Mitral regurgitation carries greater prognostic significance than mitral stenosis in patients undergoing transcatheter aortic valve replacement.

AIMS: This study assessed the outcomes of concomitant mitral valve disease and severe aortic stenosis in patients undergoing transcatheter aortic valve replacement (TAVR). METHODS: Echocardiographic data of 813 patients with severe aortic stenosis undergoing transfemoral TAVR were collected, and clinical outcomes were analyzed for individuals with mitral stenosis and mitral regurgitation. RESULTS: The final cohort includes 788 patients with severe calcific aortic stenosis. Among single parameters of mitral stenosis, a smaller baseline mitral valve area (MVA) by the continuity equation and higher postprocedural mean mitral gradients (MMG) were associated with an increased risk of death at 1 year (P-values 0.02 and <0.01, respectively), but no correlation with outcomes was demonstrated after multivariate adjustment for major prognosticators. Mitral stenosis (based on MVA + MMG) was not associated with complications or mortality. Mitral regurgitation was present in 94.6% of the population at baseline and regressed by at least one grade post-TAVR in 28% of the patients. The improvement in mitral regurgitation was associated with a greater prosthetic effective orifice area (P-value 0.03). Significant (at least moderate) residual mitral regurgitation was correlated with short-term complications and shown to be an independent predictor of 1-year mortality (P-value 0.02, odds ratio (OR) 5.37, confidence interval 1.34-21.5). CONCLUSION: Mitral regurgitation has a greater impact on TAVR patients than mitral stenosis as assessed by functional methods.

Spontaneous Right Intrapetrous Internal Carotid Dissection in a Patient With Active COVID-19.

Spontaneous cervical artery dissection, a nontraumatic tear in the wall of an internal carotid or vertebral artery, is a common cause of stroke, particularly in patients younger than 40 years of age; however, petrous internal carotid artery dissection is extremely rare. This case report describes a 50-year-old woman who had a spontaneous intrapetrous internal carotid dissection thought to be secondary to active SARS-CoV-2 infection; the dissection was treated successfully with a flow-diverter stent.

Cardiovascular Disease Management With Sodium-Glucose Cotransporter-2 Inhibitors in Patients With Type 2 Diabetes: A Cardiology Primer.

Patients with type 2 diabetes face an elevated risk of cardiovascular disease. This review centers on sodium-glucose cotransporter-2 (SGLT2) inhibitors, a class of drugs that, according to a growing body of evidence, may have major potential for managing cardiovascular disease in patients with type 2 diabetes. This review presents findings from multiple clinical trials suggesting that SGLT2 inhibitors can not only serve as preventive therapeutic agents but also play a role in the active management of heart failure. The discussion includes the mechanism of action of SGLT2 inhibitors, emphasizing that they enhance urinary glucose excretion, which could lead to improved glycemic control and contribute to metabolic shifts beneficial to cardiac function. Alongside these cardiometabolic effects, safety concerns and practical considerations for prescribing these agents are addressed, taking into account potential adverse effects such as genitourinary infections and diabetic ketoacidosis as well as the financial implications for patients. Despite these drawbacks, therapeutic indications for SGLT2 inhibitors continue to expand, including for kidney protection, although further research is necessary to fully understand the mechanisms driving the cardioprotective and kidney-protective effects of SGLT2 inhibitors. By synthesizing current knowledge, this review intends to inform and guide clinical decision-making, thereby enhancing cardiovascular disease outcomes in patients with type 2 diabetes.

Randomized, double-blind pilot study of transendocardial injection of autologous aldehyde dehydrogenase-bright stem cells in patients with ischemic heart failure.

