Atrial Fibrillation in Patients with Hypertrophic Cardiomyopathy and Cardiac Amyloidosis: From Clinical Management to Catheter Ablation Indication.

Atrial fibrillation (AF) is the most common arrhythmia in patients affected by cardiomyopathies. Reports estimate a prevalence of 27% in patients with hypertrophic cardiomyopathy (HCM) and 40% in patients with cardiac amyloidosis (CA). The presence of AF typically results in progressive functional decline, an increased frequency of hospitalizations for heart failure, and a higher thromboembolic risk. Medical management using mainly beta-blockers or amiodarone has produced variable outcomes and a high rate of recurrence. Catheter ablation reduces symptom burden and complications despite a moderate rate of recurrence. Recent evidence suggests that an early rhythm control strategy may lead to more favorable short- and long-term outcomes. In this review, we summarize contemporary data on the management of AF in patients with cardiomyopathy (HCM and CA) with particular reference to the timing and outcomes of ablation procedures.

Effects of sacubitril/valsartan on exercise capacity: a prognostic improvement that starts during uptitration.

PURPOSE: Sacubitril/valsartan is a mainstay of the treatment of heart failure with reduced ejection fraction (HFrEF); however, its effects on exercise performance yielded conflicting results. Aim of our study was to evaluate the impact of sacubitril/valsartan on exercise parameters and echocardiographic and biomarker changes at different drug doses. METHODS: We prospectively enrolled consecutive HFrEF outpatients eligible to start sacubitril/valsartan. Patients underwent clinical assessment, cardiopulmonary exercise test (CPET), blood sampling, echocardiography, and completed the Kansas City Cardiomyopathy Questionnaire (KCCQ-12). Sacubitril/valsartan was introduced at 24/26 mg b.i.d. dose and progressively uptitrated in a standard monthly-based fashion to 97/103 mg b.i.d. or maximum tolerated dose. Study procedures were repeated at each titration visit and 6 months after reaching the maximum tolerated dose. RESULTS: Ninety-six patients completed the study, 73 (75%) reached maximum sacubitril/valsartan dose. We observed a significant improvement in functional capacity across all study steps: oxygen intake increased, at peak exercise (from 15.6 ± 4.5 to 16.5 ± 4.9 mL/min/kg; p trend = 0.001), while minute ventilation/carbon dioxide production relationship reduced in patients with an abnormal value at baseline. Sacubitril/valsartan induced positive left ventricle reverse remodeling (EF from 31 ± 5 to 37 ± 8%; p trend < 0.001), while NT-proBNP reduced from 1179 [610-2757] to 780 [372-1344] pg/ml (p trend < 0.0001). NYHA functional class and the subjective perception of limitation in daily life at KCCQ-12 significantly improved. The Metabolic Exercise Cardiac Kidney Index (MECKI) score progressively improved from 4.35 [2.42-7.71] to 2.35% [1.24-4.96], p = 0.003. CONCLUSIONS: A holistic and progressive HF improvement was observed with sacubitril/valsartan in parallel with quality of life. Likewise, a prognostic enhancement was observed.

Revisiting a Prognosticating Algorithm from Cardiopulmonary Exercise Testing in Chronic Heart Failure (from the MECKI Score Population).

Cardiopulmonary exercise testing is a prognostic tool in heart failure with reduced left ventricular ejection fraction (HFrEF). Prognosticating algorithms have been proposed, but none has been validated. In 2017, a predictive algorithm, based on peak oxygen consumption (VO2), ventilatory response to exercise (ventilation [VE] carbon dioxide production [VCO2], the VE/VCO2 slope), exertional oscillatory ventilation (EOV), and peak respiratory exchange ratio, was recommended, according treatment with ß blockers: patients with HFrEF registered in the metabolic exercise test data combined with cardiac and kidney indexes (MECKIs) database were used to validated this algorithm. According to the inclusion/exclusion criteria, 4,683 MECKI patients with HFrEF were enrolled. At 3 years follow-up, the end point was cardiovascular death and urgent heart transplantation (cardiovascular events [CV]). CV events occurred in 25% in patients without ß blockers, whereas those with ß-blockers had 11% (p <0.0001). In patients without ß blockers, 36%, 24%, and 7% CV events were observed in those with peak VO2 ≤10, with peak VO2 >10 <18, and with peak VO2 ≥18 ml/kg/min (p = 0.0001), respectively; in MECKI patients with peak VO2 ≤10 and patients with intermediate exercise capacity, a peak respiratory exchange ratio (≥1.15) and VE/VCO2 slope (≥35) were diriment, respectively (p = 0.0001). EOV, when occurred, increased risk. In MECKI patients on ß blockers, 29%, 17%, and 8% CV events were noticed in those with a peak VO2 ≤8, with peak VO2 = 8 to 12, and patients with peak VO2 ≥12 ml/kg/min, respectively (p = 0.0000); when EOV was monitored an increment of risk was witnessed. In conclusion, the outcome of this algorithm was confirmed with the MECKI cohort.

