Influence of left ventricular assist device pressure-flow characteristic on exercise physiology: Assessment with a verified numerical model.

Current left ventricular assist devices are designed to reestablish patient's hemodynamics at rest but they lack the suitability to sustain the heart adequately during physical exercise. Aim of this work is to assess the performance during exercise of a left ventricular assist device with flatter pump pressure-flow characteristic and increased pressure sensitivity (left ventricular assist device 1) and to compare it to the performance of a left ventricular assist device with a steeper characteristic (left ventricular assist device 2). The two left ventricular assist devices were tested at constant rotational speed with a verified computational cardiorespiratory simulator reproducing an average left ventricular assist device patient response to exercise (EXE↑) and a left ventricular assist device patient with no chronotropic and inotropic response (EXE→). According to the results, left ventricular assist device 1 pumps a higher flow than left ventricular assist device 2 both at EXE↑ (6.3 vs 5.6 L/min) and at EXE→ (6.7 vs 6.1 L/min), thus it better unloads the left ventricle. Left ventricular assist device 1 increases the power delivered to the circulation from 0.63 W at rest to 0.67 W at EXE↑ and 0.82 W at EXE→, while left ventricular assist device 2 power shows even a minimal decrease. Left ventricular assist device 1 better sustains exercise hemodynamics and can provide benefits in terms of exercise performance, especially for patients with a poor residual left ventricular function, for whom the heart can hardly accommodate an increase of cardiac output.

The Effect of LVAD Pressure Sensitivity on the Assisted Circulation Under Consideration of a Mitral Insufficiency: An In Vitro Study.

Current left ventricular assist devices (LVADs) differ with respect to their pump characteristics as described by the pump characteristic curve (also called HQ-curve). Pressure sensitive LVADs depict a flat characteristic curve while most available LVADs have a steep, less pressure sensitive characteristic curve. This in vitro study investigated the effect of LVAD pressure sensitivity with a focus on the afterload of the right ventricle (RV) which is one out of many factors influencing right heart failure (RHF). To this end, two laboratory pumps differing in pressure sensitivity were tested as LVAD in an established, active mock circulation loop (MCL). The MCL represented patients with left heart failure and mitral insufficiency as another contributing factor to RV afterload. The results show that the pressure-volume loop (PV-loop) of the left ventricle (LV) undergoes a leftward and thus somewhat of a downward-shift for highly pressure sensitive support. Consequently, the LV is unloaded to a higher degree at comparable arterial blood pressure and identical cardiac output, pulmonary and systemic vascular resistance and ventricular contractility. This causes a concomitant decrease of RV afterload. This effect seems to be due to increased unloading during systole. In case of a severe concomitant mitral insufficiency and looking at left atrial pressure, the difference is 18.5%. Without mitral insufficiency, the difference is reduced to 10.2%.

HeartMate II ventricular assist device thrombosis-an echocardiographic approach to diagnosis: can Doppler evaluation of flow be useful?

A 68-year-old man was admitted to the hospital 4 months after HeartMate II ventricular assist device implantation, because his clinical status had deteriorated and his levels of lactate dehydrogenase and free hemoglobin had increased. Transthoracic echocardiography performed at admission revealed decreased basic diastolic continuous flow velocity with a pulsatile increase in flow velocity during ventricular contraction in both inflow and outflow cannulas. Twelve hours after beginning lytic therapy, basal diastolic continuous flow velocity had increased, and the amplitude between diastolic and systolic flow velocity had decreased. The clinical status of the patient improved, and his lactate dehydrogenase decreased. A decrease in basal diastolic flow may be a valuable marker of flow disturbance in continuous flow ventricular assist devices.

Successful correction of a total anomalous venous connection in a 63-year-old male--case report and review of the literature.

Total anomalous pulmonary venous connection is a rare variant of cyanotic congenital heart disease and usually requires surgical correction within the first few months of life. We report midterm results of a 63-year-old male with intracardiac total anomalous venous return into the coronary sinus who presented with congestive predominantly right heart failure and underwent corrective surgery with unroofing of the coronary sinus and patch closure of the secundum atrial septal defect.

The Arg16Gly-ß(2)-adrenoceptor single nucleotide polymorphism: exercise capacity and survival in patients with end-stage heart failure.

