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We investigated changes in electrocardiographic spatial QRS and T vectors as markers of electrical remodeling before and after cardiac resynchronization therapy (CRT) and their association with altered outcome.In 41 patients with LBBB, ECGpost was recorded during intrinsic rhythm after interrupting CRT pacing and compared to the pre-implant ECGpre and the ECG during CRT (ECGCRT). Mean spatial angles between QRS and T vectors were determined with the Kors matrix conversion. Left ventricular ejection fraction (LVEF) was determined with nuclear isotope ventriculography before CRT implantation (LVEFpre) and at inclusion (LVEFpost). Following CRT, LVEF improved significantly from 26 ± 10 to 36 ± 14% (p=0.01). Duration of QRSpre (168 ± 15 ms) was not different from QRSpost (166 ± 15 ms). A smaller angle between QRSCRT and Tpost was related to a greater angle between Tpre and Tpost (Pearson's R -0.61 - p0.001). During follow-up (30 ± 2 months) 9 patients (22%) died. Univariate Cox regression revealed higher mortality in the patients with lower LVEFpost (HR 1.10, p=0.01), a larger angle QRSCRTTpost (HR 1.03, p=0.03), a smaller angle QRSpreQRSpost (HR 0.97, p=0.03) and smaller angle TpreTpost (HR 0.95, p0.01). After adjusting for LVEFpost, only smaller angle TpreTpost was associated with mortality (HR 0.96, p=0.03).Electrical remodeling can be quantified by measuring the angles between spatial QRS and T vectors before, during and after CRT. In absence of QRS duration changes, more extensive electrical remodeling is associated with a significantly better survival. QRS and T vector changes deserve further investigation to better understand the individual response to CRT.

Heart transplantation has become an established therapeutic option for selected patients with end-stage heart disease. However, until the advent of effective immunosuppression, allograft rejection has been the main challenge limiting survival in the early days after transplantation. Therapeutic success in cardiac transplantation evolved particularly with the introduction of the calcineurin inhibitors (CNIs), cyclosporin, and Tacrolimus (TAC) [1, 2]. Not only infection but also rejection rates declined sharply and contributed to the improvement in survival noted. Although rejection rates continue to decline, the risk of rejection remains significant particularly in the early period following transplantation, necessitating routine surveillance for both acute cellular and antibody-mediated rejection (AMR).

Although pericardial effusion is a well-known feature of Churg-Strauss syndrome, cardiac tamponade has rarely been encountered. The present report describes a case of Churg-Strauss syndrome that presented as an acute cholecystitis and was complicated by tamponade. Histopathological exam of both pericardium and gall bladder was conclusive for Churg-Strauss syndrome.

The mature, biologically active 32-amino acid long B-type natriuretic peptide (BNP1–32), is cleaved by corin from the BNP prohormone. Recent data demonstrated that BNP1–32 might be an ideal substrate for the endogenous aminopeptidase, dipeptidyl-peptidase (DPP) IV. DPP IV removes the two amino-terminal amino acids (Ser and Pro) from BNP1–32 to produce BNP3–32, which has been detected in plasma of patients with heart failure. In a canine model, intravenous BNP3–32 infusion resulted in less natriuresis, diuresis and vasodilation compared to intravenous infusion of BNP1–32. The clinical relevance of these observations may be important for patients with high plasma BNP concentrations, which can be measured by commercially available immunoassays. Further studies are needed to explore whether DPP IV inhibitors increase the bioavailability of BNP1–32, delay the progression of heart failure and increase the efficacy of exogenously administered BNP1–32 in decompensated heart failure.

B-type natriuretic peptide (BNP) has emerged as a reliable biomarker in patients with congestive heart failure. The mature, biologically active B-type natriuretic peptide, BNP(1-32), is cleaved by corin from the 108 amino acid proBNP. However, in vivo as well as in vitro data demonstrated that this BNP(1-32) might be an ideal substrate for the endogenous aminopeptidase, dipeptidyl-peptidase IV (DPP IV). DPP IV removes the two amino terminal amino acids (Ser Pro) from BNP(1-32) to produce BNP(3-32), which has been detected in plasma of patients with congestive heart failure. The biological effects of BNP(3-32) remain undetermined. In cultured human cardiomyocytes and fibroblasts, equimolar concentrations of BNP(1-32) and BNP(3-32) both exert similar biological effects, as evidenced by their cGMP (cyclic guanylate monophosphate) generating capacity. However, in a canine model, intravenous BNP(3-32) infusion resulted in less natriuresis, diuresis, and vasodilation compared to intravenous infusion of BNP(1-32). The clinical relevance of these observations might be important for patients in whom the plasma BNP concentrations, measured by commercially available immunoassays, are high. Further studies exploring whether DPP IV inhibitors increase the bioavailability of BNP(1-32), delay the progression of heart failure, and increase the efficacy of exogenous administration of BNP(1-32) in decompensated heart failure are needed.

