Cardiac resynchronization therapy guided by interventricular conduction delay: How to choose between biventricular pacing or conduction system pacing.

BACKGROUND: Biventricular pacing (BIV) is the gold standard for cardiac resynchronization therapy (CRT). Thirty percent of patients do not respond to CRT. Conduction system pacing (CSP) represents a viable alternative. Interventricular conduction delay (IVCD), as electrical desynchrony marker, is a CRT response predictor. The aim of this study was to determine the incidence of CRT responders by selecting the best approach between BIV and CPS based on intraoperative IVCD measurement in patients with HFrEF and LBBB. METHODS: Ninety-six patients were randomly assigned in a 1:1 ratio to either a standard BIV group(control group, CG) or a group where the CRT approach was determined based on IVCD evaluation(study group, SG). If the right ventricular sensed electrogram (RVs)-left ventricular sensed electrogram (LVs) interval was ≥100 ms, the lead was left in its original position; otherwise, the LV lead was removed, and CSP was performed instead. Clinical, EKG, and echocardiographic features have been assessed pre- and 6 months post-implant. Echocardiographic and clinical responder were evaluated. RESULTS: Thirty-seven percent of patients in the SG underwent CSP, as the operative algorithm. The incidence of CRT responders was significantly higher in the SG (echocardiographic criterion: 92.5% vs. 69.8%, p:.009; clinical criterion 87.5% vs. 62.8%, p:.014). The SG showed a significantly greater difference in EF between pre- and post-implant as well as reduced end-diastolic and systolic volumes. Univariate and multivariate regression analysis indicated that enrollment in the SG was the only factor associated with CRT response. CONCLUSION: Intraoperative assessment of IVCD could help determine the optimal CRT approach between BIV and CSP, leading to a significant improvement in the rate of CRT responders.

Clinician approach to cardiopulmonary exercise testing for exercise prescription in patients at risk of and with cardiovascular disease.

Exercise training is highly recommended in current guidelines on primary and secondary prevention of cardiovascular disease (CVD). This is based on the cardiovascular benefits of physical activity and structured exercise, ranging from improving the quality of life to reducing CVD and overall mortality. Therefore, exercise should be treated as a powerful medicine and critical component of the management plan for patients at risk for or diagnosed with CVD. A tailored approach based on the patient's personal and clinical characteristics represents a cornerstone for the benefits of exercise prescription. In this regard, the use of cardiopulmonary exercise testing is well-established for risk stratification, quantification of cardiorespiratory fitness and ventilatory thresholds for a tailored, personalised exercise prescription. The aim of this paper is to provide a practical guidance to clinicians on how to use data from cardiopulmonary exercise testing towards personalised exercise prescriptions for patients at risk of or with CVD.

The importance of ventilatory thresholds to define aerobic exercise intensity in cardiac patients and healthy subjects.

BACKGROUND: Although structured exercise training is strongly recommended in cardiac patients, uncertainties exist about the methods for determining exercise intensity (EI) and their correspondence with effective EI obtained by ventilatory thresholds. We aimed to determine the first (VT1 ) and second ventilatory thresholds (VT2 ) in cardiac patients, sedentary subjects, and athletes comparing VT1 and VT2 with EI defined by recommendations. METHODS: We prospectively enrolled 350 subjects (mean age: 50.7±12.9 years; 167 cardiac patients, 150 healthy sedentary subjects, and 33 competitive endurance athletes). Each subject underwent ECG, echocardiography, and cardiopulmonary exercise testing. The percentages of peak VO2 , peak heart rate (HR), and HR reserve were obtained at VT1 and VT2 and compared with the EI definition proposed by the recommendations. RESULTS: VO2 at VT1 corresponded to high rather than moderate EI in 67.1% and 79.6% of cardiac patients, applying the definition of moderate exercise by the previous recommendations and the 2020 guidelines, respectively. Most cardiac patients had VO2  values at VT2 corresponding to very-high rather than high EI (59.9% and 50.3%, by previous recommendations and 2020 guidelines, respectively). A better correspondence between ventilatory thresholds and recommended EI domains was observed in healthy subjects and athletes (90% and 93.9%, respectively). CONCLUSIONS: EI definition based on percentages of peak HR and peak VO2  may misclassify the effective EI, and the discrepancy between the individually determined and the recommended EI is particularly relevant in cardiac patients. A ventilatory threshold-based rather than a range-based approach is advisable to define an appropriate level of EI.

