Efficacy and safety of sodium-glucose cotransporter 2 inhibitors initiation in patients with acute heart failure, with and without type 2 diabetes: a systematic review and meta-analysis.

BACKGROUND: There is uncertainty and limited data regarding initiation of sodium-glucose cotransporter 2 (SGLT2) inhibitors among patients hospitalized with acute heart failure (AHF). This systematic review and meta-analysis aim to establish the efficacy and safety of SGLT2 inhibitors initiated in patients hospitalized for AHF. METHODS: PubMed/Medline, Embase, and Cochrane library were searched using the following terms: ("sglt2" and "acute heart failure") and ("sglt2" and "worsening heart failure") from inception till November 15th, 2021 for randomized controlled trials (RCTs) comparing the efficacy and safety of initiating an SGLT2 inhibitor compared with placebo in patients with AHF. Major cardiovascular and diabetes scientific meetings in 2021 were also searched for relevant studies. Prespecified efficacy outcomes were all-cause mortality, rehospitalization for heart failure, and improvement in Kansas City Cardiomyopathy Questionnaire (KCCQ) scale score. Prespecified safety outcomes were acute kidney injury (AKI), hypotension, and hypoglycemia. Random effects odds ratio (OR) and mean difference with 95% confidence intervals (CIs) were calculated. RESULTS: Three RCTs with a total of 1831 patients were included. Initiation of SGLT2 inhibitors in patients with AHF reduced the risk of rehospitalization for heart failure (OR 0.52; 95% CI [0.42, 0.65]) and improved Kansas City Cardiomyopathy Questionnaire scores (mean difference 4.12; 95% CI [0.1.89, 6.53]). There was no statistically significant effect for initiation of SGLT2 inhibitors in patients with AHF on all-cause mortality (OR 0.70; 95% CI [0.46, 1.08]). Initiation of SGLT2 inhibitors in patients with AHF did not increase the acute kidney injury (OR 0.76; 95% CI [0.50, 1.16]), hypotension (OR 1.17; 95% CI [0.80, 1.71]), or hypoglycemia (OR 1.51; 95% CI [0.86, 2.65]). CONCLUSION: Initiation of SGLT2 inhibitors in patients hospitalized for AHF during hospitalization or early post-discharge (within 3 days) reduces the risk of rehospitalization for heart failure and improves patient-reported outcomes with no excess risk of adverse effects.

Effects of sodium-glucose cotransporter 1 and 2 inhibitors on cardiovascular and kidney outcomes in type 2 diabetes: A meta-analysis update.

In this report, we aim to provide an updated meta-analysis of the sodium-glucose cotransporter 2 (SGLT2) inhibitors trial data with the new trial data on sotagliflozin, a first-in-class dual SGLT1 and SGLT2 inhibitor. We searched Medline, Cochrane library, and Embase databases for randomized clinical trials comparing cardiovascular and kidney outcomes between SGLT2 and dual SGLT1/2 inhibitors and placebo. Nine randomized clinical trials with a total of 60,914 patients with type 2 diabetes were included. In patients with type 2 diabetes, the use of SGLT2 and dual SGLT1/2 inhibitors improves the cardiovascular and kidney outcome.

Effect of sodium-glucose cotransporter 2 inhibitors on cardiovascular and kidney outcomes-Systematic review and meta-analysis of randomized placebo-controlled trials.

