Class 1C Antiarrhythmics for Premature Ventricular Complex Suppression in Nonischemic Cardiomyopathy With Implantable Cardioverter-Defibrillators.

BACKGROUND: Premature ventricular complexes (PVCs) are common and associated with worse outcomes in patients with heart failure. Class 1C antiarrhythmic drugs (AADs) effectively suppress PVCs, but guidelines currently restrict their use in structural heart disease. OBJECTIVES: This study aimed to assess the safety and efficacy of class 1C AADs in patients with nonischemic cardiomyopathy (NICM) and implantable cardioverter-defibrillators (ICDs). METHODS: All patients with NICM and an ICD treated with flecainide or propafenone at the Hospital of the University of Pennsylvania between 2014 and 2022 were identified. PVC burden, left ventricular ejection fraction (LVEF), and biventricular pacing percentage were compared before and during class 1C AAD treatment. Safety outcomes included sustained atrial and ventricular arrhythmias, heart failure admissions, and death. RESULTS: We identified 34 patients, 23 receiving flecainide and 11 propafenone. Most patients (62%) had failed other AADs or catheter ablation (68%) prior to class 1C AAD initiation. PVC burden decreased from 20 ± 13% to 6 ± 7% (P < 0.001), LVEF increased from 33 ± 9% to 37 ± 10% (P = 0.01), and biventricular pacing percentage increased from 85 ± 9% to 93 ± 7% (P = 0.01). Sustained ventricular tachycardia (2 vs 9 patients) and admissions for decompensated heart failure (2 vs 3 patients) decreased compared with the 12 months prior to class 1C AAD initiation. CONCLUSIONS: Class 1C AADs effectively suppressed PVCs in patients with NICM and ICDs, leading to increases in LVEF and biventricular pacing percentage. In this limited sample, their use was safe. Larger studies are needed to confirm the safety of this approach.

Cymbopogon winterianus (Java Citronella Plant): A Multi-Faceted Approach for Food Preservation, Insecticidal Effects, and Bread Application.

Certain plants like Rosemarinus officinalis, Lavandula angustifolia and Origanum vulgare have been used in the food industry for centuries. Cymbopogon winterianus (Java Citronella plant) is one of the most significant plants. The objective of this study is to screen for secondary metabolites by phytochemical screening, evaluate the antioxidant contents of extracts and investigate the use of the Java Citronella plant in food preservation and as an insecticide. Java Citronella powder was added to bread and evaluated for its moisture content, and a visual and sensory analysis was performed. Sitophilus granarius (L.) weevils were exposed to Java Citronella essential oil (JCEO). The phytochemical screening revealed that the extracts were abundant in secondary metabolites. The JCEO had a yield of 0.75%. The aqueous extract had a higher total phenolic content of 49.043 ± 0.217 mg GAE/g than the ethanolic extract, which was 24.478 ± 1.956 mg GAE/g. The aqueous extract had a total flavonoids content 27,725.25 ± 54.96 µg RE/g higher than the ethanolic extract, with 24,263 ± 74 µg RE/g. The ethanolic extract had stronger antioxidant activity, with anIC50 = 196.116 µg/mL higher than the aqueous extract at 420 µg/mL. The 2% Java Citronella powder in the bread was preferred by consumers, and had a shelf life of 6 days. JCEO killed all the weevils with a high dose of 10% after 48 h. The Java Citronella showed insecticidal and food preservative activity. The results should help in future research to enhance the applications of Java Citronella in various domains, from food technology to insecticides.

Epicardial Ventricular Tachycardia Ablation: Patient Selection, Access, and Ablation Techniques and Strategies to Manage Complications.

Epicardial ventricular tachycardia ablation is an important treatment modality for refractory ventricular tachycardia. This comprehensive review guides clinicians through optimized strategies for improved procedural outcomes and patient safety during epicardial ventricular tachycardia ablation. Patient selection criteria, including cardiomyopathy type, electrocardiogram findings, and prior ablation history, are discussed. Detailed techniques for safe pericardial access are provided. Potential complications and strategies for prevention and management are explored. The review also addresses challenges and pitfalls of epicardial mapping and ablation.

Implantable cardioverter defibrillators in patients with orthotopic heart transplant: A multicenter case series.

