David D. Berg

Interruptions of Chest Compressions During Emergency Medical Systems Resuscitation

Background—Survival after nontraumatic out-of-hospital (OOH) cardiac arrest in Tucson, Arizona, has been flat at 6% (121/2177) for the decade 1992 to 2001. We hypothesized that interruptions of chest compressions occur commonly and for substantial periods during treatment of OOH cardiac arrest and could be contributing to the lack of improvement in resuscitation outcome. Methods and Results—Sixty-one adult OOH cardiac arrest patients treated by automated external defibrillator (AED)–equipped Tucson Fire Department first responders from November 2001 through November 2002 were retrospectively reviewed. Reviews were performed according to the code arrest record and verified with the AED printout. Validation of the methodology for determining the performance of chest compressions was done post hoc. The median time from “9-1-1” call receipt to arrival at the patient’s side was 6 minutes, 27 seconds (interquartile range [IQR, 25% to 75%], 5 minutes, 24 seconds, to 7 minutes, 34 seconds). An additional 54 seconds (IQR, 38 to 74 seconds) was noted between arrival and the first defibrillation attempt. Initial defibrillation shocks never restored a perfusing rhythm (0/21). Chest compressions were performed only 43% of the time during the resuscitation effort. Although attempting to follow the 2000 guidelines for cardiopulmonary resuscitation, chest compressions were delayed or interrupted repeatedly throughout the resuscitation effort. Survival to hospital discharge was 7%, not different from that of our historical control (4/61 versus 121/2177; P=0.74). Conclusions—Frequent interruption of chest compressions results in no circulatory support during more than half of resuscitation efforts. Such interruptions could be a major contributing factor to the continued poor outcome seen with OOH cardiac arrest.

Variability of individual platelet reactivity over time in patients treated with clopidogrel: insights from the ELEVATE-TIMI 56 trial.

BACKGROUND The degree of antiplatelet response to clopidogrel has been associated with clinical outcomes. Studies have investigated whether adjustment of antiplatelet therapies based on a single platelet function test is beneficial. OBJECTIVES The aim of the study was to test the stability of platelet reactivity measurements over time among patients treated with standard and double doses of clopidogrel. METHODS The ELEVATE-TIMI 56 (Escalating Clopidogrel by Involving a Genetic Strategy-Thrombolysis In Myocardial Infarction 56) investigators genotyped 333 patients with coronary artery disease and randomized them to various clopidogrel regimens. Patients with at least 2 platelet function results on the same maintenance dose of clopidogrel (75 mg or 150 mg) were analyzed. Platelet aggregation was measured using P2Y12 reaction units (PRU). RESULTS In total, the mean platelet reactivity and the total number of nonresponders (PRU ≥230) with clopidogrel did not change between 2 periods for the 75-mg (22.4% vs. 21.9%; p = 0.86) and 150-mg doses of clopidogrel (11.5% vs. 11.5%; p = 1.00). In contrast, when evaluating each patient individually, 15.7% of patients taking clopidogrel 75 mg and 11.4% of patients taking 150 mg had a change in their responder status when tested at 2 different time points (p < 0.001). Despite being treated with the same dose of clopidogrel, >40% of patients had a change in PRU >40 on serial sampling, which approximates the average PRU difference caused by increasing the clopidogrel dose from 75 mg to 150 mg. CONCLUSIONS Measurements of platelet reactivity vary over time in a significant proportion of patients. Thus, treatment adjustment according to platelet function testing at a single time point might not be sufficient for guiding antiplatelet therapy in clinical or research settings. (Escalating Clopidogrel by Involving a Genetic Strategy-Thrombolysis In Myocardial Infarction 56 [ELEVATE-TIMI 56]; NCT01235351).

The facts behind niacin

Although low-density lipoprotein cholesterol (LDL-C) lowering represents the mainstay of current lipid treatment, high-density lipoprotein cholesterol (HDL-C) has generated increasing interest as a secondary therapeutic target because of strong evidence that serum HDL-C concentration is inversely associated with coronary heart disease risk. Niacin is a lipid-altering drug that has been used to lower cholesterol since the 1950s. In addition to its LDL-C-lowering effects, niacin is the most effective agent currently available for raising HDL-C. Despite its long history as a lipid-altering drug, only limited data are available regarding its clinical benefit alone and in combination with other agents, and the majority of studies investigating its impact on clinical outcomes are from the pre-statin area. Several studies have demonstrated a beneficial effect of treatment with niacin in combination with statin therapy on surrogate cardiovascular markers (e.g. carotid intima-media thickness). However, the clinical significance of these surrogate markers has been questioned. Two large randomized trials will address whether niacin–statin combination therapy is an appropriate therapeutic alternative to statin monotherapy.

