Incremental value of larger interventricular conduction time in improving cardiac resynchronization therapy outcome in patients with different QRS duration.

INTRODUCTION: The left ventricular (LV) pacing site and the magnitude of the electrical delay within the LV, as expressed by prolonged QRS duration, are major determinants of cardiac resynchronization therapy (CRT) efficacy. We investigated the incremental value of positioning the LV lead in areas of late activation in order to enhance the response to CRT in patients with different degrees of QRS complex lengthening. METHODS AND RESULTS: This analysis was performed on 301 heart failure patients who received a CRT defibrillator. On implantation, the right ventricular (RV)-to-LV interval was measured as the delay between local activations recorded through the RV and LV leads in the final position. After 1 year, 171 (57%) patients displayed reverse LV remodeling, as measured by a ≥15% reduction in the LV end-systolic volume. Both the RV-to-LV interval and its percentage value corrected for the QRS duration were significantly associated with a positive response to CRT. An RV-to-LV interval >80 milliseconds and an RV-to-LV interval/QRS >58% yielded the best prediction of reverse remodeling. Although the response to CRT decreased with shorter QRS duration in the overall population, patients with an RV-to-LV interval >80 milliseconds showed a response rate >65% in all QRS subgroups. CONCLUSION: A longer RV-to-LV interval is associated with reverse LV remodeling after CRT. On implantation attempts could be made to maximize it when selecting the LV lead position, especially in patients with shorter QRS duration, and thus less likely to respond positively to CRT.

Role of comorbidities on the mortality in patients with SARS-CoV-2 infection: an Italian cohort study.

BACKGROUND: Cardiovascular comorbidities are a common cause of death in COVID-19 and the aim of this study is to evaluate the effect of comorbidities on mortality in COVID-19 patients. METHODS: In this retrospective observational study we enrolled 1049 patients hospitalized with confirmed SARS-CoV-2 infection in a single Italian Center from 21 February to 20 March 2020 Evaluated risk factors (RFs) were: advanced age, gender, hypertension, diabetes, atrial fibrillation, hyperlipidemia, chronic kidney disease, thyroid disease, chronic obstructive pulmonary disease, malignancy, stroke, cardiovascular disease, and peripheral vascular disease. Endpoint of the study was death from any cause. A multivariate logistic regression model was built using covariates that showed as statistically significant at univariate regression analysis. RESULTS: Median age at presentation was 71.1 years (IQR: 59.1-80.5); 244 (72.2%) were males. Primary outcome occurred in 338 patients (32.2%). In decedents, median survival from Hospitalization was 6 (IQR: 3-10) days. 264 decedents had 1 RF, 120 had 2 RFs and 39 had ≥3 RFs. At multivariate logistic regression model, variables associated with primary outcome were: age class (64-69 years) (OR 3.03, CI: 1.75-5.31, P<0.001), age class (70-88 years) (OR 10.08, CI: 6.67-15.72, P<0.001), age class (≥88 years) (OR 23.99, CI: 13.21-44.82, P<0.001), male gender (OR 1.88, CI: 1.36-2.62, P<0.001), diabetes (OR 1.56, CI: 1.07-2.26, P=0.02), stroke (OR 3.41, CI: 1.33-9.91, P=0.015). CONCLUSIONS: Age, male gender, presence of diabetes and stroke appeared as independent predictors of mortality in COVID-19 patients. A table for risk of 30 days-mortality in SARS-CoV-2 infection was built, based on odds ratios derived from multivariate regression analysis.

[Preventive cardiology: comparisons of European and Italian projects with the Cardiac Units from Emilia Romagna region. A workshop of IACPR/GICR - Emilia Romagna]. / La Cardiologia Preventiva: prospettive nazionali ed europee a confronto con le Cardiologie dell'Emilia Romagna. Workshop IACPR/GICR - Emilia Romagna.

A workshop endorsed by the Italian Association of Cardiovascular Prevention and Rehabilitation--Emilia Romagna Section--held in Piacenza in May 2011, gave the opportunity to discuss the emerging role of Preventive Cardiology in the modern era. From the new documents recently published by the European and Italian Scientific Associations, the barriers in their implementation, and the contribution of the health care providers, physicians, nurses, both in primary and secondary prevention were discussed. The local initiatives of cardiac prevention in different areas were presented and compared. A new project of secondary prevention in the follow-up and management of patients with dilated cardiomyopathy and heart failure promoted by the Emilia Romagna Region Health Authority was presented.

