Catheter Ablation for Channelopathies: When Is Less More?

Ventricular fibrillation (VF) is a common cause of sudden cardiac death in patients with channelopathies, particularly in the young population. Although pharmacological treatment, cardiac sympathectomy, and implantable cardioverter defibrillators (ICD) have been the mainstay in the management of VF in patients with channelopathies, they are associated with significant adverse effects and complications, leading to poor quality of life. Given these drawbacks, catheter ablation has been proposed as a therapeutic option for patients with channelopathies. Advances in imaging techniques and modern mapping technologies have enabled increased precision in identifying arrhythmia triggers and substrate modification. This has aided our understanding of the underlying pathophysiology of ventricular arrhythmias in channelopathies, highlighting the roles of the Purkinje network and the epicardial right ventricular outflow tract in arrhythmogenesis. This review explores the role of catheter ablation in managing the most common channelopathies (Brugada syndrome, congenital long QT syndrome, short QT syndrome, and catecholaminergic polymorphic ventricular tachycardia). While the initial results for ablation in Brugada syndrome are promising, the long-term efficacy and durability of ablation in different channelopathies require further investigation. Given the genetic and phenotypic heterogeneity of channelopathies, future studies are needed to show whether catheter ablation in patients with channelopathies is associated with a reduction in VF, and psychological distress stemming from recurrent ICD shocks, particularly relative to other available therapeutic options (e.g., quinidine in high-risk Brugada patients).

Expanding Indications of Nonvitamin K Oral Anticoagulants Beyond Nonvalvular Atrial Fibrillation and Venous Thromboembolism: A Review of Emerging Clinical Evidence.

Direct oral anticoagulants (DOAC) have emerged as a new therapy for patients who need and can tolerate oral anticoagulation. DOACs were initially approved for nonvalvular atrial fibrillation (NVAF) and treatment for deep vein thrombosis (DVT) and pulmonary embolism (PE). Ease of administration, no requirement of bridging with other anticoagulants, and less frequent dosing have made DOACs preferable choice for anticoagulation. Studies are showing promising results regarding use of DOACs beyond the common indications. Studies have been done to show the potential benefit of DOACs in valvular atrial fibrillation, heart failure, acute coronary syndrome, stroke, and peripheral arterial disease. Data have shown safety as well as comparable bleeding incidences with DOACs compared to vitamin K antagonist anticoagulants. Naturally interest is growing to see the use of DOACs apart from the NVAF, DVT, or PE. Authors have highlighted various study results to show the potential beneficial role of DOACs in the above-mentioned situations.

Incidence and Prognostic Implications of Cardiac-Implantable Device-Associated Tricuspid Regurgitation: A Meta-Analysis and Meta-Regression Analysis.

New-onset or worsening tricuspid regurgitation (TR) is a well-established complication encountered after cardiac implantable electronic devices (CIEDs). However, there are limited and conflicting data on the true incidence and prognostic implications of this complication. This study aimed to bridge this current gap in the literature. Electronic databases MEDLINE, Embase, and Web of Science were systematically searched from inception to March 2023, for studies reporting the incidence and/or prognosis of CIED-associated new or worsening TR. Potentially eligible studies were screened and selected according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A random effect model meta-analysis and meta-regression analysis were performed, and I-squared statistic was used to assess heterogeneity. A total of 52 eligible studies, with 130,759 patients were included in the final quantitative analysis with a mean follow-up period of 25.5 months. The mean age across included studies was 69.35 years, and women constituted 46.6% of the study population. The mean left ventricular ejection fraction was 50.15%. The incidence of CIED-associated TR was 24% (95% confidence interval [CI] 20% to 28%, p <0.001) with an odds ratio of 2.44 (95% CI 1.58 to 3.77, p <0.001). CIED-associated TR was independently associated with an increased risk of all-cause mortality (adjusted hazard ratio [aHR] 1.52, 95% CI 1.36 to 1.69, p <0.001), heart failure (HF) hospitalizations (aHR 1.82, 95% CI 1.19 to 2.78, p = 0.006), and the composite of mortality and HF hospitalizations (aHR 1.96, 95% CI 1.33 to 2.87, p = 0.001) in the follow-up period. In conclusion, CIED-associated TR occurred in nearly one-fourth of patients after device implantation and was associated with an increased risk of all-cause mortality and HF hospitalizations.

