Clinical review: practical recommendations on the management of perioperative heart failure in cardiac surgery.

Acute cardiovascular dysfunction occurs perioperatively in more than 20% of cardiosurgical patients, yet current acute heart failure (HF) classification is not applicable to this period. Indicators of major perioperative risk include unstable coronary syndromes, decompensated HF, significant arrhythmias and valvular disease. Clinical risk factors include history of heart disease, compensated HF, cerebrovascular disease, presence of diabetes mellitus, renal insufficiency and high-risk surgery. EuroSCORE reliably predicts perioperative cardiovascular alteration in patients aged less than 80 years. Preoperative B-type natriuretic peptide level is an additional risk stratification factor. Aggressively preserving heart function during cardiosurgery is a major goal. Volatile anaesthetics and levosimendan seem to be promising cardioprotective agents, but large trials are still needed to assess the best cardioprotective agent(s) and optimal protocol(s). The aim of monitoring is early detection and assessment of mechanisms of perioperative cardiovascular dysfunction. Ideally, volume status should be assessed by 'dynamic' measurement of haemodynamic parameters. Assess heart function first by echocardiography, then using a pulmonary artery catheter (especially in right heart dysfunction). If volaemia and heart function are in the normal range, cardiovascular dysfunction is very likely related to vascular dysfunction. In treating myocardial dysfunction, consider the following options, either alone or in combination: low-to-moderate doses of dobutamine and epinephrine, milrinone or levosimendan. In vasoplegia-induced hypotension, use norepinephrine to maintain adequate perfusion pressure. Exclude hypovolaemia in patients under vasopressors, through repeated volume assessments. Optimal perioperative use of inotropes/vasopressors in cardiosurgery remains controversial, and further large multinational studies are needed. Cardiosurgical perioperative classification of cardiac impairment should be based on time of occurrence (precardiotomy, failure to wean, postcardiotomy) and haemodynamic severity of the patient's condition (crash and burn, deteriorating fast, stable but inotrope dependent). In heart dysfunction with suspected coronary hypoperfusion, an intra-aortic balloon pump is highly recommended. A ventricular assist device should be considered before end organ dysfunction becomes evident. Extra-corporeal membrane oxygenation is an elegant solution as a bridge to recovery and/or decision making. This paper offers practical recommendations for management of perioperative HF in cardiosurgery based on European experts' opinion. It also emphasizes the need for large surveys and studies to assess the optimal way to manage perioperative HF in cardiac surgery.

Radio-frequency ablation as primary management of well-tolerated sustained monomorphic ventricular tachycardia in patients with structural heart disease and left ventricular ejection fraction over 30%.

AIMS: Patients with well-tolerated sustained monomorphic ventricular tachycardia (SMVT) and left ventricular ejection fraction (LVEF) over 30% may benefit from a primary strategy of VT ablation without immediate need for a 'back-up' implantable cardioverter-defibrillator (ICD). METHODS AND RESULTS: One hundred and sixty-six patients with structural heart disease (SHD), LVEF over 30%, and well-tolerated SMVT (no syncope) underwent primary radiofrequency ablation without ICD implantation at eight European centres. There were 139 men (84%) with mean age 62 ± 15 years and mean LVEF of 50 ± 10%. Fifty-five percent had ischaemic heart disease, 19% non-ischaemic cardiomyopathy, and 12% arrhythmogenic right ventricular cardiomyopathy. Three hundred seventy-eight similar patients were implanted with an ICD during the same period and serve as a control group. All-cause mortality was 12% (20 patients) over a mean follow-up of 32 ± 27 months. Eight patients (40%) died from non-cardiovascular causes, 8 (40%) died from non-arrhythmic cardiovascular causes, and 4 (20%) died suddenly (SD) (2.4% of the population). All-cause mortality in the control group was 12%. Twenty-seven patients (16%) had a non-fatal recurrence at a median time of 5 months, while 20 patients (12%) required an ICD, of whom 4 died (20%). CONCLUSION: Patients with well-tolerated SMVT, SHD, and LVEF > 30% undergoing primary VT ablation without a back-up ICD had a very low rate of arrhythmic death and recurrences were generally non-fatal. These data would support a randomized clinical trial comparing this approach with others incorporating implantation of an ICD as a primary strategy.

