Faculty Bibliography

BACKGROUND: . Unique identifier: NCT00798122

Takotsubo cardiomyopathy (TC) often occurs after emotional or physical stress. Norepinephrine levels are unusually high in the acute phase, suggesting a hyperadrenergic mechanism. Comparatively little is known about parasympathetic function in patients with TC. We sought to characterize autonomic function at rest and in response to physical and emotional stimuli in 10 women with a confirmed history of TC and 10 age-matched healthy women. Sympathetic and parasympathetic activity was assessed at rest and during baroreflex stimulation (Valsalva maneuver and tilt testing), cognitive stimulation (Stroop test), and emotional stimulation (event recall, patients). Ambulatory blood pressure monitoring and measurement of brachial artery flow-mediated vasodilation were also performed. TC women (tested an average of 37 months after the event) had excessive pressor responses to cognitive stress (Stroop test: p <0.001 vs baseline and p = 0.03 vs controls) and emotional arousal (recall of TC event: p = 0.03 vs baseline). Pressor responses to hemodynamic stimuli were also amplified (Valsalva overshoot: p <0.05) and prolonged (duration: p <0.01) in the TC women compared with controls. Plasma catecholamine levels did not differ between TC women and controls. Indexes of parasympathetic (vagal) modulation of heart rate induced by respiration and cardiovagal baroreflex gain were significantly decreased in the TC women versus controls. In conclusion, even long after the initial episode, women with previous episode of TC have excessive sympathetic responsiveness and reduced parasympathetic modulation of heart rate. Impaired baroreflex control may therefore play a role in TC.

BACKGROUND:Limited contemporary evidence exists on risk prediction by stress imaging and exercise electrocardiography (ECG) among patients with chronic coronary syndromes (CCS). Objectives From the ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) study, prognosis was examined by core laboratory-defined stress imaging and exercise ECG findings in CCS patients. METHODS:A total of 5,179 patients (qualifying by stress nuclear imaging [n = 2,567], echocardiography [n = 1,085], cardiac magnetic resonance [CMR] [n = 257], and ECG [n = 1,270]) were randomized. Cox models assessed associations between trial endpoints and the number of scarred and ischemic segments, rest/stress left ventricular ejection fraction (LVEF), and ST-segment depression. HRs and 95% CIs were calculated per millimeter, segment, or 5% of LVEF. We examined prognostic models for the following trial endpoints: 1) the trial's primary endpoint of cardiovascular (CV) death, myocardial infarction (MI), resuscitated cardiac arrest, or hospitalization for unstable angina or heart failure; 2) CV death; 3) spontaneous MI; 4) procedural MI; and 5) type 2 MI. RESULTS:The number of scarred segments (HR: 1.07 [95% CI: 1.02-1.13]; P = 0.0209), rest LVEF (HR: 0.88 [95% CI: 0.83-0.93]; P < 0.001), and stress LVEF (HR: 0.87 [95% CI: 0.83-0.91]; P < 0.001) predicted the trial's primary endpoint of CV death, MI, resuscitated cardiac arrest, or hospitalization for unstable angina or heart failure. The extent of scar and rest/stress LVEF on echocardiography and nuclear imaging predicted several trial endpoints. The number of ischemic segments predicted spontaneous (HR: 1.08 [95% CI: 1.03-1.14]; P = 0.0104) and procedural MI (HR: 1.14 [95% CI: 1.03-1.25]; P = 0.0015) but was of borderline significance for the trial's primary endpoint (P = 0.0746). Ischemia extent by CMR predicted the trial's primary endpoint (P = 0.0068) and spontaneous MI (P = 0.0042). CONCLUSIONS:ISCHEMIA trial findings from 320 worldwide centers revealed that stress imaging and exercise ECG measures exhibited a variable association with key trial endpoints delineating risk patterns for ischemia and infarction. Stress CMR ischemia predicted several trial endpoints, supporting an expanded role in the evaluation of patients with CCS (ISCHEMIA [International Study of Comparative Health Effectiveness With Medical and Invasive Approaches]; NCT01471522).

BACKGROUND/UNASSIGNED:Myeloproliferative neoplasms (MPN) are a group of chronic leukemias that are associated with pulmonary hypertension (PH), which has been associated with increased risk adverse outcomes. The echocardiographic characterization of PH in MPN has not been reported, and the prognostic significance of PH among patients with MPN remains unclear. METHODS/UNASSIGNED:Multicenter, retrospective cohort study of patients with MPN with ≥1 echocardiogram from 2010 to 2023. The echocardiographic probability of PH was determined according to the guidelines. The outcomes were hematologic progression and major adverse cardiovascular events. Exploratory analysis included outcomes among patients with right heart catheterization after the first echocardiogram, with PH defined as mean pulmonary artery pressure of >20 mm Hg. Multivariable Fine-Gray competing risk regression was used to estimate the subhazard ratio of hematologic progression and major adverse cardiovascular events. RESULTS/UNASSIGNED:=0.048). CONCLUSIONS/UNASSIGNED:Among patients with MPN, echocardiographic probability of PH was associated with an increased risk of hematologic progression. Prospective studies are needed to assess the optimal use of echocardiography on MPN-specific prognostication.

