Sakir Akin

The response of the microcirculation to cardiac surgery.

Purpose of review Cardiac surgery is associated with a wide range of microvascular derangements and with reduced tissue oxygenation. Although the macrohemodynamical targets during surgery may be achieved, the microcirculation may be damaged and remain dysfunctional. Direct observations of the microcirculation may enable more physiologically based approaches for diagnosis and treatment during cardiac surgery. Recent findings Microcirculation is the final destination of blood flow to the tissues for oxygen transport. Direct visualization of the microcirculation using hand-held microscopy can be considered the gold standard for tissue perfusion since the movement of single red blood cells can be observed and quantified. A new generation microcirculation-monitoring device is called CytoCam-Incident -Dark-Field imaging. This device has a high-resolution imaging sensor and shows approximately 30% more capillaries than the devices of the previous generations. On-pump and off-pump cardiac surgeries have induced different mechanism whose impact can be differentiated by observation of the sublingual microcirculation. Colloids may provide a better volume expansion and microcirculatory improvement than crystalloids although crytaloids may be more affective for hydration, and blood transfusions improves microcirculatory oxygenation by filling previously empty capillaries and reducing diffusion distances between oxygen carrying red blood cell and the parenchymal cells. Summary Direct visualization of the microcirculation using hand-held microscopy may provide the clinician the physiological feedback that is required for the early diagnosis and treatment of microcirculatory alterations during cardiac surgery. The coherence between the hemodynamic response of the macrocirculation and microcirculation during surgery seems to be essential.

Derivation and Validation of a Novel Right-Sided Heart Failure Model After Implantation of Continuous Flow Left Ventricular Assist Devices:The EUROMACS (European Registry for Patients with Mechanical Circulatory Support) Right-Sided Heart Failure Risk Score

Background: The aim of the study was to derive and validate a novel risk score for early right-sided heart failure (RHF) after left ventricular assist device implantation. Methods: The EUROMACS (European Registry for Patients with Mechanical Circulatory Support) was used to identify adult patients undergoing continuous-flow left ventricular assist device implantation with mainstream devices. Eligible patients (n=2988) were randomly divided into derivation (n=2000) and validation (n=988) cohorts. The primary outcome was early (<30 days) severe postoperative RHF, defined as receiving short- or long-term right-sided circulatory support, continuous inotropic support for ≥14 days, or nitric oxide ventilation for ≥48 hours. The secondary outcome was all-cause mortality and length of stay in the intensive care unit. Covariates found to be associated with RHF (exploratory univariate P<0.10) were entered into a multivariable logistic regression model. A risk score was then generated using the relative magnitude of the exponential regression model coefficients of independent predictors at the last step after checking for collinearity, likelihood ratio test, c index, and clinical weight at each step. Results: A 9.5-point risk score incorporating 5 variables (Interagency Registry for Mechanically Assisted Circulatory Support class, use of multiple inotropes, severe right ventricular dysfunction on echocardiography, ratio of right atrial/pulmonary capillary wedge pressure, hemoglobin) was created. The mean scores in the derivation and validation cohorts were 2.7±1.9 and 2.6±2.0, respectively (P=0.32). RHF in the derivation cohort occurred in 433 patients (21.7%) after left ventricular assist device implantation and was associated with a lower 1-year (53% versus 71%; P<0.001) and 2-year (45% versus 58%; P<0.001) survival compared with patients without RHF. RHF risk ranged from 11% (low risk score 0–2) to 43.1% (high risk score >4; P<0.0001). Median intensive care unit stay was 7 days (interquartile range, 4–15 days) versus 24 days (interquartile range, 14–38 days) in patients without versus with RHF, respectively (P<0.001). The c index of the composite score was 0.70 in the derivation and 0.67 in the validation cohort. The EUROMACS-RHF risk score outperformed (P<0.0001) previously published scores and known individual echocardiographic and hemodynamic markers of RHF. Conclusions: This novel EUROMACS-RHF risk score outperformed currently known risk scores and clinical predictors of early postoperative RHF. This novel score may be useful for tailored risk-based clinical assessment and management of patients with advanced HF evaluated for ventricular assist device therapy.

Monitoring microcirculation in critical illness.