Morbidity and prognostic factors in chronic chagasic cardiopathy

Chagas disease is a pleomorphic clinical entity that has several unique features. The aim of this study is to summarise some of the recent contributions from our research group to knowledge of the morbidity and prognostic factors in Chagas heart disease. A retrospective study suggested that ischaemic stroke associated with left ventricular (LV) apical thrombi is the first clinical manifestation of Chagas disease observed in a large proportion of patients. LV function and left atrial volume (LAV) are independent risk factors for ischaemic cerebrovascular events during follow-up of Chagas heart disease patients. Pulmonary congestion in Chagas-related dilated cardiomyopathy is common but usually mild. Although early right ventricular (RV) involvement has been described, we have shown by Doppler echocardiography that RV dysfunction is evident almost exclusively when it is associated with left ventricle dilatation and functional impairment. In addition, RV dysfunction is a powerful predictor of survival in patients with heart failure secondary to Chagas disease. We have also demonstrated that LAV provides incremental prognostic information independent of clinical data and conventional echocardiographic parameters that predict survival.

The benefits of using selenium in the treatment of Chagas disease: prevention of right ventricle chamber dilatation and reversion of Trypanosoma cruzi-induced acute and chronic cardiomyopathy in mice

Cardiac damage is a frequent manifestation of Chagas disease, which is caused by the parasite Trypanosoma cruzi. Selenium (Se) is an essential micronutrient, the deficiency of which has been implicated in the development of cardiomyopathy. Our group has previously demonstrated that Se supplementation prevents myocardial damage during acute T. cruzi infection in mice. In this study, we analyzed the effect of Se treatment in cases of T. cruzi infection using prevention and reversion schemes. In the Se prevention scheme, mice were given Se supplements (2 ppm) starting two weeks prior to inoculation with T. cruzi(Brazil strain) and continuing until 120 days post-infection (dpi). In the Se reversion scheme, mice were treated with Se (4 ppm) for 100 days, starting at 160 dpi. Dilatation of the right ventricle was observed in the infected control group at both phases of T. cruzi infection, but it was not observed in the infected group that received Se treatment. Surviving infected mice that were submitted to the Se reversion scheme presented normal P wave values and reduced inflammation of the pericardium. These data indicate that Se treatment prevents right ventricular chamber increase and thus can be proposed as an adjuvant therapy for cardiac alterations already established by T. cruziinfection.

Importance of the right ventricle in valvular heart disease.

The importance of the right ventricle as a determinant of clinical symptoms, exercise capacity, peri-operative survival and postoperative outcome has been underestimated for a long time. Right ventricular ejection fraction has been used as a measure of right ventricular function but has been found to be dependent on loading conditions, ventricular interaction as well as on myocardial structure. Altered left ventricular function in patients with valvular disease influences right ventricular performance mainly by changes in afterload but also by ventricular interaction. Right ventricular function and regional wall motion can be determined with right ventricular angiography, radionuclide ventriculography, two-dimensional echocardiography or magnetic resonance imaging. However, the complex structure of the right ventricle and its pronounced translational movements render quantification difficult. True regional wall motion analysis is, however, possible with myocardial tagging based on magnetic resonance techniques. With this technique a baso-apical shear motion of the right ventricle was observed which was enhanced in patients with aortic stenosis.

The PPARbeta/delta agonist GW0742 relaxes pulmonary vessels and limits right heart hypertrophy in rats with hypoxia-induced pulmonary hypertension.

BACKGROUND: Pulmonary vascular diseases are increasingly recognised as important clinical conditions. Pulmonary hypertension associated with a range of aetiologies is difficult to treat and associated with progressive morbidity and mortality. Current therapies for pulmonary hypertension include phosphodiesterase type 5 inhibitors, endothelin receptor antagonists, or prostacyclin mimetics. However, none of these provide a cure and the clinical benefits of these drugs individually decline over time. There is, therefore, an urgent need to identify new treatment strategies for pulmonary hypertension. METHODOLOGY/PRINCIPAL FINDINGS: Here we show that the PPARbeta/delta agonist GW0742 induces vasorelaxation in systemic and pulmonary vessels. Using tissue from genetically modified mice, we show that the dilator effects of GW0742 are independent of the target receptor PPARbeta/delta or cell surface prostacyclin (IP) receptors. In aortic tissue, vascular relaxant effects of GW0742 were not associated with increases in cGMP, cAMP or hyperpolarisation, but were attributed to inhibition of RhoA activity. In a rat model of hypoxia-induced pulmonary hypertension, daily oral dosing of animals with GW0742 (30 mg/kg) for 3 weeks significantly reduced the associated right heart hypertrophy and right ventricular systolic pressure. GW0742 had no effect on vascular remodelling induced by hypoxia in this model. CONCLUSIONS/SIGNIFICANCE: These observations are the first to show a therapeutic benefit of 'PPARbeta/delta' agonists in experimental pulmonary arterial hypertension and provide pre-clinical evidence to favour clinical trials in man.

