Jason C. Schultz

Diagnosis and Treatment of Viral Myocarditis

Myocarditis, an inflammatory disease of heart muscle, is an important cause of dilated cardiomyopathy worldwide. Viral infection is also an important cause of myocarditis, and the spectrum of viruses known to cause myocarditis has changed in the past 2 decades. Several new diagnostic methods, such as cardiac magnetic resonance imaging, are useful for diagnosing myocarditis. Endomyocardial biopsy may be used for patients with acute dilated cardiomyopathy associated with hemodynamic compromise, those with life-threatening arrhythmia, and those whose condition does not respond to conventional supportive therapy. Important prognostic variables include the degree of left and right ventricular dysfunction, heart block, and specific histopathological forms of myocarditis. We review diagnostic and therapeutic strategies for the treatment of viral myocarditis. English-language publications in PubMed and references from relevant articles published between January 1, 1985, and August 5, 2008, were analyzed. Main keywords searched were myocarditis, dilated cardiomyopathy, endomyocardial biopsy, cardiac magnetic resonance imaging, and immunotherapy.

Epidemiological trends of infective endocarditis: a population-based study in Olmsted County, Minnesota.

OBJECTIVE To provide a contemporary profile of epidemiological trends of infective endocarditis (IE) in Olmsted County, Minnesota. PATIENTS AND METHODS This study consists of all definite or possible IE cases among adults in Olmsted County from January 1, 1970, through December 31, 2006. Cases were identified using resources of the Rochester Epidemiology Project. RESULTS We identified 150 cases of IE. The age- and sex-adjusted incidences of IE ranged from 5.0 to 7.9 cases per 100,000 person-years with an increasing trend over time differential with respect to sex (for interaction, P=.02); the age-adjusted incidence of IE increased significantly in women (P=.006) but not in men (P=.79). We observed an increasing temporal trend in the mean age at diagnosis (P=.04) and a decreasing trend in the proportion of cases with rheumatic heart disease as a predisposing condition (P=.02). There were no statistically significant temporal trends in the incidence of either Staphylococcus aureus or viridans group streptococcal IE. Data on infection site of acquisition were available for cases seen in 2001 and thereafter, with 50.0% designated as health care-associated, 42.5% community-acquired, and 7.5% nosocomial. CONCLUSION The incidence of IE among women increased from 1970 to 2006. Ongoing surveillance is warranted to determine whether the incidence change in women will be sustained. Subsequent analysis of infection site of acquisition and its impact on the epidemiology of IE are planned.

Sodium nitroprusside enhanced cardiopulmonary resuscitation improves survival with good neurological function in a porcine model of prolonged cardiac arrest.