Sacubitril/Valsartan in an Elderly Patient with Heart Failure: A Case Report.

Sacubitril/valsartan has recently been approved for the treatment of heart failure with reduced ejection fraction. Given its recent introduction in the armamentarium for the treatment of heart failure (HF), "field-practice" evidence is required to deepen the clinical management of sacubitril/valsartan therapy. We report a relevant case of an elderly patient who achieved major clinical benefits after only 3 months of sacubitril/valsartan therapy. Importantly, in our assessment, we employed speckle tracking echocardiography (STE), a recent echocardiography technique that is non-Doppler and not angle dependent, which analyzes deformations of heart chambers from standard images and allows a fast, reliable, and reproducible assessment of heart function. After 3 months of therapy, NHYA class decreased from III to I-II and hypertension was controlled. Echocardiography examination also showed a marked improvement, with a reduction of left ventricular diameter, improved diastolic function (E = 0.39 m/s; A 0.69 m/s; E/A 0.55), normalized diastolic function index (E/E' TDI = 6.93), normalized atrial volume (63 mL), and improved atrial strain (15.44%). This case report documents the fast clinical and symptom improvement with sacubitril/valsartan in an elderly patient with HF; comprehensive echocardiographic assessment, including STE, also revealed a marked functional improvement with this compound.

Dapagliflozin Effects on Cardiac Deformation in Heart Failure and Secondary Clinical Outcome.

BACKGROUND: Sodium-glucose cotransporter 2 inhibitors were shown to reduce morbidity and mortality in patients with heart failure. OBJECTIVES: This study aims to assess potential effects of dapagliflozin in nondiabetic patients with heart failure with reduced ejection fraction (HFrEF) and heart failure with mildly reduced ejection fraction (HFmrEF) on cardiac function assessed by speckle tracking echocardiography (STE). METHODS: This randomized, prospective, single-center, open-label trial compared consecutive nondiabetic outpatients with HFrEF or HFmrEF receiving dapagliflozin with patients treated with optimal medical therapy (OMT) except sodium-glucose cotransporter type 2 inhibitors. Primary endpoint was the presence of a significant modification of left ventricular global longitudinal strain, diastolic function (as peak atrial longitudinal strain) and right ventricular function by STE from baseline to 6 months. Cardiovascular events and parameters of congestion were assessed as safety-exploratory endpoints. RESULTS: Overall, 88 patients (38% HFmrEF) were enrolled and randomized to start dapagliflozin on top of OMT (n = 44) or to continue with OMT (n = 44). All STE values improved in the dapagliflozin group after 6 months, whereas there was a nonsignificant improvement in OMT group. Moreover, when comparing the modification of STE parameters at follow-up in patients with HFrEF and HFmrEF, only the main treatment effect resulted statistically significant in both groups (P < 0.0001), indicating a significant difference between dapagliflozin and OMT. CONCLUSIONS: This study provided randomized data on the beneficial effect of dapagliflozin in nondiabetic patients with HFrEF and HFmrEF in terms of myocardial performance measured by the most sensitive echocardiographic technique, ie, STE. This suggests its usefulness for left ventricular reverse remodeling and better quality of life in patients with HFrEF and HFmrEF. (Effects of Dapagliflozin on cardiac deformation and clinical outcomes in heart failure with reduced and mildly reduced ejection fraction [DAPA ECHO trial]; EudraCT number: 2021-005394-66).

Biventricular or Conduction System Pacing for Cardiac Resynchronization Therapy: A Strategy for Cardiac Resynchronization Based on a Hybrid Approach.

