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Management of clinically significant rheumatic mitral stenosis (MVA ≤ 1.5 cm2)

Symptoms

NO

Yes

High risk of embolism or hemodynamic decompensation

Contraindication to PMC

Yes

NO

NO

Yes

PMC if favourable characteristics for PMC or contraindication for surgery Surgery if unfavourable charactristics for PMC

Exercise test

Contraindication or high risk for surgery

Surgery

Symptoms

Yes

NO

NO

Yes

PMC

Favourable anatomical characteristics

Follow-up

Contraindication to or unfavourable characteristics for PMC

NO

Yes

NO

Yes

Surgery

PMC

PMC

Surgery

The above algorithm adopted from 2021 ESC Guideline

Recommendations for percutaneous mitral commissurotomy and mitral valve surgery in moderate or severe mitral stenosis (valve area <1.5 cm2)
(Class I, Level of Evidence B):
❑ PMC is recommended in symptomatic patients with favourable characteristics for PMC
(Class I, Level of Evidence C):
❑PMC is recommended in any symptomatic patients who are high risk for surgery ❑Mitral valve surgery is recommended in symptomatic patients who are not appropriate for PMC in the absence of futility
(Class IIa, Level of Evidence C):
❑PMC should be considered as initial treatment in symptomatic patients with suboptimal anatomy and favourable clinical characteristics for PMC ❑PMC should be considered in asymptomatic patients with favourable clinical and anatomical characteristicsc for PMC and: High thromboembolic risk (history of systemic embolism, spontaneous contrast in the left artium, new-onset or paroxysmal AF), and/or High risk of hemodynamic decompensation (systolic pulmonary pressure >50 mmHg at rest, need for major non-cardiac surgery, desire for pregnancy)

The above table adopted from 2021 ESC Guideline

Abbreviations: PMC: Percutaneous mitral commissurotomy; AF: Atrial fibrillation; LA: Left atrium; MVA:Mitral valve area ;

• Contraindications for percutaneous mitral commissurotomy in rheumatic mitral stenosis
• MVA >1.5 cm²
• Left atrial thrombus
• More than mild mitral regurgitation
• Severe or bi-commissural calcification
• Absence of commissural fusion
• Severe concomitant aortic valve disease, or severe combined tricuspid stenosis and tricuspid regurgitation requiring surgery
• Concomitant coronary artery disease requiring bypass surgery

Management of patients with chronic severe secondary mitral regurgitation

Symptomatic despite medical therapy

*Optimazing medical therapy CRT implantation if indicated

Severe comorbidities or life expectancy < 1 year

Yes

NO

Palliative care

Presence of CAD or other cardiac disease

Yes

NO

Appropriate for surgery

Persisting severe symptomatic secondary MR

Valve surgery if fulfilling criteria

Yes

NO

CABG, MV surgery

PCI, TAVI

Persisting severe symptomatic secondary MR

Yes Appropriate for valve surgery

NO Close follow-up

Yes MV surgery

NO End-stage LV, RV failure

Yes Heart transplantation, left ventricular assist devices palliative care

NO Fulfilling criteria suggesting an increased chance of responding to TEER

Yes=TEER

NO Heart transplantation, left ventricular assist devices palliative care, TEER in selected cases or other transcatheter valve therapy if applicable for symptoms improvement

The above algorithm adopted from 2021 ESC Guideline

Abbreviations: CABG: Coronary artery bypass grafting; CRT: Cardiac resynchronization therapy; LV: Left ventricle; MV:Mitral valve ; PCI:Percutaneous coronary intervention; LVAD: Left ventricular assist devices; TEER: Transcatheter edge to edge repair; TAVI: Transcatheter aortic valve implantation; CAD: Coronary artery disease