2261 Nighttime senior intensivist coverage is an important issue, discussed at the moment in many pediatric intensive care units (PICUs) worldwide. Therefore, studies on this topic are welcome. The specific local circumstances and organization of the PICU and the hospital dictate the optimal medical rosters. In this issue of Critical Care Medicine, Nishisaki et al (1) present their experiences with implementation of 24-hr in-hospital pediatric critical care attending coverage. The special features of their PICU are the following: no admissions of cardiac surgery patients and neonates after birth, low PICU mortality (2.2–2.5%), low proportion of ventilated patients, fairly high proportion of admissions after cardiopulmonary resuscitation on the floor (about 40 patients per year), and high proportion of admissions with malignancy. Senior consultant coverage during nighttime may be especially important in: 1) PICUs with postcardiac surgery patients because the nadir of cardiac function occurs typically 6–12 hrs after separation from cardiopulmonary bypass (2); 2) PICUs with admission of neonates directly after birth because childbirths happen to take place over night; and 3) PICUs with a high proportion of ventilated patients because of artificial ventilation–related complications. These risk factors are not present in the PICU described by Nishisaki et al (1). However, the PICU management of children after cardiac arrest on the ward may benefit from nighttime attendant presence. In a study from Australia, 20% of inhospital cardiac arrests were due to septic shock and 10% were due to upper airway obstruction (3). Because cardiac arrest is usually the culmination of prolonged hypoxemia or circulatory failure, there may be sufficient time to intervene and prevent it (3). Early detection of evolving, still compensated shock or respiratory failure is difficult and needs high clinical experience. Therefore, nighttime senior consultant coverage on the ward may be as important as in PICU. Too often, children need intensive care because of deficiencies in primary health care or care on general pediatric wards (4). Nishisaki et al (1) report on a significant decrease in PIUC length of stay and duration of mechanical ventilation. This fact alone is an important achievement because the duration of mechanical ventilation is associated with complications, such as ventilator associated pneumonia, sepsis, fluid overload and malnutrition, and renal failure. The authors claim that the shorter duration of mechanical ventilation and shorter length of stay are associated with the transition from a 12-hr to a 24-hr in-hospital pediatric critical care attending physician coverage model. I wonder whether this explanation is right or whether the authors should more cautiously state that there is just a significant improvement over time. For the standardized mortality ratio (SMR), calculated with Pediatric Index of Mortality 2 (5), many intensive care units observed an improvement over time and therefore are calling for a recalibration of the score (6). Obviously, intensive care units tend to improve with time. In our PICU in Zurich (around 1,300 admissions per year), we observed a steady improvement of the SMR, along with a decrease in the duration of intubation: mean duration of intubation (unfortunately, medians are not available any more): year 2000: 7.1 days, 2001: 6.6 days, 2002: 6.1 days, 2003: 5.3 days, 2004: 4.5 days, 2005: 5.6 days, 2006: 3.3 days, 2007: 2.6 days, 2008: 2.9 days, 2009: 2.8 days; SMR (95% confidence interval): 2004: 0.99 (0.75, 1.23), 2005: 1.27 (1.02, 1.52), 2006: 0.84 (0.59, 1.09), 2007: 0.74 (0.51, 0.97), 2008: 0.59 (0.36, 0.82), 2009: 0.53 (0.31, 0.75) (B. Frey, unpublished personal data). SMR is calculated from Pediatric Index of Mortality 2, which was released in 2003 (5). For the SMR, mean Pediatric Index of Mortality 2 values were used and the 95% confidence interval were calculated according to Rapoport et al (7). We had no major management changes such as the implementation of 24-hr in hospital attending coverage (in fact, consultants stay in hospital until 11 PM and thereafter are on call at home, obliged to return to the hospital within a maximum of 30 mins, if necessary). However, we had a multitude of subtle changes (improvements) over the last years, such as new guidelines, patient safety measures, improvements in resident/fellow/nursing teaching, strengthening of clinical pharmacy, and hospital hygiene. A further issue of nighttime attendant presence is related to fellow teaching. On one hand, there may be more bedside education provided at nighttime by attending physicians (1). On the other hand, fellows may be more tightly guided by their consultant; they may be less exposed to clinical problems, reducing their autonomy and decision-making skills. Education in intensive care medicine is a tightrope walk between direct supervision and autonomy of the fellow. In conclusion, it seems obvious that nighttime consultant presence improves quality and safety of care. The article by Nishisaki et al (1) adds at least some evidence to this assumption. It is difficult to argue that there is no need of experienced intensivists at the bedside of our sickest patients at night (i.e., half of a 24-hr day!).Objective: To assess the effectiveness of sodium nitroprusside (SNP)-“enhanced” cardiopulmonary resuscitation (SNPeCPR) on 24-hr survival rates compared to standard CPR in animals after cardiac arrest. SNPeCPR consists of large intravenous SNP bolus doses during CPR enhanced by active compression-decompression CPR, an inspiratory impedance threshold device (ITD), and abdominal binding (AB). The combination of active compression-decompression CPR+ITD+AB without SNP will be called “enhanced” or eCPR. Design: Randomized, blinded, animal study. Setting: Preclinical animal laboratory. Subjects: Twenty-four female farm pigs (30 ± 1 kg). Interventions: Isoflurane anesthetized and intubated pigs were randomized after 8 mins of untreated ventricular fibrillation to receive either standard CPR (n = 8), SNPeCPR (n = 8), or eCPR (n = 8) for 25 mins followed by defibrillation. Measurements and Main Results: The primary end point was carotid blood flow during CPR and 24-hr survival with good neurologic function defined as an overall performance category score of ≤2 (1 = normal, 5 = brain dead or dead). Secondary end points included hemodynamics and end-tidal CO2. SNPeCPR significantly improved carotid blood flow and 24-hr survival rates with good neurologic function compared to standard CPR or eCPR (six of eight vs. zero of eight vs. one of eight, p < .05). The improved survival rates were associated with higher coronary perfusion pressure and ETco2 during CPR. Conclusion: In pigs, SNPeCPR significantly improved hemodynamics, resuscitation rates, and 24-hr survival rates with good neurologic function after cardiac arrest when compared with standard CPR or eCPR alone.