Outcomes in patients undergoing percutaneous ventricular assist device implantation for cardiogenic shock

Background: Percutaneous ventricular assist devices (PVADs) offer an important but resource-intensive option for management of severe cardiogenic shock (CS). Optimal selection of patients for PVAD support remains undefined. We investigated outcomes, including characteristics associated with in-hospital survival, during PVAD support for CS. Methods: We established a prospective quality improvement program among patients undergoing TandemHeart PVAD implantation for CS at Brigham and Women’s Hospital (Boston, MA). We evaluated 65 consecutive patients between 2006 and 2014, analyzing demographic, clinical, laboratory, hemodynamic, and survival data. Results: Thirty-two patients (49.2%) survived to hospital discharge, of which 12 received destination surgical therapy. Baseline characteristics associated with survival included younger age (47 ± 15 years vs 61 ± 11 years; p<0.001), non-ischemic cardiomyopathy (NICMP) vs ischemic CMP (survival 70.4% vs 34.2%, p=0.004), and, paradoxically, lower presenting left ventricular ejection fraction (LVEF) (survival 66.7% for LVEF ⩽15%, 41.2% for LVEF 16–25%, 25.0% for LVEF >25%; p=0.010). Younger age (p=0.026) and NICMP (p=0.034) remained independent predictors of survival. Twenty-four hours after PVAD placement, a more modest increase in cardiac index (⩽0.75 L/min/m2) was associated with higher in-hospital mortality (OR 6.3, 95% CI 1.8–22.1), as was lack of improvement in serum anion gap (⩽2 mEq/L; OR 5.1, 95% CI 1.6–16.6). Conclusions: Despite intensive care and provision of circulatory support, survival is poor in severe CS. Patients in CS with younger age and NICMP were more likely to survive to hospital discharge. Less robust hemodynamic improvement and persistent acidosis after 24 hours of PVAD support also identified patients less likely to survive.

Novel biomarkers in cardiovascular disease: research tools or ready for personalized medicine?

In recent years, a wide range of novel biomarkers have been evaluated for different cardiovascular disease states (eg, ischemia, congestion, and physiological stress), and many have shown promising results for the prediction of cardiovascular end points. However, to become useful for clinicians and to allow for personalized medicine, each novel biomarker must fulfill 3 fundamental criteria: (1) it must be easy to measure; (2) it must provide new information; and (3) it must help the clinician to manage patients. Although many biomarkers may be useful for prognostication, very few have been shown to improve the treatment of patients with cardiovascular disease when implemented in a clinical setting.

Outcomes in Stable Patients With Previous Atherothrombotic Events Receiving Vorapaxar Who Experience a New Acute Coronary Event (from TRA2°P-TIMI 50)

Vorapaxar is a first-in-class protease-activated receptor-1 antagonist indicated for secondary prevention in stable patients with previous myocardial infarction (MI) or peripheral artery disease and no cerebrovascular disease. Vorapaxar is not recommended for initiation in the acute phase of acute coronary syndromes (ACS) because of an unfavorable balance between bleeding and efficacy when started in that setting. The aim of this analysis was to investigate outcomes in patients who experienced a new ACS while receiving vorapaxar for long-term secondary prevention. Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic ischemic Events-Thrombolysis In Myocardial Infarction 50 was a randomized, double-blind, placebo-controlled trial of vorapaxar (n = 26,449). We evaluated bleeding and ischemic events during the acute care of patients with a new ACS during the trial. During a median follow-up of 30 months, 799 patients (8.9%) randomized to vorapaxar and 913 (10.0%) to placebo had a new ACS event (p = 0.003); 87% and 86%, respectively, were on study therapy at the time of the event. In a landmark analysis through 7 days after ACS, the rates of Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) severe bleeding were 0.8% versus 0.8% (hazard ratio [HR] 0.99, 95% CI 0.33 to 2.94) and GUSTO moderate/severe bleeding were 2.5% versus 1.6% (HR 1.59, 95% CI 0.78 to 3.24) with vorapaxar versus placebo. The effect of vorapaxar on cardiovascular death, MI, or stroke (2.4% vs 4.4%; HR 0.54, 95% CI 0.31 to 0.93; p = 0.027) was consistent with the overall trial result. In conclusion, in patients who experience a new ACS event while receiving vorapaxar for secondary prevention, continuing therapy was associated with favorable efficacy without excess severe bleeding during the period of acute ACS management.

