Cardiac Physiology and Pathophysiology in Pregnancy.

Cardiovascular disease is the leading indirect cause of maternal morbidity and mortality, accounting for nearly one third of maternal deaths during pregnancy. The burden of cardiovascular disease in pregnancy is increasing, as are the incidence of maternal morbidity and mortality. Normal physiologic adaptations to pregnancy, including increased cardiac output and plasma volume, may unmask cardiac conditions, exacerbate previously existing conditions or create de novo complications. It is important for care providers to understand the normal physiologic changes of pregnancy and how they may impact the care of patients with cardiovascular disease. This review outlines the physiologic adaptions during pregnancy and their pathologic implications for some of the more common cardiovascular conditions in pregnancy.

Outcome disparities in acute coronary syndrome patients from rural versus urban settings: A narrative review of causes, and strategies to minimize them.

Acute coronary syndrome (ACS) remains an important cause of morbidity and mortality worldwide. Critical elements of improving outcomes in ACS patients include timely access to acute care including prompt revascularization if indicated, and subsequent ongoing secondary prevention and risk factor modification, ideally with cardiovascular specialists. It is being increasingly realized that ACS patients from rural settings suffer from inferior outcomes compared to their urban counterparts due to factors such as delayed diagnosis, delayed access to acute care, and less accessibility to specialized follow up. This narrative review will examine the importance of timely access to care in ACS patients, particularly in ST-elevation myocardial infarction; how barriers in access to care affects outcomes in various rural populations; and strategies that have been shown to improve such access, and therefore hopefully achieve more equitable health outcomes compared to patients who live in urban settings.

Impact of biological sex on valvular heart disease, interventions, and outcomes.

Valvular heart disease (VHD) is common, affecting >14% of individuals aged >75, and is associated with morbidity, including heart failure and arrhythmia, and risk of early mortality. Increasingly, important sex differences are being found between males and females with VHD. These sex differences can involve the epidemiology, pathophysiology, presentation, diagnosis, and outcomes of the disease. Females are often disadvantaged, and female sex has been shown to be associated with delayed diagnosis and inferior outcomes in various forms of VHD. In addition, the unique pathophysiologic state of pregnancy is associated with increased risk for maternal and fetal morbidity and mortality in many forms of VHD. Therefore, understanding and recognizing these sex differences, and familiarity with the attendant risks of pregnancy and management of pregnant females with VHD, is of great importance for any primary care or cardiovascular medicine practitioner caring for the female patient. This review will outline sex differences in aortic, mitral, pulmonic, and tricuspid VHD, with particular focus on differences in pathophysiology, clinical presentation, and outcomes. In addition, the pathophysiology and management implications of pregnancy will be discussed.

CT perfusion for Assessment of poor Neurological outcome in Comatose Cardiac Arrest Patients (CANCCAP): protocol for a prospective study.

INTRODUCTION: Cardiac arrest remains one of the most common causes of death with the majority occurring outside of hospitals (out of hospital cardiac arrest). Despite advancements in resuscitation management, approximately 50% of comatose cardiac arrest patients (CCAP) will suffer a severe unsurvivable brain injury. To assess brain injury, a neurological examination is conducted, however, its reliability in predicting outcomes in the first days following cardiac arrest is limited. Non-contrast CT is the most employed scan to assess hypoxic changes, even though it is not sensitive to early hypoxic-ischaemic changes in the brain. CT perfusion (CTP) has shown high sensitivity and specificity in brain death patients, although its use in predicting poor neurological outcome in CCAP has not yet been explored. The purpose of this study is to validate CTP for predicting poor neurological outcome (modified Rankin scale, mRS≥4) at hospital discharge in CCAP. METHODS AND ANALYSIS: The CT Perfusion for Assessment of poor Neurological outcome in Comatose Cardiac Arrest Patients study is a prospective cohort study funded by the Manitoba Medical Research Foundation. Newly admitted CCAP receiving standard Targeted Temperature Management are eligible. Patients undergo a CTP at the same time as the admission standard of care head CT. Admission CTP findings will be compared with the reference standard of an accepted bedside clinical assessment at the time of admission. Deferred consent will be used. The primary outcome is a binary outcome of good neurological status, defined as mRs<4 or poor neurological status (mRs≥4) at hospital discharge. A total of 90 patients will be enrolled. ETHICS AND DISSEMINATION: This study has been approved by the University of Manitoba Health Research Ethics Board. The findings from our study will be disseminated through peer-reviewed journals and presentations at local rounds, national and international conferences. The public will be informed at the end of the study. TRIAL REGISTRATION NUMBER: NCT04323020.

