Multimodal Prehabilitation in Heart Transplant Recipients Improves Short-Term Post-Transplant Outcomes without Increasing Costs.

(1) Background and aim: This study aimed to investigate the impact of prehabilitation on the postoperative outcomes of heart transplantation and its cost-effectiveness. (2) Methods: This single-center, ambispective cohort study included forty-six candidates for elective heart transplantation from 2017 to 2021 attending a multimodal prehabilitation program consisting of supervised exercise training, physical activity promotion, nutritional optimization, and psychological support. The postoperative course was compared to a control cohort consisting of patients transplanted from 2014 to 2017 and those contemporaneously not involved in prehabilitation. (3) Results: A significant improvement was observed in preoperative functional capacity (endurance time 281 vs. 728 s, p < 0.001) and quality-of-life (Minnesota score 58 vs. 47, p = 0.046) after the program. No exercise-related events were registered. The prehabilitation cohort showed a lower rate and severity of postoperative complications (comprehensive complication index 37 vs. 31, p = 0.033), lower mechanical ventilation time (37 vs. 20 h, p = 0.032), ICU stay (7 vs. 5 days, p = 0.01), total hospitalization stay (23 vs. 18 days, p = 0.008) and less need for transfer to nursing/rehabilitation facilities after hospital discharge (31% vs. 3%, p = 0.009). A cost-consequence analysis showed that prehabilitation did not increase the total surgical process costs. (4) Conclusions: Multimodal prehabilitation before heart transplantation has benefits on short-term postoperative outcomes potentially attributable to enhancement of physical status, without cost-increasing.

Heart transplantation as salvage treatment of intractable infective endocarditis.

BACKGROUND: For infective endocarditis (IE) with extensive perivalvular lesions or end-stage cardiac failure, heart transplantation (HT) may be the last resort. METHODS: We retrospectively collected all cases of HT for IE within the International Collaboration on Endocarditis (ICE) network. RESULTS: Between 1991 and 2021, 20 patients (5 women, 15 men), median age 50 years [interquartile range, 29-61], underwent HT for IE in Spain (n = 9), France (n = 6), Switzerland (n = 2), Colombia, Croatia, and USA (n = 1). IE affected prosthetic (n = 10), and native valves (n = 10), primarily aortic (n = 11) and mitral (n = 6). The main pathogens were oral streptococci (n = 8), Staphylococcus aureus (n = 5), and Enterococcus faecalis (n = 2). The major complications included heart failure (n = 18), peri-annular abscess (n = 10), and prosthetic valve dehiscence (n = 4). Eighteen patients had previous cardiac surgery for this episode of IE, and four were on circulatory support before HT (left ventricular assist-device and extra-corporeal membrane oxygenation, 2 patients each). The median time interval between first symptoms of IE and HT was 44.5 days [22-91.5]. The main post-HT complication was acute rejection (n = 6). Seven patients died (35%), four during the first month post-HT. Thirteen (81%) of the 16 patients discharged from the hospital survived with a median follow-up of 35.5 months [4-96.5] after HT, and no relapse of IE. CONCLUSIONS: IE is not an absolute contraindication for HT: Our case series and the literature review support that HT may be considered as a salvage treatment in highly-selected patients with intractable IE.

Drug-drug interactions of ritonavir-boosted SARS-CoV-2 protease inhibitors in solid organ transplant recipients: experience from the initial use of lopinavir-ritonavir.