Precordial abscess inducing chest pain 20 years after surgical repair of a pentalogy of fallot.

A 25-year-old male asylum-seeker presented with chest pain, exertional dyspnea, and orthopnea 20 years after the surgical repair of a pentalogy of Fallot. An extracardiac mass compressing the right ventricle was subsequently detected and surgical decompression was performed to relieve the resulting right intraventricular hypertension. At operation, the mass proved to be a coagulase-negative, staphylococcal abscess. In addition, the removal of the mass unmasked a previously nonrecognized pulmonary outflow stenosis that required balloon dilatation and beta-blocker therapy. While infections are known to occur after sternotomy, the formation of an abscess in the anterior mediastinum several years after the intervention appears to be exceptional; this diagnosis came to mind only after the more common complications had been considered, e.g., pseudoaneurysm or pericardial hematoma. To our knowledge, this is the first report of an abscess in the anterior mediastinum that had probably formed over many years following a sternotomy, compressed the right ventricle and masked a pulmonary stenosis.

Predictors of mortality from pump failure and sudden cardiac death in patients with systolic heart failure and left ventricular dyssynchrony: results of the CARE-HF trial.

BACKGROUND: Determining a specific death cause may facilitate individualized therapy in patients with heart failure (HF). Cardiac resynchronization therapy (CRT) decreased mortality in the Cardiac Resynchronization in Heart Failure trial by reducing pump failure and sudden cardiac death (SCD). This study analyzes predictors of specific causes of death. METHODS AND RESULTS: Univariate and multivariate analyses used 8 baseline and 3-month post-randomization variables to predict pump failure and SCD (categorized as "definite," "probable," and "possible"). Of 255 deaths, 197 were cardiovascular. There were 71 SCDs with a risk reduction by CRT of 0.47 (95% confidence interval 0.29-0.76; P = .002) with similar reductions in SCD classified as definite, probable, and possible. Univariate SCD predictors were 3-month HF status (mitral regurgitation [MR] severity, plasma brain natriuretic peptide [BNP], end-diastolic volume, and systolic blood pressure), whereas randomization to CRT decreased risk. Multivariate SCD predictors were randomization to CRT 0.56 (0.53-0.96, P = .035) and 3-month MR severity 1.82 (1.77-2.60, P = .0012). Univariate pump failure death predictors related to baseline HF state (quality of life score, interventricular mechanical delay, end-diastolic volume, plasma BNP, MR severity, and systolic pressure), whereas randomization to CRT and nonischemic cardiomyopathy decreased risk; multivariate predictors of pump failure death were baseline plasma BNP and systolic pressure and randomization to CRT. CONCLUSION: CRT decreased SCD in patients with systolic HF and ventricular dyssynchrony. SCD risk was increased with increased severity of MR (including the 3-month value for MR as a time-dependent covariate) and reduced by randomization to CRT. HF death was increased related to the level of systolic blood pressure, log BNP, and randomization to CRT. These results emphasize the importance and interdependence of HF severity to mortality from pump failure and SCD.

Different degrees of ischaemic injury in the right and left ventricle in cases of severe, nonfatal, pulmonary embolism.

Pulmonary fat embolism (PFE) is a common complication of blunt force traumas with bone fractures. Severe forms cause impedance to right ventricular (RV) ejection, with eventual right heart ischaemia and failure. In a prospective study, we have investigated 220 consecutive autopsy cases (73 females, 147 males, mean age 52.1 years, min 14 years, max 91 years). PFE was detected in 52 cases that were divided into three groups according to the degree of PFE (1-3). A fourth group of cases of violent death without PFE was used for comparison. In each case, histology (H&E, Masson) and immunohistochemistry (fibronectin and C5b-9) were performed on six cardiac samples (anterior, lateral and posterior wall of both ventricles). The degree of cardiac damage was registered in each sample and the mean degree of damage was calculated in each case at the RV and left ventricle (LV). Moreover, a parameter ∆ that is the difference between the mean damage at the RV and the LV was calculated in each case. The results were compared within each group and between the groups. In the present study, we could not detect prevalent RV damage in cases of high degree PFE as we did in our previous investigation. In the group PFE3 the difference of the degree of damage between the RV and LV was higher than the one observed in the groups PFE0-2 with the antibody anti-fibronectin. Prevalent right ventricular stress in cases of severe PFE may explain this observation.

