Jerzy Pacholewicz

A differential release of matrix metalloproteinases 9 and 2 during coronary artery bypass grafting and off-pump coronary artery bypass surgery

OBJECTIVES Extracorporeal circulation is associated with the systemic inflammatory response syndrome. The objective of this study was to measure plasma and myocardial matrix metalloproteinase 2 and 9 levels in patients undergoing off-pump coronary artery bypass and coronary artery bypass grafting. METHODS Twenty patients subjected to coronary artery bypass grafting and 20 subjected to off-pump coronary artery bypass surgery were included in this study. In both procedures blood was collected in 7 equivalent time points up to 12 hours after grafting. The myocardial biopsy specimens were collected before and after extracorporeal circulation in the coronary artery bypass grafting group and after harvesting and completion of proximal anastomoses in the off-pump coronary artery bypass group. Matrix metalloproteinase levels were measured by means of zymography. Myeloperoxidase and tissue inhibitor of metalloproteinase 1 and 2 levels were measured with an enzyme-linked immunosorbent assay. RESULTS Coronary artery bypass grafting but not off-pump coronary artery bypass led to a 700- to 900-fold increase of plasma matrix metalloproteinase 9 levels. A small but significant increase in matrix metalloproteinase 2 levels was detected in both procedures. Myocardial matrix metalloproteinase 9 levels significantly increased at the end of coronary artery bypass grafting and off-pump coronary artery bypass. Increased matrix metalloproteinase 9 activity at the end of extracorporeal circulation was accompanied by augmentation of the endogenous matrix metalloproteinase inhibitors tissue inhibitor of metalloproteinase 1 and 2 in plasma, but its magnitude was unable to balance the plasma matrix metalloproteinase 9 increase. The matrix metalloproteinase 9 content in plasma at the end of extracorporeal circulation correlated with the myeloperoxidase plasma concentration (r(2) = 0.8212, P < 0.05). CONCLUSION We propose that release of matrix metalloproteinase 9 might contribute to the extracorporeal circulation-induced inflammatory reactions.

Persistent mild lesions in coronary angiography predict poor long-term survival of heart transplant recipients

BACKGROUND Even though coronary angiography (CAG) underestimates coronary allograft vasculopathy (CAV) development, especially in the distal parts of arteries, it remains a frame of reference for International Society for Heart and Lung Transplantation (ISHLT) CAV classification. A retrospective analysis was performed to assess the prognostic value of CAG findings. METHODS Among 310 orthotopic heart transplantation (OHT) recipients with at least 2 CAGs at 2-year intervals, we identified 197 (146 men and 41 women; 55 ± 13 years) without lesions (Group 0), 27 (15 men and 12 women; 58 ± 8 years) in whom mild changes remained in consecutive CAGs (Group 1), 28 (24 men and 4 women; 58 ± 10 years) in whom mild lesions decreased in consecutive CAGs (Group 1REG), and 58 (53 men and 5 women; 56 ± 10 years) in whom the stenosis criteria of ISHLT CAV 2 or 3 were covered (Group 2). We compared survival and other clinical variables among the groups. RESULTS The average follow-up was 10 ± 4 years. Forty-one (21%) deaths occurred in Group 0, 15 (56%) in Group 1 (p = 0.002), 9(31%) in Group 1REG (p = NS), and 26 (46%) in Group 2 (p = 0.004, chi-square test). Time free from all-cause death was significantly shorter in Group 1 (T1/2 = 8 years) than in Group 0 (T1/2 = 15.5 years; p = 0.00072, log-rank test). Time free from cardiovascular death was significantly shorter in Groups 1 and 2, as was time free from CAV-related death in Groups 1, 1REG, and 2. Multivariate analysis, using a Cox proportional hazards model, revealed that Group 1 inclusion criterion of CAG findings is an independent predictor of all-cause death, cardiovascular death, and CAV-related death. CONCLUSIONS Persistent mild coronary lesions, observed in consecutive CAG, predicted shorter survival of OHT recipients.

Von Willebrand factor in patients on mechanical circulatory support - a double-edged sword between bleeding and thrombosis.

Mechanical circulatory support (MCS) is an umbrella term describing the various technologies used in both short- and long-term management of patients with either end-stage chronic heart failure (HF) or acute HF. Most often, MCS has emerged as a bridge to transplantation, but more recently it is also used as a destination therapy. Mechanical circulatory support includes left ventricular assist device (LVAD) or bi-ventricular assist device (Bi-VAD). Currently, 2- to 3-year survival in carefully selected patients is much better than with medical therapy. However, MCS therapy is hampered by sometimes life-threatening complications including bleeding and device thrombosis. Von Willebrand factor (vWF) has two major functions in haemostasis. First, it plays a crucial role in platelet-subendothelium adhesion and platelet-platelet interactions (aggregation). Second, it is the carrier of factor VIII (FVIII) in plasma. Von Willebrand factor prolongs FVIII half-time by protecting it from proteolytic degradation. It delivers FVIII to the site of vascular injury thus enhancing haemostatic process. On one hand, high plasma levels of vWF have been associated with an increased risk of thrombosis. On the other, defects or deficiencies of vWF underlie the inherited von Willebrand disease or acquired von Willebrand syndrome. Here we review the pathophysiology of thrombosis and bleeding associated with vWF.