PURPOSE/OBJECTIVE:Patients with ischemia with no obstructive coronary arteries (INOCA) and myocardial infarction with no obstructive coronary arteries (MINOCA) may benefit from cardiac rehabilitation. Episodes of INOCA can be caused by different mechanisms including coronary microvascular dysfunction and coronary artery spasm, while episodes of MINOCA can be caused by plaque disruption (rupture or erosion), coronary artery spasm, or coronary embolism. Both conditions affect women more than men. REVIEW METHODS/METHODS:The current review evaluates available evidence on exercise and cardiac rehabilitation in patients with INOCA and MINOCA. SUMMARY/CONCLUSIONS:Small studies have shown that exercise training can result in improvements in endothelial function, myocardial perfusion, exercise capacity, and overall wellbeing and quality of life in patients with INOCA. Structured cardiac rehabilitation programs have also been shown to improve symptoms of angina, physical functioning, and quality of life for patients with INOCA. Studies of cardiac rehabilitation among patients with MINOCA have found that only one third participate in cardiac rehabilitation, but among those who do, observational studies and a randomized controlled trial demonstrate a lower risk of major adverse cardiovascular events (such as all-cause mortality and nonfatal myocardial infarction) with cardiac rehabilitation. However, given that INOCA and MINOCA are conditions that predominantly affect women and may be caused by non-atherosclerotic mechanisms, tailoring of traditional cardiac rehabilitation programs (eg, education components) may be desirable to meet the specific needs of these patients. Future studies should explore the effectiveness of tailored cardiac rehabilitation programs with novel delivery methods to optimize programs for patients with INOCA and MINOCA.

BACKGROUND:In the ISCHEMIA Trial, 5179 patients with stable coronary disease were randomized to initial invasive or conservative management. METHODS:PCI was recommended with a SYNTAX score 0-22 (low) and CABG with a SYNTAX score ≥33 (high). Either could be recommended for intermediate scores. The composite primary outcome was cardiovascular death, MI, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. There were two cohorts in this analysis. The descriptive cohort included patients who underwent CABG or PCI within 180 days of randomization and had no primary outcome before revascularization. The comparative cohort excluded participants with prior CABG, single vessel disease, SYNTAX score ≥ 45, and without core laboratory assessment. We focused on the intermediate (23-32) SYNTAX comparative group for which either CABG or PCI could be recommended. RESULTS:For 1935 patients in the descriptive cohort (485 CABG, 1450 PCI), the SYNTAX score was 27.3 ± 11.0 in the CABG group and 15.3 ± 8.6 in the PCI group, p<0.0001. Most patients with low SYNTAX scores underwent PCI (87.1%), while most with high SYNTAX scores underwent CABG (72.6%). For the 1203 patients (385 CABG, 818 PCI) in the entire comparative cohort, the adjusted 4-year primary event rate was 14.5% for CABG and 13.2% for PCI (difference 1.3%, 95% CI, -4.9% to 7.7%). For the 346 patients (163 CABG, 183 PCI) in the intermediate SYNTAX group, the adjusted 4-year primary event rate was 10.6% for CABG and 18.3% for PCI (difference -7.6%, 95% CI, -16.1% to 0.9%). CONCLUSIONS:Selection of revascularization method resulted in more PCI in the low SYNTAX group and more CABG in the high SYNTAX group. There was no statistical evidence of a difference between PCI and CABG in the intermediate SYNTAX group but the CIs are broad, reflecting uncertainty. GOV IDENTIFIER/UNASSIGNED:NCT01471522; https://clinicaltrials.gov/ct2/show/NCT01471522.

Pulmonary hypertension (PH) is a frequent complication of Philadelphia-negative myeloproliferative neoplasms (MPN), including essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF). However, its prognostic significance is understudied, thus we aimed to evaluate the effect of PH identified by echocardiography on risk of progression to secondary MF or acute leukemia in MPN patients. We conducted a multicenter, retrospective cohort study of MPN patients with ≥ 1 echocardiogram from 2010-2023. PH was defined as pulmonary artery systolic pressure (PASP) ≥ 40 mmHg. Outcomes were progression to secondary myelofibrosis or leukemia, major adverse cardiovascular event (MACE) and all-cause death. Multivariable Fine-Gray competing-risk regression was used to estimate subhazard ratio (SHR) of hematologic progression and MACE. 555 patients were included (42.7% PV, 41.1% ET, 16.2% MF) or which 195 (35.1%) had PH. Over a median follow-up period of 51.2 months, PH was associated with increased risk of secondary MF progression (aSHR 2.40, 95% CI 1.25-4.59), leukemia progression (aSHR 3.06, 95% CI 1.13 - 8.25), and MACE (aSHR 1.59, 95% CI 1.01- 2.49) but not all-cause death (aHR 1.48, 95% CI 0.96-2.26). Among patients with PH, absence of left heart disease (LHD) was associated with higher risk of secondary MF progression among patients with ET or PV (aSHR 2.76, 95% CI 1.19 - 6.38) and leukemia progression among patients with MF (aSHR 7.18, 95% CI 1.59-32.46). Prospective studies are needed to assess the role of echocardiography on MPNspecific prognostication.