BACKGROUND: Sudden cardiac death (SCD) is common after orthotopic heart transplant (OHT). No clear guidelines for implantable cardioverter defibrillator (ICD) implantation in OHT patients at high risk for SCD currently exist. OBJECTIVES: To assess the safety, efficacy, and benefit of ICDs and resynchronization therapy post-OHT. We also provide a systematic review of previous reports. METHODS: A retrospective multicenter cohort study within the United States. Patients with ICD post-OHT between 2000 and 2020 were identified. RESULTS: We analyzed 16 patients from 4 centers. The mean standard-deviation (SD) age was 43 (18) years at OHT and 51 (20) years at ICD implantation. The mean (SD) duration from OHT to ICD implantation was 9 (5) years. The mean (SD) left ventricular ejection fraction (LVEF) was 35% (17%). There were 2 (13%) postprocedural complications: 1 hematoma and 1 death. Mean (SD) follow-up was 24 (23) months. Survival rate was 63% (10/16) at 1 year and 56% (9/16) at 2 years, with 6/7 of those who died having LVEF < 35% at the time of the ICD implantation. Patients were more likely to receive appropriate therapy if their ICD was implanted for secondary (5/8) rather than primary (0/8) prevention (p = .007). Of those who did, 4 patients survived to 30 days post-ICD therapy. Severe CAV was not associated with the rate of appropriate therapy. CONCLUSIONS: Beneficial outcomes were observed when ICDs were implanted for secondary prevention only, and in patients with higher baseline LVEF. We also observed benefits with resynchronization therapy.

The Use of Coronary Sinus Reducer for Refractory Angina in the U.S.: A Case Series.

Chronic refractory angina remains a common and debilitating condition for millions of people, with up to 30% of patients experiencing persistent angina despite successful revascularization. We share our experience with the implantation of a coronary sinus reducer in two complex CAD patients with refractory angina despite multiple revascularization strategies and maximally tolerated medical therapy.

COVID-19 risk index (CRI): a simple and validated emergency department risk score that predicts mortality and the need for mechanical ventilation.

Although certain risk factors have been associated with morbidity and mortality, validated emergency department (ED) derived risk prediction models specific to coronavirus disease 2019 (COVID-19) are lacking. The objective of this study is to describe and externally validate the COVID-19 risk index (CRI). A large retrospective longitudinal cohort study was performed to analyze consecutively hospitalized patients with COVID-19. Multivariate regression using clinical data elements from the ED was used to create the CRI. The results were validated with an external cohort of 1799 patients from the MI-COVID19 database. The primary outcome was the composite of the need for mechanical ventilation or inpatient mortality, and the secondary outcome was inpatient mortality. A total of 1020 patients were included in the derivation cohort. A total of 236 (23%) patients in the derivation cohort required mechanical ventilation or died. Variables independently associated with the primary outcome were age ≥ 65 years, chronic obstructive pulmonary disease, chronic kidney disease, cerebrovascular disease, initial D-dimer > 1.1 µg/mL, platelet count < 150 K/µL, and severity of SpO2:FiO2 ratio. The derivation cohort had an area under the receiver operator characteristic curve (AUC) of 0.83, and 0.74 in the external validation cohort Calibration shows close adherence between the observed and expected primary outcomes within the validation cohort. The CRI is a novel disease-specific tool that assesses the risk for mechanical ventilation or death in hospitalized patients with COVID-19. Discrimination of the score may change given continuous updates in contemporary COVID-19 management and outcomes.

Hemodynamic Effects of Left-Atrial Venous Arterial Extra-Corporeal Membrane Oxygenation (LAVA-ECMO).

We report a case of a 59-year-old male in post-myocardial infarction cardiogenic shock undergoing left atrial venous arterial extracorporeal membrane oxygenation (LAVA-ECMO) as a bridge to transplantation. The unique feature of this ECMO configuration is use of a single trans-septal cannula to provide biventricular unloading and use of a single arterial access.

Atrial fibrillation prevalence and management patterns in a Middle Eastern community in the United States: A retrospective study.