Mechanical circulatory support in cardiogenic shock - what every interventional cardiologist should know.

Cardiogenic shock (CS) remains the main cause of death in patients with myocardial infarction. Conservative treatment alone does not sufficiently improve prognosis. Mortality in CS can only be significantly reduced with revascularization, both surgical and percutaneous. However some patients present with haemodynamic instability despite optimal medical treatment and complete revascularization, resulting in very high mortality rates. These patients require the implementation of mechanical circulatory support in order to increase systemic blood flow, protect against organ hypoperfusion and protect the myocardium through a decrease in oxygen consumption. In contemporary interventional cardiology it seems that every operator should be aware of all available mechanical circulatory support methods for their patients. This article aims to present the current state of knowledge and technical possibilities in this area.

Mechanical circulatory support is effective to treat pulmonary hypertension in heart transplant candidates disqualified due to unacceptable pulmonary vascular resistance

Introduction High pulmonary vascular resistance (PVR) in orthotopic heart transplantation (OHT) candidates is a risk factor of right ventricle failure after the procedure. However, the increase of PVR may be a consequence of the life-threatening deterioration of the left ventricle function. The use of mechanical circulatory support (MCS) seems to be the best solution, but it is reimbursed only in active OHT candidates. Aim We performed a retrospective analysis of MCS effectiveness in maintaining PVR at values accepted for OHT. Material and methods Starting from the year 2008 we identified 6 patients (all males, 42.8 ±17 years old) with dilated (n = 3), ischemic (n = 2), and restrictive cardiomyopathy (n = 1) in whom MCS – pulsatile left ventricle assist device (LVAD, n = 4), continuous flow LVAD (n = 1), and pulsatile biventricular assist device (BIVAD, n = 1) – was used at a time when PVR was unacceptable for OHT, and the reversibility test with nitroprusside was negative. After an average time of support of 261 ±129 days they were all transplanted. Results Right heart catheterization (RHC) results before MCS implantation were as follows: pulmonary artery systolic, diastolic, and mean pressure (PAPs/d/m) 60 ±20/28 ±7/40 ±11 mm Hg, pulmonary capillary wedge pressure (PCWP) 21 ±7 mm Hg, transpulmonary gradient (TPG) 19 ±7 mm Hg, cardiac output (CO) 3.6 ±0.8 l/min, PVR 5.7 ±2.1 Wood units (WU). Right heart catheterization results during MCS therapy were as follows: PAPs/d/s 27 ±11/12 ±4/17 ±6 mm Hg, PCWP 10 ±4 mm Hg, TPG 7 ±4 mm Hg, CO 5.1 ±0.7 l/min, PVR 1.4 ±0.6 WU. None of the patients experienced right ventricle failure after OHT with only one early loss due to multiorgan failure. Conclusions Mechanical circulatory support is an effective method of pulmonary hypertension treatment for patients disqualified for OHT due to high PVR.

Bridge to recovery in two cases of dilated cardiomyopathy after long-term mechanical circulatory support.

Ventricular assist devices (VADs) have become an established therapeutic option for patients with end-stage heart failure. Achieving the potential for recovery of native heart function using VADs is an established form of treatment in a selected group of patients with HF. We report two cases of VAD patients with different types of pump used for mechanical circulatory support, a continuous flow pump (Heart-Ware®) and a pulsatile pump (POLVAD MEV®), which allow regeneration of the native heart. Patients were qualified as INTERMACS level 3-4 for elective implantation of an LVAD. Implantations were performed without complications. The postoperative course was uncomplicated. In the HeartWare patient the follow-up was complicated by episodes of epistaxis and recurrent GIB as well as driveline infection. The follow-up of the POLVAD MEV patient was uneventful. Recurrent GIB forced us to withdraw aspirin and warfarin therapy and maintain only clopidogrel in the HeartWare patient.. In mid-February 2013 the patient was admitted due to dysfunction of the centrifugal pump with a continuous low-flow alarm and increase power consumption. Under close monitoring of the patient a decision was made to stop the pump immediately and evaluate cardiac function. The serial echocardiography studies showed significant improvement in LVEF up to 45% and no significant valvular pathology. In February 2013 LVAD explant was performed by left thoracotomy without complications. At six-month follow-up the patient was in a good clinical condition, in NYHA class I/II, and on pharmacological treatment.