Recommendations for intervention in chronic severe secondary mitral regurgitation
(Class I, Level of Evidence B):
❑ Valve surgery/intervention is recommended in symptomatic severe secondary MR despite GDMT or CRT ❑Valve surgery is recommended in patients undergoing CABG or other cardiac surgery
(Class IIa, Level of Evidence B):
❑TEER should be considered in selected symptomatic patients, not suitable for surgery and high likelihood of responding to TEER
(Class IIa, Level of Evidence C):
❑ In symptomatic inoperable patients, PCI (and/orTAVI) possibly followed by TEER (in case of persisting severe secondary MR) should be considered
(Class IIb, Level of Evidence C) :
❑ Valve surgery may be considered in symptomatic patients who are appropriate for surgery ❑In high-risk symptomatic patients not eligible for surgery and low likelihood of responding to TEER, making decision about TEER procedure or other transcatheter valve therapy and evaluation for ventricular assist device or heart transplant should be considered

The above table adopted from 2021 ESC Guideline

Abbreviations: CABG: Coronary artery bypass grafting; CRT: Cardiac resynchronization therapy; LV: Left ventricle; ERO:Effective regurgitation orifice area ; PCI:Percutaneous coronary intervention; LVEF: Left ventricular ejection fraction; TEER: Transcatheter edge to edge repair; TAVI: Transcatheter aortic valve implantation

Management of patients with severe chronic primary mitral regurgitation

Symptoms

Yes

NO

Determining the risk of surgery

LVEF ≤ 60% or LVESD ≥ 40 mm

High risk of futility Palliative therapy

High risk for surgery or inoperable

Yes

NO

Yes

NO

Surgery

New onset AF or SPAP>50 mmHg

TEER if anatomically suitable, optimal heart failure therapy

Surgery (repair whenever possible)

Yes, surgery

NO

High likelihood of durable repair, low surgical risk, and LA dilatation

NO

Yes

Follow-up

Surgical mitral valve repair

Abbreviations: AF: Atrial fibrillation; LA: Left atrial; LV: Left ventricle; LVESD:Left ventricular end systolic diameter ; SPAP:Systolic pulmonary arterial pressure; LVEF: Left ventricular ejection fraction; TEER: Transcatheter edge to edge repair;

The above algorithm adopted from 2021 ESC Guideline

Recommendations for intervention in primary mitral regurgitation
Symptomatic aortic stenosis:
(Class I, Level of Evidence B):
❑ Mitral valve repair is considered when the results of surgical technique are expected to be durable ❑ Surgery is recommended in low risk symptomatic patients ❑ Surgery is recommended in asymptomatic patients with LV dysfunction (LVESD ≥ 40 mm and/or LVEF ≤ 60%)
(Class IIa, Level of Evidence B):
❑ Surgery is recommended in asymptomatic patients with preserved LV function (LVESD <40 mm and LVEF >60%) and AF secondary to mitral regurgitation or pulmonary hypertension (SPAP at rest >50 mmHg ❑Surgical mitral valve repair is recommended in low-risk asymptomatic patients with LVEF > 60%, LVESD <40 mmd and significant LA dilatation (volume index ≥60 mL/m2 or diameter ≥55 mm)
(Class IIb, Level of Evidence B) :
❑TEER may be considered in symptomatic patients who are inoperable due to high surgical risk, with echocardiographic criteria of eligibility

Abbreviations: AF: Atrial fibrillation; LA: Left atrial; LV: Left ventricle; LVESD:Left ventricular end systolic diameter ; SPAP:Systolic pulmonary arterial pressure; LVEF: Left ventricular ejection fraction; TEER: Transcatheter edge to edge repair;

The above table adopted from 2021 ESC Guideline

Recommendations for intervention in aortic stenosis

Symptomatic aortic stenosis:

(Class I, Level of Evidence B):

❑ Intervention is considered in symptomatic patients with severe, high-gradient aortic stenosis mean gradient ≥ 40 mmHg, peak velocity ≥ 4.0 m/s, and valve area ≤ 1.0 cm2 (or ≤ 0.6 cm2/m2) ❑ntervention is considered in symptomatic patients with severe low-flow (SVi ≤35 mL/m2), low-gradient (<40 mmHg) aortic stenosis with reduced ejection fraction (<50%), and evidence of flow (contractile) reserve