BACKGROUND: Cardiac resynchronization therapy (CRT) is usually performed with biventricular pacing (BiVP), but recently, conduction system pacing (CSP) has been proposed as an alternative in case of BiVP failure. The aim of this study is to define an algorithm to choose between BiVP and CSP resynchronization using the interventricular conduction delays (IVCD) as a guide. METHODS: Consecutive patients from January 2018 to December 2020 with an indication for CRT were prospectively enrolled in the study group (delays-guided resynchronization group, DRG). A treatment algorithm based on IVCD was used to decide whether to leave the left ventricular (LV) lead to perform BiVP or pull it out and perform CSP. Outcomes from the DRG group were compared to a historical cohort of CRT patients who underwent CRT procedures between January 2016 and December 2017 (resynchronization standard guide group, SRG). The primary endpoint was a composite of cardiovascular mortality, heart failure (HF) hospitalization, or HF event at 1 year after the date of intervention. RESULTS: The study population consisted of 292 patients, of which 160 (54.8%) were in the DRG and 132 (45.2%) in the SRG. In the DRG, 41 of 160 patients underwent CSP based on the treatment algorithm (25.6%). The primary endpoint was significantly higher in the SRG (48/132, 36.4%) compared to the DRG (35/160, 21.8%) (hazard ratio (HR): 1.72; 95% confidence interval (CI): 1.12-2.65; p = 0.013). CONCLUSIONS: A treatment algorithm based on IVCD shifted one patient out of every four from BiVP to CSP, with consequent reduction in the primary endpoint after implantation. Therefore, its application could be useful to determine whether to perform BiVP or CSP.

Different Renal Function Patterns in Patients With Acute Heart Failure: Relationship With Outcome and Congestion.

Background: The role of worsening renal function during acute heart failure (AHF) hospitalization is still debated. Very few studies have extensively evaluated the renal function (RF) trend during hospitalization by repetitive measurements. Objectives: To investigate the prognostic relevance of different RF trajectories together with the congestion status in hospitalized patients. Methods: This is a post hoc analysis of a multi-center study including 467 patients admitted with AHF who were screened for the Diur-AHF Trial. We recognized five main RF trajectories based on serum creatinine and estimated glomerular filtration rate (eGFR) behavior. According to the RF trajectories our sample was divided into 1-stable (S), 2-transient improvement (TI), 3-permanent improvement (PI), 4-transient worsening (TW), and 5-persistent worsening (PW). The primary outcome was the combined endpoint of 180 days including all causes of mortality and re-hospitalization. Results: We recruited 467 subjects with a mean congestion score of 3.5±1.08 and a median creatinine value of 1.28 (1.00-1.70) mg/dl, eGFR 50 (37-65) ml/min/m2 and NTpro B-type natriuretic peptide (BNP) 7,000 (4,200-11,700) pg/ml. A univariate analysis of the RF pattern demonstrated that TI and PW patterns were significantly related to poor prognosis [HR: 2.71 (1.81-4.05); p < 0.001; HR: 1.68 (1.15-2.45); p = 0.007, respectively]. Conversely, the TW pattern showed a significantly protective effect on outcome [HR:0.34 (0.19-0.60); p < 0.001]. Persistence of congestion and BNP reduction ≥ 30% were significantly related to clinical outcome at univariate analysis [HR: 2.41 (1.81-3.21); p < 0.001 and HR:0.47 (0.35-0.67); p < 0.001]. A multivariable analysis confirmed the independently prognostic role of TI, PW patterns, persistence of congestion, and reduced BNP decrease at discharge. Conclusions: Various RF patterns during AHF hospitalization are associated with different risk(s). PW and TI appear to be the two trajectories related to worse outcome. Current findings confirm the importance of RF evaluation during and after hospitalization.

Acute and long-term efficacy and safety of sildenafil for the treatment of chronic thromboembolic pulmonary hypertension in a heart transplant recipient.

We report on the successful treatment with sildenafil of a unique case of severe chronic thromboembolic pulmonary hypertension which developed as a late complication in a 71-year-old heart transplant recipient, with focus on the potential therapeutic challenges encountered in the management of such a peculiar association of clinical conditions.

