Matteo Casenghi

Polypharmacy in heart failure patients.

In heart failure (HF), the progressive use of multiple drugs and a complex therapeutic regimen is common and is recommended by international guidelines. With HF being a common disease in the elderly, patients often have numerous comorbidities that require additional specific treatment, thus producing a heavy pill burden. Polypharmacy, defined as the chronic use of five or more medications, is an underestimated problem in the management of HF patients. However, polypharmacy has an important impact on HF treatment, as it often leads to inappropriate drug prescription, poor adherence to pharmacological therapies, drug-drug interactions, and adverse effects. The growing complexity of HF patients, whose mean age increases progressively and who present multiple comorbidities, suggests the need for newer models of primary care to improve the management of HF patients. Self-care, telemonitoring, and natriuretic peptide-guided therapy represent promising new HF care models to face the complexity of the disease and its therapeutic regimen.

Deceptive meaning of oxygen uptake measured at the anaerobic threshold in patients with systolic heart failure and atrial fibrillation

Background Oxygen uptake at the anaerobic threshold (VO2AT), a submaximal exercise-derived variable, independent of patients’ motivation, is a marker of outcome in heart failure (HF). However, previous evidence of VO2AT values paradoxically higher in HF patients with permanent atrial fibrillation (AF) than in those with sinus rhythm (SR) raised uncertainties. Design We tested the prognostic role of VO2AT in a large cohort of systolic HF patients, focusing on possible differences between SR and AF. Methods Altogether 2976 HF patients (2578 with SR and 398 with AF) were prospectively followed. Besides a clinical examination, each patient underwent a maximal cardiopulmonary exercise test (CPET). Results The follow-up was analysed for up to 1500 days. Cardiovascular death or urgent cardiac transplantation occurred in 303 patients (250 (9.6%) patients with SR and 53 (13.3%) patients with AF, p = 0.023). In the entire population, multivariate analysis including peak oxygen uptake (VO2) showed a prognostic capacity (C-index) similar to that obtained including VO2AT (0.76 vs 0.72). Also, left ventricular ejection fraction, ventilation vs carbon dioxide production slope, β-blocker and digoxin therapy proved to be significant prognostic indexes. The receiver-operating characteristic (ROC) curves analysis showed that the best predictive VO2AT cut-off for the SR group was 11.7 ml/kg/min, while it was 12.8 ml/kg/min for the AF group. Conclusions VO2AT, a submaximal CPET-derived parameter, is reliable for long-term cardiovascular mortality prognostication in stable systolic HF. However, different VO2AT cut-off values between SR and AF HF patients should be adopted.

Cardiopulmonary exercise test and sudden cardiac death risk in hypertrophic cardiomyopathy

Background In hypertrophic cardiomyopathy (HCM), most of the factors associated with the risk of sudden cardiac death (SCD) are also involved in the pathophysiology of exercise limitation. The present multicentre study investigated possible ability of cardiopulmonary exercise test in improving contemporary strategies for SCD risk stratification. Methods A total of 623 consecutive outpatients with HCM, from five tertiary Italian HCM centres, were recruited and prospectively followed, between September 2007 and April 2015. The study composite end point was SCD, aborted SCD and appropriate implantable cardioverter defibrillator (ICD) interventions. Results During a median follow-up of 3.7 years (25th–75th centile: 2.2–5.1 years), 25 patients reached the end point at 5 years (3 SCD, 4 aborted SCD, 18 appropriate ICD interventions). At multivariate analysis, ventilation versus carbon dioxide relation during exercise (VE/VCO2 slope) remains independently associated to the study end point either when challenged with the 2011 American College of Cardiology Foundation/American Heart Association guidelines-derived score (C index 0.748) or with the 2014 European Society of Cardiology guidelines-derived score (C index 0.750). A VE/VCO2 slope cut-off value of 31 showed the best accuracy in predicting the SCD end point within the entire HCM study cohort (sensitivity 64%, specificity 72%, area under the curve 0.72). Conclusions Our data suggest that the VE/VCO2 slope might improve SCD risk stratification, particularly in those HCM categories classified at low-intermediate SCD risk according to contemporary guidelines. There is a need for further larger studies, possibly on independent cohorts, to confirm our preliminary findings.

Renal Function and Peak Exercise Oxygen Consumption in Chronic Heart Failure With Reduced Left Ventricular Ejection Fraction