(Class IIa, Level of Evidence C):

❑ Intervention is recommended in symptomatic severe AS with low-flow, low-gradient (<40 mmHg) aortic stenosis with normal ejection fraction ❑ Intervention is recommended in symptomatic patients with low-flow, low-gradient severe aortic stenosis and reduced ejection fraction without flow (contractile) reserve, severe aortic stenosis proven by CCT calcium score

(Class III, Level of Evidence C) :

❑ Intervention is not recommended in patients with severe comorbidities when the intervention is unlikely to improve quality of life or prolong survival >1 year

Asymptomatic severe aortic stenosis :

(Class I, Level of Evidence B):

❑ Intervention is recommended in asymptomatic patients with severe aortic stenosis and systolic LV dysfunction (LVEF < 50%) without another cause

(Class I, Level of Evidence C):

❑ Intervention is recommended in asymptomatic patients with severe aortic stenosis, symptomtomatic on exercise testing

(Class IIa, Level of Evidence B):

❑ Intervention should be considered in asymptomatic patients with severe aortic stenosis and systolic LV dysfunction (LVEF <55%) without another cause

(Class IIa, Level of Evidence C):

❑ Interventin is recommended in asymptomatic patients with severe aortic stenosis and a sustained fall inblood pressure (>20 mmHg) during exercise testing

(Class IIa, Level of Evidence B):

❑Intervention is considered in asymptomatic patients with LVEF >55% and a normal exercise test if the procedural risk is low and in the presence of one of the following: Very severe aortic stenosis (mean gradient ≥60 mmHg or Vmax > 5 m/s Severe valve calcification ( assessed by CCT) and Vmax progression ≥0.3 m/s/year Elevated BNP levels (>3× age- and sex-corrected normal range) confirmed by repeated measurements and without other causes

Type of intervention:

(Class I, Level of Evidence C):

❑Aortic valve interventions should be performed in an experienced center

(Class I, Level of Evidence B):

❑SAVR is recommended in younger patients who are low risk for surgery (<75 yearse and STS PROM/EuroSCORE II <4%), or in patients who are operable and unsuitable for transfemoral TAVI ❑SAVR or TAVI are recommended for patients based on clinical, anatomical, and procedural characteristics

(Class I, Level of Evidence A):

❑TAVI is recommended in older patients (≥75 years), or in those who are high risk (STS PROM/EuroSCORE IIf>8%) or unsuitable for surgery

(Class IIb, Level of Evidence C):

❑ Non-transfemoral TAVI may be considered in patients who are inoperable and unsuitable for transfemoral TAVI. ❑Balloon aortic valvotomy may be considered as a bridge to SAVR or TAVI in hemodynamically unstable patients and (if feasible) in those with severe aortic stenosis who require urgent high risk non-cardiac surgery

Abbreviations: BNP: B-type natriuretic peptide; CABG: Coronary artery bypass grafting; LV: Left ventricle; LVEF:Left ventricular ejection fraction ; CCT:Cardiac computed tomography; SAVR: Surgical aortic valve replacement; STS-PROM: Society of Thoracic Surgeons - predicted risk of mortality; SVi: Stroke volume index; TAVI:Transcatheter aortic valve implantation ; Vmax:Peak transvalvular velocity

