Left Ventricular Diastolic Pressure Research Articles

Crocin treatment prevents doxorubicin-induced cardiotoxicity in rats

Doxorubicin (DOX)-induced cardiotoxicity is well-known as a serious complication of chemotherapy in patients with cancer. It is unknown whether crocin (CRO), main component of Crocus sativus L. (Saffron), could reduce the severity of DOX-induced cardiotoxicity. Therefore, this study was undertaken to assess the protective impact of CRO on DOX-induced cardiotoxicity in rats. The rats were divided into four groups: control, DOX (2mg/kg/48h, for 12days), and CRO groups that receiving DOX as in group 2 and CRO (20 and 40mg/kg/24h, for 20days) starting 4days prior to first DOX injection and throughout the study. Echocardiographic, electrocardiographic and hemodynamic studies, along with histopathological examination and MTT test were carried out. Our findings demonstrate that DOX resulted in cardiotoxicity manifested by decreased the left ventricular (LV) systolic and diastolic pressures, rate of rise/drop of LV pressure, ejection fraction, fractional shortening and contractility index, as compared to control group. In addition, histopathological analysis of heart confirmed adverse structural changes in myocardial cells following DOX administration. The results also showed that CRO treatment significantly improved DOX-induced heart damage, structural changes in the myocardium and ventricular function. In addition, CRO did not affect the in vitro antitumor activity of DOX. Taken together, our data confirm that CRO is protective against cardiovascular-related disorders produced by DOX, and clinical studies are needed to examine these findings in human.

The novel in vitro reanimation of isolated human and large mammalian heart-lung blocs.

BackgroundIn vitro isolated heart preparations are valuable tools for the study of cardiac anatomy and physiology, as well as for preclinical device testing. Such preparations afford investigators a high level of hemodynamic control, independent of host or systemic interactions. Here we hypothesize that recovered human and swine heart-lung blocs can be reanimated using a clear perfusate and elicit viable cardiodynamic and pulmonic function. Further, this approach will facilitate multimodal imaging, which is particularly valuable for the study of both functional anatomy and device-tissue interactions. Five human and 18 swine heart-lung preparations were procured using techniques analogous to those for cardiac transplant. Specimens were then rewarmed and reperfused using modifications of a closed circuit, isolated, beating and ventilated heart-lung preparation. Positive pressure mechanical ventilation was also employed, and epicardial defibrillation was applied to elicit native cardiac sinus rhythm. Videoscopy, fluoroscopy, ultrasound, and infrared imaging were performed for anatomical and experimental study.ResultsSystolic and diastolic left ventricular pressures observed for human and swine specimens were 68/2 ± 11/7 and 74/3 ± 17/5 mmHg, respectively, with associated native heart rates of 80 ± 7 and 96 ± 16 beats per minute. High-resolution imaging within functioning human pulmonary vasculature was obtained among other anatomies of interest. Note that one human specimen elicited poor cardiac performance post defibrillation.ConclusionsWe report the first dynamic videoscopic images of the pulmonary vasculature during viable cardiopulmonary function in isolated reanimated heart-lung blocs. This experimental approach provides unique in vitro opportunities for the study of novel medical therapeutics applied to large mammalian, including human, heart-lung specimens.Electronic supplementary materialThe online version of this article (doi:10.1186/s12899-016-0023-2) contains supplementary material, which is available to authorized users.

Cardiac rehabilitation program in patients with Chagas heart failure: a single-arm pilot study.

The benefit of a cardiac rehabilitation (CR) program for patients with Chagas heart failure (CHF) remains unclear. Therefore, we aimed to investigate the effects of CR for CHF patients. A single-arm pilot study, including 12 patients with CHF, was performed. Patients participated in an 8-month physical exercise intervention, comprising aerobic, strength, and stretching exercises (3 times per week, 60 minutes per session). Nutritional and pharmaceutical counseling were also performed. Functional capacity (cardiopulmonary exercise test), muscle respiratory strength (manovacuometry), and body composition (anthropometry and skinfolds) were evaluated at baseline, and after 4 and 8 months of intervention. Cardiac function (echocardiography), biomarkers (lipid profile, glucose, and glycated hemoglobin) and quality of life (Minnesota Living with Heart Failure Questionnaire) were assessed at baseline and at the end of the intervention. Seven of 12 patients included in the study completed the 8-month follow-up period. Only 2 moderate adverse events occurred during the exercise training. Functional capacity improved after 4 months of CR, while left ventricular ejection fraction (LVEF) and respiratory strength improved after 8 months. Patients with right ventricular (RV) dysfunction at baseline exhibited an improvement in functional capacity after 4 months, and improvements in left ventricular (LV) diastolic pressure, respiratory strength, and quality of life at the end of follow-up. Conversely, those with normal baseline RV function demonstrated LVEF increases that were not observed in patients with RV dysfunction. CR was feasible, safe, and has important clinical benefits for patients with CHF, specifically for cardiac function and muscle respiratory strength.