Immune-related fulminant myocarditis in a patient receiving ipilimumab therapy for relapsed chronic myelomonocytic leukaemia

A 66-year-old man with chronic myelomonocytic leukaemia (CMML) presented with myalgias and acute-onset shortness of breath, profound orthopnoea, and bilateral pedal oedema of 1 day’s duration. He had been diagnosed with CMML a year and half before presentation, and after an inadequate response to four cycles of decitabine chemotherapy, he underwent a matched unrelated donor allogeneic haematopoietic stem cell transplant 7 months before presentation. Six months after his transplant, he developed recurrent anaemia and thrombocytopenia, and bone marrow biopsy confirmed relapsed CMML. He was enrolled in an experimental protocol of ipilimumab, a monoclonal antibody (IgG1) that blocks the checkpoint protein cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), to promote anti-tumour immunity. One week after receiving his first infusion, he was admitted to the hospital with abdominal pain and diarrhoea, and was found to have colitis involving the descending and sigmoid colon. He underwent flexible sigmoidoscopy and biopsy of the inflamed tissue showed focal active colitis and ulceration with no diagnostic features of cytomegalovirus infection or graft-vs.-host disease. A diagnosis of ipilimumab-related colitis was made, and he was treated with a 7-day taper of dexamethasone. His presenting cardiopulmonary symptoms began on the day after he completed corticosteroid treatment. At presentation, his temperature was 36.8 ∘C, pulse was 108 b.p.m., blood pressure was 116/59 mmHg, respiratory rate was 24/min, and oxygen saturation was 92% on room air. His breathing was laboured and he was unable to lie flat. His jugular venous pressure was elevated at 12 cmH2O. Auscultation of the heart and lungs revealed a . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . rapid and regular heart rate, an S4 gallop, and audible crackles at the bases of both lung fields. His extremities were warm and he had 2+ bilateral symmetric pitting pedal oedema. His complete blood count was near his recent baseline with a white blood cell count of 33×103 cells/mm3 (with 44% monocytes), haematocrit was 28.9%, and platelet count was 7000/μL. Other laboratories measurements of note included a serum sodium of 132 mmol/L, alanine aminotransferase 268 U/L, aspartate aminotransferase 189 U/L, lactate 2.9 mmol/L, troponin-T 1.99 ng/mL (reference range <0.01 ng/mL), creatine kinase 1172 U/L (reference range 39–308 U/L), creatine kinase MB isoenzyme 168.5 ng/ml (reference range 0.0–7.7 mg/ml), and N-terminal-pro-B-type natriuretic peptide 2155 pg/ml (reference range <900 pg/ml). His electrocardiogram showed low voltage, sinus rhythm, and a new right bundle branch block (Figure 1), and chest radiography revealed mild interstitial oedema and small bilateral pleural effusions. Computed tomography angiography of the chest showed no evidence of pulmonary embolism. Transthoracic echocardiography demonstrated preserved left ventricular systolic function (ejection fraction 70%) with evidence of diastolic dysfunction, normal right ventricular size and function, and no significant valvular lesions. He was given intravenous furosemide for decongestion and admitted to the cardiac intensive care unit for closer monitoring. It was recommended that a pulmonary artery catheter be placed for closer haemodynamic assessment; however, the patient declined invasive monitoring. Within hours of presentation, he developed progressive hypotension requiring the initiation of dopamine as well as progressive high-grade atrioventricular block and ultimately complete heart block with a wide ventricular escape (Figure 1). He was started on empirical high-dose methylprednisolone (1000 mg daily), and was offered temporary transvenous pacing and right heart catheterization with endomyocardial biopsy, but again declined all invasive measures. Following extensive discussion between the patient, the treating oncologist, and the intensive care unit team, the patient was transitioned to comfort measures only given . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . his poor oncological prognosis. He expired within 24 h. Post-mortem examination with microscopic evaluation of skeletal muscle biopsies demonstrated inflammatory myositis, characterized by a predominantly CD3+ T-cell inflammatory infiltrate with associated myocyte necrosis (Figure 2). Microscopic evaluation of cardiac muscle was not performed because of the family’s request for a limited post-mortem examination.

