Predictors of survival in patients undergoing cardiac rehabilitation after transcatheter aortic valve replacement (TAVR): a multicenter retrospective study.

BACKGROUND: The aim of this study was to evaluate cardiac rehabilitation (CR)-derived predictors of outcome in patients discharged from rehabilitation after transcatheter aortic valve replacement (TAVR). METHODS: We retrospectively analyzed data from 232 TAVR patients (aged 82±6 years, 55% females) discharged following an average 3-week residential CR program in the period January 2009 to December 2017. Comorbidities (cumulative illness rated state-comorbidity index, CIRS-CI), echocardiography on admission, disability (Barthel Index [BI]) and functional capacity (6-min walk distance, 6MWD) at discharge, and maximal training session intensity expressed in METs/min were collected. The endpoint was all-cause mortality. RESULTS: Seventy-four (32%) deaths occurred at 3-year follow-up. At discharge, non-survivors had a higher comorbidity rate (CIRS-CI 5.2±2.3 vs. 4.1±1.9, P=0.000), higher disability level (BI 80.4±24 vs. 88.8±17, P=0.000), and worse renal function (creatinine 1.6±0.9 vs. 1.2±0.4 mg/dL, P=0.000). They were also more often on diuretics (73% vs. 53.2%, P=0.003) and beta-blocker therapy (73% vs. 57.6%, P=0.042) and had a markedly reduced functional capacity (6MWD 221±100m vs. 265±105m, P=0.001). At multivariate Cox proportional hazards regression analysis, independent predictors of survival at follow-up were lower comorbidity rate, a better-preserved renal function, lower use of diuretics, and a higher 6MWD at discharge (Harrell's C = 0.707). CONCLUSIONS: Patients attending residential CR after TAVR are very old with significant comorbidity. The overall 3-year mortality rate after CR discharge is high. Our findings suggest the need for individually tailored follow-up care in patients discharged from CR after TAVR to address their residual exercise capacity, comorbidities, and renal function impairment.

Prognostic value of 6-min walk test compared to cardiopulmonary exercise test in patients with severe heart failure.

AIMS: The 6-min walk test (6MWT) and cardiopulmonary exercise test (CPET) are both predictive in heart failure (HFrEF). Although 6MWT substitutes for CPET in HFrEF patients, as submaximal testing may be preferable, its prognostic superiority still needs to be verified, particularly in regard to beta blockers (BBs). We aimed to compare the prognostic role of CPET and 6MWT and investigate whether BB therapy influences the predictive value. METHODS: This is a single-center, retrospective study. Advanced HFrEF patients were followed up for 3 years: events were cardiovascular death or urgent heart transplantation. We analyzed the predictive capacity of CPET and 6MWT in patients, and subdivided according to use of BBs. RESULTS: In a group of 251 HFrEF patients, we found a correlation between meters and peak VO2 (r2 = 0.94). Over the 3-year follow-up, 74 events were recorded. Both CPET and 6MWT variables were correlated with outcome at univariate analysis (meter and VE/VCO2 slope, peak VO2, VO2 at ventilatory anaerobic threshold, percentage predicted of peak VO2), but only percentage predicted of peak VO2 (pppVO2) was an independent predictor. In 103 HFrEF patients on BBs (23 nonsurvivors), neither pppVO2 nor meter were predictive, while in 148 patients not treated with BB (51 with events) pppVO2 was selected as an independent prognostic parameter (P = 0.001). CONCLUSIONS: 6MWT is a valid alternative to CPET, although the percentage of predicted of peak VO2 emerged as the strongest predictor. Nonetheless, our results suggest that both functional derived parameters are not predictive among those patients treated with BBs. Further studies are necessary to confirm these findings.

Cardiovascular disease patients and predictors of length of stay of residential of cardiac rehabilitation. A specific rehabilitation is mandatory in very old patients?

