Current Opinion in Critical Care 2009;15:392-397

Severe sepsis and septic shock are among the most important causes of morbidity and mortality in patients admitted to the intensive care unit. The purpose of this review is to review current understanding of sepsis-induced cardiac dysfunction and discuss pertinent findings regarding its clinical presentation, underlying mechanisms of disease, and therapy. Recent findings: Cardiac dysfunction in sepsis is characterized by decreased contractility, impaired ventricular response to fluid therapy, and in some patients ventricular dilatation. Current data support a complex underlying physiopathology with a host of potential pathways leading to myocardial depression. Circulating factors such as cytokines (TNF-[alpha], IL-1[beta]), lysozyme c, endothelin-1 have direct inhibitory actions on myocyte contractility. Nitric oxide has a complex role in sepsis-induced cardiac dysfunction. Current data suggest a combination of deleterious and positive effects on the myocardium determined by the specific type of nitric oxide expressed. Recent studies have shown that mitochondrial dysfunction and apoptosis also play a role in the development of sepsis-induced cardiac dysfunction. Current treatment for sepsis-induced cardiac dysfunction is based on appropriate treatment for the infectious focus (antibiotics and source control) and hemodynamic support (fluids, vasopressors, and inotropes). Summary: Cardiac dysfunction is common in patients with severe sepsis and septic shock. Current understanding of the underlying mechanisms responsible is rapidly evolving and future novel therapeutic targets may be soon available. Present therapy for sepsis-induced cardiac dysfunction is based on treatment of underlying sepsis with antibiotics and hemodynamic support.

Critical Care 2009, 13:R157

Despite the key role of hemodynamic goals, there are few data addressing the question as to which hemodynamic variables are associated with outcome or should be targeted in cardiogenic shock patients. The aim of this study was to investigate the association between hemodynamic variables and cardiogenic shock mortality.

Methods
Medical records and the patient data management system of a multidisciplinary intensive care unit (ICU) were reviewed for patients admitted because of cardiogenic shock. In all patients, the hourly variable time integral of hemodynamic variables during the first 24 hours after ICU admission was calculated. If hemodynamic variables were associated with 28-day mortality, the hourly variable time integral of drops below clinically relevant threshold levels was computed. Regression models and receiver operator characteristic analyses were calculated. All statistical models were adjusted for age, admission year, mean catecholamine doses and the Simplified Acute Physiology Score II (excluding hemodynamic counts) in order to account for the influence of age, changes in therapies during the observation period, the severity of cardiovascular failure and the severity of the underlying disease on 28-day mortality.

Results
One-hundred and nineteen patients were included. Cardiac index (CI) (P = 0.01) and cardiac power index (CPI) (P = 0.03) were the only hemodynamic variables separately associated with mortality. The hourly time integral of CI drops <3, 2.75 (both P = 0.02) and 2.5 (P = 0.03) L/min/m2 was associated with death but not that of CI drops <2 L/min/m2 or lower thresholds (all P > 0.05). The hourly time integral of CPI drops <0.5-0.8 W/m2 (all P = 0.04) was associated with 28-day mortality but not that of CPI drops <0.4 W/m2 or lower thresholds (all P > 0.05).

Conclusions
During the first 24 hours after intensive care unit admission, CI and CPI are the most important hemodynamic variables separately associated with 28-day mortality in patients with cardiogenic shock. A CI of 3 L/min/m2 and a CPI of 0.8 W/m2 were most predictive of 28-day mortality. Since our results must be considered hypothesis-generating, randomized controlled trials are required to evaluate whether targeting these levels as early resuscitation endpoints can improve mortality in cardiogenic shock.

Critical Care 2009, 13:1013

Cardiogenic shock is a lethal condition. Physicians are searching for hemodynamic markers which could help risk-stratification of patients in this picture. Torgersen and coworkers present an hourly time integral of the cardiac power index and cardiac index drops to predict outcomes in the setting of cardiogenic shock. Continuous monitoring of hemodynamic markers may have a role in prediction of outcomes.