Biomarkers as Prognostic Markers for Aortic Stenosis: A Review.

Aortic stenosis (AS) is the most frequent valvular heart disease among the older individuals. Current guidelines indicate intervention for patients with symptomatic or fast progressive severe AS and asymptomatic patients with a reduced left ventricular (LV) ejection fraction by 50%. Interestingly, myocardial damage may have already happened by the time symptoms appear or LV function deteriorates. Serum biomarkers can be an early indicator to show LV function decline and AS progression even before clinical symptom onset. Studies have shown that cardiac biomarkers have prognostic value in patients with AS. Hence, cardiac biomarkers can be helpful in determining the optimum time to intervene. Transcatheter aortic valve replacement is a less invasive alternative to conventional surgical aortic valve replacement. The elevation of cardiac biomarkers at discharge has been associated with 2-year mortality after transcatheter aortic valve replacement. The correlation between biomarkers and AS-associated morbidity and mortality is an area to explore further. The authors of this review article have discussed the role of cardiac biomarkers in patients with AS for better risk stratification and identification of patients who would benefit from early intervention.

Evaluation and Management of Cardiac Sarcoidosis with Advanced Imaging.

A high clinical suspicion in the setting of appropriate history, physical exam, laboratory, and imaging parameters is often required to set the groundwork for diagnosis and management. Echocardiography may show septal thinning, evidence of systolic and diastolic dysfunction, along with impaired global longitudinal strain. Cardiac MRI reveals late gadolinium enhancement along with evidence of myocardial edema and inflammation on T2 weighted imaging and parametric mapping. 18F-FDG PET detects the presence of active inflammation and the presence of scar. Involvement of the right ventricle on MRI or PET confers a high risk for adverse cardiac events and mortality.

Trends in the Prevalence of Infiltrative Cardiomyopathy Among Patients With in-Hospital Cardiac Arrest.

Sarcoidosis, amyloidosis, hemochromatosis and scleroderma are the most forms of infiltrative/nonischemic cardiomyopathy (NICM) associated with sudden cardiac death. In patients who undergo in-hospital cardiac arrest, a high index of suspicion is required to rule out NICM as an underlying contributor. We aimed to analyze the prevalence of NICM among patients with in-hospital cardiac arrest and identify factors associated with increased mortality. We analyzed data from the National Inpatient Sample, and identified patients who were hospitalized across 10 years from 2010 to 2019 with a diagnosis of cardiac arrest and NICM. The total number of patients with in-hospital cardiac arrest was 19,34,260. The total number with NICM was 14,803 (0.77%). Mean age was 63 years. Overall prevalence of NICM across the years ranged between 0.75% to 0.9%, with a significant temporal increase (P < 0.01). Incidence of in-hospital mortality ranged between 61% to 76% for females and 30% to 38% for males. The following comorbidities were more prevalent in patients with NICM than those without: heart failure, chronic obstructive pulmonary disease (COPD), chronic kidney disease, anemia, malignancy, coagulopathy, ventricular tachycardia, acute kidney injury and stroke. The following factors were independent predictors of in-hospital mortality-age, female gender, Hispanic race, history of COPD and presence of malignancy (P = 0.042). The prevalence of infiltrative cardiomyopathy in patients with in-hospital cardiac arrest is increasing. Females, older patients and Hispanic population are at an increased risk of mortality. Sex and race-based disparities in the prevalence of NICM in patients with in-hospital cardiac arrest is an area of further research.

Incidence, predictors and outcomes of new onset systolic heart failure following orthotopic liver transplant: A systematic review.

BACKGROUND: New onset Systolic heart failure (SHF), characterized by new onset left ventricular (LV) systolic dysfunction with a reduction in ejection fraction (EF) of <40%, is a common cause of morbidity and mortality among Orthotopic liver transplant (OLT) recipients. Therefore, we aimed to evaluate the prevalence, the pre-transplant predictors, and the prognostic impact of SHF post-OLT. METHODS: We conducted a systematic review of the literature using electronic databases MEDLINE, Web of Science, and Embase for studies reporting acute systolic heart failure post-liver transplant from inception to August 2021. RESULT: Of 2604 studies, 13 met the inclusion criteria and were included in the final systematic review. The incidence of new-onset SHF post OLT ranged from 1.2% to 14%. Race, sex, or body mass index did not significantly impact the post-OLT SHF incidence. Alcoholic liver cirrhosis, pre-transplant systolic or diastolic dysfunction, troponin, brain natriuretic peptide (BNP), blood urea nitrogen (BUN) elevation, and hyponatremia were noted to be significantly associated with the development of SHF post-OLT. The significance of MELD score in the development of post-OLT SHF is controversial. Pre-transplant beta-blocker and post-transplant tacrolimus use were associated with a lower risk of developing SHF. The average 1-year mortality rate in patients with SHF post-OLT ranged from 0.00% to 35.2%. CONCLUSION: Despite low incidence, SHF post-OLT can lead to higher mortality. Further studies are required to fully understand the underlying mechanism and risk factors.

