Percutaneous extraction of a Micra AV transcatheter pacing system due to a rare sudden battery failure after 19 months from implantation: A first experience worldwide.

INTRODUCTION: Micra AV Transcatheter Pacing System (TPS) represents an innovative second-generation leadless pacemaker which represents an effective alternative to conventional devices in selected cases. Intrinsic malfunctions of these devices are rare, requiring sometimes their retrieval. When performed in experienced centers, this procedure is safe. CASE PRESENTATION: We describe a case of sudden battery malfunction of a Micra AV TPS, which required the extraction and the placement of a new pacing system in the right ventricle. DISCUSSION: This case, which has never been reported, highlights the need to a careful fluoroscopic evaluation and the usefulness of remote monitoring.

Conduction delays after transcatheter aortic valve implantation with balloon-expandable prosthesis and high implantation technique.

Performing transcatheter aortic valve implantation with high implantation technique, i.e. with an aorto-ventricular ratio > 60/40, reduces the need of permanent pacemaker implantation. Valve calcification and prosthesis oversizing are predictors of permanent pacemaker implantation, but there are no available data on their role when transcatheter aortic valve implantation is performed with an aorto-ventricular ratio > 60/40. The aim of this study was to evaluate the effect of leaflets/annulus calcification and prosthesis oversizing on the incidence of permanent pacemaker implantation after transcatheter aortic valve implantation with a high implantation technique. Transcatheter aortic valve implantation was performed in 48 patients implanting a balloon-expandable transcatheter heart valve with an aorto-ventricular ratio > 60/40. Calcium burden was assessed by preprocedural multidetector computed tomography. An invasive electrophysiological study was performed before and after transcatheter aortic valve implantation. Five patients (10.4%) needed permanent pacemaker implantation. At univariate analysis, baseline right bundle branch block and postprocedural PR, QRS and His-ventricular interval elongation significantly predicted permanent pacemaker implantation (p < 0.05). Receiver-operating characteristic curve analysis showed a correlation between transcatheter heart valve oversizing and permanent pacemaker implantation need, with the best cut-off being 17% (AUC = 0.72, p = 0.033). Linear regression analysis demonstrated that QRS complex elongation was related to total, left and non-coronary leaflet calcification (p < 0.05). This study demonstrates that, when transcatheter aortic valve implantation is performed using a balloon-expandable transcatheter heart valve deployed with an aorto-ventricular ratio > 60/40, the presence of leaflets/annulus calcification or the need to oversize the prosthesis correlate with the occurrence of pathological cardiac conduction delays.

Pro-inflammatory cytokines as emerging molecular determinants in cardiolaminopathies.

Mutations in Lamin A/C gene (lmna) cause a wide spectrum of cardiolaminopathies strictly associated with significant deterioration of the electrical and contractile function of the heart. Despite the continuous flow of biomedical evidence, linking cardiac inflammation to heart remodelling in patients harbouring lmna mutations is puzzling. Therefore, we profiled 30 serum cytokines/chemokines in patients belonging to four different families carrying pathogenic lmna mutations segregating with cardiac phenotypes at different stages of severity (n = 19) and in healthy subjects (n = 11). Regardless lmna mutation subtype, high levels of circulating granulocyte colony-stimulating factor (G-CSF) and interleukin 6 (IL-6) were found in all affected patients' sera. In addition, elevated levels of Interleukins (IL) IL-1Ra, IL-1ß IL-4, IL-5 and IL-8 and the granulocyte-macrophage colony-stimulating factor (GM-CSF) were measured in a large subset of patients associated with more aggressive clinical manifestations. Finally, the expression of the pro-inflammatory 70 kDa heat shock protein (Hsp70) was significantly increased in serum exosomes of patients harbouring the lmna mutation associated with the more severe phenotype. Overall, the identification of patient subsets with overactive or dysregulated myocardial inflammatory responses could represent an innovative diagnostic, prognostic and therapeutic tool against Lamin A/C cardiomyopathies.

Degenerative Severe Aortic Stenosis and Concomitant Coronary Artery Disease: What Is Changing in the Era of the "Transcatheter Revolution"?