When Should Rescue Breathing Be Removed From the ABCs of CPR

Cardiac arrest is a major public health problem and a leading cause of death in the United States. Nearly 300,000 Americans sustain out-of-hospital cardiac arrests OHCAs) each year, and cardiopulmonary resuscitation (CPR) is provided by emerency medical professionals for approximately 175,000 of these OHCA victims each ear. Although prompt initiation of bystander CPR substantially improves the hances of survival from OHCA, most cardiac arrest victims do not receive bystander PR. In-hospital cardiac arrests (IHCAs) and CPR are also relatively common. A ecent study has established that CPR is provided for approximately 200,000 ospitalized patients each year. Fifty years ago, Kouwenhoven and colleagues demonstrated that “closed hest cardiac massage” resulted in successful return of spontaneous circulation or 20 consecutive patients with IHCAs. Their animal studies showed that closed hest cardiac massage (without rescue breathing) was an effective technique to aintain circulation of dogs in ventricular fibrillation (VF) for up to 30 minutes, hereby allowing successful defibrillation and return of spontaneous circulation. herefore, the initial patients in this clinical series received chest compressions ithout artificial respiration. Artificial respiration was soon added to closed chest ardiac massage because of the presumed need for adequate oxygenation and entilation. The new bundle was taught as the ABCs of CPR.

Cardiac Implantable Electronic Devices in Patients With Left Ventricular Assist Systems

Recent progress and evolution in device engineering, surgical implantation practices, and periprocedural management have advanced the promise of durable support with left ventricular assist systems (LVAS) in patients with stage D heart failure. With greater uptake of LVAS globally, a growing population of LVAS recipients have pre-existing cardiac implantable electronic devices (CIEDs). Strategies for optimal clinical management of CIEDs in patients with durable LVAS are evolving, and clinicians will increasingly face complex decisions regarding implantation, programming, deactivation, and removal of CIEDs. Traditional decision-making pathways for CIEDs may not apply to LVAS-supported patients, as few patients die of arrhythmic causes and many arrhythmias may be well tolerated. Given limited data, treatment decisions must be individualized and made collaboratively among electrophysiologists, advanced heart failure specialists, and patients and their caregivers. Large, prospective, well-conducted studies are needed to better understand the contemporary utility of CIEDs in patients with newer-generation LVAS.

Prospective registry of cardiac critical illness in a modern tertiary care Cardiac Intensive Care Unit

Background: The changing landscape of care in the Cardiac Intensive Care Unit (CICU) has prompted efforts to redesign the structure and organization of advanced CICUs. Few studies have quantitatively characterized current demographics, diagnoses, and outcomes in the contemporary CICU. Methods: We evaluated patients in a prospective observational database, created to support quality improvement and clinical care redesign in an AHA Level 1 (advanced) CICU at Brigham and Women’s Hospital, Boston, MA, USA. All consecutive patients (N=2193) admitted from 1 January 2015 to 31 December 2017 were included at the time of admission to the CICU. Results: The median age was 65 years (43% >70 years) and 44% of patients were women. Non-cardiovascular comorbidities were common, including chronic kidney disease (27%), pulmonary disease (22%), and active cancer (13%). Only 7% of CICU admissions were primarily for an acute coronary syndrome, which was the seventh most common individual diagnosis. The top three reasons for admission to the CICU were shock/hypotension (26%), cardiopulmonary arrest (11%), or primary arrhythmia without arrest (9%). Respiratory failure was a primary or major secondary reason for triage to the CICU in 17%. In-hospital mortality was 17.6%. Conclusions: In a tertiary, academic, advanced CICU, patients are elderly with a high burden of non-cardiovascular comorbid conditions. Care has shifted from ACS toward predominantly shock and cardiac arrest, as well as non-ischemic conditions, and the mortality of these conditions is high. These data may be useful to guide cardiac critical care redesign.