A Comparison of COVID-19 and Influenza-Associated Myocarditis: A Nationwide Study in the United States.

We aimed to compare the characteristics and outcomes of adult patients hospitalized with myocarditis and either concomitant corona virus disease 2019 (COVID-19) or influenza, and elucidate clinical predictors associated with adverse outcomes in both groups. The study used the national inpatient sample (NIS) from 2019 to 2020 to identify 27,725 adult myocarditis hospitalizations, of which 5840 had concomitant COVID-19 and 1045 had concomitant influenza. After propensity score matching, the in-hospital mortality from myocarditis was significantly higher in COVID-19 compared to influenza. Patients with myocarditis and COVID-19 were more likely to have cardiovascular comorbidities and be older than those with influenza-associated myocarditis. Predictors of mortality were also different in both groups.

Impact of COVID-19 in patients hospitalized with stress cardiomyopathy: A nationwide analysis.

Stress cardiomyopathy was noted to occur at a higher incidence during coronavirus disease of 2019 (COVID-19) pandemic. This database analysis has been done to compare the in-hospital outcomes in patients with stress cardiomyopathy and concurrent COVID-19 infection with those without COVID-19 infection. The National Inpatient Sample database for the year 2020 was queried to identify all admissions diagnosed with stress cardiomyopathy. These patients were then stratified based on whether they had concomitant COVID-19 infection or not. A 1:1 propensity score matching was performed. Multivariate logistic regression analysis was done to identify predictors of mortality. We identified 41,290 hospitalizations for stress cardiomyopathy, including 1665 patients with concurrent diagnosis of COVID-19. The female preponderance was significantly lower in patients with stress cardiomyopathy and COVID-19. Patients with concomitant COVID-19 were more likely to be African American, diabetic and have chronic kidney disease. After propensity matching, the incidence of complications, including acute kidney injury (AKI), AKI requiring dialysis, coagulopathy, sepsis, cardiogenic shock, cases with prolonged intubation of >24 h, requirement of vasopressor and inpatient mortality, were noted to be significantly higher in patients with COVID-19. Concomitant COVID-19 infection was independently associated with worse outcomes and increased mortality in patients hospitalized with stress cardiomyopathy.

Impact of COVID-19 on Outcomes of Patients Hospitalized With STEMI: A Nationwide Propensity-matched Analysis.

Patients with ST-segment elevation myocardial infarction (STEMI) and concurrent coronavirus disease 2019 (COVID-19) have been reported to have poor outcomes. However, previous studies are small and limited. The National Inpatient Sample database for the year 2020 was queried to identify all adult hospitalizations with a primary diagnosis of STEMI, with and without concurrent COVID-19. A 1:1 propensity score matching was performed. A total of 159,890 hospitalizations with a primary diagnosis of STEMI were identified. Of these, 2210 (1.38%) had concurrent COVID-19. After propensity matching, STEMI patients with concurrent COVID-19 had a significantly higher mortality (17.8% vs 9.1%, OR 1.96, P< 0.001), lower likelihood to receive same-day percutaneous coronary intervention (PCI) (63.6% vs 70.6%, P = 0.019), with a trend towards lower overall PCI (74.9% vs 80.2%, P = 0.057) and significantly lower coronary artery bypass grafting) (3.0% vs 6.8%, P = 0.008) prior to discharge, compared with STEMI patients without COVID-19. The prevalence of cardiogenic shock, need for mechanical circulatory support, extracorporeal membrane oxygenation, cardiac arrest, acute kidney injury (AKI), dialysis, major bleeding and stroke were not significantly different between the groups. COVID-19-positive STEMI patients who received same-day PCI had significantly lower odds of in-hospital mortality (adjusted OR 0.42, 95% CI 0.20-0.85, P = 0.017). STEMI patients with concurrent COVID-19 infection had a significantly higher (almost 2 times) in-hospital mortality, and lower likelihood of receiving same-day PCI, overall (any-day) PCI, and CABG during their admission, compared with STEMI patients without COVID-19.