Purpose of reviewCritical illness includes a wide range of conditions from sepsis to high-risk surgery. All these diseases are characterized by reduced tissue oxygenation. Macrohemodynamic parameters may be corrected by fluids and/or vasoactive compounds; however, the microcirculation and its tissues may be damaged and remain hypoperfused. An evaluation of microcirculation may enable more physiologically based approaches for understanding the pathogenesis, diagnosis, and treatment of critically ill patients. Recent findingsMicrocirculation plays a pivotal role in delivering oxygen to the cells and maintains tissue perfusion. Negative results of several studies, based on conventional hemodynamic resuscitation procedures to achieve organ perfusion and decrease morbidity and mortality following conditions of septic shock and other cardiovascular compromise, have highlighted the need to monitor microcirculation. The loss of hemodynamic coherence between the macrocirculation and microcirculation, wherein improvement of hemodynamic variables of the systemic circulation does not cause a parallel improvement of microcirculatory perfusion and oxygenation of the essential organ systems, may explain why these studies have failed. SummaryCritical illness is usually accompanied by abnormalities in microcirculation and tissue hypoxia. Direct monitoring of sublingual microcirculation using hand-held microscopy may provide a more physiological approach. Evaluating the coherence between macrocirculation and microcirculation in response to therapy seems to be essential in evaluating the efficacy of therapeutic interventions.

Short-term mechanical circulatory support as a bridge to durable left ventricular assist device implantation in refractory cardiogenic shock: a systematic review and meta-analysis.

Short-term mechanical circulatory support (MCS) is increasingly used as a bridge to decision in patients with refractory cardiogenic shock. Subsequently, these patients might be bridged to durable MCS either as a bridge to candidacy/transplantation, or as destination therapy. The aim of this study was to review support duration and clinical outcome of short-term MCS in cardiogenic shock, and to analyse application of this technology as a bridge to long-term cardiac support (left ventricular assist device, LVAD) from 2006 till June 2016. Using Cochrane Register of Trials, Embase and Medline, a systematic review was performed on patients with cardiogenic shock from acute myocardial infarction, end-stage cardiomyopathy, or acute myocarditis, receiving short-term MCS. Studies on periprocedural, post-cardiotomy and cardiopulmonary resuscitation support were excluded. Thirty-nine studies, mainly registries of heterogeneous patient populations (nu2009=u20094151 patients), were identified. Depending on the device used (intra-aortic balloon pump, TandemHeart, Impella 2.5, Impella 5.0, CentriMag and peripheral veno-arterial extracorporeal membrane oxygenation), mean support duration was (range) 1.6-25 days and the mean proportion of short-term MCS patients discharged was (range) 45-66%. The mean proportion of bridge to durable LVAD was (range) 3-30%. Bridge to durable LVAD was most frequently performed in patients with end-stage cardiomyopathy (22 [12-35]%). We conclude that temporary MCS can be used to bridge patients with cardiogenic shock towards durable LVAD. Clinicians are encouraged to share their results in a large multicentre registry in order to investigate optimal device selection and best duration of support.

Results of clinical application of the modified maze procedure as concomitant surgery

OBJECTIVESnAtrial fibrillation is the most common cardiac arrhythmia and is associated with significant morbidity and mortality. The classic cut-and-sew maze procedure is successful in 85-95% of patients. However, the technical complexity has prompted modifications of the maze procedure. The objective of this study was to retrospectively evaluate the clinical safety and efficacy of the maze treatment performed at our institution.nnnMETHODSnFrom March 2001 until February 2009, 169 patients underwent a modified maze procedure for atrial fibrillation at the Erasmus MC, Rotterdam. Patient characteristics, surgical procedure and follow-up data were obtained by reviewing the medical charts and consulting with the referring physicians. The efficacy of the procedure as measured by AF recurrence was analysed with a repeated measurements model. The quality of life of the patients was assessed with the SF-36 (a short-form health survey with 36 questions) questionnaire and compared with that of the general Dutch population.nnnRESULTSnOf the 169 patients who underwent a modified maze procedure, 163 had their maze procedure as a concomitant procedure. The 30-day mortality rate was 4.7% (n = 8). The rate of post-procedural AF recurrence varied significantly over time (P < 0.0001). Decreased left ventricular function, increased age and higher preoperative creatinine levels were predictors of AF recurrence. Quality of life, as measured with the SF-36 questionnaire, was comparable with that of the Dutch population for all health domains.nnnCONCLUSIONSnConcomitant maze is a relatively safe treatment that eliminates atrial fibrillation in the majority of patients, although the probability of recurrent AF increases with the passage of time. Decreased left ventricular function, increased age and higher preoperative creatinine levels are associated with an increased risk of AF recurrence.