Heart failure (HF) is characterized by impaired myocardial ß-adrenergic signal transduction. Single nucleotide polymorphisms (SNPs) within the ß(1)- (Ser49Gly, Arg389Gly) and ß(2)-adrenoceptor (Arg16Gly, Gln27Glu, Thr164Ile) have been associated with alterations in adrenoceptor (AR) function sensitivity in vitro and in vivo and possibly contribute to HF progression. The present study evaluated the relation of those SNPs to morbidity and mortality in patients with end-stage HF. A total of 226 patients with end-stage HF (ejection fraction ≤35%) were genotyped for the two ß(1)AR SNPs and the three ß(2)AR SNPs. Outcome (death, heart transplantation (HTX)) was determined from May 2003 to June 2004. Heart rate, systolic and diastolic blood pressure, and peak oxygen uptake were measured during graded treadmill exercise. Left ventricular end-diastolic and end-systolic diameters, ejection fraction, and fractional shortening at rest were measured using two-dimensional echocardiography. Minor allele frequencies were 0.12 for Gly49 and 0.27 for Gly389 (ß(1)AR) and 0.37 for Arg16, 0.43 for Glu27 and 0.01 for Ile164 (ß(2)AR). During follow-up, 45 patients died (20%), and 27 patients underwent HTX (12%). No significant differences in the incidence or in the time-to-endpoint of death and HTX between genotypes of the different SNPs within the ß(1)- and ß(2)AR were detected. However, patients carrying the Arg16-ß(2)AR tended to have lower exercise capacity and a higher probability for death/HTX within 45 months (survival proportion 46%) than patients carrying the Gly16Gly-ß(2)AR (survival proportion 64%). In conclusion, the Arg16Gly-ß(2)AR might impact on exercise capacity and outcome in end-stage heart failure.

Global gene expression analysis in nonfailing and failing myocardium pre- and postpulsatile and nonpulsatile ventricular assist device support.

Mechanical unloading by ventricular assist devices (VAD) leads to significant gene expression changes often summarized as reverse remodeling. However, little is known on individual transcriptome changes during VAD support and its relationship to nonfailing hearts (NF). In addition no data are available for the transcriptome regulation during nonpulsatile VAD support. Therefore we analyzed the gene expression patterns of 30 paired samples from VAD-supported (including 8 nonpulsatile VADs) and 8 nonfailing control hearts (NF) using the first total human genome array available. Transmural myocardial samples were collected for RNA isolation. RNA was isolated by commercial methods and processed according to chip-manufacturer recommendations. cRNA were hybridized on Affymetrix HG-U133 Plus 2.0 arrays, providing coverage of the whole human genome Array. Data were analyzed using Microarray Analysis Suite 5.0 (Affymetrix) and clustered by Expressionist software (Genedata). We found 352 transcripts were differentially regulated between samples from VAD implantation and NF, whereas 510 were significantly regulated between VAD transplantation and NF (paired t-test P < 0.001, fold change >or=1.6). Remarkably, only a minor fraction of 111 transcripts was regulated in heart failure (HF) and during VAD support. Unsupervised hierarchical clustering of paired VAD and NF samples revealed separation of HF and NF samples; however, individual differentiation of VAD implantation and VAD transplantation was not accomplished. Clustering of pulsatile and nonpulsatile VAD did not lead to robust separation of gene expression patterns. During VAD support myocardial gene expression changes do not indicate reversal of the HF phenotype but reveal a distinct HF-related pattern. Transcriptome analysis of pulsatile and nonpulsatile VAD-supported hearts did not provide evidence for a pump mode-specific transcriptome pattern.

Solitary metastatic adenocarcinoma of the sternum treated by total sternectomy and chest wall reconstruction using a Gore-Tex patch and myocutaneous flap: a case report.