Ticagrelor as Compared to Clopidogrel Following Percutaneous Coronary Intervention for Acute Coronary Syndrome.

Dual antiplatelet therapy with acetylsalicylic acid and a P2Y12 inhibitor has become a mainstay of therapy after percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS). Although higher-potency P2Y12 inhibitors are preferred over clopidogrel in major society guidelines, recent evidence has questioned the extent of the benefit. It is important to evaluate the relative efficacy and safety of P2Y12 inhibitors in a real-world setting. This is a retrospective cohort study of all patients who underwent PCI for ACS in a Canadian province from January 1, 2015 to March 31, 2020. Baseline characteristics, including co-morbidities, medications, and bleeding risk, were obtained. Propensity matching was used to compare patients who received ticagrelor versus clopidogrel. The primary outcome was occurrence of major adverse cardiovascular events (MACEs) at 12 months, defined as death, nonfatal myocardial infarction, or unplanned revascularization. Secondary outcomes included all-cause mortality, major bleeding, stroke, and all-cause hospitalization. A total of 6,665 patients were included; 2,108 received clopidogrel and 4,214 received ticagrelor. Patients who received clopidogrel were older, had more co-morbidities, including cardiovascular risk factors, and had a higher bleeding risk. In 1.925 propensity score-matched pairs, ticagrelor was associated with a significantly lower risk of MACE (hazard ratio 0.79, 0.67 to 0.93, p <0.01) and hospitalization (hazard ratio 0.85, 0.77 to 0.95, p <0.01). No difference was observed in the risk of major bleeding. A statistically nonsignificant trend toward reduced risk of all-cause mortality was noted. In conclusion, in a real-world high-risk cohort, ticagrelor was associated with decreased risk of MACE and all-cause hospitalization compared with clopidogrel after PCI for ACS.

One-year outcomes in patients who underwent coronary intravascular shockwave lithotripsy for highly-calcified coronary lesions.

Intravascular lithotripsy (IVL) is associated with excellent angiographic and short-term results in patients with calcified lesions requiring percutaneous coronary intervention. We conducted a 1-year follow up of a retrospective cohort of 47 patients (61 lesions) who underwent IVL. The primary outcome was target vessel revascularization (TVR) at 1-year from index procedure. Four percent of patients required TVR within 1 year; 96% who underwent IVL remained free from repeat intervention on the same vessel. One patient suffered a myocardial infarction; the culprit vessel had not been previously treated with IVL. IVL is an effective and durable modality for treatment of highly calcified coronary lesions in high-risk patients.

Real-world outcomes in treatment of highly calcified coronary lesions with intravascular shockwave lithotripsy.

Real-world data regarding the efficacy and safety of coronary intravascular lithotripsy (IVL) are lacking. We conducted a study of 50 consecutive patients (64 lesions) who underwent IVL. 3 patients suffered in-hospital mortality unrelated to the IVL; there was no other occurrence of MACE up to 30 days. Angiographic success was nearly universal (98% of patients with residual stenosis <50%, 96% of patients with TIMI 3 flow) and complication was rare, including among patients undergoing IVL for in-stent restenosis or left main coronary artery lesions. In a high-risk real-world cohort, IVL was a safe and effective treatment for highly-calcified coronary lesions.

Signage as an intervention on a general medicine ward to reduce unnecessary testing.

BACKGROUND: Up to 30% of medical spending in developed countries is unnecessary. Unnecessary testing is not only wasteful economically, but can be injurious to patients. Studies have shown that interventions such as education, auditing, and restrictive ordering can reduce unnecessary testing. However, these interventions are time- and resource-intensive. We conducted a study to determine if the passive intervention of placing signs on clinicians' computers was effective in reducing unnecessary testing. AIMS: To determine the effectiveness of signage on physicians' computers to limit unnecessary testing. METHODS: We identified two acute medicine wards on which all orders are placed via computer. On one ward (Ward A), we placed signs outlining recommendations regarding responsible test-ordering. Ward B acted as a control. Data was collected during a 6-month study period to determine whether test-ordering practices differed. RESULTS: A total of 1645 patients accounting for 17 786 patient-days were included in the study. Fewer tests were ordered on Ward A than Ward B (7.38 vs 8.20 tests/patient-day; P < 0.01). Additionally, significantly fewer patients on Ward B received ≥1 complete blood count/day (36.1% vs 42.5%, P = 0.04). This effect was most pronounced among patients admitted for 7-30 days. CONCLUSION: The passive intervention of placing signs on clinicians' computers significantly reduced unnecessary testing.