OBJECTIVES: To review the drug-drug interactions between tacrolimus and lopinavir/ritonavir in 23 patients who received solid organ transplant during the first wave of COVID-19 and to determine the efficacy as well as safety of prednisone monotherapy. METHODS: Observational study performed between March and June 2020 in solid organ transplant recipients admitted with an established diagnosis of SARS-CoV-2 infection who received lopinavir/ritonavir (≥2 doses). Once lopinavir/ritonavir therapy was initiated, calcineurin inhibitor treatment was temporarily switched to prednisone monotherapy (15-20 mg/d) to avoid drug-drug interactions and toxicity. After lopinavir/ritonavir treatment completion, immunosuppressive treatment was restarted with reduced doses of prednisone-tacrolimus (target minimum blood concentration -C0- approximately 5 ng/mL). Patients were observed for 3 months to confirm the absence of rejection. RESULTS: The median time from discontinuation of tacrolimus to initiation of lopinavir/ritonavir was 14 hours (interquartile range [IQR], 12-15) and from discontinuation of lopinavir/ritonavir to resumption of tacrolimus 58 hours (IQR, 47-81). The duration of lopinavir/ritonavir treatment was 7 days (IQR, 5-7). Nine of the 21 (42.8%) patients on tacrolimus treatment had C0 above the cutoff point after lopinavir/ritonavir initiation, despite having been substituted with prednisone before lopinavir/ritonavir initiation. Three patients had very high concentrations (>40 ng/mL) and developed toxicity. No episodes of acute rejection were diagnosed. DISCUSSION: We did not observe toxicity in patients for whom tacrolimus was discontinued 24 hours before starting lopinavir/ritonavir and reintroduced at half dose 48 to 72 hours after lopinavir/ritonavir discontinuation. Prednisone monotherapy during lopinavir/ritonavir therapy was safe with no episodes of acute rejection. Experience with lopinavir/ritonavir may be applicable to the use of nirmatrelvir/ritonavir, but larger multicentre studies are needed to confirm these findings.

Conduction system pacing vs. biventricular pacing in patients with ventricular dysfunction and AV block.

BACKGROUND: It is unknown whether His-Purkinje conduction system pacing (HPCSP), as either His bundle or left bundle branch pacing, could be an alternative to cardiac resynchronization therapy (BiVCRT) for patients with left ventricular dysfunction needing ventricular pacing due to atrioventricular block. The aim of the study is to compare the echocardiographic response and clinical improvement between HPCSP and BiVCRT. METHODS: Consecutive patients who successfully received HPCSP were compared with a historical cohort of BiVCRT patients. Patients were 1:1 matched by age, LVEF, atrial fibrillation, renal function and cardiomyopathy type. Responders were defined as patients who survived, did not require heart transplantation and increased LVEF ≥5 points at 6-month follow-up. RESULTS: HPCSP was successfully achieved in 92.5% (25/27) of patients. During follow-up, 8% (2/25) of HPCSP patients died and 4% (1/25) received a heart transplant, whereas 4% (1/25) of those in the BiVCRT cohort died. LVEF improvement was 10% ± 8% HPCSP versus 7% ± 5% BiVCRT (p = .24), and the percentage of responders was 76% (19/25) HPCSP versus 64% (16/25) BiVCRT (p = .33). Among survivors, the percentage of patients who improved from baseline II-IV mitral regurgitation (MR) to 0-I MR was 9/11 (82%) versus 2/8 (25%) (p = .02). Compared to those with BiVCRT, patients with HPCSP achieved better NYHA improvement: 1 point versus 0.5 (OR 0.34; p = .02). CONCLUSION: HPCSP in patients with LVEF ≤45% and atrioventricular block improved the LVEF and induced a response similar to that of BiVCRT. HPCSP significantly improved MR and NYHA functional class. HPCSP may be an alternative to BiVCRT in these patients. (Figure 1. Central Illustration). [Figure: see text].

Septal flash correction with His-Purkinje pacing predicts echocardiographic response in resynchronization therapy.

BACKGROUND: His-Purkinje conduction system pacing (HPCSP) has been proposed as an alternative to Cardiac Resynchronization Therapy (CRT); however, predictors of echocardiographic response have not been described in this population. Septal flash (SF), a fast contraction and relaxation of the septum, is a marker of intraventricular dyssynchrony. METHODS: The study aimed to analyze whether HPCSP corrects SF in patients with CRT indication, and if correction of SF predicts echocardiographic response. This retrospective analysis of prospectively collected data included 30 patients. Left ventricular ejection fraction (LVEF) was measured with echocardiography at baseline and at 6-month follow-up. Echocardiographic response was defined as increase in five points in LVEF. RESULTS: HPCSP shortened QRS duration by 48 ± 21 ms and SF was significantly decreased (baseline 3.6 ± 2.2 mm vs. HPCSP 1.5 ± 1.5 mm p < .0001). At 6-month follow-up, mean LVEF improvement was 8.6% ± 8.7% and 64% of patients were responders. There was a significant correlation between SF correction and increased LVEF (r = .61, p = .004). A correction of ≥1.5 mm (baseline SF - paced SF) had a sensitivity of 81% and 80% specificity to predict echocardiographic response (area under the curve 0.856, p = .019). CONCLUSION: HPCSP improves intraventricular dyssynchrony and results in 64% echocardiographic responders at 6-month follow-up. Dyssynchrony improvement with SF correction may predict echocardiographic response at 6-month follow-up.