Atrial fibrillation (AF) is the most common sustained cardiac dysrhythmia in the United States, and its prevalence is expected to increase along with associated morbidity and economic burden. Prior research has demonstrated differing prevalence patterns of AF between racial and ethnic groups, with lower rates identified in Black patients. However, to date there have been no studies on AF prevalence in people of Middle Eastern descent within the United States. This retrospective cross-sectional study aimed to characterize prevalence patterns of AF in Middle Eastern patients in Southeast Michigan relative to White and Black patients. The final cohort included 919,454 patients with a median (IQR) age of 53 (33) years (515,902 [56 %] female). The overall prevalence of AF was approximately 5 %. We observed a lower prevalence of AF in Middle Eastern (2.8 %) and Black patients (3.4 %) than in White patients (6.5 %). Middle Eastern patients with AF were younger with a lower prevalence of cardiovascular risk factors than White patients. Multivariable analysis showed that Middle Eastern (OR 0.75; 95 % CI 0.71-0.80; P < 0.001) and Black racial identity (OR 0.48; 95 % CI 9.47-0.49; P < 0.001) were associated with a lower odds of AF, even after adjustment for traditional risk factors.

Right Heart Strain on Presenting 12-Lead Electrocardiogram Predicts Critical Illness in COVID-19.

OBJECTIVES: This study aimed to assess the association of new right heart strain patterns on presenting 12-lead electrocardiogram (RHS-ECG) with outcomes in patients hospitalized with COVID-19. BACKGROUND: Cardiovascular comorbidities and complications, including right ventricular dysfunction, are common and are associated with worse outcomes in patients with COVID-19. The data on the clinical usefulness of the 12-lead ECG to aid with prognosis are limited. METHODS: This study retrospectively evaluated records from 480 patients who were consecutively admitted with COVID-19. ECGs obtained at presentation in the emergency department (ED) were considered index ECGs. RHS-ECG was defined by any new right-axis deviation, S1Q3T3 pattern, or ST depressions with T-wave inversions in leads V1 to V3 or leads II, III, and aVF. Multivariable logistic regression was performed to assess whether RHS-ECGs were independently associated with primary outcomes. RESULTS: ECGs from the ED were available for 314 patients who were included in the analysis. Most patients were in sinus rhythm, with sinus tachycardia being the most frequent dysrhythmia. RHS-ECG findings were present in 40 (11%) patients. RHS-ECGs were significantly associated with the incidence of adverse outcomes and an independent predictor of mortality (adjusted odds ratio [adjOR]: 15.2; 95% confidence interval [CI]: 5.1 to 45.2; p < 0.001), the need for mechanical ventilation (adjOR: 8.8; 95% CI: 3.4 to 23.2; p < 0.001), and their composite (adjOR: 12.1; 95% CI: 4.3 to 33.9]; p < 0.001). CONCLUSIONS: RHS-ECG was associated with mechanical ventilation and mortality in patients admitted with COVID-19. Special attention should be taken in patients admitted with new signs of RHS on presenting ECG.

Microvascular Assessment of Ranolazine in Non-Obstructive Atherosclerosis: The MARINA Randomized, Double-Blinded, Controlled Pilot Trial.

BACKGROUND: Microvascular dysfunction is known to play a key role in patients with angina and nonobstructive coronary artery disease. We investigated the impact of ranolazine among patients with angina and nonobstructive coronary artery disease. METHODS: In this randomized, double-blinded, placebo-controlled pilot trial, 26 patients with angina once weekly or more, abnormal stress test, and nonobstructive coronary artery disease (<50% stenosis by angiography and fractional flow reserve >0.80) were randomized 1:1 to ranolazine or placebo for 12 weeks. Primary end point was ΔSeattle Angina Questionnaire (SAQ) angina frequency score. Baseline and 3 months follow-up SAQ, Duke Activity Status Index scores along with invasive fractional flow reserve, coronary flow reserve (CFR), hyperemic myocardial resistance, and cardiopulmonary exercise testing measurements were performed. RESULTS: No significant differences in ΔSAQ angina frequency scores (P=0.53) or Duke Activity Status Index (P=0.76) were observed between ranolazine versus placebo, although patients on ranolazine had lesser improvement in SAQ physical limitation scores (P=0.02) compared with placebo at 3 months. There were no significant differences in ΔCFR or Δhyperemic myocardial resistance between ranolazine and placebo groups. Patients treated with ranolazine, compared with placebo, had no significant improvement in maximum rate of oxygen consumption measured during incremental exercise (VO2 max) and peak metabolic equivalents of task. Interestingly, in the ranolazine group, patients with baseline CFR<2.0 demonstrated greater gain in CFR compared with those with baseline CFR≥2.0 (P=0.02). CONCLUSIONS: Ranolazine did not demonstrate improvement in SAQ angina frequency score, invasive microvascular function, or peak metabolic equivalent compared with placebo at 3 months. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02147067.