Crit Care Med 2010;38:152-160

Patients undergoing percutaneous coronary intervention (PCI) for acute myocardial infarction with cardiogenic shock (CS) are often treated with intra-aortic balloon pump counterpulsation (IABP), even though the evidence to support this is limited. We determined whether IABP as an addition to PCI-centered therapy ameliorates multiorgan dysfunction syndrome (MODS) in patients with acute myocardial infarction complicated by CS.

Design
A prospective, randomized, controlled, open-label clinical trial recruiting patients between March 2003 and June 2004

Setting
Intra-aortic balloon counterpulsation in patients with acute myocardial infarction complicated by cardiogenic shock: The prospective, randomized IABP SHOCK Trial for attenuation of multiorgan dysfunction syndromeTertiary care university hospital.

Patients and interventions
Forty-five consecutive patients with AMI and CS undergoing PCI were randomized to treatment with or without IABP.

Measurements and main results
Acute Physiology and Chronic Health Evaluation (APACHE) II scores (primary outcome measure), hemodynamic values, inflammatory markers, and plasma brain natriuretic peptide (BNP) levels (secondary outcomes) were collected over 4 days from randomization. The prospective hypothesis was that adding IABP therapy to “standard care” would improve CS-triggered MODS. The addition of IABP to standard therapy did not result in a significant improvement in MODS (measured by serial APACHE II scoring over 4 days). IABP use had no significant effect on cardiac index or systemic inflammatory activation, although BNP levels were significantly lower in IABP-treated patients. Initial and serial APACHE II scoring correlated with mortality better than cardiac index, systemic inflammatory state, and BNP levels in this group of patients. Nonsurvivors had significantly higher initial APACHE II scores (29.9 ± 2.88) than survivors (18.1 ± 1.66, p < .05). Nevertheless, discrepancies among patients within the groups cannot be ruled out and might interfere with our results.

Conclusions
In this randomized trial addressing addition of IABP in CS patients, mechanical support was associated only with modest effects on reduction of APACHE II score as a marker of severity of disease, improvement of cardiac index, reduction of inflammatory state, or reduction of BNP biomarker status compared with medical therapy alone. However, the limitations of our present trial preclude any definitive conclusion, but request for a larger prospective, randomized, multicentered trial with mortality as primary end point.

Critical Care 2009,13:R157

Despite the key role of hemodynamic goals, there are few data addressing the question as to which hemodynamic variables are associated with outcome or should be targeted in cardiogenic shock patients. The aim of this study was to investigate the association between hemodynamic variables and cardiogenic shock mortality.

Methods
Medical records and the patient data management system of a multidisciplinary intensive care unit (ICU) were reviewed for patients admitted because of cardiogenic shock. In all patients, the hourly variable time integral of hemodynamic variables during the first 24 hours after ICU admission was calculated. If hemodynamic variables were associated with 28-day mortality, the hourly variable time integral of drops below clinically relevant threshold levels was computed. Regression models and receiver operator characteristic analyses were calculated. All statistical models were adjusted for age, admission year, mean catecholamine doses and the Simplified Acute Physiology Score II (excluding hemodynamic counts) in order to account for the influence of age, changes in therapies during the observation period, the severity of cardiovascular failure and the severity of the underlying disease on 28-day mortality.

Results
One-hundred-nineteen patients were included. Cardiac index (CI) (P=0.01) and cardiac power index (CPI) (P=0.03) were the only hemodynamic variables separately associated with mortality. The hourly time integral of CI drops <3, 2.75 (both P=0.02) and 2.5 (P=0.03) L/min/m2 was associated with death but not that of CI drops <2 L/min/m2 or lower thresholds (all P>0.05). The hourly time integral of CPI drops <0.5-0.8 W/m2 (all P=0.04) was associated with 28-day mortality but not that of CPI drops <0.4 W/m2 or lower thresholds (all P>0.05).

Conclusions
During the first 24 hours after intensive care unit admission, CI and CPI are the most important hemodynamic variables separately associated with 28-day mortality in patients with cardiogenic shock. A CI of 3 L/min/m^2 and a CPI of 0.8 W/m2 were most predictive of 28-day mortality. Since our results must be considered hypothesis-generating, randomized controlled trials are required to evaluate whether targeting these levels as early resuscitation endpoints can improve mortality in cardiogenic shock.