Pick Your Threshold: A Comparison Among Different Methods of Anaerobic Threshold Evaluation in Heart Failure Prognostic Assessment.

BACKGROUND: In clinical practice, anaerobic threshold (AT) is used to guide training and rehabilitation programs, to define risk of major thoracic or abdominal surgery, and to assess prognosis in heart failure (HF). AT of oxygen uptake (V.O2; V.O2AT) has been reported as an absolute value (V.O2ATabs), as a percentage of predicted peak V.O2 (V.O2AT%peak_pred), or as a percentage of observed peak V.O2 (V.O2AT%peak_obs). A direct comparison of the prognostic power among these different ways to report AT is missing. RESEARCH QUESTION: What is the prognostic power of these different ways to report AT? STUDY DESIGN AND METHODS: In this observational cohort study, we screened data of 7,746 patients with HF with a history of reduced ejection fraction (< 40%) recruited between 1998 and 2020 and enrolled in the Metabolic Exercise Combined With Cardiac and Kidney Indexes register. All patients underwent a maximum cardiopulmonary exercise test, executed using a ramp protocol on an electronically braked cycle ergometer. RESULTS: This study considered 6,157 patients with HF with identified AT. Follow-up was median, 4.2 years (25th-75th percentiles, 1.9-5.0 years). Both V.O2ATabs (mean ± SD, 823 ± 305 mL/min) and V.O2AT%peak_pred (mean ± SD, 39.6 ± 13.9%), but not V.O2AT%peak_obs (mean ± SD, 69.2 ± 17.7%), well stratified the population regarding prognosis (composite end point: cardiovascular death, urgent heart transplant, or left ventricular assist device). Comparing area under the receiver operating characteristic curve (AUC) values, V.O2ATabs (0.680) and V.O2AT%peak_pred (0.688) performed similarly, whereas V.O2AT%peak_obs (0.538) was significantly weaker (P < .001). Moreover, the V.O2AT%peak_pred AUC value was the only one performing as well as the AUC based on peak V.O2 (0.710), with an even a higher AUC (0.637 vs 0.618, respectively) in the group with severe HF (peak V.O2 < 12 mL/min/kg). Finally, the combination of V.O2AT%peak_pred with peak V.O2 and V. per CO2 production shows the highest prognostic power. INTERPRETATION: In HF, V.O2AT%peak_pred is the best way to report V.O2 at AT in relationship to prognosis, with a prognostic power comparable to that of peak V.O2 and, remarkably, in patients with severe HF.

Comorbidities in chronic heart failure: An update from Italian Society of Cardiology (SIC) Working Group on Heart Failure.

The increasing number of patients with heart failure HF and comorbidities is due to aging population and increase of life expectancy of patients with cardiovascular disease. Encouraging results derived by recent trials may suggest some comorbidities as new targets for new drugs, highlighting the need for a better understanding of the comorbidities' effects in HF patients and the need of a multidisciplinary approach for the management of chronic HF with comorbidities. We report a brief review about main cardiovascular and non-cardiovascular comorbidities in HF patients in order to update physicians and researchers engaged in the HF research or in "fight against heart failure."

Anemia and Iron Deficiency in Heart Failure: Clinical and Prognostic Role.