Sodium-glucose cotransporter 2 inhibitor (SGLT2i) use is associated with improved cardiovascular and kidney outcomes. However, the magnitude and potential heterogeneity of effect across patients with varying types of cardiometabolic and kidney disease is unclear. To examine the effect of SGLT2i on cardiovascular and kidney outcomes among patients with type 2 diabetes mellitus (T2DM), and independent of T2DM status, among patients with heart failure (HF), and chronic kidney disease. METHOD: Medline, Embase, Cochrane library and scientific conferences were searched from inception till September 24, 2020 for randomized controlled trials comparing cardiovascular and kidney outcomes between SGLT2i and placebo. Random effects hazard ratios (HR) with 95% confidence intervals (CIs) were calculated. RESULTS: Eight trials with a combined 59,747 patients were included. In the overall population, SGLT2i reduced the risk of all-cause mortality (HR 0.84; 95% CI [0.78-0.91]), cardiovascular mortality (HR 0.84; 95% CI [0.76-0.93]) hospitalization for HF (HR 0.69; 95% CI [0.64-0.74]), myocardial infarction (HR 0.91; 95% CI [0.84-0.99]), and composite kidney outcome (HR 0.62; 95% CI [0.56-0.70]). There was no significant effect on the risk of stroke (HR 0.98; 95% CI [0.86-1.11]). Results were consistent across subgroups stratified by diabetes and HF status. SGLT2i use was not associated with a greater risk of hypoglycemia (OR 0.92; 95% CI [0.84-1.01]) or amputation (OR 1.25; 95% CI [0.97-1.62]). There were 64 diabetic ketoacidosis events with SGLT2i use and 18 with placebo (OR 2.86; 95% CI [1.39-5.86]). CONCLUSIONS: In patients with cardiometabolic and kidney disease, SGLT2i improved cardiovascular and kidney outcomes, regardless of T2DM, HF, and/or CKD status. The magnitude of risk reduction was largest for hospitalization for HF and progression of kidney disease, more modest for mortality and MI and absent for stroke.

Brugada-type patterns are easily observed in high precordial lead ECGs in collegiate athletes.

BACKGROUND: Displacement of ECG leads can result in unwarranted findings. We assessed the frequency of Brugada-type patterns in athletes when precordial leads were purposely placed upward. METHODS: Four hundred ninety-one collegiate athletes underwent two ECGs: one with standard leads, one with V1 and V2 along the 2nd intercostal space. A positive Brugada-type pattern was defined as ST elevation in V1 or V2 consistent with a Type 1, 2, or 3 pattern in the high-lead ECG. A control group was comprised of 181 outpatients. RESULTS: No Type 1 patterns were seen. In 58 athletes (11.8%), a Brugada-type 2 or 3 pattern was observed. Those with Brugada-type 2 or 3 patterns were more likely male, taller, and heavier. In the control group, 18 (9.9%) had Brugada-type 2 or 3 patterns and were more likely male. CONCLUSIONS: Proper lead positioning is essential to avoid unwarranted diagnosis of a Brugada-type ECG, especially in taller, heavier male athletes.

Inappropriate Subcutaneous Implantable Cardioverter-defibrillator Shocks-A Rare Case of Triple Counting.

Sudden cardiac death (SCD) caused by ventricular tachyarrhythmias is a significant contributor to cardiovascular deaths worldwide. Implantable cardioverter-defibrillators (ICDs) have shown efficacy in preventing and reducing mortality from SCD, but traditional transvenous ICDs have inherent challenges and drawbacks, such as lead fractures, lead-associated endocarditis, and lead failure. To address these issues, subcutaneous ICDs (S-ICDs) have been developed. S-ICDs lack pacing capacity but are a valid alternative for patients at high risk for infection or with difficult venous access. Pre-implantation screening can help prevent inappropriate device shocks. We present a case in which a patient received inappropriate S-ICD therapy, which was attributed to the triple counting of P-, R-, and T-waves in a patient with sinus rhythm. This is an unusual occurrence, and, to the best of our knowledge, there are only a limited number of case reports documenting inappropriate shocks due to the oversensing of P-waves and T-waves.

Psychopathology and symptoms of atrial fibrillation: implications for therapy.