Exercise intolerance in chronic heart failure: mechanisms and therapies. Part I.

Muscular fatigue and dyspnoea on exertion are among the most common symptoms in chronic heart failure; however their origin is still poorly understood. Several studies have shown that cardiac dysfunction alone cannot fully explain their origin, but the contribution of the multiorgan failure present in this syndrome must be highlighted. In this study, divided in two parts (see part II: pp. 643­648), we aimed to summarize the existing evidence and the most controversial aspects of the complex interplay of different factors involved in symptom generation. In this first part of the review, six key factors are revised: the heart, the lung, the skeletal muscle, the hormonal changes, the O2 delivery to the periphery, the endothelium. In the second part, the role of the excitatory reflexes and the cardiac cachexia will be presented, and finally, the potential therapeutic implications are discussed. We believe that a better knowledge of the pathophysiology of this syndrome may contribute to the management of the patients and to the improvement in their stress tolerance and quality of life.

Implantable electrical devices for prevention of sudden cardiac death: data on implant rates from a 'real world' regional registry.

AIMS: International and national consensus guidelines define appropriate indications for implantable cardioverter-defibrillators (ICDs), but the variability in implant rates in 'real world' clinical practice is still unknown. METHODS AND RESULTS: In Emilia-Romagna, an Italian region with around 4.3 million inhabitants, a web-based registry was instituted to collect data for all ICDs implanted. Between January 2006 and December 2008, data from all consecutive patients resident in this region who underwent first implant of an ICD or a biventricular ICD were collected and standardized, considering each regional area (i.e. each of the nine provinces). The overall number of implanted ICDs had an increase in years 2007 and 2008, with a relative increase in comparison to 2006, by 14 and 48% respectively, reaching an average value of 16.2 per 10,000 inhabitants in 2008. Most of the increase was due to a rise in ICDs for primary prevention. The ratio between the implant rates of the provinces with the highest and the lowest implant rates, respectively, was around 2 in 2008. CONCLUSION: Implant rates for ICDs, considering both primary and secondary prevention of sudden death, show up to two-fold variations even in a geographical region where the general level of health care is advanced and well appreciated by the population. The lack of a common strategy for sudden death prevention, approved by both physicians and institutional regional authorities, together with some degree of variability in translating guidelines into clinical practice, were identified as the main factors explaining the heterogeneity in ICD implant rates.

Global Longitudinal Strain as a Predictor of First and Subsequent Arrhythmic Events in Remotely Monitored ICD Patients With Structural Heart Disease.

OBJECTIVES: This study sought to assess speckle-tracking-derived parameters as predictors of first and subsequent ventricular events in patients with structural heart disease and implantable cardioverter-defibrillators (ICD). BACKGROUND: Left ventricular ejection fraction (LVEF), the current primary parameter of risk stratification for ventricular arrhythmias (VAs) in structural heart diseases is burdened by many limitations. METHODS: In this retrospective, observational study, all consecutive patients with structural heart disease were admitted for ICD implantation. Patients not followed by a home-monitoring system were excluded. Two-dimensional (2D) speckle-tracking analysis was used to derive global longitudinal strain (GLS), mechanical dispersion (MD), and delta contraction duration (DCD) of all patients at enrollment. Home monitoring was checked weekly to detect all VAs and ICD therapies. A recurrent event statistical approach (Prentice, Williams, and Peterson model) was applied to evaluate subsequent events after the first ones. RESULTS: A total of 203 patients were consecutively enrolled and followed for a median of 2.2 years. Kaplan-Meier curves showed an increased risk of antitachycardia pacing or shock (log-rank p = 0.003) and VAs (log-rank p = 0.001) associated with lower quartiles of GLS. An impaired GLS was independently associated with an increased risk for the first ICD therapy (hazard ratio [HR]: 1.94; 95% confidence interval [CI]: 1.30 to 2.91; p = 0.001) and (HR: 1.42; 95% CI: 1.01 to 1.98; p = 0.04) for the first VA. GLS impairment was not significantly associated with an increased risk of recurrent ICD therapies or VAs. LVEF, MD, and DCD were not associated with an increased risk of first, second, and third ICD therapies or VA. CONCLUSIONS: Impaired GLS is associated with an increased risk of VAs and appropriate ICD therapies in a consecutive "real-world," unselected population of remotely monitored patients with structural heart disease, although it does not seem reliable in predicting further arrhythmic events after the first one. MD and DCD do not predict first or subsequent arrhythmic events in ICD patients with structural heart disease.

