Self- and Goal-Directed Valsalva Maneuver vs Exercise in Eliciting Left Ventricular Outflow Tract Obstruction

Abstract

Background

In symptomatic patients with hypertrophic cardiomyopathy (HCM), eliciting left ventricular outflow tract obstruction (LVOTO) is critical. A self-directed Valsalva (SDV) and exercise (EX) are frequent tools used to unmask obstruction in HCM patients. SDV is often not performed correctly leading to variable results and underestimation of the true provocable LVOT gradient. Alternatively, a standardized, goal-directed Valsalva (GDV) approach by maintaining an intraoral pressure 40 mm Hg for 10 seconds or more provides a more objective, reproducible result. We previously demonstrated the superiority of GDV compared to SDV in eliciting LVOTO both in patients on and off cardiac myosin inhibitor therapy. However, comparison between EX and GDV is limited.

Objectives

The objective was to compare the efficacy of EX, GDV, and SDV in eliciting LVOTO in patients.

Methods

In this prospective study, patients with HCM or suspicion for obstructive physiology performed a same-day rest transthoracic echocardiogram with SDV and GDV and stress echo evaluating LVOT gradients.

Results

A total of 59 patients were included. The mean age was 55 years; 55% of patients were men, and the average wall thickness was 17 mm. Mean peak LVOT gradient was significantly higher with EX (49 mm Hg) compared to GDV (33 mm Hg) or SDV (26 mm Hg); P < 0.01. More patients were reclassified to obstructive physiology with EX (25%) compared to SDV (8%) and severe obstructive HCM (15%) compared to GDV (8%); P < 0.05.

Conclusions

While GDV is superior to SDV, post-EX stress echo remains the gold standard in evaluating symptomatic patients with clinical concern for obstructive physiology.

Central Illustration

Eliciting left ventricular outflow tract obstruction (LVOTO) is essential for the prognosis and treatment of patients with hypertrophic cardiomyopathy (HCM). About 1/3 of patients have obstruction only detectable with provocative maneuvers—like the Valsalva maneuver or exercise (EX).¹ The Valsalva maneuver—through a rise in intrathoracic pressure and decrease in preload—can provoke LVOTO and unmask previously occult left ventricular outflow tract (LVOT) gradients. Ex stress echocardiography has been shown to elicit higher gradients and be more sensitive for the detection of LVOTO compared to Valsalva.^1,2

Potentially contributing to the lower efficacy of Valsalva maneuvers are the challenges in having patients follow instructions and perform an accurate self-directed Valsalva (SDV) maneuver. Vague and subjective instructions such as “strain as if having a bowel movement,” “blow out air and hold it,” and “bear down” are typically given to patients. This results in significant variability in efficacy of SDV maneuvers and can lead to underestimation of the max LVOT gradient. An alternative method is a goal-directed Valsalva (GDV) maneuver in which patients blow into a syringe material connected to a manometer with rubber tubing and maintains an intraoral pressure of 40 mm Hg for at least 10 seconds (Video 1). A previous study in patients with HCM showed that GDV, when compared to SDV, lead to higher peak LVOT gradient (pLVOTg), increased reclassification to obstructive HCM (peak LVOT ≥30 mm Hg), and increased reclassification to severe obstructive HCM (peak LVOT ≥50 mm Hg).³ Similar results were seen when comparing GDV to SDV in patients on myosin inhibitor therapy.⁴

While there are data demonstrating the superiority of GDV to SDV and EX to SDV, direct comparison between SDV, GDV, and EX is limited in the literature.^1,3.In a study comparing SDV, GDV, and EX by Heitner et al, only 43 patients were able to EX.³ In this contemporary cohort of EX-capable adults, we aimed to compare the efficacy of SDV, GDV, and EX in eliciting LVOTO and reclassifying patients to obstructive or severe obstructive HCM.

Methods

Study design

Adult patients >18 years of age with HCM and/or symptoms concerning for LVOTO who underwent same-day rest transthoracic echocardiogram (TTE) and stress TTE at the Atlantic Health System/Morristown Medical Center Hypertrophic Cardiomyopathy Center in Morristown, New Jersey, between March 2024 and June 2025 were included in this study. The study received proper ethical oversight and was approved by the Institutional Review Board.

