Table 1.
Basic Characteristics of the Articles Included in the Meta‐Analysis of Sex Difference in the Prognosis of Hypertrophic Cardiomyopathy
| Author, year, country | Study design | Data source, study populations | Follow‐up time; sample size | Mean age, y; male, % | Baseline comorbidities or echo, female/male | End Point | Estimate effect (95% CI) or case, female/male case | Adjusted covariates | |||
|---|---|---|---|---|---|---|---|---|---|---|---|
| NYHA III/IV % | ICD % | LVEF | LVOT gradient | ||||||||
| Olivotto et al, 2001, Italy 36 | PC |
Azienda Ospedaliera Careggi; and Minneapolis Heart Institute, patients with HCM |
9.1 y; 107 | 50.0; 57.0 | NA | NA | NA | NA | AF | 1.11 (0.70–1.70), male | Univariate analysis |
| Ho et al, 2004, China 25 | RC |
Queen Mary Hospital, patients with HCM |
5.8 y; 118 | 54.0; 52.5 | NA | 14.0/14.0 | 68.0/72.0 | NA | Major cardiovascular events | 5.86 (1.77–7.21) | Age at presentation, family history of HCM, NYHA class III/IV, ECG features at presentation, types of HCM |
| Woo et al, 2005, Canada 7 | PC |
Toronto General Hospital Obstructive HCM population after septal myectomy |
7.7 y; 338 | 47.0; 60.1 | NA | NA | NA | NA | HF (HF worsening) | 3.60 (2.00–6.70) | Age, history of preoperative AF, LA diameter, septal/posterior thickness ratio, concomitant CABG |
| Major cardiovascular events | 3.30 (2.00–5.40) | ||||||||||
| Olivotto et al, 2005, Italy 2 | PC |
Azienda Ospedaliera Careggi; Minneapolis Heart Institute; Tufts‐New England Medical Center, patients with HCM |
6.2 y; 969 | 42.0; 59.4 | 18.0/6.0 | NA | NA | 62.0/58.0 | HF (HF progression) | 1.50 (1.11–2.00) | Age |
| HCM‐related death | 52/58 | ||||||||||
| SCD | 26/33 | ||||||||||
| Noncardiac death | 36/22 | ||||||||||
| Lee et al, 2007, China 6 | RC |
A tertiary referral center in Taiwan, patients with HCM |
5.3 y; 163 | 60.9; 51.5 | NA | NA | NA | NA | All‐cause mortality | 2.99 (1.13–9.87) | LVOT obstruction, AF |
| Ball et al, 2011, Canada 8 | PC |
Toronto General Hospital, patients with obstructive HCM |
7.2 y; 649 | 51.0; 56.2 | NA | NA | NA | NA | HCM‐related death | 2.10 (1.20–3.60) | Age, septal thickness, resting LVOT gradient, invasive treatment |
| All‐cause mortality | 2.00 (1.30–3.20) | ||||||||||
| Wang et al, 2014, China 9 | PC |
Fuwai Hospital, patients with HCM |
4.0 y; 621 | 47.5; 74.1 | NA | 0.6/0.7 | 67.1/67.5 | 81.9/71.9 | All‐cause mortality | 2.19 (1.21–3.95) | Age, syncope (without any invasive treatment, including ICD and septal reduction therapy), SCD family history, maximum LV wall thickness, LA diameter, AF, LVOT obstruction (without septal reduction therapy) and NYHA class at enrollment. |
|
Cardiovascular death HF (chronic HF/HF progression) |
2.19 (1.17–4.09) 1.73 (1.12–2.69) |
||||||||||
| SCD | 7/12 | ||||||||||
| HF‐related death | 6/9 | ||||||||||
| Ventricular arrhythmia | 1/3 | ||||||||||
| AF | 12/28 | ||||||||||
| Stroke | 10/19 | ||||||||||
| Terauchi et al, 2015, Japan 37 | PC |
