DeMaria, Anthony N.

Background: Treatment options for refractory angina not amenable to revascularization are limited. Extracorporeal shockwave myocardial revascularization (ESMR) is a novel non-invasive application of low intensity shock waves that stimulates angiogenesis to improve ischemia. We aimed to determine the safety and efficacy of ESMR in patients with refractory angina. Methods: A single-arm multicenter U.S. prospective trial was implemented to assess safety and efficacy of ESMR therapy in patients with Class III/Class IV refractory angina. Each patient received 9 sessions of ESMR to ischemic areas over 9 weeks. Efficacy was assessed at baseline and 4 months after treatment by maximal treadmill exercise time and ischemic burden on pharmacological single photon emission computed tomography (SPECT). Safety was assessed by incidence of adverse events, electrocardiography, echocardiography, laboratory markers, and pain questionnaires. Results: Fifteen patients with medically refractory angina were enrolled. Exercise treadmill time from baseline to last follow-up after ESMR increased significantly (38%) by 122.3±156.9 seconds (319.8±157.2 vs. 422.1±183.3 seconds, p=0.016) (Figure 1). There was no difference in the mean summed stress score (SSS) on pharmacological-SPECT 4 months after treatment vs. baseline (17.8±14.9 vs. 21.2±15.3, p=0.233). However, SPECT SSS revealed that untreated areas had greater progression in ischemic burden vs. treated areas (3.69±6.2 vs. 0.31±4.5, p=0.038). There was no significant change in the mean summed echo score from baseline to post treatment (0.4±5.1, p=0.79).There were no changes in electrocardiography, echocardiographic parameters, or laboratory markers. No serious adverse events or complications occurred, and pain with ESMR was minimal (score of 0.5±1.2 to 1.1±1.2 out of 10). Conclusions: We find that ESMR is a safe and efficacious treatment which may be clinically feasible for patients with refractory angina pectoris.

Introduction: The relationship between aortic stenosis (AS) severity, AS-related symptoms, and clinical outcomes is poorly understood. Research Question: Does a history of AS-related symptoms at the time of diagnosis affect clinical outcomes including death and AS-related hospitalization? Methods: Using a combination of natural language processing algorithms and administrative codes, we ascertained physician-assessed AS, AS severity, and AS-related symptoms (chest pain, acute coronary syndrome, syncope, presyncope, orthopnea, dyspnea, PND, and worsening heart failure) in the year prior or up to 60 days after an initial AS diagnosis among 602,821 adults with echocardiograms in a large, integrated health system from 2010-2019. We examined multivariable associations between AS severity and recent AS-related symptoms for the outcomes of death and AS-related hospitalizations using Cox models. Results: Among 40,333 patients identified with incident AS, the majority had recent AS-related symptoms (mild: 80%, mild-moderate: 77%, moderate: 77%, moderate-severe: 85%, and severe AS: 87%). Patients with recent symptoms were older (mean [SD] age 78 [10] vs 75 [11] years; p<0.01), more likely female (51% vs 47%; p<0.01), and had a higher comorbidity burden. In unadjusted analyses, symptom status was a strong discriminator of risk over a median (IQR) of 2.2 (0.8-4.3) years of follow-up ( Figure ). After multivariable adjustment, AS-related symptoms remained strongly associated with death and AS-related hospitalization across the spectrum of AS severity, with moderate symptomatic patients having risk similar to severe asymptomatic patients. Conclusions: The majority of patients diagnosed with AS have recent and/or active AS-related symptoms, which is associated with a significantly increased risk of adverse outcomes. Incorporating symptom status across the individual grades of AS may improve risk stratification beyond AS severity alone.

Abstract The concept that cell-based repair of myocardial injury might be possible was introduced almost two decades ago; however, the field of cardiovascular reparative medicine has been criticized as translation to clinically effective approaches has been slow. The recent retraction of a series of papers has further impacted perception of this area of research. As researchers, clinicians, and teachers in this field, we felt it incumbent to critically appraise the current state of cardiac cell repair, determine what can be learned from past mistakes, and formulate best practices for future work. This special communication summarizes an introspective assessment of what has fallen short, how to prevent similar issues, and how the field might best move forward in the service of science and patients.

Background— β-Blockers improve survival and reduce hospitalization in chronic heart failure (CHF) by biologically improving left ventricular ejection fraction (LVEF). However, a good predictor of improvement with this therapy has not been identified. This substudy of BEST examined whether myocardial contractile reserve, as determined by dobutamine stress echocardiography, predicts improvement in LVEF. Methods and Results— Seventy-nine patients with class III/IV CHF underwent dobutamine stress echocardiography before treatment with bucindolol (n=41) or placebo (n=38). Regional wall motion score index (WMSI) was calculated as the sum of the scores in each segment divided by the total number of segments visualized. WMSI was compared with change in LVEF after 3 months of therapy as determined by gated radionuclide scan. Change in WMSI correlated inversely with change in LVEF after 3 months of bucindolol ( r =−0.72, P <0.0001) and was the most significant multivariate predictor of change in LVEF ( P =0.0002). Patients with contractile reserve had demographics similar to those of patients without contractile reserve, including RVEF, LVEF, systolic blood pressure, and CHF duration. However, patients without contractile reserve had higher baseline plasma norepinephrine levels (687±333 versus 420±246 pg/mL, P <0.05) and greater decrease in plasma norepinephrine in response to bucindolol (−249±171 versus −35±277 pg/mL, P <0.05). Conclusions— This study suggests a direct relationship between contractile reserve and improvement in LVEF with β-blocker therapy in patients with advanced CHF. Patients without contractile reserve have higher resting adrenergic drive, as reflected by plasma norepinephrine, and may experience greater sympatholytic effects from bucindolol.