Association of Myocardial Blood Flow Reserve With Adverse Left Ventricular Remodeling in Patients With Aortic Stenosis: The Microvascular Disease in Aortic Stenosis (MIDAS) Study.

Importance: Impaired myocardial flow reserve (MFR) and stress myocardial blood flow (MBF) on positron emission tomography (PET) myocardial perfusion imaging may identify adverse myocardial characteristics, including myocardial stress and injury in aortic stenosis (AS). Objective: To investigate whether MFR and stress MBF are associated with LV structure and function derangements, and whether these parameters improve after aortic valve replacement (AVR). Design, Setting, and Participants: In this single-center prospective observational study in Boston, Massachusetts, from 2018 to 2020, patients with predominantly moderate to severe AS underwent ammonia N13 PET myocardial perfusion imaging for myocardial blood flow (MBF) quantification, resting transthoracic echocardiography (TTE) for assessment of myocardial structure and function, and measurement of circulating biomarkers for myocardial injury and wall stress. Evaluation of health status and functional capacity was also performed. A subset of patients underwent repeated assessment 6 months after AVR. A control group included patients without AS matched for age, sex, and summed stress score who underwent symptom-prompted ammonia N13 PET and TTE within 90 days. Exposures: MBF and MFR quantified on ammonia N13 PET myocardial perfusion imaging. Main Outcomes and Measures: LV structure and function parameters, including echocardiographic global longitudinal strain (GLS), circulating high-sensitivity troponin T (hs-cTnT), N-terminal pro-B-type natriuretic peptide (NT-pro BNP), health status, and functional capacity. Results: There were 34 patients with AS (1 mild, 9 moderate, and 24 severe) and 34 matched control individuals. MFR was independently associated with GLS and LV ejection fraction, (ß,-0.31; P = .03; ß, 0.41; P = .002, respectively). Stress MBF was associated with hs-cTnT (unadjusted ß, -0.48; P = .005) and log NT-pro BNP (unadjusted ß, -0.37; P = .045). The combination of low stress MBF and high hs-cTnT was associated with higher interventricular septal thickness in diastole, relative wall thickness, and worse GLS compared with high stress MBF and low hs-cTnT (12.4 mm vs 10.0 mm; P = .008; 0.62 vs 0.46; P = .02; and -13.47 vs -17.11; P = .006, respectively). In 9 patients studied 6 months after AVR, mean (SD) MFR improved from 1.73 (0.57) to 2.11 (0.50) (P = .008). Conclusions and Relevance: In this study, in AS, MFR and stress MBF were associated with adverse myocardial characteristics, including markers of myocardial injury and wall stress, suggesting that MFR may be an early sensitive marker for myocardial decompensation.

Investigating the Association Between Telemedicine Use and Timely Follow-Up Care After Acute Cardiovascular Hospital Encounters.

Background: Telemedicine use increased dramatically during the COVID-19 pandemic; however, questions remain as to how telemedicine use impacts care. Objectives: The purpose of this study was to examine the association of increased telemedicine use on rates of timely follow-up and unplanned readmission after acute cardiovascular hospital encounters. Methods: We examined hospital encounters for acute coronary syndrome, arrhythmia disorders, heart failure (HF), and valvular heart disease from a large U.S., multisite, integrated academic health system among patients with established cardiovascular care within the system. We evaluated 14-day postdischarge follow-up and 30-day all-cause unplanned readmission rates for encounters from the pandemic "steady state" period from May 24, 2020 through December 31, 2020, when telemedicine use was high and compared them to those of encounters from the week-matched period in 2019 (May 26, 2019, through December 31, 2019), adjusting for patient and encounter characteristics. Results: The study population included 6,026 hospital encounters. In the pandemic steady-state period, 40% of follow-ups after these encounters were conducted via telemedicine vs 0% during the week-matched period in 2019. Overall, 14-day follow-up rates increased from 41.7% to 44.9% (adjusted difference: +2.0 percentage points [pp], 95% CI: -1.1 to +5.1 pp, P = 0.20). HF encounters experienced the largest improvement from 50.1% to 55.5% (adjusted difference: +6.5 pp, 95% CI: +0.5 to +12.4 pp, P = 0.03). Overall 30-day all-cause unplanned readmission rates fell slightly, from 18.3% to 16.9% (adjusted difference -1.6 pp; 95% CI: -4.0 to +0.8 pp, P = 0.20). Conclusions: Increased telemedicine use during the COVID-19 pandemic was associated with earlier follow-ups, particularly after HF encounters. Readmission rates did not increase, suggesting that the shift to telemedicine did not compromise care quality.

