Newman, Darrell B.

Abstract Background Inability to reach age-predicted peak heart rate (APPHR) of >85%, or submaximal heart rates, on treadmill exercise stress testing (TMET) is associated with increased mortality risk [1]. Evidence is limited on mortality outcomes with heart rates greater than APPHR, or ‘supramaximal’ heart rates, especially when using heart rate metrics alone. Purpose Use of a comprehensive, compositive assessment of heart rate, termed ‘vigor’, to determine mortality outcomes has yet to be explored, especially for those with supramaximal heart rates. We sought to investigate this relationship. Methods We queried our stress database from 1993-2010 for patients >30 years old without cardiovascular disease and not on antichronotropic therapy. Clinical and mortality outcomes were retrieved from patient records. Patients were stratified into groups based on APPHR as achieved on TMET: <75%, 75-84%, 85-94%, 95-104%, ≥105% of APPHR. For our study, heart rate ‘vigor’ served as a composite assessment of cardiovascular fitness based solely on heart rate. This was derived from resting heart rate, heart rate recovery, and achieved percentage of APPHR. A higher Heart Rate Vigor Score (HRViS) for this study was, by definition, indicative of better cardiac responsiveness and recovery following exertion. Patients were stratified based on their achieved HRViS. Scores were determined as follows: All patients were initially assigned 3 points. 1 point was subtracted for each of the following parameters met: resting heart rate >90 beats per minute (BPM), heart rate recovery <13 BPM, or submaximal heart rates of APPHR <85%. Patients that remained at HRViS 3 and achieved supramaximal heart rates (≥105% APPHR) were assigned an additional point, amounting to HRViS 4. HRViS stratifications are detailed in Table 1. Mortality rates were calculated for all HRViS stratifications, with adjustment for FAC and known confounders. HRViS 3 was used as the referent. Results 18,961 total patients were included. 88 patients were classified with HRViS of 0; 1,763 as HRViS 1; 5,409 as HRViS 2; 9,902 as HRViS 3; and 1,799 as HRViS 4. Those with lower HRViS scores had more comorbid conditions (Table 1). 2,144 patients achieved submaximal APPHR (<85%) on TMET, and 2,917 achieved supramaximal APPHR (≥105%). HRViS 0, 1, and 2 had higher mortality risks compared to referent HRViS 3: 0 [3.76 (2.34-6.04), p<0.0001]; 1 [1.80 (1.53-2.12), p<0.0001]; 2 [1.29 (1.12-1.48), p=0.0004]. HRViS 4 had a non-statistically significant trends towards lower mortality risk compared to 3: 0.85 (0.66-1.08), p=0.1768. Conclusions HRViS 4 had a non-statistical trend towards lower mortality risk. Our findings do not support concern for adverse outcomes with excessive heart rates during exercise, and rather, may indicate a trend towards mortality benefit.HRViS Table 1

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Introduction: Hypertrophic cardiomyopathy (HCM) is a major cause of sudden cardiac death in the young and especially in young athletes. The treadmill exercise test (TEST) has an important role in the functional assessment of patients with HCM. Herein, TEST-derived peak oxygen uptake (VO2 max) is a proxy for cardiopulmonary fitness. However, the correlation between symptoms and VO2 - especially in active young patients with HCM - is unclear. Objective: To explore the relationship between TEST-derived VO2 and symptomology in athletes and non-athletes with HCM. Methods: Overall, 91 patients (40% female) with HCM and a TEST with VO 2 data were included in this case-control study. Data were abstracted from the electronic health record using the first TEST performed at Mayo Clinic. Patients were defined as an athlete if they participated in an organized, competitive sport. Results: Overall, 60 HCM patients (33% female) were categorized as an athlete. HCM athletes were younger (17 vs. 27 years; p<0.0001) and less likely to be symptomatic at the time of their TEST (OR=0.24; p=0.01). Additionally, athletes had a higher VO2 max (86% vs. 68% of predicted; p<0.0001) and reached higher exercise times (93% vs 76% of predicted; p<0.0001) compared to the non-athletes with HCM. When comparing symptomatic (n = 18) to asymptomatic patients (n = 73), symptomatic patients had i) a reduced exercise time (68% vs. 92% of predicted; p=0.002) and ii) lower VO2 max (62% vs 84% of predicted; p<0.001). Finally, among the 27 patients (30%) with a VO 2 max < 70% predicted (n=27), they i) more likely had a history of cardiac arrest (4 vs 0; p=0.006) and ii) were more likely to be symptomatic (OR=7.7; p< 0.0001) than those with VO2 ≥ 70% of predicted (n=64). Importantly, however, 15/27 (56%) patients (8 athletes/7 non-athletes) with a VO2 max < 70% were asymptomatic. Conclusions: Reduced exercise capacity is common in athletes with HCM and does not correlate with symptom status. However, if the TEST-derived VO2 max is < 70%, treatment intensification may be necessary as it may portend an adverse outcome both arrhythmically and mechanically.