Impact of COVID-19 on Patients Hospitalized With Deep Vein Thrombosis and/or Pulmonary Embolism: A Nationwide Analysis.

The Coronavirus disease 2019 (COVID-19) infection predisposes patients to develop deep vein thrombosis (DVT) and pulmonary embolism (PE). In this study, we compared the in-hospital outcomes of patients with DVT and/or PE with concurrent COVID-19 infection vs those with concurrent flu infection. The National Inpatient Sample from 2019 to 2020 was analyzed to identify all adult admissions diagnosed with DVT and PE. These patients were then stratified based on whether they had concomitant COVID-19 or flu. We identified 62,895 hospitalizations with the diagnosis of DVT and/or PE with concomitant COVID-19, and 8155 hospitalizations with DVT and/or PE with concomitant flu infection. After 1:1 propensity score match, the incidence of cardiac arrest and inpatient mortality were higher in the COVID-19 group. The incidence of cardiogenic shock was higher in the flu group. Increased age, Hispanic race, diabetes, chronic kidney disease, arrhythmia, liver disease, coagulopathy, and rheumatologic diseases were the independent predictors of mortality in patients with DVT and/or PE with concomitant COVID-19.

COVID-19, Heart Failure Hospitalizations, and Outcomes: A Nationwide Analysis.

Heart Failure (HF) patients are at a higher risk of adverse events associated with Coronavirus disease 2019 (COVID-19). Large population-based reports of the impact of COVID-19 on patients hospitalized with HF are limited. The National Inpatient Sample database was queried for HF admissions during 2020 in the United States (US), with and without a diagnosis of COVID-19 based on ICD-10-CM U07. Propensity score matching was used to match patients across age, race, sex, and comorbidities. Multivariate logistic regression analysis was used to identify predictors of mortality. A weighted total of 1,110,085 hospitalizations for HF were identified of which 7,905 patients (0.71%) had a concomitant diagnosis of COVID-19. After propensity matching, HF patients with COVID-19 had higher rate of in-hospital mortality (8.2% vs 3.7%; odds ratio [OR]: 2.33 [95% confidence interval [CI]: 1.69, 3.21]; P< 0.001), cardiac arrest (2.9% vs 1.1%, OR 2.21 [95% CI: 1.24,3.93]; P<0.001), and pulmonary embolism (1.0% vs 0.4%; OR 2.68 [95% CI: 1.05, 6.90]; P = 0.0329). During hospitalizations for HF, COVID-19 was also found to be an independent predictor of mortality. Further, increasing age, arrythmias, and chronic kidney disease were independent predictors of mortality in HF patients with COVID-19. COVID-19 is associated with increased in-hospital mortality, longer hospital stays, higher cost of hospitalization and increased risk of adverse outcomes in patients admitted with HF.

Present Knowledge on Direct Oral Anticoagulant and Novel Oral Anti Coagulants and Their Specific Antidotes: A Comprehensive Review Article.

Thromboembolic diseases are one of the leading causes of morbidity and mortality worldwide. For a long time, heparin and Vitamin K antagonist (VKA) drugs were used for treatment and prophylaxis of the thromboembolic diseases. The development of newer direct and novel oral anticoagulant medications (DOACs/NOACs) has changed clinical practice significantly. Lesser monitoring, ease with dosing, less drug interactions have made these drugs useful to the providers and the patients. But these drugs have bleeding as a side effect. There is ongoing research on the specific antidotes of these anticoagulants in case of life-threatening bleeding. Though the use of the DOACs and NOACs have increased, there is still not enough clinical evidence about the specific antidotes of these medications. Unlike heparin or VKA, reversal of life-threatening bleeding in the setting of DOAC use is still a clinical challenge. We need more data on the dose, pharmacokinetics, and clinical efficacy of those antidotes. Authors have reviewed articles on DOACs and their antidotes in Pubmed and also in the clinical trial website. Specific antidotes including Idarucizumab for Dabigatran, Andexanet alfa for factor Xa inhibitors are being used to reverse the actions of the anticoagulants. Ciraparantag is a universal antidote for the DOACs, which is still under investigation. FXaI16L is currently being investigated as a potential universal antidote for multiple anticoagulants, including dabigatran and rivaroxaban. Though mostly safe, the use of DOACs can still carry a risk of severe bleeding in patients. More data on the use of the antidotes is required to reverse the side effect of DOACs if clinically indicated.