[Heart failure and iron deficiency]. / Scompenso cardiaco e carenza marziale.

Heart failure with reduced ejection fraction (HFrEF) is a clinical reality with an incidence of >10% in the population over 65 years of age, expected to increase in the coming years. Alongside the well-known pharmacological options (e.g. angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, neprilysin inhibitors, beta-blockers, aldosterone antagonists), which have significantly improved the clinical and prognostic outcomes of HFrEF patients, we now have a new therapeutic target: iron deficiency, defined as a ferritin concentration <100 µg/l or between 100-300 µg/l in the presence of a transferrin saturation <20%. Iron plays a major role in the transport of oxygen as a component of hemoglobin, as an oxygen reservoir, and as a component of myoglobin, as well as in the formation of energy, as a constituent of respiratory chain enzymes. Iron deficiency can therefore lead to anemia, changes in cognitive performance, behavior, emotions, reduced exercise capacity and myocardial structural and functional changes. Several clinical studies have shown that intravenous iron carboxymaltose supplementation can improve anemia, NYHA class, quality of life and exercise capacity of HFrEF patients. There are no randomized studies of adequate sample size that positively correlate iron supplementation with the higher endpoints of mortality and morbidity both in chronic and acute heart failure. Several studies are ongoing to answer these questions in the next few years.

Mobile health and implantable cardiac devices: Patients' expectations.

BACKGROUND: Mobile computing and communication technologies in health services and information (so-called mHealth) have modified the traditional approach in the follow-up of patients with implantable cardiac devices, increased patient engagement and empowerment, reduced healthcare costs and improved patients' outcome. Recent developments in mobile technology, with the introduction of smartphone-compatible devices that can measure various health parameters and transfer automatically generated data, have increased the potential application of remote monitoring and the interest towards mHealth. However, little is known about the patients' interest and expectations of this new technology. OBJECTIVE: The patients' interest in the possibility of receiving data from their implantable cardiac device, clinical and health advice via remote monitoring on their smartphones were investigated. METHODS: A questionnaire entitled 'Expectations for future possibility of self-management of device data' (Likert scale scored) was submitted to 300 consecutive implantable cardiac device outpatients. The questionnaire was focused on collecting patients' expectations in receiving direct information regarding their implantable cardiac device status (item 1, five questions), their own clinical status (item 2, seven questions) and advice on healthy lifestyle promotion (item 3, nine questions). Patient characteristics associated with greater interest towards mHealth were also investigated. RESULTS: Questionnaires were completed by 268 patients (221 men, aged 69 ± 14 years). The Cronbach test reported an alpha value of 0.98 for item 1, 0.94 for item 2 and 0.97 for item 3. Patients declared to be mainly interested in the device interventions (62%) and in severe arrhythmia occurrence (61%), followed by data on heart failure severity (54%) and their performed physical activity (48%). Patients showed very little interest in ECG tracing (37%), but the lowest interest was expressed towards healthy lifestyle promotion advice (<40%). A higher education degree and the presence of the caregiver positively affected the interest towards remote monitoring information ( P < 0.001). CONCLUSIONS: The patients' interests were mainly directed at receiving information related to technical data of the implantable cardiac device and not to the overall management of the disease, underlying the insufficient awareness of patients towards the key role of self-control health status and the promotion of a healthy lifestyle.

Regional differences in exercise training implementation in heart failure: findings from the Exercise Training in Heart Failure (ExTraHF) survey.