PURPOSE OF REVIEW: To summarize epidemiology, pathophysiology, prognostic relevance, and treatment options of coronary artery disease (CAD) when coupled with severe aortic stenosis (SAS). In regard to treatment options, we focused on the most recently adopted therapeutic approaches and on the future perspectives in light of the latest percutaneous and surgical technical improvements in the field of both CAD and SAS management. RECENT FINDINGS: Nowadays, SAS is the most common valve disease requiring intervention, either surgical or percutaneous. On the other side, CAD is one of the leading causes of death in the developed countries. CAD and degenerative SAS share several predisposing factors and are often concurrently found in clinical practice. Despite in the last years the transcatheter aortic valve replacement (TAVR) has been deeply changing the therapeutic approach to SAS, the correct management of patients with concomitant CAD remains controversial due to limited and heterogeneous data in the literature. Coronary revascularization is often performed in patients with concomitant CAD and SAS. Complete surgical approach is still the standard of care according to international guidelines. However, in light of the recent results of TAVR trials, the therapeutic approach is expected to change. To date, percutaneous coronary intervention performed before TAVR is safe and feasible even if the optimal timing for revascularization remains debated. Due to the great complexity of the patients affected by SAS and CAD and until unquestionable truths will come from large randomized trials, the role of the Heart Team in the decision-making process is of primary importance to guarantee the best tailored therapeutic strategy for the single patient.

Late gadolinium enhancement role in arrhythmic risk stratification of patients with LMNA cardiomyopathy: results from a long-term follow-up multicentre study.

AIMS: We aimed at addressing the role of late gadolinium enhancement (LGE) in arrhythmic risk stratification of LMNA-associated cardiomyopathy (CMP). METHODS AND RESULTS: We present data from a multicentre national cohort of patients with LMNA mutations. Of 164 screened cases, we finally enrolled patients with baseline cardiac magnetic resonance (CMR) including LGE sequences [n = 41, age 35 ± 17 years, 51% males, mean left ventricular ejection fraction (LVEF) by echocardiogram 56%]. The primary endpoint of the study was follow-up (FU) occurrence of malignant ventricular arrhythmias [MVA, including sustained ventricular tachycardia (VT), ventricular fibrillation, and appropriate implantable cardioverter-defibrillator (ICD) therapy]. At baseline CMR, 25 subjects (61%) had LGE, with non-ischaemic pattern in all of the cases. Overall, 23 patients (56%) underwent ICD implant. By 10 ± 3 years FU, eight patients (20%) experienced MVA, consisting of appropriate ICD shocks in all of the cases. In particular, the occurrence of MVA in LGE+ vs. LGE- groups was 8/25 vs. 0/16 (P = 0.014). Of note, no significant differences between LGE+ and LGE- patients were found in currently recognized risk factors for sudden cardiac death (male gender, non-missense mutations, baseline LVEF <45% and non-sustained VT), all P-value >0.05. CONCLUSIONS: In LMNA-CMP patients, LGE at baseline CMR is significantly associated with MVA. In particular, as suggested by this preliminary experience, the absence of LGE allowed to rule-out MVA at 10 years mean FU.

Cardiac and Neuromuscular Features of Patients With LMNA-Related Cardiomyopathy.

Background: Mutations in the LMNA (lamin A/C) gene have been associated with neuromuscular and cardiac manifestations, but the clinical implications of these signs are not well understood. Objective: To learn more about the natural history of LMNA-related disease. Design: Observational study. Setting: 13 clinical centers in Italy from 2000 through 2018. Patients: 164 carriers of an LMNA mutation. Measurements: Detailed cardiologic and neurologic evaluation at study enrollment and for a median of 10 years of follow-up. Results: The median age at enrollment was 38 years, and 51% of participants were female. Neuromuscular manifestations preceded cardiac signs by a median of 11 years, but by the end of follow-up, 90% of the patients had electrical heart disease followed by structural heart disease. Overall, 10 patients (6%) died, 14 (9%) received a heart transplant, and 32 (20%) had malignant ventricular arrhythmias. Fifteen patients had gait loss, and 6 had respiratory failure. Atrial fibrillation and second- and third-degree atrioventricular block were observed, respectively, in 56% and 51% of patients with combined cardiac and neuromuscular manifestations and 37% and 33% of those with heart disease only. Limitations: Some of the data were collected retrospectively. Neuromuscular manifestations were more frequent in this analysis than in previous studies. Conclusion: Many patients with an LMNA mutation have neurologic symptoms by their 30s and develop progressive cardiac manifestations during the next decade. A substantial proportion of these patients will have life-threatening neurologic or cardiologic conditions. Primary Funding Source: None.

