Jan Bělohlávek

Angiotensin Receptor Neprilysin Inhibition Compared With Enalapril on the Risk of Clinical Progression in Surviving Patients With Heart Failure

Background— Clinical trials in heart failure have focused on the improvement in symptoms or decreases in the risk of death and other cardiovascular events. Little is known about the effect of drugs on the risk of clinical deterioration in surviving patients. Methods and Results— We compared the angiotensin-neprilysin inhibitor LCZ696 (400 mg daily) with the angiotensin-converting enzyme inhibitor enalapril (20 mg daily) in 8399 patients with heart failure and reduced ejection fraction in a double-blind trial. The analyses focused on prespecified measures of nonfatal clinical deterioration. In comparison with the enalapril group, fewer LCZ696-treated patients required intensification of medical treatment for heart failure (520 versus 604; hazard ratio, 0.84; 95% confidence interval, 0.74–0.94; P=0.003) or an emergency department visit for worsening heart failure (hazard ratio, 0.66; 95% confidence interval, 0.52–0.85; P=0.001). The patients in the LCZ696 group had 23% fewer hospitalizations for worsening heart failure (851 versus 1079; P<0.001) and were less likely to require intensive care (768 versus 879; 18% rate reduction, P=0.005), to receive intravenous positive inotropic agents (31% risk reduction, P<0.001), and to have implantation of a heart failure device or cardiac transplantation (22% risk reduction, P=0.07). The reduction in heart failure hospitalization with LCZ696 was evident within the first 30 days after randomization. Worsening of symptom scores in surviving patients was consistently more common in the enalapril group. LCZ696 led to an early and sustained reduction in biomarkers of myocardial wall stress and injury (N-terminal pro–B-type natriuretic peptide and troponin) versus enalapril. Conclusions— Angiotensin-neprilysin inhibition prevents the clinical progression of surviving patients with heart failure more effectively than angiotensin-converting enzyme inhibition. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01035255.

Primary angioplasty in acute myocardial infarction with right bundle branch block: should new onset right bundle branch block be added to future guidelines as an indication for reperfusion therapy?

Aims The current guidelines recommend reperfusion therapy in acute myocardial infarction (AMI) with ST-segment elevation or left bundle branch block (LBBB). Surprisingly, the right bundle branch block (RBBB) is not listed as an indication for reperfusion therapy. This study analysed patients with AMI presenting with RBBB [with or without left anterior hemiblock (LAH) or left posterior hemiblock (LPH)] and compared them with those presenting with LBBB or with other electrocardiographic (ECG) patterns. The aim was to describe angiographic patterns and primary angioplasty use in AMI patients with RBBB. Methods and results A cohort of 6742 patients with AMI admitted to eight participating hospitals was analysed. Baseline clinical characteristics, ECG patterns, coronary angiographic, and echocardiographic data were correlated with the reperfusion therapies used and with in-hospital outcomes. Right bundle branch block was present in 6.3% of AMI patients: 2.8% had RBBB alone, 3.2% had RBBB + LAH, and 0.3% had RBBB + LPH. TIMI flow 0 in the infarct-related artery was present in 51.7% of RBBB patients vs. 39.4% of LBBB patients (P = 0.023). Primary percutaneous coronary intervention (PCI) was performed in 80.1% of RBBB patients vs. 68.3% of LBBB patients (P< 0.001). In-hospital mortality of RBBB patients was similar to LBBB (14.3 vs. 13.1%, P = 0.661). Patients with new or presumably new blocks had the highest (LBBB 15.8% and RBBB 15.4%) incidence of cardiogenic shock from all ECG subgroups. Percutaneous coronary intervention was done more frequently (84.8%) in patients with new or presumably new RBBB when compared with other patients with blocks (old RBBB 66.0%, old LBBB 62.3%, new or presumably new LBBB 73.0%). In-hospital mortality was highest (18.8%) among patients presenting with new or presumably new RBBB, followed by new or presumably new LBBB (13.2%), old LBBB (10.1%), and old RBBB (6.4%). Among 35 patients with acute left main coronary artery occlusion, 26% presented with RBBB (mostly with LAH) on the admission ECG. Conclusion Acute myocardial infarction with RBBB is frequently caused by the complete occlusion of the infarct-related artery and is more frequently treated with primary PCI when compared with AMI + LBBB. In-hospital mortality of patients with AMI and RBBB is highest from all ECG presentations of AMI. Restoration of coronary flow by primary PCI may lead to resolution of the conduction delay on the discharge ECG. Right bundle branch block should strongly be considered for listing in future guidelines as a standard indication for reperfusion therapy, in the same way as LBBB.