COVID-19: A Multidisciplinary Review.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a novel coronavirus that is responsible for the 2019-2020 pandemic. In this comprehensive review, we discuss the current published literature surrounding the SARS-CoV-2 virus. We examine the fundamental concepts including the origin, virology, pathogenesis, clinical manifestations, diagnosis, laboratory, radiology, and histopathologic findings, complications, and treatment. Given that much of the information has been extrapolated from what we know about other coronaviruses including severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), we identify and provide insight into controversies and research gaps for the current pandemic to assist with future research ideas. Finally, we discuss the global response to the coronavirus disease-2019 (COVID-19) pandemic and provide thoughts regarding lessons for future pandemics.

Cardiac Injury Patterns and Inpatient Outcomes Among Patients Admitted With COVID-19.

Although certain risk factors have been associated with increased morbidity and mortality in patients admitted with Coronavirus Disease 2019 (COVID-19), the impact of cardiac injury and high-sensitivity troponin-I (hs-cTnI) concentrations are not well described. In this large retrospective longitudinal cohort study, we analyzed the cases of 1,044 consecutively admitted patients with COVID-19 from March 9 until April 15. Cardiac injury was defined by hs-cTnI concentration >99th percentile. Patient characteristics, laboratory data, and outcomes were described in patients with cardiac injury and different hs-cTnI cut-offs. The primary outcome was mortality, and the secondary outcomes were length of stay, need for intensive care unit care or mechanical ventilation, and their different composites. The final analyzed cohort included 1,020 patients. The median age was 63 years, 511 (50% patients were female, and 403 (40% were white. 390 (38%) patients had cardiac injury on presentation. These patients were older (median age 70 years), had a higher cardiovascular disease burden, in addition to higher serum concentrations of inflammatory markers. They also exhibited an increased risk for our primary and secondary outcomes, with the risk increasing with higher hs-cTnI concentrations. Peak hs-cTnI concentrations continued to be significantly associated with mortality after a multivariate regression controlling for comorbid conditions, inflammatory markers, acute kidney injury, and acute respiratory distress syndrome. Within the same multivariate regression model, presenting hs-cTnI concentrations were not significantly associated with outcomes, and undetectable hs-cTnI concentrations on presentation did not completely rule out the risk for mechanical ventilation or death. In conclusion, cardiac injury was common in patients admitted with COVID-19. The extent of cardiac injury and peak hs-cTnI concentrations were associated with worse outcomes.

Biventricular implantable cardioverter-defibrillator device placement in patients with hostile tricuspid valve anatomy: two case reports and review of the literature.

AIMS: Right ventricular (RV) lead placement can be contraindicated in patients after tricuspid valve (TV) surgery. Placement of the implantable cardiac-defibrillator (ICD) lead in the middle cardiac vein (MCV) can be a viable option in these patients who have an indication for biventricular (BiV) ICD. We aim to describe the case of two patients with MCV lead placement and provide a comprehensive review of patients with complex TV pathology and indications for RV lead placement. METHODS AND RESULTS: We describe the cases of two patients with TV pathology unsuitable for the standard transvenous or surgical RV lead placement and undergoing BiV ICD implantation. Their characteristics, procedure, and outcomes are summarized. The BiV ICD was successfully placed with the RV lead positioned in the MCV in both patients. The procedures had no complications and were well-tolerated. On follow-up, both patients had appropriate tachytherapy with no readmissions for heart failure or worsening of cardiac function. CONCLUSION: Right ventricular lead placement of BiV ICD in the MCV can be an excellent alternative in patients with significant TV pathology and poor surgical candidacy.