Chronic kidney disease (CKD) is common after heart transplantation (HTx). This study assessed the influence of CKD on exercise capacity and ventilatory efficiency after HTx.This cross-sectional study included 79 HTx patients (age 64 +/- 10 years, 66 men) at 8.1 +/- 4.3 years post-HTx who underwent maximal exercise testing, cardiac function assessment, and blood analysis. According to estimated glomerular filtration rate (eGFR, ml/min/1.73 m(2)), patients were categorized as having severe (Group 1, GFRor = 30; n = 15), moderate (Group 2, GFR 30-60; n = 40), and mild (Group 3, GFR60; n = 24) renal impairment.Patients in Group 1 were older, had lower peakVO(2) and impaired ventilatory efficiency compared with Groups 2 and 3 (all p0.05) Peak Watts, peak ventilation, and peak heart rate were lower in Group 1 compared with Group 3 (all p0.05). Exercise-derived variables did not differ significantly between Groups 2 and 3. GFR correlated with peakVO(2)/kg (r = 0.47; p0.01) and peak Watts (r = 0.34, p0.01). GFR (adjusted r(2) = 0.34), mean arterial pulmonary pressure, and age were the strongest independent predictors of peakVO(2). The proposed model explained 48% of variability in peakVO(2). By receiver operator characteristic analysis, eGFR was superior in distinguishing patients with impaired from those with preserved exercise capacity (peakVO(2)18 vs18 ml/kg/min).Chronic KD after HTx is associated with impaired maximal exercise capacity and decreased ventilatory efficiency. GFR is a strong independent non-exercise-derived predictor of peak VO(2) in these patients.

Background: Cardiac resynchronization therapy (CRT) leads to better cardiopulmonary performance in congestive heart failure (CHF) patients (pts). Mechanisms underlying the benefits are not fully elucidated. Aim: To investigate factors and mechanisms associated with improved cardiopulmonary performance after CRT. Methods: Twenty-three pts (EF 26±7%, QRS complex 170±26 msec) were studied by simultaneous quantitative semi-supine exercise echocardiography and cardiopulmonary exercise testing before and 3 months after CRT. Pts with an increase (Δ) in peak VO 2 ≥1.1 ml/kg/min were considered clinical responderes. Effective regurgitant orifice (ERO) of the mitral regurgitation (MR) was assessed using the PISA method. Results: In the entire population, CRT was associated with a decrease in LV dyssynchrony from 53±2 to 23±9 msec (p2 (p2 increased from 11.6±2.3 to 12.9±3.6 ml/kg/min (p ), ERO at rest was similar but exercise-induced ERO and Nt-pro BNP were significantly lower in responders vs nonresponders. Change in peak VO 2 correlated inversely with the extent of exercise-induced MR at follow-up (r=−0.47, p Conclusions. Improved cardiopulmonary performance after CRT is related to changes in exercise-induced MR rather than resting MR. Thus, effects on the exercise-induced MR in parallel to reverse LV remodelling appear to contribute to improved cardiopulmonary performance and clinical benefits of the CRT.

