Myocardial Cytoskeletal Adaptations in Advanced Kidney Disease.

Background The myocardial cytoskeleton functions as the fundamental framework critical for organelle function, bioenergetics and myocardial remodeling. To date, impairment of the myocardial cytoskeleton occurring in the failing heart in patients with advanced chronic kidney disease has been largely undescribed. Methods and Results We conducted a 3-arm cross-sectional cohort study of explanted human heart tissues from patients who are dependent on hemodialysis (n=19), hypertension (n=10) with preserved renal function, and healthy controls (n=21). Left ventricular tissues were subjected to pathologic examination and next-generation RNA sequencing. Mechanistic and interference RNA studies utilizing in vitro human cardiac fibroblast models were performed. Left ventricular tissues from patients undergoing hemodialysis exhibited increased myocardial wall thickness and significantly greater fibrosis compared with hypertension patients (P<0.05) and control (P<0.01). Transcriptomic analysis revealed that the focal adhesion pathway was significantly enriched in hearts from patients undergoing hemodialysis. Hearts from patients undergoing hemodialysis exhibited dysregulated components of the focal adhesion pathway including reduced ß-actin (P<0.01), ß-tubulin (P<0.01), vimentin (P<0.05), and increased expression of vinculin (P<0.05) compared with controls. Cytoskeletal adaptations in hearts from the hemodialysis group were associated with impaired mitochondrial bioenergetics, including dysregulated mitochondrial dynamics and fusion, and loss of cell survival pathways. Mechanistic studies revealed that cytoskeletal changes can be driven by uremic and metabolic abnormalities of chronic kidney disease, in vitro. Furthermore, focal adhesion kinase silencing via interference RNA suppressed major cytoskeletal proteins synergistically with mineral stressors found in chronic kidney disease in vitro. Conclusions Myocardial failure in advanced chronic kidney disease is characterized by impairment of the cytoskeleton involving disruption of the focal adhesion pathway, mitochondrial failure, and loss of cell survival pathways.

2021 Update on Safety of Magnetic Resonance Imaging: Joint Statement From Canadian Cardiovascular Society/Canadian Society for Cardiovascular Magnetic Resonance/Canadian Heart Rhythm Society.

Magnetic resonance imaging (MRI) is often considered the gold-standard test for characterizing cardiac as well as noncardiac structure and function. However, many patients with cardiac implantable electronic devices (CIEDs) and/or severe renal dysfunction are unable to undergo this test because of safety concerns. In the past 10 years, newer-generation CIEDs and gadolinium-based contrast agents (GBCAs) as well as coordinated care between imaging and heart rhythm device teams have mitigated risk to patients and improved access to MRI at many hospitals. The purpose of this statement is to review published data on safety of MRI in patients with conditional and nonconditional CIEDs in addition to patient risks from older and newer GBCAs. This statement was developed through multidisciplinary collaboration of pan-Canadian experts after a relevant and independent literature search by the Canadian Agency for Drugs and Technologies in Health. All recommendations align with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. Key recommendations include: (1) the development of standardized protocols for patients with a CIED undergoing MRI; (2) patients with MRI nonconditional pacemakers and pacemaker dependency should be programmed to asynchronous mode and those with MRI nonconditional transvenous defibrillators should have tachycardia therapies turned off during the scan; and (3) macrocyclic or newer linear GBCAs should be used in preference to older GBCAs because of their better safety profile in patients at higher risk of nephrogenic systemic fibrosis.

The Guideline-Policy Gap in Direct-Acting Oral Anticoagulants Usage in Atrial Fibrillation: Evidence, Practice, and Public Policy Considerations.

Atrial fibrillation has a high disease burden-both in prevalence and associated consequences. Despite anticoagulation being an effective treatment in atrial fibrillation, stroke prevention is slow to reflect evidence-based practice. Real-world data reveal a substantial portion of patients who would benefit from anticoagulation, yet do not receive it adequately or at all. A large part of this suboptimal treatment is due to the underutilization of direct oral anticoagulants (DOACs). In response to abundant evidence published over a short timeframe, international guidelines have adopted DOAC usage ahead of policy and fund holders. This paper reviews the evidence and values that influence published guidelines, patient-physician decision making, and policy framework on DOAC usage. An important factor is the access gap between patients who qualify for DOAC according to evidence-based guidelines and the subset of this cohort who are eligible for DOAC based on government funded policy. We analyse the Canadian health system in detail-including drug approval and funding process. Health care systems in other countries are explored, with emphasis on similar universal health care systems that may help overcome barriers common to Canada. We will discuss strategies to: (1) improve awareness of the risk and preventability of stroke; (2) enable physicians to provide evidence-based DOAC usage; (3) empower patients to improve adherence and persistence; (4) collect real-life data that encourages patient self-monitoring, physician outcomes auditing, and building evidence that is useful for policy makers; and (5) use postmarketing data in negotiating shared risk management between pharmaceuticals and government to improve access to DOACs.

