Protection Against Myocardial Ischemia and Reperfusion: Preconditioning, postconditioning and hibernation

Ischemic heart disease is currently the leading cause of morbidity and mortality in the industrialized world and is expected to become the leading cause of death world wide by the year 2020 when it will surpass infectious diseases.1, 2 In 2006 42,522 people died of cardiovascular disease (CVD) in the Netherlands. This translates into an average of 116 people per day that die due to CVD. When looking at all cause mortality one in every three persons dies due to CVD. Ischemic heart disease is the main component of this group with 12,491 deaths, while 9,976 deaths are due to cerebrovascular disease. Together they are responsible for 52% of the deaths in CVD. Around 70% of the people with ischemic heart disease die due to an acute myocardial infarction (AMI).3 The impact of CVD on health care is refl ected by the number of invasive interventions: the number of percutaneous coronary interventions (PCI) is still increasing (33,678 in 2006), while the number of open heart surgeries (coronary artery bypass grafting or CABG) is stable over the past 5 years (around 15,000).3 After myocardial infarction, the surviving myocardium undergoes a complex sequence of cardiac remodeling, which may have a benefi cial eff ect on cardiovascular performance in the short-term, but which become detrimental in the long-term and ultimately causes heart failure. In experimental studies, the degree of deleterious remodeling is highly aff ected by the size of the infarct.4 Accordingly, clinical reports indicate that infarct size estimated by peak plasma creatine kinase activity is an independent predictor of left ventricular remodeling and the subsequent devel

Remote monitoring of pulmonary artery pressures with cardiomems in patients with chronic heart failure and nyha class III: First experiences in the Netherlands

We report the first patient experiences with the CardioMEMS device in the Erasmus MC Thorax Center in the Netherlands. In line with clinical trial evidence, the device is applicable in patients with chronic heart failure in functional New York Heart Association class III with at least 1 admission for heart failure in the past 12 months. CardioMEMS has been shown to be safe and reliable, and effective in reducing the number of hospitalisations for heart failure by guided therapy based on pulmonary artery pressures

Transhepatic echocardiography: a novel approach for imaging in left ventricle assist device patients with difficult acoustic windows

Aims A significant proportion of left ventricle assist device (LVAD) patients have very difficult transthoracic echocardiographic images. The aim of this study was to find an echocardiographic window which would provide better visualization of the heart in LVAD patients with limited acoustic windows. ................................................................................................................................................................................................... Methods and results Based on the anatomic relationships in LVAD patients, a right intercostal transhepatic approach was proposed. By using a computer simulator, we searched for the appropriate probe orientation. Further, 15 ambulatory LVAD patients (age 56 ± 15 years, 73% males) underwent two echocardiographic studies: one normal transthoracic echocardiography following the institutional protocol (Echo 1) and a second study which included the transhepatic approach (Echo 2). The two exams were performed by two different sonographers and the results validated by a third observer for agreement. The transhepatic intercostal window was feasible in all patients, with an image quality allowing good visualization of structures in 93%. Precise quantification of the left ventricular (LV) and right ventricular (RV) function was achieved more often in the Echo 2 (10 vs. 3 patients for LV, P = 0.03 and 14 vs. 8 patients for RV, P = 0.04). A significant difference existed also in the quantification of the LVAD inflow cannula flow by pulsed Doppler (11 patients in Echo 2 vs. 3 patients in Echo 1, P = 0.009). ................