Virtual optimization of guideline-directed medical therapy in hospitalized patients with heart failure with reduced ejection fraction: the IMPLEMENT-HF pilot study.

AIMS: Implementation of guideline-directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF) remains incomplete. Non-cardiovascular hospitalization may present opportunities for GDMT optimization. We assessed the efficacy and durability of a virtual, multidisciplinary 'GDMT Team' on medical therapy prescription for HFrEF. METHODS AND RESULTS: Consecutive hospitalizations in patients with HFrEF (ejection fraction ≤40%) were prospectively identified from 3 February to 1 March 2020 (usual care group) and 2 March to 28 August 2020 (intervention group). Patients with critical illness, de novo heart failure, and systolic blood pressure <90 mmHg in the preceeding 24 hs prior to enrollment were excluded. In the intervention group, a pharmacist-physician GDMT Team provided optimization suggestions to treating teams based on an evidence-based algorithm. The primary outcome was a GDMT optimization score, the sum of positive (+1 for new initiations or up-titrations) and negative therapeutic changes (-1 for discontinuations or down-titrations) at hospital discharge. Serious in-hospital safety events were assessed. Among 278 consecutive encounters with HFrEF, 118 met eligibility criteria; 29 (25%) received usual care and 89 (75%) received the GDMT Team intervention. Among usual care encounters, there were no changes in GDMT prescription during hospitalization. In the intervention group, ß-blocker (72% to 88%; P = 0.01), angiotensin receptor-neprilysin inhibitor (6% to 17%; P = 0.03), mineralocorticoid receptor antagonist (16% to 29%; P = 0.05), and triple therapy (9% to 26%; P < 0.01) prescriptions increased during hospitalization. After adjustment for clinically relevant covariates, the GDMT Team was associated with an increase in GDMT optimization score (+0.58; 95% confidence interval +0.09 to +1.07; P = 0.02). There were no serious in-hospital adverse events. CONCLUSIONS: Non-cardiovascular hospitalizations are a potentially safe and effective setting for GDMT optimization. A virtual GDMT Team was associated with improved heart failure therapeutic optimization. This implementation strategy warrants testing in a prospective randomized controlled trial.

Fewer Hospitalizations for Acute Cardiovascular Conditions During the COVID-19 Pandemic.

BACKGROUND: Although patients with cardiovascular disease face excess risks of severe illness with coronavirus disease-2019 (COVID-19), there may be indirect consequences of the pandemic on this high-risk patient segment. OBJECTIVES: This study sought to examine longitudinal trends in hospitalizations for acute cardiovascular conditions across a tertiary care health system. METHODS: Acute cardiovascular hospitalizations were tracked between January 1, 2019, and March 31, 2020. Daily hospitalization rates were estimated using negative binomial models. Temporal trends in hospitalization rates were compared across the first 3 months of 2020, with the first 3 months of 2019 as a reference. RESULTS: From January 1, 2019, to March 31, 2020, 6,083 patients experienced 7,187 hospitalizations for primary acute cardiovascular reasons. There were 43.4% (95% confidence interval [CI]: 27.4% to 56.0%) fewer estimated daily hospitalizations in March 2020 compared with March 2019 (p < 0.001). The daily rate of hospitalizations did not change throughout 2019 (-0.01% per day [95% CI: -0.04% to +0.02%]; p = 0.50), January 2020 (-0.5% per day [95% CI: -1.6% to +0.5%]; p = 0.31), or February 2020 (+0.7% per day [95% CI: -0.6% to +2.0%]; p = 0.27). There was significant daily decline in hospitalizations in March 2020 (-5.9% per day [95% CI: -7.6% to -4.3%]; p < 0.001). Length of stay was shorter (4.8 days [25th to 75th percentiles: 2.4 to 8.3 days] vs. 6.0 days [25th to 75th percentiles: 3.1 to 9.6 days]; p = 0.003) and in-hospital mortality was not significantly different (6.2% vs. 4.4%; p = 0.30) in March 2020 compared with March 2019. CONCLUSIONS: During the first phase of the COVID-19 pandemic, there was a marked decline in acute cardiovascular hospitalizations, and patients who were admitted had shorter lengths of stay. These data substantiate concerns that acute care of cardiovascular conditions may be delayed, deferred, or abbreviated during the COVID-19 pandemic.