Elevated ventricular wall stress disrupts cardiomyocyte t-tubule structure and calcium homeostasis.

AimsInvaginations of the cellular membrane called t-tubules are essential for maintaining efficient excitation–contraction coupling in ventricular cardiomyocytes. Disruption of t-tubule structure during heart failure has been linked to dyssynchronous, slowed Ca2+ release and reduced power of the heartbeat. The underlying mechanism is, however, unknown. We presently investigated whether elevated ventricular wall stress triggers remodelling of t-tubule structure and function.Methods and resultsMRI and blood pressure measurements were employed to examine regional wall stress across the left ventricle of sham-operated and failing, post-infarction rat hearts. In failing hearts, elevated left ventricular diastolic pressure and ventricular dilation resulted in markedly increased wall stress, particularly in the thin-walled region proximal to the infarct. High wall stress in this proximal zone was associated with reduced expression of the dyadic anchor junctophilin-2 and disrupted cardiomyocyte t-tubular structure. Indeed, local wall stress measurements predicted t-tubule density across sham and failing hearts. Elevated wall stress and disrupted cardiomyocyte structure in the proximal zone were also associated with desynchronized Ca2+ release in cardiomyocytes and markedly reduced local contractility in vivo. A causative role of wall stress in promoting t-tubule remodelling was established by applying stretch to papillary muscles ex vivo under culture conditions. Loads comparable to wall stress levels observed in vivo in the proximal zone reduced expression of junctophilin-2 and promoted t-tubule loss.ConclusionElevated wall stress reduces junctophilin-2 expression and disrupts t-tubule integrity, Ca2+ release, and contractile function. These findings provide new insight into the role of wall stress in promoting heart failure progression.

A polymorphism in the norepinephrine transporter gene is associated with affective and cardiovascular disease through a microRNA mechanism.

Norepinephrine released from sympathetic nerves is removed from the neuroeffector junction via the action of the norepinephrine transporter (NET). NET impairment is evident in several clinically important conditions including major depressive disorder (MDD), panic disorder (PD), essential hypertension and the postural orthostatic tachycardia syndrome (POTS). We aimed to determine whether a single nucleotide polymorphism (SNP) in the 3' untranslated region (UTR) of the NET gene is associated with NET impairment and to elucidate the mechanisms involved. The analyses were carried out in two cohorts of European ancestry, which included healthy controls and MDD, PD, hypertensive and POTS patients. Compared with controls, cases had significantly higher prevalence of the T allele of rs7194256 (C/T), arterial norepinephrine, depression and anxiety scores, larger left ventricular mass index, higher systolic and diastolic blood pressures, and heart rate. Bioinformatic analysis identified that the microRNA miR-19a-3p could bind preferentially to the sequence created by the presence of the T allele. This was supported by results of luciferase assays. Compared with controls, cases had significantly lower circulating miR-19a-3p, which was associated with pathways related to blood pressure and regulation of neurotransmission. In vitro norepinephrine downregulated miR-19a-3p. In conclusion, the T allele of the rs7194256 SNP in the 3'UTR of the NET gene is more prevalent in diseases where NET impairment is evident. This might be explained by the creation of a binding site for the microRNA miR-19a-3p. A defect in NET function may potentiate the sympathetic neurochemical signal, predisposing individuals with affective diseases to increased risk of cardiovascular disease development.

Acute effects of nandrolone decanoate on cardiodynamic parameters in isolated rat heart.

Despite worldwide use of anabolic steroids in last decades, there is still contradictory information about their acute influence on myocardium. The aim of this study was to examine the acute effects of nandrolone decanoate (ND) on cardiodynamics and coronary flow in isolated rat heart. The hearts of male Wistar albino rats (n = 48, 12 per group, age 8 weeks, body mass 180-200 g) were excised and perfused according to the Langendorff technique at gradually increased coronary perfusion pressures (40-120 cmH2O). After the control sets of experiments, the hearts in different groups were perfused with different doses of ND (1, 10, or 100 μmol/L separately). Using a sensor placed in the left ventricle, we registered maximum and minimum rate of pressure development in the left ventricle (dP/dtmax and dP/dtmin), systolic and diastolic left ventricular pressure (SLVP and DLVP), and heart rate (HR). Coronary flow (CF) was measured flowmetrically. The results clearly show the depression in cardiac function caused by higher doses of ND. The highest concentration of ND (100 μmol/L) induced the most deleterious impact on the myocardial function and perfusion of the heart (coronary circulation), which could be of clinical significance.