BACKGROUND: The optimal type of stem cell for use in patients with ischemic heart disease has not been determined. A primitive population of bone marrow-derived hematopoietic cells has been isolated by the presence of the enzyme aldehyde dehydrogenase and comprises a multilineage mix of stem and progenitor cells. Aldehyde dehydrogenase-bright (ALDH(br)) cells have shown promise in promoting angiogenesis and providing perfusion benefits in preclinical ischemia studies. We hypothesize that ALDH(br) cells may be beneficial in treating ischemic heart disease and thus conducted the first randomized, controlled, double-blind study to assess the safety of the transendocardial injection of autologous ALDH(br) cells isolated from the bone marrow in patients with advanced ischemic heart failure. METHODS: Aldehyde dehydrogenase-bright cells were isolated from patients' bone marrow on the basis of the expression of a functional (aldehyde dehydrogenase) marker. We enrolled 20 patients (treatment, n = 10; control, n = 10). Safety (primary end point) and efficacy (secondary end point) were assessed at 6 months. RESULTS: No major adverse cardiovascular or cerebrovascular events occurred in ALDH(br)-treated patients in the periprocedural period (up to 1 month); electromechanical mapping-related ventricular tachycardia (n = 2) and fibrillation (n = 1) occurred in control patients. Aldehyde dehydrogenase-bright-treated patients showed a significant decrease in left ventricular end-systolic volume at 6 months (P = .04) and a trend toward improved maximal oxygen consumption. The single photon emission computed tomography delta analysis showed a trend toward significant improvement in reversibility in cell-treated patients (P = .053). CONCLUSIONS: We provide preliminary evidence that treatment with the novel cell population, ALDH(br) cells, is safe and may provide perfusion and functional benefits in patients with chronic myocardial ischemia.

Artificial Intelligence in Echocardiography.

Artificial intelligence in diagnostic cardiac-imaging platforms is advancing rapidly. In particular, artificial intelligence algorithms have increased the efficiency and accuracy of echocardiographic cardiovascular imaging, resulting in more complex echocardiographic imaging techniques and expanded use among noncardiologists. Here, we provide an overview of real-world applications of artificial intelligence in echocardiography including automatic high-quality computer-optimized image acquisition sequences, automated measurements, and algorithms for the rapid and accurate interpretation of cardiac physiology. These advances will not replace physicians but will improve their productivity, workflow, and diagnostic performance.

Evaluation of Factors Underlying Sex-Based Disparities in Cardiovascular Care in Adults With Self-reported Premature Atherosclerotic Cardiovascular Disease.

IMPORTANCE: There are limited data regarding sex-based differences in physical and mental health domains and health care access in adults with premature atherosclerotic cardiovascular disease (ASCVD). OBJECTIVE: To study the association of sex with physical and mental health domains as well as health care access-related factors among adults with self-reported premature ASCVD. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort analysis of 748 090 adults aged 18 to 55 years in the Behavioral Risk Factor Surveillance System 2016 to 2019 in the US. Data were analyzed from June to July 2021. EXPOSURES: Self-reported ASCVD, defined as having a history of coronary artery disease, myocardial infarction, or stroke. MAIN OUTCOMES AND MEASURES: Self-reported physical and mental health and measures of health care access, including self-reported cost-related medication nonadherence and inability to see a physician due to cost. RESULTS: Between 2016 and 2019, 748 090 adults aged 18-55 years were identified, of whom 28 522 (3.3%) had self-reported premature ASCVD. Of these, 14 358 (47.0%) were women. Compared with men, women with premature ASCVD were more likely to report being clinically depressed (odds ratio [OR], 1.73; 95% CI, 1.41-2.14; P < .001), have cost-related medication nonadherence (OR, 1.42; 95% CI, 1.11-1.82; P = .005), have not seen a physician due to cost-related issues (OR, 4.52; 95% CI, 2.24-9.13; P < .001), and were more likely to report overall poor physical health (OR, 1.39; 95% CI, 1.09-1.78; P = .008) despite being more likely to have health care coverage (85.3% vs 80.8%; P = .04) and a primary care physician (84.2% vs 75.7%; P < .001). CONCLUSIONS AND RELEVANCE: Results from this study indicate that women with premature ASCVD were more likely to report worse overall physical and mental health, inability to see a physician due to cost, and cost-related medical nonadherence. Interventions addressing mental health and out-of-pocket costs are needed in adults with premature ASCVD.

