Vaccination Recommendations in Solid Organ Transplant Adult Candidates and Recipients.

Prevention of infections is crucial in solid organ transplant (SOT) candidates and recipients. These patients are exposed to an increased infectious risk due to previous organ insufficiency and to pharmacologic immunosuppression. Besides infectious-related morbidity and mortality, this vulnerable group of patients is also exposed to the risk of acute decompensation and organ rejection or failure in the pre- and post-transplant period, respectively, since antimicrobial treatments are less effective than in the immunocompetent patients. Vaccination represents a major preventive measure against specific infectious risks in this population but as responses to vaccines are reduced, especially in the early post-transplant period or after treatment for rejection, an optimal vaccination status should be obtained prior to transplantation whenever possible. This review reports the currently available data on the indications and protocols of vaccination in SOT adult candidates and recipients.

Cardiac Magnetic Resonance for Prophylactic Implantable-Cardioverter Defibrillator Therapy in Ischemic Cardiomyopathy: The DERIVATE-ICM International Registry.

BACKGROUND: Implantable cardioverter-defibrillator (ICD) therapy is the most effective prophylactic strategy against sudden cardiac death (SCD) in patients with ischemic cardiomyopathy (ICM) and left ventricle ejection fraction (LVEF) ≤35% as detected by transthoracic echocardiograpgy (TTE). This approach has been recently questioned because of the low rate of ICD interventions in patients who received implantation and the not-negligible percentage of patients who experienced SCD despite not fulfilling criteria for implantation. OBJECTIVES: The DERIVATE-ICM registry (CarDiac MagnEtic Resonance for Primary Prevention Implantable CardioVerter DebrillAtor ThErapy; NCT03352648) is an international, multicenter, and multivendor study to assess the net reclassification improvement (NRI) for the indication of ICD implantation by the use of cardiac magnetic resonance (CMR) as compared to TTE in patients with ICM. METHODS: A total of 861 patients with ICM (mean age 65 ± 11 years, 86% male) with chronic heart failure and TTE-LVEF <50% participated. Major adverse arrhythmic cardiac events (MAACE) were the primary endpoints. RESULTS: During a median follow-up of 1,054 days, MAACE occurred in 88 (10.2%). Left ventricular end-diastolic volume index (HR: 1.007 [95% CI: 1.000-1.011]; P = 0.05), CMR-LVEF (HR: 0.972 [95% CI: 0.945-0.999]; P = 0.045) and late gadolinium enhancement (LGE) mass (HR: 1.010 [95% CI: 1.002-1.018]; P = 0.015) were independent predictors of MAACE. A multiparametric CMR weighted predictive derived score identifies subjects at high risk for MAACE compared with TTE-LVEF cutoff of 35% with a NRI of 31.7% (P = 0.007). CONCLUSIONS: The DERIVATE-ICM registry is a large multicenter registry showing the additional value of CMR to stratify the risk for MAACE in a large cohort of patients with ICM compared with standard of care.

AI Cardiac MRI Scar Analysis Aids Prediction of Major Arrhythmic Events in the Multicenter DERIVATE Registry.