Protective effects of naringenin in cardiorenal syndrome

BackgroundCardiorenal syndrome is a complicated and bidirectional interrelationship between the heart and kidneys. Naringenin (NG) is a naturally occurring flavonoid possessing various biological and pharmacological properties. Materials and methodsWe tested whether NG could improve cardiac and renal function in a rat model of cardiorenal syndrome. ResultsThe results showed that NG-attenuated cardiac remodeling and cardiac dysfunction in rats with cardiorenal syndrome, as evidenced by decrease of left ventricle weight (LVW), increase of body weight (BW), decrease of LVW/BW, decrease of concentrations of serum creatinine, blood urea nitrogen, type-B natriuretic peptide, aldosterone, angiotensin (Ang) II, C-reactive protein, and urine protein, increase of left ventricular systolic pressure and falling rates of left ventricular pressure (dp/dtmax), and decrease of left ventricular diastolic pressure, left ventricular end-diastolic pressure, and −dp/dtmax. NG significantly inhibited the increase of lipid profiles including low-density lipoprotein, TC, and TG in rats. In addition, NG significantly inhibited the increase of cardiac expression of IL-1β, IL-6, and interferon γ. Moreover, NG decreased malonaldehyde level, increased superoxide dismutase activity and glutathione content in rats, and increased the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and catalytic subunit of γ-glutamylcysteine ligase (GCLc) in rats and Ang II-treated cardiac fibroblasts. Inhibition of Nrf2 and glutathione synthesis significantly suppressed NG-induced decrease of ROS level. Inhibition of Nrf2 markedly suppressed NG-induced increase of GCLc expression in Ang II-treated cardiac fibroblasts. ConclusionsThe data provide novel options for therapy of patients and new insights into the cardioprotective effects of NG in cardiorenal syndrome.

Cardioprotective Effect of Phenytoin on Doxorubicin-induced Cardiac Toxicity in a Rat Model.

Doxorubicin (DOX) is an effective anticancer agent, but adverse cardiotoxic effects limit its use. Compounds reducing DOX cardiotoxicity could improve its therapeutic index. This study investigated the protective effects of phenytoin (Phen) for DOX-induced cardiomyopathy. Male Wistar rats were randomized into 5 groups to receive either saline, DOX (2 mg/kg per 48 hours, 6 doses, intraperitoneally) or DOX + Phen (5, 10, or 20 mg/kg/d, starting 4 days before DOX, intraperitoneally). The animals were assessed 24 hours after the last injection. Left ventricular (LV) function and hemodynamic parameters were assessed using transthoracic echocardiography, electrocardiography, and a Millar pressure catheter. Histopathological studies were performed, and the effect of Phen on the cytotoxicity of DOX was evaluated in vitro for the human breast adenocarcinoma cell line. DOX-impaired LV function significantly decreased the LV systolic and diastolic pressures, rate of rise/decrease of LV pressure, ejection fraction, fractional shortening, and contractility index. DOX caused structural changes in myocardial cells. Treatment with Phen decreased DOX-induced toxicity, significantly improved ventricular function, and ameliorated structural changes in the myocardium. Phen also did not interfere with the antitumor effect of DOX. The results confirm the cardioprotective effect of Phen against DOX-induced cardiomyopathy without removing antitumor effect of DOX.

A Moderate Carnitine Deficiency Exacerbates Isoproterenol-Induced Myocardial Injury in Rats.

The myocardium is largely dependent upon oxidation of fatty acids for the production of ATP. Cardiac contractile abnormalities and failure have been reported after acute emotional stress and there is evidence that catecholamines are responsible for acute stress-induced heart injury. We hypothesized that carnitine deficiency increases the risk of stress-induced heart injury. Carnitine deficiency was induced in Wistar rats by adding 20mmol/L of sodium pivalate to drinking water (P). Controls (C) received equimolar sodium bicarbonate and a third group (P+Cn) received pivalate along with 40mmol/L carnitine. After 15days, 6 rats/group were used to evaluate function of isolated hearts under infusion of 0.1μM isoproterenol and 20 rats/group were submitted to a single subcutaneous administration of 50mg/kg isoproterenol. Isoproterenol infusion in C markedly increased the heart rate, left ventricular (LV) systolic pressure and coronary flow rate. In P rats, isoproterenol increased the heart rate and LV systolic pressure but these increases were not paralleled by a rise in the coronary flow rate and LV diastolic pressure progressively increased. Subcutaneous isoproterenol induced 15% mortality rate in C and 50% in P (p<0.05). Hearts of surviving P rats examined 15days later appeared clearly dilated, presented a marked impairment of LV function and a greater increase in tumor necrosis factor α (TNFα) levels. All these detrimental effects were negligible in P+Cn rats. Our study suggests that carnitine deficiency exposes the heart to a greater risk of injury when sympathetic nerve activity is greatly stimulated, for example during emotional, mental or physical stress.