Functional study of a KCNH2 mutant: Novel insights on the pathogenesis of the LQT2 syndrome.

The K+ voltage-gated channel subfamily H member 2 (KCNH2) transports the rapid component of the cardiac delayed rectifying K+ current. The aim of this study was to characterize the biophysical properties of a C-terminus-truncated KCNH2 channel, G1006fs/49 causing long QT syndrome type II in heterozygous members of an Italian family. Mutant carriers underwent clinical workup, including 12-lead electrocardiogram, transthoracic echocardiography and 24-hour ECG recording. Electrophysiological experiments compared the biophysical properties of G1006fs/49 with those of KCNH2 both expressed either as homotetramers or as heterotetramers in HEK293 cells. Major findings of this work are as follows: (a) G1006fs/49 is functional at the plasma membrane even when co-expressed with KCNH2, (b) G1006fs/49 exerts a dominant-negative effect on KCNH2 conferring specific biophysical properties to the heterotetrameric channel such as a significant delay in the voltage-sensitive transition to the open state, faster kinetics of both inactivation and recovery from the inactivation and (c) the activation kinetics of the G1006fs/49 heterotetrameric channels is partially restored by a specific KCNH2 activator. The functional characterization of G1006fs/49 homo/heterotetramers provided crucial findings about the pathogenesis of LQTS type II in the mutant carriers, thus providing a new and potential pharmacological strategy.

Time-dependent benefits of pre-treatment with new oral P2Y12 -inhibitors in patients addressed to primary PCI for acute ST-elevation myocardial infarction.

OBJECTIVES: The aim of this observational study was to determine the benefits of the novel, orally delivered P2Y12 -inhibitors (Is) in terms of angiographic endpoints and in relation to the time of the loading dose (LD) administration. BACKGROUND: The goal of ST-elevation myocardial infarction (STEMI) treatment is timely reperfusion. The P2Y12 -Is prasugrel and ticagrelor have improved the angiographic outcome of primary percutaneous coronary intervention (pPCI) and patients' prognosis. However, their onset of action is impaired in STEMI and delayed by their oral administration. METHODS: The 328 eligible patients with STEMI consecutively referred for pPCI were divided into three groups depending on the interval of "P2Y12 -I LD administration-to-balloon time": Group 2 included patients that received P2Y12 -I LD at least 60 min prior to pPCI, Group 1 within 60 min prior to pPCI, and Group 0 at the moment of pPCI. Angiographic, clinical, and biochemical parameters were evaluated. Pre- and post-pPCI TIMI flow grade (TFG) and ST resolution (STR) were used as outcome measures to determine efficacy and optimal timing of pretreatment. RESULTS: Pre-pPCI TFG improved with increasing P2Y12 -I LD administration-to-balloon time; pre-PCI TFG 0/1 was 74.5% in Group 0, 65.5% in Group 1 and 54.9% in Group 2 (P < 0.002). Post-pPCI TFG 3 results also differed significantly between the three groups: 85.2% in Group 0, 88.1% in Group 1, 97.6% in Group 2 (P < 0.013). ST resolution rates were also positively associated with longer pretreatment intervals. CONCLUSIONS: This observational study suggests that the angiographic benefit of P2Y12 -I administration is time-dependent: longer pretreatment improves coronary reperfusion in terms of pre- and post-pPCI TFG and STR.

Risk stratification of cardiovascular and heart failure hospitalizations using integrated device diagnostics in patients with a cardiac resynchronization therapy defibrillator.