Omecamtiv mecarbil in precision-cut living heart failure slices: A story of a double-edged sword

Heart failure (HF) is a rapidly growing pandemic while medical treatment options remain limited. Omecamtiv mecarbil (OM) is a novel HF drug that directly targets the myosin heads of the cardiac muscle. This study used living myocardial slices (LMS) from patients with HF to evaluate the direct biomechanical effects of OM as compared to dobutamine. LMS were produced from patients with end-stage HF undergoing cardiac transplantation or left ventricular assist device implantation and cultured under electromechanical stimulation (diastolic preload: ca. 1 mN, stimulation frequency: 0.5 Hz). Dobutamine and omecamtiv mecarbil (OM) were administered on consecutive days and biomechanical effects were continuously recorded with dedicated force transducers. OM and dobutamine significantly increased contractile force to a similar maximum force, but OM also increased median time-to-peak with 48 % (p = 0.046) and time-to-relaxation with 68 % (p = 0.045). OM administration led to impaired relaxation of HF LMS with increasing stimulation frequencies, which was not observed with dobutamine. Furthermore, the functional refractory period was significantly shorter after administration of OM compared to dobutamine (235 ms (200–265) vs. 270 ms (259–283), p = 0.035). In conclusion, OM increased contractile force and systolic duration of HF LMS, indicating an improvement in cardiac function and normalization of systolic time intervals in patients with HF. Conversely, OM slowed relaxation, which could lead to diastolic filling abnormalities. As such, OM showed benefits on systolic function on one hand but potential hindrances of diastolic function on the other hand

Omecamtiv mecarbil in precision-cut living heart failure slices: A story of a double-edged sword

Heart failure (HF) is a rapidly growing pandemic while medical treatment options remain limited. Omecamtiv mecarbil (OM) is a novel HF drug that directly targets the myosin heads of the cardiac muscle. This study used living myocardial slices (LMS) from patients with HF to evaluate the direct biomechanical effects of OM as compared to dobutamine. LMS were produced from patients with end-stage HF undergoing cardiac transplantation or left ventricular assist device implantation and cultured under electromechanical stimulation (diastolic preload: ca. 1 mN, stimulation frequency: 0.5 Hz). Dobutamine and omecamtiv mecarbil (OM) were administered on consecutive days and biomechanical effects were continuously recorded with dedicated force transducers. OM and dobutamine significantly increased contractile force to a similar maximum force, but OM also increased median time-to-peak with 48 % (p = 0.046) and time-to-relaxation with 68 % (p = 0.045). OM administration led to impaired relaxation of HF LMS with increasing stimulation frequencies, which was not observed with dobutamine. Furthermore, the functional refractory period was significantly shorter after administration of OM compared to dobutamine (235 ms (200–265) vs. 270 ms (259–283), p = 0.035). In conclusion, OM increased contractile force and systolic duration of HF LMS, indicating an improvement in cardiac function and normalization of systolic time intervals in patients with HF. Conversely, OM slowed relaxation, which could lead to diastolic filling abnormalities. As such, OM showed benefits on systolic function on one hand but potential hindrances of diastolic function on the other hand

Preventing LVAD implantation by early short-term mechanical support and prolonged inodilator therapy

Cardiogenic shock continues to be a life-threatening condition carrying a high mortality and morbidity, where the prognosis remains poor despite intensive modern treatment modalities. In recent years, mainly technical improvements have led to a more widespread use of short- and long-term mechanical circulatory support, such as veno-arterial extracorporeal membrane oxygenation (VA-ECMO) and left ventricular assist devices (LVADs). Currently, LVADs are indispensable as 'bridge' to cardiac recovery, heart transplantation (HTX), and/or as destination therapy Importantly, both LVADs and HTX put a vast burden on financial resources, besides significant short- and long-term risks of morbidity and mortality. These considerations underscore the importance of optimal timing and appropriate patient selection for LVAD therapy, avoiding as much as possible an unfortunate and costly clinical path. In this report, we present a series of three cases with acute refractory cardiogenic shock ('crash and burn', INTERMACS profile 1) successfully treated by ECMO and early optimal medical therapy preventing a certain path towards LVAD and/or HTX, for which they were initially referred. This conservative approach in INTERMACS profile one patients warrants very early introduction of adequate medical heart failure therapy under the umbrella of a combination of short-term mechanical circulatory and inotropic support by phosphodiesterase inhibitors. Therefore, this novel combined medical-mechanical approach could have important clinical implications for this extremely challenging patient category, as it may avoid an unnecessary and costly clinical path towards LVAD and/or heart transplantation