Incidence of chronic heart failure with preserved left ventricular ejection fraction in patients with hypertension and isolated mild diastolic dysfunction

Heart failure (HF) with preserved ejection fraction (HFPEF) is still a challenge in clinical practice. The prognosis of patients with HFPEF is similar to or only slightly better than that of patients with HF with reduced ejection fraction (HFREF). Impaired relaxation is the mildest form of diastolic dysfunction, which should not be accompanied by symptoms of HFPEF. The aim of the study was to assess the incidence of chronic HFPEF in patients with hypertension and isolated mild diastolic dysfunction. It was a cross-sectional study including 210 patients (mean age, 56.11 ±6.24 years; women, 58%) with isolated abnormalities of left ventricular relaxation and arterial hypertension. In addition, we identified patients with type 2 diabetes to compare the incidence of HFPEF between patients with and without diabetes. HFPEF was diagnosed when clinical symptoms of HF were present simultaneously with echocardiographic markers of elevated left ventricular diastolic pressure, pulmonary congestion on chest X-ray, or elevated serum brain natriuretic peptide (BNP) levels. HFPEF was diagnosed in 42% of the patients with impaired relaxation. An elevated left atrial volume index (>34 ml/m²) was observed in 38% of the patients; E/e' ratio exceeding 8, in 37%; elevated BNP levels, in 39%; and pulmonary congestion on chest X-ray, in 41%. Independent predictors of HFPEF were age, systolic blood pressure of 140 mmHg or higher, type 2 diabetes, coronary artery disease, and an estimated glomerular filtration rate of less than 60 ml/min/1.73 m². In diabetic patients, a positive correlation was found between an insulin dose (>80 units/day) and BNP levels. Patients with isolated relaxation abnormalities constitute a clinically heterogeneous group because some of these individuals present with symptoms of HFPEF and a simultaneous increase in BNP levels. Therefore, the question of whether diastolic dysfunction is mild should be readdressed, and it should be emphasized that these patients have a serious prognosis with the risk of HF. In diabetic patients, a positive correlation between high insulin doses and BNP levels requires further research.

Cardiosphere-Derived Cells Reverse Heart Failure With Preserved Ejection Fraction in Rats by Decreasing Fibrosis and Inflammation

SummaryThe pathogenesis of heart failure with a preserved ejection fraction (HFpEF) is unclear. Myocardial fibrosis, inflammation, and cardiac hypertrophy have been suggested to contribute to the pathogenesis of HFpEF. Cardiosphere-derived cells (CDCs) are heart-derived cell products with antifibrotic and anti-inflammatory properties. This study tested whether rat CDCs were sufficient to decrease manifestations of HFpEF in hypertensive rats. Starting at 7 weeks of age, Dahl salt-sensitive rats were fed a high-salt diet for 6 to 7 weeks and randomized to receive intracoronary CDCs or placebo. Dahl rats fed normal chow served as controls. High-salt rats developed hypertension, left ventricular (LV) hypertrophy, and diastolic dysfunction, without impairment of ejection fraction. Four weeks after treatment, diastolic dysfunction resolved in CDC-treated rats but not in placebo. The improved LV relaxation was associated with lower LV end-diastolic pressure, decreased lung congestion, and enhanced survival in CDC-treated rats. Histology and echocardiography revealed no decrease in cardiac hypertrophy after CDC treatment, consistent with the finding of sustained, equally-elevated blood pressure in CDC- and placebo-treated rats. Nevertheless, CDC treatment decreased LV fibrosis and inflammatory infiltrates. Serum inflammatory cytokines were likewise decreased after CDC treatment. Whole-transcriptome analysis revealed that CDCs reversed changes in numerous transcripts associated with HFpEF, including many involved in inflammation and/or fibrosis. These studies suggest that CDCs normalized LV relaxation and LV diastolic pressure while improving survival in a rat model of HFpEF. The benefits of CDCs occurred despite persistent hypertension and cardiac hypertrophy. By selectively reversing inflammation and fibrosis, CDCs may be beneficial in the treatment of HFpEF.

0282: Rest and exercise pulmonary hypertension in hypertrophic cardiomyopathy

Heart failure (HF) symptoms, related to pulmonary capillary hypertension, are frequent in hypertrophic cardiomyopathy (HCM). Pulmonary hypertension (PH) is the consequence of left ventricular (LV) diastolic pressure elevation and/or functional mitral regurgitation. We aimed to evaluate determinants and prognostic significance of rest and exercise in HCM. We included 235 patients referred for clinical work-up of HCM. Rest pulmonary artery systolic pressure (PASP) was measurable in 214 (91%) patients (48±16 years, 161 males). A symptom-limited semi-supine bicycle exercise was carried out in 188 patients. PASP was measurable during exercise in 108 patients (57%). Resting PH (≥36mmHg) was present in 56 patients (26.2%) and exercise PH (≥60mmHg) in 38 patients (35.2%). Mutivariate correlates of rest PASP were sinus rhythm (β=–0.15, P=0.021), LV obstruction tract (LVOT) peak gradient (β=0.22, P=0.001) and left atrial volume (β=0.39, P<0.0001). Multivariate resting correlates of exercise PASP were PASP (β=0.28, p=0.001) and mitral regurgitation (MR) grade (β=0.48, P<0.0001). LVOT peak gradient emerged as an independent correlate of exercise PASP when MR was excluded. Patients with rest PH had a worse event-free survival at 4 years (24.8±8.8 vs 66.2±5.2%, P<0.0001), survival without HF (55.6±10.5 vs 81.8±4.3%, P=0.005), and overall survival (84.2±7.1 vs 97.1±1.7%, P=0.001). Patients with exercise PH had also a worse event-free survival (47.7±9.5 vs 65.7±7.5%, P=0.007) and a worse survival without HF (64.1±9.4 vs 83.4±5.5%, P=0.016). By contrast, there was no difference regarding overall survival (p=0.49). In patients with HCM, the main determinants of rest PH are sinus rhythm, LVOT peak gradient and left atrium volume. Determinants of exercise PH are rest PASP, grade of MR and rest LVOT gradient. Rest and exercise PH predict a poor outcome in HCM.