Crit Care Med 2009;37:1837-1844

Plasma N-terminal pro-B-type natriuretic peptide (Nt-pro-BNP) levels are frequently elevated in critically ill patients and are associated with an increased mortality. In this study, we determined Nt-pro-BNP levels in patients with cardiogenic shock (CS) and evaluated its association with clinical and hemodynamic parameters and 30-day mortality.

Design
Retrospective study.

Setting
Two, eight-bed intensive care units at a university and a community hospital.

Patients
Retrospective study on stored plasma samples of 58 patients with CS, obtained at admission to the intensive care unit.

Interventions
None.

Measurements and main results
Massively elevated Nt-pro-BNP concentrations showed no significant association with duration of shock, total Sequential Organ Failure Assessment score, or invasive hemodynamic parameters at the time of blood sampling but a significant association with estimated glomerular filtration rate (p < 0.001), C-reactive protein (p = 0.03), age (p = 0.005), and body weight (p = 0.03). Both in univariate and multivariate survival analyses, Nt-pro-BNP levels above the median (>12,782 pg/mL) were significant predictors of 30-day mortality (p < 0.001) and showed a complementary role with interleukin (IL)-6 in predicting outcome. Patients with IL-6 >195 pg/mL and Nt-pro-BNP above the median value had the highest 30-day mortality (93.7%), whereas patients with lower IL-6 levels together with lower Nt-pro-BNP levels had significantly better survival (mortality rate 26.3%). Among patients who had acute myocardial infarction, those with Nt-pro-BNP concentrations above the median level showed a highly impaired clinical course even if coronary revascularization was successful (30-day mortality 90.9% vs. 29.4%, p = 0.001), whereas survival of patients with unsuccessful revascularization did not differ significantly with respect to the median of Nt-pro-BNP (30-day survival rate 81.8% vs. 75.0%, p = 0.71).

Conclusion
The massive elevations of Nt-pro-BNP observed in the early phase of CS seem to be independent of ventricular performance. Nt-pro-BNP levels are nevertheless predictive of 30-day survival in patients with CS especially in those with successful revascularization and might be used in combination with IL-6 for estimation of outcome early on.

JAMA. 2009;301:286-294

Limited information exists regarding the role of left ventricular function in predicting exercise capacity and impact on age- and sex-related differences.

Objectives
To determine the impact of measures of cardiac function assessed by echocardiography on exercise capacity and to determine if these associations are modified by sex or advancing age.

Design
Cross-sectional study of patients undergoing exercise echocardiography with routine measurements of left ventricular systolic and diastolic function by 2-dimensional and Doppler techniques. Analyses were conducted to determine the strongest correlates of exercise capacity and the age and sex interactions of these variables with exercise capacity.

Setting
Large tertiary referral center in Rochester, Minnesota, in 2006.

Participants
Patients undergoing exercise echocardiography using the Bruce protocol (N = 2867). Patients with echocardiographic evidence of exercise-induced ischemia, ejection fractions lower than 50%, or significant valvular heart disease were excluded.

Main outcome measure
Exercise capacity in metabolic equivalents (METs).

Results
Diastolic dysfunction was strongly and inversely associated with exercise capacity. Compared with normal function, after multivariate adjustment, those with moderate/severe resting diastolic dysfunction (–1.30 METs; 95% confidence interval [CI], –1.52 to –0.99; P < .001) and mild resting diastolic dysfunction (–0.70 METs; 95% CI, –0.88 to –0.46; P < .001) had substantially lower exercise capacity. Variation of left ventricular systolic function within the normal range was not associated with exercise capacity. Left ventricular filling pressures measured by resting E/e’ of 15 or greater (–0.41 METs; 95% CI, –0.70 to –0.11; P = .007) or postexercise E/e’ of 15 or greater (–0.41 METs; 95% CI, –0.71 to –0.11; P = .007) were similarly associated with a reduction in exercise capacity, each in separate multivariate analyses. Individuals with impaired relaxation (mild dysfunction) or resting E/e’ of 15 or greater had a progressive increase in the magnitude of reduction in exercise capacity with advancing age (P < .001 and P = .02, respectively). Other independent correlates of exercise capacity were age (unstandardized β coefficient, –0.85 METs; 95% CI, –0.92 to –0.77, per 10-year increment; P < .001), female sex (–1.98 METs; 95% CI, –2.15 to –1.84; P < .001), and body mass index greater than 30 (–1.24 METs; 95% CI, –1.41 to –1.10; P < .001).

