Dilated Cardiomyopathy: �A Comprehensive Approach to Diagnosis and Treatment
PGS. TS. Phạm Nguyễn Vinh
Trung tâm Tim mạch BVĐK Tâm Anh TPHCM
Khoa Y Đại học Tân Tạo
Đại học Y khoa Phạm Ngọc Thạch
Viện Tim TPHCM
Clinical Case
2
XQ+ ECG
3
XQ:
ECG:
- Sinus rhythm
- Left ventricular hypertrophy
ECHOCARDIOGRAPHY
4
CMR
5
LGE: mid-wall at the basal and mid of ventricular septum, anterior wall and inferior wall
6
Pericardial effusion : blue arrow
LGE: mid-wall at the basal and mid of ventricular septum, anterior wall and inferior wall
7
Pericardial effusion : blue arrow
8
24-hour HOLTER ECG monitoring
RBM20- CARDIOMYOPATHY
Genetic testing
Definitions
A cardiomyopathy is defined as ‘a myocardial disorder in which the heart muscle is structurally and functionally abnormal, in the absence of coronary artery disease (CAD), hypertension, valvular disease, and congenital heart disease (CHD) sufficient to cause the observed myocardial abnormality’
9
Classification of cardiomyopathy/ESC 2008 and AHA 2006 guideline
10
TL: - Circulation 2006 Apr 11; 113 : 1807-1816. Eur Heart J 2008 Jan 29 (2): 270-276
Clinical diagnostic workflow of cardiomyopathy
ARVC, arrhythmogenic right ventricular cardiomyopathy; CMP, cardiomyopathy; CMR, cardiac magnetic resonance; DCM, dilated cardiomyopathy; ECG, electrocardiogram; HCM, hypertrophic cardiomyopathy; NDLVC, non-dilated left ventricular cardiomyopathy; RCM, restrictive cardiomyopathy.
11
Source: Arbelo E. et al. 2023 ESC guidelines for the management of cardiomyopathies, Eur HJ (2023) 44, 3503-3626. doi:10.1093
Dilated cardiomyopathy
Dilated cardiomyopathy (DCM) is defined as the presence of LV dilatation and global or regional systolic dysfunction unexplained solely by abnormal loading conditions (e.g. hypertension, valve disease, CHD or CAD).
12
Source: Arbelo E. et al. 2023 ESC guidelines for the management of cardiomyopathies, Eur HJ (2023) 44, 3503-3626. doi:10.1093
Worked example of the non-dilated left ventricular cardiomyopathy phenotype
ACM, arrhythmogenic cardiomyopathy; ALVC, arrhythmogenic left ventricular cardiomyopathy; DCM, dilated cardiomyopathy; DSP, desmoplakin; ECG, electrocardiogram; EF, ejection fraction; LV, left ventricular; NDLVC, non-dilated left ventricular cardiomyopathy; SCD, sudden cardiac death; VE, ventricular extrasystole. Worked example of the NDLVC phenotype showing how a systematic multiparametric approach to clinical phenotyping, starting from the recognition of a clinical phenotype and integrating extended phenotypic information and targeted diagnostics, including genetic testing, can be used to arrive at highly specific phenotypic descriptions that can result in personalized treatment plans. In this worked example, the diagnosis transforms from a simplistic categorization to a complex genetic disorder characterized by myocardial scar and a propensity to ventricular arrhythmia.