Aims: Cardiac resynchronization therapy defibrillators (CRT-D) are able to monitor various parameters that may be combined by an automatic algorithm to provide a heart failure risk status (HFRS). We sought to validate the HFRS for stratifying patient risk, evaluate its association with heart failure (HF) symptoms, and investigate its utility for triage of automatic alerts. Methods and results: Data from 722 patients included in the MORE-CARE trial were analysed in a post hoc analysis. A high HFRS was associated with a significantly increased risk of admission over the next 30 days with a relative risk for cardiovascular hospitalization (CVH) of 4.5 (95% CI: 3.1-6.6, P < 0.001), of HF hospitalization of 6.3 (95% CI: 3.9-10.2, P < 0.001) and of non-HF related CVH of 3.5 (95% CI: 2.0-6.9, P < 0.001). The negative predictive value of low or medium HFRS for these admissions was ≥98%. A high HFRS was associated with an increased risk of HF symptoms. Of all the automatic remote monitoring alerts generated during the study, only 10% had a high HFRS. Conclusion: The HFRS is able to risk-stratify CRT-D patients, which is potentially useful for managing automatic remote monitoring alerts, by focusing attention on the minority of high-risk patients. Clinical Trial Registration: The trial was registered at www.clinicaltrials.gov under number NCT00885677.

Impact of the third generation cryoballoon on atrial fibrillation ablation: An useful tool?

BACKGROUND: Third-generation cryoballoon (CB3) is characterized by a 40% shorter distal tip designed to increase the rate of pulmonary veins real-time signal recording in order to measure time necessary to isolate veins, the "Time to effect" (TTE). Few data are currently available on clinical follow up of CB3 treated patients. METHODS: Sixtyeight consecutive patients (mean age 57.8 ±â€¯9.6 years, 48 male) with paroxysmal or persistent atrial fibrillation (AF) were enrolled. Thirthyfour (25 paroxysmal AF) underwent to a 28 mmCB3 pulmonary veins isolation and were compared to 34 treated (21 paroxysmal AF) with 28 mmCB2. RESULTS: CB3 use was correlated to significant increase of the possibility to measure TTE in every treated veins (left superior 82,35% vs 23,53%, left inferior 70,59% vs 38,24%, right superior 58,82% vs 14,71%, right inferior 52,94% vs 17,65%). When it is measured, TTE wasn't different between two groups. Higher nadir temperature was observed in CB3 patients (-39.4 ±â€¯5.2 °C vs -43.0 ±â€¯7.2 °C, p = 0.03). CB3 procedures were shorter (91.4 ±â€¯21.7 vs 110.9 ±â€¯31.8 min, p = 0.018), with a significant reduction in cryoenergy delivery time (24.2 ±â€¯8.5 vs 20.3 ±â€¯6.7 min, p < 0.05), and a significant reduction in left atrium dwell time (59.3 ±â€¯9.8 vs 69.3 ±â€¯10.8 min, p = 0.02, p < 0.05). At one year follow up period the Kaplan-Meier curve didn't show any significant difference in AF-free survival (Log p = 0,49). CONCLUSIONS: Novel CB3 is a useful tool in order to simplify AF cryoballoon ablation when compared to second generation cryoballoon, as observed in our experience. Follow up data seem confirm a clinical CB3 efficacy at least comparable CB2.

The expression of Lamin A mutant R321X leads to endoplasmic reticulum stress with aberrant Ca2+ handling.

Mutations in the Lamin A/C gene (LMNA), which encodes A-type nuclear Lamins, represent the most frequent genetic cause of dilated cardiomyopathy (DCM). This study is focused on a LMNA nonsense mutation (R321X) identified in several members of an Italian family that produces a truncated protein isoform, which co-segregates with a severe form of cardiomyopathy with poor prognosis. However, no molecular mechanisms other than nonsense mediated decay of the messenger and possible haploinsufficiency were proposed to explain DCM. Aim of this study was to gain more insights into the disease-causing mechanisms induced by the expression of R321X at cellular level. We detected the expression of R321X by Western blotting from whole lysate of a mutation carrier heart biopsy. When expressed in HEK293 cells, GFP- (or mCherry)-tagged R321X mislocalized in the endoplasmic reticulum (ER) inducing the PERK-CHOP axis of the ER stress response. Of note, confocal microscopy showed phosphorylation of PERK in sections of the mutation carrier heart biopsy. ER mislocalization of mCherry-R321X also induced impaired ER Ca2+ handling, reduced capacitative Ca2+ entry at the plasma membrane and abnormal nuclear Ca2+ dynamics. In addition, expression of R321X by itself increased the apoptosis rate. In conclusion, R321X is the first LMNA mutant identified to date, which mislocalizes into the ER affecting cellular homeostasis mechanisms not strictly related to nuclear functions.

