Tricuspid leaflet flail after Micra™ leadless pacemaker implantation: a case report.

Background: Currently, the leadless pacemaker indications are limited to few and highly selected cases. Case summary: We describe the first reported case of an atrioventricular Micra™ leadless pacemaker implantation complicated by tricuspid posterior leaflet flail with severe regurgitation in a 29-year-old man affected by asymptomatic and progressive high degree atrio-ventricular block. The patient was then treated with endoscopic tricuspid valve repair, leadless pacemaker removal and implantation of an epicardial pacemaker. Discussion: Leadless pacemaker complications are multiple, hence it is essential to ensure a safe procedure, especially in the younger patients. We thought that the application of a transesophageal echocardiography guidance might mitigate the risk of major complications.

Substrate-dependent risk stratification for implantable cardioverter defibrillator therapies using cardiac magnetic resonance imaging: The importance of T1 mapping in nonischemic patients.

INTRODUCTION: The role of implantable cardioverter defibrillators (ICDs) in nonischemic cardiomyopathy is unclear and better risk-stratification is required. We sought to determine if T1 mapping predicts appropriate defibrillator therapy in patients with nonischemic cardiomyopathy. We studied a mixed cohort of ischemic and nonischemic patients to determine whether different cardiac magnetic resonance (CMR) applications (T1 mapping, late gadolinium enhancement, and Grayzone) were selectively predictive of therapies for the different arrhythmic substrates. METHODS AND RESULTS: We undertook a prospective longitudinal study of consecutive patients receiving defibrillators in a tertiary cardiac center. Participants underwent CMR myocardial tissue characterization using T1 mapping and conventional CMR scar assessment before device implantation. QRS duration and fragmentation on the surface electrocardiogram were also assessed. The primary endpoint was appropriate defibrillator therapy. One-hundred thirty patients were followed up for a median of 31 months (IQR ± 9 months). In nonischemic patients, T1_native was the sole predictor of the primary endpoint (hazard ratio [HR] 1.12 per 10 millisecond increment in value [95% confidence interval [CI] 1.04-1.21; P ≤ 0.01]). In ischemic patients, Grayzone_2SD-3SD was the strongest predictor of appropriate therapy (HR 1.34 per 1% left ventricular increment in value [95% CI 1.03-1.76; P = 0.03]). QRS fragmentation correlated well with myocardial scar core (receiver operating characteristic area under the curve [ROC AUC] 0.64; P = 0.02) but poorly with T1_native (ROC AUC 0.4) and did not predict appropriate therapy. CONCLUSIONS: In the medium-long term, T1_native mapping was the only independent predictor of therapy in nonischemic patients, whereas Grayzone was a better predictor in ischemic patients. These findings suggest a potential role for T1_native mapping in the selection of patients for ICDs in a nonischemic population.

Pathogenesis of target organ damage in hypertension: role of mitochondrial oxidative stress.

Hypertension causes target organ damage (TOD) that involves vasculature, heart, brain and kidneys. Complex biochemical, hormonal and hemodynamic mechanisms are involved in the pathogenesis of TOD. Common to all these processes is an increased bioavailability of reactive oxygen species (ROS). Both in vitro and in vivo studies explored the role of mitochondrial oxidative stress as a mechanism involved in the pathogenesis of TOD in hypertension, especially focusing on atherosclerosis, heart disease, renal failure, cerebrovascular disease. Both dysfunction of mitochondrial proteins, such as uncoupling protein-2 (UCP2), superoxide dismutase (SOD) 2, peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α), calcium channels, and the interaction between mitochondria and other sources of ROS, such as NADPH oxidase, play an important role in the development of endothelial dysfunction, cardiac hypertrophy, renal and cerebral damage in hypertension. Commonly used anti-hypertensive drugs have shown protective effects against mitochondrial-dependent oxidative stress. Notably, few mitochondrial proteins can be considered therapeutic targets on their own. In fact, antioxidant therapies specifically targeted at mitochondria represent promising strategies to reduce mitochondrial dysfunction and related hypertensive TOD. In the present article, we discuss the role of mitochondrial oxidative stress as a contributing factor to hypertensive TOD development. We also provide an overview of mitochondria-based treatment strategies that may reveal useful to prevent TOD and reduce its progression.

Pathogenesis of chronic cardiorenal syndrome: is there a role for oxidative stress?

Cardiorenal syndrome is a frequently encountered clinical condition when the dysfunction of either the heart or kidneys amplifies the failure progression of the other organ. Complex biochemical, hormonal and hemodynamic mechanisms underlie the development of cardiorenal syndrome. Both in vitro and experimental studies have identified several dysregulated pathways in heart failure and in chronic kidney disease that lead to increased oxidative stress. A decrease in mitochondrial oxidative metabolism has been reported in cardiomyocytes during heart failure. This is balanced by a compensatory increase in glucose uptake and glycolysis with consequent decrease in myocardial ATP content. In the kidneys, both NADPH oxidase and mitochondrial metabolism are important sources of TGF-ß1-induced cellular ROS. NOX-dependent oxidative activation of transcription factors such as NF-kB and c-jun leads to increased expression of renal target genes (phospholipaseA2, MCP-1 and CSF-1, COX-2), thus contributing to renal interstitial fibrosis and inflammation. In the present article, we postulate that, besides contributing to both cardiac and renal dysfunction, increased oxidative stress may also play a crucial role in cardiorenal syndrome development and progression. In particular, an imbalance between the renin-angiotensin-aldosterone system, the sympathetic nervous system, and inflammation may favour cardiorenal syndrome through an excessive oxidative stress production. This article also discusses novel therapeutic strategies for their potential use in the treatment of patients affected by cardiorenal syndrome.