13
DSP Trp I 80*
DSP-related non-dilated LV cardiomyopathy phenotype
DSP Trp 180*
Source: Arbelo E. et al. 2023 ESC guidelines for the management of cardiomyopathies, Eur HJ (2023) 44, 3503-3626. doi:10.1093
Aetiologies of dilated cardiomyopathy (1)
14
Source: Pinto Y.M et al, Esc Working Group On Myocardial And Pericardial Diseases: Key Messages On Dilated Cardiomyopathy, European Heart Journal, Volume 37, Issue 23, 14 June 2016, Pages 1850–1858, https://doi.org/10.1093/eurheartj/ehv727
Group | Subtype disease or agent | Comments |
Genetics | | |
Main genes associated with predominant cardiac phenotype: | Titin (TTN) Lamin A/C (LMNA) Myosin heavy chain (MYH7) Troponin T (TNNT2) Myosin-binding protein C (MYBPC3) RNA-binding Motif-20 (RBM20) Myopalladin (MYPN) Sodium channel alpha unit (SCN5A) BaCl2-associated athanogene 3 (BAG3) Phospholamban (PLN) | ∼20–25% of familial DCM; autosomal-dominant (AD) mode ∼6%; AD mode; associated with AVB and VA; can also cause Limb-Girdle myopathy ∼4%; AD mode ∼2%; AD mode ∼2%; AD mode ∼2%; AD mode ∼2%; AD mode ∼2%; AD mode ∼2%; AD mode ∼1%; AD mode; low QRS voltage on ECG |
Neuromuscular disorders | Duchenne muscular dystrophy (DMD) Becker muscular dystrophy (BMD) Myotonic dystrophy or Steinert (MD) | X-linked mode; CK elevation; paediatric patients X-linked mode; CK elevation; paediatric or adult patients AD mode; AV block |
Syndromic �diseases | Mitochondrial diseases | Mitochondrial inheritance syndromic expression including skeletal myopathy |
Tafazin (TAZ/G4.5) | X-linked mode; paediatric patients; Barth syndrome |
Aetiologies of dilated cardiomyopathy (2)
15
Source: Pinto Y.M et al, Esc Working Group On Myocardial And Pericardial Diseases: Key Messages On Dilated Cardiomyopathy, European Heart Journal, Volume 37, Issue 23, 14 June 2016, Pages 1850–1858, https://doi.org/10.1093/eurheartj/ehv727
Group | Subtype disease or agent | Comments |
Drugs | Antineoplastic drugs | Anthracyclines; antimetabolites; alkylating agents; Taxol; hypomethylating agent; monoclonal antibodies; tyrosine kinase inhibitors; immunomodulating agents |
Psychiatric drugs | Clozapine, olanzapine; chlorpromazine, risperidone, lithium; methylphenidate; tricyclic antidepressants; | |
Other drugs | Chloroquine; all-trans retinoic acid; antiretroviral agents; phenothiazines | |
Toxic and overload | Ethanol | Risk proportional to entity and duration of alcohol intake. Frequent good response after withdrawal |
Cocaine, amphetamines, ecstasy | Chronic users | |
Other toxic | Arsenic; cobalt; anabolic/androgenic steroids | |
Iron overload | Transfusions; haemochromatosis | |
Nutritional deficiency | Selenium deficiency | Rare, high frequency in some regions in China (Keshan disease) |
Thiamine deficiency (Beri-Beri) | Favoured by malnutrition, alcohol abuse. High-output dilated cardiac failure | |
Zinc and copper deficiency | Possible contributors to DCM | |
Carnitine deficiency | Paediatric patients | |
Electrolyte disturbance | Hypocalcemia, hypophosphatemia | |
Endocrinology | Hypo- and hyper-thyroidism�Cushing/addison disease Phaeocromocytoma, Acromegaly | |
Diabetes mellitus | |
Aetiologies of dilated cardiomyopathy (3)
16
Source: Pinto Y.M et al, Esc Working Group On Myocardial And Pericardial Diseases: Key Messages On Dilated Cardiomyopathy, European Heart Journal, Volume 37, Issue 23, 14 June 2016, Pages 1850–1858, https://doi.org/10.1093/eurheartj/ehv727
Group | Subtype disease or agent | Comments |
Infection | Viral (including HIV), bacterial (including Lyme disease), mycobacterial, fungal, parasitic (Chagas disease) | DCM caused by infectious myocarditis.�Atrio-ventricular block (AVB) in Lyme disease. Chagas' disease: DCM develops after a long latent infection |
Auto-immune diseases | | |
Organspecific | Giant-cell myocarditis (GCM) | Multinucleated giant cell; frequent AV block and ventricular arrhythmia |
| Inflammatory DCM | DCM caused by biopsy-proven, non-infectious myocarditis |