Conclusion
In this large cross-sectional study of those referred for exercise echocardiography and not limited by ischemia, abnormalities of left ventricular diastolic function were independently associated with exercise capacity.

Critical Care 2008;12:R118

Increased serum B-type natriuretic peptide (BNP) has been identified for diagnosis and prognosis of impaired cardiac function in patients suffering from congestive heart failure, ischemic heart disease, and sepsis. However, the prognostic value of BNP in multiple injured patients developing multiple organ dysfunction syndrome (MODS) remains undetermined. Therefore, the aims of this study were to assess N-terminal pro-BNP (NT-proBNP) in multiple injured patients and to correlate the results with invasively assessed cardiac output and clinical signs of MODS.

Methods
Twenty-six multiple injured patients presenting a New Injury Severity Score of greater than 16 points were included. The MODS score was calculated on admission as well as 24, 48, and 72 hours after injury. Patients were subdivided into groups: group A showed minor signs of organ dysfunction (MODS score less than or equal to 4 points) and group B suffered from major organ dysfunction (MODS score of greater than 4 points). Venous blood (5 mL) was collected after admission and 6, 12, 24, 48, and 72 hours after injury. NT-proBNP was determined using the Elecsys proBNP® assay. The hemodynamic monitoring of cardiac index (CI) was performed using transpulmonary thermodilution.

Results
Serum NT-proBNP levels were elevated in all 26 patients. At admission, the serum NT-proBNP values were 116 ± 21 pg/mL in group A versus 209 ± 93 pg/mL in group B. NT-proBNP was significantly lower at all subsequent time points in group A in comparison with group B (P < 0.001). In contrast, the CI in group A was significantly higher than in group B at all time points (P < 0.001). Concerning MODS score and CI at 24, 48, and 72 hours after injury, an inverse correlation was found (r = -0.664, P < 0.001). Furthermore, a correlation was found comparing MODS score and serum NT-proBNP levels (r = 0.75, P < 0.0001).

Conclusions
Serum NT-proBNP levels significantly correlate with clinical signs of MODS 24 hours after multiple injury. Furthermore, a distinct correlation of serum NT-proBNP and decreased CI was found. The data of this pilot study may indicate a potential value of NT-proBNP in the diagnosis of post-traumatic cardiac impairment. However, further studies are needed to elucidate this issue.

Critical Care Medicine 2008:36:2257-2266

Cardiogenic shock is the leading cause of death in patients hospitalized for acute myocardial infarction. The objectives were to investigate the effects of levosimendan, a novel inodilator, compared with the phosphodiesterase-III inhibitor enoximone in refractory cardiogenic shock complicating acute myocardial infarction, on top of current therapy.

Design
Prospective, randomized, controlled single-center clinical trial.

Setting
Medical and coronary intensive care unit in a university hospital.

Patients
Thirty-two patients with refractory cardiogenic shock for at least 2 hrs requiring additional therapy.

Interventions
Infusion of either levosimendan (12 ug/kg over 10 min, followed by 0.1 ug/kg/min over 50 min, and of 0.2 ug/kg/min for the next 23 hrs) or enoximone (fractional loading dose of 0.5 mg/kg, followed by 2-10 ug/kg/min continuously) after initiation of current therapy, always including revascularization, intra-aortic balloon pump counterpulsation, and inotropes.

Measurements and main results
Survival rate at 30 days was significantly higher in the levosimendan-treated group (69%, 11 of 16) compared with the enoximone group (37%, 6 of 16, p = 0.023). Invasive hemodynamic parameters during the first 48 hrs were comparable in both groups. Levosimendan induced a trend toward higher cardiac index, cardiac power index, left ventricular stroke work index, and mixed venous oxygen saturation. In addition, lower cumulative values for catecholamines at 72 hrs and for clinical signs of inflammation were seen in the levosimendan-treated patients. Multiple organ failure leading to death occurred exclusively in the enoximone group (4 of 16 patients).