Echocardiography

Patients underwent resting and stress hemodynamic TTE following American Society of Echocardiography guidelines.⁵ Imaging was acquired by an accredited sonographer with specific training in HCM-specific protocols and interpreted by a cardiologist with board certification in echocardiography and expertise in HCM imaging.

Measurement of LVOT gradients

From the apical view 3- and 5-chamber view, pulse-wave Doppler was used to precisely localize the site of LVOTO. Continuous-wave Doppler was used to estimate the pLVOTg at rest and with SDV, GDV, and EX. Doppler signals were carefully obtained to distinguish LVOT signal from mitral regurgitation jet. Careful assessment to distinguish mid-cavitary from true LVOT signal was also made. Multiple attempts were made to attain the pLVOTg at rest and following provocative measures. Significant LVOT was defined with a pLVOTg of ≥30 mm Hg. Patients with isolated mid-cavitary gradient or apical HCM were not included in this study.

Methods of provocation

All patients underwent SDV and GDV during rest TTE followed by stress TTE. If the patient followed instructions and adequate imaging was obtained by sonographer, repeat SDV or GDV was avoided to prevent patient fatigue. Patients were given adequate time to recover between SDV and GDV. No patient required more than 30 seconds between SDV and GDV.⁶ SDV and GDV were performed sequentially during the rest TTE, followed immediately by stress TTE without delay.

Self-directed Valsalva maneuver

While lying in the left lateral decubitus position, patients were instructed to “strain as if moving your bowels” or “bear down.” Patients were encouraged to hold the strain phase for as long as they could tolerate.

Goal-directed Valsalva maneuver

To measure intraoral pressure, an aneroid manometer was connected to a disposable 3 mL syringe with rubber tubing. While lying in the left lateral decubitus position for TTE, patients were instructed by the sonographer to blow into the syringe and maintain a pressure of 40 mm Hg for at least 10 s (Video 1).

Exercise

Standard Bruce protocol was performed in all patients with an upright treadmill EX per standard Bruce protocol. Patients taking cardiac medications (beta-blockers, calcium-channel blockers, and/or disopyramide) were instructed to continue their medications as prescribed. Echocardiographic and Doppler data on LVOTO were acquired at rest and immediately following peak EX, with the patient in the supine position.

Data analysis

Data analysis was performed using Microsoft Excel (Office 16). Data are expressed as mean ± SD for continuous variables and as proportions for categorical variables. Mean pLVOTg at rest, SDV, GDV, and EX was calculated and recorded. The increment in pLVOTg with provocation from rest was also calculated for each patient, and means were computed for each group (SDV, GDV, and EX). Means were compared using the paired t-test. Proportions were compared using the McNemar chi-square test. Pearson correlation coefficients were calculated to assess the association between pLVOTg measurements obtained during the different provocative maneuvers. Bland-Altman plots (Supplemental Figure 1) were used to assess agreement between Ex and GDV pLVOTg. A P value of <0.05 was considered to indicate statistical significance.

For analysis, patients with <30 mm Hg rest pLVOTg and subsequent SDV, GDV, or Ex pLVOTg ≥30 mm Hg were labeled as “reclassified to obstructive HCM.” Similarly, subsequent SDV, GDV, or Ex pLVOTg ≥50 mm Hg were labeled as “reclassified to severe obstructive HCM.”

Results

Between June 2023 and March 2024, 59 patients with clinical concern for LVOTO underwent same-day rest and stress TTE at Morristown Atlantic Health HCM Center in Morristown, New Jersey. Baseline demographics and clinical characteristics of the 59 patients are shown in Table 1. The mean age was 55 years; men were 55% of patients. Average wall thickness was 17 mm.

Table 1.

