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.

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.

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.

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.

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.

Endomyocardial nitric oxide synthase and left ventricular preload reserve in dilated cardiomyopathy.

BACKGROUND: Patients with heart failure have modified myocardial expression of nitric oxide synthase (NOS), as is evident from induction of calcium-insensitive NOS isoforms. The functional significance of this modified NOS gene expression for left ventricular (LV) contractile performance was investigated in patients with dilated nonischemic cardiomyopathy. METHODS AND RESULTS: In patients with dilated, nonischemic cardiomyopathy, invasive measures of LV contractile performance were derived from LV microtip pressure recordings and angiograms and correlated with intensity of gene expression of inducible (NOS2) and constitutive (NOS3) NOS isoforms in simultaneously procured LV endomyocardial biopsies (n=20). LV endomyocardial expression of NOS2 was linearly correlated with LV stroke volume (P=0.001; r=0.66), LV ejection fraction (P=0.007; r=0.58), and LV stroke work (P=0.003; r=0.62). In patients with elevated LV end-diastolic pressure (>16 mm Hg), a closer correlation was observed between endomyocardial expression of NOS2 and LV stroke volume (P=0.001; r=0.74), LV ejection fraction (P=0.0007; r=0.77), and LV stroke work (r=0.82; P=0.0002). LV endomyocardial expression of NOS3 was linearly correlated with LV stroke volume (P=0.01; r=0.53) and LV stroke work (P=0.01; r=0.52). To establish the role of nitric oxide (NO) as a mediator of the observed correlations, substance P (which causes endothelial release of NO) was infused intracoronarily (n=12). In patients with elevated LV end-diastolic pressure, an intracoronary infusion of substance P increased LV stroke volume from 72+/-13 to 91+/-16 mL (P=0.06) and LV stroke work from 67+/-11 to 90+/-15 g. m (P=0.03) and shifted the LV end-diastolic pressure-volume relation to the right. CONCLUSIONS: In patients with dilated cardiomyopathy, an increase in endomyocardial NOS2 or NOS3 gene expression augments LV stroke volume and LV stroke work because of a NO-mediated rightward shift of the diastolic LV pressure-volume relation and a concomitant increase in LV preload reserve.

Myocardial contractile effects of L-arginine in the human allograft.

OBJECTIVES: In the present study, we investigated, in transplant recipients, whether L-arginine (L-arg) potentiates the myocardial contractile effects of receptor-mediated coronary endothelial stimulation. Moreover, because inducible nitric oxide synthase (iNOS) is frequently expressed in transplanted myocardium, we also performed intracoronary infusion of L-arg in the absence of receptor-mediated coronary endothelial stimulation to investigate whether similar left ventricular (LV) contractile effects could be induced by providing more substrate for iNOS. BACKGROUND: Nitric oxide (NO), released from coronary endothelium after receptor-mediated stimulation by substance P (SP), affects vascular smooth muscle tone and modulates LV contractile performance. L-arg augments receptor-mediated endothelium-dependent coronary vasodilation in transplant recipients by increasing substrate availability for endothelial NO production. METHODS: Sixteen transplant recipients were studied at the time of annual coronary angiography. In eight transplant recipients, microtip LV pressures were recorded before and during intracoronary (IC) SP (20 pmol/min) and after the addition of IC L-arg (160 mumol/min) to IC SP. In eight transplant recipients, microtip LV pressures were recorded before and during IC L-arg (160 mumol/min) alone, and in six of these patients, endomyocardial biopsy samples were obtained to detect the expression of iNOS gene by reverse transcription-polymerase chain reaction. RESULTS: Addition of IC L-arg to IC SP induced a fall (mean +/- SEM) in LV peak systolic pressure (-16 +/- 4 mm Hg), which was larger (p < 0.01) than that observed during IC SP (-7 +/- 2 mm Hg). During IC L-arg alone, there was no change in LV peak systolic pressure despite the presence of iNOS mRNA in five of the six biopsy samples. CONCLUSIONS: In transplant recipients, L-arg potentiates the paracrine myocardial contractile effects of receptor-mediated coronary endothelial stimulation, probably by providing more substrate for endothelial NO production. Despite the myocardial expression of iNOS gene, L-arg alone fails to elicit similar contractile effects.

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.

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.

Pacing induced mitral regurgitation following radiofrequency ablation of the atrioventricular conduction system: case report and potential mechanism.

We describe a patient with hemodynamic deterioration and worsening mitral regurgitation related to right ventricular apex pacing. Time-dependent changes in papillary muscle contraction as well as ventricular remodeling by right ventricular apex pacing might be responsible for this rare but serious complication.

ECG diagnosis of native heart ventricular tachycardia in a heterotopic heart transplant recipient.

A case is reported of haemodynamic collapse in a 51 year old male heterotopic heart transplant recipient caused by native heart ventricular tachycardia. An accurate diagnosis was made by selective right and left sided electrocardiography. Synchronised electrical cardioversion of the native heart (200 J) resulted in restoration of sinus rhythm with prompt relief of symptoms and amelioration of the clinical situation.

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.

Inappropriate rate response in a VVI-R pacemaker.

The search for a pacemaker that accurately and easily mimics normal physiology is a continuing effort. Present pacing developments include AV synchrony and rate adaptiveness. The usefulness and clinical value of some of the new pacing systems remain unclear. Although the hemodynamic advantages of rate responsive pacing over classical ventricular pacing are well established (Kristensson et al., 1985), an ideal sensor for physiological demands has not been established. We report a case of apparently unequivocal increase in heart rate during upper limb movements in a patient with a VVI-R pacemaker using minute ventilation as a sensor. Inappropriate heart rate acceleration may result from changes in transthoracic impedance due to upper limb exercise and it does not necessarily represent sensor malfunction. Although this complication is well-known in VVI-R pacemakers using respiratory rate or minute ventilation as sensor (Santomauro et al., 1992), one must remain aware of this sensor-related problem. In this particular patient the problem could be solved by implanting the pacemaker can more medially.

Pacing in cardiomyopathy.

Permanent cardiac pacing is an established treatment for the prevention of syncope or sudden death in patients with heart block or sinus node disease. Recent observations underscore the use of pacing in patients with various forms of cardiomyopathy, i.e. hypertrophic, dilated and tachycardia-induced cardiomyopathy. The evidence favouring the use of pacing in patients with cardiomyopathy is mainly derived from retrospective and uncontrolled investigations and the data from the scarce randomized investigations are rather disappointing. Therefore, the indications for pacing remain controversial.

Thrombotic thrombocytopenic purpura: a rare but potential life-threatening complication following ticlopidine administration.

Thrombotic thrombocytopenic purpura (TTP) is a known, although rare, complication of ticlopidine treatment. It typically appears within the first days or weeks after initiation of therapy. We describe a case of TTP in a 75-year-old patient, due to ticlopidine, occurring three weeks after coronary stent implantation. The patient responded favourably to fresh frozen plasma exchanges. We are reporting this case to emphasize that prognosis depends on prompt diagnosis and early treatment, implying careful biochemical monitoring.

Differential leucocyte cell counts from the pygoscelid penguins of Antarctica.

Differential leucocyte counts were obtained for three cogeneric species of wild antarctic penguins, Pygoscelis adelie (adelie), Pygoscelis papua (gentoo), and Pygoscelis antarctica (chinstrap). Significant differences between the differential leucocyte counts of the three species were not observed.