Cardiac Transplantation in Danon Disease.

BACKGROUND: Danon disease (DD) is a rare X-linked dominant cardioskeletal myopathy caused by mutations in the lysosome-associated membrane protein-2 (LAMP-2) gene that is usually lethal without cardiac transplantation. The purpose of this study was to characterize post-transplant outcomes in a large cohort of patients with DD who underwent cardiac transplantation. METHODS: The clinical phenotype and outcome data of patients with DD who underwent cardiac transplantation (n = 38; 19 males and 19 females) were obtained from 8 centers. Study outcomes included graft survival, defined as death or retransplantation, and episodes of acute cellular and antibody-mediated rejection and cardiac allograft vasculopathy at 1 year. RESULTS: Median follow-up time after transplantation for the entire cohort was 4.4 years (IQR: 1.5-12.8 years). The median age at transplant for the cohort was 20.2 years (15.8-27.9 years), with no difference in age between sexes. Median pretransplant left-ventricular ejection fraction for the entire cohort was 30% (range 11%-84%). Males had higher pretransplant aspartate aminotransferase, alanine aminotransferase and creatine phosphokinase levels than females (P < 0.001). There were 2 deaths in the entire cohort and 2 retransplants. There was no difference in actuarial graft survival between males and females (P = 0.8965); the estimated graft survival was 87.1% (95%CI: 63.6%-95.9%) at 5 years. One episode (2.7%) of antibody-mediated rejection, grade 2, and 7 episodes (19%) of acute cellular rejection, grade 2 or 3, were reported in patients who survived to discharge (6 females and 1 male; P = 0.172). CONCLUSIONS: Heart transplantation outcomes are acceptable in DD with high probabilities of 5-year graft survival for males and females suggesting that cardiac transplantation is an effective treatment option for DD patients.

Study design and rationale of the pAtients pResenTing with cOngenital heaRt dIseAse Register (ARTORIA-R).

AIM: Due to improved therapy in childhood, many patients with congenital heart disease reach adulthood and are termed adults with congenital heart disease (ACHD). ACHD often develop heart failure (HF) as a consequence of initial palliative surgery or complex anatomy and subsequently require advanced HF therapy. ACHD are usually excluded from trials evaluating heart failure therapies, and in this context, more data about heart failure trajectories in ACHD are needed to guide the management of ACHD suffering from HF. METHODS AND RESULTS: The pAtients pResenTing with cOngenital heaRt dIseAse Register (ARTORIA-R) will collect data from ACHD evaluated or listed for heart or heart-combined organ transplantation from 16 countries in Europe and the Asia/Pacific region. We plan retrospective collection of data from 1989-2020 and will include patients prospectively. Additional organizations and hospitals in charge of transplantation of ACHD will be asked in the future to contribute data to the register. The primary outcome is the combined endpoint of delisting due to clinical worsening or death on the waiting list. The secondary outcome is delisting due to clinical improvement while on the waiting list. All-cause mortality following transplantation will also be assessed. The data will be entered into an electronic database with access to the investigators participating in the register. All variables of the register reflect key components important for listing of the patients or assessing current HF treatment. CONCLUSION: The ARTORIA-R will provide robust information on current management and outcomes of adults with congenital heart disease suffering from advanced heart failure.

Cardiac Resynchronization Therapy Response Is Equalized in Men and Women by Electrical Optimization: PR Matters.