INTRODUCTION: The consequences of bone metastasis are often devastating. Although the exact incidence of bone metastasis is unknown, it is estimated that 350,000 people die of bone metastasis annually in the United States. The incidence of local recurrences after mastectomy and breast-conserving therapy varies between 5% and 40% depending on the risk factors and primary therapy utilized. So far, a standard therapy of local recurrence has not been defined, while indications of resection and reconstruction considerations have been infrequently described. This case report reviews the use of sternectomy for breast cancer recurrence, highlights the need for thorough clinical and radiologic evaluation to ensure the absence of other systemic diseases, and suggests the use of serratus anterior muscle flap as a pedicle graft to cover full-thickness defects of the anterior chest wall. CASE PRESENTATION: We report the case of a 70-year-old Caucasian woman who was referred to our hospital for the management of a retrosternal mediastinal mass. She had undergone radical mastectomy in 1999. Computed tomography and magnetic resonance imaging revealed a 74.23 x 37.7 x 133.6-mm mass in the anterior mediastinum adjacent to the main pulmonary artery, the right ventricle and the ascending aorta. We performed total sternectomy at all layers encompassing the skin, the subcutaneous tissues, the right pectoralis major muscle, all the costal cartilages, and the anterior part of the pericardium. The defect was immediately closed using a 0.6 mm Gore-Tex cardiovascular patch combined with a serratus anterior muscle flap. Our patient had remained asymptomatic during her follow-up examination after 18 months. CONCLUSION: Chest wall resection has become a critical component of the thoracic surgeon's armamentarium. It may be performed to treat either benign conditions (osteoradionecrosis, osteomyelitis) or malignant diseases. There are, however, very few reports on the results of full-thickness complete chest wall resections for locally recurrent breast cancer with sufficient safety margins, and even fewer reports that describe the operative technique of using the serratus anterior muscle as a pedicled flap.

23S rDNA real-time polymerase chain reaction of heart valves: a decisive tool in the diagnosis of infective endocarditis.

AIMS: A new diagnostic strategy to improve the detection of pathogens in heart valves (HVs) from patients with infective endocarditis (IE) was evaluated. METHODS AND RESULTS: Three hundred and fifty seven HVs surgically removed from 326 patients with proven IE or suspicious intra-operative findings, examined by 16S rDNA polymerase chain reaction (PCR) and culture were retrospectively analysed according to the predictive value of various PCR methods. Patients were classified into four categories: active IE, IE with ambiguous infective status, healed IE, and valve diseases but no IE. Retained samples of 200 HVs were analysed by real-time PCR targeting bacterial 23S rDNA, fungal 28S rDNA, and mycoplasmal tuf gene. 16S rDNA PCR revealed 80.6% sensitivity, 100% specificity, 100% positive predictive value, and 71% negative predictive value (NPV), compared with cultivation with 33.4, 96.6, 95.5, and 40.9%, respectively. The use of real-time PCR increased diagnostic sensitivity to 96.4%, and NPV to 92.5%. Bacterial load, C-reactive protein, and white blood cell counts (WBCs) decreased during antibiotic treatment. Bacterial load showed no correlation to C-reactive protein or WBCs, whereas C-reactive protein and WBCs were significantly correlated. CONCLUSION: 23S rDNA real-time PCR of surgically removed HVs improves the diagnosis of IE. Polymerase chain reaction analysis of explanted HVs allow the optimization of the antimicrobial therapy, especially in patients with culture-negative IE.

K201 improves aspects of the contractile performance of human failing myocardium via reduction in Ca2+ leak from the sarcoplasmic reticulum.

In heart failure, intracellular Ca2+ leak from cardiac ryanodine receptors (RyR2s) leads to a loss of Ca2+ from the sarcoplasmic reticulum (SR) potentially contributing to decreased function. Experimental data suggest that the 1,4-benzothiazepine K201 (JTV-519) may stabilise RyR2s and thereby reduce detrimental intracellular Ca2+ leak. Whether K201 exerts beneficial effects in human failing myocardium is unknown. Therefore, we have studied the effects of K201 on muscle preparations from failing human hearts. K201 (0.3 microM; extracellular [Ca2+]e 1.25 mM) showed no effects on contractile function and micromolar concentrations resulted in negative inotropic effects (K201 1 microM; developed tension -9.8 +/- 2.5% compared to control group; P < 0.05). Interestingly, K201 (0.3 microM) increased the post-rest potentiation (PRP) of failing myocardium after 120 s, indicating an increased SR Ca2+ load. At high [Ca2+]e concentrations (5 mmol/L), K201 increased PRP already at shorter rest intervals (30 s). Strikingly, treatment with K201 (0.3 microM) prevented diastolic dysfunction (diastolic tension at 5 mmol/L [Ca2+]e normalised to 1 mmol/L [Ca2+]e: control 1.26 +/- 0.06, K201 1.01 +/- 0.03, P < 0.01). In addition at high [Ca2+]e) K201 (0.3 microM) treatment significantly improved systolic function [developed tension +27 +/- 8% (K201 vs. control); P < 0.05]. The beneficial effects on diastolic and systolic functions occurred throughout the physiological frequency range of the human heart rate from 1 to 3 Hz. Upon elevated intracellular Ca2+ concentration, systolic and diastolic contractile functions of terminally failing human myocardium are improved by K201.

