A counterpoint paper: Comments on the electrocardiographic part of the 2018 Fourth Universal Definition of Myocardial Infarction endorsed by the International Society of Electrocardiology and the International Society for Holter and Noninvasive Electrocardiology

The Fourth Universal Definition of Myocardial Infarction (FUDMI) focuses on the distinction between nonischemic myocardial injury and myocardial infarction (MI), along with the role of cardiovascular magnetic resonance, in order to define the etiology of myocardial injury. As a consequence, there is less emphasis on updating the parts of the definition concerning the electrocardiographic (ECG) changes related to MI. Evidence of myocardial ischemia is a prerequisite for the diagnosis of MI, and the ECG is the main available tool for (a) detecting acute ischemia, (b) triage, and (c) risk stratification upon presentation. This review focuses on multiple aspects of ECG interpretation that we firmly believe should be considered for incorporation in any future update to the Universal Definition of MI.     

Is there an overlap between Brugada syndrome and arrhythmogenic right ventricular cardiomyopathy/dysplasia?

The Brugada syndrome is a congenital syndrome displaying an autosomal dominant mode of transmission in patients with a structurally normal heart. The disease has been linked to mutations in SCN5A , a gene located on the short arm of chromosome 3 (p21-24) that encodes for the alpha subunit of the sodium channel. The syndrome is characterized by a dynamic ST-segment elevation (accentuated J wave) in leads V 1 to V 3 of the ECG followed by negative T wave. Right bundle-branch block of varying degrees is observed in some patients. The syndrome is associated with syncope and a relatively high incidence of sudden cardiac death secondary to the development of polymorphic ventricular tachycardia that may degenerate into ventricular fibrillation. An acquired form of the Brugada syndrome is also recognized, caused by a wide variety of drugs and conditions that alter the balance of currents active during the early phases of the action potential. Among patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia, there is a subpopulation with a clinical and electrocardiographic pattern similar to that of the Brugada syndrome. These cases of arrhythmogenic right ventricular cardiomyopathy/dysplasia are thought to represent an early or concealed form of the disease. This review examines the overlap between these 2 syndromes.     

Brief Review of the Recently Described Short QT Syndrome and Other Cardiac Channelopathies

There are many diseases related to ion‐channel disorders, so‐called “channelopathies.” Hereditary short QT syndrome is a clinical‐electrocardiographic entity with autosomal‐dominant mode of transmission and it is the most recently described channelopathy. The syndrome may affect infants, children, or young adults with strong positive family background of sudden cardiac death. Short QT syndrome is characterized by short QT and heart‐rate‐corrected QTc intervals. It is frequently associated with tall‐, peaked‐, and narrow‐based T waves that are reminiscent of the typical “desert tent” T waves of hyperkalemia. There is a high tendency for paroxysmal atrial fibrillation due to the heterogeneous abbreviation of action potential duration and refractoriness of atrial myocytes. The arrhythmia can also be induced by programmed electrical stimulation. The safest treatment suggested is an implantable cardioverter defibrillator, though the possibilities of inappropriate shocks have caused some concern, especially in teenagers. The ability of quinidine to prolong the QT interval has the potential to be an effective therapy for patients with short QT syndrome. This is particularly important in developing countries, where the implantable cardioverter‐defibrillator therapy is not always available. Since these patients are at risk of sudden cardiac death from birth, and implantable cardioverter‐defibrillator implantation has a lot of limitations in very young children, the utility of quinidine has to be evaluated further. Clinicians need to be aware of this deadly electrocardiographic (ECG) pattern as it portends a high risk of sudden cardiac death in otherwise healthy subjects with structurally normal hearts.     

Idiopathic trigeminal neuralgia: sensory features and pain mechanisms

We present a case report of a patient with the typical sensory features of idiopathic trigeminal neuralgia (ITN). The pain was elicited by innocuous stimuli, summated with repeated stimulation, radiated outside the stimulus zone, referred to a distant site, persisted beyond the period of stimulation, and exhibited a variable refractory period. Unusual sensory features included multiple trigger zones that changed over time and involved all 3 trigeminal divisions. Our sensory evaluation indicated that the pain was evoked by repetitive activation of rapidly adapting, A beta, low-threshold mechanoreceptive afferents. However, activation of such mechanoreceptive afferents alone never produces pain in normal situations and often leads to a suppression of pain responsivity. The findings support the idea that the mechanism of pain in ITN involves pathophysiological mechanisms in the central nervous system. Our hypothesis is that structural and functional changes in the trigeminal system result in an alteration in the receptive field organization of wide-dynamic-range (WDR) neurons. There appears to be an alteration in the surround inhibition mechanism of these neurons leading to an expansion of their touch receptive fields. This results in touch stimuli producing activity in WDR neurons that mimics the activity produced under normal conditions by noxious stimuli. Since WDR neurons participate in the encoding of the perceived intensity of noxious stimuli, a series of punctate tactile stimuli are now perceived as localized, pin-prick or electric shock-like sensations. Similar pathophysiological mechanisms may explain, in part, the pain of peripheral neuropathies associated with postherpetic neuralgia, diabetes and causalgia.     

Early neuroprotective effect of nitric oxide in developing rat brain irradiated in utero

Pregnant Wistar rats were exposed on day 17 of gestation to 1 Gy gamma irradiation from a Co(60) source. Even though it is established that gamma radiation-dependent damage is mainly due to free radical generation neither the ascorbyl radical/ascorbate ratio nor the lipid radical content in developing rat brain were affected by prenatal irradiation. A distinctive EPR signal for the adduct NO-Fe-MGD (g=2.03 and a(N)=12.5 G) was detected in brain homogenates prepared from irradiated rats. Nitric oxide (NO)-dependent EPR signal increased in a time-dependent manner up to 2h post-irradiation. NO concentration in unirradiated brains was 37+/-4 pmol/g brain and 45+/-2, 77+/-5 and 216+/-6 after 30, 60 and 120 min post-irradiation, respectively. Total nitric oxide synthase activity was increased by 77 and 51% after 30 and 60 min post-irradiation, respectively, and returned to control values after 120 min. Thus, increased NO steady-state concentration could be ascribed to an increase in NOS activity. Taken as a whole, these results suggest that NO might act to protect the developing brain from the cytotoxicity of reactive species.     

Spinal lamina I neurons projecting to the parabrachial area of the cat midbrain

We have observed a population of lamina I neurons in the cat that has projections to the parabrachial area (parabrachial and cuneiform nuclei). A subpopulation of these neurons also projects to the contralateral thalamus. The majority of projecting cells responded exclusively to noxious stimuli, a few wide-dynamic-range neurons were also observed. Conduction velocities for antidromic activation from the midbrain ranged from 1 to 18 m/s. We stained 14 cells intracellularly with horseradish peroxidase. These findings suggest that a major nociceptive projection pathway originating in lamina I and terminating in the parabrachial area exists in the cat.