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.

The Future of Exercise-Based Cardiac Rehabilitation for Patients With Heart Failure.

Cardiac rehabilitation (CR) is a comprehensive program that includes exercise training, titration of medical therapy, lifestyle modification, educational support, and psychosocial assessment. All these components are safe and beneficial resulting in significant improvements in quality of life, functional capacity, mortality, and hospital readmission. Current guidelines support its use in a broad spectrum of cardiac disease. This review focuses on exercise-based CR for heart failure (HF) patients in whom CR is a recommended treatment. Exercise should be prescribed according to a personalized approach, optimizing, and tailoring the rehabilitative program to the patient's characteristics. Specific CR programs are dedicated to older patients, those with HF and preserved ejection fraction, and recipients of cardiac implantable electronic devices or left ventricular assistance device. Telemedicine may increase CR participation and overcome some of the barriers that limit its utilization.

Exertional and nocturnal periodic breathing after successful cardiac transplantation. A case report.

We present a case report of a heart failure patient who underwent cardiopulmonary exercise testing and sleep screening 12 months before and after heart transplantation (HTx). Severe Cheyne-Stokes respiration (CSR) with central sleep apnoea (CSA) was identified either before and after HTx, while periodic breathing during exercise vanished. We suggest that optimization of hemodynamics and medical therapy (low dose of diuretic) did not withdraw the central mechanisms underlying the diathesis for CSR-CSA. While periodic breathing during exercise reversal may support a closer link with an exertional central hemodynamic. This observation indirectly neglects the possible unifying mechanistic background of CSR and periodic breathing, during exercise, in this setting.

Aortic root 3D parametric morphological model from 2D-echo images.

The gold standard for the study of the macro-anatomy of the aortic root are multi-detector computed tomography (MDCT) and magnetic resonance (MR) imaging. Both technologies have major advantages and limitations. Although 4D echo is entering the study of the aortic root, 2D echo is the most commonly used diagnostic tool in daily practice. We designed and developed an algorithm for 3D modeling of the aortic root based on measures taken routinely at 2D echocardiography from 20 healthy individuals with normal aortic root. The tool was then translated in 12 patients who underwent both echo and MDCT. The results obtained with the 3D modeling program were quantitatively and qualitatively compared with 3D reconstruction from MDCT. Ad hoc ratios describing the morphology of the aortic root in MDCT and in the 3D model were used for comparison. In 12 patients with aortic root dilatation, the ratios obtained with our model are in good agreement with those from MDCT. Linear correlation for both long axis and short axis ratios was strong. The 3D modeling software can be easily adopted by cardiologists routinely involved in clinical evaluation of the pathology of the aortic root. The tool is easy to apply, does not require additional costs, and may be used to generate a set of data images for monitoring the evolution of the morphology and dimension of the aortic root, flanking the 3D MDCT and MR that remain the gold standard tools.

Quantitative expression of the mutated lamin A/C gene in patients with cardiolaminopathy.

OBJECTIVES: The authors sought to investigate the gene and protein expression in Lamin A/C (LMNA)-mutated dilated cardiolaminopathy (DCM) patients (DCM(LMNAMut)) versus LMNA-wild-type DCM (DCM(LMNAWT)), and normal controls (CTRL(LMNAWT)). BACKGROUND: Dilated cardiolaminopathies are clinically characterized by high arrhythmogenic risk and caused by LMNA mutations. Little is known regarding quantitative gene expression (QGE) of the LMNA gene in blood and myocardium, as well as regarding myocardial expression of the lamin A/C protein. METHODS: Using the comparative ΔΔCT method, we evaluated the QGE of LMNA (QGE(LMNA)) in peripheral blood and myocardial RNA from carriers of LMNA mutations, versus blood and myocardial samples from DCM(LMNAWT) patients and CTRL(LMNAWT) individuals. After generating reference values in normal controls, QGE(LMNA) was performed in 311 consecutive patients and relatives, blind to genotype, to assess the predictive value of QGE(LMNA) for the identification of mutation carriers. In parallel, Lamin A/C was investigated in myocardial samples from DCM(LMNAMut) versus DCM(LMNAWT) versus normal hearts (CTRL(LMNAWT)). RESULTS: LMNA was significantly underexpressed in mRNA from peripheral blood and myocardium of DCM(LMNAMut) patients versus DCM(LMNAWT) and CTRL(LMNAWT). In 311 individuals, blind to genotype, the QGE(LMNA) showed 100% sensitivity and 87% specificity as a predictor of LMNA mutations. The receiver-operating characteristic curve analysis yielded an area under the curve of 0.957 (p < 0.001). Loss of protein in cardiomyocytes' nuclei was documented in DCM(LMNAMut) patients. CONCLUSIONS: The reduced expression of LMNA gene in blood is a novel potential predictive biomarker for dilated cardiolaminopathies with parallel loss of protein expression in cardiomyocyte nuclei.

Diagnostic work-up and risk stratification in X-linked dilated cardiomyopathies caused by dystrophin defects.

OBJECTIVES: We sought to describe the diagnostic work-up, phenotype, and long-term evolution of dilated cardiomyopathy (DCM) associated with Dystrophin (DYS) defects. BACKGROUND: X-linked DCM associated with DYS defects can be clinically indistinguishable from other types of DCM. METHODS: The series comprises 436 consecutive male patients diagnosed with DCM. Patients underwent endomyocardial biopsy (EMB). Genetic testing employed multiplex polymerase chain reaction and multiple ligation dependent probe assay for deletions and direct sequencing of the 79 exons and flanking regions of the gene for point mutations or small rearrangements. RESULTS: We identified DYS defects in 34 of 436 patients (7.8%) (onset age 34 ± 11 years, age range 17 to 54 years); 30 had proven X-linked inheritance. The 2 phenotypes included DCM with mild skeletal myopathy and/or increased serum creatine phosphokinase (n = 28) or DCM only (n = 6). The EMB showed defective dystrophin immunostain. The DYS defects consisted of 21 in-frame deletions and 11 out-of-frame deletions as well as 1 stop and 1 splice-site mutation. During a median follow-up of 60 months (interquartile range: 11.25 to 101.34 months) we observed 17 events, all related to heart failure (HF) (median event-free survival: 83.5 months). Eight patients (23%) underwent transplantation, and 9 (26%) died of HF while waiting for transplantation. Eight patients received an implantable cardioverter-defibrillator, although none had device intervention during a median follow-up of 14 months (interquartile range: 5 to 25 months). No patient died suddenly, suffered syncope, or developed life-threatening ventricular arrhythmias. CONCLUSIONS: DYS-related DCM should be suspected in male patients with increased serum creatine phosphokinase (82%) and X-linked inheritance. The disease shows a high risk of end-stage HF but a lower risk of life-threatening arrhythmias.