A randomized study of transendocardial injection of autologous bone marrow mononuclear cells and cell function analysis in ischemic heart failure (FOCUS-HF).

BACKGROUND: Autologous bone marrow mononuclear cell (ABMMNC) therapy has shown promise in patients with heart failure (HF). Cell function analysis may be important in interpreting trial results. METHODS: In this prospective study, we evaluated the safety and efficacy of the transendocardial delivery of ABMMNCs in no-option patients with chronic HF. Efficacy was assessed by maximal myocardial oxygen consumption, single photon emission computed tomography, 2-dimensional echocardiography, and quality-of-life assessment (Minnesota Living with Heart Failure and Short Form 36). We also characterized patients' bone marrow cells by flow cytometry, colony-forming unit, and proliferative assays. RESULTS: Cell-treated (n = 20) and control patients (n = 10) were similar at baseline. The procedure was safe; adverse events were similar in both groups. Canadian Cardiovascular Society angina score improved significantly (P = .001) in cell-treated patients, but function was not affected. Quality-of-life scores improved significantly at 6 months (P = .009 Minnesota Living with Heart Failure and P = .002 physical component of Short Form 36) over baseline in cell-treated but not control patients. Single photon emission computed tomography data suggested a trend toward improved perfusion in cell-treated patients. The proportion of fixed defects significantly increased in control (P = .02) but not in treated patients (P = .16). Function of patients' bone marrow mononuclear cells was severely impaired. Stratifying cell results by age showed that younger patients (≤60 years) had significantly more mesenchymal progenitor cells (colony-forming unit fibroblasts) than patients >60 years (20.16 ± 14.6 vs 10.92 ± 7.8, P = .04). Furthermore, cell-treated younger patients had significantly improved maximal myocardial oxygen consumption (15 ± 5.8, 18.6 ± 2.7, and 17 ± 3.7 mL/kg per minute at baseline, 3 months, and 6 months, respectively) compared with similarly aged control patients (14.3 ± 2.5, 13.7 ± 3.7, and 14.6 ± 4.7 mL/kg per minute, P = .04). CONCLUSIONS: ABMMNC therapy is safe and improves symptoms, quality of life, and possibly perfusion in patients with chronic HF.

Hemodynamic outcomes after valve-in-valve transcatheter aortic valve replacement: a single-center experience.

BACKGROUND: Valve-in-valve transcatheter aortic valve replacement (ViV-TAVR) has emerged as a safe, effective alternative to redo aortic valve surgery in high-risk patients with degenerated surgical bioprosthetic valves. However, ViV-TAVR has been associated high postprocedural valvular gradients, compared with TAVR for native-valve aortic stenosis. METHODS: We performed a retrospective study of all patients who underwent ViV-TAVR for a degenerated aortic valve bioprosthesis between January 1, 2013 and March 31, 2019 at our center. The primary outcome was postprocedural mean aortic valve gradient. Outcomes were compared across surgical valve type (stented versus stentless), surgical valve internal diameter (≤19 versus >19 mm), and transcatheter aortic valve type (self-expanding vs. balloon-expandable). RESULTS: Overall, 89 patients underwent ViV-TAVR. Mean age was 69.0±12.6 years, 61% were male, and median Society of Thoracic Surgeons Predicted Risk of Mortality score was 5.4 [interquartile range, 3.2-8.5]. Bioprosthesis mode of failure was stenotic (58% of patients), regurgitant (24%), or mixed (18%). The surgical valve was stented in 75% of patients and stentless in 25%. The surgical valve's internal diameter was ≤19 mm in 45% of cases. A balloon-expandable transcatheter valve was used in 53% of procedures. Baseline aortic valve area and mean gradients were 0.87±0.31 cm2 and 36±18 mmHg, respectively. These improved after ViV-TAVR to 1.38±0.55 cm2 and 18±11 mmHg at a median outpatient follow-up of 331 [67-394] days. Higher postprocedural mean gradients were associated with surgical valves having an internal diameter ≤19 mm (24±13 versus 16±8, P=0.002) and with stented surgical valves (22±11 versus 12±6, P<0.001). CONCLUSIONS: ViV-TAVR is an effective option for treating degenerated surgical aortic bioprostheses, with acceptable hemodynamic outcomes. Small surgical valves and stented surgical valves are associated with higher postprocedural gradients.