Kochi Medical School Hospital, patients with HCM |
13.0 y; 50 | 47.0; 54.0 | 17.0/0 | NA | 67.0/65.0 | NA | HCM‐related death | 3/5 | Univariate analysis |
| HCM‐related events | 11/7 | ||||||||||
| HF | 10/5 | ||||||||||
| Debonnaire et al, 2017, Netherlands 22 | PC |
Leiden University Medical Center, patients with HCM |
4.8 y; 242 | 53.0; 64.5 | NA | NA | NA | NA | AF (new‐onset AF) | 1.41 (0.75–2.63), male | Univariate analysis |
| Geske et al, 2017, United States 10 | RC |
Mayo Clinic, patients with HCM |
12.7 y; 3673 | 55.0; 54.8 | 45.0/35.0 | 6.0/7.0 | 71.0/69.0 | 36.0/23.0 | All‐cause mortality | 1.13 (1.03–1.22) | Age, NYHA Class III/IV symptoms, and history of AF, CAD, hypertension, ICD implantation, and beta receptor antagonist use |
| Ho et al, 2018, United States 5 | RC | SHARE registry, patients with HCM | 5.4 y; 4591 | 44.3; 62.9 | NA | NA | NA | NA | Composite end point | 0.88 (0.77–1.01) | Family proband status, SARC+, SARC VUS and race |
| Kubo et al, 2018, Japan 30 | PC |
Kochi Cardiomyopathy Network, patients with HCM |
6.1 y; 293 | 56.0; 67.2 | NA | NA | NA | NA | HCM‐related events | 0.93 (0.54–1.60), male | Age at registration, NYHA class III, presence of AF, maximum LV wall thickness, LVFS, and presence of LVOT obstruction |
| Van Velzen et al, 2018, Netherlands 13 | RC |
Erasmus Medical Center in Rotterdam, patients with HCM |
6.8 y; 1007 | 52.0; 61.6 | NA | 6.0/4.0 | NA | NA | All‐cause mortality | 1.25 (0.91–1.73) | Family relatedness |
| Cardiovascular death | 1.22 (0.83–1.79) | ||||||||||
| SCD | 0.75 (0.44–1.30) | ||||||||||
| HF‐related death | 1.77 (0.95–3.27) | ||||||||||
| Stroke‐ related death | 5.57 (0.55–56.8) | ||||||||||
| Noncardiac death | 2.11 (1.21–3.69) | ||||||||||
| Choi et al, 2019, Korea 21 | PC |
Two tertiary referral centers, patients with HCM |
4288 person‐years; 730 | 57.1; 75.5 | NA | NA | NA | NA | SCD | 3.83 (1.39–10.60) | HCM SCD‐risk score |
| Lorenzini et al, 2019, Italy 32 | RC |
7 European centers, patients with HCM |
6.1 y; 4893 | 49.2; 63.9 | 17.1/7.5 | 15.9/17.1 | 66.0/65.0 | 10.0/8.0 | Composite end point | 1.19 (1.06–1.30) | Age at presentation, previous VF/VT, NYHA class, EF ≤50%, MWT, LA diameter, LVOT max, AF, NSVT on Holter, family history of sudden death, syncope, septal myectomy, ASA |
| HF‐related death | 1.44 (1.25–1.59) | ||||||||||
| SCD | 0.80 (0.40–1.10) | ||||||||||
| All‐cause mortality | 2.87 (2.57–3.19) | ||||||||||
| HCM‐related death | 51/52 | ||||||||||
| Noncardiac death | 96/114 | ||||||||||
| Ghiselli et al, 2019, Italy 23 | RC |
IRCCS Sacro Cuore Don Calabria Hospital, patients with HCM |
5.9 y; 292 | 46.0; 72.3 | 11.0/6.0 | NA | 67.0/67.0 | 14.0/18.0 | Composite end point | 2.32 (1.04–5.22) | Univariate analysis |
| Jang et al, 2019, Korea 28 | PC |
Inha University Hospital, patients with nonobstructive HCM |
34.0 mo; 202 | 63.0; 69.8 | 14.8/2.1 | NA | 65.1/64.9 | NA | HF (HF presentation) | 5.01 (2.05–12.26) | Age |