Effect of collaterals on deaths and re-infarctions in patients with coronary artery disease: a meta-analysis

BackgroundIt is generally believed that there is a beneficial effect of collaterals on death and re-infarction statistics in patients with coronary artery disease (CAD) but studies to date are small and inconsistent.ObjectiveTo meta-analyse the studies published in this field in order to obtain more powerful information.MethodsWe searched Medline and major journals (2000 to 2011) for studies evaluating the effect of coronary collaterals on mortality. Publication bias, lack of heterogeneity, and lack of robustness were assessed using the standard procedures for such purposes.ResultsA total of 10 studies describing mortality, enrolling 6791 participants, were included in this analysis. In patients with collateralisation a significant relation with reduced mortality was seen compared with those without collateralisation, at an odds ratio of 0.47, pu2009<u20090.0001, and a reduction in deaths and re-infarctions at 0.54, pu2009<u20090.0001. Some publication bias, some heterogeneity and some lack of robustness were demonstrated. A meta-regression with the odds ratios of the presence of traditional atherosclerotic risk factors as predictors and the odds ratios of mortality and the composite deaths and re-infarctions as outcome showed no relationships.ConclusionsIn CAD patients from the post-percutaneous coronary intervention era the presence of collaterals reduced mortality by 0.47 (pu2009<u20090.0001) and deaths and re-infarctions by 0.54 (pu2009<u20090.0001). Furthermore, in the present meta-data, the atherosclerotic risk factors were no more present in patients with collaterals than they were in those without.

Haemolysis as a first sign of thromboembolic event and acute pump thrombosis in patients with the continuous-flow left ventricular assist device HeartMate II

BackgroundDespite advances in pump technology, thromboembolic events/acute pump thrombosis remain potentially life-threatening complications in patients with continuous-flow left ventricular assist devices (CF-LVAD). We sought to determine early signs of thromboembolic event/pump thrombosis in patients with CF-LVAD, which could lead to earlier intervention.MethodsWe analysed all HeartMate II recipients (nu2009=u200940) in our centre between December 2006 and July 2013. Thromboembolic event/pump thrombosis was defined as a transient ischaemic attack (TIA), ischaemic cerebrovascular accident (CVA), or pump thrombosis.ResultsDuring median LVAD support of 336 days [IQR: 182–808], 8 (20u2009%) patients developed a thromboembolic event/pump thrombosis (six TIA/CVA, two pump thromboses). At the time of the thromboembolic event/pump thrombosis, significantly higher pump power was seen compared with the no-thrombosis group (8.2u2009±u20093.0 vs. 6.4u2009±u20091.4xa0W, pu2009=u20090.02), as well as a trend towards a lower pulse index (4.1u2009±u20091.5 vs. 5.0u2009±u20091.0, pu2009=u20090.05) and a trend towards higher pump flow (5.7u2009±u20091.0 vs. 4.9u2009±u20091.9xa0L m, pu2009=u20090.06).The thrombosis group had a more than fourfold higher lactate dehydrogenase (LDH) median 1548 [IQR: 754–2379] vs. 363 [IQR: 325–443] U/L, pu2009=u20090.0001). Bacterial (nu2009=u20094) or viral (nu2009=u20091) infection was present in 5 out of 8 patients. LDH >u2009735xa0U/L predicted thromboembolic events/pump thrombosis with a positive predictive value of 88u2009%.ConclusionsIn patients with a CF-LVAD (HeartMate II), thromboembolic events and/or pump thrombosis are associated with symptoms and signs of acute haemolysis as manifested by a high LDH, elevated pump power and decreased pulse index, especially in the context of an infection.