The above table adopted from 2021 ESC Guideline

Clinical characteristics	Favours TAVI	Favours SAVR
Lower surgical risk	_	+
Higher surgical risk	+	_
Younger age	_	+
Older age	+	_
Previous cardiac surgery (CABG)	+	_
Severe frailty	+	_
Endocarditis	_	+
Anatomical and procedural factors
TAVI feasible via transfemoral approach	+	_
Inaccessable Transfemoral approach or SAVR feasible	_	+
Sequelae of chest radiation	+	_
Porcelain aorta	+	_
High likelihood of severe patient-prosthesis mismatch (AVA <0.65 cm2/m2 BSA)	+	_
Severe chest deformity or scoliosis	+	_
Unsuitable aortic annular dimensions for TAVI device	_	+
Bisuspid aortic valve	_	+
Unfavourable valve morphology for TAVI (high risk of coronary obstruction due to low coronary ostia or heavy leaflet/LVOT calcification	_	+
Thrombus in aorta or left ventricle	_	+
Concomitant cardiac conditions requiring interventio
Significant multi-vessel CAD requiring surgical revascularization	_	+
Severe primary mitral valve disease	_	+
Severe tricuspid valve disease	_	+
Significant dilatation/aneurysm of the aortic root and/or ascending aorta	_	+
Septal hypertrophy requiring myomectomy	_	+

Abbreviations: AV: Aortic valve; AVA: Aortic valve area; LVOT: Left ventricular outflow tract ; SAVR: Surgical aortic valve replacement; TAVI: Transcatheter aortic valve implantation; BSA: Body surface area; CAD: Coronary artery disease

The above table adopted from 2021 ESC Guideline

Valvular AS Assessment of velocity, gradient

Low-gradient AS Vmax < 4 m/s ΔPm < 40 mmHg

High-gradient AS Vmax ≥ 4 m/s, ΔPm ≥ 40 mmHg

AVA ≤ 1.0 cm2

High flow status

Yes Determination of flow status

NO Moderate AS

Yes Assessment of normal flow condition

NO Severe AS

Normal flow SVi > 35 mL/m2

Low flow SVi ≤ 35 mL/m2

Severe AS unlikely

LVEF ≥ 50%

NO DSE flow reservec

Yes CCT to assess AV calcification

NO, CCT to assess AV calcification

Yes, AVA ≤ 1.0 cm2

Yes Severe AS

NO Pseudo-severe AS

Abbreviations: AS: Aortic stenosis; AV: Aortic valve; AVA: Aortic valve area; LVEF: Left ventricular ejection fraction ; CT: Computed tomography; △Pm: Mean pressure gradient; DSE: Dobutamine stress echocardiography; LV: Left ventricular; SVi: Stroke volume index; Vmax: Peak transvalvular velocity

The above table adopted from 2021 ESC Guideline

• High flow is reversible in conditions such as anemia, hyperthyroidism orarterio-venous fistula and may also be present in patients with hypertrophic obstructive cardiomyopathy.
• The definition of Normal flow by pulsed Doppler echocardiography is  :

  Cardiac index 4.1 L/min/m2 in men and women

  SVi 54 mL/m2 in men, 51 mL/m2 in women

• DSE flow reserve is defined as > 20% increase in stroke volume in response to low-dose dobutamine.
• Pseudo-severe aortic stenosis is defined as AVA >1.0 cm2 with increased flow.
• CT measurement of aortic valve calcification (Agatston units) for definition of high likely severe AS:

  men >3000, women>1600

  Likely: men >2000, women >1200

  Unlikely: men <1600, women <800

Management of aortic regurgitation

Significant enlargement of ascending aorta

Severe aortic regurgitation

Surgery

Symptoms

Yes Surgery

NO LVEF≤ 50% or LVESD > 50 mm (or > 25 mm/m2 BSA)

Yes Surgery

The above algorithm adopted from 2021 ESC Guideline

Recommendations for surgery in severe aortic regurgitation and aortic root or tubular ascending aortic aneurysm

Severe aortic regurgitation (Class I, Level of Evidence B):

❑ Surgery is recommended in symptomatic patients regardless of LV function ❑ Surgery is recommended in asymptomatic patients with LVESD > 50 mm or LVESD > 25 mm/m2 BSA (in patients with small body size) or resting LVEF ≤ 50%

(Class IIb, Level of Evidence C):

❑ Surgery may be considered in asymptomatic patients with LVESD >20 mm/m2 BSA (especially in patients with small body size) or resting LVEF ≤ 55%, in low risk condition ❑Aortic valve repair may be considered in selected patients at experienced centres when durable results are expected