INTRODUCTION: Current guidelines recommend that the choice of AF management strategy be guided by the symptomatic status of the patient when in AF. However, little is known regarding what drives AF symptoms. Several limited studies suggest that psychological distress may be linked with AF symptom severity. METHODS: A total of 300 patients with documented AF completed a questionnaire assessing general health and well-being, including a comprehensive psychological assessment as well as disease-specific measures of AF symptom severity. AF burden was determined by 1-week continuous looping monitor in a subset of patients. Analysis of covariance was used to determine the association between individual measures of depression, anxiety, and somatization disorder symptom severity with measures of general health status and AF-specific symptom severity, adjusting for important confounders. RESULTS: Patients with worsened severity of depression, anxiety, or somatization disorder symptoms had an associated increase in the severity of symptoms attributed to AF regardless of AF severity scale used (P < 0.0001 for each measure of psychological distress). This association persisted after adjusting for important confounders. Increasing severity of depression and anxiety symptoms were also associated with increased visits to medical care for AF management. CONCLUSIONS: Our study demonstrates the consequence of psychological distress on AF-specific symptom severity and healthcare resource utilization. Psychological well-being may strongly influence symptom severity and healthcare utilization. An assessment of psychological distress may be an important adjunct to standard AF management that warrants further study, particularly if symptom relief is the primary goal.

Educational attainment is associated with atrial fibrillation symptom severity.

BACKGROUND: Atrial fibrillation (AF), the most common arrhythmia encountered in clinical practice, is often managed with a rhythm control strategy. Despite the emphasis on symptom relief as the motivation for a rhythm controlling strategy in AF, it remains unclear what factors affect the patient's experienced severity of AF symptoms. We hypothesize that demographic variables may affect AF symptom severity as many AF symptoms (palpitations, dyspnea, fatigue) are nonspecific and may require particular patient insight. METHODS: We assessed demographic variables, cardiac and noncardiac comorbidities, AF burden, and AF-specific self-reported symptom severity in a cohort of 300 outpatients with AF presenting to outpatient electrophysiology clinics. RESULTS: In unadjusted analyses, decreased educational attainment, unemployed working status, and non-Caucasian race were associated with worsened AF symptom severity. After adjusting for potential confounders, the association of decreased educational attainment with worsened AF symptom severity persisted. CONCLUSIONS: Possible links between these demographic features and AF symptom severity are socioeconomic status and health literacy. Further study into the relationship between educational attainment and AF symptom severity is warranted.

Is heart rate in post-hematopoietic stem cell transplant patients clinically relevant?

Patients with hematological malignancies undergoing hematopoietic stem cell transplantation (HSCT) have become a critical treatment option in the treatment of many hematological malignancies, myeloproliferative disorders, and some solid tumors.Although HSCT has the potential of offering either a cure or minimizing disease burden while improving overall survival, HSCT is associated with some morbidity and mortality, particularly hypertension, diabetes, dyslipidemia, and renal disease with an increased cumulative incidence of cardiovascular (CVD) complications.Aside from the usual heart failure and arrhythmias, a less described complication is sinus tachycardia. The latter was once considered an innocuous finding in post-HSCT patients and mostly attributed to dehydration, low counts, deconditioning, chemotherapy, and/or infection.However, new data has shown that a number of these post-HSCT patients may harbor inappropriate sinus tachycardia, which can be associated with the eventual development of heart failure if not identified and treated.We believe that discussion of this topic not only is needed to raise awareness of this condition as patients might no longer be under the care of their oncologists but, most importantly, could be seen at any age, and general health practitioners might otherwise not be aware of this literature.

COVID-19: an unprecedented pandemia with a potential arrhythmic undertone.

Data has shown that intense impact events such as large magnitude earthquakes and the US terrorist attacks of 11 September 2001 have shown us that unforeseen catastrophic events are followed by a significant increase of ventricular arrhythmias (VA) and sudden cardiac death (SCD). We are concerned that similarly, the recent COVID-19 pandemia that not only has dismantled our way of living, in a matter of weeks, but also has challenged all of us beyond our abilities might be also related to an increase in prevalence of VA and SCD. In addition to such provocative suggestions raise in this article we want to convey the message that we must remain vigilant long after we have silenced COVID-19.

Endocardial and Epicardial Rhythmia HDx™ Mapping Verifies Surgical Cox Maze IV Lesion Pattern.