| Cardiovascular death | 5.18 (1.32–20.34) | ||||||||||
| HF (HF hospitalization) | 6.86 (1.43–32.99) | ||||||||||
| Lu et al, 2019, United States 33 | RC |
Johns Hopkins HCM Registry, patients with HCM |
2.1 y; 728 | 53.3; 62.0 | 21.0/7.0 | NA | 67.0/65.0 | 35.0/26.0 | HF | 3.00 (1.10–8.40) | Age, NYHA III‐IV, LA diameter, and LV global longitudinal peak systolic strain |
| Composited end point | 1.90 (1.20–2.90) | ||||||||||
| AF | 18/12 | ||||||||||
| Ventricular arrhythmia | 5/9 | ||||||||||
| All‐cause mortality | 4/2 | ||||||||||
| Meghji et al, 2019, United States 34 | RC |
Mayo Clinic HCM population after septal myectomy |
8.2 y; 2506 | 55.1; 55.0 | 90.8/84.8 | 12.8/14.2 | 73.0/70.0 | 67.0/50.0 | All‐cause mortality | 0.98 (0.76–1.26) | Age, year of surgery, BMI, diabetes, NYHA class, amiodarone, pacemaker using, NSVT, hypertension, disopyramide, use of ACEi or angiotensin receptor blockers, presyncope, dyslipidemia, prior septal reduction, syncope, mitral valve regurgitation grade, race, β‐blocker, calcium‐channel blocker, family history of HCM and SCD, ethnicity, anteroseptal wall thickness, ICD. |
| Rowin et al, 2019, United States 11 | PC |
Tufts HCM Institution, patients with HCM |
4.7 y; 2123 | 47.2; 62.6 | 39.0/23.0 | 24.0/25.0 | 64.0/63.0 | NA | SCD | 0.92 (0.60–1.50) | Age |
| All‐cause mortality | 1.32 (0.92–1.91) | ||||||||||
| Noncardiac death | 55/46 | ||||||||||
| Cardiovascular death | 4/3 | ||||||||||
| HCM‐related death | 1.50 (0.70–3.40) | ||||||||||
| HF | 1.60 (1.20–2.10) | ||||||||||
| Stroke‐related death | 1/2 | ||||||||||
| Huurman et al, 2020, Netherlands 27 | PC |
Erasmus Medical Center HCM population after septal myectomy |
5.9 y; 162 | 52.1; 61.1 | 79.0/78.0 | 11.0/15.0 | NA | 93.0/82.0 | Composite end point | 2.32 (0.79–6.83), male | Age, NYHA class ≥III, AF, hypertension, hypercholesterolemia, diabetes, pathogenic gene variant, negative inotropic therapy, HF therapy, ICD, time from symptom onset, time from diagnosis, preoperative peak LVOT gradient, maximal wall thickness, LA diameter, LV end‐diastolic diameter, impaired systolic function, diastolic function, systolic anterior motion of the mitral valve, mitral regurgitation |
| SCD | 0/2 | ||||||||||
| All‐cause mortality | 5/10 | ||||||||||
| Huang et al, 2020, China 26 | PC |
West China Hospital, patients from HCM database with HCM |
3.2 y; 576 | 54.9; 54.9 | 46.9/30.7 | 4.2/6.0 | 66.9/66.4 | 33.0/24.0 | Cardiovascular death | 0.64 (0.32–1.30) | Univariate analysis |
| All‐cause mortality | 23/32 | ||||||||||
| Lakdawala et al, 2020, United States 31 | RC | Patients from SHARE registry with HCM | 7.7 y; 5873 | 46.7; 62.1 | 21.6/9.3 | 22.1/20.6 | 66.0/64.6 | 35.5/26.6 | HF (HF composite) | 1.85 (1.48–2.32) | Age, hypertension, and history of AF |
| All‐cause mortality | 1.45 (1.16–1.82) | ||||||||||
| Ventricular arrhythmia composite | 111/202 | ||||||||||
| AF (incident AF) | 1.21 (1.01–1.46) | ||||||||||
