The effect of three major co-morbidities on quality of life and outcome of patients with heart failure with reduced ejection fraction.

AIMS: Diabetes mellitus, chronic obstructive pulmonary disease, and chronic kidney disease are prevalent in patients with heart failure with reduced ejection fraction (HFrEF). We have analysed the impact of co-morbidities on quality of life (QoL) and outcome. METHODS AND RESULTS: A total of 397 patients (58.8 ± 11.0 years, 73.6% with New York Heart Association functional class ≥3) with stable advanced HFrEF were followed for a median of 1106 (inter-quartile range 379-2606) days, and 68% of patients (270 patients) experienced an adverse outcome (death, urgent heart transplantation, and implantation of mechanical circulatory support). Chronic obstructive pulmonary disease was present in 16.4%, diabetes mellitus in 44.3%, and chronic kidney disease in 34.5% of patients; 33.5% of patients had none, 40.0% had one, 21.9% had two, and 3.8% of patient had three co-morbidities. Patients with more co-morbidities reported similar QoL (assessed by Minnesota Living with Heart Failure Questionnaire, 45.46 ± 22.21/49.07 ± 21.69/47.52 ± 23.54/46.77 ± 23.60 in patients with zero to three co-morbidities, P for trend = 0.51). Multivariable regression analysis revealed that furosemide daily dose, systolic blood pressure, New York Heart Association functional class, and body mass index, but not the number of co-morbidities, were significantly (P < 0.05) associated with QoL. Increasing co-morbidity burden was associated with worse survival (P < 0.0001), lower degree of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker treatment (P = 0.001), and increasing levels of BNP (mean of 685, 912, 1053, and 985 ng/L for patients with zero to three co-morbidities, P for trend = 0.008) and cardiac troponin (sm-cTnI, P for trend = 0.0496), which remained significant (P < 0.05) after the adjustment for left ventricular ejection fraction, left ventricular end-diastolic diameter, right ventricular dysfunction grade, body mass index, and estimated glomerular filtration rate. CONCLUSIONS: In stable advanced HFrEF patients, co-morbidities are not associated with impaired QoL, but negatively affect the prognosis both directly and indirectly through lower level of HF pharmacotherapy and increased myocardial stress and injury.

Clinical correlates of B-type natriuretic peptide monitoring in outpatients with left ventricular assist device.

BACKGROUND: B-type natriuretic peptide (BNP) is a strong predictor of prognosis in chronic heart failure. We aimed to evaluate the clinical correlates and interpretation of BNP monitoring in LVAD out-patient recipients. METHODS: We performed a prospective study in 136 individuals after HeartMate II LVAD implantation. During follow-up they were divided into group A (severe adverse events requiring hospitalisation), group B (mild to moderate adverse events) and group C (an uneventful course). BNP was measured pre-implant, at the first out-patient visit, and then every 2 months. We identified the lowest level, and the level at the clinical event and/or the highest value in patients without clinical events (BNP peak). RESULTS: During a median follow-up of 298 days, 8 patients (6%) died, 21 patients (15%) experienced a severe adverse event (group A) and 38 patients (28%) had other adverse event (group B). Both the absolute value of BNP peak and its percentage values relative to pre-implant, first visit and minimum BNP had similar areas under the curve (AUC) to identify individuals with adverse events (group A and B) from group C. The performance of BNP peak rose from detection of infection to diagnosis of heart failure and culminated in individuals with pump thrombosis (AUC 0.68 vs. 0.75 vs. 0.93). CONCLUSIONS: Serial measurement of BNP in outpatients with LVAD correlates with the occurrence of adverse events. Assessment of absolute values of BNP peak seems to have a similar accuracy to analysis of intra-individual variation of BNP and it is more practical.

Biphasic response in number of stem cells and endothelial progenitor cells after left ventricular assist device implantation: A 6month follow-up.