As more adults are living into old age, they are predisposed to cardiovascular disease (CVD) and the demand for cardiac rehabilitation is increasing. We aimed to verify predictors of length of stay (LOS) in young (Y) vs older (O) vs very old (VO) CVD patients, admitted to residential cardiac rehabilitation. Patients' demographic and clinical characteristics at admission, as well as Barthel index (BI), Cumulative Illness Rating Scale (CIRS), comorbidity severity/complexity, NYHA classification, left ventricular ejection fraction (LVEF), physical activity level were compared in Y (≤65 years) vs O (between >65 and <76 years) vs VO patients (with an age of ≥76 years) against LOS. In 5,070 consecutively CVD patients were included; they were 1392 Y (38%) 1944 O (35%) 1334 VO patients (27%) and LOS duration was 16±7, 19±9 and 22±10 days, respectively (p<0.0001). In Y, LOS was linked to BI (p=0.000) and to LVEF (p=0.000) at multivariable analysis with area under ROC curve of 0.82, whereas in O, LOS was associated to gender (p=0.013) CIRS severity (p=0.000), BI (p=0.000), LVEF (p=0.000), and in those VO to gender (p=0.004), BI (p=0.000) and medical infusion (p=0.000) at multivariable with ROC curve of 0.83 and 0.74, respectively. In very old patients, a prolonged LOS is related to extra-cardiac conditions. Therefore, we promote a specific cardiac rehabilitation for these patients.

Cardiopulmonary exercise testing in patients with asymptomatic left ventricular dysfunction: lack of prognostic predictive power of ventilatory variables.

AIMS: The indication for cardiopulmonary exercise testing (CPET) in predictive evaluation has been extended beyond chronic heart failure (HF) patients to include asymptomatic left ventricular dysfunction (ALVD) patients, but its prognostic value is still unclear. We aimed to verify if CPET can predict outcome in ALVD and to identify which of the CPET parameters predictive in chronic HF are also effective in ALVD patients. METHODS AND RESULTS: We screened ALVD (LVEF ≤ 40% without HF symptoms) and HF patients for cardiac death, and compared peak oxygen consumption (pVO2), exertional oscillatory ventilation (EOV), and ventilatory response (VE/VCO2 slope) between survivors and non-survivors. Asymptomatic left ventricular dysfunction and HF patients formed the study population (585 ALVD and 695 HF). Both groups had similar male prevalence (98% vs. 98%; P = 0.345) but ALVD patients were younger (52 ± 10 vs. 60 ± 10 years, P = 0.004). Cardiac death was observed in 142 patients (5% of ALVD, 15% of HF). Exertional oscillatory ventilation occurred in 4% of ALVD, whereas VE/VCO2 slope was significantly lower (30 ± 7 vs. 35 ± 4) and pVO2 higher (16 ± 4 vs. 14 ± 3 mL/kg/min) than in chronic HF patients. Asymptomatic left ventricular dysfunction non-survivors had a significantly greater EOV incidence (13% vs. 3%, P = 0.003), lower pVO2 (13 ± 4 vs. 16 ± 3 mL/kg/min P = 0.000) and higher VE/VCO2 slope (33 ± 7 vs. 31 ± 5, P = 0.032). No ventilatory parameter had prognostic value at multivariable analysis in ALVD patients. CONCLUSIONS: Cardiopulmonary exercise testing can predict events in ALVD patients, but the risk stratification relies on different parameters than in HF patients. Further analysis in a multi-centre trial is required to better quantify the predictive impact of CPET risk parameters in ALVD patients.

Functional capacity assessment and Minimal Clinically Important Difference in post-acute cardiac patients: the role of Short Physical Performance Battery.