Oxidative Stress Is Associated With Diastolic Dysfunction in Women With Ischemia With No Obstructive Coronary Artery Disease.

Background Women with signs and symptoms of ischemia and no obstructive coronary artery disease often have evidence of diastolic dysfunction. Oxidative stress (OS) is associated with cardiovascular risk factors and adverse outcomes. The relationship between systemic OS and diastolic dysfunction is unknown. Methods and Results A subgroup of women (n=75) with suspected ischemia and no obstructive coronary artery disease who had both cardiac magnetic resonance imaging and OS measurements were enrolled in the WISE-CVD (Women Ischemia Syndrome Evaluation-Coronary Vascular Dysfunction) study. Left ventricular end-diastolic pressure was measured invasively. Left ventricular end-diastolic volume and peak filling rate were assessed using cardiac magnetic resonance imaging. Aminothiol levels of plasma cystine and glutathione were measured as markers of OS. Spearman correlation and linear regression analyses were conducted. The group mean age was 54±11 years, and 61% had a resting left ventricular end-diastolic pressure >12 mm Hg. Cystine levels correlated negatively with the peak filling rate (r=-0.31, P=0.007) and positively with left ventricular end-diastolic pressure (r=0.25; P=0.038), indicating that increased OS was associated with diastolic dysfunction. After multivariate adjustment including multiple known risk factors for diastolic dysfunction and cardiovascular medications, cystine levels continued to be associated with peak filling rate (ß=-0.27, P=0.049) and left ventricular end-diastolic pressure (ß=0.25; P=0.035). Glutathione levels were not associated with indices of diastolic function. Conclusions OS, measured by elevated levels of cystine, is associated with diastolic dysfunction in women with evidence of ischemia and no obstructive coronary artery disease, indicating the role of OS in patients with ischemia and no obstructive coronary artery disease. Its role in the progression of heart failure with preserved ejection fraction should be explored further.

Soluble Urokinase Receptor and Acute Kidney Injury.

BACKGROUND: Acute kidney injury is common, with a major effect on morbidity and health care utilization. Soluble urokinase plasminogen activator receptor (suPAR) is a signaling glycoprotein thought to be involved in the pathogenesis of kidney disease. We investigated whether a high level of suPAR predisposed patients to acute kidney injury in multiple clinical contexts, and we used experimental models to identify mechanisms by which suPAR acts and to assess it as a therapeutic target. METHODS: We measured plasma levels of suPAR preprocedurally in patients who underwent coronary angiography and patients who underwent cardiac surgery and at the time of admission to the intensive care unit in critically ill patients. We assessed the risk of acute kidney injury at 7 days as the primary outcome and acute kidney injury or death at 90 days as a secondary outcome, according to quartile of suPAR level. In experimental studies, we used a monoclonal antibody to urokinase plasminogen activator receptor (uPAR) as a therapeutic strategy to attenuate acute kidney injury in transgenic mice receiving contrast material. We also assessed cellular bioenergetics and generation of reactive oxygen species in human kidney proximal tubular (HK-2) cells that were exposed to recombinant suPAR. RESULTS: The suPAR level was assessed in 3827 patients who were undergoing coronary angiography, 250 who were undergoing cardiac surgery, and 692 who were critically ill. Acute kidney injury developed in 318 patients (8%) who had undergone coronary angiography. The highest suPAR quartile (vs. the lowest) had an adjusted odds ratio of 2.66 (95% confidence interval [CI], 1.77 to 3.99) for acute kidney injury and 2.29 (95% CI, 1.71 to 3.06) for acute kidney injury or death at 90 days. Findings were similar in the surgical and critically ill cohorts. The suPAR-overexpressing mice that were given contrast material had greater functional and histologic evidence of acute kidney injury than wild-type mice. The suPAR-treated HK-2 cells showed heightened energetic demand and mitochondrial superoxide generation. Pretreatment with a uPAR monoclonal antibody attenuated kidney injury in suPAR-overexpressing mice and normalized bioenergetic changes in HK-2 cells. CONCLUSIONS: High suPAR levels were associated with acute kidney injury in various clinical and experimental contexts. (Funded by the National Institutes of Health and others.).