Demographics and Clinical Characteristics of 59 Patients With HCM Included in the Study

Age (y)	54.4 ± 15.9
Men	33 (57)
Women	25 (43)
Body mass index (kg/m2)	28.2 ± 4.9
Systemic hypertension	33 (57)
NYHA functional class
I	17 (29)
II	30 (52)
III	11 (19)
IV	0 (0)
Maximal septal wall thickness (mm)	17.7 ± 3.9
Family history of HCM	13 (22)
Baseline peak rest LVOTg (mm Hg)	17.3 ± 17.8
Baseline peak SDV LVOT gradient (mm Hg)	25.2 ± 23.2
Baseline peak GDV LVOT gradient (mm Hg)	32.4 ± 29.2
Baseline peak exercise LVOT gradient (mm Hg)	48.8 ± 42.2
LVEDD (mm)	44.3 ± 6.0
Mitral regurgitation
Mild	48 (83)
Moderate or severe	10 (17)
Aortic stenosis	2 (3)
Medications
BB/CCB	44 (76)
Disopyramide	1 (2)
Septal reduction therapies
Septal myectomy	3 (5)
Alcohol septal ablation	0 (0)
Myosin inhibitors	2 (3)
Pacemaker	0 (0)
Atrial fibrillation/atrial flutter	13 (22)
Nonsustained ventricular tachycardia	4 (7)
Implantable cardioverter-defibrillator	5 (9)
Hemodynamic stress exercise echocardiography (n = 59)
METs	11.1 ± 3.9

BB = β-blocker; CCB = calcium-channel blocker; GDV = goal-directed Valsalva; HCM = hypertrophic cardiomyopathy; LVOT = left ventricular outflow tract; LVEDD = left ventricular end-diastolic diameter; METs = metabolic equivalents; SDV = self-directed Valsalva; LVOTg = left ventricular outflow tract gradient.

Values are mean ± SD or n (%).

Exercise vs SDV and GDV

Mean pLVOTg was significantly higher with EX compared with both SDV and GDV (49 ± 43 mm Hg vs 26 ± 23 mm Hg and 33 ± 29 mm Hg, respectively; both P < 0.001) (Table 2, Figure 1). The mean incremental increase in pLVOTg from rest was also greater with EX compared with SDV and GDV (32 ± 31 mm Hg vs 8 ± 9 mm Hg and 15 ± 16 mm Hg, respectively; both P < 0.001) (Table 2, Figure 2).

Table 2.

Comparison of Provocative Maneuvers

	Ex vs GDV vs SDV (n = 59)
	EX	SDV	P Value∗	GDV	P Value∗
Mean pLVOTg (mm Hg)	49 (43)	26 (23)	<0.001	33 (29)	<0.001
Mean increment in pLVOTg (mm Hg)	32 (31)	8 (9)	<0.001	15 (16)	<0.001
Reclassified to obstructive HCM	15 (25%)	5 (9%)	0.002	10 (17%)	0.096
Reclassified to severe obstructive HCM	9 (15%)	2 (3%)	0.008	5 (9%)	0.046

EX = exercise; pLVOTg = peak left ventricular outflow tract gradient; other abbreviations as in Table 1.

Values are mean (SD) or n (%).

Figure 1.

Comparison of pLVOTg Means: SDV, GDV, and Exercise

All P value comparisons on pLVOTg means (SDV vs. GDV, SDV vs. Ex and GDV vs. Ex) differed significantly, with P < 0.001 for each comparison. EX = exercise; GDV = goal-directed Valsalva; LVOT = left ventricular outflow tract; pLVOTg = peak left ventricular outflow tract gradient; SDV = self-directed Valsalva.

Figure 2.

Comparison of Increments in pLVOTg From Rest With SDV, GDV, and Exercise

All P value comparisons on pLVOTg means increments (SDV vs. GDV, SDV vs. Ex and GDV vs. Ex) differed significantly, with P < 0.001 for each comparison. Abbreviations as in Figure 1.

Among provocative maneuvers, GDV resulted in a higher mean pLVOTg compared with SDV (33 ± 29 mm Hg vs 26 ± 23 mm Hg; P < 0.01) (Supplemental Table 1, Supplemental Figure 1), as well as a greater mean incremental increase from rest (15 ± 16 mm Hg vs 8 ± 9 mm Hg; P < 0.01) (Supplemental Table 1, Figure 2).

Patients receiving nodal-blocking agents demonstrated a numerically higher incremental rise in pLVOTg with EX compared with those not receiving these agents (18 ± 10 mm Hg vs 12 ± 6 mm Hg), although this difference did not reach statistical significance (P = 0.17). Patients with the greatest increase in LVOT gradient during EX compared with SDV or GDV were more likely to be male, older than 55 years, hypertensive, and able to achieve workloads >11 metabolic equivalents.