BACKGROUND: The Short Physical Performance Battery (SPPB) test is a well-established tool to assess physical performance, and to identify frail patients. Assessment of the SPPB in a specific population of elder patients in cardiac rehabilitation phase after a cardiac event is missing. AIM: The aim of this study was to correlate SPPB and the cardiac rehabilitation outcome in a group of elder patients after a cardiac event and to identify the Minimal Clinically Important Difference (MCID) of the SPPB. METHODS: Consecutive (n = 392) patients aged ≥75 years, in the rehabilitation phase after cardiac surgery (70.1%), congestive heart failure (7.4%), or acute coronary syndrome (22.5%), were enrolled. SPPB was performed twice: on admission and discharge. The MCID was assessed with the 'anchor method', and the Patient Global Impression of Change was employed as the anchor. RESULTS: On admission, SPPB classified 56, 117, 116, and 94 patients as severe, moderate, mild, or minimal/no limitations, respectively. Patients with the lower SPPB had the longer length of stay, and the higher complications rate. At receiver operating characteristic analysis, an SPPB improvement >1 was identified as the MCID (area-under-curve 0.77, 95% CI 0.67-0.85). Overall, 285 patients (74.2%) had a 'clinically significant' improvement in SPPB, with a rate of improvement higher in patients with severe/moderate limitations (83.0%) and lower in those with mild (78.9%) or minimal/no limitations (53.6%). CONCLUSION: A lower SPPB score is associated with a higher complications rate in the post-acute phase. An improvement >1 point of SPPB was identified as the MCID; this reference value could serve as the goal for rehabilitation interventions.

Integrated care of chronic degenerative non-communicable diseases and rehabilitation: the odd couple?

Chronic degenerative non-communicable diseases affecting different organs and systems are considered by the World Health Organization (WHO) as the emergent epidemic in the third millennium...

High dosage of a fixed combination oxycodone/naloxone prolonged release: efficacy and tolerability in patients with chronic cancer pain.

PURPOSE: Opioids are associated with side effects in the treatment of moderate-to-severe chronic cancer pain. Oral combination of opioid agonist-antagonist oxycodone-naloxone (OXN-PR) attenuates gastrointestinal side effects; however, evidence on high-dose OXN-PR treatment is scant. This study evaluates the efficacy and tolerability of high-dose OXN-PR in chronic cancer pain. PATIENTS AND METHODS: This was a multicenter, prospective 60-day observation on consecutive cancer patients with uncontrolled moderate-severe chronic pain or intolerant to other analgesics, who were switched at entry visit (T0) to OXN-PR ≥80 mg daily. Patients were reassessed 14, 30, 45, and 60 days later (T60). Primary endpoint of the study was analgesic response rate (decrease ≥30% of pain intensity from baseline, measured on a 0-10 numerical rating scale, NRS) after 30 days on OXN-PR. Additional endpoints assessed at every visit were the impact of pain on quality of life (QoL), breakthrough cancer pain (BTCP) episodes, opioid dosage escalation index, bowel dysfunction, safety, and other side effects. RESULTS: One hundred nineteen patients were included (age 64 ± 12, metastatic disease in 91.6%); 101 of them (84.9%) completed the 60-day observation. At T0, the majority had severe pain (NRS ≥7 in 79.8%; neuropathic features in 83.2%). Response rate at 30-day visit was 79.8% (n = 95). OXN-PR resulted in a significant reduction in pain over time (T0: 7.4 ± 1.3; T60: 3.3 ± 1.8; p < 0.001), and the number of daily (BTCP) declined (3.9 ± 2.2 vs. 2.0 ± 0.6, p < 0.001). Daily dosage of OXN-PR slightly increased (T0: 81.3 ± 6.0; T60: 93.6 ± 34.0; p < 0.001). The impact of pain on QoL abated (p < 0.0001), and bowel function improved overtime (p < 0.001). After the switch to OXN-PR, the number of patients complaining for side effects decreased overall (p < 0.0001); laxatives and antiemetic use also declined significantly. CONCLUSIONS: OXN-PR was highly effective and well tolerated even at high doses in cancer patients with chronic pain. The agonist-antagonist combination rapidly alleviated pain and its impact on life style, reducing the number of BTCP and improving opioid side effects.

Comparative analysis of iterative reconstruction algorithms with resolution recovery and new solid state cameras dedicated to myocardial perfusion imaging.