Cardiac Platypnea‐Orthodeoxia Syndrome: An Often Unrecognized Malady

Platypnea‐orthodeoxia syndrome (POS) is a rare but clinically important form of dyspnea. The syndrome is characterized by dyspnea and arterial oxygen desaturation that occurs in the upright position and improves with recumbency. In cardiac POS, an atrial septal defect or patent foramen ovale allows communication between the right‐ and left‐sided circulations. A second defect, such as a dilated aorta, prominent eustachian valve, or pneumonectomy, then contributes to right‐to‐left shunting through the interatrial connection. Diagnosis is made through pulse oximetry to confirm orthodeoxia and through transesophageal echocardiography with bubble study to visualize the shunt. Although data are limited for this rare syndrome, percutaneous closure has thus far proven safe and effective.

Cardiac platypnea-orthodeoxia syndrome

Platypnea‐orthodeoxia syndrome (POS) is a rare but clinically important form of dyspnea. The syndrome is characterized by dyspnea and arterial oxygen desaturation that occurs in the upright position and improves with recumbency. In cardiac POS, an atrial septal defect or patent foramen ovale allows communication between the right‐ and left‐sided circulations. A second defect, such as a dilated aorta, prominent eustachian valve, or pneumonectomy, then contributes to right‐to‐left shunting through the interatrial connection. Diagnosis is made through pulse oximetry to confirm orthodeoxia and through transesophageal echocardiography with bubble study to visualize the shunt. Although data are limited for this rare syndrome, percutaneous closure has thus far proven safe and effective.

Sodium nitroprusside enhanced cardiopulmonary resuscitation (SNPeCPR) improves vital organ perfusion pressures and carotid blood flow in a porcine model of cardiac arrest

PURPOSE OF THE STUDY To describe a new method of CPR that optimizes vital organ perfusion pressures and carotid blood flow. We tested the hypothesis that a combination of high dose sodium nitroprusside (SNP) as well as non-invasive devices and techniques known independently to enhance circulation would significantly improve carotid blood flow (CBF) and return of spontaneous circulation (ROSC) rates in a porcine model of cardiac arrest. METHODS 15 isofluorane anesthetized pigs (30±1 kg), after 6 min of untreated ventricular fibrillation, were subsequently randomized to receive either 15 min of standard CPR (S-CPR) (8 animals) or 5 min epochs of S-CPR followed by active compression-decompression (ACD)+inspiratory impedance threshold device (ITD) CPR followed by ACD+ITD+abdominal binding (AB) with 1mg of SNP administered at minutes 2, 7, 12 of CPR (7 animals). Primary endpoints were CBF and ROSC rates. ANOVA and Fishers exact test were used for comparisons. RESULTS/CONCLUSION There was significant improvement in the hemodynamic parameters in the SNP animals. ROSC was achieved in 7/7 animals that received SNP and in 2/8 in the S-CPR (p=0.007). CBF and end tidal CO(2) (ETCO(2)) were significantly higher in the ACD+ITD+AB+SNP (SNPeCPR) animals during CPR. Bolus doses of SNP, when used in conjunction with ACD+ITD+AB CPR, significantly improve CBF and ROSC rates compared to S-CPR.

