Heart failure with preserved ejection fraction or non-cardiac dyspnea in paroxysmal atrial fibrillation: The role of left atrial strain.

BACKGROUND: Diagnosis of heart failure with preserved ejection fraction (HFpEF) in patients with dyspnea and paroxysmal atrial fibrillation (AF) is challenging. Speckle tracking-derived left atrial strain (LAS) provides an accurate estimate of left ventricular (LV) filling pressures and left atrial (LA) phasic function. However, data on clinical utility of LAS in patients with dyspnea and AF are scarce. OBJECTIVE: To assess relationship between the LAS and the probability of HFpEF in patients with dyspnea and paroxysmal AF. METHODS: The study included 205 consecutive patients (62 ± 10 years, 58% males) with dyspnea (NYHA≥II), paroxysmal AF and preserved LV ejection fraction (≥50%), who underwent speckle tracking echocardiography during sinus rhythm. Probability of HFpEF was estimated using H2FPEF and HFA-PEFF scores, which combine clinical characteristics, echocardiographic parameters and natriuretic peptides. RESULTS: Patients with high probability of HFpEF were significantly older, had higher body mass index, NT-proBNP, E/e', pulmonary artery pressure and larger LA volume index than patients in low-to-intermediate probability groups (all p < 0.05). All components of LAS and LA strain rate showed proportional impairment with increasing probability of HFpEF (all p < 0.05). Out of the speckle tracking-derived parameters, reservoir LAS showed the largest area under the curve (AUC = 0.78, p < 0.001) and the strongest independent predictive value (OR: 1.22, 95% CI 1.08-1.38) to identify patients with high probability of HFpEF. CONCLUSIONS: Reservoir LAS shows a high diagnostic performance to distinguish HFpEF from non-cardiac causes of dyspnea in symptomatic patients with paroxysmal AF.

In vitro performance of combinations of anti-siphon devices with differential pressure valves in relation to the spatial position.

BACKGROUND: Programmable differential pressure (DP) valves combined with an anti-siphon device (ASD) represent the current standard of care in preemtping overdrainage associated with ventriculoperitoneal shunting for hydrocephalus. OBJECTIVE: We aimed to provide comparative data of four combinations of two ASDs of different working principles in combination with two DP valves in an in vitro model in order to achieve a better understanding of the flow characteristics and potential clinical application. METHODS: We analyzed the flow performance of four possible combinations of two DP valves (CHPV [HM]; proGAV 2.0[PG]) in combination with either a gravity-regulated (Shuntassistant [SA]) or a flow-regulated (SiphonGuard [SG]) ASD in an in vitro setup. A DP between 4 and 60 cmH2O was generated, and the specific flow characteristics were measured. In addition, the two combinations with gravity-regulated ASDs were measured in defined spatial positions. RESULTS: Flow characteristics of the SA combinations corresponded to the DP in linear fashion and to the spatial position. Flow characteristics of the SG combinations were dependent upon the DP in a non-linear fashion and independent of the spatial position. Highest mean flow rate of the PG-SG- (HM-SG-) combination was 1.41 ± 0.24 ml/min (1.16 ± 0.06 ml/min). The mean flow rates sharply decreased with increasing inflow pressure and subsequently increased slowly up to 0.82 ± 0.26 ml/min (0.77 ± 0.08 ml/min). CONCLUSION: All tested device combinations were able to control hydrostatic effect and prevent consecutive excessive flow, to varying degrees. However, significant differences in flow characteristics can be seen, which might be relevant for their clinical application.

Wasted septal work in left ventricular dyssynchrony: a novel principle to predict response to cardiac resynchronization therapy.

AIMS: Cardiac resynchronization therapy (CRT) in heart failure is limited by many non-responders. This study explores whether degree of wasted left ventricular (LV) work identifies CRT responders. METHODS AND RESULTS: Twenty-one patients who received CRT according to guidelines were studied before and after 8 ± 3 months. By definition, segments that shorten in systole perform positive work, whereas segments that lengthen do negative work. Work was calculated from non-invasive LV pressure and strain by speckle tracking echocardiography. For each myocardial segment and for the entire LV, wasted work was calculated as negative work in percentage of positive work. LV wall motion score index (WMSI) was assessed by echocardiography. Response to CRT was defined as ≥15% reduction in end-systolic volume (ESV). Responder rate to CRT was 71%. In responders, wasted work for septum was 117 ± 102%, indicating more negative than positive work, and decreased to 14 ± 12% with CRT (P < 0.01). In the LV free wall, wasted work was 19 ± 16% and showed no significant change. Global LV wasted work decreased from 39 ± 21 to 17 ± 7% with CRT (P < 0.01). In non-responders, there were no significant changes. In multiple linear regression analysis, septal wasted work and WMSI were the only significant predictors of ESV reduction (ß = 0.14, P = 0.01; ß = 1.25, P = 0.03). Septal wasted work together with WMSI showed an area under the curve of 0.86 (95% confidence interval 0.71-1.0) for CRT response prediction. CONCLUSION: Wasted work in the septum together with WMSI was a strong predictor of response to CRT. This novel principle should be studied in future larger studies.