New technologies are available in myocardial perfusion imaging. They include new software that recovers image resolution and limits image noise, multifocal collimators and dedicated cardiac cameras in which solid-state detectors are used and all available detectors are constrained to imaging just the cardiac field of view. These innovations resulted in shortened study times or reduced administered activity to patients, while preserving image quality. Many single center and some multicenter studies have been published during the introduction of these innovations in the clinical practice. Most of these studies were lead in the framework of "agreement studies" between different methods of clinical measurement. They aimed to demonstrate that these new software/hardware solutions allow the acquisition of images with reduced acquisition time or administered activity with comparable results (as for image quality, image interpretation, perfusion defect quantification, left ventricular volumes and ejection fraction) to the standard-time or standard-dose SPECT acquired with a conventional gamma camera and reconstructed with the traditional FBP method, considered as the gold standard. The purpose of this review is to provide the reader with a comprehensive understanding of the pro and cons of the different approaches summarizing the achievements reached so far and the issues that need further investigations.

Comparative analysis of iterative reconstruction algorithms with resolution recovery and time of flight modeling for 18F-FDG cardiac PET: A multi-center phantom study.

BACKGROUND: The purpose of this study was to evaluate the image quality in cardiac 18F-FDG PET using the time of flight (TOF) and/or point spread function (PSF) modeling in the iterative reconstruction (IR). METHODS: Three scanners and an anthropomorphic cardiac phantom with an insert simulating a transmural defect (TD) were used. Two sets of scans (with/without TD) were acquired, and four reconstruction schemes were considered: (1) IR; (2) IR + PSF, (3) IR + TOF, and (4) IR + TOF + PSF. LV wall thickness (FWHM), contrast between LV wall and inner chamber (C IC), and TD contrast in LV wall (C TD) were evaluated. RESULTS: Tests of the reconstruction protocols showed a decrease in FWHM from IR (13 mm) to IR + PSF (11 mm); an increase in the C IC from IR (65%) to IR + PSF (71%) and from IR + TOF (72%) to IR + TOF + PSF (77%); and an increase in the C TD from IR + PSF (72%) to IR + TOF (75%) and to IR + TOF + PSF (77%). Tests of the scanner/software combinations showed a decrease in FWHM from Gemini_TF (13 mm) to Biograph_mCT (12 mm) and to Discovery_690 (11 mm); an increase in the C IC from Gemini_TF (65%) to Biograph_mCT (73%) and to Discovery_690 (75%); and an increase in the C TD from Gemini_TF/Biograph_mCT (72%) to Discovery_690 (77%). CONCLUSION: The introduction of TOF and PSF increases image quality in cardiac 18F-FDG PET. The scanner/software combinations exhibit different performances, which should be taken into consideration when making cross comparisons.

Advances in image reconstruction software in nuclear cardiology: Is all that glitters gold?

The cornerstone results of nuclear cardiology in the last 25 years were obtained with the Filtered Back Projection as the preferred reconstruction method for tomographic studies. Recently, evolution of the OSEM iterative reconstruction algorithms was implemented by different vendors. The value and limitations of the new methods are briefly addressed.

Differences in polar-map patterns using the novel technologies for myocardial perfusion imaging.

BACKGROUND: New technologies are available in MPI. Our aim was to evaluate their impact on the uniformity of normal myocardial uptake in the polar-map representation, over different count statistics, with and without the attenuation (AC) and scatter corrections (SC). METHODS: A phantom study was performed using 5 Anger gamma cameras with filtered back projection or iterative reconstruction with resolution recovery (IRR), with or without SCAC; a D530c, with or without AC; and a D-SPECT. Count statistics ranged up to a quarter of the reference for the conventional gamma cameras and up to one half for the advanced scanners. Using polar maps, the segmental uptakes and their uncertainties, the 'global uniformity' of polar maps expressed as the coefficient of variation (COV) among the segmental uptakes and the anterior/inferior (ANT/INF) ratio were calculated. RESULTS: Both segmental uptakes and their uncertainties did not depend on the count statistics in the range studied. An increase in the segmental uptakes was found from IRR to IRR + SCAC (78.0% ± 13.5% vs 86.1% ± 9.4%; P < .0001). COV was lower for D-SPECT (10.1% ± 0.5%) and after SCAC for both conventional (9.9% ± 3.0%) and advanced systems (8.9% ± 1.7%). The ANT/INF ratio was above 1 for IRR (1.12 ± 0.07) and fell slightly below 1 for IRR + SCAC (0.97 ± 0.05). CONCLUSIONS: To compare data from the analysis of polar maps across different systems will require the adoption of specific normality databases, developed for each system and reconstruction method employed.