External validation demonstrated the Ottawa SAH prediction models can identify pSAH using health administrative data.

OBJECTIVES: The objective of the study is to externally validate three primary subarachnoid hemorrhage (pSAH) identification models. STUDY DESIGN AND SETTING: We evaluated three models that identify pSAH using recursive partitioning (A), logistic regression (B), and a prevalence-adjusted logistic regression(C), respectively. Blinded chart review and/or linkage to existing registries determined pSAH status. We included all patients aged ≥18 in four participating center registries or whose discharge abstracts contained ≥1 administrative codes of interest between January 1, 2012 and December 31, 2013. RESULTS: A total of 3,262 of 193,190 admissions underwent chart review (n = 2,493) or registry linkage (n = 769). A total of 657 had pSAH confirmed (20·1% sample, 0·34% admissions). The sensitivity, specificity, and positive predictive value (PPV) were as follows: i) model A: 98·3% (97·0-99·2), 53·5% (51·5-55·4), and 34·8% (32·6-37·0); ii) model B (score ≥6): 98·0% (96·6-98·9), 47·4% (45·5-49·4), and 32·0% (30·0-34·1); and iii) model C (score ≥2): 95·7% (93·9-97·2), 85·5% (84·0-86·8), and 62·3 (59·3-65·3), respectively. Model C scores of 0, 1, 2, 3, or 4 had probabilities of 0·5% (0·2-1·5), 1·5% (1·0-2·2), 24·8% (21·0-29·0), 90·0% (86·8-92·0), and 97·8% (88·7-99·6), without significant difference between centers (P = 0·86). The PPV of the International Classification of Diseases code (I60) was 63·0% (95% confidence interval: 60·0-66·0). CONCLUSIONS: All three models were highly sensitive for pSAH. Model C could be used to adjust for misclassification bias.

Clinical utility of echocardiography for the diagnosis of native valve infective endocarditis in Staphylococcus aureus bacteremia.

BACKGROUND: The incidence of Staphylococcus aureus infective endocarditis (IE) is steadily rising due to advances in health care delivery. Routine echocardiography is essential in the management of Staphylococcus aureus bacteremia (SAB). The aim of this retrospective cohort study was to characterize the real-world use of echocardiography in adult patients with SAB and native valve S aureus IE. METHODS: Using an academic hospital microbiological database, all cases of SAB in adults between 2010 and 2016 were identified. Demographic, echocardiographic, and clinical features were recorded. RESULTS: A total of 738 episodes of SAB were identified, of which 504 (68%) patients underwent transthoracic echocardiography (TTE) within 30 days. Of 73 patients with definite IE, 46 (63%) patients had definite IE diagnosed on the initial TTE. An additional 14 (19%) patients had definite IE diagnosed on repeat TTE, 6 (8%) on transesophageal echocardiography (TEE), and 7 (10%) were diagnosed without fulfilling Duke echocardiographic criteria. The yield of repeat TTE was comparable to that of TEE for identifying new vegetations not identified on the initial TTE (17% vs 21%, P = .78). CONCLUSIONS: Most cases of IE in SAB were identified using TTE alone, with repeat TTE improving the diagnostic yield in the setting of clinical decompensation.

Routine creatine kinase testing does not provide clinical utility in the emergency department for diagnosis of acute coronary syndromes.