Coronary versus carotid blood flow and coronary perfusion pressure in a pig model of prolonged cardiac arrest treated by different modes of venoarterial ECMO and intraaortic balloon counterpulsation

IntroductionExtracorporeal membrane oxygenation (ECMO) is increasingly used in cardiac arrest (CA). Adequacy of carotid and coronary blood flows (CaBF, CoBF) and coronary perfusion pressure (CoPP) in ECMO treated CA is not well established. This study compares femoro-femoral (FF) to femoro-subclavian (FS) ECMO and intraaortic balloon counterpulsation (IABP) contribution based on CaBF, CoBF, CoPP, myocardial and brain oxygenation in experimental CA managed by ECMO.MethodsIn 11 female pigs (50.3 ± 3.4 kg), CA was randomly treated by FF versus FS ECMO ± IABP. Animals under general anesthesia had undergone 15 minutes of ventricular fibrillation (VF) with ECMO flow of 5 to 10 mL/kg/min simulating low-flow CA followed by continued VF with ECMO flow of 100 mL/kg/min. CaBF and CoBF were measured by a Doppler flow wire, cerebral and peripheral oxygenation by near infrared spectroscopy. CoPP, myocardial oxygen metabolism and resuscitability were determined.ResultsCaBF reached values > 80% of baseline in all regimens. CoBF > 80% was reached only by the FF ECMO, 90.0% (66.1, 98.6). Addition of IABP to FF ECMO decreased CoBF to 60.7% (55.1, 86.2) of baseline, P = 0.004. FS ECMO produced 70.0% (49.1, 113.2) of baseline CoBF, significantly lower than FF, P = 0.039. Addition of IABP to FS did not change the CoBF; however, it provided significantly higher flow, 76.7% (71.9, 111.2) of baseline, compared to FF + IABP, P = 0.026. Both brain and peripheral regional oxygen saturations decreased after induction of CA to 23% (15.0, 32.3) and 34% (23.5, 34.0), respectively, and normalized after ECMO institution. For brain saturations, all regimens reached values exceeding 80% of baseline, none of the comparisons between respective treatment approaches differed significantly. After a decline to 15 mmHg (9.5, 20.8) during CA, CoPP gradually rose with time to 68 mmHg (43.3, 84.0), P = 0 .003, with best recovery on FF ECMO. Resuscitability of the animals was high, both 5 and 60 minutes return of spontaneous circulation occured in eight animals (73%).ConclusionsIn a pig model of CA, both FF and FS ECMO assure adequate brain perfusion and oxygenation. FF ECMO offers better CoBF than FS ECMO. Addition of IABP to FF ECMO worsens CoBF. FF ECMO, more than FS ECMO, increases CoPP over time.

Long-term prognostic impact of hyponatremia in the ST-elevation myocardial infarction

