D. L. Jardine

A 2-Hour Diagnostic Protocol for Possible Cardiac Chest Pain in the Emergency Department: A Randomized Clinical Trial

IMPORTANCE Patients with chest pain represent a high health care burden, but it may be possible to identify a patient group with a low short-term risk of adverse cardiac events who are suitable for early discharge. OBJECTIVE To compare the effectiveness of a rapid diagnostic pathway with a standard-care diagnostic pathway for the assessment of patients with possible cardiac chest pain in a usual clinical practice setting. DESIGN, SETTING, AND PARTICIPANTS A single-center, randomized parallel-group trial with blinded outcome assessments was conducted in an academic general and tertiary hospital. Participants included adults with acute chest pain consistent with acute coronary syndrome for whom the attending physician planned further observation and troponin testing. Patient recruitment occurred from October 11, 2010, to July 4, 2012, with a 30-day follow-up. INTERVENTIONS An experimental pathway using an accelerated diagnostic protocol (Thrombolysis in Myocardial Infarction score, 0; electrocardiography; and 0- and 2-hour troponin tests) or a standard-care pathway (troponin test on arrival at hospital, prolonged observation, and a second troponin test 6-12 hours after onset of pain) serving as the control. MAIN OUTCOMES AND MEASURES Discharge from the hospital within 6 hours without a major adverse cardiac event occurring within 30 days. RESULTS Fifty-two of 270 patients in the experimental group were successfully discharged within 6 hours compared with 30 of 272 patients in the control group (19.3% vs 11.0%; odds ratio, 1.92; 95% CI, 1.18-3.13; P = .008). It required 20 hours to discharge the same proportion of patients from the control group as achieved in the experimental group within 6 hours. In the experimental group, 35 additional patients (12.9%) were classified as low risk but admitted to an inpatient ward for cardiac investigation. None of the 35 patients received a diagnosis of acute coronary syndrome after inpatient evaluation. CONCLUSIONS AND RELEVANCE Using the accelerated diagnostic protocol in the experimental pathway almost doubled the proportion of patients with chest pain discharged early. Clinicians could discharge approximately 1 of 5 patients with chest pain to outpatient follow-up monitoring in less than 6 hours. This diagnostic strategy could be easily replicated in other centers because no extra resources are required. TRIAL REGISTRATION anzctr.org.au Identifier: ACTRN12610000766011.

Autonomic control of vasovagal syncope

In the pathophysiological study of vasovagal syncope, the nature of the interaction between baroreceptor sensitivity (BS), sympathetic withdrawal, and parasympathetic activity has yet to be ascertained. Altered BS may predispose toward abnormal sympathetic and parasympathetic responses to orthostasis, causing hypotension that may progress to syncope if there is sympathetic withdrawal. To examine this hypothesis, we monitored blood pressure (BP), heart rate (HR), BS, forearm blood flow, and muscle nerve sympathetic activity (MNSA) continuously in 18 vasovagal patients during 60° head-up tilt, syncope, and recovery. Results were compared with those of 17 patients who were able to tolerate tilt for 45 min. During early tilt, BP was maintained in both groups by an increase in HR and MNSA from baseline ( P < 0.01), but BS decreased more in the syncopal group ( P < 0.05). At the start of presyncope (mean 2.7 ± 0.2 min before syncope and 15.2 ± 12 min after tilt), when BP fell, HR and sympathetic activity remained increased from baseline ( P< 0.01). Thereafter, BP and HR correlated directly with sympathetic activity and regressed in linear fashion until syncope ( P < 0.001), whereas BS increased to baseline. At syncope, BP, HR, and sympathetic activity fell below baseline ( P < 0.01, P < 0.05, and P < 0.01, respectively), but BS did not increase. During recovery, sympathetic activity increased to baseline and BS increased ( P < 0.05), whereas HR and BP remained low ( P < 0.01 and P < 0.05, respectively). The mechanism for the initiation of hypotension during presyncope remains unknown, but BS may contribute. Vasodilatation and bradycardia during presyncope appear to be more closely related to withdrawal of sympathetic activity than to increased parasympathetic cardiac activity.In the pathophysiological study of vasovagal syncope, the nature of the interaction between baroreceptor sensitivity (BS), sympathetic withdrawal, and parasympathetic activity has yet to be ascertained. Altered BS may predispose toward abnormal sympathetic and parasympathetic responses to orthostasis, causing hypotension that may progress to syncope if there is sympathetic withdrawal. To examine this hypothesis, we monitored blood pressure (BP), heart rate (HR), BS, forearm blood flow, and muscle nerve sympathetic activity (MNSA) continuously in 18 vasovagal patients during 60 degrees head-up tilt, syncope, and recovery. Results were compared with those of 17 patients who were able to tolerate tilt for 45 min. During early tilt, BP was maintained in both groups by an increase in HR and MNSA from baseline (P < 0.01), but BS decreased more in the syncopal group (P < 0.05). At the start of presyncope (mean 2.7 +/- 0.2 min before syncope and 15.2 +/- 12 min after tilt), when BP fell, HR and sympathetic activity remained increased from baseline (P < 0.01). Thereafter, BP and HR correlated directly with sympathetic activity and regressed in linear fashion until syncope (P < 0.001), whereas BS increased to baseline. At syncope, BP, HR, and sympathetic activity fell below baseline (P < 0.01, P < 0.05, and P < 0.01, respectively), but BS did not increase. During recovery, sympathetic activity increased to baseline and BS increased (P < 0.05), whereas HR and BP remained low (P < 0.01 and P < 0.05, respectively). The mechanism for the initiation of hypotension during presyncope remains unknown, but BS may contribute. Vasodilatation and bradycardia during presyncope appear to be more closely related to withdrawal of sympathetic activity than to increased parasympathetic cardiac activity.