Transcatheter aortic valve replacement after chest radiation: A propensity-matched analysis.

BACKGROUND: Chest radiation therapy (CRT) for malignant thoracic neoplasms is associated with development of valvular heart disease years later. As previous radiation exposure can complicate surgical treatment, transcatheter aortic valve replacement (TAVR) has emerged as an alternative. However, outcomes data are lacking for TAVR patients with a history of CRT. METHODS: We conducted a retrospective study of all patients who underwent a TAVR procedure at a single institution between September 2012 and November 2018. Among 1341 total patients, 50 had previous CRT. These were propensity-matched in a 1:2 ratio to 100 patients without history of CRT. Thirty-day adverse events were analyzed with generalized estimating equation models. Overall mortality was analyzed with stratified Cox regression modelling. RESULTS: Median clinical follow-up was 24 months (interquartile range [IQR], 12-44 months). There was no difference between CRT and non-CRT patients in overall mortality (hazard ratio [HR] 0.84 [0.37-1.90], P = 0.67), 30-day mortality (HR 3.1 [0.49-20.03], P = 0.23), or 30-day readmission rate (HR 1.0 [0.43-2.31], P = 1). There were no differences in the rates of most adverse events, but patients with CRT history had higher rates of postprocedural respiratory failure (HR 3.63 [1.32-10.02], P = 0.01) and permanent pacemaker implantation (HR 2.84 [1.15-7.01], P = 0.02). CONCLUSIONS: For patients with aortic valve stenosis and previous CRT, TAVR is safe and effective, with outcomes similar to those in the general aortic stenosis population. Patients with history of CRT are more likely to have postprocedural respiratory failure and to require permanent pacemaker implantation.

Young athletes: Preventing sudden death by adopting a modern screening approach? A critical review and the opening of a debate.

Preventing sudden cardiac death (SCD) in athletes is a primary duty of sports cardiologists. Current recommendations for detecting high-risk cardiovascular conditions (hr-CVCs) are history and physical examination (H&P)-based. We discuss the effectiveness of H&P-based screening versus more-modern and accurate methods. In this position paper, we review current authoritative statements and suggest a novel alternative: screening MRI (s-MRI), supported by evidence from a preliminary population-based study (completed in 2018), and a prospective, controlled study in military recruits (in development). We present: 1. Literature-Based Comparisons (for diagnosing hr-CVCs): Two recent studies using traditional methods to identify hr-CVCs in >3,000 young athletes are compared with our s-MRI-based study of 5,169 adolescents. 2. Critical Review of Previous Results: The reported incidence of SCD in athletes is presently based on retrospective, observational, and incomplete studies. H&P's screening value seems minimal for structural heart disease, versus echocardiography (which improves diagnosis for high-risk cardiomyopathies) and s-MRI (which also identifies high-risk coronary artery anomalies). Electrocardiography is valuable in screening for potentially high-risk electrophysiological anomalies. 3. Proposed Project : We propose a prospective, controlled study (2 comparable large cohorts: one historical, one prospective) to compare: (1) diagnostic accuracy and resulting mortality-prevention performance of traditional screening methods versus questionnaire/electrocardiography/s-MRI, during 2-month periods of intense, structured exercise (in military recruits, in advanced state of preparation); (2) global costs and cost/efficiency between these two methods. This study should contribute significantly toward a comprehensive understanding of the incidence and causes of exercise-related mortality (including establishing a definition of hr-CVCs) while aiming to reduce mortality.

Histopathological study of healing after allogenic mesenchymal stem cell delivery in myocardial infarction in dogs.

