Guideline-Directed Low-Density Lipoprotein Cholesterol Management After Acute Ischemic Stroke: Findings from a National Health Care Service.

Patients with ischemic stroke are at high risk for future cardiovascular events and should be treated intensively with lipid-modifying agents. Combination lipid-lowering therapies are often needed to achieve updated guideline-directed treatment goals. However, real-world data on intensification of lipid-lowering therapies and attainment of low-density lipoprotein cholesterol (LDL-C) targets early after ischemic stroke are limited. We extracted data from the largest healthcare provider in Israel on patients hospitalized with acute ischemic stroke between January 2020 and February 2022. Included were 3,027 patients surviving ≥1 year after stroke, with documented LDL-C levels and lipid-lowering medications at 2 time periods (0 to 3 months and 6 to 12 months after discharge). Participants were classified according to preexisting stroke and/or coronary artery disease. The use of combination lipid-lowering therapy (ezetimibe and/or proprotein convertase subtilisin/kexin type 9 [monoclonal antibodies] inhibitor plus statin) in the study population increased between the 2 timepoints from 3.6% to 5.1%, reaching 10.5% in those with previous coronary artery disease and stroke. LDL-C levels <70 and <55 mg/100 ml were attained by 42.3% and 22.9% of patients early after hospitalization, and in 49.5% and 27.1% during 6 to 12 months after hospitalization, respectively. Attainment of guideline-recommended LDL-C goals was higher in patients treated with combination lipid-lowering therapies and in those with preexisting cardiovascular disease. In conclusion, despite the advances in drug development and the availability of several mechanisms to lower cholesterol levels, the attainment of guideline-recommended LDL-C targets after acute ischemic stroke is suboptimal. Intensification of treatment with combination lipid-lowering therapies after hospitalization is uncommonly performed in clinical practice, even in those with preexisting cardiovascular disease.

Direct Oral Anticoagulants Versus Warfarin in Patients With Atrial Fibrillation and Valve Replacement or Repair.

Background We sought to examine outcomes of direct oral anticoagulants (DOACs) versus warfarin in atrial fibrillation with valve repair/replacement. Methods and Results Two atrial fibrillation cohorts from Medicare were identified from 2015 to 2019. They comprised patients who underwent surgical or transcatheter mitral valve repair (MV repair cohort) and surgical aortic or mitral bioprosthetic or transcatheter aortic valve replacement (bioprosthetic cohort). Each cohort was divided into warfarin and DOACs (apixaban, rivaroxaban, and dabigatran) groups. Study outcomes included mortality, stroke, and major bleeding. Inverse probability weighting was used for adjustment between the 2 groups in each cohort. The MV repair cohort included 1178 patients. After a median of 468 days, DOACs were associated with lower risk of mortality (hazard ratio [HR], 0.67 [95% CI, 0.55-0.82], P<0.001), ischemic stroke (HR, 0.72 [95% CI, 0.52-1.00], P=0.05) and bleeding (HR, 0.79 [95% CI, 0.63-0.99], P=0.04) compared with warfarin. The bioprosthetic cohort included 8089 patients. After a median follow-up of 413 days, DOACs were associated with similar risk of mortality (adjusted HR, 0.93 [95% CI, 0.86-1.01], P=0.08), higher risk of ischemic stroke (adjusted HR, 1.27 [95% CI, 1.13-1.43], P<0.001), and lower risk of bleeding (adjusted HR, 0.86 [95% CI, 0.80-0.93], P<0.001) compared with warfarin. Conclusions In patients with atrial fibrillation, DOACs are associated with similar mortality, lower bleeding, but higher stroke with bioprosthetic valve replacement and lower risk of all 3 outcomes with MV repair compared with warfarin.

Super and Nonresponders to Catheter Ablation for Atrial Fibrillation: A Quality-of-Life Assessment Using Patient Reported Outcomes.

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Assessment of Low LDL Cholesterol in Patients Treated by PCSK9 Inhibition: Comparison of Martin/Hopkins and Friedewald Estimations.