Increased cardiac sympathetic nerve activity following acute myocardial infarction in a sheep model

The time course of cardiac sympathetic nerve activity (CSNA) following acute myocardial infarction (MI) is unknown. We therefore undertook serial direct recordings of CSNA, arterial blood pressure (MAP) and heart rate (HR) in 11 conscious sheep before and after MI, and compared them with 10 controls. Conscious CSNA recordings were taken daily from electrodes glued into the thoracic cardiac nerves. Infarction was induced under pethidine and diazepam analgesia by applying tension to a coronary suture. MI size was assessed by left ventricular planimetry (%) at postmortem, peak troponin T and brain natriuretic peptide levels (BNP). Baroreflex slopes were assessed daily using phenylephrine‐nitroprusside ramps. The mean infarcted area was 14.4 ± 2.9%, troponin T 1.88 ± 0.39 μg l−1 and BNP 8.4 ± 1.3 pmol l−1. There were no differences in haemodynamic parameters or CSNA between groups at baseline. MAP and HR remained constant following MI. CSNA burst frequency increased from baseline levels of 55.8 ± 7.1 bursts min−1 to levels of 77.5 ± 8.7 bursts min−1 at 2 h post‐MI, and remained elevated for 2 days (P < 0.001). CSNA burst area also increased and was sustained for 7 days following MI (P= 0.016). Baroreflex slopes for pulse interval and CSNA did not change. CSNA increases within 1 h of the onset of MI and is sustained for at least 7 days. The duration of this response may be longer because the recording fields decrease with time. This result is consistent with a sustained cardiac excitatory sympathetic reflex.

A Comparative Study of Blood Pressure Control with Short In-Center versus Long Home Hemodialysis

We conducted a randomized crossover trial to establish, within patients, whether long-slow hemodialysis (HD) was associated with better blood pressure (BP) control than standard HD. Nine home HD patients, not on antihypertensive drugs, were dialyzed to the same eKt/Vurea and target weights for 6–8 h (LD) at home and for 3.5–4.5 h (SD) in the dialysis center 3 times weekly in randomized sequence, with each phase lasting 8 weeks. Ambulatory BP, bioimpedance, neurohormones and autonomic function were measured in each phase. Pre- and postdialysis systolic, ambulatory systolic and diastolic BP were all higher with SD than with LD and intradialysis hypotension was more common. Weight, ECF volume and neurohormones did not differ between treatments. Muscle sympathetic activity was increased in both phases and cardiac sympathetic activity tended higher during SD. These findings suggest that additional factors to ECF volume may contribute to the superior BP control produced by long-slow HD.