Role of nuclear Lamin A/C in cardiomyocyte functions.

Lamin A/C is a structural protein of the nuclear envelope (NE) and cardiac involvement in Lamin A/C mutations was one of the first phenotypes to be reported in humans, suggesting a crucial role of this protein in the cardiomyocytes function. Mutations in LMNA gene cause a class of pathologies generically named 'Lamanopathies' mainly involving heart and skeletal muscles. Moreover, the well-known disease called Hutchinson-Gilford Progeria Syndrome due to extensive mutations in LMNA gene, in addition to the systemic phenotype of premature aging, is characterised by the death of patients at around 13 typically for a heart attack or stroke, suggesting again the heart as the main site sensitive to Lamin A/C disfunction. Indeed, the identification of the roles of the Lamin A/C in cardiomyocytes function is a key area of exploration. One of the primary biological roles recently conferred to Lamin A/C is to affect contractile cells lineage determination and senescence. Then, in differentiated adult cardiomyocytes both the 'structural' and 'gene expression hypothesis' could explain the role of Lamin A in the function of cardiomyocytes. In fact, recent advances in the field propose that the structural weakness/stiffness of the NE, regulated by Lamin A/C amount in NE, can 'consequently' alter gene expression.

Rate, causes, and impact on patient outcome of implantable device complications requiring surgical revision: large population survey from two centres in Italy.

AIMS: The long-term impact of implantable device-related complications on the patient outcome has not been thoroughly evaluated. The aims of this retrospective, bi-centre study were to analyse the rate and nature of device-related complications requiring surgical revision in a large series of patients undergoing device implantation, elective generator replacement and pacing system upgrade and to systematically assess the impact of such complications on patient outcome and healthcare utilization. METHODS AND RESULTS: Data from 2671 consecutive procedures (1511 device implantations, 1034 elective generator replacements, and 126 pacing system upgrades) performed between January 2006 and March 2011 were retrospectively analysed. The outcome measures recorded were complication-related mortality, number of re-operations, need for complex surgical procedures, number of re-hospitalizations, and additional hospital treatment days. Over a median follow-up of 27 months, the overall rate of complications was 2.8% per procedure-year [9.5% in cardiac resynchronisation therapy (CRT) device implantation, 6.1% in pacing system upgrade, 3.5% in implantable cardioverter defibrillator implantation, 1.7% in pacemaker implantation, and 1.7% in generator replacement). The procedure with the highest risk of complications was CRT device implantation (odds ratio: 6.6; P < 0.001); these complications primarily involved coronary sinus lead dislodgement and device infection. Patients with complications had a significantly higher number of device-related hospitalizations (2.3 ± 0.6 vs. 1.0 ± 0.1; P < 0.001) and hospital treatment days (15.7 ± 25.1 vs. 3.6 ± 1.1; P < 0.001) than those without complications. Device infection was the complication with the greatest negative impact on patient outcome. CONCLUSION: Cardiac resynchronisation therapy implantation was the procedure with the highest risk of complications requiring surgical revision. Complications were associated with substantial clinical consequences and a significant increase in the number and length of hospitalizations.

Independent role of left ventricular global longitudinal strain in predicting prognosis of chronic heart failure patients.

