The prognostic value of peak oxygen uptake in obstructive hypertrophic cardiomyopathy: a literature review to inform economic model development

Figures & data

Table 1. Inclusion and exclusion criteria.

Criteria	Inclusion	Exclusion
Population	Patients with cardiovascular conditions related to HCM	Healthy populations Other non-related conditions Pediatric population Stroke patients Fontan patients
Treatment	Any treatment	No restriction
Surrogate Endpoint	pVO2 Change in pVO2 Percentage predicted pVO2	Other, non-relevant endpoints
Outcomes	Clinical outcomes: Mortality/death Cardiac arrest/sudden cardiac death Hospitalization Re-hospitalization Time to events Adverse events Atrial fibrillation Ventricular fibrillation Supraventricular tachycardia Stroke Heart failure Stress cardiomyopathy Re-hospitalization post-SRT Heart transplantation Humanistic outcomes: Quality-of-life Disutility Quality-adjusted life year Work productivity Functional impairment (Incremental) cost-effectiveness Direct/indirect costs Healthcare resource utilization Cost–benefit analysis	No potentially predictive relationship quantified between pVO2 and the endpoint of interest Other, non-relevant endpoint (e.g. laboratory values, surrogate-type endpoints)
Study Design	All clinical studies reporting on the use of pVO2 Primary studies with cost-effectiveness analyses or HTA-related studies and reports	Narrative reviews Conference abstracts
Limits	Language: English Geography: All geographies Human studies only	Not meeting inclusion criteria

Abbreviations. HCM, hypertrophic cardiomyopathy; HTA, health technology assessment; oHCM, obstructive hypertrophic cardiomyopathy; pVO2, peak oxygen uptake; SRT, septal reduction therapy.

Table 2. Data extracted from selected studies.

Study characteristics	Population characteristics	pVO2 potentially prognostic relationships^a
Author Title Journal Year DOI number Study name Study design Data source Geography Sample size Intervention Study duration	Main diagnosis Further diagnosis Age (mean) Male (%) Ethnicity (white, black, Asian, other [%]) Baseline mean pVO2 Patient distribution across NYHA classes I–IV (%) Pre-/post-transplant status	Proxy endpoint pVO2 threshold (if relevant) Endpoint category Composite endpoint (Y/N) Endpoint Relationship (type) Relationship (value) Relationship (CI) Statistical significance (Y/N)

^aEndpoints were reported for each relationship identified.

Abbreviations. CI, confidence interval; DOI, digital object identifier; N, no; NYHA, New York Heart Association; pVO2, peak oxygen uptake; Y, yes.

Figure 1. PRISMA diagram. Abbreviations: FT, full text; PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses; pVO2, peak oxygen consumption.

Table 3. HCM study characteristics.

Author (Year) Country	Study design	Population	Sample size	Age (mean)	Male (%)	White (%)	NYHA I/II/III/IV (%)
Coats (2015)^35 United Kingdom	Observational – prospective	oHCM	1,898	46	67	76	NR for all
Azarbal (2014)^36 USA	Observational – prospective	HCM	265	52	61	64	59.8/28/12.2/0
Smith (2020)^41 USA	Observational – retrospective	oHCM	295	50	56	NR	2.9 (mean)
Masri (2015)^37 USA	Observational – retrospective	HCM	1,005	50	64	NR	32/46/22/0
Magri (2018)^38 Italy	Observational – prospective	HCM	681	48	68	NR	95 (for I and II combined)/5/0
Moneghetti (2017)^39 USA	Observational – prospective	HCM	130	52	63	NR	21 for III
Finocchiaro (2015)^42 USA	Observational – prospective	HCM	156	51	62	NR	14 for III
Sorajja (2020)^40 USA	Observational – prospective	oHCM	182	53	65	NR	51/49/0/0
Rodrigues (2021)^34 Global	Systematic review	HCM	NA	NA	NA	NA	NA for all

Abbreviations. HCM, hypertrophic cardiomyopathy; NA, not applicable; NR, not reported; NYHA, New York Heart Association; oHCM, obstructive hypertrophic cardiomyopathy.

Table 4. pVO2 as a predictor of single and composite endpoints.

Author (Year)	pVO2 threshold	Baseline pVO2	Endpoint	Association
				Type	Value	95% CI
Single
Coats (2015)^35	Continuous (per unit, mL/kg/min)	22	Death	HR	0.82	0.77–0.88
			Transplant		0.87	0.79–0.96
			CV death		0.80	0.75–0.86
			Sudden cardiac death		1.03	1.00–1.06
Azarbal (2014)^36		25.8	Paroxysmal AF	OR	0.76	0.60–0.97
			Permanent AF		0.76	0.61–0.96
Smith (2020)^41	Non-responders^a	18.8	Death	HR	1.77	1.06–3.34
			NYHA class	OR	1.43	1.14–1.86
			Atrial fibrillation	OR	0.91*	0.59–1.40
Composite
Masri (2015)^37	Continuous (per unit, mL/kg/min)	21	Death, appropriate defibrillator, discharges, resuscitated sudden death, stroke, and heart failure admission	HR	0.90	0.87–0.94
Magri (2018)^38		21.6	Death from HF, cardiac transplantation, progression to NYHA class III–IV caused by end-stage phase with or without LVEF 50%, hospitalization, and septal reduction procedure		0.85	0.81–0.89
			Sudden cardiac death, aborted SCD, and appropriate ICD shock on ventricular fibrillation or sustained ventricular tachycardia		0.91	0.84–0.98
Coats (2015)^35		22	Heart failure/transplant		0.81	0.77–0.86
			SCD or equivalent		1.01*	0.98–1.03
			Death or transplant		0.79	0.74–0.83
Moneghetti (2017)^39		26	Death, worsening of HF		0.57^b	0.42–0.76
Finocchiaro (2015)^42	Per 5 ml/kg/min	26	Cardiac-related death, heart transplant, and functional deterioration leading to septal reduction therapy (myectomy or septal alcohol ablation)		0.52	0.45–0.60
Sorajja (2020)^40	Continuous (per unit, mL/kg/min)	22.7	Death or onset of severe symptoms	RR	0.98	0.96–0.99

*Statistically non-significant.

^aThe study aimed to determine clinical predictors of patients experiencing decreased pVO2 following surgical myectomy by investigating pVO2 before and after myectomy, therefore the pVO2 threshold used was <0% change in pVO2, indicating non-responsiveness.

^bThe value is reported as “VO2 max”. The study was included as the authors use the terms “pVO2” and “VO2 max” interchangeably.

Abbreviations. AF, atrial fibrillation; CI, confidence interval; CV, cardiovascular; HCRU, health care resource use; HF, heart failure; HR, hazard ratio; ICD, implantable cardiac defibrillator; LVEF, left ventricular ejection fraction; NYHA, New York Heart Association; OR, odds ratio; pVO2, peak oxygen consumption; RR, risk ratio; SCD, sudden cardiac death.

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