Abstract Aims. The aim of the study was to analyse in-hospital outcomes and long-term prognostic implications of reduced sodium serum level (S-Na) in the early phase of ST elevation myocardial infarction (STEMI) treated, primarily, with direct percutaneous coronary intervention (dPCI). Methods and results. The study included 218 consecutive patients (144 males, the mean age 64 ± 13 years) with no history of heart failure admitted with acute STEMI. Out of them, 193 (88.5%) patients were treated with dPCI. The mean follow-up period was 39 ± 21 months. Hyponatremia was defined as S-Na value < 135 mmol/L. A total of 72 (33%) patients reached hyponatremia level; 51(23.4%) of them at admission and 21 (9.6%) later during hospitalization. The hyponatremic patients more frequently presented with reduced left ventricular systolic function, Killip class III or IV and were at increased risk of developing cardiogenic shock compared to patients with normonatremia. Compared to the rest of the population, patients who developed hyponatremia later during hospitalization had higher incidence of acute renal failure; (12 patients/6.1% vs. 5 patients/25.5%, p < 0.05). The difference in long-term survival between the hyponatremia and normonatremia groups was significant (p = 0.01, log-rank test). The multiple analysis of variance identified decrease of S-Na levels at admission independently associated with total mortality (p = 0.05). Conclusion. Patients who developed hyponatremia in the early phase of STEMI were at higher risk of worse in-hospital clinical outcome. During the long-term follow-up, higher mortality rates were recorded in hyponatremic patients.

Extra corporeal membrane oxygenation in the therapy of cardiogenic shock (ECMO-CS): rationale and design of the multicenter randomized trial: Extra Corporeal Membrane Oxygenation in the therapy of Cardiogenic Shock (ECMO-CS)

Extracorporeal membrane oxygenation (ECMO) in veno‐arterial configuration represents an increasingly used method for circulatory support. ECMO in cardiogenic shock offers rapid improvement of circulatory status and significant increase in tissue perfusion. Current evidence on the use of ECMO in cardiogenic shock remains insufficient. The aim of the ECMO‐CS trial is to compare two recognized therapeutic approaches in the management of severe cardiogenic shock: early conservative therapy and early implantation of veno‐arterial ECMO on the background of standard care.

Time to start of cardiopulmonary resuscitation and the effect of target temperature management at 33 °C and 36 °C☆

INTRODUCTION The optimal temperature during targeted temperature management (TTM) for comatose patients resuscitated from out-of-hospital cardiac arrest is unknown. It has been hypothesized that patients with long no-flow times, for example those without bystander CPR would have the most to gain from temperature management at lower temperatures. METHODS We analysed data from an international clinical trial randomizing cardiac arrest patients to targeted temperature management at 33°C and 36°C for an interaction between no-flow time and intervention group, with neurological function at six months after cardiac arrest as the primary outcome. A cerebral performance category (CPC) score of 1 or 2 was considered a good outcome. RESULTS No-flow time (min) was associated with poor neurological outcome (OR 1.13, 95% confidence interval 1.06-1.20, p<0.001). There was no statistically significant interaction between no flow-time and intervention group (p=0.11), which may imply that the non-superior effect of 33°C was consistent for all no-flow times. Bystander CPR was not independently associated with neurological function. CONCLUSIONS TTM at 33°C compared to 36°C was not associated with an increased probability of a good neurological function for patients with longer no-flow times.

A rationale for early extracorporeal membrane oxygenation in patients with postinfarction ventricular septal rupture complicated by cardiogenic shock: ECMO in patients with ventricular septal rupture

Ventricular septal rupture (VSR) became a rare mechanical complication of myocardial infarction in the era of percutaneous coronary interventions but is associated with extreme mortality in patients who present with cardiogenic shock (CS). Promising outcomes have been reported with the use of circulatory support allowing haemodynamic stabilization, followed by delayed repair. Therefore, we analysed our experience with an early use of Veno‐Arterial Extracorporeal Membrane Oxygenation (V‐A ECMO) for postinfarction VSR.

Early vancomycin, amikacin and gentamicin concentrations in pulmonary artery and pulmonary tissue are not affected by VA ECMO (venoarterial extracorporeal membrane oxygenation) in a pig model of prolonged cardiac arrest