| Stroke | 1.48 (1.11–1.98) | ||||||||||
| HCM‐related death | 1.50 (1.13–1.99) | ||||||||||
| Montenegro Sa´ et al, 2020, Portugal 35 | RC |
Portuguese Registry of patients with HCM |
65.0 mo; 1042 | 53.3; 58.8 | 16.1/10.8 | 10.9/15.6 | 65.6/64.3 | 16.9/14.6 | All‐cause mortality | 2.05 (1.11–3.75) | Age, symptoms, HF, mitral regurgitation, diastolic dysfunction, CAD. |
| Cardiovascular death | 3.16 (1.25–7.99) | ||||||||||
| HF‐related death | 11/5 | ||||||||||
| Stroke‐related death | 2/1 | ||||||||||
| SCD | 15/18 | ||||||||||
| Wang et al, 2020, China 38 | RC |
A large tertiary hospital in North‐eastern China. HCM population after alcohol septal ablation |
7.5 y; 320 | 51.6; 49.4 | 67.3/56.3 | 6.8/5.7 | 62.0/60.0 | NA | All‐cause mortality | 1.12 (1.08–1.27) | Age, NYHA III/IV, AF, CAD, hypertension, diabetes, beta receptor antagonist use, CCB use, alcohol dose, LVEF, residual LVWT >3 mo postprocedure, reduction in LVOT gradient >3 mo postprocedure, persistent complete AVB. |
| Kim et al, 2021, Korea 29 | PC |
Korea National Health Insurance Service claims database patients with HCM |
4.4 y; 9524 | 51.7; 77.6 | NA | NA | NA | NA | Composite end point | 1.43 (1.22–1.68) | Propensity score‐matched (age, income, underlying disease, current medication, Charlson comorbidity index) |
| Cardiovascular death | 1.27 (0.91–1.78) | ||||||||||
| HF (new‐onset HF admission) | 1.54 (1.30–1.82) | ||||||||||
| All‐cause mortality | 0.91 (0.69–1.21) | ||||||||||
| Bongioanni et al, 2021, Italy 39 | RC |
Mauriziano Hospital, patients with HCM |
86.5 mo; 573 | 53.0; 61.4 | 7.9/3.0 | 8.0/7.0 | 63.0/65.0 | 34.0/24.0 | HCM‐related death | 1.52 (0.91–2.52) | Univariate analysis |
| All‐cause mortality | 32/31 | ||||||||||
| SCD | 3/13 | ||||||||||
| Stroke‐related death | 4/2 | ||||||||||
| Noncardiac death | 5/6 | ||||||||||
ACEi indicates angiotensin‐converting enzyme inhibitor; AF, atrial fibrillation; ASA, alcohol septal ablation; AVB, atrioventricular block; CABG, concomitant coronary artery bypass grafting; CAD, coronary artery disease; CCB, calcium channel blocker; EF, ejection fraction; HCM, hypertrophic cardiomyopathy; HF, heart failure; ICD, internal cardiac defibrillator; IRCCS, Istituto di Ricovero e Cura a Carattere Scientifico; LA, left atrial; LV, left ventricular; LVEDD, left ventricular end diastolic diameter; LVEF, left ventricular ejection fraction; LVFS, left ventricular fractional shortening; LVOT, left ventricular outflow tract; LVWT, left ventricular wall thickness; MWT, left ventricular maximum wall thickness; NA, not applicable; NSVT, nonsustained ventricular tachycardia; NYHA, New York Heart Association; PC, prospective cohort; RC, retrospective cohort; SARC VUS, sarcomere variant of unknown significance present; SARC, sarcomere mutation; SARC+, at least 1 pathogenic or likely pathogenic variant in any of the above sarcomere genes; SCD, sudden cardiac death; VF, ventricular fibrillation; and VT, ventricular tachycardia.