Conclusions
In severe and refractory cardiogenic shock complicating acute myocardial infarction, levosimendan, added to current therapy, may contribute to improved survival compared with enoximone.

Crit Care Med 2008;36:2023-2033

The objective of this study was to examine the relationship between right ventricular involvement (RVI) in acute myocardial infarction (AMI) and the increase in mortality and morbidity frequently suggested in the last two decades.

Design
The authors conducted a systematic review and meta-analysis.

Setting
This study was conducted at an academic medical center.

Data Source
The authors reviewed PubMed, BioMedCentral, and the Cochrane database and conducted a manual review of article bibliographies.

Study Selection and Data Extraction
Using a prespecified search strategy, 22 relevant studies involving a total of 7,136 patients with AMI at baseline, of whom 1,963 had RVI (27.5%), were included in a meta-analysis using a random effects model. Pooled relative risks of the impact of RVI on patient mortality and morbidity were calculated.

Main Results
An overall pooled relative risk mortality increase of 2.59 (95% confidence interval, 2.02-3.31) was found (Z = 7.57; p < .00001). RVI in AMI was also associated with a statistically significant increase in all secondary end points assessed, including cardiogenic shock, ventricular arrhythmias, advanced atrioventricular block, and mechanical complications.

Conclusions
Our results support the view that early recognition of RVI, namely by means of right electrocardiographic leads in acute myocardial infarction, may have prognostic value. Whether or not this recognition will permit improvement of outcomes through more aggressive percutaneous coronary intervention would need to be tested in future studies.

Crit Care Med 2008;36:1701-1706

To evaluate the actual incidence of global left ventricular hypokinesia in septic shock.

Method
All mechanically ventilated patients treated for an episode of septic shock in our unit were studied by transesophageal echocardiography, at least once a day, during the first 3 days of hemodynamic support. In patients who recovered, echocardiography was repeated after weaning from vasoactive agents. Main measurements were obtained from the software of the apparatus. Global left ventricular hypokinesia was defined as a left ventricular ejection fraction of <45%.

Measurements and Main Results
During a 3-yr period (January 2004 through December 2006), 67 patients free from previous cardiac disease, and who survived for >48 hrs, were repeatedly studied. Global left ventricular hypokinesia was observed in 26 of these 67 patients at admission (primary hypokinesia) and in 14 after 24 or 48 hrs of hemodynamic support by norepinephrine (secondary hypokinesia), leading to an overall hypokinesia rate of 60%. Left ventricular hypokinesia was partially corrected by dobutamine, added to a reduced dosage of norepinephrine, or by epinephrine. This reversible acute left ventricular dysfunction was not associated with a worse prognosis.

Conclusion
Global left ventricular hypokinesia is very frequent in adult septic shock and could be unmasked, in some patients, by norepinephrine treatment. Left ventricular hypokinesia is usually corrected by addition of an inotropic agent to the hemodynamic support.

NEJM 2008;358:2667-2677

It is common practice to restore and maintain sinus rhythm in patients with atrial fibrillation and heart failure. This approach is based in part on data indicating that atrial fibrillation is a predictor of death in patients with heart failure and suggesting that the suppression of atrial fibrillation may favorably affect the outcome. However, the benefits and risks of this approach have not been adequately studied.

Methods
We conducted a multicenter, randomized trial comparing the maintenance of sinus rhythm (rhythm control) with control of the ventricular rate (rate control) in patients with a left ventricular ejection fraction of 35% or less, symptoms of congestive heart failure, and a history of atrial fibrillation. The primary outcome was the time to death from cardiovascular causes.