Low-dose modified-release prednisone in axial spondyloarthritis: 3-month efficacy and tolerability.

BACKGROUND: Oral glucocorticoids (GCs) have been shown to be effective in reducing the inflammatory symptoms of rheumatoid arthritis, but their use is not supported by evidence in spondyloarthritis (SpA). Modified-release (MR) oral prednisone taken at bedtime has been shown to be more effective than immediate-release prednisone taken in the morning. The efficacy of low-dose MR prednisolone in patients with SpA is unknown. PATIENTS AND METHODS: This single-center cohort study retrospectively assessed the effectiveness and safety of 12-week low-dose MR prednisone (5 mg daily, bedtime administration) in GC-naïve adult patients with symptomatic axial SpA. A 50% improvement of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) or a final BASDAI score of <4 according to disease activity at baseline was chosen as the primary outcome parameter after MR prednisone. RESULTS: Fifty-seven patients were evaluated; of them, 41 had an active disease (BASDAI score of ≥4) at baseline. MR prednisone significantly reduced BASDAI (from 5.5±2.6 to 3.0±2.8, P<0.001) as well as inflammatory symptoms, pain, fatigue and morning stiffness. The overall response rate after MR prednisone was 52.6% (53.7% in patients with active SpA and 50.0% in patients with low-active disease; nonsignificant). At multivariable analysis, none of the considered clinical findings independently predicted the response to MR prednisone in subjects with active SpA. Overall, seven patients (11.8%) had nonserious adverse drug reactions after MR prednisone. CONCLUSION: In patients with symptomatic SpA and naïve to GCs, low-dose MR prednisone reduced the symptoms and clinical indexes of disease activity and showed a positive safety profile.

Critical appraisal of appropriateness in nuclear cardiology.

Radionuclide myocardial perfusion imaging (MPI) is a large component of the healthcare spending both in developed and developing countries. MPI is also responsible for a significant increase in the exposition of patients and health care operators to ionizing radiations for medical purposes. Thus, health-care systems and pertinent scientific societies were involved in developing criteria to contain the non-appropriate use by implementing Appropriate Use Criteria and Clinical Indications Guidelines. The present manuscript will review the concept and limitations of such an approach.

Analgesic effectiveness and tolerability of oral oxycodone/naloxone and pregabalin in patients with lung cancer and neuropathic pain: an observational analysis.

INTRODUCTION: Cancer-related pain has a severe negative impact on quality of life. Combination analgesic therapy with oxycodone and pregabalin is effective for treating neuropathic cancer pain. We investigated the efficacy and tolerability of a dose-escalation combination therapy with prolonged-release oxycodone/naloxone (OXN-PR) and pregabalin in patients with non-small-cell lung cancer and severe neuropathic pain. METHODS: This was a 4-week, open-label, observational study. Patients were treated with OXN-PR and pregabalin. Average pain intensity ([API] measured on a 0-10 numerical rating scale) and neuropathic pain (Douleur Neuropathique 4) were assessed at study entry and at follow-up visits. The primary endpoint was response to treatment, defined as a reduction of API at T28 ≥30% from baseline. Secondary endpoints included other efficacy measures, as well as patient satisfaction and quality of life (Brief Pain Inventory Short Form), Hospital Anxiety and Depression Scale, and Symptom Distress Scale; bowel function was also assessed. RESULTS: A total of 56 patients were enrolled. API at baseline was 8.0±0.9, and decreased after 4 weeks by 48% (4.2±1.9; P<0.0001 vs baseline); 46 (82.1%) patients responded to treatment. Significant improvements were also reported in number/severity of breakthrough cancer pain episodes (P=0.001), Brief Pain Inventory Short Form (P=0.0002), Symptom Distress Scale (P<0.0001), Hospital Anxiety and Depression Scale depression (P=0.0006) and anxiety (P<0.0001) subscales, and bowel function (P=0.0003). At study end, 37 (66.0%) patients were satisfied/very satisfied with the new analgesic treatment. Combination therapy had a good safety profile. CONCLUSION: OXN-PR and pregabalin were safe and highly effective in a real-world setting of severe neuropathic cancer pain, with a high rate of satisfaction, without interference on bowel function.