BACKGROUND Chronic kidney disease is associated with sympathetic activation and muscle abnormalities, which may contribute to decreased exercise capacity. We investigated the correlation of renal function with peak exercise oxygen consumption (V̇O2) in heart failure (HF) patients. METHODS AND RESULTS: We recruited 2,938 systolic HF patients who underwent clinical, laboratory, echocardiographic and cardiopulmonary exercise testing. The patients were stratified according to estimated glomerular filtration rate (eGFR). Mean follow-up was 3.7 years. The primary outcome was a composite of cardiovascular death and urgent heart transplantation at 3 years. On multivariable regression, eGFR was predictor of peakV̇O2(P<0.0001). Other predictors were age, sex, body mass index, HF etiology, NYHA class, atrial fibrillation, resting heart rate, B-type natriuretic peptide, hemoglobin, and treatment. After adjusting for significant covariates, the hazard ratio for primary outcome associated with peakV̇O2<12 ml·kg(-1)·min(-1)was 1.75 (95% confidence interval (CI): 1.06-2.91; P=0.0292) in patients with eGFR ≥60, 1.77 (0.87-3.61; P=0.1141) in those with eGFR of 45-59, and 2.72 (1.01-7.37; P=0.0489) in those with eGFR <45 ml·min(-1)·1.73 m(-2). The area under the receiver-operating characteristic curve for peakV̇O2<12 ml·kg(-1)·min(-1)was 0.63 (95% CI: 0.54-0.71), 0.67 (0.56-0.78), and 0.57 (0.47-0.69), respectively. Testing for interaction was not significant. CONCLUSIONS Renal dysfunction is correlated with peakV̇O2. A peakV̇O2cutoff of 12 ml·kg(-1)·min(-1)offers limited prognostic information in HF patients with more severely impaired renal function.

Heart Failure Progression in Hypertrophic Cardiomyopathy – Possible Insights From Cardiopulmonary Exercise Testing –

BACKGROUND Heart failure (HF) progression and its complications represent major emergent concerns in hypertrophic cardiomyopathy (HCM). We investigated the possible adjunctive role of cardiopulmonary exercise testing (CPET) in predicting HF-related events. An exercise-derived risk model, theHYPertrophicExercise-derivedRiskHF(HYPERHF), has been developed. METHODSANDRESULTS A multicenter cohort of 620 consecutive HCM outpatients was recruited and followed (2007 to 2015). The endpoint was death from HF, cardiac transplantation, NYHA III-IV class progression, severe functional deterioration leading to hospitalization for septal reduction, and hospitalization for HF worsening. During a median follow-up of 3.8 years (25-75th centile: 2.3-5.3 years), 84 patients reached the endpoint. Peak circulatory power (peak oxygen consumption * peak systolic blood pressure), ventilatory efficiency and left atrial diameter were independently associated with the endpoint and, accordingly, integrated into the HYPERHFmodel (C index: 0.849; best cutoff value equal to 15%). CONCLUSIONS CPET is useful in the evaluation of HCM patients. In this context, the HYPERHFscore might allow early identification of those patients at high risk of HF progression and its complications. (Circ J 2016; 80: 2204-2211).

Spatial QT Dispersion Predicts Nonsustained Ventricular Tachycardia and Correlates with Confined Systodiastolic Dysfunction in Hypertrophic Cardiomyopathy.

Objectives: An increased dispersion of myocardial repolarization represents one of the mechanisms underlying the arrhythmic risk in hypertrophic cardiomyopathy (HCM). We investigated spatial myocardial repolarization dispersion indices in HCM patients with nonsustained ventricular tachycardia (NSVT) and, contextually, their main clinical determinants. Methods: Fifty-two well-matched HCM outpatients were categorized into two groups according to the presence or the absence of NSVT at 24-hour Holter electrocardiogram (ECG) monitoring. Each patient underwent a clinical examination, including Doppler echocardiogram integrated with tissue Doppler imaging, cardiac magnetic resonance, and 12-lead surface ECG to calculate the dispersion for the following intervals: QRS, Q-Tend (QTe), Q-Tpeak, Tpeak-Tend (TpTe), J-Tpeak, and J-Tend. Results: The NSVT group showed only QTe dispersion and TpTe dispersion values to be significantly higher than their counterparts. NSVT occurrence was independently predicted by late gadolinium enhancement presence (p = 0.021) and QTe Bazett dispersion (p = 0.030), the latter strongly associated with the myocardial performance index (MPI) obtained at the basal segment of the interventricular septum (p = 0.0004). Conclusion: Our data support QTe dispersion as an easy and noninvasive tool for identifying HCM patients with NSVT propensity. The strong relationship between QTe dispersion and MPI allows us to hypothesize an intriguing link between electrical instability and confined myocardial areas of systodiastolic dysfunction.

Intra-QT spectral coherence as a possible noninvasive marker of sustained ventricular tachycardia

Sudden cardiac death is the main cause of mortality in patients affected by chronic heart failure (CHF) and with history of myocardial infarction. No study yet investigated the intra-QT phase spectral coherence as a possible tool in stratifying the arrhythmic susceptibility in patients at risk of sudden cardiac death (SCD). We, therefore, assessed possible difference in spectral coherence between the ECG segment extending from the q wave to the T wave peak (QTp) and the one from T wave peak to the T wave end (T e) between patients with and without Holter ECG-documented sustained ventricular tachycardia (VT). None of the QT variability indexes as well as most of the coherences and RR power spectral variables significantly differed between the two groups except for the QTp-T e spectral coherence. The latter was significantly lower in patients with sustained VT than in those without (0.508 ± 0.150 versus 0.607 ± 0.150, P < 0.05). Although the responsible mechanism remains conjectural, the QTp-T e spectral coherence holds promise as a noninvasive marker predicting malignant ventricular arrhythmias.

