Bojan Vrtovec

Prolonged QTc Interval and High B-Type Natriuretic Peptide Levels Together Predict Mortality in Patients With Advanced Heart Failure

Background—The role of QTc interval prolongation in heart failure remains poorly defined. To better understand it, we analyzed the QTc interval duration in patients with heart failure with high B-type natriuretic peptide (BNP) levels and analyzed the combined prognostic impact of prolonged QTc and elevated BNP. Methods and Results—QTc intervals were measured in 241 patients with heart failure who had BNP levels >400 pg/mL. QT interval duration was determined by averaging 3 consecutive beats through leads II and V4 on a standard 12-lead ECG and corrected by using the Bazett formula. QTc intervals were prolonged (>440 ms) in 122 (51%) patients and normal in 119 (49%). The BNP levels in these 2 groups were not significantly different (786±321 pg/mL in the prolonged QTc group versus 733±274 pg/mL in the normal QTc group, P =0.13). During 6 months of follow-up, 46 patients died, 9 underwent transplantation, and 17 underwent left ventricular assist device implantation. The deaths were attributed to pump failure (n=24, 52%), sudden cardiac death (n=18, 39%), or noncardiac causes (n=4, 9%). Kaplan-Meier survival rates were 3 times higher in the normal QTc group than in the prolonged QTc group (P <0.0001). On multivariate analysis, prolonged QTc interval was an independent predictor of all-cause death (P =0.0001), cardiac death (P =0.0001), sudden cardiac death (P =0.004), and pump failure death (P =0.0006). Conclusions—Prolonged QTc interval is a strong, independent predictor of adverse outcome in patients with heart failure with BNP levels >400 pg/mL.

Biventricular support with the Jarvik 2000 axial flow pump: a feasibility study.

Patients with congestive heart failure who are supported with a left ventricular assist device (LVAD) may experience right ventricular dysfunction or failure that requires support with a right ventricular assist device (RVAD). To determine the feasibility of using a clinically available axial flow ventricular assist device as an RVAD, we implanted Jarvik 2000 pumps in the left ventricle and right atrium of two Corriente crossbred calves (approximately 100 kg each) by way of a left thoracotomy and then analyzed the hemodynamic effects in the mechanically fibrillated heart at various LVAD and RVAD speeds. Right atrial implantation of the device required no modification of either the device or the surgical technique used for left ventricular implantation. Satisfactory biventricular support was achieved during fibrillation as evidenced by an increase in mean aortic pressure from 34 mm Hg with the pumps off to 78 mm Hg with the pumps generating a flow rate of 4.8 L/min. These results indicate that the Jarvik 2000 pump, which can provide chronic circulatory support and can be powered by external batteries, is a feasible option for right ventricular support after LVAD implantation and is capable of completely supporting the circulation in patients with global heart failure.

Left ventricular assist devices: an alternative to medical therapy for end-stage heart failure.

Although aggressive medical therapy and ultimately cardiac transplantation have long been the therapeutic mainstays for patients with end-stage heart failure, the left ventricular assist device (LVAD), which was originally used clinically as a bridge to transplantation, may also be used as destination therapy. LVAD therapy for selected patients has been shown in the REMATCH trial to be superior to medical therapy in ameliorating symptoms and improving outcome in patients with terminal heart failure. LVAD therapy has also proved useful in improving native heart function by neuroendocrine modulation and reverse remodeling. Furthermore, current evidence suggests that when LVAD therapy is utilized to improve ventricular function, it may be further enhanced when combined with aggressive medical therapy.

Significance of anaemia in patients with advanced heart failure receiving long-term mechanical circulatory support

The aim of this study was to analyse the prognostic impact of anaemia in patients receiving long‐term left ventricular assist device (LVAD) support.

Stem cell therapy for chronic heart failure.

Purpose of review The aim of this review was to discuss recent advances in clinical aspects of stem cell therapy in heart failure with emphasis on patient selection, stem cell types and delivery methods. Recent findings Several stem cell types have been considered for the treatment of patients with heart failure. In nonischemic heart failure, transplantation of CD34+ cells improved myocardial performance, functional capacity and neurohumoral activation. In ischemic heart failure, cardiosphere-derived cells were shown to reduce myocardial scar burden with concomitant increase in viable tissue and regional systolic wall thickening. Both autologous and allogeneic mesenchymal stem cells were shown to be effective in improving heart function in patients with ischemic heart failure; this may represent an important step toward the development of a standardized stem cell product for widespread clinical use. Summary Although trials of stem cell therapy in heart failure have shown promising results, the findings are not consistent. Given the wide spectrum of heart failure, it may be difficult to define a uniform stem cell therapy for all subsets of patients; instead, future stem cell therapeutic strategies should aim for a more personalized approach by establishing optimal stem cell type, dose and delivery method for an individual patient and disease state.

Mitral regurgitation and axial flow left ventricular assist device: a computer simulation study.