Noninvasive model including right ventricular speckle tracking for the evaluation of pulmonary hypertension.

To find parameters from transthorathic echocardiography (TTE) including speckle-tracking (ST) analysis of the right ventricle (RV) to identify precapillary pulmonary hypertension (PH). Forty-four patients with suspected PH undergoing right heart catheterization (RHC) were consecutively included (mean age 63.1 ± 14 years, 61% male gender). All patients underwent standardized TTE including ST analysis of the RV. Based on the subsequent TTE-derived measurements, the presence of PH was assessed: Left ventricular ejection fraction (LVEF) was calculated by Simpsons rule from 4Ch. Systolic pulmonary artery pressure (sPAP) was assessed with continuous wave Doppler of systolic tricuspid regurgitant velocity and regarded raised with values ≥ 30 mmHg as a surrogate parameter for RA pressure. A concomitantly elevated PCWP was considered a means to discriminate between the precapillary and postcapillary form of PH. PCWP was considered elevated when the E/e' ratio was > 12 as a surrogate for LV diastolic pressure. E/e' ratio was measured by gauging systolic and diastolic velocities of the lateral and septal mitral valve annulus using TDI mode. The results were then averaged with conventional measurement of mitral valve inflow. Furthermore, functional testing with six minutes walking distance (6MWD), ECG-RV stress signs, NT pro-BNP and other laboratory values were assessed. PH was confirmed in 34 patients (precapillary PH, n = 15, postcapillary PH, n = 19). TTE showed significant differences in E/e' ratio (precapillary PH: 12.3 ± 4.4, postcapillary PH: 17.3 ± 10.3, no PH: 12.1 ± 4.5, P = 0.02), LV volumes (ESV: 25.0 ± 15.0 mL, 49.9 ± 29.5 mL, 32.2 ± 13.6 mL, P = 0.027; EDV: 73.6 ± 24.0 mL, 110.6 ± 31.8 mL, 87.8 ± 33.0 mL, P = 0.021) and systolic pulmonary arterial pressure (sPAP: 61.2 ± 22.3 mmHg, 53.6 ± 20.1 mmHg, 31.2 ± 24.6 mmHg, P = 0.001). STRV analysis showed significant differences for apical RV longitudinal strain (RVAS: -7.5% ± 5.6%, -13.3% ± 4.3%, -14.3% ± 6.3%, P = 0.03). NT pro-BNP was higher in patients with postcapillary PH (4677.0 ± 7764.1 pg/mL, precapillary PH: 1980.3 ± 3432.1 pg/mL, no PH: 367.5 ± 420.4 pg/mL, P = 0.03). Patients with precapillary PH presented significantly more often with ECG RV-stress signs (P = 0.001). Receiver operating characteristics curve analyses displayed the most significant area under the curve (AUC) for RVAS (cut-off < -6.5%, AUC 0.91, P < 0.001), sPAP (cut-off > 33 mmHg, AUC 0.86, P < 0.001) and ECG RV stress signs (AUC 0.83, P < 0.001). The combination of these parameters had a sensitivity of 82.8% and a specificity of 17.2% to detect precapillary PH. The combination of non-invasive measurements allows feasible assessment of PH and seems beneficial for the differentiation between the pre- and postcapillary form of this disease.