Introduction and Hypothesis: In patients with hypertrophic cardiomyopathy (HCM), ventricular tachycardia (VT) is associated with adverse prognosis. Cardiopulmonary exercise testing (CPET) is part of the standard clinical evaluation in HCM. However, limited data are available on the incidence of VT and other adverse events during CPET in HCM. Methods: We reviewed the Mayo Clinic’s Integrated Stress Center Database for CPETs performed on HCM patients between January 2011 and July 2016. Patients were referred for clinical CPET by a physician, and medications were continued for the test. Electronic medical records were reviewed for clinical information and CPET data. Results: A total of 1,208 CPETs were performed on 976 HCM patients during the study period. Most tests were symptom-limited (94.6%), most common symptom was dyspnea (55%). Despite the relatively high number of patients with a history of VT (10.4%) and/or cardiac arrest (1.6%), there was a low rate of adverse events. Non-sustained VT occurred in 6 patients, most frequently during active recovery (3/6), and 2 of these 6 patients had prior history of VT. A 34 year-old female patient experienced sustained VT degenerating into ventricular fibrillation terminated by ICD shock. One patient had syncope during the test but no arrhythmia. Importantly, none of the patients died within 48 hours of the exercise test. Conclusions: In a large cohort of HCM patients, the incidence of VT or other adverse events was a rare finding during symptom-limited CPET.

Background: COVID-19 reveals new manifestations not only in the acute phase but also in the long term. The latter is what has been termed as ‘post acute sequelae of SARS-CoV-2 infection’ (PASC) — or “long COVID”— with dyspnea as one of its hallmarks. Cardiopulmonary stress testing (CPET) is increasingly being used to better evaluate such patients. Objective: To compare CPET findings of long COVID patients versus non-COVID patients with undifferentiated dyspnea on exertion seen at Mayo Clinic. Methods: A cohort study was carried out using Mayo Clinic’s exercise testing database. The study group included 77 PASC patients confirmed by a positive antigen or PCR test with no prior history of heart or lung disease. PASC patients were compared to 766 non-COVID patients with unspecified dyspnea without known diagnosis of cardiac or pulmonary disease. ANOVA according to the general linear model and Pearson’s Chi square were used for the bivariate analysis of the quantitative and categorical variables, respectively. Analyses were controlled for age, sex, and beta blocker use as appropriate. Both HR and SBP at rest and peak exercise were significantly different between groups, although the absolute differences were small. Results: Compared with the control group, the post-COVID patients were younger (mean age 47 SD ±14.9 years versus 50.5 SD ±10.1 years) and more likely to be female (70.1% (54 of 77) vs 57.6% (441 of 766)). Although there were many significant differences in the CPET results, the most outstanding were a lower FAC (73 SD ±19.4% vs 85.2 SD ±20.8%) and peak VO2 (22 SD ±6.4 ml/kg/min vs 25.8 SD ±7.37 ml/kg/min) in the study group (p<.0001). Also, CNS changes during CPET were reported at higher rates (19.5% (15 of 77) vs 11.4% (87 of 766)) while dyspnea at lower rates (55.8% (43 of 77) vs 65.7% (503 of 766)) in post-COVID patients (p=0.02). When adjusting for age and sex, weight was significantly higher in the study group (p=0.03) although the absolute difference was modest and BMI remained not significant. PFTs did not suggest any pulmonary abnormalities. Conclusions: We identified a high rate of severe exercise limitation among long COVID patients. Young women may be at higher risk for these complications. Pre-exercise PFTs and absence of objective respiratory limitation during CPET argue against a primary pulmonary cause of the observed limitations, though evaluation of cardiac, autonomic, and muscular impairment is pending. Further studies are warranted to untangle the physiologic abnormalities responsible for these observations.