Results
A total of 1376 patients were enrolled (682 in the rhythm-control group and 694 in the rate-control group) and were followed for a mean of 37 months. Of these patients, 182 (27%) in the rhythm-control group died from cardiovascular causes, as compared with 175 (25%) in the rate-control group (hazard ratio in the rhythm-control group, 1.06; 95% confidence interval, 0.86 to 1.30; P=0.59 by the log-rank test). Secondary outcomes were similar in the two groups, including death from any cause (32% in the rhythm-control group and 33% in the rate-control group), stroke (3% and 4%, respectively), worsening heart failure (28% and 31%), and the composite of death from cardiovascular causes, stroke, or worsening heart failure (43% and 46%). There were also no significant differences favoring either strategy in any predefined subgroup.

Conclusions
In patients with atrial fibrillation and congestive heart failure, a routine strategy of rhythm control does not reduce the rate of death from cardiovascular causes, as compared with a rate-control strategy.

NEJM 2008;359:142-151

Noninvasive ventilation (continuous positive airway pressure [CPAP] or noninvasive intermittent positive-pressure ventilation [NIPPV]) appears to be of benefit in the immediate treatment of patients with acute cardiogenic pulmonary edema and may reduce mortality. We conducted a study to determine whether noninvasive ventilation reduces mortality and whether there are important differences in outcome associated with the method of treatment (CPAP or NIPPV).

Methods
In a multicenter, open, prospective, randomized, controlled trial, patients were assigned to standard oxygen therapy, CPAP (5 to 15 cm of water), or NIPPV (inspiratory pressure, 8 to 20 cm of water; expiratory pressure, 4 to 10 cm of water). The primary end point for the comparison between noninvasive ventilation and standard oxygen therapy was death within 7 days after the initiation of treatment, and the primary end point for the comparison between NIPPV and CPAP was death or intubation within 7 days.

Results
A total of 1069 patients (mean [±SD] age, 77.7±9.7 years; female sex, 56.9%) were assigned to standard oxygen therapy (367 patients), CPAP (346 patients), or NIPPV (356 patients). There was no significant difference in 7-day mortality between patients receiving standard oxygen therapy (9.8%) and those undergoing noninvasive ventilation (9.5%, P=0.87). There was no significant difference in the combined end point of death or intubation within 7 days between the two groups of patients undergoing noninvasive ventilation (11.7% for CPAP and 11.1% for NIPPV, P=0.81). As compared with standard oxygen therapy, noninvasive ventilation was associated with greater mean improvements at 1 hour after the beginning of treatment in patient-reported dyspnea (treatment difference, 0.7 on a visual-analogue scale ranging from 1 to 10; 95% confidence interval [CI], 0.2 to 1.3; P=0.008), heart rate (treatment difference, 4 beats per minute; 95% CI, 1 to 6; P=0.004), acidosis (treatment difference, pH 0.03; 95% CI, 0.02 to 0.04; P<0.001), and hypercapnia (treatment difference, 0.7 kPa [5.2 mm Hg]; 95% CI, 0.4 to 0.9; P<0.001). There were no treatment-related adverse events.

Conclusions
In patients with acute cardiogenic pulmonary edema, noninvasive ventilation induces a more rapid improvement in respiratory distress and metabolic disturbance than does standard oxygen therapy but has no effect on short-term mortality.

Anaesthesia 2008;63:482-487

Heart failure is a major risk factor for adverse postoperative events following non-cardiac surgery. The use of transthoracic echocardiogram as a pre-operative investigation to assess cardiac dysfunction has limitations in this setting. The N-Terminal fragment of B-Type natriuretic peptide (NT proBNP) has been used in screening for heart failure. We have investigated the use of NT proBNP as a screening tool for left ventricular systolic dysfunction to reduce the requirement for pre-operative echocardiograms. Ninety-eight pre-operative non-cardiac surgical patients scheduled to undergo echocardiography were assessed clinically and with an NT proBNP measurement. Echocardiogram was used to define two groups of patients depending on the presence or absence of abnormal left ventricular function and the NT proBNP level was compared between the groups using non-parametric and receiver-operator-characteristic (ROC) curve analysis. In terms of pre-operative screening, a NT proBNP of <38.2 pmol.l⁻¹ had a 100% negative predictive value in predicting patients with normal left ventricular systolic function and would have prevented the requirement for echocardiogram in 43% of pre-operative patients. NT proBNP was superior to electrocardiological and clinical criteria for detection of a normal echocardiogram. This may have significant impact in the pre-operative assessment of patients undergoing non-cardiac surgery.