BACKGROUND: Continuous blood flow could have deleterious effects on endothelium and vascular health. This could have serious consequences in patients with heart failure treated with continuous flow left ventricular assist devices (LVAD). Therefore, we studied effect of LVAD on three circulating vascular biomarkers: stem cells (SC), endothelial progenitor cells (EPC) and microparticles (MP). METHODS: In 23 patients (5 women) with end-stage heart failure, SC, EPC and MP were measured before, and 3 and 6months after implantation of LVAD (HeartMate II). SC were defined using determination of surface antigen expression as mononuclear CD34+/CD45low+ cells and EPC as mononuclear CD34+/CD45low+/KDR+ cells. MP concentrations were determined by ELISA method. RESULTS: Three months after LVAD implantation numbers of SC and EPC significantly decreased (p=0.01 and p=0.001, respectively). On the contrary, between 3rd and 6th month after implantation they significantly increased (p=0.006 and p=0.003, respectively).MP did not change significantly during the study despite exerting similar trend as SC and EPC. CONCLUSIONS: Observed biphasic changes of SC and EPC might reflect two processes. First, shortly after LVAD implantation, improved tissue perfusion could lead to decrease in ischemic stimuli and ensuing decrease of SC and EPC. Second, continuous flow between 3rd and 6th month produced by LVAD could lead to increase of SC and EPC through activation of endothelium. This explanation could be supported also by similar trend in the changes of concentrations of MP.

Bridge to transplantation with long-term mechanical assist device in adults after the Mustard procedure.

BACKGROUND: There is limited clinical experience with bridging to transplant with a left ventricular assist device (VAD) in patients with previously palliated transposition of great arteries. METHODS: Five adult patients presenting with systemic right ventricular failure 30 years after a Mustard operation were implanted with a HeartMate II VAD. The implant was completed using standard procedures with only minor modifications to accommodate right ventricular cannulation. RESULTS: All 5 patients were men, with a mean age of 31.5 ± 1.8 years and a median time since Mustard operation of 30 (range 28 to 32) years. All patients had sternal closure on Post-operative Day (POD) 1, and 2 patients required additional re-operation for bleeding. One patient required temporary support of the non-systemic ventricle. The mean duration of VAD support was 284 ± 177 days; 3 patients underwent heart transplant and 2 died on PODs 502 and 34, respectively. Both deaths were due to progressive heart failure and pump thrombosis. Comorbidities, anatomy and mediastinal scarring did not preclude implantation and heart failure symptoms improved in all patients. CONCLUSIONS: With the increased prevalence of late post-Mustard heart failure, bridge to transplant with a VAD may be a suitable treatment option for patients who are severely ill.

[30 years heart transplantation program in Institute for Clinical and Experimental Medicine in Prague]. / 30 let programu transplantace srdce v Institutu klinické a experimentální medicíny v Praze.

Heart transplantation has become in recent decades an established method for the treatment of advanced heart failure. Precisely, it was in January 2014 when 30 years have passed since the start of clinical heart transplantation program at the Institute for Clinical and Experimental Medicine. 936 heart transplants were performed by the end of 2013. The transplant program has reached considerable development since its beginnings. The knowledge of whole issue has deepened, indication criteria have been extended, new immunosuppressives are available and many of them are still in research. Life expectancy of patients has been prolonged and quality of life has improved. Nevertheless, the care of transplant patient is very complicated task for medical professionals and brings a lot of problems to solve.

Case report: atypical fungal obstruction of the left ventricular assist device outflow cannula.

We describe a very rare case of outflow cannula obstruction with fungal infectious thrombus formation. Discussion includes the etiology, diagnosis, and management of fungal infection complications related with long-term mechanical circulatory support. Left ventricular assist devices (LVADs) are increasingly used as bridge to transplant and permanent long-term therapy in the population with end-stage heart failure. Even though better clinical outcomes have been achieved with the newer-generation continuous-flow devices, infection complications are still a major risk for patients with continuous-flow LVAD implantation in long-term follow-up [Ann Thorac Surg 90:1270-1277, 2010]. Device-related infections can be categorized as driveline infections, pump-pocket infections, and LVAD-associated endocarditis [Expert Rev Med Devices 8: 627-634, 2011]. The microbiological profile is very heterogeneous; the most common pathogens are Staphylococcus, Pseudomonas, Streptococcus species, and Candida. Severe fungal infection may lead to dysfunction of the LVAD due to obstructive mass formation within the device. Due to the only anecdotal reports in the current literature, we present a very rare case of outflow fungal infectious thrombus formation leading to outflow cannula obstruction in patient with LVAD.