Background Scar burden with late gadolinium enhancement (LGE) cardiac MRI (CMR) predicts arrhythmic events in patients with postinfarction in single-center studies. However, LGE analysis requires experienced human observers, is time consuming, and introduces variability. Purpose To test whether postinfarct scar with LGE CMR can be quantified fully automatically by machines and to compare the ability of LGE CMR scar analyzed by humans and machines to predict arrhythmic events. Materials and Methods This study is a retrospective analysis of the multicenter, multivendor CarDiac MagnEtic Resonance for Primary Prevention Implantable CardioVerter DebrillAtor ThErapy (DERIVATE) registry. Patients with chronic heart failure, echocardiographic left ventricular ejection fraction (LVEF) of less than 50%, and LGE CMR were recruited (from January 2015 through December 2020). In the current study, only patients with ischemic cardiomyopathy were included. Quantification of total, dense, and nondense scars was carried out by two experienced readers or a Ternaus network, trained and tested with LGE images of 515 and 246 patients, respectively. Univariable and multivariable Cox analyses were used to assess patient and cardiac characteristics associated with a major adverse cardiac event (MACE). Area under the receiver operating characteristic curve (AUC) was used to compare model performances. Results In 761 patients (mean age, 65 years ± 11, 671 men), 83 MACEs occurred. With use of the testing group, univariable Cox-analysis found New York Heart Association class, left ventricle volume and/or function parameters (by echocardiography or CMR), guideline criterion (LVEF of ≤35% and New York Heart Association class II or III), and LGE scar analyzed by humans or the machine-learning algorithm as predictors of MACE. Machine-based dense or total scar conferred incremental value over the guideline criterion for the association with MACE (AUC: 0.68 vs 0.63, P = .02 and AUC: 0.67 vs 0.63, P = .01, respectively). Modeling with competing risks yielded for dense and total scar (AUC: 0.67 vs 0.61, P = .01 and AUC: 0.66 vs 0.61, P = .005, respectively). Conclusion In this analysis of the multicenter CarDiac MagnEtic Resonance for Primary Prevention Implantable CardioVerter DebrillAtor ThErapy (DERIVATE) registry, fully automatic machine learning-based late gadolinium enhancement analysis reliably quantifies myocardial scar mass and improves the current prediction model that uses guideline-based risk criteria for implantable cardioverter defibrillator implantation. ClinicalTrials.gov registration no.: NCT03352648 Published under a CC BY 4.0 license. Supplemental material is available for this article.

Cardiac magnetic resonance for prophylactic implantable-cardioverter defibrillator therapy international study: prognostic value of cardiac magnetic resonance-derived right ventricular parameters substudy.

AIMS: Right ventricular systolic dysfunction (RVSD) is an important determinant of outcomes in heart failure (HF) cohorts. While the quantitative assessment of RV function is challenging using 2D-echocardiography, cardiac magnetic resonance (CMR) is the gold standard with its high spatial resolution and precise anatomical definition. We sought to investigate the prognostic value of CMR-derived RV systolic function in a large cohort of HF with reduced ejection fraction (HFrEF). METHODS AND RESULTS: Study cohort comprised of patients enrolled in the CarDiac MagnEtic Resonance for Primary Prevention Implantable CardioVerter DefibrillAtor ThErapy registry who had HFrEF and had simultaneous baseline CMR and echocardiography (n = 2449). RVSD was defined as RV ejection fraction (RVEF) <45%. Kaplan-Meier curves and cox regression were used to investigate the association between RVSD and all-cause mortality (ACM). Mean age was 59.8 ± 14.0 years, 42.0% were female, and mean left ventricular ejection fraction (LVEF) was 34.0 ± 10.8. Median follow-up was 959 days (interquartile range: 560-1590). RVSD was present in 936 (38.2%) and was an independent predictor of ACM (adjusted hazard ratio = 1.44; 95% CI [1.09-1.91]; P = 0.01). On subgroup analyses, the prognostic value of RVSD was more pronounced in NYHA I/II than in NYHA III/IV, in LVEF <35% than in LVEF ≥35%, and in patients with renal dysfunction when compared to those with normal renal function. CONCLUSION: RV systolic dysfunction is an independent predictor of ACM in HFrEF, with a more pronounced prognostic value in select subgroups, likely reflecting the importance of RVSD in the early stages of HF progression.

Impact of secondary mitral valve chordal cutting on valve geometry in obstructive hypertrophic cardiomyopathy with marked septal hypertrophy.

