A Tough Time Running Around the Block
A 61-year-old man with diabetes mellitus, hypertension, and sleep apnea presented with exertional dyspnea. One year prior cardiopulmonary exercise testing was performed showing peak oxygen consumption of 19.9 mL/(min·kg; 66% predicted) with peak heart rate 90 beats per minute but no record of arrhythmia or ST-segment deviation. Physical examination was normal, with body mass index of 30.5 kg/m2. The resting ECG showed right bundle branch block and first-degree atrioventricular block. Plasma NT-proBNP (N-terminal pro-B-type natriuretic peptide) was 403 pg/mL. Echocardiography revealed a left ventricular ejection fraction of 66%, no valve disease, left atrial enlargement (39 mL/m2), estimated right ventricular systolic pressure 30 mm Hg, and medial E/e′ ratio 9. The H2FPEF score was 4, suggesting intermediate likelihood of heart failure with preserved ejection fraction (HFpEF). The patient was referred for invasive hemodynamic cardiopulmonary exercise testing to determine the cause of exertional dyspnea.
Baseline right atrial pressure and pulmonary capillary wedge pressure were normal (Figure [A]), with a resting heart rate of 59 beats per minute. With leg raise, the pulmonary capillary wedge pressure increased to 20 mm Hg, with a prominent V wave (Figure [B]). Shortly after beginning exercise, the patient became markedly dyspneic. At this time, grouped beating was noted on ECG, with PR interval prolongation followed by dropped beats (Figure [C]). Following conducted beats, there was progressive PR prolongation, with P waves superimposed on the preceding T waves, such that atrial systole either preceded mitral valve opening or coincided with early rapid filling. This resulted in development of fused cannon A-V waves up to 50 mm Hg in amplitude (Figure [C]). Peak oxygen consumption was severely depressed at 7.5 mL/(min·kg), peak heart rate was 70 beats per minute, and peak cardiac output was 7.27 L/min (6% of the predicted increase based upon metabolic demand).
Figure. Pulmonary capillary wedge pressure (PCWP) at different stages of the exercise test.A, Resting PCWP in red was normal with normal amplitude a and v waves. Lead II from the ECG is shown in green. B, With passive leg elevation before exercise, there is an increase in PCWP, with a striking increase in the amplitude of the v wave. C, During exercise the P wave preceding the second QRS complex (*) is conducted with a PR interval of 266 ms. The corresponding a wave in the PCWP tracing is normal in amplitude. Following this beat there is prolongation of the PR interval, such that the P wave is buried within the T wave of the second beat (†). Because ventricular systole had not yet ended, the left atrium contracted against a closed mitral valve during this beat, causing a cannon a wave that became superimposed with the v wave (a+v). In the next beat, the P wave (‡) is not conducted due to Mobitz Type I second degree atrioventricular block, resulting in another cannon a wave superimposed on the v wave in the PCWP tracing. This sequence of PR prolongation with dropped beats continued.
A 12-lead ECG was obtained immediately following exercise and confirmed the presence of Mobitz type I atrioventricular block, with 3:2 atrioventricular block alternating with 2:1 atrioventricular block. The patient underwent dual chamber permanent pacemaker implantation, resulting in substantial improvement of his dyspnea, which was noted immediately.
Discussion
Exertional dyspnea is a very common complaint encountered in practice, and diagnosis can be challenging.1 In the case presentation, left ventricular ejection fraction was normal, and although there was no evidence of hypervolemia on physical examination, it is known that many patients with HFpEF display hemodynamic abnormalities exclusively during exercise.2,3 This patient displayed an intermediate pretest probability that HFpEF was present based upon the calculated H2FPEF score, which is a common clinical scenario where invasive hemodynamic exercise testing is most useful to establish the diagnosis.1,4
Hemodynamics were normal at rest, but pulmonary capillary wedge pressure increased strikingly with passive leg raise. This indicates even before exercise that HFpEF is present, as the increase in venous return from the legs could not be accommodated without excessive increase in filling pressure.3 Although the prominent V wave with leg elevation can be caused by dynamic mitral regurgitation, in most patients with HFpEF, this simply reflects reduced left atrial compliance.5 Further assessments during exercise however indicated that this was not a case of garden variety HFpEF alone, as the patient developed exercise-induced atrioventricular block during low-level exercise.
Atrioventricular block is commonly considered to contribute to exercise intolerance predominantly through chronotropic incompetence, which was evidenced in this case by the peak heart rate of only 70 beats per minute, resulting in severe cardiac output reserve limitation. However, this case also illustrates how significant diastolic abnormalities are observed related to the loss of atrioventricular synchrony. With prolongation of the PR interval, atrial contraction moves closer to the end of ventricular systole, resulting in a P on T phenomenon, where the atrium contracts against an incompletely relaxed ventricle, or even closed atrioventricular valve. In addition to causing superimposed cannon a-v waves in the atria (Figure [C]), this atrioventricular dyssynchrony compromises ventricular filling through loss of atrial booster function in late diastole, which is even more poorly tolerated in patients with HFpEF.
Exercise-induced atrioventricular block in patients with 1:1 atrioventricular conduction at rest is rare6,7 because conduction through the His-Purkinje system is relatively unaffected by increased sympathetic discharge and may actually worsen during exercise as compared to conduction through the atrioventricular node. In our case, alternating Wenkebach periods were noted which are usually attributed to multilevel block due to transverse (horizontal) dissociation of one, or several, segments of the atrioventricular conduction system (atria, atrioventricular node, and His bundle).8 Pacemaker implantation substantially improved symptoms, likely related to both improvements in chronotropic reserve and restoration of atrioventricular synchrony.
In conclusion, the presented case emphasizes the extent to which patients with HFpEF, in particular, rely on optimal atrioventricular synchrony and chronotropic reserve to cope with the heightened metabolic demands of physical activity. The case also illustrates the value of hemodynamic exercise testing to identify the cause of symptoms among patients with unexplained dyspnea, allowing for actionable pathophysiologic insights that can guide treatment.
Sources of Funding
Dr Borlaug is supported by R01 HL128526 and U01 HL125205.
Footnotes
References
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