Fungal infections associated with long-term mechanical circulatory support-diagnosis and management.

Left ventricular assist devices (LVADs) are increasingly used as a treatment option for advanced heart failure. Fungal infections present a serious concern given the high association with major adverse events including death in this group of patients. The objective of this review is to summarize the incidence, risk factors, method for diagnosis, complication rate, and outcomes in patients with VADs who develop fungal infections.

Is severe cardiac dysfunction a contraindication for complex combined oncotherapy of Hodgkin's lymphoma? Not any more.

Hodgkin's lymphoma is a quite frequent diagnosis, particularly in younger patients, which is normally treated effectively with combined chemotherapy and radiotherapy. Cardiomyopathy induced by these treatments is not uncommon and may progress to advanced-stage heart failure. Due to the cardiotoxicity of chemotherapy for Hodgkin's disease, preexisting heart failure precludes usual therapy. We present a novel strategy of hemodynamic stabilization with an implantable left ventricular assist device (LVAD) prior to radical oncotherapy for Hodgkin's lymphoma. A 33-year-old man with a short history of progressive heart failure was hospitalized due to progressive symptoms. An echocardiogram revealed a dilated left ventricle with an ejection fraction of 18%, moderate right ventricular dysfunction, and moderate to severe tricuspid regurgitation. Supradiaphragmatic-stage Hodgkin's lymphoma was also diagnosed. Due to severe cardiac dysfunction, the patient was not a candidate for the usual chemotherapy and radiotherapy prescribed for this diagnosis. After multidisciplinary consultation and consent from the patient, an LVAD was implanted with tricuspid valve repair. Additionally, affected lymph nodes from the ventral upper mediastinum were excised, and pathological analysis confirmed the lymphoma diagnosis. The patient recovered from surgery and the postoperative course was uneventful. With LVAD support and normalized hemodynamics, chemotherapy and radiotherapy for his Hodgkin's lymphoma were completed, and the patient remains in complete remission documented by positron emission tomography/computed tomography and is well one since LVAD implantation.

The impact of left ventricle assist device on circulating endothelial microparticles - pilot study.

OBJECTIVES: Recent technological breakthroughs in the design of reliable systems for long term non-pulsatile mechanical heart support offer the possibility to study the effect of continuous blood flow in the vascular system. Generally, it is assumed that the absence of physiological pulsatile flow leads to prothrombogenic and proatherogenic changes. We investigated the change in the circulating endothelial microparticle concentration as a marker of endothelial damage in patients implanted with a continuous-flow left ventricle assist device (LVAD). METHODS: Endothelial microparticles were measured in 8 males (mean age 54.1±11.5 years) with terminal heart failure before and 3 months after implantation of an LVAD. The group consisted of 3 patients with dilated cardiomyopathy, 3 patients with ischemic cardiomyopathy, 1 patient with both conditions and 1 patient with congenital valvular disease. The concentration of endothelial microparticles was determined by ELISA Zymutest MP activity test. RESULTS: We did not observe a significant change in the concentration of circulating endothelial microparticles measured before and 3 months after implantation (p=0.669). High inter-individual variability in response to implantation was found. However, no association between a change in endothelial microparticle concentration and heart failure aetiology or a significant clinical complication attributed to LVAD implantation was observed. CONCLUSION: Results from this preliminary pilot study do not indicate that LVADs contribute to short-term vascular damage as defined by an increase in circulating endothelial microparticles.

The hemodynamic effect of right ventricle (RV), RT3DE targeted left ventricle (LV) and biventricular (BIV) pacing in the early postoperative period after cardiac surgery.