AIMS: In patients with obstructive hypertrophic cardiomyopathy (HCM) and mild septal thickness undergoing myectomy, resecting fibrotic anterior mitral leaflet (AML) secondary chordae moves the mitral valve (MV) away from the outflow tract and ejection flow, reducing the need for a deep septal excision. Aim of the present study was to assess whether chordal resection has similarly favourable effects in patients with important hypertrophy, who represent the majority of patients with obstructive HCM. METHODS AND RESULTS: The MV position in the ventricular cavity, assessed from echocardiography as AML-annulus ratio, was compared before and after chordal resection in 150 consecutive HCM patients with important (≥20 mm) and 62 with mild (≤19 mm) septal thickness undergoing myectomy. Preoperatively, MV position was displaced towards the septum to a similar extent in both groups. Postoperatively, AML-annulus ratio increased of an equal degree in both groups, from 0.43 ± 0.05 to 0.55 ± 0.06 (P < 0.001) a 28% increase, and from 0.43 ± 0.06 to 0.55 ± 0.06 (P < 0.001) a 26% increase, respectively, indicating a similar MV shift away from the outflow tract. When AML-annulus ratio was compared in the study cohort and 124 normal subjects, MV position was within normal range in <4% of patients preoperatively and normalized in >50% postoperatively. CONCLUSIONS: In obstructive HCM, displacement of the MV apparatus into the outflow tract interferes with the ejection flow. Resection of fibrotic secondary chordae moves the MV apparatus away from the outflow tract and enlarges the outflow area independently of septal thickness, facilitating septal myectomy by reducing the need for a deep muscular excision.

Right and left ventricular structures and functions in acute HFpEF: comparing the hypertensive pulmonary edema and worsening heart failure phenotypes.

BACKGROUND: Limited data are available on right (RV) and left (LV) ventricular structures and functions in acute heart failure with preserved ejection fraction (AHF-pEF) presenting with hypertensive pulmonary edema (APE) versus predominant peripheral edema (peHF). METHODS AND RESULTS: In a prospective study of consecutive patients with AHF-pEF, 80 patients met inclusion and not exclusion criteria, and underwent echocardiographic and laboratory examination in the emergency ward. The survived (94%) were re-evaluated at the discharge. At admission, systolic, diastolic, pulse blood pressure (BP), and high sensitivity troponin I were higher (all P < 0.05) with APE than with peHF while brain-type natriuretic peptide (BNP), hemoglobin and estimated glomerular filtration rate (eGFR) did not differ between the two phenotypes. LV volumes and EF were comparable between APE and peHF, but APE showed lower relative wall thickness (RWT), smaller left atrial (LA) volume, higher pulse pressure/stroke volume (PP/SV), and higher ratio between the peak velocities of the early diastolic waves sampled by traditional and tissue Doppler modality (mitral E/e', all P < 0.05). Right ventricular and atrial (RA) areas were smaller, tricuspid anular plane systolic excursion (TAPSE) and estimated pulmonary artery peak systolic pressure (sPAP) were higher with APE than with peHF (all P < 0.05) while averaged degree of severity of tricuspid insufficiency was greater with peHF than with APE. At discharge, PP/SV, mitral E/e', sPAP, RV sizes were reduced from admission in both phenotypes (all P < 0.05) and did not differ anymore between phenotypes, whereas LV EF and TAPSE did not show significant changes over time and treatments. CONCLUSION: In AHF-pEF, at comparable BNP and LV EF, hypertensive APE showed eccentric LV geometry but smaller RV and RA sizes, and higher RV systolic function, increased LV ventricular filling and systemic arterial loads. AHF resolution abolished the differences in PP/SV and LV diastolic load between APE and peHF whereas APE remained associated with more eccentric RV and higher TAPSE.

Ventricular arrhythmias and ARNI: is it time to reappraise their management in the light of new evidence?