Surgical treatment of left ventricular aneurysm.

When a left ventricular aneurysm leads to pulmonary congestive symptoms, aneurysmectomy may provide relief. This retrospective study included 269 patients who underwent aneurysmectomy between 1993 and 2002, by the classic Cooley operation in 164 and by Dor ventriculoplasty in 105. There were no significant differences in early and late survival between groups, although the frequency of extended anteroseptal infarction was higher in patients undergoing the Dor procedure. Postoperative echocardiographic findings showed significant improvements in left ventricular function in both groups, in terms of end-diastolic and end-systolic dimensions and ejection fraction. Left ventricular aneurysmectomy significantly improved the clinical status and hemodynamic parameters of symptomatic patients. The choice of surgical technique depends on the extent of the scar segment, especially the presence of an anteroseptal scarred area. The Dor procedure is more suitable for restoring normal left ventricular geometry in patients with extensive septal infarction.

Long-term results of heart transplantation for end-stage valvular heart disease.

BACKGROUND: In general, heart transplantation for patients with heart failure improves survival. However, the outcomes of heart transplantation for patients with end-stage valvular heart disease are less well reported. This is a substantial group of patients, many of whom have had previous cardiac surgery. They therefore may be considered a subgroup with a poor prognosis. This study reports on the outcomes of heart transplantation for patients with end-stage valvular heart disease. PATIENTS AND METHODS: From March 1989 to December 2004, 75 consecutive adult heart transplantations were performed for end-stage valvular heart disease. Clinical characteristics were retrieved from a computerized database. RESULTS: The early mortality risk in heart transplantation for end-stage valvular heart disease was 13%, compared to 8% for other indications (p = 0.12). The main causes of early death were rejection (20%) and right ventricular failure (20%). The total follow-up time was 415 patient-years. During the follow-up, another 23 patients died (55/1000 patient-years of late mortality rate), mostly due to infection (43%) and multiorgan failure (22%). Multivariable analysis demonstrated that increased waiting time to heart transplantation correlated with increased survival (HR = 0.998, p = 0.04). The survival at 1, 5, 10, and 15 years was 70%, 64%, 56%, and 46% compared to 78%, 68%, 53%, and 41% for other indications, respectively (p = 0.5). CONCLUSION: The outcomes of heart transplantation for patients with end-stage valvular heart disease are similar to those for other patients. Apparently, the longer the waiting time to heart transplantation the better the outcome becomes.

Reconstructive surgery for an akinetic anterior ventricular wall in ischemic cardiomyopathy.

BACKGROUND: The purpose of this prospective study is to analyze the postoperative outcome after only left ventricular reconstruction (LVR) versus LVR combined with coronary artery bypass grafting (CABG) and/or mitral valve (MV) procedure in ischemic cardiomyopathy (ICM) as a result of an akinetic anterior ventricular wall. METHODS AND RESULTS: Nineteen patients underwent only LVR, and 37 underwent a concomitant LVR procedure. In both groups, New York Heart Association (NYHA) classification improved significantly from 3.5 +/- 0.6 to 2.2 +/- 0.5 (LVR group) and 3.4 +/- 0.7 to 2.5 +/- 0.5 (combined LVR group). Ejection fraction improved significantly from 25.1 +/- 3.2 to 35.3 +/- 4.5% in the LVR group and 28.1 +/- 2.2 to 37.6 +/- 5.5% in the combined LVR group. Cardiac index improved significantly from 1.8 +/- 0.6 to 2.3 +/- 0.5 l/min/m2 in the LVR group and 1.6 +/- 0.4 to 2.2 +/- 0.6 l/min/m2 in the combined LVR group. An additional concomitant procedure increased the mortality rate only slightly. The overall 1- and 5-year actuarial survival rates were 90% and 75% in the LVR group and 80% and 70% in the combined LVR group. CONCLUSIONS: The LVR for akinetic ventricular wall shows very satisfactory early and long-term results. The LVR, with or without concomitant procedures, has considerable benefits for operative therapy.