(Class I, Level of Evidence C) :

❑ Surgery is recommended in symptomatic and asymptomatic patients with severe aortic regurgitation undergoing CABG or surgery of the ascending aorta or of another valve

Aortic root or tubular ascending aortic aneurysmc (irrespective of the severity of aortic regurgitation (Class I, Level of Evidence B):

❑ Valve-sparing aortic root replacement is recommended in young patients with aortic root dilation

(Class I, Level of Evidence C):

❑ Ascending aortic surgery is recommended in patients with Marfan syndrome and ascending aortic diameter ≥ 50 mm

(Class IIa, Level of Evidence C):

❑ Ascending aortic surgery is recommended with ascending aorta size of: >_55 mm in all patients >_45 mm in Marfan syndrome and additional risk factors or in the presence of TGFBR1 or TGFBR2 mutation (including Loeys Dietz syndrome) Risk factors: family history of aortic dissection (or personal history of spontaneous vascular dissection), severe aortic or mitral regurgitation, desire for pregnancy, uncontrolled systemic arterial hypertension , aortic size increase >3 mm/year >_50 mm in the presence of a bicuspid valve with additional risk factorsd or coarctation ❑ In the presence of primarily indication for the surgery of aortic valve, replacement of the aortic root or tubular ascending aorta should be considered when ≥ 45 mm

Abbreviations: BSA: Body surface area; CABG: Coronary artery bypass grafting; LV: Left ventricle; LVEF:Left ventricular ejection fraction ; LVESV:Left ventricular end-systolic diamete

The above table adopted from 2021 ESC Guideline

Recommendations for management of atrial fibrillation in valvular heart disease

NOAC (Class I, Level of Evidence A):

❑ In AF patients and mitral regurgitation, aortic regurgitation, and aortic stenosis, NOACs are preferred to VKAs for prevention of stroke .

NOAC (Class III, Level of Evidence C):

❑ NOACs is not recommended in patients with AF and moderate to severe mitral stenosis

AF ablation:(Class IIa, Level of Evidence A) :

❑ Concomitant AF ablation should be considered in patients undergoing valve surgery with respect to risk factors of recurrence (LA dilatation, years in AF, age, renal dysfunction, and other cardiovascular risk factors

LAA occlusion : (Class IIa, Level of Evidence B)

❑ LAA occlusion should be considered to reduce the thromboembolic risk in patients with AF and a CHA2DS2VASc score ≥ 2 undergoing valve surgery

Abbreviations: AF: Atrial fibrillation; LA: Left atrium; LAA: Left atrial appendage; NOAC:Non vitamin-K antagonist oral anticoagulant ; OAC:Oral anticoagulation; VKA: Vitamin-K antagonist

The above table adopted from 2021 ESC Guideline

Recommendations for management of CAD in valvular heart disease

Coronary angiography (Class I, Level of Evidence C):

❑ Coronary angiography is recommended before valve surgery in patients with severe VHD and any of the following: History of cardiovascular disease Suspected myocardial ischemia Left ventricular systolic dysfunction In men >40 years of age and postmenopausal women One or more cardiovascular risk factors Evaluation of severe mitral regurgitation

Coronary CT angiography (Class I, Level of Evidence C):

❑ Coronary CT angiography is recommended as an alternative to coronary angiography before valve surgery in patients with severe VHD and low probability of CAD

CABG:(Class I, Level of Evidence C) :

❑ CABG is considered in patients undergone aortic/mitral/tricuspid valve surgery and coronary artery diameter stenosis ≥ 70%

CABG : (Class IIa, Level of Evidence C)

❑ CABG is recommended in patients undergone aortic/mitral/tricuspid valve surgery and coronary artery diameter stenosis ≥ 50-70%

PCI : (Class IIa, Level of Evidence C)