BACKGROUND: Despite the high sensitivity and negative predictive value of contemporary high-sensitivity troponin T assays (hsTnT), creatine kinase (CK) continues to be routinely tested for the diagnosis of acute coronary syndrome (ACS). We conducted a study to identify the clinical utility of routine CK measurement, its relevance in clinical decision making in the era of hsTnT, and the potential cost-savings achievable by limiting its use. METHODS: We conducted a retrospective review of all adult patients presenting to a tertiary care center in the year 2017. We identified patients presenting with cardiac complaints who had non-diagnostic hsTnT and positive CK. These patients underwent chart review to determine whether a diagnosis of AMI was made. RESULTS: A total of 36,251 presentations were reviewed. 9951 had cardiac complaints and 8150 had CK measured. 82% of these patients had hsTnT and CK measured; 2012 of these patients had non-diagnostic hsTnT with positive CK. Of these 2012 patients, only 1 was subsequently diagnosed with AMI (0.012%). CK provided no diagnostic benefit over hsTnT alone in > 99.9% of cases. With a cost for CK of $4/test, we estimated that routine CK testing costs at least $32,000 per year in our center, and over $100,000 per year across the region. CONCLUSION: Routine CK testing does not provide a significant benefit to patient care and therefore represents an unnecessary system cost. Routine CK testing for the diagnosis of AMI should be eliminated from emergency departments in the era of hsTnT assays.

Inadvertent Removal of a Right Ventricular Pacemaker Lead by a Knotted Transvenous Pacing Wire.

We report an unusual complication of permanent pacemaker (PPM) implantation in a patient with a temporary transvenous pacemaker (TVP) in situ, in which the TVP lead formed a knot around the newly-placed right ventricular (RV) lead, complicating TVP removal. The case underscores the fact that suboptimal TVP lead placement, such as looping in the RV, can result in complications during implantation of a permanent pacemaker. HOW TO CITE THIS ARTICLE: Wiens EJ, Seifer CM et al. Inadvertent Removal of a Right Ventricular Pacemaker Lead by a Knotted Transvenous Pacing Wire. Indian J of Crit Care Med 2019;23(2):102-103.

Delivery of End-of-Life Care in Patients Requesting Withdrawal of a Left Ventricular Assist Device Using Intranasal Opioids and Benzodiazepines.

With the increasing prevalence of the left ventricular assist device (LVAD) in patients with end-stage cardiomyopathies, an increasing number of these patients are dying of noncardiac conditions. It is likely that the palliative care clinician will have an ever-increasing role in managing end of life for patients with LVADs, including discontinuation of LVAD support. There exists a paucity of literature describing strategies for effective delivery of palliative care in patients requesting discontinuation of LVAD therapy. Here, we present a case of a patient with metastatic cancer who requested LVAD discontinuation. Because of practical concerns and patient preference, the patient did not have intravenous (IV) access and medications requiring IV administration could not be used. Therefore, a strategy using intranasal midazolam and sufentanil was applied, the LVAD was deactivated, and the patient died comfortably. This case is, to our knowledge, the first to describe a strategy for delivery of palliative care in patients requesting discontinuation of LVAD support, particularly in the absence of IV access. Such a strategy may be applicable to patients wishing to die at home, and therefore allow greater latitude for patients and clinicians in their approach to the end of life.

The C-terminal cytoplasmic portion of the NhaP2 cation-proton antiporter from Vibrio cholerae affects its activity and substrate affinity.

In this work, we report the phenotypic and biochemical effects of deleting the C-terminal cytoplasmic portion of the NhaP2 cation/proton antiporter from Vibrio cholerae. While the deletion changed neither the expression nor targeting of the Vc-NhaP2 in an antiporter-less Escherichia coli strain, it resulted in a changed sensitivity of the host to sodium ions at neutral pH, indicating an altered Na(+) transport through the truncated variant. When assayed in inside-out sub-bacterial vesicles, the truncation was found to result in greatly reduced K(+)/H(+) and Na(+)/H(+) antiport activity at all pH values tested and a greater than fivefold decrease in the affinity for K(+) (measured as the apparent K m) at pH 7.5. Being expressed in trans in a strain of V. cholerae bearing a chromosomal nhaP2 deletion, the truncated nhaP2 gene was able to complement its inability to grow in potassium-rich medium at pH 6.0. Thus the residual K(+)/H(+) antiport activity associated with the truncated Vc-NhaP2 was still sufficient to protect cells from an over-accumulation of K(+) ions in the cytoplasm. The presented data suggest that while the cytoplasmic portion of Vc-NhaP2 is not involved in ion translocation directly, it is necessary for optimal activity and substrate binding of the Vc-NhaP2 antiporter.