Improvement in quality of life with sacubitril/ /valsartan in cardiac resynchronization non-responders: The RESINA (RESynchronization plus an Inhibitor of Neprilysin/Angiotensin) registry.

BACKGROUND: Clinical management of cardiac resynchronization therapy (CRT) non-responders is difficult, and their prognosis is poor. The aim of the present study was to evaluate whether treatment with sacubitril/valsartan can improve quality of life (QoL) parameters in these patients. METHODS: Thirty five non-responders to CRT were included (75 ± 7 years, 28% females, mean left ventricular ejection fraction 28 ± 8%, 54% non-ischemic cardiomyopathy) with maximally optimized drug therapy and New York Heart Association class II-III. They were all on angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers and were switched to sacubitril/valsartan. One week before and 6 months after initiation of the therapy they completed both the Minnesota Living with Heart Failure (MLWHF) and the 12-item Kansas City Cardiomyopathy Questionnaires (KCCQ-12). The primary outcome was the effect of sacubitril/valsartan on the physical, clinical, social and emotional QoL parameters and number of hospitalizations. RESULTS: The mean total scores of both questionnaires improved from baseline to the follow-up visit at 6-months (KCCQ-12 40 ± 10 to 47 ± 10; p < 0.001; MLWHF 40 ± 15 to 29 ± 15; p < 0.001). The best results were seen in the KCCQ-12 total symptom domains (77% improvement), the MLWHF physical domain (81% improvement), and the MLWHF emotional domain (71% improvement). Two patients died during follow-up. The mean number of hospitalizations reduced significantly (1 ± 0.6 vs. 0.5 ± 0.8; p = 0.003) CONCLUSIONS: In CRT non-responders, sacubitril/valsartan significantly improved overall QoL, physical limitations and emotional domains and reduced the number of hospitalizations.

A novel simple, fast, and safe approach for effective superior vena cava isolation using the third-generation cryoballoon.

BACKGROUND: Superior vena cava (SVC) isolation with radiofrequency energy remains a challenge due to potential side effects, especially phrenic nerve (PN) or sinus node injury. The purpose of this study was to evaluate the feasibility of a novel SVC isolation technique using the third-generation cryoballoon (CB3). METHODS: Patients undergoing atrial fibrillation (AF) ablation were prospectively included. The procedure was performed with the CB3, beginning with the pulmonary veins and ending with SVC isolation. During applications in the SVC, continuous PN capture and sinus rate were monitored. Once reached SVC isolation during the application, 60 s more was applied, with no bonus application. If after 90 s the SVC was not isolated, application was stopped. A maximum number of four applications were permitted. RESULTS: Thirty patients (62 ± 9 years; 74% male, 78% paroxysmal AF) were included. No SVC activity was observed in two patients. Success rate for SVC isolation was 89%. Mean number of applications per patient was 2.3 ± 1. Mean time to SVC isolation was 37 ± 20  s. Mean duration of application was 92 ± 15 s. Mean total time of procedure for SVC isolation was 218 ± 43 s. We recorded only two complications: one transient PN palsy and one short and transient sinus arrest. After a mean follow-up of 5 ± 2 months, 89% are free from arrhythmia recurrence. CONCLUSIONS: We present a promising simple SVC-isolation technique using CB3, featuring a high success rate and very low incidence of complications.

Detecting Atrial Fibrillation in Patients With an Embolic Stroke of Undetermined Source (from the DAF-ESUS registry).

Atrial fibrillation (AF) causes a substantial proportion of embolic strokes of undeterminded source (ESUS). Effective detection of subclinical AF (SCAF) has important therapeutic implications. We conducted a prospective study to determine the prevalence of SCAF in patients with ESUS through of a 21-day Holter monitoring. In an early-monitoring group, Holter was initiated immediately after hospital discharge. The results were compared with a previous cohort of patients in whom the Holter was initiated at least 1 week after hospital discharge (late-monitoring group). We included 100 patients (50 each group; 69 ± 13 years, 56% male). Mean time from ESUS to Holter was 1.2 ± 1 day in the early-monitoring group and 30 ± 15 days in the late-monitoring group. SCAF was detected in 22% of patients in the early-monitoring and 6% in the late-monitoring group (p <0.05). Patients with SCAF were older (77 ± 9 vs 67 ± 11 years, p <0.05), with a higher rate of left atrial enlargement (50% vs 20%, p<0.05), renal impairment (28% vs 5%; p<0.01), and a slower mean heart rate (55 ± 6 vs 70 ± 6 beats/min; p<0.001). On multivariate analysis, the presence of persistent bradycardia (≤60 beats/min) in the 21-day Holter was a powerful and significant risk factor for SCAF. In conclusion, the sooner 21-day Holter electrocardiogram monitoring is initiated after ESUS, the more likely SCAF can be detected. Sinus bradycardia is a powerful predictor of SCAF in patients with ESUS.