Microcirculatory assessment of patients under VA-ECMO

BackgroundVeno-arterial extracorporeal membrane oxygenation (VA-ECMO) is an effective technique for providing emergency mechanical circulatory support for patients with cardiogenic shock. VA-ECMO enables a rapid restoration of global systemic organ perfusion, but it has not been found to always show a parallel improvement in the microcirculation. We hypothesized in this study that the response of the microcirculation to the initiation of VA-ECMO might identify patients with increased chances of intensive care unit (ICU) survival.MethodsTwenty-four patients were included in this study. Sublingual microcirculation measurements were performed using the CytoCam-IDF (incident dark field) imaging device. Microcirculatory measurements were performed at baseline, after VA-ECMO insertion (T1), 48–72xa0h after initiation of VA-ECMO (T2), 5–6 days after (T3), 9–10 days after (T4), and within 24xa0h of VA-ECMO removal.ResultsOf the 24 patients included in the study population, 15 survived and 9 died while on VA-ECMO. There was no significant difference between the systemic global hemodynamic variables at initiation of VA-ECMO between the survivors and non-survivors. There was, however, a significant difference in the microcirculatory parameters of both small and large vessels at all time points between the survivors and non-survivors. Perfused vessel density (PVD) at baseline (survivor versus non-survivor, 19.21 versus 13.78xa0mm/mm2, pu2009=u20090.001) was able to predict ICU survival on initiation of VA-ECMO; the area under the receiver operating characteristic curve (ROC) was 0.908 (95xa0% confidence interval 0.772–1.0).ConclusionPVD of the sublingual microcirculation at initiation of VA-ECMO can be used to predict ICU mortality in patients with cardiogenic shock.

Pre-operative proteinuria in left ventricular assist devices and clinical outcome

BACKGROUNDnThis study evaluated the association of pre-operative proteinuria before continuous flow left ventricular assist device (CF-LVAD) implantation in relation to mortality and the need for renal replacement therapy (RRT) during the first year of follow-up.nnnMETHODSnThis retrospective, multicenter cohort study evaluated all patients (n = 241) who underwent CF-LVAD implantation in the 2 participating tertiary referral centers. Patients were included if a urine dipstick was performed within 7 days before CF-LVAD implantation. Proteinuria was defined as trace or higher.nnnRESULTSnIn total, 173 patients (72%) were included (78% men; mean age, 52.3 ± 13.3; mean estimated glomerular filtration rate, 60.1 ± 25.9 mL/min/1.73 m2), and 42 patients (24%) had pre-operative proteinuria. The observed survival in patients with proteinuria vs without proteinuria was 57% vs 86% at 3 months and 52% vs 78% at 1 year (log-rank p < 0.001), respectively. In addition, during the first year after implantation, 32% of the patients with proteinuria and 15% of the patients without proteinuria required RRT (log-rank p = 0.02). Multivariate Cox regression analysis confirmed that pre-operative proteinuria was an independent predictor for mortality (adjusted hazard ratio, 2.09; 95% confidence interval, 1.10-3.80, p = 0.02) and for the need of RRT during the first year (adjusted hazard ratio, 2.23; 95% confidence interval, 1.13-4.84; p = 0.02).nnnCONCLUSIONSnProteinuria, which was present in 25% of all tested LVAD patients, predicts worse outcome in all-cause mortality and need of RRT in patients with a CF-LVAD. This warrants the use of proteinuria in risk stratification when selecting patients for CF-LVAD therapy.

Acute kidney injury and 1-year mortality after left ventricular assist device implantation

BACKGROUNDnData on the consequences of acute kidney injury (AKI) after continuous-flow left ventricle assist device (LVAD) implantation are scarce and inconsistent. In this study, we evaluated the incidence, predictors and the impact of AKI on mortality and renal function in the first year after LVAD implantation.nnnMETHODSnA retrospective, multicenter cohort study was conducted, including all patients (age ≥18 years) undergoing LVAD implantation (91% with a HeartMate II device and 9% with a HeartWare device). The definition proposed by the Kidney Disease Improving Global Outcome (KDIGO) criteria was used to define AKI.nnnRESULTSnOverall, 241 patients (mean age 52.4 ± 12.9 years, 76% males) were included in the study. AKI criteria were met in 169 (70%) patients, of whom 109 (45%) were in AKI Stage I, 22 (9%) in Stage II and 38 (16%) in Stage III. Two factors, the need for pre-operative inotropic support and pre-existent chronic kidney disease Stage ≤II (estimated glomerular filtration rate [eGFR] <30 ml/min/1.73 m2), were independently associated with the development of AKI and the severity of AKI stages. One-year mortality rates in patients without AKI and AKI Stages I, II and III were 18.7%, 26.4%, 23%, and 51%, respectively (log rank, p = 0.001). In the multivariable analysis, AKI Stage ≥II was independently associated with mortality (hazard ratio 2.2 [95% confidence interval 1.1 to 4.5], p = 0.027) and worse renal function (β = -7.4 [95% confidence interval -12.6 to -2.1], p < 0.01) at 1 year.nnnCONCLUSIONnAKI is highly frequent after LVAD implantation. More severe AKI stages are associated with higher mortality rates and impaired renal function at 1 year after LVAD implantation.