PURPOSE: Recent guidelines recommend further reduction of low-density lipoprotein cholesterol (LDL-C) in high-risk populations. The use of proprotein convertase subtilisin/kexin type-9 inhibitors (PCSK9i) enables many patients to achieve profound reduction in LDL-C. However, in patients with low cholesterol, the commonly used Friedewald equation tends to underestimate LDL-C, which may result in undertreatment. We aimed to compare Friedewald LDL-C estimation with the more novel Martin/Hopkins method in PCSK9i-treated patients achieving low LDL-C. METHODS: We investigated high-risk patients treated by PCSK9i in whom Friedewald LDL-C levels were < 70 mg/dL and triglycerides ≤ 300 mg/dL. LDL-C was additionally assessed by the Martin/Hopkins method. The compatibility between estimations was evaluated using methods of concordance and reclassification between LDL-C categories (< 25, 25-40, 40-55, 55-70 mg/dL) and according to triglyceride strata. RESULTS: Mean age was 65 ± 10 years. The correlation coefficient between LDL-C estimations was r = 0.898. Martin/Hopkins reclassified 269 of the 608 patients (44%) to a higher LDL-C category, with 14% of the patients reaching LDL-C > 70 mg/dL. Of the 390 patients achieving Friedewald LDL-C < 55 mg/dL, 113 (29%) were estimated to have LDL-C ≥ 55 mg/dL by the Martin/Hopkins equation. The magnitude of discordance between LDL-C estimates was more pronounced in hypertriglyceridemic patients in whom LDL-C reclassification from < 55 to ≥ 55 mg/dL was observed in 48%. CONCLUSIONS: In real-world practice of high-risk patients achieving low LDL-C under PCSK9i, Martin/Hopkins algorithm displayed significant proportion of LDL-C upward discordance compared to the Friedewald equation, particularly observed in patients with elevated triglycerides, identifying patients that may need treatment intensification.

Low venous thromboembolism incidence in high risk medical patients in an Israeli hospital. Can risk assessment be extrapolated to different populations?

BACKGROUND: Guidelines recommend venous thromboembolism (VTE) prophylaxis in hospitalized medical patients with Padua prediction score (PPS) ≥4 points. This recommendation is based on the high risk of symptomatic VTE observed among these patients in the Italian PPS derivation study, and the fivefold risk reduction with VTE-prophylaxis. This study aims to assess the incidence of VTE in high risk medical patients in a medium sized hospital in Israel. METHOD: In this retrospective cohort study, data was collected of all medical patients hospitalized between January and June 2014. Patients were classified into low and high risk groups according to their PPS score, and according to whether they received anticoagulant thromboprophylaxis for VTE. Patients were further randomly selected to compare high risk patients that did or did not receive anticoagulant thromboprophylaxis. We further compared VTE incidence in high and low risk patients not treated with thromboprophylaxis. A search was conducted for diagnoses of venous thromboembolism and death during hospitalization and the following 90 days. RESULTS: 568 high risk patients (PPS ≥4 points) were included, 284 treated with prophylactic anticoagulation and 284 not. There were no VTE events in either group. There was no difference in mortality. A total of 642 non anticoagulated patients were randomly selected, 474 low risk and 168 high risk. There were no VTE events in either group. CONCLUSIONS: The risk of VTE appears to be very low in our study, suggesting that among medical patients with PPS ≥4, the risk of VTE may differ dramatically between populations.

Impact of Atrial Fibrillation on Exercise Capacity and Mortality in Heart Failure With Preserved Ejection Fraction: Insights From Cardiopulmonary Stress Testing.