Lyme Carditis and High-Degree Atrioventricular Block.

Canada has seen a sixfold increase in Lyme disease since being nationally notifiable in 2009. This is the first Canadian series on Lyme carditis manifested as high-degree atrioventricular block. We report 5 recent cases presented over a 2-year period. The variation of nonspecific presentations requires a high index of suspicion for prompt diagnosis and correct management. Recognizing this early would curtail the progression of conduction disorders and potentially avoid permanent pacemaker implantation.

Suspicious index in Lyme carditis: Systematic review and proposed new risk score.

BACKGROUND: Lyme carditis (LC), an early manifestation of Lyme disease that most commonly presents as high-degree atrioventricular block (AVB), usually resolves with antibiotic treatment. When LC is not identified as the cause of AVB, a permanent pacemaker may be inappropriately implanted in a reversible cardiac conduction disorder. HYPOTHESIS: The likelihood that a patient's high-degree AVB is caused by LC can be evaluated by clinical characteristics incorporated into a risk stratification tool. METHODS: A systematic review of all published cases of LC with high-degree AVB, and five cases from the authors' experience, was conducted. The results informed the development of a new risk stratification tool, the Suspicious Index in LC (SILC) score. The SILC score was then applied to each case included in the review. RESULTS: Of the 88 cases included, 51 (58%) were high-risk, 31 (35.2%) intermediate-risk, and 6 (6.8%) low-risk for LC according to the SILC score (sensitivity 93.2%). For the subset of 32 cases that reported on all SILC variables, 24 (75%) cases were classified as high-risk, 8 (25%) intermediate-risk, and 0 low-risk (sensitivity 100%). Specificity could not be assessed (no control group). Notably, 6 of the 11 patients who received permanent pacemakers had reversal of AVB with antibiotic treatment. CONCLUSION: The SILC risk score and COSTAR mnemonic (constitutional symptoms; outdoor activity; sex = male; tick bite; age < 50; rash = erythema migrans) may help to identify LC in patients presenting with high-degree AVB, and ultimately, minimize the implantation of unnecessary permanent pacemakers.

Progression of heart failure after biventricular pacing: Is there a subgroup of "favorable nonresponders"?

BACKGROUND: Left bundle branch block (LBBB) and dominant R wave in lead V1 (RV1) post-biventricular pacing (BiVp) are associated with better clinical outcomes. However, some patients continue to deteriorate despite these favorable electrocardiographic changes. OBJECTIVE: We tested the hypothesis that baseline LBBB and post-BiVp RV1 are associated with better cardiac function and clinical outcomes in patients with progressive deterioration in heart failure after BiVp ("clinical nonresponders") than in patients without these electrocardiographic criteria. METHODS: Consecutive patients with advanced heart failure and BiVp were included. An increase in R-wave amplitude of over 4.5 times the baseline value was defined as RV1. Clinical outcome was survival free of heart transplantation and/or implantation of mechanical circulatory support. RESULTS: A total of 179 (100 (56%) with LBBB; 79 (44%) with non-LBBB) patients with advanced heart failure and BiVp were included. Of the 100 patients with LBBB, 67 (67%) developed RV1 (group 1) but 33 (33%) patients did not develop RV1 (group 2). Of the 79 patients with non-LBBB, 49 (62%) developed RV1 (group 3) and the remaining 30 (38%) patients did not develop RV1 (group 4). Changes in left ventricular ejection fraction and left ventricular end-systolic volume index were not significant in group 1, but deteriorated in the other groups (P < .05). The change in left ventricular end-systolic volume index was associated with the change in QRS duration and absence of RV1 (P < .01). Clinical outcome was most favorable in group 1 (LBBB and RV1). Changes in left ventricular ejection fraction, tricuspid annular plane systolic excursion, and right atrial pressure were associated with clinical outcomes. CONCLUSION: Despite progressive deterioration in heart failure, patients with LBBB and RV1 post-BiVp demonstrate more stable cardiac function and more favorable clinical outcomes than did patients with non-LBBB with or without RV1 post-BiVp.

Culture-negative endocarditis: "whatever remains, however improbable, must be the truth"; the importance of asking the right questions!

The complicated case of a patient with recurrent culture-negative endocarditis with a history of repeated mitral valve replacement is described. Investigations disqualified common pathology but serology revealed a diagnosis of Q fever endocarditis. The ongoing problematic management of this patient is described, followed by a brief review of the clinical features, investigations and treatment of Q fever.