BACKGROUND: Congestive heart failure negatively impacts the prognosis in patients after cardiac surgery. The aim of our study was to assess the value of targeted cardiac resynchronization therapy (CRT) within 72 hours after cardiac surgery in patients with mechanical dyssynchrony, who had an ejection fraction ≤ 35%, QRS ≥150 ms or between 120 and 150 ms. METHODS: A prospective randomized trial based on three-dimensional echocardiography (RT3DE) and optimized sequential dual-chamber (DDD ) pacing in patients after cardiac surgery. DDD epicardial pacing (Medtronic coaxial epicardial leads 6495) was provided by a modified Medtronic INSYNC III Pacemaker (Medtronic Inc., Minneapolis, MN, USA). SUMMARY OF RESULTS: The study included 21 patients with ischemic heart disease (HD) or valvular HD (16 men, 5 women, average age 69 years) with left ventricle (LV) dysfunction after cardiac surgery . Patients with biventricular (BIV) (CO 6.7 ± 1.7 L/min, CI 3.5 ± 0.8 L/min/m(2) ) and LV (CO 6.2 ± 1.5 L/min, CI 3.2 ± 0.7 L/min/m(2) ) pacing had statistically significantly higher CO and CI than patients with right ventricular (RV) (CO 5.4 ± 1.4 L/min, CI 2.8 ± 0.6 L/min/m(2) ) pacing (BIV vs RV P ≤ 0.001; LV vs RV P ≤ 0.05; BIV vs LV P ≤ 0.05). CONCLUSIONS: RT3DE targeted and optimized CRT in the early postperative period after cardiac surgery provided better hemodynamic results than RV pacing.

How does successful bridging with ventricular assist device affect cardiac transplantation outcome?

A best evidence topic in cardiac surgery was written according to a structured protocol. The issue was to determine the impact of bridge-to-transplant ventricular assist device support on survival after cardiac transplantation. Altogether 428 papers were found using the reported search, of which 12 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. The treatment options for patients with advanced heart failure or those with deteriorating end-organ function on maximal medical therapy are limited to intravenous inotropes and mechanical assistance with intra-aortic balloon pump (IABP) or ventricular assist device (VAD). Studies exploring the effect of VADs on post-transplant mortality have yielded conflicting results. The Registry of the International Society for Heart and Lung Transplantation continues to identify mechanical support as a risk factor for decreased survival after transplantation. A limitation of this report is that the multivariable adjustment uses variables recorded not at the time of device implant but at the time of transplant. Some of the recipient characteristics thus may be altered by the device implant. Compared with the previous reports the latest data show improvement in post-transplant survival in the recent era. In addition, the excess risk appears to be limited to the early post-transplant period. Experienced centers consistently report outstanding post-transplant results with left ventricular assist device (LVAD) bridging. Of the 12 papers seven showed no difference in survival, and five showed a reduced survival. In the papers showing no difference, one year survival averaged from 85% in supported patients to 87% in non-supported patients. In papers reporting a difference in outcome, one year averaged survival was 74% in LVAD recipients compared to 90% in non-bridged patients. Decreased survival is associated with patients suffering from dilated cardiomyopathy, transplanted within two weeks of LVAD implantation and bridged to transplantation before 2003 as opposed to patients transplanted more recently. Based on the available evidence we conclude that in selected patients survival after heart transplantation in patients bridged with VAD is comparable to those who did not receive the device.

[Benefit of paracorporeal pulsatile assist device in multiorgan failing patients in terminal stage of heart failure]. / Prínos dlouhodobé pulzatilní mechanické srdecní podpory u multiorgánove selhávajících pacientu v terminálním srdecním selhání.

BACKGROUND: Prevalence of terminal forms of heart failure is steadily increasing and thus waiting time for heart transplantation, too. Increasing mortality on waiting list has urged implementation of mechanical circulatory support as an adjunct to the programme of heart transplantation. The objective of the study is to review 7-years experience with paracorporeal assist device in bridging to transplantation. MATERIAL AND METHODS: Retrospective review of 53 transplant candidates treated since April 2003. 50 patients received paracorporeal assist devices in biventricular configuration. Most frequent diagnosis was dilated cardiomyopathy in 51%. RESULTS: Despite a high risk profile of the patients, 37 of them were successfully transplanted (69.8%). Cumulative support has reached 3513 days. Local exit sites infection was identified as a most frequent complication, sepsis as a most frequent cause of death on support (18.8%). 30-days post-transplant mortality remained low at 5.7%. CONCLUSIONS: Paracorporeal mechanical circulatory assist devices remain effective alternative for terminal stage heart transplant candidates, especially for those in multiorgan failure who require biventricular support. Success rate of bridging to transplantation is acceptable, as well as complications rate and quality of life while on support. Long-term post-transplant survival is not inferior to the results of procedures performed without necessity of previous implantation of the assist device.