We studied whether functional improvement after cardiac resynchronization therapy (CRT) is associated with reversal of the heart failure (HF) gene program.Cardiac resynchronization therapy improves exercise tolerance and survival in patients with advanced congestive HF and dyssynchrony.Twenty-four patients referred for CRT underwent left ventricular (LV) endomyocardial biopsies immediately before CRT implantation (baseline). In addition, 17 of them underwent LV endomyocardial biopsy procurement 4 months later (follow-up). In 6 control patients with normal LV function, LV biopsies were obtained at the time of coronary artery bypass grafting. The LV messenger ribonucleic acid (mRNA) levels of contractile and calcium regulatory genes were measured by quantitative real time polymerase chain reaction and normalized for glyceraldehyde 3-phosphate dehydrogenase (GAPDH). The HF patients showing an improvement in New York Heart Association (NYHA) functional class by1 score and a relative increase in LV ejection fractionor =25% at 4 months after CRT were considered as responders.The HF patients were characterized by lower LV mRNA levels of alpha-myosin heavy chain (alpha-MHC), beta-myosin heavy chain (beta-MHC), sarcoplasmic reticulum calcium ATPase 2alpha (SERCA), phospholamban (PLN), and higher brain natriuretic peptide (BNP) mRNA levels as compared with control subjects. Responders to CRT (n = 11) showed an increase in LVEF (p0.001), a decrease in left ventricular end-diastolic diameter (p = 0.003), and NYHA functional class (p = 0.002), and a reduction in N-terminal proBNP levels (p = 0.032) as compared with baseline. This was associated with an increase in mRNA levels of alpha-MHC (p = 0.035), SERCA (p = 0.032), a decrease in BNP mRNA levels (p = 0.002), and an increase in the ratio of alpha-/beta-MHC (p = 0.018) and SERCA/PLN (p = 0.012). No significant changes in molecular profile were observed in nonresponders.In HF patients with electromechanical cardiac dyssynchrony, functional improvement related to CRT is associated with favorable changes in established molecular markers of HF, including genes that regulate contractile function and pathologic hypertrophy.

Recently, a new linear measure of ventilatory response to exercise, the oxygen uptake efficiency slope (OUES), was proposed in the evaluation of heart failure patients. No data are available on the response of the OUES after orthotopic heart transplantation (HTx).Thirty patients who underwent HTx between 1999 and 2003 were included in the study. Data from maximal cardiopulmonary exercise test, resting pulmonary function and hemodynamic assessment were collected before the transplant at time of screening and 1 year after HTx.During the first year after HTx, OUES and normalized OUES for body weight (OUES/kg) increased significantly from 15.6 +/- 4.9 to 19.7 +/- 4.8 (p0.05). Changes in OUES/kg were significantly correlated with changes in peak VO2, VAT and peak VE, and inversely to changes in peak VD/VT, but not to changes in VE/VCO2 slope (all p0.05). Changes in OUES or OUES/kg did not correlate with any changes in measures of resting lung volumes or capacities and measures of central hemodynamic function after HTx.OUES improved significantly after HTx, but, similar to other exercise parameters, remained considerably impaired. The changes in OUES were highly correlated with the improvements in other exercise variables, but did not correlate with marked improvements in central hemodynamics or resting lung function.

Cardiac dyssynchrony is frequent in advanced heart failure, and cardiac resynchronization therapy (CRT) may offer an alternative to heart transplantation. We aimed to investigate the impact of CRT on freedom from Tx and death in transplant candidates with end-stage heart failure.Over a period of 2 years, 46 consecutive patients with refractory congestive heart failure due to dilated cardiomyopathy were referred for heart transplant evaluation. Patients with cardiac dyssynchrony107 milliseconds according to tissue Doppler imaging (TDI) or QRS duration150 milliseconds were treated with CRT (CRT group, n = 24), whereas patients without dyssynchrony were not treated (non-CRT group, n = 22).At baseline, both groups showed similar hemodynamic and functional parameters, including ejection fraction (19 +/- 10% vs 21 +/- 12%, not statistically significant [NS]) and Vo2max (11.9 +/- 2.0 vs 12.0 +/- 1.8 ml/kg/min, NS). After a follow-up of 488 +/- 346 days, cumulative survival with freedom from transplantation and death was higher in CRT vs non-CRT patients (92% vs 39%; p0.001). CRT patients showed a decrease in New York Heart Association (NYHA) class from 3.2 +/- 1.1 to 2.2 +/- 0.9 (p = 0.003) and an increase in Vo2max from 11.9 +/- 2.0 to 13.1 +/- 1.8 ml/kg/min (p = 0.02), and 71% (17 of 24) of these patients were successfully removed from the waiting list.In heart transplant candidates with significant dyssynchrony, CRT delays heart transplantation and improves NYHA class and exercise capacity. For these patients, CRT should be considered before heart transplantation.