BACKGROUND ECMO (extracorporeal membrane oxygenation) is increasingly used in severe hemodynamic compromise and cardiac arrest (CA). Pulmonary infections are frequent in these patients. Venoarterial (VA) ECMO decreases pulmonary blood flow and antibiotic availability in lungs during VA ECMO treated CA is not known. We aimed to assess early vancomycin, amikacin and gentamicin concentrations in the pulmonary artery as well as tracheal aspirate and to determine penetration ratios of these antibiotics to lung tissue in a pig model of VA ECMO treated CA. METHODS Twelve female pigs, body weight 51.5 ± 3.5 kg, were subjected to prolonged CA managed by different modes of VA ECMO. Anesthetized animals underwent 15 min of ventricular fibrillation (VF) followed by continued VF with ECMO flow of 100 mL/kg/min. Immediately after institution of ECMO, a 30 min vancomycin infusion (10 mg/kg) was started and amikacin and gentamicin boluses (7.5 and 3 mg/kg, respectively) were administered. ECMO circuit, aortic, pulmonary arterial, and tracheal aspirate concentrations of antibiotics were measured at 30 and 60 min after administration; penetration ratios were calculated. RESULTS All 30 min antibiotic concentrations and 60 min concentration for gentamicin in the pulmonary artery were no different than the aorta. However, the 60 min pulmonary artery vancomycin and amikacin values were significantly higher than aortic, 19.8 (14.3-21.6) vs. 17.6 (14.2-19.0) mg/L, p = 0.009, and 15.6 mg/L (11.0-18.6) vs. 11.2 (10.4-17.2) mg/L, p = 0.036, respectively. One hour penetration ratios were 18.5% for vancomycin, 34.9% for gentamicin and 38.8% for amikacin. CONCLUSION In a pig model of VA ECMO treated prolonged CA, despite diminished pulmonary flow, VA ECMO does not decrease early vancomycin, gentamicin, and amikacin concentrations in pulmonary artery. Within 1 h post administration, antibiotics can be detected in tracheal aspirate in adequate concentrations.

Postinfarction Ventricular Septal Rupture – A Rare Complication Remains Challenge for Cardiac Surgical Team

The incidence of post infarction ventricular septal rupture (PIVSR) is decreasing in the last years due to aggressive treatment of myocardial infarction with early percutaneous coronary interventions. As a consequence patients with PIVSR are referred to surgery more often with significant heart failure. The aim of this retrospective study was to assess the influence of these on the operative results and to identify the risk factors of operative mortality. A retrospective analysis of prospectively collected data of patients with the PIVSR admitted to our center from November 2004 to February 2012 was performed. Variables were analyzed using two-dimensional correspondence analysis. There were 25 patients (12 males and 13 females) with mean age 70.2 years (47-82) operated on; 17 (68%) presented with anterior and 8 (32%) with posterior PIVSR. Eighteen patients (72%) had acute heart failure, 13 (52%) presented with cardiogenic shock. Before surgery, intraaortic balloon pump (IABP) had 20 (80%) patients; in 4 (16%) a ventricular assist device was used, either Extracorporeal Membrane Oxygenation (ECMO) or centrifugal pumps as biventricular assist. Operative mortality was 40% (10 pts.). Four patients (12%) had small non-significant recurrent shunt on postoperative echocardiography. Although majority of patients with PIVSR have significant heart failure prior to surgery the operative mortality remains comparable to older studies. Predictors of perioperative death were concomitant surgical reconstruction of the left ventricle, renal impairment before operation, male gender, history of coronary artery disease, PIVSR location posterior, and shock at surgery.

Microvascular perfusion in cardiac arrest: a review of microcirculatory imaging studies

Cardiac arrest represents a leading cause of mortality and morbidity in developed countries. Extracorporeal cardiopulmonary resuscitation (ECPR) increases the chances for a beneficial outcome in victims of refractory cardiac arrest. However, ECPR and post-cardiac arrest care are affected by high mortality rates due to multi-organ failure syndrome, which is closely related to microcirculatory disorders. Therefore, microcirculation represents a key target for therapeutic interventions in post-cardiac arrest patients. However, the evaluation of tissue microcirculatory perfusion is still demanding to perform. Novel videomicroscopic technologies (Orthogonal polarization spectral, Sidestream dark field and Incident dark field imaging) might offer a promising way to perform bedside microcirculatory assessment and therapy monitoring. This review aims to summarise the recent body of knowledge on videomicroscopic imaging in a cardiac arrest setting and to discuss the impact of extracorporeal reperfusion and other therapeutic modalities on microcirculation.