AIMS: To evaluate the independent prognostic role of two-dimensional (2D) strain measures reflecting global longitudinal left ventricular (LV) systolic function in outpatients affected by chronic heart failure (CHF). METHODS AND RESULTS: Global longitudinal LV systolic strain (GLS) was assessed in 308 outpatients affected by CHF, by analyzing standard views with 2D speckle tracking technique. During a mean follow-up of 26 ± 13 months 37 patients died (29 due to cardiovascular causes), 10 patients underwent heart transplantation, and 75 patients experienced at least 1 episode of hospitalization due to acute decompensated heart failure (ADHF). Thirty-one patients without a history of major ventricular arrhythmic events experienced the occurrence of ventricular fibrillation and/or tachycardia or sudden death was observed. Multivariate Cox regression analysis showed that GLS was significantly associated with all-cause mortality (HR: 1.15; 95%CI: 1.02-1.30; P: 0.026), cardiovascular death (HR: 1.20; 95%CI: 1.04-1.39; P: 0.011), cardiovascular death or heart transplantation (HR: 1.24; 95%CI: 1.09-1.41; P: 0.001), ADHF-related hospitalizations (HR: 1.15; 95%CI: 1.05-1.25; P: 0.003), and arrhythmic events (HR: 1.17; 95%CI: 1.03-1.33; P: 0.018). CONCLUSIONS: Quantifying LV longitudinal systolic function in CHF outpatients on the basis of 2D speckle tracking analysis provides a new parameter that independently predicts patient outcome, thus, strengthening its possible role in current clinical practice.

The MOnitoring Resynchronization dEvices and CARdiac patiEnts (MORE-CARE) randomized controlled trial: phase 1 results on dynamics of early intervention with remote monitoring.

BACKGROUND: Remote monitoring (RM) in patients with advanced heart failure and cardiac resynchronization therapy defibrillators (CRT-D) may reduce delays in clinical decisions by transmitting automatic alerts. However, this strategy has never been tested specifically in this patient population, with alerts for lung fluid overload, and in a European setting. OBJECTIVE: The main objective of Phase 1 (presented here) is to evaluate if RM strategy is able to reduce time from device-detected events to clinical decisions. METHODS: In this multicenter randomized controlled trial, patients with moderate to severe heart failure implanted with CRT-D devices were randomized to a Remote group (with remote follow-up and wireless automatic alerts) or to a Control group (with standard follow-up without alerts). The primary endpoint of Phase 1 was the delay between an alert event and clinical decisions related to the event in the first 154 enrolled patients followed for 1 year. RESULTS: The median delay from device-detected events to clinical decisions was considerably shorter in the Remote group compared to the Control group: 2 (25(th)-75(th) percentile, 1-4) days vs 29 (25(th)-75(th) percentile, 3-51) days respectively, P=.004. In-hospital visits were reduced in the Remote group (2.0 visits/patient/year vs 3.2 visits/patient/year in the Control group, 37.5% relative reduction, P<.001). Automatic alerts were successfully transmitted in 93% of events occurring outside the hospital in the Remote group. The annual rate of all-cause hospitalizations per patient did not differ between the two groups (P=.65). CONCLUSIONS: RM in CRT-D patients with advanced heart failure allows physicians to promptly react to clinically relevant automatic alerts and significantly reduces the burden of in-hospital visits. TRIAL REGISTRATION: Clinicaltrials.gov NCT00885677; http://clinicaltrials.gov/show/NCT00885677 (Archived by WebCite at http://www.webcitation.org/6IkcCJ7NF).

Performance of a multisensor implantable defibrillator algorithm for heart failure monitoring related to co-morbidities.

AIMS: The HeartLogic algorithm combines multiple implantable defibrillator (ICD) sensor data and has proved to be a sensitive and timely predictor of impending heart failure (HF) decompensation in cardiac resynchronization therapy (CRT-D) patients. We evaluated the performance of this algorithm in non-CRT ICD patients and in the presence of co-morbidities. METHODS AND RESULTS: The HeartLogic feature was activated in 568 ICD patients (410 with CRT-D) from 26 centres. The median follow-up was 26 months [25th-75th percentile: 16-37]. During follow-up, 97 hospitalizations were reported (53 cardiovascular) and 55 patients died. We recorded 1200 HeartLogic alerts in 370 patients. Overall, the time IN the alert state was 13% of the total observation period. The rate of cardiovascular hospitalizations or death was 0.48/patient-year (95% CI: 0.37-0.60) with the HeartLogic IN the alert state and 0.04/patient-year (95% CI: 0.03-0.05) OUT of the alert state, with an incidence rate ratio of 13.35 (95% CI: 8.83-20.51, P < 0.001). Among patient characteristics, atrial fibrillation (AF) on implantation (HR: 1.62, 95% CI: 1.27-2.07, P < 0.001) and chronic kidney disease (CKD) (HR: 1.53, 95% CI: 1.21-1.93, P < 0.001) independently predicted alerts. HeartLogic alerts were not associated with CRT-D versus ICD implantation (HR: 1.03, 95% CI: 0.82-1.30, P = 0.775). Comparisons of the clinical event rates in the IN alert state with those in the OUT of alert state yielded incidence rate ratios ranging from 9.72 to 14.54 (all P < 0.001) in all groups of patients stratified by: CRT-D/ICD, AF/non-AF, and CKD/non-CKD. After multivariate correction, the occurrence of alerts was associated with cardiovascular hospitalization or death (HR: 1.92, 95% CI: 1.05-3.51, P = 0.036). CONCLUSIONS: The burden of HeartLogic alerts was similar between CRT-D and ICD patients, while patients with AF and CKD seemed more exposed to alerts. Nonetheless, the ability of the HeartLogic algorithm to identify periods of significantly increased risk of clinical events was confirmed, regardless of the type of device and the presence of AF or CKD.