Isolated surgical left atrial appendage closure: Revisiting utility and indications in a burgeoning era of percutaneous therapy.

BACKGROUND AND AIM: Oral anticoagulation (AC) and percutaneous left atrial appendage (LAA) occlusion are the primary treatment modalities for stroke prevention in atrial fibrillation (AF), but there remains a subset of patients in whom these approaches present excess risk and isolated surgical LAA excision should be considered. We describe a 63-year-old female with AF and recurrent thromboembolic events who presented with an acute intraparenchymal hemorrhage and was found to have an intracardiac thrombus. METHODS: Given contraindications to AC and LAA occlusion, an isolated LAA surgical excision was pursued. RESULTS: She underwent successful surgical LAA excision and has since remained event-free. CONCLUSION: It is important to recall the utility of therapies that have been previously used with success for intracardiac thrombi and still remain as viable options.

Non-functional tricuspid valve disease.

Only 75% of severe tricuspid regurgitation is classified as functional, or related primarily to pulmonary hypertension, right ventricular dysfunction, or a combination of both. Non-functional tricuspid regurgitation occurs when there is damage to the tricuspid leaflets, chordae, papillary muscles, or annulus, independent of right ventricular dysfunction or pulmonary hypertension. The entities that cause non-functional tricuspid regurgitation include rheumatic and myxomatous disease, acquired and genetic connective tissue disorders, endocarditis, sarcoid, pacing, RV biopsy, blunt trauma, radiation, carcinoid, ergot alkaloids, dopamine agonists, fenfluramine, cardiac tumors, atrial fibrillation, and congenital malformations. Over time, severe tricuspid regurgitation that is initially non-functional, can blend into functional tricuspid regurgitation, related to progressive right ventricular dysfunction. Symptoms and signs, including a falling right ventricular ejection fraction, cardiac cirrhosis, ascites, esophageal varices, and anasarca, may occur insidiously and late, but are associated with substantial morbidity and mortality. Attempted valve repair or replacement at late stages carries a high mortality. Crucial to following patients with severe non-functional tricuspid regurgitation is attention to echo quantification of the tricuspid regurgitation and right ventricular function, patient symptoms, and the physical examination.

Sex, clinical symptoms, and angiographic findings in patients with diabetes mellitus and coronary artery disease (from the Bypass Angioplasty Revascularization Investigation [BARI] 2 Diabetes trial).

Previous studies have reported differences in presenting symptoms and angiographic characteristics between women and men undergoing evaluation for suspected coronary artery disease (CAD). We examined the relation between symptoms and extent of CAD in patients with type 2 diabetes mellitus and known CAD enrolled in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial. Of 1,775 patients (533 women, 30%, and 1,242 men, 70%), women were more likely than men to have angina (65% vs 56%, p <0.001) or an atypical angina/anginal equivalent (71% vs 58%, p <0.001). More women reported unstable angina (17% vs 13%, p = 0.047) or were in a higher Canadian Cardiology Society class compared to men (Canadian Cardiology Society classes II to IV 78% vs 68%, p = 0.002). Fewer women than men had no symptoms (14% vs 22%, p <0.001). Women had a lower mean myocardial jeopardy index (42.5 ± 24.3 vs 47.9 ± 24.3, p <0.001), smaller number of total significant lesions (2.3 ± 1.7 vs 2.7 ± 1.8, p <0.001), and fewer jeopardized left ventricular regions (p <0.001 for distribution) or long-term occlusions (29% vs 42%, p <0.001). After adjustment for relevant covariates, the odds of having CAD symptoms were still higher in women than men (odds ratio for angina 1.31, 95% confidence interval 1.02 to 1.69; odds ratio for atypical angina 1.52, 95% confidence interval 1.17 to 1.96). In conclusion, in a high-risk group of patients with known CAD and diabetes mellitus, women were more symptomatic than men but had less obstructive CAD. These data suggest that factors other than epicardial CAD severity influence symptom presentation in women in this population.