BACKGROUND: Atrial fibrillation (AF) has been objectively associated with exercise intolerance in patients with heart failure with reduced ejection fraction; however, its impact in patients with heart failure with preserved ejection fraction has not been fully scrutinized. METHODS AND RESULTS: We identified 1744 patients with heart failure and ejection fraction ≥50% referred for cardiopulmonary stress testing at the Cleveland Clinic (Cleveland, OH), 239 of whom had AF. We used inverse probability of treatment weighting to balance clinical characteristics between patients with and without AF. A weighted linear regression model, adjusted for unbalanced variables (age, sex, diagnosis, hypertension, and ß-blocker use), was used to compare metabolic stress parameters and 8-year total mortality (social security index) between both groups. Weighted mean ejection fraction was 58±5.9% in the entire population. After adjusting for unbalanced weighted variables, patients with AF versus those without AF had lower mean peak oxygen consumption (18.5±6.2 versus 20.3±7.1 mL/kg per minute), oxygen pulse (12.4±4.3 versus 12.9±4.7 mL/beat), and circulatory power (2877±1402 versus 3351±1788 mm Hg·mL/kg per minute) (P<0.001 for all comparisons) but similar submaximal exercise capacity (oxygen consumption at anaerobic threshold, 12.0±5.1 versus 12.4±6.0mL/kg per minute; P =0.3). Both groups had similar peak heart rate, whereas mean peak systolic blood pressure was lower in the AF group (150±35 versus 160±51 mm Hg; P<0.001). Moreover, AF was associated with higher total mortality. CONCLUSIONS: In the largest study of its kind, we demonstrate that AF is associated with peak exercise intolerance, impaired contractile reserve, and increased mortality in patients with heart failure with preserved ejection fraction. Whether AF is the primary offender in these patients or merely a bystander to worse diastolic function requires further investigation.

Urinary tract infections in patients with type 2 diabetes mellitus: review of prevalence, diagnosis, and management.

Urinary tract infections are more common, more severe, and carry worse outcomes in patients with type 2 diabetes mellitus. They are also more often caused by resistant pathogens. Various impairments in the immune system, poor metabolic control, and incomplete bladder emptying due to autonomic neuropathy may all contribute to the enhanced risk of urinary tract infections in these patients. The new anti-diabetic sodium glucose cotransporter 2 inhibitors have not been found to significantly increase the risk of symptomatic urinary tract infections. Symptoms of urinary tract infection are similar to patients without diabetes, though some patients with diabetic neuropathy may have altered clinical signs. Treatment depends on several factors, including: presence of symptoms, severity of systemic symptoms, if infection is localized in the bladder or also involves the kidney, presence of urologic abnormalities, accompanying metabolic alterations, and renal function. There is no indication to treat diabetic patients with asymptomatic bacteriuria. Further studies are needed to improve the treatment of patients with type 2 diabetes and urinary tract infections.

Risk factors for 1-year mortality among patients with cardiac implantable electronic device infection undergoing transvenous lead extraction: the impact of the infection type and the presence of vegetation on survival.

AIMS: Infections of cardiac implantable electronic devices (CIEDs) are infrequent but carry significant morbidity and mortality. We aimed to assess risk factors for 1-year mortality among patients with CIED infection and to evaluate if the type of infection and the presence of vegetation affect survival. METHODS AND RESULTS: We reviewed records of all patients with infected CIEDs who underwent transvenous lead extraction at our tertiary care centre between 2002 and 2008. Patients who presented with infection involving the device pocket were classified as 'pocket infection', and those who presented with bacteraemia with or without vegetation and a pocket that looked benign were classified as 'endovascular infection' (EVI). One-year mortality was examined using the social security death index. Five hundred and two patients were identified (68.5 ± 15 years); 289 (58%) had pocket infection and 213 (42%) had EVI. One-year mortality rate was 20%. Using multivariable Cox regression model, EVI was associated with significantly higher 1-year mortality (hazard ratio 2.1, P-value 0.0008). Among patients with EVI, 100 patients had vegetation on transoesophageal echo; however, there was no difference in 1-year mortality between patients with EVI and vegetation compared with patients with EVI and no vegetation (27, 27 vs. 40, 35%; P-value 0.188). Risk factors for 1-year mortality among patients with EVI included renal failure, worse functional class, and bleeding requiring transfusion. The presence of vegetation was not associated with increased 1-year mortality. CONCLUSION: One-year mortality is higher among patients with EVI compared with patients with pocket infection; this increased mortality does not seem to be related to the presence of vegetations.

Outcomes after endocarditis or device infection in patients with left ventricular epicardial leads versus coronary sinus leads.