Ascites as a Manifestation of Constrictive Pericarditis

In the United States, ascites is most often due to portal hypertension related to liver cirrhosis. We describe a case of constrictive pericarditis presenting with abnormal liver function tests, anasarca, and ascites. A 50-year-old Caucasian man presented with anasarca. Two years prior to presentation, he experienced dyspnea, lower extremity swelling extending to the scrotum, and a 40 pound weight gain. One year later, he started developing ascites. On physical exam, he was found to have jugular venous distention, marked hepatomegaly, dullness in flanks, and anasarca. Laboratory tests revealed mildly elevated alkaline phosphatase, INR, and indirect bilirubin. Workup for chronic liver disease was unrevealing and ultrasound of the liver showed ascites and hepatosplenomegaly without evidence of cirrhosis, portal vein, or hepatic vein thrombosis. Paracentesis revealed an elevated serum-ascites albumin gradient (SAAG) and increased total protein in the ascites fluid. Computed tomography of the chest showed pericardial thickening and moderate ascites. A right heart catheterization showed a positive Kussmaul sign with markedly elevated and equal filling pressures in the heart consistent with constrictive pericarditis. The patient subsequently underwent a full pericardial resection with resolution of his symptoms and normalization of his liver tests. A cardiac cause of ascites can be easily mistaken for primary hepatic cirrhosis when a patient presents with ascites, elevated liver function tests, and peripheral edema. A SAAG of greater than or equal to 1.1 g/dL and an ascites fluid total protein level of greater than 2.5 g/dL suggest constrictive pericarditis. In cirrhosis, the SAAG is much greater than 1.1 g/dL while the ascites fluid total protein level is less than 2.5 g/dL. A right heart catheterization showing elevation and equalization of the right atrial pressure, pulmonary capillary wedge pressure, mean pulmonary arterial pressure, right ventricular diastolic pressure, and left ventricular diastolic pressure can support the diagnosis of constrictive pericarditis. In cases of constrictive pericarditis, diagnosis and treatment in a timely manner is important, as most patients have resolution of symptoms with pericardiectomy.Figure 1

Influence of central apneas and chemoreflex activation on pulmonary artery pressure in chronic heart failure

BackgroundPulmonary artery hypertension (PH), associated with increased left ventricular (LV) diastolic pressure and pulmonary vasoconstriction, is frequently observed in heart failure (HF), where it holds prognostic significance. We hypothesized that Cheyne–Stokes respiration (CSR) may contribute to increased pulmonary arterartery pressure (PAP) and right ventricular (RV) remodeling in HF, via hypoxia/hypercapnia cycles and adrenergic activation by the chemoreflex stimulation. MethodsSeventy-two HF patients(57 males, aged 65.1 SD 12.3years, LV ejection fraction <50%, 33.2 SD 7.5%), on guideline recommended pharmacological/device treatment underwent thorough clinical, echocardiographic and neurohormonal assessment, 24-hour cardiorespiratory screening for arrhythmias and CSR, and chemoreflex test for hypoxic (HVR) and hypercapnic (HCVR) ventilatory responses. ResultsTwenty patients (28%) showed significant CSR (24-hour apnea–hypopnea index, AHI≥15). Patients with CSR presented with: a) higher systolic pulmonary artery pressure (sPAP: 42.8 standard deviation—SD 10.1 vs 32.3 SD 5.7mmHg, p<0.001), despite similar LV systolic and diastolic function; b) indexes of right chamber remodeling (all p<0.05); c) enhanced HVR (median 0.78, interquartile range—IR 0.46–1.22 vs 0.42, IR 0.18–0.67L/min/%, p=0.01) and HCVR (1.17, IR 0.97–1.29 vs 0.72, IR 0.47–0.93L/min/mmHg, p=0.02); d) increased plasma norepinephrine levels (690, IR 477–868 vs 366, IR 226–508ng/L, p<0.001). Univariate predictors of sPAP>35mmHg were AHI, HVR, HCVR; only AHI maintained its predictive value at multivariate analysis (p=0.017). ConclusionsCSR may contribute to increased pulmonary artery pressure and right chamber remodeling in HF, independently of the severity of LV systolic and diastolic dysfunction, likely via recurrent hypoxia/hypercapnia cycles and chemoreflex mediated adrenergic discharge.

Atrial fibrillation may be a hidden factor for the development of cognitive impairment in patients with heart failure.

To the editor We read the article entitled ‘Cognitive impairment in heart failure patients’ by Leto, et al. [1] with great interest. In this review, they demonstrated pathophysiological determinants of cognitive impairment in heart failure (HF) population. HF prevalence is increasing in the general population throughout the world. As HF is a complex clinical entity, underlying mechanisms with HF and cognitive impairment are mixed and intertwined. HF is a well known risk factor for dementia and functional brain abnormalities. Co-morbidities such as hypertension and diabetes are main reasons for the association between HF and cognitive impairment as well as decreased cerebral perfusion due to systolic dysfunction. Medications in HF populations also play a role in development of cognitive impairment through side effects on cerebral perfusion. [2] In the present review, the authors pointed out important variables that can be related with HF and cognitive impairment such as left ventricular ejection fraction, systolic and diastolic blood pressure, NYHA functional class and B-type natriuretic peptide. However, atrial fibrillation (AF) which is a most prevalent arrhythmia in general population has also shown to be related to cognitive decline. [3] Furthermore, due to the silent attacks, undiagnosed episodes of paroxysmal AF have been frequently encountered in this subjects. The incidence of AF was increased in the elderly patients. The prevalence of AF was found to be 9% in individuals > 80 years of age and 0.1% in subjects < 55 years of age. [4] These data are derived from the trials in which the diagnosis was based on a 12-lead electrocardiogram obtained during an office visit. According to the duration of the episodes, AF is classified into 3 types: paroxysmal AF, persistent AF, and permanent AF. While the other types of AF can be easily diagnosed with routine 12-lead ECG, paroxysmal AF may be overlooked. In order to determine attacks of paroxysmal AF, ambulatory monitoring is required. Therefore, it is presumed that the real-world prevalence of AF is higher than those determined in the trials. The cognitive impairment due to AF in elderly patients is both related with micro-emboli and a decline in cerebral perfusion. It seems that AF may exacerbate HF and subsequent cerebral blood flow reduction. Independently from its type, AF increases the risk of thromboembolism five times. [4] CHADS-VASc scoring system has been using in patients with AF in order to quantify the risk for thromboembolism. According to this scoring system, existence of congestive heart failure, hypertension, age 65 to 74 years, age ≥ 75 years (doubled risk), diabetes mellitus, prior stroke or transient ischemic attack or thromboembolism (doubled risk), vascular disease and female gender are risk factors for thromboembolic stroke in patients with AF. [5] It has been particularly indicated in this scoring system that the embolic risk of the elderly people with AF is as high as the patients with prior stroke. With the aging population in our modern world, it is obvious to be an incremental rise in the prevalence of AF. Furthermore, it is important to shed light on the relationship between cognitive impairment and AF as a main problem in patients with HF, so that preventative efforts will lead way to reduce the burden of cognitive impairment in HF patients. Therefore, in a review addressing cognitive impairment in HF population, we believe that discussing AF might be useful for researchers dealing with this group of patients.

