There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality.

Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …

I and i

Importance Definitions of sepsis and septic shock were last revised in 2001. Considerable advances have since been made into the pathobiology (changes in organ function, morphology, cell biology, biochemistry, immunology, and circulation), management, and epidemiology of sepsis, suggesting the need for reexamination. Objective To evaluate and, as needed, update definitions for sepsis and septic shock. Process A task force (n = 19) with expertise in sepsis pathobiology, clinical trials, and epidemiology was convened by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine. Definitions and clinical criteria were generated through meetings, Delphi processes, analysis of electronic health record databases, and voting, followed by circulation to international professional societies, requesting peer review and endorsement (by 31 societies listed in the Acknowledgment). Key Findings From Evidence Synthesis Limitations of previous definitions included an excessive focus on inflammation, the misleading model that sepsis follows a continuum through severe sepsis to shock, and inadequate specificity and sensitivity of the systemic inflammatory response syndrome (SIRS) criteria. Multiple definitions and terminologies are currently in use for sepsis, septic shock, and organ dysfunction, leading to discrepancies in reported incidence and observed mortality. The task force concluded the term severe sepsis was redundant. Recommendations Sepsis should be defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. For clinical operationalization, organ dysfunction can be represented by an increase in the Sequential [Sepsis-related] Organ Failure Assessment (SOFA) score of 2 points or more, which is associated with an in-hospital mortality greater than 10%. Septic shock should be defined as a subset of sepsis in which particularly profound circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than with sepsis alone. Patients with septic shock can be clinically identified by a vasopressor requirement to maintain a mean arterial pressure of 65 mm Hg or greater and serum lactate level greater than 2 mmol/L (>18 mg/dL) in the absence of hypovolemia. This combination is associated with hospital mortality rates greater than 40%. In out-of-hospital, emergency department, or general hospital ward settings, adult patients with suspected infection can be rapidly identified as being more likely to have poor outcomes typical of sepsis if they have at least 2 of the following clinical criteria that together constitute a new bedside clinical score termed quickSOFA (qSOFA): respiratory rate of 22/min or greater, altered mentation, or systolic blood pressure of 100 mm Hg or less. Conclusions and Relevance These updated definitions and clinical criteria should replace previous definitions, offer greater consistency for epidemiologic studies and clinical trials, and facilitate earlier recognition and more timely management of patients with sepsis or at risk of developing sepsis.

https://jamanetwork.com/journals/jama/articlepdf/2492881/jsc160002.pdf

The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)