Not organ specific | Polymyositis/dermatomyositis; Churg–Strauss syndrome; Wegener's granulomatosis; systemic lupus erythematosus, sarcoidosis | In cardiac sarcoidosis there is granulomatous myocarditis; AV block is frequent DCM is possible but uncommon in these diseases |
Peripartum | | Risk factors: multiparity, African descent, familial DCM, autoimmunity |
Integrated approach for the diagnostic work-up and risk stratification of DCM (1)
17
Source: Ferreira A. et al, Dilated Cardiomyopathy: A Comprehensive Approach to Diagnosis and Risk Stratification, Biomedicines 2023, 11, 834. https://doi.org/10.3390/ biomedicines11030834
3-generational family history
Cardiac magnetic resonance
Genetic testing
≥ 35 years or CV risk factors/ischemic symptoms
Initial workup
Valvular heart disease
Arrhythmia as presentation?
DCM vs ACM
Familial/genetic DCM
Integrated approach for the diagnostic work-up and risk stratification of DCM (2)
18
Source: Ferreira A. et al, Dilated Cardiomyopathy: A Comprehensive Approach to Diagnosis and Risk Stratification, Biomedicines 2023, 11, 834. https://doi.org/10.3390/ biomedicines11030834
Electrocardiography
Electrocardiography
Echocardiography
Cardiac magnetic resonance
Genetic testing
Diagnostic work-up for aetiology assessment
19
Source: Pinto Y.M et al, Esc Working Group On Myocardial And Pericardial Diseases: Key Messages On Dilated Cardiomyopathy, European Heart Journal, Volume 37, Issue 23, 14 June 2016, Pages 1850–1858, https://doi.org/10.1093/eurheartj/ehv727
Basic evaluation
Diagnostic clues
Second-level evaluation
aetiology
Genetic testing (restricted panel**)
Diagnostic work-up according to age (1)
20
Source: Pinto Y.M et al, Esc Working Group On Myocardial And Pericardial Diseases: Key Messages On Dilated Cardiomyopathy, European Heart Journal, Volume 37, Issue 23, 14 June 2016, Pages 1850–1858, https://doi.org/10.1093/eurheartj/ehv727
Neonates
Children
Adolescents/Adults
Diagnostic work-up according to age (2)
21
Source: Pinto Y.M et al, Esc Working Group On Myocardial And Pericardial Diseases: Key Messages On Dilated Cardiomyopathy, European Heart Journal, Volume 37, Issue 23, 14 June 2016, Pages 1850–1858, https://doi.org/10.1093/eurheartj/ehv727
Work-up:
Work-up:
Work-up:
Diagnostic work-up according to red flags
22
Source: Pinto Y.M et al, Esc Working Group On Myocardial And Pericardial Diseases: Key Messages On Dilated Cardiomyopathy, European Heart Journal, Volume 37, Issue 23, 14 June 2016, Pages 1850–1858, https://doi.org/10.1093/eurheartj/ehv727
Examples of signs and symptoms that raise the suspicion of specific aetiologies | |
Finding | DCM |
Intellectual disability | Dystrophinopathies • Mitochondrial diseases • Myotonicdystrophy FKTN mutations |
Sensorineuraldeafness | Epicardin mutation • Mitochondrial diseases |
Visual impairment | CRYAB (polar cataract) • Type 2 myotonic dystrophy (subcapsular cataract) |
Gaitdisturbance | Dystrophinopathies • Sarcoglycanopathies • Myofibrillar myopathies |
Myotonia (involuntary muscle contraction with delayed relaxation) | Myotonic dystrophy (type 1 and Type 2) |
Muscle weakness | Dystrophinopathies • Sarcoglycanopathies • Laminopathies • MyotonicDystrophy Desminopathy |
Palpebral ptosis | Mitochondrial disease |
Pigmentation of skin and scars | Haemochromatosis |
Palmoplantarkeratoderma and woolly hair | Carvajal syndrome |
Multiparametric approach to arrhythmic risk stratification in dilated-cardiomyopathy patients
23
Source: Ferreira A. et al, Dilated Cardiomyopathy: A Comprehensive Approach to Diagnosis and Risk Stratification, Biomedicines 2023, 11, 834. https://doi.org/10.3390/ biomedicines11030834
TTNtv
PLN
RBM 20
SCN5A
LMNA
FLNC
Intermediate
Low
High
Therapy for Dilated Cardiomyopathy
24
Therapy for DCM
25
Specific causes of DCM
26
Phân loại suy tim theo phân suất tống máu thất trái
27
TL: Heidenreich P, Bozkurt B, et al. 2022 AHA/ACC/HFSA Guideline for theManagement of Heart Failure: Executive Summary. J Am CollCardiol.null2022, 0 (0).