The remarkable scientific progress in the treatment of patients with heart failure (HF) and reduced ejection fraction (HFrEF) has more than halved the risk of sudden cardiac death (SCD) in this setting. However, SCD remains one of the major causes of death in this patient population. Beyond the acknowledged role of beta blockers and inhibitors of the renin-angiotensin-aldosterone system (RAAS), a new class of drugs, the angiotensin receptor neprilysin inhibitors (ARNI), proved to reduce the overall cardiovascular mortality and, more specifically, the risk of SCD in HFrEF patients. The mechanism by which ARNI may reduce the mortality connected with harmful ventricular arrhythmias is not utterly clear. A variety of direct and indirect mechanisms have been suggested, but a favorable left ventricular reverse remodeling seems to play a key role in this setting. Furthermore, the well-known protective effect of implantable cardioverter-defibrillator (ICD) has been debated in HFrEF patients with non-ischemic cardiomyopathy (NICM) arguing against the role of primary prevention ICD in this setting, particularly when ARNI therapy is considered. The purpose of this review was to provide insights into the SCD mechanisms involved in HFrEF patients together with the current role of electrical therapies and new drug agents in this setting. Graphical abstract.

The myosin activator: is another step forward in heart failure therapy?

Selective cardiac myosin activators constitute a new class of drugs capable of increasing cardiac contractility independently of intracellular calcium concentrations. In the GALACTIC-HF study, the first of this class of molecules, omecamtiv mercabil, was compared with the standard of care according to current guidelines, showing a significant reduction in the composite endpoint of first episode of heart failure or mortality due to cardiovascular causes in patients exposed to treatment compared with placebo. In particular, the effect was more pronounced for decreasing ejection fraction values, suggesting a potential further benefit of selective cardiac myosin activators in this category of patients.

Association between sleep disordered breathing, neurocognitive impairment and diastolic function in acute heart failure patients: an insight after the vulnerable phase of the hospitalization.

Sleep disordered breathing (SDB) and neurocognitive impairment (NI) are a typical feature of HF (heart failure), especially with preserved ejection fraction (HFpEF). So far, very few data exist regarding changes in the severity of SDB, the degree of NI, and the diastolic function in acute HF (AHF) patients and during follow up. In a population of 24 AHF patients (12 with reduced ejection fraction-HFrEF- and 12 HFpEF) with SDB a complete echocardiogram, a set of NI tests, and a polysomnography were performed in the acute phase and after 90 days. A control group of 12 non-HF patients hospitalized for other cardiovascular causes was considered. At baseline, SDB were present both in HFpEF and HFrEF, and a consistent reduction of apneic events was observed at follow up. Improvements in diastolic and right ventricular function were documented at three months compared to baseline, both in HFpEF and in HFrEF. Compared to HFrEF patients and controls, HFpEF patients showed lower NI scores at baseline tests, but a more significant improvement at three months follow-up. In AHF patients with SDB the achievement of a better compensation could lead to important beneficial effect not only on echocardiographic variables and nocturnal respiratory profile, but also on NI, especially in HFpEF.

An unexpected recovery of patients with pulmonary arterial hypertension and SARS-CoV-2 pneumonia: a case series.

Since the beginning of the SARS-CoV-2 outbreak, few cases of COVID-19 pneumonia in patients with pulmonary arterial hypertension have been reported. We present four patients with known history of PAH admitted to our hospital with SARS-CoV-2 pneumonia to analyze the impact of this disease on their clinical outcome.

Short-term echocardiographic evaluation by global longitudinal strain in patients with heart failure treated with sacubitril/valsartan.