OBJECTIVES: This study hypothesized that the shorter intrinsic PR interval observed in women allows a greater degree of fusion with intrinsic conduction, achieving a shorter QRS interval duration and, thus, a better response. BACKGROUND: Women benefit more from cardiac resynchronization therapy (CRT) than men. However, the reason for this difference remains elusive. METHODS: A cohort of 180 patients included in the BEST (Fusion based optimization in resynchronization therapy [ECG Optimization of CRT: Evaluation of Mid-Term Response]; NCT01439529) study were retrospectively analyzed. Patients were initially randomized to either nonoptimized CRT (NON-OPT group; n = 89) or electrocardiographically optimized CRT based on the fusion-optimized intervals (FOI) method (FOI group; n = 91). Echocardiographic response was defined as a >15% decrease in left ventricular end-systolic volume at the 12-month follow-up. RESULTS: The basal PR interval was shorter in women as compared to men. In the NON-OPT group, CRT resulted in a shorter paced QRS interval in women than in men (134 ± 21 ms vs. 151 ± 21 ms, respectively; p = 0.003, 95% confidence interval [CI]: -27 to -5.6) and better response in women than in men: 70.4% vs. 46.4%, respectively (odds ratio: 0.37; p = 0.04; 95% CI: 0.14 to 0.97). There were no differences in paced QRS interval duration (126 ± 13 ms vs. 129 ± 17 ms; p = 0.47) or response between women and men in the FOI group (68% vs. 70.5%; odds ratio: 1.12; p = 0.82; 95% CI: 0.41 to 3.07). FOI extended the atrioventricular interval to obtain the best fusion; the atrioventricular intervals tended to require greater extension in men than in women (22 ± 33 ms vs. 8 ± 28 ms, respectively; p = 0.07). CONCLUSIONS: Women had a shorter PR interval, which was associated with a shorter QRS interval and better response to CRT. The difference in QRS interval duration and response between men and women did not persist when CRT was optimized using fusion with intrinsic conduction (FOI programming).

A propensity score-matched analysis of mortality in solid organ transplant patients with COVID-19 compared to non-solid organ transplant patients.

In the context of COVID-19 pandemic, we aimed to analyze the epidemiology, clinical characteristics, risk factors for mortality and impact of COVID-19 on outcomes of solid organ transplant (SOT) recipients compared to a cohort of non transplant patients, evaluating if transplantation could be considered a risk factor for mortality. From March to May 2020, 261 hospitalized patients with COVID-19 pneumonia were evaluated, including 41 SOT recipients. Of these, thirty-two were kidney recipients, 4 liver, 3 heart and 2 combined kidney-liver transplants. Median time from transplantation to COVID-19 diagnosis was 6 years. Thirteen SOT recipients (32%) required Intensive Care Unit (ICU) admission and 5 patients died (12%). Using a propensity score match analysis, we found no significant differences between SOT recipients and non-transplant patients. Older age (OR 1.142; 95% [CI 1.08-1.197]) higher levels of C-reactive protein (OR 3.068; 95% [CI 1.22-7.71]) and levels of serum creatinine on admission (OR 3.048 95% [CI 1.22-7.57]) were associated with higher mortality. The clinical outcomes of SARS-CoV-2 infection in our cohort of SOT recipients appear to be similar to that observed in the non-transplant population. Older age, higher levels of C-reactive protein and serum creatinine were associated with higher mortality, whereas SOT was not associated with worse outcomes.

Initial experience with bosentan for the management of pulmonary hypertension after heart transplantation.

BACKGROUND: Pulmonary hypertension (PH) after heart transplantation (HT) is associated to right ventricular (RV) dysfunction and increased morbidity and mortality. We present our experience with bosentan for the treatment of PH after HT. METHODS: A retrospective evaluation of patients with PH receiving bosentan post-transplant was performed. Pulmonary hemodynamics before and after bosentan (BG) and clinical outcomes were assessed and compared to a historical control group (CG) not receiving bosentan. RESULTS: Between 2013 and 2016, 21 patients were treated post-transplant with bosentan. Twenty-four hours after bosentan initiation, there were significant decreases in systolic (42.5 ± 8 to 38.1 ± 8 mm Hg, P = 0.015), diastolic (21.4 ± 4 to 17.8 ± 6 mm Hg, P = 0.008) and mean (29.6 ± 5 to 25 ± 6 mm Hg, P = 0.001) pulmonary artery pressures (PAP), transpulmonary gradient (13.1 ± 3 to 9.7 ± 4 mm Hg, P < 0.001), diastolic gradient (5.2 ± 4 to 2.3 ± 3 mm Hg, P = 0.001) and pulmonary vascular resistance (PVR) (2.2 ± 1 to 1.6 ± 1WU, P = 0.015). This effect was maintained at day 3. Compared with CG, BG showed significantly more decrease in PVR (0.7 ± 0.9 vs 0.3 ± 1.7WU, P = 0.025) and mean PAP (4.6 ± 5.2 vs 1.5 ± 4.4 mm Hg, P = 0.040). RV function 7 days post-transplant was significantly better in BG compared to CG, P = 0.004. There were not clinically significant interactions between bosentan and immunosuppressive treatment. CONCLUSIONS: Bosentan, initiated early post-transplant, was associated with a significant decrease in PVR. Bosentan was well tolerated and did not interact with immunosuppressive treatment.