Reclassified to obstructive HCM

When compared to SDV, EX was superior in reclassifying patients to obstructive HCM (25% vs 9%; P < 0.01) (Table 2, Figure 3). When compared to GDV, EX had a higher rate of patients reclassify to obstructive HCM but this did not meet statistical significance (25% vs 17%; P = 0.10) (Table 2, Figure 2). GDV was superior compared to SDV in reclassification to obstructive HCM (17% vs 8%; P < 0.01) (Supplemental Table 1, Figure 3).

Figure 3.

Reclassification of HCM Severity From SDV, GDV, and Ex

Reclassification to obstructive HCM was higher with EX compared to SDV but not GDV (P < 0.002, 0.096, respectively). Reclassification to severe obstructive HCM was higher with EX compared to both SDV and GDV (P < 0.008, 0.046, respectively). HCM = hypertrophic cardiomyopathy; other abbreviations as in Figure 1.

Reclassified to severe obstructive HCM

When compared to SDV, EX was superior in reclassifying patients to severe obstructive HCM (15% vs 3%; P < 0.01) (Table 2, Figure 3). When compared to GDV, EX was also superior in reclassifying to severe obstructive HCM (15% vs 9%; P = 0.05). GDV was superior compared to SDV in reclassification to severe obstructive HCM (8% vs 3%; P < 0.01) (Supplemental Table 1).

The linear Pearson correlations between different provocative maneuvers are depicted in Figure 4. Correlation coefficients I were 0.87 for GDV and EX and 0.93 for GDV and SDV. Bland-Altman analysis (Supplemental Figure 1) demonstrated a positive bias of 16.4 mm Hg, indicated that EX systematically elicited higher LVOT gradients than GDV, with wide limits of agreement. Despite strong correlation between GDV and EX measurements, the magnitude and variability of the differences indicate that the 2 methods are not interchangeable for the assessment of provocable LVOTO.

Figure 4.

Reclassification of Degree of Obstruction With SDV, GDV, and Ex

In terms of reclassifying patients with mild obstruction, exercise reclassified 10 patients when compared to GDV. GDV reclassified fewer patients to mild obstruction⁷ when compared to SDV. In terms of reclassifying patients with severe obstruction, exercise reclassified 3 patients when compared to GDV. GDV reclassified more patients to severe obstruction⁴ when compared to SDV. Abbreviations as in Figure 1.

Discussion

In this study, we reclassified LVOTO via 3 provocative maneuvers: SDV, GDV, and EX. This was the largest study (n = 59) to date comparing same-day SDV, GDV, and EX in patients suspected to have LVOTO. Our study findings demonstrated that EX was superior in eliciting LVOTO compared to SDV and GDV (Central Illustration). The fact that EX was superior compared to GDV and SDV in reclassifying to severe obstructive HCM has important clinical implications as this would warrant medical or surgical therapy in symptomatic patients. Our findings were significantly different than prior study by Heitner in 2018 (n = 52, 43 with EX) which compared GDV to SDV and EX.³ In Heitner study, EX was not significantly different than GDV with respect to pLVOTg (58 mm Hg vs 52 mm Hg, P = 0.42), increment in pLVOTg (32 mm Hg vs 25 mm Hg, P = 0.31), reclassified to obstructive HCM (50% vs38%, P = 0.51), and reclassified to severe obstructive HCM (30% vs 30%; P > 0.999).³

Central Illustration.

Exercise vs Self-Directed Valsalva and Goal-Directed Valsalva

The figure compares the efficacy of exercise, SDV, and GDV and provides an example of a patient with HCM and symptoms with exertion. At rest, his peak LVOT gradient was only 13 mm Hg and rose to 70 mm Hg with GDV. With exercise, the LVOT gradient rose to near 120 mm Hg consistent with severe obstruction. Abbreviations as in Figures 1 and 3.

There are several potential reasons why our findings were different from the prior study by Heitner. All of the patients in our study were able to EX compared to only 43 of 52 in the Heitner study. Despite similar average age (54) and proportion of men (56%), the average metabolic equivalents on stress test in our study were 11 compared to 9 in the Heitner study. Further increase in EX capacity with increased augmentation of HR would correlate with higher LVOTg. A significant reduction in afterload with only a modest increase in preload with EX would also lead to higher LVOTg. Further potential explanations include differences in the sonographer technique and techniques between both institutions to elicit LVOTO. It should be noted that both sites had experienced and trained HCM sonographers and cardiologists who interpreted studies. We had significantly higher correlation values between GDV and Ex (r = 0.87), compared to Heitner study (r = 0.61).