[Cardiopulmonary exercise testing: an essential tool for a tailored exercise prescription in patients with cardiac disease]. / Il test da sforzo cardiopolmonare: uno strumento fondamentale per una prescrizione personalizzata dell'esercizio fisico nei pazienti con malattia cardiovascolare.

Cardiovascular diseases are the leading cause of death in high-income countries. Exercise prescription is an effective tool for primary and secondary cardiovascular prevention and the cardiovascular benefits of physical activity are well established, ranging from improving the quality of life to reducing mortality. A tailored approach based on patient's personal and clinical characteristics represents a cornerstone for the benefits of exercise prescription. The use of cardiopulmonary exercise testing is well-established for a tailored exercise prescription, as ventilatory thresholds allow to define exercise intensity in a highly individualized manner.

Survival in acute heart failure in intensive cardiac care unit: a prospective study.

The aim of this study is to identify the best predictors of mortality among clinical, biochemical and advanced echocardiographic parameters in acute heart failure (AHF) patients admitted to coronary care unit (CCU). AHF is a clinical condition characterized by high mortality and morbidity. Several studies have investigated the potential prognostic factors that could help the risk assessment of cardiovascular events in HF patients, but at the moment it has not been found a complete prognostic score (including clinical, laboratory and echocardiographic parameters), univocally used for AHF patients. Patients (n = 118) admitted to CCU due to AHF de novo or to an exacerbation of chronic heart failure were enrolled. For each patient, clinical and biochemical parameters were reported as well as the echocardiographic data, including speckle tracking echocardiography analysis. These indexes were then related to intra- and extrahospital mortality. At the end of the follow-up period, the study population was divided into two groups, defined as 'survivors' and 'non-survivors'. From statistical analysis, C-reactive protein (CRP) (AUC = 0.75), haemoglobin (AUC = 0.71), creatinine clearance (AUC = 0.74), left atrial strain (AUC = 0.73) and freewall right ventricular strain (AUC = 0.76) showed the strongest association with shortterm mortality and they represented the items of the proposed risk score, whose cut-off of 3 points is able to discriminate patients at higher risk of mortality. AHF represents one of the major challenges in CCU. The use of a combined biochemical and advanced echocardiographic score, assessed at admission, could help to better predict mortality risk, in addition to commonly used indexes.

Influence of aetiology on long-term effects of resynchronization on cardiac structure and function in patients treated with ß-blockers.

OBJECTIVES: Cardiac resynchronization therapy (CRT) elicits more beneficial effects on left-ventricular (LV) structure and function, and long-term clinical outcomes in nonischemic heart failure patients. Rates of ß-blocker use in recent heart failure trials are higher than in CRT trials and this may influence the response to CRT. This study examined the long-term effects of CRT on LV structure and function in New York Heart Association class III-IV ß-blocker-treated patients. METHODS: One hundred and four (41 ischemic and 63 nonischemic) CRT patients, who were receiving ß-blockers before and throughout 12 months following device implantation, were retrospectively selected. Variations in echocardiographic parameters recorded before, and 6 and 12 months after CRT were analyzed. RESULTS: Selected patients were all stable on ß-blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (97%) and diuretics (97%) before implantation. CRT was associated with significant improvements in LV morphological and systo-diastolic functional parameters at 6 months, with further improvements between 6 and 12 months seen in nonischemic patients only. Accordingly, rates of echocardiographic response to CRT were similar at 6 months but significantly higher in nonischemic patients after 1 year. The degree of reduction in LV diameters and volumes, and of increase in ejection fraction, was significantly larger in nonischemic patients at both 6 and 12 months. In addition, a significant reduction in LV mass and severity of mitral regurgitation was more evident in nonischemic patients both 6 and 12 months following CRT. CONCLUSIONS: Ischemic aetiology of heart failure is associated with less favorable long-term effects of CRT on LV structure and function despite the systematic use of ß-blockers.