Diverse effects of renal denervation on ventricular hypertrophy and blood pressure in DOCA-salt hypertensive rats

Cardiac hypertrophy that accompanies hypertension seems to be a phenomenon of multifactorial origin whose development does not seem to depend on an increased pressure load alone, but also on local growth factors and cardioadrenergic activity. The aim of the present study was to determine if sympathetic renal denervation and its effects on arterial pressure level can prevent cardiac hypertrophy and if it can also delay the onset and attenuate the severity of deoxycorticosterone acetate (DOCA)-salt hypertension. DOCA-salt treatment was initiated in rats seven days after uninephrectomy and contralateral renal denervation or sham renal denervation. DOCA (15 mg/kg, sc) or vehicle (soybean oil, 0.25 ml per animal) was administered twice a week for two weeks. Rats treated with DOCA or vehicle (control) were provided drinking water containing 1% NaCl and 0.03% KCl. At the end of the treatment period, mean arterial pressure (MAP) and heart rate measurements were made in conscious animals. Under ether anesthesia, the heart was removed and the right and left ventricles (including the septum) were separated and weighed. DOCA-salt treatment produced a significant increase in left ventricular weight/body weight (LVW/BW) ratio (2.44 ± 0.09 mg/g) and right ventricular weight/body weight (RVW/BW) ratio (0.53 ± 0.01 mg/g) compared to control (1.92 ± 0.04 and 0.48 ± 0.01 mg/g, respectively) rats. MAP was significantly higher (39%) in DOCA-salt rats. Renal denervation prevented (P>0.05) the development of hypertension in DOCA-salt rats but did not prevent the increase in LVW/BW (2.27 ± 0.03 mg/g) and RVW/BW (0.52 ± 0.01 mg/g). We have shown that the increase in arterial pressure level is not responsible for cardiac hypertrophy, which may be more related to other events associated with DOCA-salt hypertension, such as an increase in cardiac sympathetic activity

Effects of mercury on the arterial blood pressure of anesthetized rats

The available data suggests that hypotension caused by Hg2+ administration may be produced by a reduction of cardiac contractility or by cholinergic mechanisms. The hemodynamic effects of an intravenous injection of HgCl2 (5 mg/kg) were studied in anesthetized rats (N = 12) by monitoring left and right ventricular (LV and RV) systolic and diastolic pressures for 120 min. After HgCl2 administration the LV systolic pressure decreased only after 40 min (99 ± 3.3 to 85 ± 8.8 mmHg at 80 min). However, RV systolic pressure increased, initially slowly but faster after 30 min (25 ± 1.8 to 42 ± 1.6 mmHg at 80 min). Both right and left diastolic pressures increased after HgCl2 treatment, suggesting the development of diastolic ventricular dysfunction. Since HgCl2 could be increasing pulmonary vascular resistance, isolated lungs (N = 10) were perfused for 80 min with Krebs solution (continuous flow of 10 ml/min) containing or not 5 µM HgCl2. A continuous increase in pulmonary vascular resistance was observed, suggesting the direct effect of Hg2+ on the pulmonary vessels (12 ± 0.4 to 29 ± 3.2 mmHg at 30 min). To examine the interactions of Hg2+ and changes in cholinergic activity we analyzed the effects of acetylcholine (Ach) on mean arterial blood pressure (ABP) in anesthetized rats (N = 9) before and after Hg2+ treatment (5 mg/kg). Using the same amount and route used to study the hemodynamic effects we also examined the effects of Hg2+ administration on heart and plasma cholinesterase activity (N = 10). The in vivo hypotensive response to Ach (0.035 to 10.5 µg) was reduced after Hg2+ treatment. Cholinesterase activity (µM h-1 mg protein-1) increased in heart and plasma (32 and 65%, respectively) after Hg2+ treatment. In conclusion, the reduction in ABP produced by Hg2+ is not dependent on a putative increase in cholinergic activity. HgCl2 mainly affects cardiac function. The increased pulmonary vascular resistance and cardiac failure due to diastolic dysfunction of both ventricles are factors that might contribute to the reduction of cardiac output and the fall in arterial pressure.

