Survival and Neurologic Outcomes From Pharmacologic Peptide Administration During Cardiopulmonary Resuscitation of Pulseless Electrical Activity.

BACKGROUND: Outcomes from cardiopulmonary resuscitation (CPR) following sudden cardiac arrest are suboptimal. Postresuscitation targeted temperature management has been shown to have benefit in subjects with sudden cardiac arrest due to ventricular fibrillation, but there are few data for outcomes from sudden cardiac arrest due to pulseless electrical activity. In addition, intra-CPR cooling is more effective than postresuscitation cooling. Physical cooling is associated with increased protein kinase B activity. Therefore, our group developed a novel peptide, TAT-PHLPP9c, which regulates protein kinase B. We hypothesized that when given during CPR, TAT-PHLPP9c would improve survival and neurologic outcomes following pulseless electrical activity arrest. METHODS AND RESULTS: In 24 female pigs, pulseless electrical activity was induced by inflating balloon catheters in the right coronary and left anterior descending arteries for ≈7 minutes. Advanced life support was initiated. In 12 control animals, epinephrine was given after 1 and 3 minutes. In 12 peptide-treated animals, 7.5 mg/kg TAT-PHLPP9c was also administered at 1 and 3 minutes of CPR. The balloons were removed after 2 minutes of support. Animals were recovered and neurologically scored 24 hours after return of spontaneous circulation. Return of spontaneous circulation was more common in the peptide group, but this difference was not significant (8/12 control versus 12/12 peptide; P=0.093), while fully intact neurologic survival was significantly more common in the peptide group (0/12 control versus 11/12 peptide; P<0.00001). TAT-PHLPP9c significantly increased myocardial nicotinamide adenine dinucleotide levels. CONCLUSIONS: TAT-PHLPP9c resulted in improved survival with full neurologic function after sudden cardiac arrest in a swine model of pulseless electrical activity, and the peptide shows potential as an intra-CPR pharmacologic agent.

Role of Multimodality Imaging in the Assessment of Myocardial Infarction With Nonobstructive Coronary Arteries: Beyond Conventional Coronary Angiography.

Myocardial infarction with nonobstructive coronary arteries (MINOCA) is a heterogeneous clinical entity, encompassing multiple different causes, and a cause of substantial morbidity and mortality. Current guidelines suggest a multimodality imaging approach in establishing the underlying cause for MINOCA, which is considered a working diagnosis. Recent studies have suggested that an initial workup consisting of cardiac magnetic resonance and invasive coronary imaging can yield the diagnosis in most patients. Cardiac magnetic resonance is particularly helpful in excluding nonischemic causes that can mimic MINOCA including myocarditis and Takotsubo cardiomyopathy, as well as for long-term prognostication. Additionally, intracoronary imaging with intravascular ultrasound or optical coherence tomography may be warranted to evaluate plaque composition, or evaluate for plaque disruption or spontaneous coronary dissection. The role of noninvasive imaging modalities such as coronary computed tomography angiography is currently being investigated in the diagnostic approach and follow-up of MINOCA and may be appropriate in lieu of invasive coronary angiography in select patients. In recent years, many strides have been made in the workup of MINOCA; however, significant knowledge gaps remain in the field, particularly in terms of treatment strategies. In this review, we summarize recent society guideline recommendations and consensus statements on the initial evaluation of MINOCA, review contemporary multimodality imaging approaches, and discuss treatment strategies including an ongoing clinical trial.

Pulseless Electrical Activity as the Initial Cardiac Arrest Rhythm: Importance of Preexisting Left Ventricular Function.

Background Pulseless electrical activity (PEA) is a common initial rhythm in cardiac arrest. A substantial number of PEA arrests are caused by coronary ischemia in the setting of acute coronary occlusion, but the underlying mechanism is not well understood. We hypothesized that the initial rhythm in patients with acute coronary occlusion is more likely to be PEA than ventricular fibrillation in those with prearrest severe left ventricular dysfunction. Methods and Results We studied the initial cardiac arrest rhythm induced by acute left anterior descending coronary occlusion in swine without and with preexisting severe left ventricular dysfunction induced by prior infarcts in non-left anterior descending coronary territories. Balloon occlusion resulted in ventricular fibrillation in 18 of 34 naïve animals, occurring 23.5±9.0 minutes following occlusion, and PEA in 1 animal. However, all 18 animals with severe prearrest left ventricular dysfunction (ejection fraction 15±5%) developed PEA 1.7±1.1 minutes after occlusion. Conclusions Acute coronary ischemia in the setting of severe left ventricular dysfunction produces PEA because of acute pump failure, which occurs almost immediately after coronary occlusion. After the onset of coronary ischemia, PEA occurred significantly earlier than ventricular fibrillation (<2 minutes versus 20 minutes). These findings support the notion that patients with baseline left ventricular dysfunction and suspected coronary disease who develop PEA should be evaluated for acute coronary occlusion.

CPR and ECMO: The Next Frontier.

Cardiopulmonary resuscitation (CPR) is a first-line therapy for sudden cardiac arrest, while extracorporeal membrane oxygenation (ECMO) has traditionally been used as a means of countering circulatory failure. However, new advances dictate that CPR and ECMO could be complementary for support after cardiac arrest. This review details the emerging science, technology, and clinical application that are enabling the new paradigm of these iconic circulatory support modalities in the setting of cardiac arrest.