Stroke-induced chronic systolic dysfunction driven by sympathetic overactivity.

OBJECTIVE: Cardiac diseases are established risk factors for ischemic stroke incidence and severity. Conversely, there is increasing evidence that brain ischemia can cause cardiac dysfunction. The mechanisms underlying this neurogenic heart disease are incompletely understood. Although it is established that ischemic stroke is associated with cardiac arrhythmias, myocardial damage, elevated cardiac enzymes, and plasma catecholamines in the acute phase, nothing is known about the delayed consequences of ischemic stroke on cardiovascular function. METHODS: To determine the long-term cardiac consequences of a focal cerebral ischemia, we subjected young and aged mice to a 30-minute transient middle cerebral artery occlusion and analyzed cardiac function by serial transthoracic echocardiography and hemodynamic measurements up to week 8 after surgery. Finally, animals were treated with metoprolol to evaluate a pharmacologic treatment option to prevent the development of heart failure. RESULTS: Focal cerebral ischemia induced a long-term cardiac dysfunction with a reduction in left ventricular ejection fraction and an increase in left ventricular volumes; this development was associated with higher peripheral sympathetic activity. Metoprolol treatment prevented the development of chronic cardiac dysfunction by decelerating extracellular cardiac remodeling and inhibiting sympathetic signaling relevant to chronic autonomic dysfunction. INTERPRETATION: Focal cerebral ischemia in mice leads to the development of chronic systolic dysfunction driven by increased sympathetic activity. If these results can be confirmed in a clinical setting, treating physicians should be attentive to clinical signs of heart failure in every patient after ischemic stroke. Therapeutically, the successful ß-blockade with metoprolol in mice could also have future clinical implications. Ann Neurol 2017;82:729-743.

Ablation Parameters Predicting Pulmonary Vein Reconnection after Very High-Power Short-Duration Pulmonary Vein Isolation.

BACKGROUND: Recurrences due to discontinuity in ablation lines are substantial after pulmonary vein isolation (PVI) with radiofrequency ablation for atrial fibrillation. Data are scarce regarding the durability predictors for very high-power short-duration (vHPSD, 90 W/4 s) ablation. METHODS: A total of 20 patients were enrolled, who underwent 90 W PVI and a mandatory remapping procedure at 3 months. First-pass isolation (FPI) gaps, and acute pulmonary vein reconnection (PVR) sites were identified at the index procedure; and chronic PVR sites were identified at the repeated procedure. We analyzed parameters of ablation points (n = 1357), and evaluated their roles in predicting a composite endpoint of FPI gaps, acute and chronic PVR. RESULTS: In total, 45 initial ablation points corresponding to gaps in the ablation lines were analyzed. Parameters associated with gaps were interlesion distance (ILD), baseline generator impedance, mean current, total charge, and loss of catheter-tissue contact. The optimal ILD cut-off for predicting gaps was 3.5 mm anteriorly, and 4 mm posteriorly. CONCLUSIONS: Biophysical characteristics dependent on generator impedance could affect the efficacy of vHPSD PVI. The use of smaller ILDs is required for effective and durable PVI with vHPSD compared to the consensus targets with lower power ablation, and lower ILDs for anterior applications seem necessary compared to posterior points.

Adherence to the CLOSE Protocol and Low Baseline Generator Impedance Are Independent Predictors of Durable Pulmonary Vein Isolation.

Background: Atrial fibrillation (AF) recurrence after pulmonary vein isolation (PVI) is predominantly attributed to pulmonary vein reconnection (PVR). Predictors of AF recurrence have been widely studied; however, data are scarce on procedural parameters that predict chronic PVR. We aimed to study PVR rates and predictors of PVR. Methods: We retrospectively included 100 patients who underwent repeated ablation due to AF recurrence after initial PVI with the CARTO system. PVR was determined during the repeated procedure by electrophysiological evaluation, and initial procedural characteristics predicting PVR were studied, including adherence to the CLOSE protocol, use of high power, first-pass isolation (FPI), and baseline generator impedance (BGI). Results: Thirty-eight patients underwent initial CLOSE-guided PVI, and sixty-two underwent initial non-CLOSE PVI. A repeat procedure was performed 23 ± 16 months after the initial procedure. In total, PVR was found in 192 of 373 PVs (51.5%), and all PVs were isolated in 17/100 (17%) patients. Factors associated with all PVs being isolated were adherence to the CLOSE protocol, a higher power setting, the presence of bilateral FPI, and lower BGI (88% vs. 28%, p < 0.0001; 37.5 W vs. 30 W, p = 0.0276; 88.2% vs. 40.4%, p = 0.0007; and 127.6 Ω vs. 136.6 Ω, p = 0.0027, respectively). In initial procedures with adherence to the CLOSE protocol, the FPI rate was significantly higher (73.7% vs. 25%, p < 0.0001), while there were no significant differences in terms of procedure time and left atrial dwell time (81 vs. 85 min, p = 0.83; and 60 vs. 58 min, p = 0.08, respectively). BGI ≥ 130 Ω (AUC = 0.7403, sensitivity: 77.1%, specificity: 68.8%, p = 0.0032) was associated with a significantly higher probability of PVR (OR = 6.757; p < 0.0001). In multivariable analysis, independent predictors for PVR were non-adherence to the CLOSE protocol and BGI ≥ 130 Ω. Conclusions: Our findings indicate that adherence to the CLOSE protocol and baseline generator impedance < 130 Ω during AF ablation are independent predictors of PVI durability.

Pathophysiology of Heart Failure.

Heart failure is considered an epidemic disease in the modern world affecting approximately 1% to 2% of adult population. It presents a multifactorial, systemic disease, in which--after cardiac injury--structural, neurohumoral, cellular, and molecular mechanisms are activated and act as a network to maintain physiological functioning. These coordinated, complex processes lead to excessive volume overload, increased sympathetic activity, circulation redistribution, and result in different, parallel developing clinical signs and symptoms. These signs and symptoms sum up to an unspecific clinical picture; thus invasive and noninvasive diagnostic tools are used to get an accurate diagnosis and to specify the underlying cause. The most important, outcome determining factor in heart failure is its constant progression. Constant optimizing of pharmatherapeutical regimes, novel targets, and fine regulation of these processes try to keep these compensatory mechanisms in a physiological range. Beside pharmacological therapy, interventional and surgical therapy options give new chances in the management of heart failure. For the optimization and establishment of these and novel therapeutical approaches, complete and comprehensive understanding of the underlying mechanisms is essentially needed. Besides diagnosis and treatment, efforts should be made for better prevention in heart failure by treatment of risk factors, or identifying and following risk groups. This summary of the pathophysiology of heart failure tries to give a compact overview of basic mechanisms and of the novel unfolding, progressive theory of heart failure to contribute to a more comprehensive knowledge of the disease.