Valve replacement in octogenarians: arguments for an earlier surgical intervention.

BACKGROUND AND AIM OF THE STUDY: In octogenarians with symptomatic aortic valve stenosis (AS), aortic valve replacement (AVR) is frequently not performed in due time, because the prognostic benefit is underestimated, while perioperative morbidity and mortality are overestimated. The severely impaired prognosis and quality of life after myocardial decompensation then urges AVR with a significantly increased perioperative risk. METHODS: Between 2003 and 2006, all octogenarians with isolated symptomatic AS (indexed aortic valve opening area <0.5 cm2/m2) referred to the authors' unit were prospectively included in the survey. Among the 83 patients enrolled (51 women, 32 men; mean age 84 +/- 5.1 years), 38 patients (26 women, 12 men; mean age 84 +/- 2.3 years) had signs of chronic myocardial decompensation (dilated left ventricle and/or reduced left ventricular function; left ventricular ejection fraction (LVEF) 43 +/- 18% (range: 25-53%). These patients comprised group A. All other patients (group B) had normal left ventricular dimensions, a normal LVEF (>55%), and no clinical episodes of myocardial decompensation. All patients underwent AVR, while 23 (28%) underwent simultaneous coronary revascularization. RESULTS: In group A, the 30-day mortality rate was 5.3% (n = 2). Octogenarians without chronic myocardial decompensation had a lower 30-day mortality (1/45; 2.2%). The incidences of major postoperative complications (reversible acute renal failure, stroke, mechanical circulatory support) were significantly higher in group A (26.3% versus 8.9%, p < 0.05). During late follow up (mean 24.2 +/- 12.8 months), another four patients in group A (11.1%) and five in group B (11.4%) died. Octogenarians in group B had a significantly (p < 0.01) more favorable cumulative survival rate (87% versus 78% after 24 months; 81% versus 68% after 46 months). CONCLUSION: AVR can be performed in octogenarians with a low mortality and morbidity, but should not be postponed. The decision to perform for AVR may take into consideration any life-limiting comorbidities, but should be made independent of the patient's age.

Genomic profiling of developing cardiomyocytes from recombinant murine embryonic stem cells reveals regulation of transcription factor clusters.

Cardiomyocytes derived from pluripotent embryonic stem cells (ESC) have the advantage of providing a source for standardized cell cultures. However, little is known on the regulation of the genome during differentiation of ESC to cardiomyocytes. Here, we characterize the transcriptome of the mouse ESC line CM7/1 during differentiation into beating cardiomyocytes and compare the gene expression profiles with those from primary adult murine cardiomyocytes and left ventricular myocardium. We observe that the cardiac gene expression pattern of fully differentiated CM7/1-ESC is highly similar to adult primary cardiomyocytes and murine myocardium, respectively. This finding is underlined by demonstrating pharmacological effects of catecholamines and endothelin-1 on ESC-derived cardiomyocytes. Furthermore, we monitor the temporal changes in gene expression pattern during ESC differentiation with a special focus on transcription factors involved in cardiomyocyte differentiation. Thus, CM7/1-ESC-derived cardiomyocytes are a promising new tool for functional studies of cardiomyocytes in vitro and for the analysis of the transcription factor network regulating pluripotency and differentiation to cardiomyocytes.

Impact of prior percutaneous coronary intervention on the outcome of coronary artery bypass surgery: a multicenter analysis.