Am Fem Physician 2007;73:841-846

Diastolic heart failure occurs when signs and symptoms of heart failure are present but left ventricular systolic function is preserved (i.e., ejection fraction greater than 45 percent). The incidence of diastolic heart failure increases with age; therefore, 50 percent of older patients with heart failure may have isolated diastolic dysfunction. With early diagnosis and proper management the prognosis of diastolic dysfunction is more favorable than that of systolic dysfunction. Distinguishing diastolic from systolic heart failure is essential because the optimal therapy for one may aggravate the other. Although diastolic heart failure is clinically and radiographically indistinguishable from systolic heart failure, normal ejection fraction and abnormal diastolic function in the presence of symptoms and signs of heart failure confirm diastolic heart failure. The pharmacologic therapies of choice for diastolic heart failure are angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, diuretics, and beta blockers.

Ann Intern Med. 2007;147:251-262

Patients with left ventricular (LV) systolic dysfunction have an increased risk for ventricular arrhythmias.

Purpose
To summarize the evidence about benefits and harms of implantable cardioverter defibrillators (ICDs) in adult patients with LV systolic dysfunction.

Data Sources
A search of electronic databases (including MEDLINE, EMBASE, Cochrane Central, and U.S. Food and Drug Administration reports) from 1980 through April 2007, not limited by language of publication, was supplemented by hand searches and contact with study authors and device manufacturers.

Study Selection
Two reviewers independently selected studies on the basis of prespecified criteria. They selected 12 randomized, controlled trials (RCTs) (8516 patients) that reported on mortality and 76 observational studies (96 951 patients) that examined safety or effectiveness.

Data Extraction
Data were extracted in duplicate and independently by 2 reviewers.

Data Synthesis
In adult patients with LV systolic dysfunction, 86% of whom had New York Heart Association class II or III symptoms, ICDs reduced all-cause mortality by 20% (95% CI, 10% to 29%) in the RCTs and by 46% (CI, 32% to 57%) in the observational studies. Death associated with implantation of ICDs occurred during 1.2% (CI, 0.9% to 1.5%) of procedures. The frequency of postimplantation complications per 100 patient-years included 1.4 (CI, 1.2 to 1.6) device malfunctions, 1.5 (CI, 1.3 to 1.8) lead problems, and 0.6 (CI, 0.5 to 0.8) site infection. Rates of inappropriate discharges per 100 patient-years ranged from 19.1 (CI, 16.5 to 22.0) in RCTs to 4.9 (CI, 4.5 to 5.3) in observational studies.

Limitations
Studies were of short duration and infrequently reported nonfatal outcomes. Few studies evaluated dual-chamber ICDs. Lack of individual-patient data prevents identification of subgroup-specific effects.

Conclusions
Implantable cardioverter defibrillators are efficacious in reducing mortality for adult patients with LV systolic dysfunction, and this benefit extends to nontrial populations. Improved risk stratification tools to identify patients who are most likely to benefit from ICD are needed.

British Journal of Anaesthesia 2007;99:170-176

B-type natriuretic peptide (BNP) levels predict cardiovascular risk in several settings. We hypothesized that they would identify individuals at increased risk of early cardiac complications after major non-cardiac surgery. The current study tests this hypothesis.

Methods
Two hundred and four patients undergoing major non-cardiac surgery were studied. The primary end-point was the development of acute myocardial injury [defined as cardiac troponin I (cTnI) level > 0.32 ng ml^–1] or death in the 3 days after surgery.

Results
Preoperative BNP levels were raised in patients who died or suffered perioperative myocardial injury (median 52.2 vs 22.2 pg ml^–1, P = 0.01) and BNP predicted this outcome with an area under the receiver operating characteristic curve of 0.72 [95% confidence interval (CI) 0.59–0.86, P = 0.01]. A preoperative BNP value > 40 pg ml^–1 was associated with an increased risk of death or perioperative myocardial injury [odds ratio (OR) 6.8, 95% CI 1.8–25.9, P = 0.003], and remained independently predictive after correction for the Revised Cardiac Risk Index. Preoperative BNP levels were higher in patients who exhibited new onset atrial fibrillation or ST/T-wave changes on their postoperative ECG (median 50.5 vs 22.5 pg litre^–1, P = 0.01). They were also higher in patients who had either elevation of cTnI > 0.32 ng ml^–1 or postoperative ECG abnormalities (median 50.4 vs 21.5 pg ml^–1, P < 0.001).