Low-dose dobutamine test associated with interventricular dyssynchrony: a useful tool to identify cardiac resynchronization therapy responders: data from the LOw dose DObutamine stress-echo test in Cardiac Resynchronization Therapy (LODO-CRT) phase 2 study.

BACKGROUND: Cardiac resynchronization therapy (CRT) is effective in patients with heart failure, but 30% to 50% of subjects are classified as nonresponders. Identifying responders remains a challenging task. AIMS: The LODO-CRT trial investigated the association between left ventricular contractile reserve (LVCR) and clinical and echocardiographic long-term CRT response. METHODS: This is a multicenter, prospective, observational study. Left ventricular contractile reserve was detected using a dobutamine stress echocardiography test, defined as an ejection fraction increase of >5 points. Clinical CRT response was defined as the absence of major cardiovascular events (ie, cardiovascular death or heart failure hospitalization). Echocardiographic response was defined as a left ventricle end-systolic volume reduction of >10%. RESULTS: A total of 221 CRT-indicated patients were studied (80% presented LVCR). During a mean follow-up of 15 ± 5 months, 17 patients died and 16 were hospitalized due to heart failure. The proportion of clinical responders was 155 (88%) of 177 and 33 (75%) of 44 (P = .036) in the groups with and without LVCR, respectively. Kaplan-Meier analysis showed a significant difference in cardiac survival/hospitalization between patients with and without LVCR. The proportion of echocardiographic responders was 144 (87%) of 166 and 16 (42%) of 38 in the groups with and without LVCR (P < .001), respectively; LVCR showed 90% sensitivity and 87% positive predictive value to prefigure echocardiographic CRT responders. Multivariable analysis identified LVCR and interventricular dyssynchrony as independent predictors of CRT response. The concomitant presence of both factors showed 99% specificity and 83% sensitivity in detecting responders. CONCLUSION: The presence of LVCR helps in predicting a clinical and echocardiographic CRT response. Concomitant assessment of LVCR and interventricular dyssynchrony accurately stratifies responder and nonresponder patients.

Closed-loop cardiac pacing vs. conventional dual-chamber pacing with specialized sensing and pacing algorithms for syncope prevention in patients with refractory vasovagal syncope: results of a long-term follow-up.

AIMS: Closed-loop stimulation (CLS) pacing has shown greater efficacy in preventing the recurrence of vasovagal syncope (VVS) in patients with a cardioinhibitory response to head-up tilt test (HUTT) compared with conventional pacing. Moreover, there is no conclusive evidence to support the superiority of CLS over the conventional algorithms for syncope prevention. This study retrospectively evaluated the effectiveness of CLS pacing compared with dual-chamber pacing with conventional specialized sensing and pacing algorithms for syncope prevention in the prevention of syncope recurrence in patients with refractory VVS and a cardioinhibitory response to HUTT during a long-term follow-up. METHODS AND RESULTS: Forty-one patients (44% male, 53 ± 16 years) with recurrent, refractory VVS (26% with trauma) and a cardioinhibitory response to HUTT who had undergone pacemaker implantation were included in the analysis. Twenty-five patients received a dual-chamber CLS pacemaker (CLS group) and 16 patients received a dual-chamber pacemaker with conventional algorithms for syncope prevention (conventional pacing group): 9 patients with Medtronic rate drop response algorithm and 7 patients with Guidant-Boston Scientific sudden brady response algorithm. During the follow-up (mean 4.4 ± 3.0 years, interquartile range 2.2-7.4 years) one patient (4%) in the CLS group and six (38%) in the conventional pacing group had syncope recurrences (P= 0.016). The Kaplan-Meier actuarial estimate of first recurrence of syncope after 8 years was 4% in the CLS group and 40% in the conventional pacing group (P= 0.010). CONCLUSIONS: The results of this retrospective analysis show that, in order to prevent a recurrence of VVS in patients with a cardioinhibitory response to HUTT, dual-chamber CLS pacing was more effective than dual-chamber pacing with conventional algorithms for syncope prevention in preventing bradycardia-related syncope.