Atrial fibrillation (AF) remains the most common cardiac dysarrhythmia, with a significant impact on the health-care economy. AF occurs as a result of electrical conduction delays within the atrial tissue, which may stem from fibrosis or other mediators that alter atrial tissue conduction substrate. The Cox maze III and IV procedures block these reentry circuits by directly dividing, or breaking, the self-perpetuating circuit and by isolating these circuits away from the intrinsic cardiac conduction pathway. The Convergent procedure, a hybrid approach to AF ablation, coordinates the electrophysiologist and the cardiac surgeon in a simultaneous or sequential endocardial and epicardial procedure. Because the heart remains electrically active, electroanatomical maps, not anatomical landmarks, guide therapy. However, lesion transmurality and contiguity remain inconsistent. The Rhythmia HDx™ mapping system (Boston Scientific, Natick, MA, USA) offers detailed maps of acute lesion patterns during the ablation procedure. However, these maps require instrumentation and technology found in the electrophysiology laboratory, not in the operating room. We herein present a case during which we performed a Cox maze IV procedure and also applied the Rhythmia HDx™ electroanatomical mapping system (Boston Scientific, Natick, MA, USA) at the time of operation. Through this novel approach, we were able to verify the completeness of the lesions created and reach a procedural endpoint confirmed by both epicardial and endocardial maps of successful electrical isolation of the left atrium posterior wall and pulmonary vein pedicle.

Mobile-ECG screening in rural pharmacies: rates of atrial fibrillation and associated risk factors.

INTRODUCTION: Atrial fibrillation (AFib) is a growing health concern, affecting more than 40 million patients worldwide and increasing stroke risk by five times. Community screening initiatives in rural healthcare establishments are becoming more feasible with the development of innovative, mobile-ECG (mECG) technology. The purpose of this research was to characterize increased rates of stroke risk factors and to determine AFib incidence in rural, pharmacy settings. METHODS: The researchers examined the prevalence of risk factors associated with AFib and calculated CHA2DS2-VASc stroke risk scores in a previously undiagnosed AFib community sample of 250 participants. Eligible participants at two rural pharmacies were administered a 1-lead mECG reading. Participants were then asked to complete questionnaires on demographic and medical history information. All participants were given educational materials on AFib and medical referrals when indicated. RESULTS: Prevalence rates of six, known independent stroke risk factors (CHA2DS2-VASc scores: (2.68 ± 1.35)) were significantly higher in the study sample than reported national US averages. Screening via mECG indicated preliminary AFib rates of approximately 4%; however, upon independent adjudication of the readings from three electrophysiologists AFib prevalence ranged between 1% and 8%. DISCUSSION: Collectively, an alarming rate of untreated stroke risk in a rural pharmacy sample was identified by the researchers utilizing mECG technology. These results suggest potential value to the use of mECG technology to screen for AFib in at-risk communities.

Real-time rotational ICE imaging of the relationship of the ablation catheter tip and the esophagus during atrial fibrillation ablation.

INTRODUCTION: Atrioesophageal fistula is a rare complication of atrial fibrillation (AF) ablation that should be avoided. We investigated whether rotational intracardiac echocardiography (ICE) can help to minimize ablation close to the esophagus. METHODS AND RESULTS: We studied 41 patients referred for catheter ablation of refractory AF. A rotational ICE catheter was inserted into the (LA) to determine the location of the esophagus. The esophagus was identified to be either adjacent to the pulmonary vein (PV) ostium or to a cuff 2 cm outside the ostium. Circumferential ablation was performed at the PV ostium, with the exact ablation location determined by ICE. The relationship of the catheter tip to the esophagus was imaged during energy delivery, allowing interruption when respiration moved the tip closer to the esophagus. Out of 41 patients, the esophagus was seen near left-sided PVs in 32 and near right-sided PVs in three patients. The median distance from LA endocardium to esophagus was 2.2 mm (range, 1.4-6 mm). In 21 of 35 patients with a closely related esophagus, ablation over the esophagus was avoided by ablating either lateral or medial to the esophagus. In 14 patients, the esophagus could not be avoided, and risk was minimized by limiting lesion size. Significant movement (>10 mm) of the esophagus during the procedure occurred in 3/41 cases. CONCLUSION: Rotational ICE can accurately determine the distance of ablation sites from the esophagus. Real-time imaging of the relationship of the ablation catheter tip to the esophagus may reduce the incidence of esophageal injury.