❑ PCI is recommended in patients undergoing TAVI and coronary artery diameter stenosis > 70% in proximal segments ❑ PCI is recommended in patients undergoing transcatheter mitral valve intervention and coronary artery diameter stenosis > 70% in proximal segments

Abbreviations: CAD: Coronary artery disease; CABG: Coronary artery bypass grafting; PCI: Percutaneous coronary intervention; TAVI:Transcatheter aortic valve implantation; VHD:Valvular heart disease

The above table adopted from 2021 ESC Guideline

Endocarditis prophylaxis

• Antibiotic prophylaxis should be considered for high-risk procedures in patients with prosthetic valves including:

  Transcatheter valves

  Valve repaired using prosthetic material

  History of previous episode(s) of infective endocarditis

• Specific attention to dental and cutaneous hygiene and strict aseptic measures during any invasive procedure are recommended.
• Antibiotic prophylaxis should be considered in dental procedures including the manipulation of the gingival or periapical region of the teeth or manipulation of the oral mucosa

Recommendations for anticoagulant therapy in valvular heart disease

NOAC (Class I, Level of Evidence A):

❑ Except those with rheumatic mitral stenosis, NOAC is recommended in patients with AF and VHD , or who received a bioprothesis valve > 3 months ago on the basis of CHA2DS2-VASc score

VKA (Class I, Level of Evidence C):

❑ Long term VKA oral anticoagulation is recommended in patients with AF and rheumatic MS

VKA:(Class IIa, Level of Evidence B) :

❑ Anticoagulation with VKA is reasonable in patients with new onset AF ≤ 3 months after surgical or transcatheter bioprothetic valve replacement

NOAC : (Class III: Harm, Level of Evidence B)

❑ NOAC is not recommended in patients with mechanical valve with or without AF, and VKA should be continued for prevention of valve thrombosis formation

Abbreviations: CAD: Coronary artery disease; VKA: Vitamin-K antagonist; AF: Artial fibrillation

The above table adopted from 2020 AHA Guideline

Prophylaxis for rheumatic fever

• Antibiotic therapy of group A Streptococcus infection throat is necessary in primary prevention of rheumatic fever.
• Screening with [[Echocardiographic] in combination with secondary prevention by antibiotic prophylaxis in children with evidence of latent rheumatic heart disease are considered to reduce the prevalence of disease in endemic regions.
• Recommendation for secondary long-term prophylaxis against rheumatic fever in patients with established rheumatic heart disease is benzathine benzyl penicillin 1.2 MUI every 3 to 4 weeks over 10 years.
• Lifelong prophylaxis is recommended in high-risk patients based upon the severity of VHD and exposure to group A Streptococcus.

Recommendations for anticoagulation for atrial fibrillation in valvular heart disease

NOAC (Class I, Level of Evidence A):

❑ Except those with rheumatic mitral stenosis, NOAC is recommended in patients with AF and VHD , or who received a bioprothesis valve > 3 months ago on the basis of CHA2DS2-VASc score

VKA (Class I, Level of Evidence C):

❑ Long term VKA oral anticoagulation is recommended in patients with AF and rheumatic MS

VKA:(Class IIa, Level of Evidence B) :

❑ Anticoagulation with VKA is reasonable in patients with new onset AF ≤ 3 months after surgical or transcatheter bioprothetic valve replacement

NOAC : (Class III: Harm, Level of Evidence B)

❑ NOAC is not recommended in patients with mechanical valve with or without AF, and VKA should be continued for prevention of valve thrombosis formation

Abbreviations: NOAC: Novel oral anticoagulant; VKA: Vitamin-K antagonist; AF: Artial fibrillation

The above table adopted from 2020 AHA Guideline

Median OperativeMortality Rates for Specific Surgical Procedures

Procedure	Mortality rate (%)
AVR	2.2
AVR + CABG	4
AVR + Mitral valve replacement	9
Mitral valve replacement	5
Mitral valve replacement + CABG	9
Mitral valve repair	1
Mitral valve repair +CABG	5