Mechanisms of sex differences in atrial fibrillation: role of hormones and differences in electrophysiology, structure, function, and remodelling.

Atrial fibrillation (AF) is the clinically most prevalent rhythm disorder with large impact on quality of life and increased risk for hospitalizations and mortality in both men and women. In recent years, knowledge regarding epidemiology, risk factors, and patho-physiological mechanisms of AF has greatly increased. Sex differences have been identified in the prevalence, clinical presentation, associated comorbidities, and therapy outcomes of AF. Although it is known that age-related prevalence of AF is lower in women than in men, women have worse and often atypical symptoms and worse quality of life as well as a higher risk for adverse events such as stroke and death associated with AF. In this review, we evaluate what is known about sex differences in AF mechanisms-covering structural, electrophysiological, and hormonal factors-and underscore areas of knowledge gaps for future studies. Increasing our understanding of mechanisms accounting for these sex differences in AF is important both for prognostic purposes and the optimization of (targeted, mechanism-based, and sex-specific) therapeutic approaches.

Ictal asystole: A condition between neurology and cardiology.

Ictal asystole can appear in patients with focal epilepsy, even in early phases. We present our experience of 7 cases, remarking the electrocardiographic characteristics, the role of apnea, treatment and long-term evolution. Awareness of this entity and collaboration between neurologists and cardiologists are essential for a correct diagnosis and management.

An "inappropriately appropriate" shock in a subcutaneous implantable cardioverter-defibrillator: The importance of the SMART pass algorithm.

We report on a case of a 78-years-old patient with a subcutaneous implantable cardioverter defibrillator (S-ICD) and an episode of a sustained ventricular tachycardia (VT) at a rate slower than the programmed shock zone. Because of T-wave oversensing the device interpreted it as fast VT that triggered the delivery of an "inappropriately appropriate shock" that terminated it. The patient had again more VT episodes but after programming the SMART pass algorithm (previously programmed "OFF") the device showed no longer frequent T-wave oversensing and no additional inappropriate shocks occurred.

CorVue algorithm efficacy to predict heart failure in real life: Unnecessary and potentially misleading information?

BACKGROUND: Heart failure (HF) hospitalizations have a negative impact on quality of life and imply important costs. Intrathoracic impedance (ITI) variations detected by cardiac devices have been hypothesized to predict HF hospitalizations. Although Optivol™ algorithm (Medtronic, Minneapolis, MN, USA) has been widely studied, CorVue™ algorithm's (St. Jude Medical, St. Paul, MN, USA) long-term efficacy has not been systematically evaluated in a "real-life" cohort. METHODS: CorVue™ was activated in implantable cardioverter defibrillator (ICD)/cardiac resynchronization therapy defibrillator (CRT-D) patients to store information about ITI measures. Clinical events (new episodes of HF requiring treatment and hospitalizations) and CorVue™ data were recorded every 3 months. Appropriate CorVue™ detection for HF was considered if it occurred in the 4 prior weeks to the clinical event. RESULTS: Fifty-three ICD/CRT-D (26 ICD and 27 CRT-D) patients (67 ± 1 years old, 79% male) were included. Device position was subcutaneous in 28 patients. At inclusion, mean left ventricular ejection fraction was 25 ± 7% and 27 patients (51%) were in New York Heart Association class I, 18 (34%) in class II, and eight (15%) in class III. After a mean follow-up of 17 ± 9 months, 105 ITI drops alarms were detected in 32 patients (60%). Only six alarms were appropriate (true positive) and required hospitalization. Eighteen patients (34%) presented 25 clinical episodes (12 hospitalizations and 13 emergency room/ambulatory treatment modifications). Nineteen of these clinical episodes (76%) remained undetected by the CorVue™ (false negative). Sensitivity of CorVue™ resulted in 24%, specificity was 70%, positive predictive value of 6%, and negative predictive value of 93%. CONCLUSIONS: CorVue™ showed a low sensitivity to predict HF events. Therefore, routinely activation of this algorithm could generate misleading information.