BACKGROUND: There is scant data about outcomes in patients with left ventricular epicardial (LVE) leads who develop endocarditis or device-related infection. OBJECTIVE: This retrospective study evaluated mortality and recurrence of infection among patients with LVE leads in comparison to patients with endovascular coronary sinus (CS) leads after the development of endocarditis or device-related infection. METHODS: Patients with cardiac resynchronization therapy (CRT) devices who developed endocarditis or pocket infection over 5 years at Cleveland Clinic were included in the study. The groups were all patients with LVE leads versus CRT devices without epicardial leads that developed endocarditis or pocket infection. Mortality was assessed using the Social Security Death Index and re-infection was assessed by reviews of the medical record. RESULTS: Prospective extraction of the CRT device and leads occurred among all 50 patients with CS leads and 8 of the 14 patients with LVE leads. The survival rate was 92.9 versus 92 % and freedom from re-infection rate was 64.3 versus 80 % in the patients with LVE leads versus CS leads, respectively, over 1 year (P value = 0.918 and 0.226, respectively). At 3 years, the survival rate in LVE lead group was 92.9 % and freedom from re-infection rate was 64.3 % in comparison to survival rate of 90 % and freedom from re-infection rate of 68 % in the CS group (P value = 0.751 and 0.798, respectively). CONCLUSION: After development of endocarditis or pocket infection, no statistically significant differences were seen in mortality, or recurrent infection between patients with LVE leads and those with CS leads.

Implantable cardioverter-defibrillator FDA safety advisories: Impact on patient mortality and morbidity.

BACKGROUND: A significant proportion of implantable cardioverter-defibrillators (ICDs) have been subject to Food and Drug Administration (FDA) advisories. The impact of device advisories on mortality or patient care is poorly understood. Although estimated risks of ICD generators under advisory are low, dependency on ICD therapies to prevent sudden death justifies the assessment of long-term mortality. OBJECTIVE: To test the association of FDA advisory status with long-term mortality. METHODS: The study was a retrospective, single-center review of clinical outcomes, including device malfunctions, in patients from implantation to either explant or death. Patients with ICDs first implanted at Cleveland Clinic between August 1996 and May 2004 who became subject to FDA advisories on ICD generators were identified. Mortality was determined by using the Social Security Death Index. RESULTS: In 1644 consecutive patients receiving first ICD implants, 704 (43%) became subject to an FDA advisory, of which 172 (10.5%) were class I and 532 (32.3%) were class II. ICDs were explanted before advisory notifications in 14.0% of class I and 10.1% of class II advisories. Among ICDs under advisory, 28 (4.0%) advisory-related and 15 non-advisory- related malfunctions were documented. Over a median follow-up of 70 months, 814 patients died. Kaplan-Meier 5-year survival rate was 65.6% overall, and 64.2, 61.1, and 69.3% in patients with no, class I, and class II advisories, respectively (P = .17). CONCLUSIONS: ICD advisories impacted 43% of the patients. Advisory-related malfunctions affected 4% within the combined advisory group. Based on a conservative management strategy, ICDs under advisory were not associated with increased mortality over a background of significant disease-related mortality.

Assessment of left atrial mechanics in patients with atrial fibrillation: comparison between two-dimensional speckle-based strain and velocity vector imaging.

BACKGROUND: Two-dimensional (2D) speckle tracking-derived left atrial (LA) strain (ε) facilitates comprehensive evaluation of LA contractile, reservoir, and conduit function; however, its dependence on the individual software used for assessment has not been evaluated. The aim of this study was to compare LA ε derived from two different speckle-tracking software technologies, Velocity Vector Imaging (VVI) and 2D speckle-tracking echocardiography (STE). METHODS: VVI-derived and 2D STE-derived global longitudinal LA ε and ε rate (SR) were directly compared in 127 patients (mean age, 62 ± 10 years) with atrial fibrillation. Peak negative, peak positive, and total ε (corresponding to LA contractile, conduit, and reservoir function) were measured during sinus rhythm. Late negative (LA contraction), peak positive (left ventricular systole), and early negative (left ventricular early diastole) SR were also measured. RESULTS: The measurement of LA ε and SR by both software was feasible in high proportions of patients (93% with VVI and 93% with 2D STE). The average analysis of ε(negative) was -7.24 ± 3.87% by VVI and -7.30 ± 3.37% by 2D STE (P = .84). The average analysis of ε(positive) was 14.52 ± 5.82% by VVI and 10.74 ± 4.51% by 2D STE (P < .01). The average analysis of ε(total) was 21.76 ± 7.39% by VVI and 18.04 ± 5.98% by 2D STE (P < .01). VVI-derived and 2D STE-derived ε(positive), ε(negative), and ε(total) had good correlations with one another (R = 0.79, R = 0.75, and R = 0.80), with low mean differences. Late negative, peak positive, and early negative SR were correlated less well (R = 0.78, R = 0.71, and R = 0.67). CONCLUSIONS: LA ε measurement using both VVI and 2D STE is feasible in a large proportion of patients in clinical practice. VVI and 2D STE provide comparable LA ε and SR measurements for LA contractile function.