Electrical remodeling reflected by QRS and T vector changes following cardiac resynchronization therapy is related to survival in heart failure patients with left bundle branch block.

INTRODUCTION: 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. METHODS AND RESULTS: 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 - p<0.001). 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, p<0.01). After adjusting for LVEFpost, only smaller angle TpreTpost was associated with mortality (HR 0.96, p=0.03). CONCLUSIONS: 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.

Epicardial catheter-based ventricular reconstruction (ECVR) in a patient with ischemic heart failure and an anteroapical aneurysm.

Extended anterior myocardial infarction (MI) is frequently followed by left ventricular (LV) remodeling ensuing in heart failure and aneurysmatic transformation of the infarcted myocardial segment. Therapies that attenuate or reverse pathological LV remodeling have been shown to improve functional status and outcomes. This case reports our recent experience with a catheter based technique for ventricular restoration.

Chronic monitoring of pulmonary artery pressure in patients with severe heart failure: multicentre experience of the monitoring Pulmonary Artery Pressure by Implantable device Responding to Ultrasonic Signal (PAPIRUS) II study.

OBJECTIVE: To evaluate the feasibility and safety of home monitoring of chronic heart failure (CHF) patients using acoustic wireless communication with an implant directly measuring pulmonary artery (PA) pressures. DESIGN: The PAPIRUS (Pulmonary Artery Pressure by Implantable device Responding to Ultrasonic Signal) II trial was a prospective, multicentre phase I study. PATIENTS: 31 patients with CHF in New York Heart Association class III-IV. INTERVENTIONS: Implantation of a miniature device in the right pulmonary artery (PA) responding to ultrasonic signal that enables wireless recording of a complete PA pressure curve. MAIN OUTCOME MEASURES: The primary end points were rates of serious adverse device- or implantation-related events at 6 months. Secondary end points included accuracy of the measured PA pressure, functionality of the system and evaluation of pressure readings at different postures. RESULTS: The two safety end points were met with no serious adverse events related to the device or implantation. Pressure tracings at 6 months were almost identical to those obtained simultaneously by Millar catheter. Variations of PA diastolic pressure were observed in relation to posture (standing 6.4 (SD 3.4) mm Hg lower than supine, p<0.001). A total of 4627 home measurements were successfully performed by 23 patients using a simple-to-operate hand-held home-unit for daily measurements. The median compliance with daily monitoring was 86%. CONCLUSIONS: Meeting the prespecified safety objective of this study warrants a randomised trial to fully evaluate the potential of home monitoring by this miniature PA implant in guiding long-term management in CHF.

Bone marrow stem cell therapy for cardiac repair: challenges and perspectives.

UNLABELLED: Bone marrow (BM) stem cells can differentiate into multiple cell types, including vascular cells and, possibly, cardiac myocytes. Stem and progenitor cells are mobilized into the peripheral circulation early after myocardial infarction. Experimental evidence suggests that BM-derived cells injected into infarcted hearts can improve cardiac function. However, mechanisms underlying functional improvements remain unclear. Initial randomized, placebo-controlled trials in patients with acute myocardial infarction have provided controversial RESULTS: On the one hand, a modest but significant and sustained improvement in left ventricular function was observed in the Reinfusion of Enriched Progenitor Cells and Infarct Remodeling in Acute Myocardial Infarction (REPAIR-AMI) study contributing to the better clinical course. Results of other studies were neutral. Differences in the study design, cell processing or timing of cell delivery might explain, in part, different outcomes among studies. Furthermore, studies in patients with chronic ischemic heart disease remain observational, and therapeutic effects using surrogate end-points needs to be demonstrated. Thus, there is a need for further coordinated research with well designed, hypothesis-driven clinical trials, in parallel with fundamental research aimed at understanding the mechanisms underlying the biological and functional effects of BM cell therapy for cardiac repair.

Head to head comparison of N-terminal pro-B-type natriuretic peptide and B-type natriuretic peptide in patients with/without left ventricular systolic dysfunction.

