Prevalence of heart disease in patients with mitochondrial abnormalities on skeletal muscle biopsy.

OBJECTIVE: Mitochondrial DNA mutations are associated with an increased risk of heart disease. Whether an increased prevalence of cardiovascular disease is present in patients presenting with mitochondrial abnormalities on skeletal muscle biopsy remains unknown. This study was designed to determine the prevalence of cardiac conduction disease and structural heart disease in patients presenting with mitochondrial abnormalities on skeletal muscle biopsy. METHODS: This is a retrospective cohort study of 103 patients with mitochondrial abnormalities on skeletal muscle biopsy who were referred for evaluation of muscle weakness at a single tertiary care referral center from 2012 to 2018. Of these patients, 59 (57.3%) had an electrocardiogram available and were evaluated for the presence of conduction disease. An echocardiogram was available in 43 patients (42%) who were evaluated for the presence of structural heart disease. The prevalence of cardiac disease was compared to control cohort populations (Framingham and the Atherosclerosis Risk in Communities, ARIC cohorts). RESULTS: Mitochondrial abnormalities associated with cardiac conduction disease (defined as QRS duration ≥ 120 msec) were present in 8.9%, versus 2.0% (p < 0.001) in the Framingham population and 2.6% (p = 0.003) in the ARIC cohort. LV systolic dysfunction (LVEF ≤ 50%) was present in 11.6%, versus 3.6% (p < 0.01) in the Framingham and 3% (p < 0.01) in the ARIC populations. Left ventricular hypertrophy was present in 28.6%, versus 13.6% (p < 0.02) in the Framingham and 10.4% (p < 0.001) in the ARIC populations. INTERPRETATION: Given the increased prevalence of cardiovascular disease, patients with mitochondrial abnormalities on skeletal muscle biopsy should undergo routine cardiac screening with physical exam, electrocardiography, and cardiac imaging.

Evaluating and managing bradycardia.

Bradycardia is a commonly observed arrhythmia and a frequent occasion for cardiac consultation. Defined as a heart rate of less than 50-60 bpm, bradycardia can be observed as a normal phenomenon in young athletic individuals, and in patients as part of normal aging or disease (Table 1). Pathology that produces bradycardia may occur within the sinus node, atrioventricular (AV) nodal tissue, and the specialized His-Purkinje conduction system. Given the overlap of heart rate ranges with non-pathologic changes, assessment of symptoms is a critical component in the evaluation and management of bradycardia. Treatment should rarely be prescribed solely on the basis of a heart rate lower than an arbitrary cutoff or a pause above certain duration. In the 2018 ACC/AHA/HRS Guideline on the Evaluation and Management of Patients with Bradycardia and Cardiac Conduction Delay (referred to hereafter as the 2018 Bradycardia Guideline), there was a significant shift in emphasis from prior guidelines that emphasized device-based implantation recommendations to a focus on evaluation and management of disease states [1,2]. In this review, we will highlight the changes in the new guideline as well as describe the key elements in evaluation and management of patients presenting with bradycardia.

Efficacy and Safety of Transnasal CoolStat Cooling Device to Induce and Maintain Hypothermia.