Background Impaired vasodilator myocardial blood flow response has been observed in dilated cardiomyopathy (DCMP). However, the mechanisms responsible for this blunted response are not clear. In the present study, we investigated whether the blunted vasodilator flow response is related to indices of left ventricular performance in patients with idiopathic dilated cardiomyopathy. Methods and results Eighteen DCMP patients and 12 healthy subjects (C) underwent transoesophageal echocardiography within 48h from cardiac catheterization. Coronary flow velocity reserve (CFR) was measured in the proximal LAD as the ratio of the peak diastolic coronary flow velocity (Vd-M) after intravenous administration of adenosine to peak baseline diastolic flow velocity (Vd-R). Left ventricular (LV) mass index was positively correlated with baseline coronary diastolic velocity ( r =0.415; p =0.043) and inversely correlated with coronary flow reserve ( r =−0.570; p =0.003). The baseline coronary diastolic velocity was higher in DCMP vs C (56±13cm/s vs 35±12cm/s; p =0.04). In DCMP pts Vd-R positively correlated with end-diastolic wall stress ( r =0.654; p =0.01). Vd increased in both C (96±32cm/s; p

Purpose: Cardiac memory (CM) is considered to reflect electrical remodeling and has been described following right ventricular pacing or intermittent LBBB. We investigated whether CM occurs following cardiac resynchronization therapy (CRT) and whether it influences outcome. Methods: In 41 CRT patients (>95% BiV pacing) 12 lead ECGs were recorded during intrinsic rhythm after interrupting CRT pacing (ECG POST) and compared to the pre-implant ECG (ECG PRE). Mean spatial angles (MSA) between QRS and T vectors were determined with the Kors conversion method. LVEF was determined at CRT POST. Cardiac mortality was the primary endpoint. Results: 41 patients (age 69±11 years, all LBBB PRE CRT, 56% ischemic cardiomyopathy) were included in the study. Following CRT, LVEF improved significantly from 26±10 to 36±14% (p=0.01). Follow-up started after recording of ECG POST and lasted 30±2 months. 9 patients (22%) died. Univariate Cox regression revealed a higher cardiac mortality in the patients with lower LVEF POST CRT (HR 1.10, p

A 67-year-old woman with advanced heart failure accompanying idiopathic dilated cardiomyopathy had a broad QRS complex on the ECG and significant inter- and intraventricular asynchrony as shown by tissue Doppler echocardiography. She had no history of syncope, no documentation of any ventricular arrhythmias, and no metabolic or electrolyte abnormalities. Implantation of a biventricular pacemaker was indicated. When left ventricular stimulation was started, …

Purpose: Transplant coronary vasculopathy (TCV) remains a leading cause of morbidity and mortality in transplant (Tx) recipients. Coronary angiography as well as IVUS, the most common methods to detect TCV, lack sensitivity. Recently it was shown that VH-IVUS (Virtual HistologyIVUS, Volcano Therapeutics Inc, Rancho Cordova, CA, USA), based on spectral analysis of backscattered intravascular ultrasound, has the potential to discern plaque components, thereby allowing in-vivo plaque classification. The present study investigated tissue characterization of TCV with intravascular VH-IVUS imaging. Methods and Materials: Sixty one patients (62 10 years) underwent IVUS examination of the left anterior descending coronary artery 6.4 4.8 years after Tx. Offline spectral analysis of IVUS radiofrequency data was done with IVUS-VH software. Results: Minimal Lumen Diameter on QCA was 3.24 0.63 mm, reference diameter 3.65 0.52 mm. In the whole study population, the mean percentage of fibrous, fibrofatty, dense calcified and necrotic core plaques in a mean length of 45 mm LAD analyzed, were 62, 16, 3, 7 %. Eleven patients had significant lesion on QCA and underwent PCI. They had a mean percentage of fibrous, fibrofatty, dense calcified and necrotic core plaques of 54, 11, 5 and 0.2 %. These patients undergoing PCI had a relatively higher Calcium content compared to stable pts (calcified 2 0.5 vs 5 1 %). In addition plaques in recently transplanted hearts demonstrated a more fibrous composition whereas the dominant plaque type late after Tx was fibrofatty and calcified. Conclusions: Simultaneous assessment of virtual histology with IVUS is feasible and adds important information in the evaluation of transplant recipients. The different composition of the plaques observed early and late after Tx could reflect progression of the disease.