Surgical treatment of left main disease and severe carotid stenosis: does the off-pump technique provide a better outcome?

OBJECTIVES Left main disease (LMD), combined with carotid artery stenosis (CAS), constitutes a high-risk patient population. Priority is often given to coronary revascularization, due to the severity of the angina. However, the choice of revascularization strategy [off-pump coronary artery bypass (OPCAB) vs coronary artery bypass grafting (CABG)] remains elusive. METHODS A total of 1340 patients with LMD were non-randomly assigned to either on-pump (CABG group, n = 680) or off-pump (OPCAB group, n = 634) revascularization between 1 January 2006 and 21 September 2010. Multivariable regression was used to determine the risk-adjusted impact of a revascularization strategy on a composite in-hospital outcome (MACCE), and proportional hazards regression was used to define the variables affecting long-term survival. RESULTS Significant CAS was found in 130 patients: 84 (13.1%) patients underwent OPCAB, while 46 patients (6.8%) underwent CABG (P < 0.05). Patients with a history of stroke/transient ischaemic attack were also more likely to receive OPCAB (7.1 vs 4.7%; P = 0.08). OPCAB patients were older, in a higher New York Heart Association (NYHA) class, with a lower LVEF and higher EuroSCORE. A calcified aorta was found in 79 patients [OPCAB-CABG: 49 (7.73%) vs 30 (4.41%); P = 0.016] and resulted in a less complex revascularization (OPCAB-CABG: 2.3 ± 0.71 vs 3.19 ± 0.82; P < 0.05), and 30-day mortality was insignificantly higher in the CABG (2.7 vs 2.8%) as well as MACCE (11.2 vs 12.2%; P = NS). This trend reversed when late mortality was evaluated; however, it did not reach significance at 60 months. Preoperative renal impairment requiring dialysis was found to be a technique-independent predictor of MACCE. The number of arterial conduits also influenced MACCE. CONCLUSIONS Off-pump coronary revascularization may offer risk reduction of neurological complications in patients with a significant carotid artery disease and a history of previous stroke, but a larger study population is needed to support this thesis. The growing discrepancy in long-term survival should draw attention to a more complete revascularization in OPCAB patients.

Simplified, less-invasive left ventricular assist device implantation in patients with post-coronary artery bypass grafting

Less-invasive left ventricular assist device implantation is becoming the technique of choice for implementation of new-generation heart pumps. The less-invasive technique is particularly useful for patients with a history of cardiac surgical procedures, such as coronary artery bypass grafting. Yet, in redo cases, severe pericardial adhesions may force experienced operators to opt for alternative outflow graft placement, such as in the descending aorta. We propose a surgical technique in which the left ventricular device is implanted through a limited thoracic incision, with the outflow graft anastomosed to the ascending aorta, avoiding collision with coronary bypass grafts. The key element of the proposed technique is a tunnel connecting 2 pleural cavities, in which the outflow graft is placed, entirely bypassing the pericardium.

Emergency HeartWare Ventricular Assist Device (HVAD) exchange due to pump thrombosis using minimally invasive technique

Left ventricular assist device (LVAD) thrombosis remains a dreadful complication of mechanical circulatory support, with an incidence of 8–12% depending on the pump type and patient’s comorbidities. Fibrinolysis may be considered early in pump thrombosis, but when contraindicated a pump exchange remains the only alternative. This short report documents an emergency LVAD exchange in a 55-year-old man who underwent LVAD (HeartWare Inc) implantation in 2013 as a bridge to transplantation. Four months after the initial surgery, he suffered from a hemorrhagic stroke despite properly managed anticoagulation. On February 17th, 2017 he was re-admitted with LVAD pump thrombosis. As fibrinolysis was contraindicated, an emergency pump exchange was performed via a limited thoracic incision in order to minimize surgical trauma, reduce intraoperative complications and facilitate immediate post-operative recovery. This report documents the very first LVAD pump exchange as well as the first one performed via a minimally invasive approach in Poland.

Non-invasive assessment of thromboembolism in rotary blood pumps: case study

Thromboembolic complications are one of the major problems in mechanical heart support of patients suffering from critical heart failure. The goal of the study was to present and discuss methodology of non-invasive assessment of embolization in rotary blood pumps. The study was carried out based on power consumption trend analysis as well as spectral analysis of acoustic signal produced by the pump during its operation. It has been demonstrated that the trend of power rising and presence of 3rd harmonic in acoustic spectrum corresponds to the clinical symptoms of pump embolization.