OBJECTIVES: Do prior percutaneous coronary interventions adversely affect the outcome of subsequent coronary artery bypass grafting? We investigated this effect on a multicenter basis. METHODS: Eight cardiac surgical centers provided outcome data of 37,140 consecutive patients who underwent isolated first-time coronary bypass grafting between January 2000 and December 2005. Twenty-two patient characteristics and outcome variables were retrieved. Three groups of patients were analysed for in-hospital mortality and in-hospital major adverse cardiac events: patients without a previous percutaneous coronary intervention, with 1 previous intervention, and with 2 or more previous percutaneous coronary interventions before bypass grafting. A total of 29,928 patients with complete information for prior percutaneous coronary intervention underwent final analysis. Unadjusted univariate and risk-adjusted multivariate logistic regression analysis as well as computed propensity score matching were performed, based on 14 major risk factors to correct for and minimize selection bias. RESULTS: A total of 10.3% of patients had 1 previous percutaneous coronary intervention, and 3.7% of patients had 2 or more previous interventions. Risk-adjusted multivariate logistic regression analysis revealed a significant association of 2 or more previous percutaneous coronary interventions with in-hospital mortality (odds ratio [OR], 2.0; confidence interval [CI], 1.4-3.0; P = .0005) and major adverse cardiac events (OR, 1.5; CI, 1.2-1.9; P = .0013). After propensity score matching, conditional logistic regression analysis confirmed the results of adjusted analysis. A history of 2 or more previous percutaneous coronary interventions was significantly associated with in-hospital mortality (OR, 1.9; CI, 1.3-2.7; P = .0016) and major adverse cardiac events (OR, 1.5; CI, 1.2-1.9; P = .0019). CONCLUSIONS: Multicenter analysis confirms that a history of multiple previous percutaneous coronary interventions increases in-hospital mortality and the incidence of major adverse cardiac events after subsequent coronary artery bypass grafting. Critical discussion of the treatment strategy in these patients is warranted.

Cardiac resynchronization therapy: long-term alternative to cardiac transplantation?

BACKGROUND: Cardiac transplantation remains the gold standard for treating end-stage heart failure. However, because of donor shortage and posttransplant complications alternative options are needed. METHODS: We investigated the impact of cardiac resynchronization therapy on clinical outcome in 545 patients with left bundle-branch block and interventricular asynchrony, who fulfilled the cardiac criteria for cardiac transplantation listing. Primary end point was heart failure death. Secondary end points were New York Heart Association class, functional (cardiopulmonary exercise tolerance, 6-minute hall walk distance), and morphologic (left ventricular end-diastolic diameter) factors. RESULTS: The average follow-up period was 39.6 months (standard deviation, 26.1 months). In total, 1,784 years of observation were accrued. The percentage of nonresponders (no functional and morphologic improvement during follow-up) was 21.2%. One-year and 3-year freedom from heart failure death was 92.3% and 77.3%, respectively. Functional variables improved, but the left ventricular end-diastolic diameter decreased during the first 6 months of cardiac resynchronization therapy only in patients who survived during follow-up. Under cardiac resynchronization therapy, 42.5% (n = 34) of the cardiac transplantation candidates with atrial fibrillation at baseline returned to sinus rhythm. CONCLUSIONS: Our data suggest that cardiac resynchronization therapy is a reliable long-term therapeutic option for the treatment of end-stage heart failure and intraventricular asynchrony.

Prevalent platelet dysfunction in patients with aortic valve disease.

BACKGROUND AND AIM OF THE STUDY: In patients with heart valve disease, the valve leaflets display a gapped, rough endothelial lining often covered with calcified areas. As a consequence, blood flow is disturbed and a stimulation of components of the hemostasis system is assumed. The possible mechanisms of this process are, however, unclear at present. METHODS: Platelet function was studied in 660 patients considered for isolated coronary artery bypass graft (CABG) surgery, and in 421 patients considered for single aortic valve replacement (AVR). Platelet function was monitored preoperatively using the platelet function analyzer device (PFA-100). The test results were reported as closure time of the membrane hole at the end of a capillary tube. The von Willebrand factor antigen, and its collagen-binding activity, were also determined among subgroups of 40 AVR and 50 CABG candidates. RESULTS: Platelet dysfunction was displayed by only 22% of CAD patients, but by 83% of AVR candidates. The mean PFA closure time in AVR patients was considerably higher than in CAD patients (231 +/- 59 s versus 153 +/- 60 s, respectively; p < 0.01). The mean platelet volume, platelet distribution width and von Willebrand factor collagen binding and antigen levels did not differ between the patient groups. CONCLUSION: It is assumed that, due to disturbed flow and shear exposition, following an initial activation, the platelets are partially degranulated, shed microparticles, and might become involved in the pathogenesis of microvascular dysfunction and thrombotic events in patients with aortic valve disease.