Endoscopic fiberoptic assessment of balloon occlusion of the pulmonary vein ostium in humans: comparison with phased-array intracardiac echocardiography.

BACKGROUND: Anatomic pulmonary vein (PV) variants may affect the ability to position balloon catheter systems at the left atrium (LA)-PV junction with complete circumferential contact, resulting in ineffective PV isolation. OBJECTIVES: This feasibility study was performed to assess the use of the fiberoptic endoscopic light ring balloon catheter (ELRBC) in accessing the PVs and achieving adequate contact at the LA-PV junction, as visualized by phased-array intracardiac echocardiography (ICE). METHODS: We enrolled five men (mean age 59 +/- 8 years) with drug-refractory atrial fibrillation. The ELRBC consisted of a 25-mm balloon catheter with an integral endoscope contained within the balloon and a custom deflectable sheath. At the end of conventional PV isolation, the ELRBC was inserted into the LA in an attempt to position the balloon at each PV ostium. The real position of the ELRBC at this level was assessed by ICE in all patients. RESULTS: All but two PVs (right inferior PVs) (89%) were accessed with the ELRBC in a mean time of 17 +/- 3 minutes, and complete circumferential contact was visualized with the fiberoptic endoscopic component in 15 of 16 PVs accessed (94%). Contact was also confirmed by the absence of color Doppler flow through the balloon-occluded PV, as seen on ICE. On two occasions a gap was seen with the fiberoptic endoscope and visualized by the ICE only after optimization of the echo window. No complications were observed. CONCLUSIONS: The ELRBC is able to access the PV without complications. The endoscope and ICE were complementary for positioning of the balloon at the LA-PV junction and for the definition of circumferential contact.

Assessment of temperature, proximity, and course of the esophagus during radiofrequency ablation within the left atrium.

BACKGROUND: Left atrioesophageal fistula is a devastating complication of atrial fibrillation ablation. There is no standard approach for avoiding this complication, which is caused by thermal injury during ablation. The objectives of this study were to evaluate the course of the esophagus and the temperature within the esophagus during pulmonary vein antrum isolation (PVAI) and correlate these data with esophagus tissue damage. METHODS AND RESULTS: Eight-one patients presenting for PVAI underwent esophagus evaluation that included temperature probe placement. Esophagus course was obtained with computed tomography, 3D imaging (NAVX), or intracardiac echocardiography. For each lesion, the power, catheter and esophagus temperature, location, and presence of microbubbles were recorded. Lesion location and esophagus course were defined with 6 predetermined left atrial anatomic segments. Endoscopy evaluated tissue changes during and after PVAI. Of 81 patients, the esophagus coursed near the right pulmonary veins in 23 (28.4%), left pulmonary veins in 31 (38.3%), and mid-posterior wall in 27 (33%). Esophagus temperature was significantly higher during left atrial lesions along its course than with lesions elsewhere (38.9+/-1.4 degrees C, 36.8+/-0.5 degrees C, P<0.01). Lesions that generated microbubbles had higher esophagus temperatures than those without (39.3+/-1.5 degrees C, 38.5+/-0.9 degrees C, P<0.01). Power was not predictive of esophagus temperatures. Distance between the esophagus and left atrium was 4.4+/-1.2 mm. CONCLUSIONS: Lesions near the course of the esophagus that generated microbubbles significantly increased esophagus temperature compared with lesions that did not. Power did not correlate with esophagus temperatures. Esophagus variability makes the avoidance of lesions along its course difficult. Rather than avoiding posterior lesions, emphasis could be placed on better esophagus monitoring for creation of safer lesions.