Background: Left ventricular outflow tract (LVOT) obstruction is an important determinant in management of hypertrophic cardiomyopathy (HCM). Valsalva maneuver and amyl nitrite are used in clinical practice during resting echocardiography to induce latent obstruction (LVOT gradient <30 mmHg at rest, ≥30 mmHg with maneuver). With a nationwide shortage of amyl nitrite in 2019, we implemented a “repetitive squat-to-stand” maneuver to provoke LVOT obstruction during echocardiography. Methods: Patients with known or suspected HCM without resting obstruction who underwent repetitive squat-to-stand maneuver during echocardiography between February and September 2019 were included. Maximal instantaneous gradients were recorded. Provocable gradients were compared utilizing a two-sided t-test. Amyl nitrite was not available during the study period. Results: Squat-to-stand assessments were available in 125 patients without resting obstruction (age 58 ± 15 years, 67% male); 114 also performed Valsalva maneuver. 47 of 125 patients (37.6%) demonstrated provocable obstruction. 46 (36.8%) demonstrated latent obstruction provoked by squat-to-stand, which was severe (gradient ≥50 mmHg) in 29 (23.2%). Of the 46 patients, 19 demonstrated latent obstruction only with squat-to-stand but not with Valsalva, 13 of which demonstrated severe obstruction. Among patients with latent obstruction who performed both Valsalva and squat-to-stand maneuver (n=41), squat-to-stand resulted in a higher gradient than Valsalva maneuver (p<0.0001, Figure). Conclusion: Repetitive squat-to-stand maneuver is a clinically useful adjunct to the traditional echocardiographic exam in HCM. This maneuver appears to be more sensitive than the Valsalva maneuver for identifying severe dynamic LVOT obstruction. Use of repetitive squat-to-stand warrants further study in comparison to amyl nitrite, particularly regarding cost savings and diagnostic performance.

Abstract Background Left ventricular outflow tract (LVOT) obstruction is an important determinant of the management of hypertrophic cardiomyopathy (HCM). With a nationwide shortage of amyl nitrite in 2019, we implemented a ‘repetitive squat-to-stand’ manoeuvre to provoke LVOT obstruction during echocardiography. Case summary A 64-year-old female was referred with symptomatic HCM refractory to pharmacologic therapy. Transthoracic echocardiography showed minor LVOT obstruction with conventional imaging at rest and during Valsalva manoeuvre, but severe obstruction was confirmed with the repetitive squat-to-stand manoeuvre. Alcohol septal ablation via the first septal perforator was performed with subsequent resolution of symptoms. Discussion Due to the dynamic nature of LVOT obstruction, a series of provocative manoeuvres including Valsalva manoeuvre, inhalation of amyl nitrite, and exercise are often necessary to maximally augment ventricular obstruction. The recent unavailability of amyl nitrite during a nationwide shortage prompted the implementation of a protocol of repetitive squat-to-stand manoeuvre in our echocardiography laboratory. Rising from the squatting position decreases preload and afterload, both of which augment dynamic LVOT obstruction. Repetition of squatting and standing appears to enhance the sensitivity of the manoeuvre, particularly when exertional symptoms are reproduced. In this case, repetitive squat-to-stand manoeuvre led to the identification of severe LVOT obstruction which may not have been diagnosed otherwise, alteration of treatment to septal reduction therapy, and subsequent resolution of symptoms.