A case-crossover analysis of the relationship of air pollution with out-of-hospital sudden unexpected death in Wake County, North Carolina (2013-2015).

Out-of-hospital sudden unexpected deaths are non-accidental deaths that occur without obvious underlying causes and may account for 10% of natural deaths before age 65. Short-term exposure to ambient air pollution is associated with all-cause (non-accidental) and cause-specific (e.g., cardiovascular) mortality, and with immediate exposures often yielding the highest magnitude risk estimates. Few studies have focused on short-term exposure to air pollution and sudden unexpected deaths. Using the University of North Carolina Sudden Unexpected Death in North Carolina population, we examine associations between short-term criteria air pollutant exposures with sudden unexpected deaths using a time-stratified case-crossover design, with data on criteria air pollutants from the Environmental Protection Agency's Air Quality System. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using conditional logistic regression with air pollutant exposures scaled to roughly inter-quartile ranges; models were adjusted for average temperature and relative humidity on event day and preceding 3 days. Potential for confounding by co-pollutants were examined in two pollutant models. ORs for PM2.5 at lag day 1 were elevated (adjusted OR for 5 µg/m3 increase: 1.17 (0.98, 1.40)), and were robust to co-pollutant adjustment. Elevated odds were observed for SO2 at lag day 0, and reduced odds for O3 at lag day 0; however, these associations were somewhat attenuated toward the null (SO2) or were not robust (O3) to co-pollutant adjustment. This analysis in a racially and socioeconomically diverse cohort, with a more inclusive definition of sudden unexpected death than is typically employed offers evidence that PM2.5 may be a clinically relevant trigger of sudden unexpected deaths in susceptible individuals.

Characterization of the mitral isthmus for atrial fibrillation ablation using intracardiac ultrasound from within the coronary sinus.

BACKGROUND: Atrial fibrillation (AF) ablation involving the mitral isthmus and/or the coronary sinus (CS) may result in circumflex artery (Cx) or other collateral structure damage. OBJECTIVE: The purpose of this study was to investigate the feasibility of intracardiac echocardiographic (ICE) imaging from within the CS to characterize mitral isthmus anatomy and guide ablation. METHODS: A 9-Fr sheath was introduced into the CS of 30 patients before AF ablation. A 9-Fr rotational ICE catheter was then advanced within the sheath to the distal CS adjacent to the lateral left atrial (LA) wall. Serial cross-sectional images to document the relations of the LA, Cx, CS, esophagus, and pericardium were obtained at multiple points within the CS during a pullback to the CS ostium. RESULTS: The Cx was identified in 62/150 positions in 25/30 patients. The median (range) of the LA-Cx distance was 3.3 mm (0.7-19.6 mm), and the median CS-Cx distance was 2.0 mm (0.4-9.7 mm). The esophagus was seen in 36/150 positions in 17/30 patients. The median CS-esophagus distance was 4.0 mm (1.4-16.2 mm). The proximity of the Cx and esophagus to the LA and CS varied considerably. The median CS-mitral annulus distance was 11.9 mm (4.1-21.6 mm). After CS cannulation, the ICE imaging took 5 +/- 2 minutes and required 120 +/- 60 seconds of fluoroscopy. CONCLUSIONS: Mitral isthmus anatomy can be accurately characterized by rotational ICE imaging from within the CS. There is great variability in the location and proximity of the Cx, CS, esophagus, and pericardium to the LA. Real-time identification of these structures could help to plan ablation strategies and potentially reduce complications.