BACKGROUND: Exercise training programmes (ETPs) are a crucial component in cardiac rehabilitation in heart failure (HF) patients. The Exercise Training in HF (ExTraHF) survey has reported poor implementation of ETPs in countries affiliated to the European Society of Cardiology (ESC). The aim of the present sub-analysis was to investigate the regional variations in the implementation of ETPs for HF patients. METHODS AND RESULTS: The study was designed as a web-based survey of cardiac units, divided into five areas, according to the geographical location of the countries surveyed. Overall, 172 centres replied to the survey, in charge of 78 514 patients, differentiated in 52 Northern (n = 15 040), 48 Southern (n = 27 127), 34 Western (n = 11 769), 24 Eastern European (n = 12 748), and 14 extra-European centres (n = 11 830). Greater ETP implementation was observed in Western (76%) and Northern (63%) regions, whereas lower rates were seen in Southern (58%), Eastern European (50%) and extra-European (36%) regions. The leading barrier was the lack of resources in all (83-65%) but Western region (37%) where patients were enrolled in dedicated settings and specialized units (75%). In 40% of centres, non-inclusion of ETP in the national or local guideline pathway accounted for the lack of ETP implementation. CONCLUSION: Exercise training programmes are poorly implemented in the ESC affiliated countries, mainly because of the lack of resources and/or national and local guidelines. The linkage with dedicated cardiac rehabilitation centres (as in the Western region) or the model of local rehabilitation services adopted in Northern countries may be considered as options to overcome these gaps.

Exercise oscillatory ventilation and prognosis in heart failure patients with reduced and mid-range ejection fraction.

AIMS: Exercise oscillatory ventilation (EOV) is a pivotal cardiopulmonary exercise test parameter for the prognostic evaluation of patients with chronic heart failure (HF). It has been described in patients with HF with reduced ejection fraction (<40%, HFrEF) and with HF with preserved ejection fraction (>50%, HFpEF), but no data are available for patients with HF with mid-range ejection fraction (40-49%, HFmrEF). The aim of the study was to evaluate the prognostic role of EOV in HFmrEF patients. METHODS AND RESULTS: We analysed 1239 patients with HFmrEF and 4482 patients with HFrEF, enrolled in the MECKI score database, with a 2-year follow-up. The study endpoint was the composite of cardiovascular death, urgent heart transplant, and ventricular assist device implantation. We identified EOV in 968 cases (16% and 17% of cases in HFmrEF and HFrEF, respectively). HFrEF EOV+ patients were significantly older, and their parameters suggested a more severe HF than HFrEF EOV- patients. A similar behaviour was found in HFmrEF EOV+ vs. EOV- patients. Kaplan-Meier analysis, irrespective of ejection fraction, showed that EOV is associated with a worse survival, and that patients with HFrEF and HFmrEF EOV+ had a significantly worse outcome than the EOV- of the same ejection fraction groups. EOV-associated survival differences in HFmrEF patients started after 18 months of follow-up. CONCLUSION: Exercise oscillatory ventilation has a similar prevalence and ominous prognostic value in both HFmrEF and HFrEF patients, indicating a group of patients in need of a more intensive follow-up and a more aggressive therapy. In HFmrEF, the survival curves between EOV+ and EOV- patients diverged only after 18 months.

Time course of effects of cardiac resynchronization therapy in chronic heart failure: benefits in patients with preserved exercise capacity.

OBJECTIVES: To assess in patients with chronic heart failure the effect of cardiac resynchronization therapy (CRT) over 12 months' follow-up the time course of the changes in functional and neurohormonal indices and to identify responders to CRT. METHODS: Eighty-nine patients (74.1 +/- 1 years, left ventricular ejection fraction [LVEF] < 35%), QRS complex duration >150 ms, in stable New York Heart Association (NYHA) class III or IV on optimal medical treatment were prospectively randomized either in a control (n = 45) or CRT (n = 44) group and underwent clinical evaluation, cardiopulmonary exercise testing (CPET), 2D-Echo, heart rate variability (HRV), carotid baroreflex (BRS), and BNP assessments before and at 6- and 12-month follow-up. RESULTS: In the CRT group, improvement of cardiac indices and BNP concentration were evident at medium term (over 6 months) follow-up, and these changes persisted on a longer term (12 months) (all P < 0.05). Instead CPET indices and NYHA class improved after 12 months associated with restoration of HRV and BRS (all P < 0.05). We identified 26 responders to CRT according to changes in LVEF and diameters. Responders presented less depressed hemodynamic (LVEF 25 +/- 1.0 vs 22 +/- 0.1%), functional (peak VO(2) 10.2 +/- 0.2 vs 6.9 +/- 0.3 ml/kg/min), and neurohormonal indices (HRV 203.6 +/- 15.7 vs 147.6 +/- 10.ms, BRS 4.9 +/- 0.2 vs 3.6 +/- 0.3 ms/mmHg) (all P < 0.05). In the multivariate analysis, peak VO(2) was the strongest predictor of responders. CONCLUSIONS: Improvement in functional status is associated with restoration of neurohormonal reflex control at medium term. Less depressed functional status (peak VO(2)) was the strongest predictor of responders to CRT.