197 Left Atrial Remodelling and Atrioventricular Coupling in a Canine Model of Early Heart Failure with Preserved Ejection Fraction

Background Left atrial (LA) compliance and contractility are key determinants of left ventricular (LV) stroke volume. LA remodelling and dysfunction in heart failure with preserved ejection fraction (HFpEF) are considered to be late presenting features, secondary to hypertension-induced LV diastolic dysfunction and chronic LA pressure overload. However, a recent unifying hypothesis has stipulated that systemic and coronary microvascular inflammation drive HFpEF pathophysiology. Considering this paradigm, we hypothesised that diminished LA compliance and contractile function occur early during HFpEF development and further impair cardiac performance. Methods Cardiac magnetic resonance imaging, echocardiography, invasive LV and LA pressure volume (PV) analysis and tissue analysis were performed in an experimental model of early-stage HFpEF (elderly dogs with renal wrap induced hypertension and exogenous aldosterone; n = 9) and young control dogs (sham surgery; n = 13). Results Early HFpEF was associated with LA enlargement, LA myocyte hypertrophy, and enhanced LA contractile function (LA active emptying fraction 18 ± 6 vs 12 ± 2%, p = 0.03; LA end-systolic PV relationship slope: 2.7 ± 0.9 HFpEF vs 1.5 ± 0.6 mmHg/mL controls, p = 0.01). However left atrioventricular systolic coupling was impaired (ratio of LV to LA end-systolic PV relationship slope 1.3 ± 0.4 HFpEF vs 0.8 ± 0.4 Controls, p 2 , p = 0.07) and inversely correlated with LA s (r=-0.66, p = 0.006). Titin isoform composition (N2BA/N2B ratio) was similar between groups, but titin hyperphosphorylation was seen in HFpEF LA and LV tissue. LA titin hyperphosphorylation correlated with LA s (r = 0.54, p = 0.03). LA microvascular reactivity was also diminished in HFpEF versus controls. Conclusions Maladaptive LA remodelling is present in early-stage experimental HFpEF and compromises overall cardiac performance. Reduced LA compliance in HFpEF may relate to contributions from LA ischaemia and titin-based cardiomyocyte stiffening. Thus, pathophysiological mechanisms involved in the development of HFpEF directly affect both atrial and ventricular myocardium.

Congenital heart disease in the older adult: a scientific statement from the American Heart Association.

The population of adults with congenital heart disease (ACHD) has increased dramatically over the past few decades, with many people who are now middle-aged and some in the geriatric age range. This improved longevity is leading to increased use of the medical system for both routine and episodic care, and caregivers need to be prepared to diagnose, follow up, and treat the older adult with congenital heart disease (CHD). The predictable natural progression of CHD entities and sequelae of previous interventions must now be treated in the setting of late complications, acquired cardiac disease, multiorgan effects of lifelong processes, and the unrelenting process of aging. Despite the advances in this field, death rates in the population from 20 to >70 years of age may be twice to 7 times higher for the ACHD population than for their peers.1 This American Heart Association (AHA) scientific statement will focus on the older adult (>40 years old) with CHD. It is meant to be complementary to the 2008 American College of Cardiology (ACC)/AHA guidelines for ACHD and orient the reader to the natural history, ramifications of childhood repair, and late initial diagnosis of CHD in the older adult. This population with CHD is unique and distinct from both the pediatric and young adult populations with CHD. Much of the information we provide is from scientific research combined with clinical experience from longitudinal care. We emphasize that this is the beginning of a discussion regarding this rapidly growing population, and continued research aimed at the progression of disease and complications reviewed here is necessary to advance the field of ACHD with the scientific rigor it deserves. ACHD encompass a broad range of presentations. There are people who are diagnosed for the first time in adulthood, as well as those with prior palliative repair …