The history of diagnosing carotid sinus hypersensitivity: why are the current criteria too sensitive?

The carotid sinus syndrome and carotid sinus hypersensitivity (CSH) are closely related disorders. The first is characterized by syncope triggered by manipulation of the carotid sinus in daily life (e.g. shaving). According to the current European Society of Cardiology guidelines, CSH is diagnosed when carotid sinus massage elicits ≥3 s asystole, a fall in systolic blood pressure of ≥50 mmHg, or both, with symptoms. The question is, however, whether symptoms can be expected when these criteria are met. Although they are widely accepted, we will show that their basis is primarily in arbitrary clinical observations and that in the original publications the link between classification and clinical symptoms was often dubious. The current criteria for CSH are thus too sensitive, explaining the reported high prevalence of CSH in the general older population. The review will conclude with suggesting a stricter set of criteria for CSH that should be evaluated in future studies.

Neurohormonal response to head-up tilt and its role in vasovagal syncope.

In a controlled study, 26 patients with a history of recurrent syncope were found to have increased arginine vasopressin, corticotrophin, and atrial natriuretic factor levels after 5 minutes of 60 degrees head-up tilt, long before they became hypotensive. The exaggerated neurohormonal response in these patients may indicate a greater sensitivity to central hypovolemia which may predispose to vasovagal syncope, mediated by the vasodilatory effects of atrial natriuretic factor or the sensitization of mechanoreceptors by arginine vasopressin.

Effectiveness of EDACS Versus ADAPT Accelerated Diagnostic Pathways for Chest Pain: A Pragmatic Randomized Controlled Trial Embedded Within Practice.

STUDY OBJECTIVE A 2-hour accelerated diagnostic pathway based on the Thrombolysis in Myocardial Infarction score, ECG, and troponin measures (ADAPT-ADP) increased early discharge of patients with suspected acute myocardial infarction presenting to the emergency department compared with standard care (from 11% to 19.3%). Observational studies suggest that an accelerated diagnostic pathway using the Emergency Department Assessment of Chest Pain Score (EDACS-ADP) may further increase this proportion. This trial tests for the existence and size of any beneficial effect of using the EDACS-ADP in routine clinical care. METHODS This was a pragmatic randomized controlled trial of adults with suspected acute myocardial infarction, comparing the ADAPT-ADP and the EDACS-ADP. The primary outcome was the proportion of patients discharged to outpatient care within 6 hours of attendance, without subsequent major adverse cardiac event within 30 days. RESULTS Five hundred fifty-eight patients were recruited, 279 in each arm. Sixty-six patients (11.8%) had a major adverse cardiac event within 30 days (ADAPT-ADP 29; EDACS-ADP 37); 11.1% more patients (95% confidence interval 2.8% to 19.4%) were identified as low risk in EDACS-ADP (41.6%) than in ADAPT-ADP (30.5%). No low-risk patients had a major adverse cardiac event within 30 days (0.0% [0.0% to 1.9%]). There was no difference in the primary outcome of proportion discharged within 6 hours (EDACS-ADP 32.3%; ADAPT-ADP 34.4%; difference -2.1% [-10.3% to 6.0%], P=.65). CONCLUSION There was no difference in the proportion of patients discharged early despite more patients being classified as low risk by the EDACS-ADP than the ADAPT-ADP. Both accelerated diagnostic pathways are effective strategies for chest pain assessment and resulted in an increased rate of early discharges compared with previously reported rates.