Lifestyle modification in secondary prevention.

A healthy lifestyle is the cornerstone of prevention. Its promotion is a major task for all healthcare providers with the collaboration of the family and caregivers. It includes intervention in personal behaviour and risk factors (such as lack of physical activity, use of tobacco, unhealthy food habits and overweight), and all interventions aimed at changing lifestyle should be lifelong.

Zofenopril or irbesartan plus hydrochlorothiazide in elderly patients with isolated systolic hypertension untreated or uncontrolled by previous treatment: a double-blind, randomized study.

OBJECTIVE: To compare zofenopril + hydrochlorothiazide (Z + H) vs. irbesartan + hydrochlorothiazide (I + H) efficacy on daytime SBP in elderly (>65 years) patients with isolated systolic hypertension (ISH), untreated or uncontrolled by a previous monotherapy. METHODS: After a 1-week run-in, 230 ISH patients (office SBP ≥ 140  mmHg and DBP < 90  mmHg + daytime SBP ≥ 135  mmHg and daytime DBP < 85  mmHg) were randomized double-blind to 18-week treatment with Z + H (30 + 12.5  mg) or I + H (150 + 12.5  mg) once daily, in an international, multicenter study. Z and I doses could be doubled after 6 and 12 weeks, and nitrendipine 20  mg added at 12 weeks in nonnormalized patients. RESULTS: In the full analysis set (n = 216) baseline-adjusted average (95% confidence interval) daytime SBP reductions after 6 weeks (primary study end point) were similar (P = 0.888) with Z + H [7.7 (10.7, 4.6)  mmHg, n = 107] and I + H [7.9 (10.7, 5.0)  mmHg, n = 109]. Daytime SBP reductions were sustained during the study, and larger (P = 0.028) with low-dose Z + H at study end [16.2 (20.0, 12.5)  mmHg vs. 11.2 (14.4, 7.9)  mmHg I + H]. Daytime SBP normalization (<135 mmHg) rate was similar under Z + H and I + H at 6 and 12 weeks, but more common under Z + H at 18 weeks (68.2 vs. 56.0%, P = 0.031). Both drugs equally reduced SBP in the last 6 h of the dosing interval and homogeneously reduced SBP throughout the 24 h. The proportion of patients reporting drug-related adverse events was low (Z + H: 4.4% vs. I + H: 6.0%; P = 0.574). CONCLUSION: Elderly patients with ISH respond well to both low and high-dose Z or I combined with H.

Transient QRS amplitude attenuation is associated with clinical recovery in patients with takotsubo cardiomyopathy.

BACKGROUND/OBJECTIVES: Low voltage QRS complexes (LQRSV) and amplitude attenuation of QRS voltage (AAQRS) have been described in takotsubo (TC) patients, and postulated as valuable pre-angiographic markers. The aim of this observational study is to evaluate potential diagnostic and prognostic features of QRS amplitude in TC and acute coronary syndrome (ACS) patients. METHODS: Fifty-eight patients with TC were matched with 58 patients with ACS according to age, gender, and presence or absence of ST elevation at hospital admission. A 12-lead ECG was recorded within 12h after symptoms onset, the day after coronary angiography (CA) and before hospital discharge. When available, ECGs prior and subsequent to the acute event were also collected. RESULTS: QRS amplitude showed a time related trend, with a first phase characterized by an initial decrease in amplitude in both groups and a second phase, with a progressive recovery of QRS amplitude in TC patients up to pre-event levels, while QRS amplitude in ACS patients remained substantially unchanged from admission onwards. Rise in AAQRS during hospitalization showed a positive linear association with systolic function recovery and both troponin I and CK-MB decrease (all p<0.01) in TC patients. A 20% increase of mean AAQRS from admission is able to predict LVEF recovery and troponin I and CK-MB normalization in TC patients with good sensitivity and specificity. CONCLUSIONS: LQRSV and AAQRS are not reliable in differentiating ACS from TC. However, QRS amplitude attenuation in TC is transient, and is linearly associated with systolic function recovery and cardiac biomarkers normalization.