Cardiorenal Syndrome Triggered by Slowly Progressive Drugs Toxicity-Induced Renal Failure along with Minimal Mitral Disease: A Case Report.

BACKGROUND: We report the case of a 93-year-old patient with normal left ventricular function and severe mitral annulus calcification, with mild mitral steno-insufficiency. CASE PRESENTATION: She had developed creeping drugs-induced renal toxicity that is generally totally overlooked, due mainly to statins, a proton pump inhibitor, and aspirin. The Na and fluid retention, along with hypertension that ensued, although not severe, caused acute heart failure (sub-pulmonary edema) by worsening the mitral insufficiency. This occurred due to a less efficient calcific mitral annulus contraction during systole and an increasing mitral transvalvular gradient, as the transvalvular mitral gradient has an exponential relation to flow. After the suspension of the nephrotoxic drugs and starting intravenous furosemide, she rapidly improved. At 6 months follow-up, she is stable, in an NYHA 1-2 functional class, despite the only partial recovery of the renal function. CONCLUSION: Progressive renal failure can functionally worsen even minimal mitral valvulopathy. Drug-induced nephrotoxicity can always be suspected in case of renal failure of unknown etiology. The suspension of the culprit drugs can improve renal function and dramatically improve the clinical symptoms even in a nonagenarian.

Wellens' Syndrome from COVID-19 Infection Assessed by Enhanced Transthoracic Coronary Echo Doppler: A Case Report.

Wellens' syndrome (WS) is a preinfarction state caused by a sub-occlusion of the proximal left anterior descending coronary artery (LAD). In this case report, for the first time, we describe how this syndrome can be caused by COVID-19 infection and, most importantly, that it can be assessed bedside by enhanced transthoracic coronary echo Doppler (E-Doppler TTE). This seasoned technique allows blood flow Doppler to be recorded in the coronaries and at the stenosis site but has never been tested in an acute setting. Two weeks after clinical recovery from bronchitis allegedly caused by COVID-19 infection on the basis of epidemiologic criteria (no swab performed during the acute phase but only during recovery, at which time it was negative), our patient developed typical angina for the first time, mainly during effort but also at rest. He was admitted to our tertiary center, where pharyngeal swabs tested positive for COVID-19. A typical EKG finding supporting WS prompted an assessment of the left main coronary artery (LMCA) and the whole LAD blood flow velocity by E-Doppler TTE. Localized high velocity (transtenotic velocity) (100 cm/s) was recorded in the proximal LAD, with the reference velocity being 20 cm/s. This indicated severe stenosis with 90% area narrowing according to the continuity equation, as confirmed by coronary angiography. During follow-up after successful stenting, E-Doppler TTE showed a decrease in the transtenotic acceleration, confirming stent patency and a normal coronary flow reserve (3.2) and illustrating a normal microcirculatory function. Conclusion: COVID infection can trigger a coronary syndrome like WS. E-Doppler TTE, an ionizing radiation-free method, allows safe and rapid bedside management of the syndrome. This new strategy can be pivotal in distinguishing true WS from pseudo-WS. In cases of pseudo-WS, coronary angiography can be avoided. If E-Doppler TTE confirms the stenosis and PCI (percutaneous coronary intervention) is performed, the same method can allow assessment over time of the precise residual stenosis after stenting and verify the microvasculature status by evaluating coronary flow reserve.