ABCD
: Appropriate Blood pressure Control in Diabetes
ABI
: ankle–brachial index
ABPM
: ambulatory blood pressure monitoring
ACCESS
: Acute Candesartan Cilexetil Therapy in Stroke Survival
ACCOMPLISH
: Avoiding Cardiovascular Events in Combination Therapy in Patients Living with Systolic Hypertension
ACCORD
: Action to Control Cardiovascular Risk in Diabetes
ACE
: angiotensin-converting enzyme
ACTIVE I
: Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events
ADVANCE
: Action in Diabetes and Vascular Disease: Preterax and Diamicron-MR Controlled Evaluation
AHEAD
: Action for HEAlth in Diabetes
ALLHAT
: Antihypertensive and Lipid-Lowering Treatment to Prevent Heart ATtack
ALTITUDE
: ALiskiren Trial In Type 2 Diabetes Using Cardio-renal Endpoints
ANTIPAF
: ANgioTensin II Antagonist In Paroxysmal Atrial Fibrillation
APOLLO
: A Randomized Controlled Trial of Aliskiren in the Prevention of Major Cardiovascular Events in Elderly People
ARB
: angiotensin receptor blocker
ARIC
: Atherosclerosis Risk In Communities
ARR
: aldosterone renin ratio
ASCOT
: Anglo-Scandinavian Cardiac Outcomes Trial
ASCOT-LLA
: Anglo-Scandinavian Cardiac Outcomes Trial—Lipid Lowering Arm
ASTRAL
: Angioplasty and STenting for Renal Artery Lesions
A-V
: atrioventricular
BB
: beta-blocker
BMI
: body mass index
BP
: blood pressure
BSA
: body surface area
CA
: calcium antagonist
CABG
: coronary artery bypass graft
CAPPP
: CAPtopril Prevention Project
CAPRAF
: CAndesartan in the Prevention of Relapsing Atrial Fibrillation
CHD
: coronary heart disease
CHHIPS
: Controlling Hypertension and Hypertension Immediately Post-Stroke
CKD
: chronic kidney disease
CKD-EPI
: Chronic Kidney Disease—EPIdemiology collaboration
CONVINCE
: Controlled ONset Verapamil INvestigation of CV Endpoints
CT
: computed tomography
CV
: cardiovascular
CVD
: cardiovascular disease
D
: diuretic
DASH
: Dietary Approaches to Stop Hypertension
DBP
: diastolic blood pressure
DCCT
: Diabetes Control and Complications Study
DIRECT
: DIabetic REtinopathy Candesartan Trials
DM
: diabetes mellitus
DPP-4
: dipeptidyl peptidase 4
EAS
: European Atherosclerosis Society
EASD
: European Association for the Study of Diabetes
ECG
: electrocardiogram
EF
: ejection fraction
eGFR
: estimated glomerular filtration rate
ELSA
: European Lacidipine Study on Atherosclerosis
ESC
: European Society of Cardiology
ESH
: European Society of Hypertension
ESRD
: end-stage renal disease
EXPLOR
: Amlodipine–Valsartan Combination Decreases Central Systolic Blood Pressure more Effectively than the Amlodipine–Atenolol Combination
FDA
: U.S. Food and Drug Administration
FEVER
: Felodipine EVent Reduction study
GISSI-AF
: Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico-Atrial Fibrillation
HbA1c
: glycated haemoglobin
HBPM
: home blood pressure monitoring
HOPE
: Heart Outcomes Prevention Evaluation
HOT
: Hypertension Optimal Treatment
HRT
: hormone replacement therapy
HT
: hypertension
HYVET
: HYpertension in the Very Elderly Trial
IMT
: intima-media thickness
I-PRESERVE
: Irbesartan in Heart Failure with Preserved Systolic Function
INTERHEART
: Effect of Potentially Modifiable Risk Factors associated with Myocardial Infarction in 52 Countries
INVEST
: INternational VErapamil SR/T Trandolapril
ISH
: Isolated systolic hypertension
JNC
: Joint National Committee
JUPITER
: Justification for the Use of Statins in Primary Prevention: an Intervention Trial Evaluating Rosuvastatin
LAVi
: left atrial volume index
LIFE
: Losartan Intervention For Endpoint Reduction in Hypertensives
LV
: left ventricle/left ventricular
LVH
: left ventricular hypertrophy
LVM
: left ventricular mass
MDRD
: Modification of Diet in Renal Disease
MRFIT
: Multiple Risk Factor Intervention Trial
MRI
: magnetic resonance imaging
NORDIL
: The Nordic Diltiazem Intervention study
OC
: oral contraceptive
OD
: organ damage
ONTARGET
: ONgoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial
PAD
: peripheral artery disease
PATHS
: Prevention And Treatment of Hypertension Study
PCI
: percutaneous coronary intervention
PPAR
: peroxisome proliferator-activated receptor
PREVEND
: Prevention of REnal and Vascular ENdstage Disease
PROFESS
: Prevention Regimen for Effectively Avoiding Secondary Strokes
PROGRESS
: Perindopril Protection Against Recurrent Stroke Study
PWV
: pulse wave velocity
QALY
: Quality adjusted life years
RAA
: renin-angiotensin-aldosterone
RAS
: renin-angiotensin system
RCT
: randomized controlled trials
RF
: risk factor
ROADMAP
: Randomized Olmesartan And Diabetes MicroAlbuminuria Prevention
SBP
: systolic blood pressure
SCAST
: Angiotensin-Receptor Blocker Candesartan for Treatment of Acute STroke
SCOPE
: Study on COgnition and Prognosis in the Elderly
SCORE
: Systematic COronary Risk Evaluation
SHEP
: Systolic Hypertension in the Elderly Program
STOP
: Swedish Trials in Old Patients with Hypertension
STOP-2
: The second Swedish Trial in Old Patients with Hypertension
SYSTCHINA
: SYSTolic Hypertension in the Elderly: Chinese trial
SYSTEUR
: SYSTolic Hypertension in Europe
TIA
: transient ischaemic attack
TOHP
: Trials Of Hypertension Prevention
TRANSCEND
: Telmisartan Randomised AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease
UKPDS
: United Kingdom Prospective Diabetes Study
VADT
: Veterans' Affairs Diabetes Trial
VALUE
: Valsartan Antihypertensive Long-term Use Evaluation
WHO
: World Health Organization

### 1.1 Principles

The 2013 guidelines on hypertension of the European Society of Hypertension (ESH) and the European Society of Cardiology …

/pdf/2013-esh-esc-guidelines-for-the-management-of-arterial-4ydvs5ifsx.pdf

2013 ESH/ESC Guidelines for the management of arterial hypertension: The Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC).

https://caltcm.memberclicks.net/assets/documents/acc_aha_chf_2013_guidelines.pdf

2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines

https://hull-repository.worktribe.com/preview/1797952/1-s2.0-S0140673618322797-main.pdf

Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016

Women with signs and symptoms of myocardial ischemia often have no obstructive coronary artery disease by invasive coronary angiography when compared to men. Microvascular coronary dysfunction (MCD) is thought to be a key contributory mechanism for myocardial ischemia in women with chest pain and no obstructive CAD. We report a case of a 53-year-old post-menopausal female with hyperlipidemia evaluated for persistent chest pain following a non-ST elevation myocardial infarction (NSTEMI) and no obstructive CAD by coronary angiography. Vital signs and physical examination were within normal limits. Prior EKG showed diffuse abnormal T wave inversion and flattening in anterior and inferior leads. Echocardiography demonstrated an ejection fraction of 72% with no regional wall motion abnormalities. Laboratory values revealed a positive heterozygote factor V Leiden mutation. Given the constellation of persistent chest pain, no obstructive CAD, and prior NSTEMI, a diagnosis of MCD was suspected and she underwent coronary reactivity testing (CRT) with intracoronary infusions of adenosine, acetylcholine, and nitroglycerin to test non-endothelial and endothelial dependent, micro- and macrovascular coronary function. CRT results were consistent with a diagnosis of MCD. A statin and angiotensin converting enzyme inhibitor was added to her existing treatment of beta-blocker and nitrates. Additionally, she was started on warfarin therapy due to a positive factor V Leiden in the setting of prior NSTEMI. Her symptoms improved at one-month follow-up and she is currently asymptomatic by self- report. In women with signs and symptoms of myocardial ischemia and no obstructive CAD, it is important to identify and diagnose MCD, as inadequate diagnosis is associated with an increased risk of adverse cardiovascular events including myocardial infarction, congestive heart failure, and sudden cardiac death. Identification of MCD and clinical awareness are vital for optimal medical therapy and reduced CVD risk. Clinical trials testing efficacy of traditional and novel interventions are needed in MCD populations. doi: http://dx.doi.org/10.4021/jmc1048w

https://www.journalmc.org/index.php/JMC/article/viewFile/1048/625

Microvascular Coronary Dysfunction in a Woman With Signs and Symptoms of Myocardial Ischemia but No Obstructive Coronary Artery Disease


 
 
 Excess fat accumulation around the heart (i.e., pericardial fat) is positively associated with cardiovascular disease. Pericardial fat is composed of two distinct depots: (1) epicardial fat, which is a metabolically active adipose tissue located between the heart and the pericardium, and (2) paracardial fat, which is the fat deposit in the mediastinum outside of the parietal pericardium. Both depots are visible on the horizontal long axis cardiac magnetic resonance (CMR) cine (i.e., four chamber view), offering an attractive opportunity to quantify pericardial fat from standard CMR cine images.
 
 
 
 To validate pericardial fat area measured from a single horizontal long axis CMR cine against whole-heart volumetric non-contrast cardiac computed tomography (CT) measurements.
 
 
 
 To accomplish our goal, we leveraged 25 cases from the Women's Ischemia Syndrome Evaluation – Coronary Vascular Dysfunction Continuation cohort who underwent both cardiac MRI and cardiac CT within a median of 35 days apart. For MRI, pericardial fat area was measured from a single high resolution steady state free precession cine image in the horizontal long axis imaging plane using commercially available software (CVI42 V5.13.5, Circle Cardiovascular Imaging, Figure 1A). For CT, pericardial fat volume was measured using a fully automated deep learning algorithm (QFAT 2.0, Figure 1A).
 
 
 
 Fat area measured from a single horizontal long axis cine image was closely related to fat volume measured by three-dimensional cardiac CT, with strong correlations for epicardial fat (R2=0.72, p<0.01, Figure 1B), paracardial fat (R2=0.80, p<0.01, Figure 1C), and pericardial fat (R2=0.91, p<0.01, Figure 1D).
 
 
 
 Measuring pericardial fat area, and its constituent parts, from a single horizontal long axis cine image is both feasible and strongly related to reference standard pericardial fat volume by cardiac CT.
 
 
 
 Type of funding sources: Public Institution(s). Main funding source(s): National Institutes of Health


/pdf/pericardial-fat-from-a-single-horizontal-long-axis-cardiac-2s43ktzp.pdf

Pericardial fat from a single horizontal long axis cardiac magnetic resonance cine image: a validation study against three-dimensional cardiac computed tomography

Baseline characteristics of smidt heart institute takotsubo registry participants

Since 1996, the National Heart, Lung, and Blood Institute-sponsored Women’s Ischemia Syndrome Evaluation (WISE) has been investigating pathophysiological processes underlying ischemic heart disease in women and related outcomes. Recent findings have focused on women with signs and symptoms of ischemia and no obstructive coronary arteries (INOCA) and their elevated risk for heart failure with preserved ejection fraction (HFpEF). This review summarizes the latest WISE findings related to INOCA and pre-HFpEF characteristics, addressing our understanding of contributions from traditional vs nontraditional risk factors in women. 

C. Noel Bairey Merz

Papers

Microvascular Coronary Dysfunction in a Woman With Signs and Symptoms of Myocardial Ischemia but No Obstructive Coronary Artery Disease

Pericardial fat from a single horizontal long axis cardiac magnetic resonance cine image: a validation study against three-dimensional cardiac computed tomography

Baseline characteristics of smidt heart institute takotsubo registry participants

Latest from the WISE: Contributions to the Understanding of Ischemia and Heart Failure among Women with No Obstructive Coronary Arteries

Regional variation in takotsubo syndrome diagnoses across the united states