Điều trị suy tim PSTM giảm
28
Nguồn: Phạm Nguyễn Vinh, Phạm Mạnh Hùng và cộng sự. Khuyến cáo của hội tim mạch quốc gia về chẩn đoán và điều trị suy tim cấp và suy tim mạn 2022.
SR: sinus rythm (Nhịp xoang)
Lợi ích của điều trị dựa trên chứng cứ bệnh nhân suy tim phân suất tống máu giảm
29
TL: Heidenreich P, Bozkurt B, et al. 2022 AHA/ACC/HFSA Guideline for theManagement of Heart Failure: Executive Summary. J Am CollCardiol.null2022, 0 (0).
Liều lượng một số thuốc điều trị STPSTMG (1)
30
Nguồn: Phạm Nguyễn Vinh, Phạm Mạnh Hùng và cộng sự. Khuyến cáo của hội tim mạch quốc gia về chẩn đoán và điều trị suy tim cấp và suy tim mạn 2022.
Liều lượng một số thuốc điều trị STPSTMG (2)
31
Nguồn: Phạm Nguyễn Vinh, Phạm Mạnh Hùng và cộng sự. Khuyến cáo của hội tim mạch quốc gia về chẩn đoán và điều trị suy tim cấp và suy tim mạn 2022.
Điều trị suy tim bằng dụng cụ
32
GDMT: guideline-directed medical therapy;
LVESD, left ventricular end systolic dimension;
MV, mitral valve;
MR, mitral regurgitation;
NP, natriuretic peptide;
NSR, normal sinus rhythm;
PASP, pulmonary artery systolic pressure.
Surgical revascularization
(1)
Optimization of GDMT before an intervention for secondary MR
(1)
TL: Heidenreich P, Bozkurt B, et al. 2022 AHA/ACC/HFSA Guideline for theManagement of Heart Failure: Executive Summary. J Am CollCardiol.null2022, 0 (0).
Once GDMT Optimized
Điều trị suy tim PXTM bảo tồn
33
Khuyến cáo | Mức khuyến cáo | Mức chứng cứ |
Ức chế thụ thể SGLT2 (empagliflozin, dapagliflozin, ) được khuyến cáo ở bệnh nahan STPSTM bảo tồn nhằm làm giảm nguy cơ nhập viện và tử vong tim mạch | I | A |
Tầm soát, điều trị nguyên nhân và các bệnh đồng mắc tim mạch và không tim mạch được khuyến cáo ở bệnh nhân STPSTM bảo tồn | I | C |
Lợi tiểu được khuyên dùng ở bệnh nhân STPSTM bảo tồn có triệu chứng sung huyết để làm giảm triệu chứng | I | C |
Nguồn: Phạm Nguyễn Vinh, Phạm Mạnh Hùng và cộng sự. Khuyến cáo của hội tim mạch quốc gia về chẩn đoán và điều trị suy tim cấp và suy tim mạn 2022.