In this histological study, we assessed the role of mesenchymal stem cells (MSCs) in the healing process that takes place during the subacute phase of myocardial infarction in dogs. Seven days after occlusion of the left anterior descending coronary artery, adult mongrel dogs received 100 x 10(6) 4'-6-diamidino-2-phenylindole (DAPI)-labeled allogenic bone marrow-derived MSCs by the transendocardial (TE, n=6) and intracoronary (IC, n=4) routes; control dogs (n=6) received no infusion. The dogs were euthanized at 21 days after occlusion. Hearts were excised and sliced from apex to base into four transverse sections, which were divided into nine segments. Paraffin sections from each segment were stained with hematoxylin and eosin, trichrome, picrosirius red, and antibodies against several extracellular matrix components. Frozen sections were immunostained for host cardiac phenotypical markers and analyzed by epifluorescence and deconvolution fluorescence microscopy (DFM). We found less unresolved necrotic myocardium and more extracellular matrix deposition in MSC-treated dogs than in controls 2 weeks after cell delivery. By DFM, no DAPI+ MSC nuclei were observed within native cardiac cells. MSCs delivered during the subacute phase of acute myocardial infarction positively affect healing, apparently by mechanisms other than differentiation into mature native cardiac cells.

Comparison of intracoronary and transendocardial delivery of allogeneic mesenchymal cells in a canine model of acute myocardial infarction.

This study assessed safety of transendocardial (TE) electromechanical-guided delivery of bone marrow mesenchymal stem cells (MSCs) after acute myocardial infarction (AMI) and compared intracoronary (IC) delivery with TE delivery. In a canine acute myocardial ischemia model, 100 x 10(6) MSCs were delivered 7 days after AMI via IC and TE routes. Functional assessment was performed by 2D echocardiogram, and detailed histopathologic analyses were performed to assess the impact of cell therapy in vascular density and fibrosis. Patterns of cell distribution in both delivery methods were also compared. There was a statistically significant reduction in the amount of myocardial ischemia in the TE group (P=0.007). Left ventricular ejection fraction (LVEF) increased 13% (mean) in the TE group (21-day follow-up) and was significantly better than that of the controls (P=0.01), but did not improve in the IC-delivery group. Dissimilar patterns of cell distribution were noted between the IC and TE groups. This study suggests that MSC treatment is probably safe and effective after AMI. In the comparison of TE and IC delivery, the TE group showed higher cell retention (clusters even in the injury center of the infarct) with an increased vascularity and greater functional improvement than did the IC group (no clusters; cells at the border of the infarct). The higher local cell density in the TE group may be important for therapeutic effectiveness.

Right-to-left interatrial shunt with hypoxemia caused by a right atrial thrombus.

A right-to-left shunt in the presence of normal pulmonary artery pressure is an unusual cause of hypoxemia in an adult who has a patent foramen ovale. We report a rare case of such a shunt-the result of a right atrial thrombus that formed in a hypercoagulable patient after placement of an indwelling central venous catheter for chemotherapy. In order to ascertain the nature of the right atrial mass and to decrease the risk of systemic embolization, the thrombus was surgically removed with the patient on cardiopulmonary bypass.

Mesenchymal stem cells differentiate into an endothelial phenotype, enhance vascular density, and improve heart function in a canine chronic ischemia model.

BACKGROUND: Bone marrow-derived stem cells are under investigation as a treatment for ischemic heart disease. Mesenchymal stem cells (MSCs) have been used preferentially in the acute ischemia model; data in the chronic ischemia model are lacking. METHODS AND RESULTS: Twelve dogs underwent ameroid constrictor placement. Thirty days later, they received intramyocardial injections of either MSCs (100x10(6) MSCs/10 mL saline) (n=6) or saline only (10 mL) (controls) (n=6). All were euthanized at 60 days. Resting and stress 2D echocardiography was performed at 30 and 60 days after ameroid placement. White blood cell count (WBC), C-reactive protein (CRP), creatine kinase MB (CK-MB), and troponin I levels were measured. Histopathological and immunohistochemical analyses were performed. Mean left ventricular ejection fraction was similar in both groups at baseline but significantly higher in treated dogs at 60 days. WBC and CRP levels were similar over time in both groups. CK-MB and troponin I increased from baseline to 48 hours, eventually returning to baseline. There was a trend toward reduced fibrosis and greater vascular density in the treated group. MSCs colocalized with endothelial and smooth muscle cells but not with myocytes. CONCLUSIONS: In a canine chronic ischemia model, MSCs differentiated into smooth muscle cells and endothelial cells, resulting in increased vascularity and improved cardiac function.