Protective effect of proanthocyanidins against myocardial damage induced by mechanical trauma in rats

Objective To evaluate the effect of proanthocyanidins on cardiocyte apoptosis and cardiac dysfunction following mechanical trauma (MT) in rats and discuss its mechanism. Methods A total of 120 SD rats were allocated to normal group, trauma group, and trauma solvent group (treated with proanthocyanidins) and trauma vehicle group (treated with saline solution) according to the random number table, with 30 rats per group. Small animal quantitative wound instrument was used to prepare the MT model in rats. Cardiocyte apoptosis was measured by TUNEL staining. Changes in left ventricular diastolic pressure were recorded by left ventricular intubation via the right common carotid artery. Reactive oxygen species (ROS) produced by H9c2 cells before and after proanthocyanidins administration was detected with flow cytometry. Level of Ca2+ in cardiocytes marked by Fluo-4AM was determined with laser scanning confocal microscope. Ultrastructure changes in cardiocytes were observed under electronic microscope. Results After the induction of MT, apoptosis index of cardiocytes in trauma group, trauma solvent group and trauma vehicle group was (7.96±1.16)%, (2.44±0.70)%, and (7.76±1.14)% respectively, far higher than (0.64±0.59)% in normal group (P 0.05) but substantial reduction was detected in trauma solvent group (P<0.05). The + dp/dtmax of cardiac function in trauma and trauma vehicle groups was (3294.55±180.95)mmHg/s and (3337.80±220.11)mmHg/s respectively lowered from (4030.04±293.70) mmHg/s in normal group (P<0.01), and was (3926.72±364.95)mmHg/s in trauma solvent group lowered in contrast with trauma group (P<0.05). The -dp/dtmax in trauma and trauma vehicle groups was (2294.55±298.69)mmHg/s and (2291.20±348.72)mmHg/s respectively lowered significantly from (2830.04±334.63) mmHg/s in normal group (P<0.05), and was (2801.52±266.25)mmHg/s increased significantly in contrast with trauma group (P<0.05). Compared with normal group, trauma group showed chromatin margination and condensation as well as marked vacuolization in the epithelium from intramuscular capillaries. However, the pathological changes were improved after proanthocyanidins therapy. Conclusion Proanthocyanidins is effective in heart protection after the mechanical trauma by attenuating the pathological changes of myocardial ultrastructure and myocardial apoptosis and improving cardiac function. Key words: Proanthocyanidins; Heart injuries; Oxidative stress

0045 : Rest and exercise pulmonary hypertension in hypertrophic cardiomyopathy

Heart failure (HF) symptoms, related to pulmonary capillary hypertension, are frequent in hypertrophic cardiomyopathy (HCM). Pulmonary hypertension (PH) is the consequence of left ventricular (LV) diastolic pressure elevation and/or functional mitral regurgitation. We aimed to evaluate determinants and prognostic significance of rest and exercise PH in HCM. We included 235 patients referred for clinical work-up of HCM. Rest pulmonary artery systolic pressure (PASP) was measurable in 214 (91%) patients (48±16 years, 161 males). A symptom-limited semi-supine bicycle exercise was carried out in 188 patients. PASP was measurable during exercise in 108 patients (57%). Resting PH (≥36mm Hg) was present in 56 patients (26.2%) and exercise PH (≥60mm Hg) in 38 patients (35.2%). Mutivariate correlates of rest PASP were sinus rhythm (β= –0.15, P=0.021), LV obstruction tract (LVOT) peak gradient (β= 0.22, P=0.001) and left atrial volume (β= 0.39, P<0.0001). Multivariate resting correlates of exercise PASP were PASP (β=0.28, p=0.001) and mitral regurgitation (MR) grade (β=0.48, P<0.0001). LVOT peak gradient emerged as an independent correlate of exercise PASP when MR was excluded. Patients with rest PH had a worse event-free survival at 4 years (24.8 ± 8.8 vs 66.2 ± 5.2%, P < 0.0001), survival without HF (55.6 ± 10.5 vs 81.8 ± 4.3%, P = 0.005), and overall survival (84.2 ± 7.1 vs 97.1 ± 1.7%, P = 0.001). Patients with exercise PH had also a worse event-free survival (47.7 ± 9.5 vs 65.7 ± 7.5%, P = 0.007) and a worse survival without HF (64.1 ± 9.4 vs 83.4 ± 5.5%, P = 0.016). By contrast, there was no difference regarding overall survival (p = 0.49). In patients with HCM, the main determinants of rest PH are sinus rhythm, LVOT peak gradient and left atrium volume. Determinants of exercise PH are rest PASP, grade of MR and rest LVOT gradient. Rest and exercise PH predict a poor outcome in HCM.