Improvement of Reverse Remodeling Using Electrocardiogram Fusion-Optimized Intervals in Cardiac Resynchronization Therapy: A Randomized Study.

OBJECTIVES: The aim of this study was to compare patient response to cardiac resynchronization therapy (CRT) using fusion-optimized atrioventricular (AV) and interventricular (VV) intervals versus nominal settings. BACKGROUND: The additional benefit obtained by AV- and VV-interval optimization in patients undergoing CRT remains controversial. Previous studies show short-term benefit in hemodynamic parameters; however, midterm randomized comparison between electrocardiogram optimization and nominal parameters is lacking. METHODS: A group of 180 consecutive patients with left bundle branch block treated with CRT were randomized to fusion-optimized intervals (FOI) or nominal settings. In the FOI group, AV and VV intervals were optimized according to the narrowest QRS, using fusion with intrinsic conduction. Clinical response was defined as an increase >10% in the 6-min walk test or an increment of 1 step in New York Heart Association functional class. The left ventricular (LV) remodeling was defined as >15% decrease in left ventricular end-systolic volume (LVESV) at 12-month follow-up. Additionally, patients with LVESV reduction >30% relative to baseline were considered super-responders; by contrast, negative responders had increased LVESV relative to baseline. RESULTS: Participant characteristics included a mean age of 65 ± 10 years, 68% male, 37% with ischemic cardiomyopathy, LV ejection fraction 26 ± 7%, and QRS 180 ± 22 ms. Baseline QRS was shortened significantly more by FOI, compared with nominal settings (-56.55 ± 17.65 ms vs. -37.81 ± 22.07 ms, respectively; p = 0.025). At 12 months, LV reverse remodeling was achieved in a larger proportion of the FOI group (74% vs. 53% [odds ratio: 2.02 (95% confidence interval: 1.08 to 3.76)], respectively; p = 0.026). No significant differences were observed in clinical response (61% vs. 53% [odds ratio: 1.43 (95% confidence interval: 0.79 to 2.59)], respectively; p = 0.24). CONCLUSIONS: Device optimization based on FOI achieves greater LV remodeling, compared with nominal settings. (ECG Optimization of CRT: Evaluation of Mid-Term Response [BEST]; NCT01439529).

Long-term vagal stimulation for heart failure: Eighteen month results from the NEural Cardiac TherApy foR Heart Failure (NECTAR-HF) trial.

BACKGROUND: The NECTAR-HF study evaluated safety and feasibility of vagal nerve stimulation (VNS) for the treatment of heart failure patients. The first six-month randomized phase of the study did not show improvement in left ventricular remodelling in response to VNS. This study reports the 18-month results and provides novel findings aiming to understand the lack of efficacy of VNS, including a new technique assessing the effects of VNS. METHODS: Ninety-six patients were randomized 2:1 to active or inactive VNS for 6months, thereafter VNS was activated for all patients. The primary safety endpoint was 18-month all-cause mortality. RESULTS: Ninety-one patients continued in the long-term evaluation with active VNS. The on-therapy survival estimate at 18months was 95% with a 95% one-sided lower confidence limit of 91%, (better than the predefined criterion). Left ventricular systolic volume decreased in the crossover group (VNS OFF→ON; 144±37 to 139±40, p<0.05) after VNS activation; LVESD (5.02±0.77 to 4.96±0.82, p>0.05) and LVEF (33.2±4.9 to 33.3±6.5, p>0.05) did not change. A new technique to detect subtle heart rate changes during Holter recordings, i.e. "heat maps", revealed that VNS evoked heart rate response in only 13/106 studies (12%) at 6 and 12months with active VNS. CONCLUSIONS: Although a favourable long-term safety profile was found, improvements in the efficacy endpoints were not seen with VNS. A new technique for detecting acute heart rate responses to VNS suggests that the recruitment of nerve fibres responsible for heart rate changes were substantially lower in NECTAR-HF than in pre-clinical models.