Sodium nitroprusside-enhanced cardiopulmonary resuscitation improves resuscitation rates after prolonged untreated cardiac arrest in two porcine models.

Objective:Sodium nitroprusside-enhanced cardiopulmonary resuscitation consists of active compression-decompression, an impedance threshold device, abdominal binding, and large intravenous doses of sodium nitroprusside. We hypothesize that sodium nitroprusside-enhanced cardiopulmonary resuscitation will significantly increase carotid blood flow and return of spontaneous circulation compared to standard cardiopulmonary resuscitation after prolonged ventricular fibrillation and pulseless electrical activity cardiac arrest. Design:Prospective randomized animal study. Setting:Hennepin County Medical Center Animal Laboratory. Subjects:Forty Yorkshire female farm-bred pigs weighing 32 ± 2 kg. Interventions:In protocol A, 24 isoflurane-anesthetized pigs underwent 15 mins of untreated ventricular fibrillation and were subsequently randomized to receive standard cardiopulmonary resuscitation (n = 6), active compression-decompression cardiopulmonary resuscitation + impedance threshold device (n = 6), or sodium nitroprusside-enhanced cardiopulmonary resuscitation (n = 12) for up to 15 mins. First defibrillation was attempted at minute 6 of cardiopulmonary resuscitation. In protocol B, a separate group of 16 pigs underwent 10 mins of untreated ventricular fibrillation followed by 3 mins of chest compression only cardiopulmonary resuscitation followed by countershock-induced pulseless electrical activity, after which animals were randomized to standard cardiopulmonary resuscitation (n = 8) or sodium nitroprusside-enhanced cardiopulmonary resuscitation (n = 8). Measurements and Main Results:The primary end point was carotid blood flow during cardiopulmonary resuscitation and return of spontaneous circulation. Secondary end points included end-tidal CO2 as well as coronary and cerebral perfusion pressure. After prolonged untreated ventricular fibrillation, sodium nitroprusside-enhanced cardiopulmonary resuscitation demonstrated superior rates of return of spontaneous circulation when compared to standard cardiopulmonary resuscitation and active compression-decompression cardiopulmonary resuscitation + impedance threshold device (12 of 12, 0 of 6, and 0 of 6 respectively, p < .01). In animals with pulseless electrical activity, sodium nitroprusside-enhanced cardiopulmonary resuscitation increased return of spontaneous circulation rates when compared to standard cardiopulmonary resuscitation. In both groups, carotid blood flow, coronary perfusion pressure, cerebral perfusion pressure, and end-tidal CO2 were increased with sodium nitroprusside-enhanced cardiopulmonary resuscitation. Conclusions:In pigs, sodium nitroprusside-enhanced cardiopulmonary resuscitation significantly increased return of spontaneous circulation rates, as well as carotid blood flow and end-tidal CO2, when compared to standard cardiopulmonary resuscitation or active compression-decompression cardiopulmonary resuscitation + impedance threshold device.

Sodium nitroprusside enhanced cardiopulmonary resuscitation prevents post-resuscitation left ventricular dysfunction and improves 24-hour survival and neurological function in a porcine model of prolonged untreated ventricular fibrillation.