BACKGROUND: Human pro-B-type natriuretic peptide is cleaved into the active B-type natriuretic peptide (BNP) and the inactive fragment NT-proBNP. It is unclear if, similar to BNP, NT-proBNP can be used as a marker of impaired left ventricular (LV) ejection fraction (EF). This study evaluated the analytical performance of both assays to detect LV systolic dysfunction. METHODS: In 72 patients with various degrees of left ventricular systolic dysfunction (LVSD), blood analysis for BNP and NT-proBNP was performed prior to cardiac catheterization, using a point-of-care analyzer (Biosite) and a fully automated laboratory analyzer (Roche-Elecsys), respectively. The within-run and between-run imprecision for BNP and NT-proBNP was calculated. RESULTS: Both markers were able to detect impaired LV EF with the largest area under the receiver-operating-characteristic curve for NT-proBNP (NT-proBNP: 0.851 (0.747-0.924); BNP: 0.803 (0.692-0.887) 95% confidence interval; P = 0.07). A significant correlation was observed between BNP and NT-proBNP (r = 0.9; P < 0.0001). Estimating the within-run imprecision, the coefficient of variance for BNP was 3.14% (n = 20, mean 316 ng/L) to 3.32% (n = 20, mean 820 ng/L) and for NT-proBNP 0.9% (n = 20, mean 4390.8 ng/L) to 1.4% (n = 20, mean 225 ng/L). The between-run imprecision for NT-proBNP ranged between 2.1% (n = 20, mean 224.6 ng/L) and 2% (n = 20, mean 4391 ng/L). Optimal discriminator values for BNP and NT-proBNP were 139 ng/L and 358 ng/L, respectively. However, adjusting the BNP cut-off value to 54 ng/L improved the negative predictive value and sensitivity of the assay. CONCLUSION: Similar to BNP, NT-proBNP is a promising marker in identifying LVSD. Although both assays are reliable and have good analytical performance, their diagnostic cut-off value is dynamic and population-dependent. The slightly wider detection range and the more stable structure of NT-proBNP compared to the BNP assay suggest that NT-proBNP could play an additional role in the evaluation of patients with LV systolic dysfunction.

Myocardial cytokine gene expression is higher in aortic stenosis than in idiopathic dilated cardiomyopathy.

OBJECTIVE: To investigate cytokine gene expression in patients with aortic valve stenosis (AS) and with idiopathic dilated cardiomyopathy (DCM), and to correlate wall stress with myocardial proinflammatory cytokine gene expression. METHODS: Human left ventricular (LV) myocardial biopsies were obtained for subsequent reverse transcription polymerase chain reaction of tumour necrosis factor alpha (TNFalpha), interleukin (IL)-1beta, and IL-6 mRNA. The study population consisted of 24 patients with AS and 10 patients with idiopathic DCM. RESULTS: Patients with AS had a larger ejection fraction (56 (5) v 37 (4)%, p < 0.01), smaller LV end diastolic volumes (146 (11) v 267 (21) ml, p < 0.01), and lower end systolic wall stress (44 (7) v 112 (11) kdyn/cm2, p < 0.001). Upregulation of TNFalpha, IL-1beta, and IL-6 gene expression was detected in both groups. However, TNFalpha gene expression was significantly higher in AS than in DCM (p = 0.009). No correlation was found between haemodynamic parameters and TNFalpha gene expression. In patients with AS there was a strong inverse relation between circulating TNFalpha and TNFalpha gene expression (r = -0.685, p = 0.014), between circulating TNFalpha and IL-1beta gene expression (r = -0.664, p = 0.018), and between soluble TNF receptor 2 and TNFalpha gene expression (r = -0.685, p = 0.020). Myocardial gene expression of TNFalpha was significantly higher in patients with well compensated AS than in patients with decompensated AS (p = 0.017). Similarly, patients with decompensated DCM were characterised by significantly lower TNFalpha gene expression than were patients with well compensated DCM (p = 0.011). CONCLUSION: TNFalpha gene expression is significantly higher in patients with pressure overload than in normal hearts, in patients with idiopathic DCM, and in patients with compensated versus decompensated heart failure. Secondly, in patients with AS proinflammatory cytokine gene expression did not affect systolic performance. The higher TNFalpha gene expression in patients with compensated heart failure suggests that cytokine gene expression has an adaptive role in the early phase of LV remodelling.

Preservation of renal function after heart transplantation: initial single-center experience with sirolimus.