Delayed pulmonary hypertension following splenectomy for congenital spherocytosis

A 57-year-old man presented in 1991 with increasing shortness of breath over five years. He reported no other chest symptoms and 10 years earlier had given up a 30-year smoking habit. As a young man, he underwent splenectomy for congenital spherocytosis, which resulted in a normalisation of his haemoglobin concentration and exercise tolerance. Chest examination was normal and there were no features of right heart failure. The full blood count and chest X-ray were normal; the electrocardiogram demonstrated peaked P waves and the echocardiogram showed normal left ventricular function with a dilated right heart. Spirometry results included a 1-second-forced expiratory volume of 2.7 L (82% predicted), a forced vital capacity of 4.2 L (99% predicted) and a residual volume of 2.1 L (96% predicted). Carbon monoxide diffusion capacity, corrected for lung volume, was 3.82 mL/min per mmHg per L (88% predicted). Pulmonary angiography showed multiple pulmonary emboli in the right lower lobe. He was started on longterm warfarin. His dyspnoea progressed and when reexamined in 1994 he was cyanosed at rest with giant V waves in the neck, a loud S2 and a tricuspid regurgitant murmur. Doppler demonstrated a right ventricular systolic pressure of 60 mmHg and arterial pO2 was 8.5 kPa, so he was started on domicillary oxygen. Ventilation-perfusion lung scan showed subsegmental mismatched areas. Right heart catheterisation pressures were as follows: mean right atrial 8 mmHg, pulmonary artery 90/35 mmHg, capillary wedge 5 mmHg and pulmonary vascular resistance 1282 dynes/s per cm–5. Cardiac output was 3.12 L/min. Repeat angiography showed proximally dilated pulmonary arteries, pouch and web defects in the right lower lobe and attenuation of distal vessels (Figure 1). Ultrasound of the deep leg veins was normal. In 1995 he underwent pulmonary angioscopy in San Diego but no resectable thromboembolic disease was present and inhaled nitric oxide did not decrease pulmonary resistance. The risks of lung transplantation were considered prohibitive because of his age and he continued to deteriorate despite pharmacological treatment. He subjectively improved on nebulised prostacyclin (Iloprost trometamol 10 μg b.d.) but required frusemide for peripheral oedema and liver capsule pain. Oxypentifylline and aspirin were used in the hope of improving small vessel pulmonary blood flow and finally, sildenafil was started 6 months before his death in 2002. Autopsy showed extensive atherosclerosis of the pulmonary arteries and right ventricular hypertrophy. There was severe muscular hypertrophy and intimal fibrosis in the medium-sized pulmonary arteries and plexiform change in the smaller vessels. Subtle features of previous thromboembolism were present. Chronic thromboembolic pulmonary hypertension (CTPH) is rare, occurring in only 0.1% of pulmonary embolism survivors and the diagnosis is difficult because first, up to 50% do not have a history of pulmonary embolism.1 Second, the physical findings of pulmonary hypertension may be subtle (before right ventricular failure develops), and even when found are often attributed to obstructive airways disease.1,2 In our patient, pulmonary angiography was undertaken because symptoms were progressive and his stable spirometry results were not consistent with the echo findings of pulmonary hypertension. Finally, although angiographic features of large artery chronic thromboembolism were found in the right lower lobe, only subsegmental defects were seen on the ventilation perfusion scan. The absence of segmental (or greater) areas of mismatch makes significant proximal disease very unlikely. Unfortunately, computed tomography does not add to the sensitivity of these investigations and angioscopy was undertaken because, occasionally, perfusion defects understate the magnitude of the proximal lesions.3 It is vital to exclude

Vasovagal syncope interrupting sleep

Clinical data are reported for 13 patients who were referred with recurrent loss of consciousness at night interrupting their sleep. Most of the patients were women (10 of 13) with a mean age of 45 years (range 21–72 years). The histories were more consistent with vasovagal syncope than with epilepsy. This was supported by electroencephalographic and tilt test results. More polysomnographic monitoring data are required to confirm the diagnosis of vasovagal syncope interrupting sleep. This will be difficult because, although the condition may not be rare, the episodes are usually sporadic.

Respiratory failure secondary to diabetic neuropathy affecting the phrenic nerve

We report a patient with Type 2 diabetes mellitus complicated by neuropathy affecting the phrenic nerves, resulting in fatal respiratory failure. Diabetic mononeuropathy is common and usually recovers spontaneously, but bilateral phrenic nerve involvement appears to be uncommon and difficult to treat. The pathology of diabetic mononeuropathy is not well understood and we believe this to be the first histological report of a phrenic nerve biopsy in this condition.