Chronic vagal stimulation for the treatment of low ejection fraction heart failure: results of the NEural Cardiac TherApy foR Heart Failure (NECTAR-HF) randomized controlled trial.

AIM: The neural cardiac therapy for heart failure (NECTAR-HF) was a randomized sham-controlled trial designed to evaluate whether a single dose of vagal nerve stimulation (VNS) would attenuate cardiac remodelling, improve cardiac function and increase exercise capacity in symptomatic heart failure patients with severe left ventricular (LV) systolic dysfunction despite guideline recommended medical therapy. METHODS: Patients were randomized in a 2 : 1 ratio to receive therapy (VNS ON) or control (VNS OFF) for a 6-month period. The primary endpoint was the change in LV end systolic diameter (LVESD) at 6 months for control vs. therapy, with secondary endpoints of other echocardiography measurements, exercise capacity, quality-of-life assessments, 24-h Holter, and circulating biomarkers. RESULTS: Of the 96 implanted patients, 87 had paired datasets for the primary endpoint. Change in LVESD from baseline to 6 months was -0.04 ± 0.25 cm in the therapy group compared with -0.08 ± 0.32 cm in the control group (P = 0.60). Additional echocardiographic parameters of LV end diastolic dimension, LV end systolic volume, left ventricular end diastolic volume, LV ejection fraction, peak V02, and N-terminal pro-hormone brain natriuretic peptide failed to show superiority compared to the control group. However, there were statistically significant improvements in quality of life for the Minnesota Living with Heart Failure Questionnaire (P = 0.049), New York Heart Association class (P = 0.032), and the SF-36 Physical Component (P = 0.016) in the therapy group. CONCLUSION: Vagal nerve stimulation as delivered in the NECTAR-HF trial failed to demonstrate a significant effect on primary and secondary endpoint measures of cardiac remodelling and functional capacity in symptomatic heart failure patients, but quality-of-life measures showed significant improvement.

Mechanical abnormalities detected with conventional echocardiography are associated with response and midterm survival in CRT.

OBJECTIVES: Our aim was to identify "correctable abnormalities" using conventional grayscale and blood-pool Doppler echocardiography and evaluate their ability to predict both response and midterm survival. BACKGROUND: Identification of mechanical abnormalities that may be corrected with cardiac resynchronization therapy (CRT) is useful for predicting echocardiographic response at 1-year follow-up. METHODS: A total of 200 CRT patients were included. Clinical evaluation and echocardiography were performed before and after CRT to assess the presence of the mechanical abnormalities of interest (septal flash, abnormal ventricular filling, or exaggerated interventricular dependence). Response to CRT was defined as a reduction in left ventricular (LV) end-systolic volume (ESV) ≥15%. Four subgroups of extent of response were defined: LVESV reduction >26.68% (extensive remodeling); LVESV reduction 6.8% to 26.68% (slight remodeling); LVESV reduction <6.8% (no remodeling) and clinical response; and LVESV reduction <6.8% without clinical response or the occurrence of death or heart transplantation. Midterm cardiovascular survival was evaluated (mean follow-up 38 ± 19 months). RESULTS: The presence of a correctable abnormality was independently associated with a better rate (odds ratio: 0.03 [95% confidence interval (CI): 0.01 to 0.10], p < 0.001) and extent of response to CRT (n = 59 [96.7%] for the extensive remodeling subgroup vs. n = 53 [85.5%] for the slight remodeling subgroup vs. n = 19 [47.5%] for the no remodeling with clinical response subgroup vs. n = 17 [45.9%] for the no remodeling without clinical response subgroup, p = 0.0001), as well as with increased midterm survival (hazard ratio: 0.11 [95% CI: 0.2 to 0.6]). Other independent predictors included creatinine level and LV end-systolic diameter for response; New York Heart Association functional class IV, creatinine, LV end-systolic diameter, and transmurality index for extent of response; and New York Heart Association functional class IV for cardiovascular mortality. CONCLUSIONS: The presence of a correctable abnormality evaluated by conventional echocardiography is associated with LV reverse remodeling and better survival at midterm follow-up. Clinical characteristics and myocardial viability also have an influence.