AIM OF STUDY Sodium nitroprusside-enhanced CPR, or SNPeCPR, consists of active compression-decompression CPR with an impedance threshold device, abdominal compression, and intravenous sodium nitroprusside (SNP). We hypothesize that SNPeCPR will improve post resuscitation left ventricular function and neurological function compared to standard (S) CPR after 15 min of untreated ventricular fibrillation in a porcine model of cardiac arrest. METHODS Pigs (n = 22) anesthetized with isoflurane underwent 15 min of untreated ventricular fibrillation, were then randomized to 6 min of S-CPR (n = 11) or SNPeCPR (n = 11) followed by defibrillation. The primary endpoints were neurologic function as measured by cerebral performance category (CPC) score and left ventricular ejection fraction. RESULTS SNPeCPR increased 24-hour survival rates compared to S-CPR (10/11 versus 5/11, p = 0.03) and improved neurological function (CPC score 2.5 ± 1, versus 3.8 ± 0.4, respectively, p = 0.004). Left ventricular ejection fractions at 1, 4 and 24 hours after defibrillation were 72 ± 11, 57 ± 11.4 and 64 ± 11 with SNPeCPR versus 29 ± 10, 30 ± 17 and 39 ± 6 with S-CPR, respectively (p < 0.01 for all). CONCLUSIONS In this pig model, after 15 min of untreated ventricular fibrillation, SNPeCPR significantly improved 24-hour survival rates, neurologic function and prevented post-resuscitation left ventricular dysfunction compared to S-CPR.

Modifiers of Symptomatic Embolic Risk in Infective Endocarditis

OBJECTIVE To ascertain the impact of prior antiplatelet and statin therapy on symptomatic embolic events in [corrected] infective endocarditis (IE). PATIENTS AND METHODS We studied a retrospective cohort of adult patients with a diagnosis of IE who presented to Mayo Clinic (Rochester, MN) from January 1, 2003, to December 31, 2006. Patients were grouped into those who received treatment before infection or controls who did not receive treatment for both antiplatelet therapy and, separately, statin therapy. Because of the retrospective study design and thus the nonrandomized treatment groups, a propensity score approach was used to account for the confounding factors that may have influenced treatment allocation. Antiplatelet therapy included aspirin, dipyridamole, clopidogrel, ticlopidine or any combination of these agents. Statin therapy included atorvastatin, simvastatin, pravastatin, lovastatin, rosuvastatin, or fluvastatin. The primary end point was a symptomatic embolic event that occurred before or during hospitalization. Multivariable logistic regression was used to assess the propensity-adjusted effects of continuous daily therapy with antiplatelet and statin agents on risk of symptomatic emboli. Likewise, Cox proportional hazards regression was used to test for an independent association with 6-month mortality for each of the treatments. RESULTS The study cohort comprised 283 patients with [corrected] IE. Twenty-eight patients (24.1%) who received prior continuous antiplatelet therapy developed a symptomatic embolic event compared with 66 (39.5%) who did not receive such treatment. After adjusting for propensity to treat, the effect of antiplatelet therapy on embolic risk was not statistically significant (odds ratio, 0.71; 95% confidence interval [CI], 0.37-1.36; P=.30). Only 14 patients (18.2%) who received prior continuous statin therapy developed a symptomatic embolic event compared with 80 (39.4%) of the 203 patients who did not. After adjusting for propensity to treat with statin therapy, the benefit attributable to statins was significant (odds ratio, 0.30; 95% CI, 0.14-0.62; P=.001). The 6-month mortality rate of the entire cohort was 28% (95% CI, 23%-34%). No significant difference was found in the propensity-adjusted rate of 6-month mortality between patients who had and had not undergone prior antiplatelet therapy (P=.91) or those who had and had not undergone prior statin therapy (P=.87). CONCLUSION The rate of symptomatic emboli associated with IE was reduced in patients who received continuous daily statin therapy before onset of IE. Despite fewer embolic events observed in patients who received antiplatelet agents, a significant association was not found after adjusting for propensity factors. A continued evaluation of these drugs and their potential impact on subsequent embolism among IE patients is warranted.

Acute Catheter-Based Mechanical Circulatory Support

Procedural and technology-based advances in circulatory support have enabled an increased number of patients to receive percutaneous coronary intervention (PCI). Without these advances, many patients would not have been considered for the procedure because of their elevated risk for complications. This chapter describes transcatheter-based circulatory support devices in clinical use today as well as data that support their usage and suggested protocols.