Safety and efficacy of bone marrow-derived autologous CD133+ stem cell therapy.

The Phase I clinical study was designed to assess the safety and feasibility of a dose escalating intracoronary infusion of autologous bone marrow (BM)-derived CD133+ stem cell therapy to the patients with chronic total occlusion (CTO) and ischemia. Nine patients were received CD133+ cells into epicardial vessels supplying collateral flow to areas of viable ischemic myocardium in the distribution of the CTO. There were no major adverse cardiac events (MACE), revascularization, re-admission to the hospital secondary to angina, or acute myocardial infarction (AMI) for the 24-month period following cellular infusion. In addition, there were no periprocedural infusion-related complications including malignant arrhythmias, loss of normal coronary blood flow or acute neurologic events. Cardiac enzymes were negative in all patients. There was an improvement in the degree of ischemic myocardium, which was accompanied by a trend towards reduction in anginal symptoms. Intracoronary infusion of autologous CD133+ marrow-derived cells is safe and feasible. Cellular therapy with CD133+ cells to reduce anginal symptoms and to improve ischemia in patients with CTO awaits clinical investigation in Phase II/III trials.

Is chronic kidney disease comparable to diabetes as a coronary artery disease risk factor?

BACKGROUND: Chronic kidney disease (CKD) is one of the known risk factors for coronary heart disease (CHD). Though electrocardiograms (ECGs) have limited accuracy in determining the true prevalence of CHD, we wondered whether CKD and diabetes mellitus (DM) controlled for hypertension (HTN), had similar prevalences of ECG abnormalities that could reflect underlying coronary heart disease. METHOD: Data were collected for 5,942 men and women aged 30 to 69 years in the Tehran Lipid and Glucose Study (TLGS), a crosssectional phase of a large epidemiologic study first initiated in 1999. ECG findings of all subjects were coded according to Minnesota ECG coding criteria. The Whitehall criteria for abnormal ECG findings that could represent ischemia were utilized. Creatinine clearance (Crcl) was estimated using the Cockroft-Gault equation and diabetes was defined according to the American Diabetic Association (ADA) criteria. Subjects with moderate CKD and without DM were compared with the patients with DM without CKD. HTN prevalence was similar. The analysis was performed for all Whitehall ECG ischemia abnormalities combined, and separately for pathologic Q waves. RESULTS: In spite of an overall similar prevalence of smoking, and a lower incidence of dyslipidemia and HTN, moderate CKD patients had a higher prevalence of Whitehall criteria abnormal ECG findings compared with the patients with DM. Over 19% of patients with CKD had abnormal ECG findings while 14.7% of diabetic patients had abnormal ECGs (P = 0.02). The prevalence of Q waves was 11.5% in patients with CKD and 10.8% in patients with DM. In an age-matched subgroup of patients with DM and no CKD, the prevalence of ECG abnormalities was 19.3%, similar to the patients with moderate CKD and no DM (19.7%) (P = 0.9). The prevalence of pathologic Q waves in an age-matched group was 11.45%, compared with 11.5%, respectively. CONCLUSION: Moderate CKD is a major risk factor for the development of the Whitehall ECG criteria which have been associated with ischemic heart disease. The importance of CKD as a risk factor for ECG abnormalities is comparable with DM. Patients with moderate CKD probably are candidates for aggressive CHD risk modification.

Cardiogenic shock in hypothyroidism.

A patient with minimal coronary artery disease presented in cardiogenic shock when her previously undiagnosed hypothyroid state was complicated by an episode of AV nodal re-entrant tachycardia. She did not respond to multiple pressors, and recovered dramatically after starting thyroid supplementation. Hypothyroidism caused her lack of responsiveness to pressors and perpetuated her hypotension and increased filling pressures long after she reverted to a sinus rhythm. Our case dramatically demonstrates the severe lack of physiologic reserve that can be associated with hypothyroidism.

Is it time to prescribe statins to patients with calcified aortic stenosis?

Aortic stenosis (AS) is a common disease especially in the older population. It is associated with high mortality and morbidity. Recent data suggest that coronary artery disease and AS share common risk factors. Retrospective studies suggest that statins might slow the progression of AS but there are no randomized clinical trial data available. It would seem that statins can be considered for medical treatment of AS; however, this needs to be investigated in future randomized clinical trials.