Effect of cardiac resynchronization therapy on left ventricular diastolic function: implications for clinical outcome.

Background: The definition of response to cardiac resynchronization therapy (CRT) remains controversial,with variable rates of response depending on the criteria used. Our aim was to analyze the impact of CRT on diastolic function in different degrees of response, particularly in patients with positive clinical but no echocardiographic response.Methods and Results: In 250 CRT patients clinical evaluation and echocardiography were performed before and after CRT. Absolute response to CRT was defined as a reduction in left ventricular (LV)end-systolic volume of ≥ 15% at 1-year follow-up. Additionally, patients were classified into 4 subgroups according to their amount of response: extensive reverse remodeling (RR), slight RR, clinical response without RR, and neither clinical response nor RR. An improvement in estimates of LV filling pressure and a decrease in left atrial dimensions were observed only in responders to CRT. Patients with clinical but no echocardiographic response had significant improvement in E-wave and deceleration time and nonsignificant improvement in other parameters.Conclusions: LV diastolic function improves with CRT. Clinical responders without echocardiographic response show improvement in parameters of diastolic function. That suggests that clinical-only response to CRT is secondary to a real effect of the therapy, rather than a placebo effect.

Effect of cardiac resynchronization therapy on left ventricular diastolic function: implications for clinical outcome.

BACKGROUND: The definition of response to cardiac resynchronization therapy (CRT) remains controversial, with variable rates of response depending on the criteria used. Our aim was to analyze the impact of CRT on diastolic function in different degrees of response, particularly in patients with positive clinical but no echocardiographic response. METHODS AND RESULTS: In 250 CRT patients clinical evaluation and echocardiography were performed before and after CRT. Absolute response to CRT was defined as a reduction in left ventricular (LV) end-systolic volume of ≥15% at 1-year follow-up. Additionally, patients were classified into 4 subgroups according to their amount of response: extensive reverse remodeling (RR), slight RR, clinical response without RR, and neither clinical response nor RR. An improvement in estimates of LV filling pressure and a decrease in left atrial dimensions were observed only in responders to CRT. Patients with clinical but no echocardiographic response had significant improvement in E-wave and deceleration time and nonsignificant improvement in other parameters. CONCLUSIONS: LV diastolic function improves with CRT. Clinical responders without echocardiographic response show improvement in parameters of diastolic function. That suggests that clinical-only response to CRT is secondary to a real effect of the therapy, rather than a placebo effect.

Everolimus asociado a tacrolimus durante el primer año postrasplante cardíaco: experiencia inicial / Association of everolimus with tacrolimus during the first year after heart transplantation: Initial experience

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Long-term prognostic value of elevated heart rate one year after heart transplantation.

BACKGROUND: Elevated heart rate (HR) is associated with adverse cardiovascular outcome in the general population and in patients with cardiovascular disease. Elevated HR due to graft denervation is often found in heart transplantation (HTx) patients; the effect on graft survival and vasculopathy is unclear. Thus, the aim of this study was to evaluate the role of elevated HR at 12 months post-HTx and its power to predict HTx long-term outcome. METHODS: We evaluated retrospectively a prospective database of 312 patients undergoing HTx at two centers. HR was registered at 12 months post-HTx. The median HR was used as a cutoff point. Cox regression analysis was performed with variables known to be clinically relevant to mortality and those selected from the univariate analysis. RESULTS: During a mean follow-up of 5.5 ± 2.8 years there were 58 deaths (19%). Patients with a HR ≥ 90 bpm (median HR) at 12 months had an increased risk for all-cause mortality (Hazard Ratio=2.4, 95% CI 1.2 to 4.5, p=0.009) and mortality related to coronary allograft vasculopathy (CAV) (Hazard Ratio=3.0, 95% CI 1.25-7.14, p=0.01). Multivariate analysis showed that a HR ≥ 90 bpm independently predicted mortality (HR 3.2, 95% CI 1.4-7.1, p=0.004). CONCLUSIONS: Elevated HR measured at 12 months after HTx is an independent predictor of all-cause mortality in HTx recipients. A HR ≥ 90 bpm identifies a group of patients at high risk of death and CAV-related mortality at mid- to long-term.