Association of gender with morbidity and mortality after isolated coronary artery bypass grafting. A propensity score matched analysis.

INTRODUCTION: There is conflicting evidence about the impact of gender on outcomes after coronary artery bypass grafting (CABG). METHODS: We performed a multivariate logistic regression and propensity score matched analyses in 13,115 patients (75% men) who underwent CABG between January 1, 1995 and December 31, 2009. The primary outcome was in-hospital mortality. Secondary outcomes included post-operative respiratory failure, stroke, myocardial infarction, sternal and leg wound infections, atrial fibrillation (AF), renal failure, need for postoperative intra-aortic balloon pump (IABP) support, and length of hospital stay. RESULTS: A higher proportion of women (184; 5.6%) suffered in-hospital death compared to men (264; 2.7%), p<0.0001. After propensity score matching (n=3600 total, 1800 in each group), female gender was an independent predictor of mortality after isolated CABG (odds ratio [OR]=1.84; 95% confidence interval [CI] 1.22-2.78). Women also experienced a higher incidence of postoperative complications including stroke (3.8% vs. 2.3%, OR 1.37; 95% CI 1.08-1.73) and leg wound infection (3.4% vs. 1.7%, OR 1.75; 95% CI 1.36-2.54) on multivariate regression analyses. However, these differences were not significant after propensity score matching. We also observed a lower risk of post-operative AF (21.2% vs. 22.1%, OR 0.78; 95% CI 0.70-0.86) in women that remained significant after propensity matching (O.R. 0.76; 95% C.I. 0.65-0.90). Length of hospital stay was longer in women compared with men (11.9 ± 9.0 vs. 10.4 ± 9.2 days, p<0.0001). CONCLUSIONS: Female gender is an independent predictor of increased mortality and a lower incidence of post-operative AF after isolated CABG.

Identify and treat depression for reduced cardiac risk and improved outcomes.

Why do we stay in prison when the door is wide open? - Jalal ad-Din Rumi. Depression is an independent risk factor for the development of CAD. Patients with CAD have a high rate of depression, which worsens their prognosis. Screening CAD patients with the 2-question PHQ-2 to identify those at greatest risk of depression is strongly recommended, as is referring patients for further evaluation and possible treatment when depression has been identified by the PHQ-9. Treating depression is likely to improve cardiovascular outcomes. The PHQs are in the public domain and free to use. To download and for more information, visit www. phqscreeners.com.

An evidence-based guide for coronary calcium scoring in asymptomatic patients without coronary heart disease.

As public awareness and clinical use of CAC screening increases, physicians should, at a minimum, know the following information: 1) The presence of CAC indicates underlying CHD but does not predict luminal obstruction. 2) Non-contrast, prospectively ECG-gated cardiac EBCT and MDCT are sensitive, reproducible, rapid, and essentially equivalent imaging techniques commonly used to screen for CAC. 3) Currently, CAC screening is appropriate for all intermediate- risk patients and low-risk patients with a family history of premature CHD, and might be appropriate for all low-risk women. 4) The risks associated with CAC screening are a small but measurable excess risk of cancer and the risk of unnecessary downstream tests and procedures. 5) A CAC score of zero has a very high negative predictive value for CHD events. 6) Increasingly positive (non-zero) CAC scores are directly proportional to increased CHD event risk, and a CAC score >100 or greater than the 75th percentile indicates high risk. 7) Repeat screening to determine CAC progression or regression is not currently recommended.