Targeted temperature management (TTM) is recommended as a standard of care for postcardiac arrest patients. Current TTM methods have significant limitations to be used in an ambulatory setting. We investigated the efficacy and safety of a novel noninvasive transnasal evaporative cooling device (CoolStat™). Eleven Yorkshire pigs underwent hypothermia therapy using the CoolStat device. CoolStat induces evaporative cooling by blowing dehumidified ambient air over the nasal turbinates in a unidirectional fashion. CoolStat's efficacy and safety were assessed by applying different cooling strategies (groups A, B and C). In group A (efficacy study; n = 5, TTM for 8 hours), time to achieve brain target temperature (2°C reduction from baseline), and the percentage of time in which the temperature ranged within ±0.5°C after reaching the target temperature were investigated. In the safety assessment (groups B and C), two worst-case therapy situations were reproduced: in group B (n = 3), continuous maximum air flow (65 L/min) was applied without temperature control and, in group C (n = 3), subjects underwent 24-hour TTM (prolonged therapy). Hemodynamic and respiratory parameters, nasal mucosa integrity (endoscopic assessment), and other therapy-related adverse effects were evaluated. Efficacy study: CoolStat cooling therapy successfully induced and sustained managed hypothermia in all subjects. Brain target temperature was achieved in 0.5 ± 0.6 hours and kept within a ±0.5°C range for the therapy duration (99.9% ± 0.1%). All animals completed the safety studies. Maximum air flow (group B) and 24-hour (group C) therapies were well tolerated and no significant damage was observed on nasal mucosa for neither of the groups. CoolStat was able to efficiently induce and maintain hypothermia using unidirectional high flow of dry air into the nostrils of porcine models. CoolStat therapy was well tolerated and no damage to nasal mucosa was observed under either maximum air flow or prolonged therapy.

Minimally invasive transtracheal cardiac plexus block for sympathetic neuromodulation.

BACKGROUND: Bilateral thoracoscopic stellectomy has antiarrhythmic effects, but the procedure is invasive with associated morbidity. Sympathetic nerves from both stellate ganglia form the deep cardiac plexus (CP) in the aortopulmonary window, anterior to the trachea. OBJECTIVE: The purpose of this study was to demonstrate a novel and minimally invasive transtracheal approach to block the CP in porcine models. METHODS: In 12 Yorkshire pigs, right (RSG) and left (LSG) stellate ganglia were electrically stimulated and sympathetic baseline response recorded (hemodynamic parameters and T-wave pattern). Aortopulmonary window was accessed transtracheally with endobronchial ultrasound guidance, and local stimulation of CP confirmed the location. Injection of 1% lidocaine (n = 10) or saline solution (n = 2) was performed, and RSG and LSG responses were re-evaluated and compared with baseline. RESULTS: Transtracheal lidocaine injection into the CP successfully blocked bilateral sympathetic induced changes (%) in T-wave amplitude (282.8% ± 152.2% vs 20.1% ± 16.5%; P <.001 [LSG]; 338.9% ± 189.8% vs 28% ± 18.3%; P <.001 [RSG]), Tp-Te interval (87.9% ± 37.2% vs 6.9% ± 6.7%; P <.001 [LSG]; 32.6% ± 27.4% vs 6.9% ± 4.7%; P <.035 [RSG]), and left ventricular dP/dTmax (148.3% ± 108.5% vs 16.5% ± 13.4%; P <.001 [LSG]; 243.1% ± 105.2% vs 19.0% ± 12.4%; P <.001 [RSG]). RSG-induced elevations of systemic, left ventricular, and pulmonary arterial pressures were blocked by lidocaine injection into CP (P <.005 for all comparisons). Stellate ganglia response was not affected in sham studies. No complications were observed during the procedures. CONCLUSION: Minimally invasive transtracheal injection of lidocaine into the CP blocked the sympathetic response of either RSG and LSG. Transtracheal assessment of CP may allow for minimally invasive and selective ablation of cardiac innervation, extending the cardiac sympathectomy denervation benefits to those not suitable for surgery.

The on- and off-target effects of morphine in acute coronary syndrome: A narrative review.

With potent analgesic properties, perceived hemodynamic benefits and limited alternatives, morphine is the analgesic mainstay for patients with nitrate resistant chest pain due to acute Myocardial Infarction (MI). However, observational data suggest that morphine administration during MI may have negative consequences. While vomiting, hypotension and respiratory depression are established side effects, recent reports have demonstrated attenuated and delayed oral anti-platelet agent absorption, as well as suboptimal reperfusion after MI, all of which may translate into adverse cardiovascular outcomes. These data have resulted in reduced support for morphine in recent European and U.S. clinical practice guidelines for MI; despite the absence of any prospective randomized outcomes trials addressing this question. As such, randomized trials are now necessary to confirm whether or not morphine, which is administered in up to 30% of MI cases, causes adverse clinical outcomes in these patients. However, given that placebo-controlled randomized trial designs evaluating morphine in MI are limited by an ethical requirement for appropriate analgesia, alternative investigational approaches may be necessary. In this article we review the updated evidence for morphine in MI and outline novel strategies that may facilitate future investigation of this clinical dilemma.