Inappropriate automatic mode switching episodes: What's the mechanism?

We present a case series of five patients reporting abnormal automatic mode switching (AMS) episodes during routinary cardiac defibrillator (ICD) and pacemaker (PM) follow-up. This non-previously described phenomenon was reported to St. Jude Medical (Abbott) Technical Support that confirmed the inappropriate automatic mode switching.

P-wave and interatrial block: New predictor for atrial high rate episodes in patients with cardiac implantable electronic devices.

BACKGROUND: The presence of interatrial block (IAB) is associated with the development of atrial fibrillation (AF). The aim of this study was to determine whether P-wave duration and presence of IAB before the implantation of a cardiac implantable electronic device (CIED) are associated with the presence of atrial high rate episodes (AHRE), during long-term follow-up. METHODS: 380 patients (57% men; 75 ± 10 years) were included. IAB was defined according to the International Consensus Criteria. AHRE was defined as an episode of atrial rate ≥225 beats/min with a minimum duration of 5 minutes. RESULTS: Documented paroxysmal AF before the implantation was present in 24% of the patients; 80% had hypertension and 32% structural heart disease. Mean P-wave duration was 123 ± 23 ms, and 39% of the patients had IAB (32% partial, 7% advanced). After a mean follow-up of 18 ± 12 months, 33% of the patients presented AHRE. Patients with AHRE had a P-wave duration significantly longer (130 ± 24 ms vs 119 ± 21 ms; P < 0.001) and a greater prevalence of IAB (53% vs 32%; P < 0.001). In a multivariate analysis, predictors of AHRE were: IAB (odds ratio [OR] 2.1; 95% confidence interval [CI] [1.3-3.4], P < 0.001) and previous paroxysmal AF (OR 2.6; 95% CI [1.5-4.3], P < 0.001). In patients without previous AF, the presence of IAB was also a significant predictor of AHRE (OR 3.1; 95% CI [1.8-5.5], P < 0.001). CONCLUSIONS: IAB is a strong predictor of AHRE in patients with CIED. This finding is independent of the presence of prior paroxysmal AF.

Silent atrial fibrillation in pacemaker early post-implantation period: an unintentionally provoked situation?

Aims: Atrial high-rate episodes (AHREs) compatible with silent AF detected in pacemakers (PM) are related to an increased risk of stroke and silent ischaemic brain lesions (IBL) on CT scan. AHREs soon after PM implantation could be related with the procedure itself and the prognosis might be different. Methods and results: We analysed the incidence of AHREs >5 min and the presence of silent IBL in 110 patients (56% men, aged 75 ± 9 year-old) with PM and no history of AF, in relation to time from implantation (≤3 months vs. >3 months) and the atrial lead fixation (LF) (active vs. passive). Mean CHADS2 and CHA2DS2VASc scores were 1.9 ± 1.2 and 3.5 ± 1.5, respectively. Time from implantation was ≤3 months in 88 patients (80%). Active LF was used in 55 patients (50%). After 24 ± 9 months, AHREs were present in 40 patients (36.4%). CT-scan showed silent IBL in 26 patients (23.6%). The presence of AHREs at 3 months was more frequent in the patients with recent PM implantation (17% vs. 4.5%, P = 0.09) and significantly related to active LF (OR 5.36, 1.43-20.07; P < 0.05). The presence of silent IBL was related to the detection of AHREs during follow up (OR 3.12, 1.29-7.97; P < 0.05) but not with AHREs at first 3 months (OR 1.58, 0.49-5.05; P = 0.44). Conclusions: AHREs occur frequently during the first 3 months after PM implantation and could be related with procedure itself and the use of active LF. AHREs in this period might not be related to worse outcomes and should be interpreted cautiously.

Silent brain infarcts in high blood pressure patients with cardiac implantable electronic devices: unmasking silent atrial fibrillation.