Switching to low-dose oral prolonged-release oxycodone/naloxone from WHO-Step I drugs in elderly patients with chronic pain at high risk of early opioid discontinuation.

PURPOSE: Chronic pain has a high prevalence in the aging population. Strong opioids also should be considered in older people for the treatment of moderate to severe pain or for pain that impairs functioning and the quality of life. This study aimed to assess the efficacy and safety of the direct switch to low-dose strong opioids (World Health Organization-Step III drugs) in elderly, opioid-naive patients. PATIENTS AND METHODS: This was a single-center, retrospective, observational study in opioid-naive patients aged ≥75 years, with moderate to severe chronic pain (>6-month duration) and constipation, who initiated treatment with prolonged-release oxycodone/naloxone (OXN-PR). Patients were re-evaluated after 15, 30, and 60 days (T60, final observation). Response to treatment was defined as an improvement in pain of ≥30% after 30 days of therapy without worsening of constipation. RESULTS: One-hundred and eighty-six patients (mean ± SD age 80.7±4.7 years; 64.5% women) with severe chronic pain (mean average pain intensity 7.1±1.0 on the 11-point numerical rating scale) and constipation (mean Bowel Function Index 64.1±24.4; 89.2% of patients on laxatives) were initiated treatment with OXN-PR (mean daily dose 11.3±3.5 mg). OXN-PR reduced pain intensity rapidly and was well tolerated; 63.4% of patients responded to treatment with OXN-PR. At T60 (mean daily OXN-PR dose, 21.5±9.7 mg), the pain intensity was reduced by 66.7%. In addition, bowel function improved (mean decrease of Bowel Function Index from baseline to T60, -28.2, P<0.0001) and the use of laxatives decreased. Already after 15 days and throughout treatment, ~70% of patients perceived their status as much/extremely improved. Only 1.6% of patients discontinued treatment due to adverse events. CONCLUSION: Low-dose OXN-PR in elderly patients naive to opioids proved to be an effective option for the treatment of moderate to severe chronic pain. Large-scale trials are needed to improve clinical guidance in the assessment and treatment of pain in older people.

Five-year hospitalisations and survival in patients admitted to inpatient cardiac rehabilitation after cardiac surgery.

BACKGROUND: The effect of an early comprehensive rehabilitation programme on the evolution of disability after cardiac surgery and the long-term effect of the residual functional status has not yet been investigated. AIM: To analyse the recovery from disability after cardiac surgery and to assess the impact of residual disability on long-term outcomes. METHODS: Data prospectively recorded from 5261 patients, consecutively admitted to an inpatient rehabilitation programme after cardiac surgery, were retrospectively analysed. Disability was assessed twice, on admission (to evaluate the post-surgery disability) and at discharge (to evaluate the recovery after rehabilitation). Study cohort survival at 5-year follow-up was also compared with that of a reference population matched for age and sex. RESULTS: On admission, severe, moderate, mild or no disability was documented in 18.2%, 29.4%, 39.8% and 12.5% of patients, respectively. After rehabilitation, 75.1% of patients with severe disability improved their functional status, with an associated 50% reduction in mortality at 5-year follow-up. The Barthel index was the major predictor of survival and hospitalisations at follow-up. Comparison of the observed versus expected survival showed a worse outcome in patients with persistent moderate to severe residual disability. CONCLUSIONS: The reduction in all-cause mortality at follow-up documented in those patients with severe disability post-surgery who improved after rehabilitation underscores the effectiveness of a comprehensive inpatient cardiac rehabilitation programme and should encourage a more widespread use of rehabilitation early after an acute cardiac event.