Monitored atrial fibrillation duration predicts arterial embolic events in patients suffering from bradycardia and atrial fibrillation implanted with antitachycardia pacemakers.

OBJECTIVES: The aim of our study was to evaluate arterial embolism (AE) occurrence rates and predictors in patients suffering from bradycardia and wearing a pacemaker with antitachycardia pacing therapies. BACKGROUND: Atrial fibrillation (AF) is associated with a high incidence of AE. METHODS: A total of 725 patients (360 men, age 71 +/- 11 years) were implanted with a DDDRP pacemaker (Medtronic AT500, Medtronic Inc., Minneapolis, Minnesota). At baseline 225 (31.0%) patients received antiplatelet therapy and 264 (36.4%) patients received anticoagulation agents. RESULTS: Over a median 22-month follow-up (25th to 75th interquartile range 16 to 30 months), AE occurred in 14 (1.9%) patients: 7 patients suffered a nonfatal ischemic stroke (0.6% per year), 4 patients had transient ischemic attack (0.34% per year), and 3 patients had embolic complications. Among baseline patients' characteristics, multivariate logistic analysis showed that embolic events are independently associated to ischemic heart disease (7.0 odds ratio [OR], 95% confidence interval [CI] 2.3 to 21.3, p = 0.001), prior embolic event (7.3 OR, 95% CI 1.2 to 43.9, p = 0.029), diabetes (5.0 OR, 95% CI 1.2 to 15.7, p = 0.032), and hypertension (4.1 OR, 95% CI 1.1 to 15.6, p = 0.036). The risk of embolism, adjusted for known risk factors, was 3.1 times increased (95% CI 1.1 to 10.5, p = 0.044) in patients with device-detected atrial fibrillation episodes longer than one day during follow-up. CONCLUSIONS: In a cohort of patients with bradycardia and AF, arterial embolism was common in patients with ischemic cardiopathy, hypertension, diabetes mellitus, and in patients with known stroke risk factors. Atrial fibrillation occurrences longer than one day were independently associated with embolic events.

Capture of atrial fibrillation reduces the atrial defibrillation threshold.

The effect of the atrial activity synchronization by single site right atrial pacing on atrial defibrillation threshold (ADFT) was investigated in patients with AF. Two series of randomized incremental cardioversion tests, with increasing energy levels from 0.5 to 10 J, were performed in 15 patients with recurrent episodes of idiopathic paroxysmal AF using two 7 Fr "single coil" catheters for internal cardioversion. After induction of sustained AF (> 10 minutes), shocks were delivered, preceded or not by 10 seconds of overdrive local atrial pacing, according to the randomization, using an external cardioverter defibrillator. A total of 187 shocks was delivered to the study population. ADFT was reduced when overdrive atrial stimulation preceded the cardioversion (3.6 +/- 1.6 vs 2.9 +/- 1.7 J, P = 0.02). Local atrial capture was considered on the basis of 1:1 phase locking between stimulus and atrial activation wave, and constant morphology of atrial wave criteria. Effective atrial capture was obtained in 8 of 15 patients. There was not significant difference in the mean of FF intervals of patients in which atrial capture was or was not stable (209 +/- 22 vs 208 +/- 28 ms). Patients were then considered according to the outcome of atrial pacing before direct current shock. A marked ADFTreduction was observed in patients with stable capture (3.8 +/- 1.7 vs 2.5 +/- 1.7 J, P = 0.0003), while no significant difference in ADFT was found when capture was not achieved (3.4 +/- 1.6 vs 3.6 +/- 1.5 J, P = NS). In conclusion, regularization of atrial electrical activity by atrial capture reduces the ADFT. A constant pacing entrainment seems to lower the energy required for electrical cardioversion by reducing the amount of fibrillating tissue.