The results of our study should not minimize the importance of performing GDV in all HCM patients on resting TTE. GDV is superior to SDV and can significantly impact clinical management of patients as GDV can lead to 20% more reclassification to obstructive HCM compared to SDV, as shown in our and Heitner study.³ Even in patients on cardiac myosin inhibitor therapy, GDV has been shown to change management in titrating myosin inhibitor therapy.⁴ In many patients, GDV may be sufficient to elicit an adequate LVOTO assessment and confirm the etiology of their symptoms. The true value of our study is that in patients who are symptomatic despite “normal” SDV or GDV, EX evaluation is critical. In patients who cannot EX and there remains a high suspicion for obstruction, other methods of provocation such as isoproterenol-guided transesophageal echocardiogram can be pursued.^7,8

Given the prognostic and therapeutic implications, obtaining accurate LVOT gradients and thoroughly searching for obstruction in HCM patients is critical.⁹ As shown in our study and prior work, EX is a powerful tool in eliciting obstruction and more sensitive than SDV maneuver.⁶ Studies estimate that a significant proportion of patients with obstructive HCM are underdiagnosed and up to 1/3 require provocation to elicit obstruction.² It is also important to consider LVOTO in the symptomatic patient with anatomic setup for LVOTO (elongated anterior mitral valve leaflet) even in the absence of wall thickness meeting HCM criteria. We had one patient with 10 mm wall thickness with no significant gradient at rest who developed severe LVOTO> 100 mm Hg with stress and underwent mitral valve plication with resolution of symptoms.

Study Limitations

There were several limitations to this study. Foremost, all studies were performed at one institution. We assumed normality, and some numerical variables may not follow normal distribution. The McNemar chi-square test was used to keep consistency with prior studies in this space, although accuracy may be limited with small sample size. There may have been institutional and interinstitutional variability between sonographers in encouraging SDV, although attempts were made to adhere to a strict HCM-tailored TTE protocol. Future multicenter studies across varied patient populations are necessary to expand generalizability of our study. Furthermore, these results cannot be extrapolated to patients who are unable engage in EX. There is no universally accepted gold standard for measurement of maximum LVOT gradients. Small errors in LVOT measurement of peak velocity would have led to significant alteration in LVOT gradient based on the Bernoulli’s principle. In the setting of EX, obtaining accurate gradients can be challenging. However, very careful examination of gradients was performed by HCM-specialized and echocardiography-certified cardiologist.

Conclusions

While GDV is superior to SDV in eliciting LVOTO in HCM patients, EX stress echocardiography remains the most potent tool in eliciting LVOTO. Ex led to increased reclassification to obstructive HCM compared to SDV and severe obstructive HCM compared to GDV and SDV. In all HCM patients, doing both SDV and GDV is critical on resting TTE. In those who are symptomatic but do not demonstrate clear LVOTO with SDV or GDV, EX must be pursued if possible.

Perspectives.

COMPETENCY IN MEDICAL KNOWLEDGE: Our study demonstrated how EX remains the most potent method of detecting LVOTO in HCM patients and was superior to both GDV and SDV.

TRANSLATIONAL OUTLOOK: GDV is a critical tool in assessing LVOTO in patients with HCM to evaluate for obstruction. GDV has been shown to be superior to SDV even in patients on background cardiac myosin inhibitors. While GDV is a useful tool, our study shows that it is not an adequate substitute for EX in the symptomatic patient and EX is a more potent unmasker of LVOTO. Therefore, in symptomatic HCM patients who do not have LVOTO by SDV or GDV, EX must be pursued.

Funding support and author disclosures

Dr Martinez has served as a consultant for Bristol Meyers Squib, Cytokinetics, and VizAI. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Supplementary material

Supplemental Video 1

Example of SDV and GDV.

Demonstration of the SDV and GDV in a patient with symptomatic obstructive HCM undergoing diagnostic TTE.