Conclusions
In the setting of major non-cardiac surgery, preoperative BNP levels are higher in patients who experience perioperative death and myocardial injury. Larger studies are required to confirm these data and to clarify what BNP levels may add to existing methods of risk stratification.

British Journal of Anaesthesia 2007;99:151-154

There is presently much interest in the preoperative identification of high-risk patients undergoing major surgery—with the aim of adopting management strategies which may reduce postoperative morbidity and mortality. In the non-cardiac surgical patient, data for the UK suggest that there may be up to 8000 cardiovascular deaths per year for 5 million surgical procedures performed, with an incidence of 10 times that with regard to morbidity (myocardial infarction, congestive cardiac failure, malignant arrhythmias, and cardiac arrest). The major pathological disorder responsible for these adverse outcomes is ischaemic heart disease, either overt or covert, secondary to atherosclerosis. We, and others, have recently reviewed the role of biomarkers in the identification of at-risk cardiac patients.

For a test to be useful as a biomarker, it should to be able to differentiate between the ‘healthy’ and the ‘compromised’ patient. In epidemiological terms, it needs to have a high sensitivity (probability that the biomarker….

N Engl J Med 2006;355:1922-25

Heart failure is increasing in incidence and prevalence, is expensive to treat, and is associated with substantial morbidity and mortality.1 In the nomenclature of the guidelines of the American Heart Association and the American College of Cardiology, the majority of patients with heart failure are classified as having stage C heart failure, characterized by structural heart disease that is or has been symptomatic.2 Numerous drugs (e.g., angiotensin converting–enzyme [ACE] inhibitors or angiotensin-receptor blockers, beta-blockers, and aldosterone blockers) and electrophysiological devices may temporarily halt, slow, or even reverse the pathophysiological processes in patients with stage C heart failure. Reversion of the heart toward more normal shape and function is called reverse remodeling.

N Engl J Med 2006;355:1873-84

In patients with severe heart failure, prolonged unloading of the myocardium with the use of a left ventricular assist device has been reported to lead to myocardial recovery in small numbers of patients for varying periods of time. Increasing the frequency and durability of myocardial recovery could reduce or postpone the need for subsequent heart transplantation.

Methods
We enrolled 15 patients with severe heart failure due to nonischemic cardiomyopathy and with no histologic evidence of active myocarditis. All had markedly reduced cardiac output and were receiving inotropes. The patients underwent implantation of left ventricular assist devices and were treated with lisinopril, carvedilol, spironolactone, and losartan to enhance reverse remodeling. Once regression of left ventricular enlargement had been achieved, the 2-adrenergic–receptor agonist clenbuterol was administered to prevent myocardial atrophy.

Results
Eleven of the 15 patients had sufficient myocardial recovery to undergo explantation of the left ventricular assist device a mean (±SD) of 320±186 days after implantation of the device. One patient died of intractable arrhythmias 24 hours after explantation; another died of carcinoma of the lung 27 months after explantation. The cumulative rate of freedom from recurrent heart failure among the surviving patients was 100% and 88.9% 1 and 4 years after explantation, respectively. The quality of life as assessed by the Minnesota Living with Heart Failure Questionnaire score at 3 years was nearly normal. Fifty-nine months after explantation, the mean left ventricular ejection fraction was 64±12%, the mean left ventricular end-diastolic diameter was 59.4±12.1 mm, the mean left ventricular end-systolic diameter was 42.5±13.2 mm, and the mean maximal oxygen uptake with exercise was 26.3±6.0 ml per kilogram of body weight per minute.

Conclusions
In this single-center study, we found that sustained reversal of severe heart failure secondary to nonischemic cardiomyopathy could be achieved in selected patients with the use of a left ventricular assist device and a specific pharmacologic regimen.