patients with end-stage renal disease undergoing renal transplantation. Transplant Proc. 2009; 41: 2753-2756 Abstract Full Text Full Text PDF PubMed Scopus (54) Google Scholar ]. The leading mechanism underlying pulmonary hypertension in this setting is represented by the volume/pressure overload imposed by the shunt which increases right ventricular (RV) output and pulmonary pressures [ 2 Trespalacios F.C. Taylor A.J. Agodoa L.Y. Bakris G.L. Abbott K.C. Heart failure as a cause for hospitalization in chronic dialysis patients. Am J Kidney Dis. 2003; 41: 1267-1277 Abstract Full Text Full Text PDF PubMed Scopus (128) Google Scholar , 4 Stern A.B. Klemmer P.J. High-output heart failure secondary to arteriovenous fistula. Hemodial Int. 2011; https://doi.org/10.1111/j.1542-4758.2010.00518.x Crossref PubMed Scopus (57) Google Scholar ].

In patients with end-stage renal disease (ESRD) heart failure is the leading cause of cardiovascular death [ 1 Zoccali C. Left ventricular systolic dysfunction: a sudden killer in end-stage renal disease patients. Hypertension. 2010; 56: 187-188 Crossref PubMed Scopus (19) Google Scholar , 2 Trespalacios F.C. Taylor A.J. Agodoa L.Y. Bakris G.L. Abbott K.C. Heart failure as a cause for hospitalization in chronic dialysis patients. Am J Kidney Dis. 2003; 41: 1267-1277 Abstract Full Text Full Text PDF PubMed Scopus (128) Google Scholar ]. However, mechanisms underlying left ventricular (LV) dysfunction in this population still remain scarcely characterized. Recently, it has been reported that in patients with renal dysfunction left ventricular mass (LVM) exceeds compensatory values for individual cardiac load and this finding has been described as inappropriate LVM (ILVM) [ 3 Nardi E. Palermo A. Mulè G. Cusimano P. Cottone S. Cerasola G. Left ventricular hypertrophy and geometry in hypertensive patients with chronic kidney disease. J Hypertens. 2009; 27: 633-641 Crossref PubMed Scopus (95) Google Scholar , 4 Palmieri V. de Simone G. Roman M.J. Schwartz J.E. Pickering T.G. Devereux R.B. Ambulatory blood pressure and metabolic abnormalities in hypertensive subjects with inappropriately high left ventricular mass. Hypertension. 1999; 34: 1032-1040 Crossref PubMed Scopus (84) Google Scholar ]. ILVM has generated a considerable interest over the last few years since it has shown to predict systolic dysfunction and cardiovascular mortality [ [5] de Simone G. Verdecchia P. Pede S. Gorini M. Maggioni A.P. Prognosis of inappropriate left ventricular mass in hypertension: the MAVI study. Hypertension. 2002; 40: 470-476 Crossref PubMed Scopus (144) Google Scholar ]. Excessive LVM has been attributed to an increase in body size, adverse metabolic profile or to the presence of myocardial fibrosis as a consequence of different stimuli such as inflammation or hormonal changes [ 6 Celentano A. Pietropaolo I. Palmieri V. et al. Inappropriate left ventricular mass and angiotensin converting enzyme gene polymorphism. J Hum Hypertens. 2001; 15: 811-813 Crossref PubMed Scopus (10) Google Scholar , 7 Muiesan M.L. Salvetti M. Paini A. et al. Inappropriate left ventricular mass in patients with primary aldosteronism. Hypertension. 2008; 52: 529-534 Crossref PubMed Scopus (104) Google Scholar , 8 López B. Castellano J.M. González A. Barba J. Díez J. Association of increased plasma cardiotrophin-1 with inappropriate left ventricular mass in essential hypertension. Hypertension. 2007; 50: 977-983 Crossref PubMed Scopus (37) Google Scholar ].

Pheochromocytoma is a neuroendocrine tumour of the adrenal gland that secretes an excessive amount of catecholamines, leading to a rapid rise and fall in blood pressure, headache, sweating and palpitations. The clinical scenario of pheochromocytoma, however, may be extremely variable and may include atypical cardiovascular manifestations, eventually leading to delays or mistakes in diagnosis. This issue is crucial since a missed diagnosis of pheochromocytoma may imply fatal consequences. This article reports a case of pheochromocytoma presenting with quite atypical cardiovascular manifestations such as transient left ventricular dysfunction and ventricular tachycardia. The pathophysiological determinants underlying uncommon clinical presentations of pheochromocytoma are also discussed.

BACKGROUND:While chronic dialysis treatment has been suggested to increase pulmonary pressure values, right ventricular dysfunction (RVD) is a major cause of death in patients with end-stage renal disease. We investigated the impact of different dialysis treatments on right ventricular function.METHODS:We examined 220 subjects grouped as follows: healthy controls (n = 100), peritoneal dialysis (PD; n = 26), hemodialysis (HD) with radial arteriovenous fistula (AVF; n = 62), and HD with brachial AVF (n = 32). Echocardiography including tissue Doppler imaging (TDI) of the right ventricle was performed in all patients.RESULTS:Pulmonary pressure values progressively rose from controls across the 3 dialysis groups (21.7 ± 6.8, 29.7 ± 6.7, 37.9 ± 6.7 and 40.8 ± 6.6 mm Hg, respectively; p < 0.001). TDI indices of right ventricular function were more impaired in HD patients, particularly in those with brachial AVF. RVD, assessed by TDI myocardial performance index, was higher in HD patients compared with PD patients (71.3 vs. 34.6%, p < 0.001). Moreover, the prevalence of RVD further increased in patients with brachial AVF compared with the radial access (90.6 vs. 61.3%, p < 0.001).CONCLUSIONS:Compared to DP, HD increases the risk of RVD, particularly in the presence of brachial AVF. TDI may detect early functional failure of the right ventricle in HD patients.