EMPEROR-Preserved study design
34
*Randomized, double-blind, placebo-controlled trial.
Phase III trial* in patients with HFpEF
Aim: To investigate the safety and efficacy of empagliflozin versus placebo in patients with HF with preserved ejection fraction
Population: T2D and non-T2D, aged ≥18 years, chronic HF (NYHA class II–IV)
EMPEROR-Preserved
LVEF >40%
5988 patients
Median follow-up 26.2 months
Placebo
Empagliflozin 10 mg OD
CONFIRMATORY KEY SECONDARY ENDPOINTS
COMPOSITE PRIMARY ENDPOINT
CKD-EPI, Chronic Kidney Disease Epidemiology Collaboration; eGFR, estimated glomerular filtration rate; NYHA, New York Heart Association; OD, once daily. Anker S et al. N Engl J Med. 2021;XX:XXX.
Empagliflozin demonstrated a clinically meaningful 21% RRR
in the composite primary endpoint of CV death or HHF
35
25
20
15
10
5
0
Estimated cumulative incidence (%)
0 3 6 9 12 15 18 21 24 27 30 33 36
Months since randomization
Patients at risk
Empagliflozin:
415 (13.8%) patients with event Rate: 6.9/100 patient-years Placebo:
Placebo | 2991 2888 2786 2706 2627 2424 2066 1821 1534 1278 | 961 | 681 | 400 | 511 (17.1%) patients with event |
Empagliflozin | 2997 2928 2843 2780 2708 2491 2134 1858 1578 1332 | 1005 | 709 | 402 | Rate: 8.7/100 patient-years |
HR: 0.79
(95% CI: 0.69, 0.90)
p<0.001
NNT*=31
RRR
21%
ARR 3.3%
Placebo
Empagliflozin
*During a median trial period of 26 months. ARR, absolute risk reduction; CI, confidence interval; HR, hazard ratio; NNT, number needed to treat; RRR, relative risk reduction. Anker S et al. N Engl J Med. 2021;XX:XXX.
Early statistically significant
from day 18
Điều trị suy tim PSTM/BT
36
Management of patients with heart failure with preserved ejection fraction. CV, cardiovascular; HFpEF, heart failure with preserved ejection fraction.
TL: McDonagh TA et al. European Heart Journal (2023) 00,1 - 13
Tương tác các bệnh đồng mắc STPSTM/BT
37
∗Hypertension, diabetes mellitus, and obesity can result in coronary artery disease, atrial fibrillation, sleep apnea, and chronic kidney disease. Chronic kidney disease and sleep apnea can, in turn, worsen hypertension. These factors all influence the pathogenesis and outcomes of individuals with HFpEF. CAD = coronary artery disease; HFpEF = heart failure with preserved ejection fraction; HTN = hypertension.
TL: Kittleson M.M et al., ACC Expert Consensus Decision Pathway on Management of HFpEF, https://doi.org/10.1016/j.jacc.2023.03.393
Xử trí các bệnh đồng mắc với STPSTM/BT
38
ARB = angiotensin receptor blocker; ARNI = angiotensin receptor–neprilysin inhibitor; ASCVD = atherosclerotic cardiovascular disease; BB = beta-blocker; BP = blood pressure; CCB = calcium-channel blocker; CPAP = continuous positive airway pressure; eGFR = estimated glomerular filtration rate; GLP1-RA = glucagon-like peptide-1 receptor agonist; HbA1c = glycosylated hemoglobin; MRA = mineralocorticoid antagonist; OSA = obstructive sleep apnea; RAS = renin-angiotensin system; SGLT2i = sodium-glucose cotransporter 2 inhibitor.
TL: Kittleson M.M et al., ACC Expert Consensus Decision Pathway on Management of HFpEF, https://doi.org/10.1016/j.jacc.2023.03.393
Take home messages
39