BACKGROUND: Long-term survivors of heart transplantation are often confronted with chronic kidney disease, by definition related to the intake of calcineurin-inhibitors. Sirolimus is increasingly proposed as an alternative immunosuppressive agent due to its absence of nephrotoxicity. METHODS: Between November 2002 and November 2003, 9 adult heart transplant candidates with moderate to severe chronic renal disease were switched from cyclosporine to sirolimus. The conversion scheme consisted of an immediate stop of cyclosporine and an 8-mg loading dose of sirolimus, followed by 3 mg/d; after 1 week, the sirolimus dose was adjusted to maintain trough levels between 5 and 15 microg/L. The majority of patients were on corticosteroids, and on either azathioprine or mycophenolate mofetil. At conversion, the mean serum creatinine level was 2.11 (+/-0.4) mg/dL and the mean glomerular filtration rate (GFR) was 32 (+/-7) mL/min/1.73 m(2). Prior to conversion, the renal dysfunction was predominantly stable. RESULTS: After conversion, there were 7 dropouts (75%) due to several side effects related to sirolimus: edema (n = 2), general discomfort (n = 2), delayed wound healing (n = 1), cardiac thrombus (n = 1), and diarrhea (n = 1). The median treatment time with Sirolimus, therefore, was only 4.0 months. While on sirolimus, the renal function of all patients remained unchanged or showed even some improvement. Retrospective nephrological review revealed severe renal artery stenoses in 2 patients and serious generalized abdominal and renal atheromatosis in 7 patients. No cardiac dysfunction was seen. CONCLUSION: Conversion from cyclosporine to sirolimus was problematic due to sirolimus side effects, occurring at any time after the switch. One should also question whether chronic kidney disease after heart transplantation is routinely caused by the administration of calcineurin-inhibitors, in view of the generalized renal and abdominal atheromatosis.

Acute type A aortic dissection in a cardiac allograft recipient: case report and review of the literature.

Dissection of the ascending aorta is uncommon in cardiac allograft recipients and usually affects the native aorta. The diagnosis is often made at necropsy. The first case is reported of a Bentall procedure performed in a heart transplant recipient who presented with ascending aortic dissection of the donor aorta and concomitant aortic regurgitation seven years after orthotopic transplantation.

Ventricular outflow tract obstruction secondary to leiomyosarcoma of the right ventricle.

Primary leiomyosarcomas of the heart, particularly those affecting the right ventricle, are uncommon. We report the case of a 70-year-old Belgian woman presenting with the symptoms of progressive exertional dyspnea and left-sided pleuritic pain. A leiomyosarcoma which originated from the right lateral ventricle wall, causing pulmonary outflow obstruction, was diagnosed. Pathology revealed a neoplasm with a myxoid stroma, high mitotic activity and nuclei expressing atypia. Immunohistochemical staining was positive for vimentine and desmin. Seven months after complete surgical resection the tumor relapsed. This case demonstrates the poor outcome, the high relapse rate and inefficiency of treatment associated with primary cardiac leiomyosarcomas. The current literature regarding the incidence, diagnostic techniques, treatment strategies and survival rates of this rare but terminal disease is reviewed.

A synthetic factor-Xa inhibitor (ORG31540/SR9017A) as an adjunct to fibrinolysis in acute myocardial infarction. The PENTALYSE study.

BACKGROUND: ORG31540/SR90107A, a synthetic pentasaccharide, is a selective inhibitor of factor-Xa. It was hypothesized that prolonged factor-Xa inhibition with pentasaccharide may be an effective and safe antithrombotic co-therapy in acute myocardial infarction. METHODS AND RESULTS: Patients (n=333) with evolving ST-segment elevation acute myocardial infarction were treated with aspirin and alteplase and randomized to unfractionated heparin, given intravenously during 48 to 72 h, or to a low, medium or high dose of pentasaccharide, administered daily for 5 to 7 days, intravenously on the first day, then subcutaneously. Coronary angiography was performed at 90 min and on days 5 to 7. Thrombolysis in Myocardial Infarction (TIMI) flow grade 3 rates at 90 min were similar in the four treatment groups. Among patients with TIMI 3 flow at 90 min and who did not undergo a coronary intervention (n=155), a trend towards less reocclusion of the infarct-related vessel on days 5 to 7 was observed with pentasaccharide: 0.9% vs 7.0% with unfractionated heparin (P=0.065). Also, fewer revascularizations during the 30-day follow-up period were performed in patients given pentasaccharide (39% vs 51% for unfractionated heparin;P=0.054). The primary safety end-point, the combined incidence of intracranial haemorrhage and need for blood transfusion, was identical with pentasaccharide and unfractionated heparin (7.1%). One non-fatal intracranial haemorrhage occurred in the 241 patients given pentasaccharide (0.4%). CONCLUSIONS: In this study, pentasaccharide given together with alteplase was safe and as effective as unfractionated heparin in restoring coronary artery patency. Prolonged administration of pentasaccharide was associated with a trend towards less reocclusion and fewer revascularizations. Selective factor-Xa-inhibition seems to be an attractive therapeutic concept in patients presenting with ST-segment elevation acute myocardial infarction.

Unstable angina due to spontaneous dissection of a LIMA graft.

We report a case of a spontaneous dissection of a left internal mammary artery grafted on the diagonal branch and the left anterior descendens. The clinical and diagnostic features of this condition are discussed. Despite an extensive literature search, no such case could be found. This case report must be regarded as the first. We speculate that extensive kinking of the left internal mammary artery contributed in the pathogenesis of this syndrome.