Sex Differences in Periprocedural and Long-Term Outcomes Following Transcatheter Left Atrial Appendage Occlusion: A Systematic Review and Meta-Analysis.

BACKGROUND: Atrial fibrillation (AF) is among the most common arrhythmias associated with an increased risk of cardioembolic phenomena, including stroke. Percutaneous left atrial appendage occlusion (LAAO) has proven beneficial in reducing stroke and mortality in patients with atrial fibrillation who have contraindications to anticoagulation. However, the sex differences in outcomes following LAAO have not been studied systematically. METHODS: Electronic databases PUBMED, Embase, and Web of Science were systematically searched until March 2022 for studies evaluating patient outcomes following LAAO for AF. The primary outcomes of interest were the risks of periprocedural stroke, major bleeding, pericardial complications, and all-cause mortality. Secondary outcomes included stroke risks, major bleeding, device-related thrombus, cardiovascular and all-cause mortality on long-term follow-up. A random-effects model meta-analysis was conducted, and heterogeneity was assessed using the I-squared test. RESULTS: Sixteen studies were included in the final analysis encompassing 111,775 patients, out of which 45,441 (40.7 %) were women. Women had a significantly higher risk of peri-procedural complications including all-cause mortality [relative risk (RR), 95 % confidence intervals (CI); RR 1.94, 95 % CI 1.40-2.69], stroke [RR 1.85, 95 % CI 1.29-2.67], major bleeding [RR 1.63, 95 % CI 1.08-2.44], and pericardial events [RR 1.80, 95 % CI 1.58-2.05]. However, there were no statistically significant differences between sexes in terms of risk of stroke, major bleeding, device-related thrombus, cardiovascular and all-cause mortality on long-term follow-up. CONCLUSION: Among patients undergoing LAAO implantation, women were at higher risk of periprocedural complications than men. This risk was not significant on long-term follow-up.

Recent Advances and Future Prospects of Treatment of Pulmonary Hypertension.

Pulmonary hypertension is one of the difficult situations to treat. Complex pathophysiology, association of the multiple comorbidities make clinical scenario challenging. Recently it is being shown that patients who had recovered from coronavirus disease infection, are at risk of developing pulmonary hypertension. Studies on animals have been going on to find out newer treatment options. There are recent advancements in the treatment of pulmonary hypertension. Role of anticoagulation, recombinant fusion proteins, stem cell therapy are emerging as therapeutic options for affected patients. SGLT2 inhibitors have potential to have beneficial effects on pulmonary hypertension. Apart from the medical managements, advanced interventions are also getting popular. In this review article, the authors have discussed pathophysiology, recent advancement of treatments including coronavirus disease patients, and future aspect of managing pulmonary hypertension. We have highlighted treatment options for patients with sleep apnea, interstitial lung disease to discuss the challenges and possible options to manage those patients.

SGLT2 inhibitors in hypertension: Role beyond diabetes and heart failure.

Type 2 Diabetes Mellitus (T2DM) is a pandemic that affects millions of patients worldwide. Diabetes affects multiple organ systems leading to comorbidities including hypertension. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) recently have been approved for the treatment of T2DM and heart failure with reduced and preserved ejection fraction. Retrospective analyses of clinical trials have noted SGLT2 inhibitors to have a promising effect on blood pressure. Moreover, the observed blood pressure reduction is not just an acute effect of treatment initiation but has been shown to have a long-term impact on both systolic and diastolic blood pressure. The mechanism of action leading to the blood pressure reduction is still unclear; however, proposed mechanisms are related to the natriuretic effect, modification of the renin-angiotensin-aldosterone system, and/or the reduction in the sympathetic nervous system, SGLT2i should be considered as second-line medication in those patients with diabetes or heart disease and concomitant hypertension. This article reviews the pharmacology, side effect profile, and clinical trials surrounding the use of SGLT2i for the treatment of hypertension.