Therapeutic Hypothermia After Cardiac Arrest.

OPINION STATEMENT: Resuscitated cardiac arrest continues to carry a poor prognosis despite advances in medical care. One such advance, therapeutic hypothermia, is neuroprotective and has been demonstrated to improve clinical outcomes in patients who remain unresponsive despite return of spontaneous circulation after arrhythmogenic cardiac arrest. Two landmark randomized controlled trials, both reported in 2002, led to endorsements by major American and European guidelines for therapeutic hypothermia as a viable treatment option for the prevention of adverse outcomes related to anoxic encephalopathy. Since then, significant research has been conducted to better understand the optimum strategies to maximize the neuroprotective effects of hypothermia. However, dissemination of therapeutic hypothermia guideline recommendations into clinical practice has been slow and incomplete. In this review article, we discuss the historical background and physiologic rationale for therapeutic hypothermia, review the recent literature supporting this intervention, and outline practical considerations.

Three-dimensional 123I-meta-iodobenzylguanidine cardiac innervation maps to assess substrate and successful ablation sites for ventricular tachycardia: feasibility study for a novel paradigm of innervation imaging.

BACKGROUND: Innervation is a critical component of arrhythmogenesis and may present an important trigger/substrate modifier not used in current ventricular tachycardia (VT) ablation strategies. METHODS AND RESULTS: Fifteen patients referred for ischemic VT ablation underwent preprocedural cardiac (123)I- meta-iodobenzylguanidine ((123)I-mIBG) imaging, which was used to create 3-dimensional (3D) innervation models and registered to high-density voltage maps. 3D (123)I-mIBG innervation maps demonstrated areas of complete denervation and (123)I-mIBG transition zone in all patients, which corresponded to 0% to 31% and 32% to 52% uptake. (123)I-mIBG denervated areas were ≈2.5-fold larger than bipolar voltage-defined scar (median, 24.6% [Q1-Q3, 18.3%-34.4%] versus 10.6% [Q1-Q3, 3.9%-16.4%]; P<0.001) and included the inferior wall in all patients, with no difference in the transition/border zone (11.4% [Q1-Q3, 9.5%-13.2%] versus 16.6% [Q1-Q3, 12.0%-18.8%]; P=0.07). Bipolar/unipolar voltages varied widely within areas of denervation (0.8 mV [Q1-Q3, 0.3-1.7 mV] and 4.0 mV [Q1-Q3, 2.9-5.6 mV]) and (123)I-mIBG transition zones (0.8 mV [Q1-Q3, 0.4-1.8 mV] and 4.6 mV [Q1-Q3, 3.2-6.3 mV]). Bipolar voltages in denervated areas and (123)I-mIBG transition zones were <0.5 mV, 0.5 to 1.5 mV, and >1.5 mV in 35%, 36%, and 29%, as well as 35%, 35%, and 30%, respectively (P>0.05). Successful ablation sites were within bipolar voltage-defined scar (7%), border zone (57%), and areas of normal voltage (36%), but all ablation sites were abnormally innervated (denervation/(123)I-mIBG transition zone in 50% each). CONCLUSIONS: (123)I-mIBG innervation defects are larger than bipolar voltage-defined scar and cannot be detected with standard voltage criteria. Thirty-six percent of successful VT ablation sites demonstrated normal voltages (>1.5 mV), but all ablation sites were within the areas of abnormal innervation. (123)I-mIBG innervation maps may provide critical information about triggers/substrate modifiers and could improve understanding of VT substrate and facilitate VT ablation. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique Identifier: NCT01250912.