Good right ventricular function is one of the major determinants of long-term outcomes in patients with implanted left ventricular assist devices (LVADs). In the present study, a computer model was developed to assess the impact of mitral regurgitation on right ventricular workload at different levels of LVAD support. Left ventricular assist device was simulated by a model of HeartMate II. The computer model has shown that the regurgitant volume of the mitral valve falls significantly only after the systolic pressure in the left ventricle decreases, which occurs at higher LVAD revolutions per minute (RPM) when there is no ejection through the aortic valve. However, at low LVAD RPM, the pressures in the left atrium and the pulmonary artery decrease significantly, despite a small decrease in regurgitant volume. According to the computer model, LVAD support decreases mitral regurgitation. Furthermore, regurgitant volume has a smaller impact on the right ventricular afterload when compared with a heart without LVAD support.

Outcomes in patients with low left ventricular ejection fraction after heart transplantation.

OBJECTIVES Low left ventricular ejection fraction (EF) after heart transplantation (HT) is considered an ominous sign. We reviewed our database in order to determine outcomes in patients with low EF after HT and to identify a subset of patients who would benefit from immediate retransplantation. METHODS We identified 825 patients who underwent HT at our institution between December 1983 and July 1999. Of these, 81 patients (70 men, 11 women; age, 48+/-12 years) had low (<35%) EF as determined by radionuclide ventriculography. Post-transplantation survival; duration of low-EF episodes (>2 years vs. <2 years); and incidence of transplant rejection, infection, and transplant coronary artery disease (CAD) were determined for these patients. RESULTS On average, low EF developed 800+/-1029 days after HT and lasted 550+/-756 days until improvement, repeat HT, or death of the patient. Actuarial survival was 79% at 1 year, 55% at 3 years, and 46% at 5 years. Shorter (<2-year) episodes of low EF tended to have an earlier onset than prolonged (>2-year) episodes (656 days vs. 1341 days) (P=0.014). Patients with prolonged episodes (n=17) survived longer than patients with shorter episodes (n=64) (2247 days vs. 1266 days) (P=0.002). The incidence of hemodynamically significant rejection was lower in the prolonged low-EF group (6% [1/17] vs. 26% [17/64]) (P=0.03). The incidence of infection (31% vs. 53%) and incidence of transplant CAD (47% vs. 39%) did not differ significantly between the prolonged and shorter low-EF groups. CONCLUSIONS Low EF after HT, especially with later onset, is not associated with poor survival and is not related to hemodynamically significant rejection. These data further indicate that the presence of low EF even in the setting of CAD is not by itself an indication for repeat HT.

LVAD as a Bridge to Heart Transplantation in a Patient with Left Ventricular Noncompaction Cardiomyopathy and Advanced Heart Failure

Left ventricular noncompaction cardiomyopathy (LVNC) is a rare hereditary cardiomyopathy characterized by the formation of an outer compacted and inner noncompacted layer of the myocardium. The latter is characterized by prominent trabeculations and deep intertrabecular recesses and is functionally inferior to the compacted myocardium. As there is no specific treatment for patients with LVNC who develop heart failure, the management of these patients is limited and many patients progress to advanced stages of the disease. For LVNC patients with advanced heart failure, the data regarding the use of mechanical circulatory support are scarce. We report a case of a 29-year-old patient with LVNC and advanced refractory heart failure, who was successfully bridged to heart transplantation using a long-term continuous-flow left ventricular assist device.

Use of a Totally Artificial Heart for a Complex Postinfarction Ventricular Septal Defect

The incidence of cardiac rupture complicating myocardial infarction has declined since the introduction of thrombolytic therapy. Despite the advances in the management of myocardial infarction, cardiac rupture remains an important cause of death among infarction-related fatalities. We discuss a patient who presented to our hospital with myocardial infarction and who subsequently developed a complex ventricular septal rupture, for which surgical repair was not feasible. Implantation of a CardioWest Total Artificial Heart (SynCardia Systems) allowed for immediate hemodynamic stabilization and served as a bridge to transplantation.

Cell Therapy for Nonischemic Cardiomyopathy: Current Status and Future Perspectives

Currently, noni schemic dilated cardiomyopathy (NICM) represents the leading cause of advanced heart failure, accounting for >50% of all heart transplantation procedures. We propose that when compared with patients with ischemic heart failure (IHF), patients with NICM demonstrate a more favorable clinical response to cell therapy, which offers a potential novel promising treatment approach for this patient population. Chronic heart failure represents one of the most important healthcare problems worldwide. Although survival after diagnosis of heart failure has improved, overall mortality remains high.1 In the recent years, several novel approaches for heart failure management have been tested in clinical trials, with cell therapy representing one of potentially more promising treatment modalities. The majority of clinical trials of cell therapy in chronic heart failure have been focusing on patients with IHF. In this cohort, early trials demonstrated clinical benefits and an improvement in left ventricular function after cell therapy; however, subsequent larger trials failed to confirm these findings. Furthermore, a recent meta-analysis of 38 randomized controlled trials in IHF found only low-quality evidence that treatment with bone marrow-derived cells reduces mortality and improves left ventricular ejection fraction (LVEF).2 Although the reasons for the inconsistent results remain poorly defined, they could be partially explained by the fact that despite the potential beneficial effects on the myocardium, cell therapy does not affect the progression of atherosclerosis, which may limit the clinical efficacy of this approach in patients with IHF. In the last decade, NICM has become the leading cause of advanced heart failure, accounting for >50% of all heart transplantations.1 These trends indicate that patients with NICM may represent the largest subpopulation of heart failure patients with a particular need for alternative treatment modalities, including cell therapy. The disease progression …