AIMS: The angiotensin receptor neprilysin inhibitor (ARNI) sacubitril/valsartan reduces mortality and hospitalizations in patients with heart failure and reduced ejection fraction (HFrEF). Favourable effects on haemodynamic and functional parameters have been observed in patients with HFrEF undergoing ARNI therapy, using standard transthoracic echocardiography. Global longitudinal strain (GLS) assessment uses a semi-automatic procedure to provide a reliable and repeatable method that improves the detection of early changes of contractile function. We aimed to assess the effects of ARNI on GLS and myocardial mechanics in patients with HFrEF. METHODS AND RESULTS: Thirty patients with New York Heart Association class II-III HFrEF were treated with ARNI and monitored using standard echocardiographic examination and GLS measurements at baseline, 3 months, and 6 months. ARNI therapy resulted in a significant reduction of ventricular volumes and a significant increase in left ventricular ejection fraction at 6 months but not 3 months by standard transthoracic echocardiography (left ventricular ejection fraction from 28 ± 8% at baseline to 34 ± 12% at 6 months, P < 0.001). Non-significant differences in the size of the left atrium, right ventricular function, and pulmonary pressures were found at 6 months. By using GLS, there was a progressive improvement of all strain parameters by 3 months. The improvement showed a progressive trend over time and maintained significance at 6 months: GLS 4ch -7.2 ± 4.8% at baseline vs. -7.5 ± 3.9% at 3 months (P = 0.025) and - 9.2 ± 5.2% at 6 months (P = 0.0001); AVG GLS -6.9 ± 4.3 at baseline vs. -7.9 ± 4.2 at 3 months (P = 0.04) and - 8.8 ± 4.4 at 6 months (P = 0.035); GLS endo 8.2 ± 4.8 at baseline vs. -9.0 ± 4.8 at 3 months (P = 0.05) and - 10.1 ± 5.1 at 6 months (P = 0.001). CONCLUSIONS: Sacubitril/valsartan induces an early benefit on left ventricular remodelling, which is captured by myocardial strain and not by standard echocardiography. Strain method represents a practical tool to assess early and minimal variations of left ventricular systolic function.

Takotsubo cardiomyopathy associated with Kounis syndrome: A clinical case of the "ATAK complex".

A 60-year-old female developed cardiac arrest after experiencing an anaphylactic shock during administration of plasma-expanders. An electrocardiogram registered after restoration of sinus rhythm showed mild ST-elevation in the anterior precordial leads and T waves changes followed by appearance of echocardiographic alterations of left ventricular apex kinesis. Coronary angiography revealed normal coronary arteries, and cardiovascular magnetic resonance confirmed apical ballooning with late gadolinium enhancement in the segments with abnormal contractility. This uncommon clinical case confirms how takotsubo and Kounis syndrome may converge in a single nosological entity, the so-called "ATAK complex" (Adrenaline, Tako-Tsubo, Anaphylaxis, and Kounis), with a specific management and prognostic implications. .

Physical activity in the prevention of peripheral artery disease in the elderly.

Aging is a well-known cardiovascular risk factor and cardiovascular diseases (CVD) are estimated to be the most common cause of death in the elderly. Peripheral arterial disease (PAD) represents an important clinical manifestation of CVD leading to increase morbidity and mortality, especially in elderly population. The correct management of PAD population includes the prevention of cardiovascular events and relief of symptoms, most commonly intermittent claudication. Progressive physical activity is an effective treatment to improve walking distance and to reduce mortality and cardiovascular events in patients with PAD, however the ability to effectively engage in physical activity often declines with increasing age. The maintenance and increase of reserve functional capacity are important concepts in the elderly population. Ultimately, the goal in participation of physical activity in the healthy elderly population is maintenance and development of physical functional reserve capacity. Therefore, for individuals suffering of PAD, appropriate physical activity in the form of supervised exercise may serve as a primary therapy. Although there are few direct comparisons of therapeutic exercise programs vs. pharmacological or surgical interventions, these increases in walking distance are greater than those reported for the most widely used agents for claudication, pentoxyphylline, and cilostazol. Despite a reduction in mortality and improvement of quality of life caused by physical activity in the PAD population, the molecular, cellular, and functional changes that occur during physical activity are not completely understood. Therefore, this review article aims at presenting an overview of recent established clinical and molecular findings addressing the role of physical activity on PAD in the older population.