Noninvasive prognostic markers for cardiac death and ventricular arrhythmia in long-term follow-up of subjects with chronic Chagas' disease

The objective of the present study was to investigate clinical, echocardiographic and electrocardiographic (12-lead resting ECG, 24-h ambulatory ECG monitoring and signal-averaged ECG (SAECG)) parameters in subjects with chronic Chagas' disease in a long-term follow-up as prognostic markers for adverse outcomes. Fifty adult outpatients (34 to 74 years old, 31 females) staged according to Los Andes class I, II or III and complaining of palpitation were enrolled in a longitudinal study. SAECG was analyzed in time and frequency domains and the endpoint was a composite of cardiac death and ventricular tachycardia. During a follow-up of 84.2 ± 39.0 months, 34.0% of the patients developed adverse outcomes (9 cardiac deaths and 11 episodes of ventricular tachycardia). After optimal dichotomization, in a stepwise multivariate Cox-hazard regression model, apical aneurysm (HR = 3.7; 95% CI = 1.2-1.3; P = 0.02), left ventricular ejection fraction <62% (HR = 4.60; 95% CI = 1.39-15.24; P = 0.01) and incidence of ventricular premature contractions >614 per 24 h (hazard ratio = 6.1; 95% CI = 1.7-22.6; P = 0.006) were independent predictors of the composite endpoint. Although a high frequency content in SAECG demonstrated association with the presence of left ventricular dysfunction and myocardial fibrosis, its predictive value for the composite endpoint was not significant. Apical aneurysms, reduced left ventricular function and a high incidence of ventricular ectopic beats over a 24-h period have a strong predictive value for a composite endpoint of cardiac death and ventricular tachycardia in subjects with chronic Chagas' disease.

Ventricular performance and Na+-K+ ATPase activity are reduced early and late after myocardial infarction in rats

Myocardial infarction leads to compensatory ventricular remodeling. Disturbances in myocardial contractility depend on the active transport of Ca2+ and Na+, which are regulated by Na+-K+ ATPase. Inappropriate regulation of Na+-K+ ATPase activity leads to excessive loss of K+ and gain of Na+ by the cell. We determined the participation of Na+-K+ ATPase in ventricular performance early and late after myocardial infarction. Wistar rats (8-10 per group) underwent left coronary artery ligation (infarcted, Inf) or sham-operation (Sham). Ventricular performance was measured at 3 and 30 days after surgery using the Langendorff technique. Left ventricular systolic pressure was obtained under different ventricular diastolic pressures and increased extracellular Ca2+ concentrations (Ca2+e) and after low and high ouabain concentrations. The baseline coronary perfusion pressure increased 3 days after myocardial infarction and normalized by 30 days (Sham 3 = 88 ± 6; Inf 3 = 130 ± 9; Inf 30 = 92 ± 7 mmHg; P < 0.05). The inotropic response to Ca2+e and ouabain was reduced at 3 and 30 days after myocardial infarction (Ca2+ = 1.25 mM; Sham 3 = 70 ± 3; Inf 3 = 45 ± 2; Inf 30 = 29 ± 3 mmHg; P < 0.05), while the Frank-Starling mechanism was preserved. At 3 and 30 days after myocardial infarction, ventricular Na+-K+ ATPase activity and contractility were reduced. This Na+-K+ ATPase hypoactivity may modify the Na+, K+ and Ca2+ transport across the sarcolemma resulting in ventricular dysfunction.

Myocardial remodeling and bioelectric changes in tachycardia-induced heart failure in dogs

In this study, electrical and structural remodeling of ventricles was examined in tachycardia-induced heart failure (HF). We studied two groups of weight-matched adult male mongrel dogs: a sham-operated control group (n=5) and a pacing group (n=5) that underwent ventricular pacing at 230 bpm for 3 weeks. Clinical symptoms of congestive HF were observed in both groups. Their hemodynamic parameters were determined and the severity of the HF was evaluated by M-mode echocardiography. Changes in heart morphology were observed by scanning electron and light microscopy. Ventricular action potential duration (APD), as well as the 50 and 90% APD were measured in both groups. All dogs exhibited clinical symptoms of congestive HF after rapid right ventricular pacing for 3 weeks. These data indicate that rapid, right ventricular pacing produces a useful experimental model of low-output HF in dogs, characterized by biventricular pump dysfunction, biventricular cardiac dilation, and non-ischemic impairment of left ventricular contractility. Electrical and structural myocardial remodeling play an essential role in congestive HF progression, and should thus be prevented.