BACKGROUND: Hypertensive patients present a higher risk for developing atrial fibrillation and its complications. Cardiac implantable electronic devices (CIEDs) have shown reliable atrial fibrillation detection as atrial high-rate episodes (AHREs). The presence of AHRE more than 5 min has been related to increased risk of stroke, but a high proportion of ischemic brain lesions (IBLs) could be subclinical and thromboembolic risk underestimated. METHODS: We included hypertensive patients with CIED and we analyzed the incidence of AHRE and the presence of IBL on computed tomography (CT) scan. RESULTS: One hundred and twenty-three patients (57% men) aged 77 ± 8 years were evaluated during a mean follow-up of 15 ± 9 months. AHREs were documented in 46 patients (37%). Cranial CT scan showed silent IBL in 34 patients (27%). Univariate analysis showed that age, CHADS2 and CHADS2VA2Sc scores, history of prior stroke/ transient ischemic attack and the presence of AHRE were significantly related to higher risk for IBL on CT scan (P < 0.05). Multivariate analysis showed that the presence of AHRE more than 5 min [odds ratio 3.05 (1.19-7.81; P < 0.05)] was an independent predictor of IBL. CONCLUSION: Silent atrial fibrillation detected by CIED as AHRE is really prevalent in hypertensive patients. AHREs were independently associated with a higher incidence of silent IBL on CT scan.

Silent ischaemic brain lesions related to atrial high rate episodes in patients with cardiac implantable electronic devices.

AIMS: Monitoring capabilities of cardiac implantable electronic devices have revealed that a large proportion of patients present silent atrial fibrillation (AF) detected as atrial high rate episodes (AHREs). Atrial high rate episodes >5 min have been linked to increased risk of clinical stroke, but a high proportion of ischaemic brain lesions (IBLs) could be subclinical. METHODS AND RESULTS: We prospectively analysed the incidence of AHRE > 5 min in 109 patients (56% men, aged 74 ± 9 years) and the presence of silent IBL on computed tomography (CT) scan. Mean CHADS2 and CHA2DS2VASc scores were 2.3 ± 1.3 and 3.9 ± 1.6, respectively. Seventy-five patients (69%) had no history of AF or stroke/transient ischaemic attack (TIA). After 12 months, 28 patients (25.7%) showed at least one AHRE. Patients with AHREs were more likely to have history of AF. Computed tomography scan showed silent IBL in 28 (25.7%). The presence of IBL was significantly related to older patients, prior history of AF or stroke/TIA, higher CHADS2 or CHA2DS2VASc scores, and the presence of AHRE. Multivariable analysis demonstrated that AHRE was an independent predictor for silent IBL in overall population [hazard ratio (HR) 3.05 (1.06-8.81; P < 0.05)] but also in patients without prior history of AF or stroke/TIA [HR 9.76 (1.76-54.07; P < 0.05)]. CONCLUSION: Cardiac implantable electronic devices can accurately detect AF as AHRE. Atrial high rate episodes were associated to a higher incidence of silent IBL on CT scan. Atrial high rate episodes represent a kind of silent AF where management recommendations are lacking despite the fact that a higher embolic risk is present.

Long-term outcomes of ivabradine in inappropriate sinus tachycardia patients: appropriate efficacy or inappropriate patients.

BACKGROUND: Inappropriate sinus tachycardia (IST) is characterized by persistent and disproportional elevation of heart rate (HR). Ivabradine has been successfully used in some patients. METHODS: Twenty-four patients (18 women, 41 ± 13 year olds) were diagnosed with IST according to current guidelines criteria. Patients were treated with 5-7.5 mg of ivabradine twice a day. Twenty-four-hour Holter recordings and the SF-36 Health Survey were performed at 6 months to evaluate both HR control and clinical status. RESULTS: Holter recordings before and after 6 months on treatment showed a significant reduction in the average maximal HR of 155 ± 18 beats/min versus 132 ± 16 beats/min, mean HR of 97 ± 6 beats/min versus 79 ± 8 beats/min (mean daytime HR of 103 ± 8 beats/min vs 84 ± 10 beats/min) and minimal HR of 58 ± 12 beats/min versus 48 ± 7 beats/min (Wilcoxon analysis, P < 0.05). The SF-36 mean score showed a significant improvement on ivabradine treatment (57 ± 23 vs 76 ± 20), with a better physical and mental status scores (56 ± 25 vs 74 ± 22 and 58 ± 24 vs 78 ± 18, respectively) (Wilcoxon analysis, P < 0.001). Mean dose of ivabradine was 5.8 ± 1.4 mg. No episodes of severe bradycardia or syncope were reported. After 1 year, patients were asked to stop treatment to reevaluate the situation. Twenty patients were on treatment and only 10 patients accepted to stop ivabradine. Only two patients (20%) remained on IST criteria. CONCLUSIONS: IST patients treated with ivabradine showed both HR normalization and quality-of-life improvement maintained in the long-term follow-up. Stopping ivabradine after 1 year unexpectedly showed that HR remained in the normal limits in 80% of the patients.