Management of HFrEF

(Class I) ACE-I/ARNI Beta-blocker Mineralocorticoid receptor antagonist Dapagliflozin/Empagliflozin Loop diuretic for fluid retention

LVEF ≤35% and QRS <130 ms

LVEF >35% or device therapy not indicated or inappropriate

Sinus rhythm and LVEF ≤35% and QRS ≥130 ms

ICD implantation Ischemic (class I) Non-ischemic (class IIa)

If symptoms persist, consider therapies (class II)

CRT-D/-P QRS ≥150 ms (Class I) QRS 130-149 ms (Class IIa)

Management of patients with pulmonary edema

Oxygen (Class I) or ventilatory support (Class IIa)

Systolic blood pressure ≥110 mmHg

Yes

NO

Loop diuretics (Class I) and/or vasodilators (Class IIb)

Signs of hypoperfusion

Yes

NO

Loop diuretics (Class I) and inotropes/vasopressors(Class IIb)

Loop diuretics (Class I)

Congestion relief

Yes

NO

Optimized medical therapy

Renal replacement therapy Mechanical circulatory support Palliative therapy

The above algorithm adopted from 2021 ESC Guideline

Recommendations for initial treatment of acute heart failure

Oxygen, ventilation support (Class I, Level of Evidence C):

❑ Oxygen is recommended in hypoxic patients with SpO2<90% or PaO2 <60 mmHg ❑ Intubation is recommended in the presence of progressive respiratory failure in spite of oxygen administration or non-invasive ventilation

Oxygen, ventilation support (Class IIa, Level of Evidence B):

❑ In patients with respiratory distress (respiratory rate >25 breaths/min, SpO2<90%), non-invasive positive pressure ventilation is recommended to decrease respiratory distress and reduce the rate of mechanical endotracheal intubation

Diuretics :(Class I, Level of Evidence C) :

❑ Intravenous loop diuretics are considered for all admitted patients with acute heart failure presented with signs, symptoms of fluid overload

Diuretics : (Class IIa, Level of Evidence B)

❑ In patients with resistant edema who do not respond to an increase in loop diuretic doses, combination of a loop diuretic with thiazide type diuretic should be considered

Vasodilators: (Class IIb, Level of Evidence B)

❑ In order to improve symptoms and reduce congestion in patients with AHF and SBP >110 mmHg, vasodilators may be considered as initial therapy

Inotropic agents : (Class 2b, Level of Evidence C)

❑ Inotropic agents may be considered in patients with SBP <90 mmHg and evidence of hypoperfusion without response to fluid challenge, to improve [[peripheral perfusion]] and maintain end-organ function

Inotropic agents]] (Class III, Level of Evidence C):

❑ Routinely administration of inotropic agents are not recommended , due to safety concerns, unless the patient has symptomatic hypotension and evidence of hypoperfusion

Vasopressors: (ClassIIb, Level of Evidence B)

❑ In patients with cardiogenic shock, a vasopressor, preferably norepinephrine, may be indicated to increase blood pressure and vital organ perfusion

Anticoagulant therapy: (ClassI, Level of Evidence A)

❑ Thromboembolism prophylaxis such as LMWH is recommended in patients not already anticoagulated and no contraindication to anticoagulation, to prevent the risk of deep venous thrombosis and pulmonary embolism

Opiates: (ClassIII, Level of Evidence C)

❑ Opiates is not routinely recommended, unless in selected patients with severe, intractable pain or anxiety

Abbreviations: AHF: Acute heart failure; LMWH: Low-molecular-weight heparin; PaO2: Partial pressure of oxygen  ; SpO2: Transcutaneous oxygen saturation;

The above table adopted from 2021 ESC Guideline

Approach to stable chest pain and ischemia and no obstructive CAD (INOCA)

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Stable chest pain suspected INOCA

Non-invasive test more prevalent Invasive test more comprehensive

Invasive coronary functional testing

Stress PET, Stress CMR, Stress echocardiography