Clinical and prognostic impact of chronotropic incompetence in patients with hypertrophic cardiomyopathy

BACKGROUND A blunted heart rate (HR) response is associated with an impaired peak oxygen uptake (pVO2), a powerful outcome predictor in hypertrophic cardiomyopathy (HCM). The present multicenter study sought to determine the prognostic role for exercise-induced HR response in HCM. METHODS A total of 681 consecutive HCM outpatients on optimized treatment were recruited. The heart failure (HF) end-point was death due to HF, cardiac transplantation, NYHA III-IV class progression, HF worsening leading to hospitalization and severe functional deterioration leading to septal reduction. The sudden cardiac death (SCD) end-point included SCD, aborted SCD and appropriate implantable cardioverter defibrillator discharges. RESULTS During a median follow-up of 4.2 years (25-75th centile: 3.9-5.2), 81 patients reached the HF and 23 the SCD end-point. Covariates with independent effects on the HF end-point were left atrial diameter, left ventricular ejection fraction, maximal left ventricular outflow tract gradient and exercise cardiac power (ECP = pVO2∗systolic blood pressure) (C-Index = 0.807) whereas the HCM Risk-SCD score and the ECP remained associated with the SCD end-point (C-Index = 0.674). When the VO2-derived variables were not pursued, peak HR (pHR) re-entered in the multivariate HF model (C-Index = 0.777) and, marginally, in the SCD model (C-index = 0.656). A pHR = 70% of the maximum predicted resulted as the best cut-off value in predicting the HF-related events. CONCLUSIONS The cardiopulmonary exercise test is pivotal in the HCM management, however the pHR remains a meaningful alternative parameter. A pHR < 70% identified a HCM population at high risk of HF-related events, thus calling for a reappraisal of the chronotropic incompetence threshold in HCM.

Pulmonary hypertension and clinical correlates in hypertrophic cardiomyopathy

BACKGROUND Pulmonary hypertension (PH) in patients with hypertrophic cardiomyopathy (HCM) has been investigated in a small number of studies. Purpose of this study was to assess the prevalence and its association with outcome in a population of consecutive HCM outpatients. METHODS We retrospectively analyzed data of 361 consecutive HCM outpatients in whom echocardiographic measurements of pulmonary artery systolic pressure (PASP) were available at initial and most recent evaluation. Four different clinical groups were specifically investigated: patients without left ventricular outflow tract obstruction (group A, 165), with obstruction (group B, 126), patients diagnosed at the age≥65 (group C, 50) and patients with end stage (ES) HCM (group D, 20). RESULTS PH was identified in 41 (11.4%) of the 361 patients at initial evaluation while it has been recognized in 25 (7,8% [1.1%/year]) during a median follow-up of 3.4years. Analysis of subgroups showed that prevalence of PH increased from patient group A to D (8%, group A, 19%, group B, 28% group C, 70%, group D, respectively, p<0,01). During follow-up, patients with PH showed a significant higher HCM-related mortality (p=0.01) and morbidity (p<0.001) as compared with those without PH, but in multivariable analysis, PH resulted an independent risk factor only for HCM-related morbidity (HR=2.50, 95% CI 1.08-5.79, p=0.03). CONCLUSION PH affects a significant proportion of patients with HCM. Its prevalence varies according to different clinical profiles. It is associated with an unfavorable clinical outcome and is an independent predictor of morbidity.

Long-Term Left Ventricular Remodeling of Patients With Hypertrophic Cardiomyopathy

In hypertrophic cardiomyopathy (HC), a process of left ventricular (LV) remodeling carrying an adverse prognosis has been described. Conversely, a gradual and benign LV wall thinning has been suggested but never investigated. Therefore, we studied a HC cohort over a long period of time to evaluate the occurrence of a LV remodeling with a benign clinical course. Data of HC patients aged 18 to 65 years and without any condition known to influence LV remodeling were analyzed over a mean follow-up of 7.6 ± 5.7 years. Of 231 HC patients (65% males, mean age 46 ± 12 years), 47 (20%) developed LV remodeling, of whom 23 (10%) had a thinning ≥15% of LV maximal wall thickness from baseline without systolic dysfunction (MWT thinning); 13 (6%) progressed to a LV ejection fraction <50% (end-stage HC) and 11 (5%) developed an apical aneurysm. Follow-up length (odds ratio 1.07, 95% confidence interval 1.00 to 1.15, p = 0.06) and maximal LV wall thickness at baseline (odds ratio 1.14, 95% confidence interval 1.04 to 1.25, p = 0.004) were the main predictors of MWT thinning. Compared with patients with end-stage HC and apical aneurysm, those with MWT thinning showed lower HC-related morbidity (92% and 36% vs 22%, p = 0.003) and mortality (31% and 27% vs 4%, p = 0.02). Furthermore, they showed a combined HC-related morbidity and mortality similar to patients without LV remodeling (incidence 29/1000 vs 26/1000 patient-year, p = 0.77). In conclusion, a process of LV wall thinning with a benign outcome can occur over the long term in patients with HC. The prognostic importance of LV remodeling varies in relation to the different changes in LV morphology and function.