Anemia and iron deficiency (ID) represent 2 prevalent, often interrelated, comorbidities in heart failure (HF). Both of them are significantly related to functional capacity and are undoubted predictors of poor prognosis in patients with HF. Although anemia and ID both have "global" detrimental effects, these 2 conditions are too often overlooked in cardiology daily clinical practice. The present review sought to summarize briefly the prevalence and the underlying pathophysiologic mechanisms of anemia and ID as regards HF severity (ie, exercise capacity) and prognosis.

Time- and frequency-domain analysis of beat to beat P-wave duration, PR interval and RR interval can predict asystole as form of syncope during head-up tilt.

To seek possible differences in short-period temporal RR interval, P-wave and PR interval dispersion and spectral coherence in patients with a head-up tilt test positive for vasovagal syncope with or without prolonged asystole, severe symptoms and at high risk of trauma. We retrospectively reviewed 5 min ECG and blood pressure recordings obtained at baseline, at rest and during head-up tilt in 40 patients diagnosed as having recurrent vasovagal syncope confirmed at a head-up tilt test. We analysed autoregressive spectral power for all the ECG-derived variables, focusing on temporal P-wave and PR interval dispersion indexes as well as their spectral coherence calculated on the same 5 min recordings at rest and during tilt. ECG recordings obtained during tilt before syncope showed significantly lower P → PR spectral coherence and higher RR standard deviations in patients with tilt-induced asystole than in those without (0.567 ± 0.097 versus 0.670 ± 0.127, p: 0.010 and 84 ± 36 versus 46 ± 22 ms2, p < 0.0001). Differences in the RR standard deviations persisted also on the last hundred beats (-100) (113 ± 54 versus 34 ± 17 ms2, p < 0.0001). Multiple regression analysis identified a significantly negative association between the maximum RR intervals and P → PR coherence at rest (ß: -0.3, p < 0.05) and positive association with RR-100 standard deviation during tilt-induced syncope (ß: 0.621, p < 0.001). P → PR spectral coherence could be used to assess the risk of prolonged asystole in patients with tilt-induced vasovagal syncope as well as as a possible surrogate for tilt-testing during these patients' follow-up.

ACE-Inhibition Benefit on Lung Function in Heart Failure is Modulated by ACE Insertion/Deletion Polymorphism.

PURPOSE: The benefit of angiotensin converting enzyme (ACE) inhibition in chronic heart failure (HF) is partially due to its effects on pulmonary function and particularly on lung diffusion, the latter being counteracted by acetylsalicylic acid (ASA). Tissue ACE activity is largely determined by an insertion/deletion (I/D) polymorphism resulting in three possible genotypes (DD, ID and II). It is not clear if ACE inhibitor therapy could exert different effects in these genotypes. The aim of the study was to understand whether I/D polymorphism interferes with ACE inhibitor's protection of the lungs in HF during acute fluid overload. METHODS: 100 HF patients (left ventricular ejection fraction ≤40 %) in stable clinical conditions, treated with enalapril but without ASA performed pulmonary function tests including lung diffusion (DLco) and its subcomponents, membrane diffusion (Dm) and capillary volume (Vcap), and a cardiopulmonary exercise test before and immediately after rapid infusion of 500 cc saline. RESULTS: ACE I/D genotype prevalence was: DD = 28, ID =55 and II = 17 cases. No significant differences in major pulmonary function and exercise parameters were observed before saline infusion among ACE genotypes. After fluid challenge, DD patients presented a higher DLco and Dm reduction than ID and II (DLco -2.3 ± 1.3 vs. -0.8 ± 1.9 and -0.6 ± 1 mL/mmHg/min, p < 0.0001 and p < 0.01; Dm -7 ± 5 vs. -3.2 ± 7.4 and -1.3 ± 5 mL/mmHg/min, p < 0.05, respectively) and a higher increase in VE/VCO2 slope than II (1.8 ± 1.9 vs. -0.8 ± 2.3, p = 0.01). CONCLUSIONS: ACE DD genotype is associated with higher vulnerability of the alveolar-capillary membrane to acute fluid overload in HF patients treated with ACE inhibitors.

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 (Te) 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-Te 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-Te spectral coherence holds promise as a noninvasive marker predicting malignant ventricular arrhythmias.

Determinants of peak oxygen uptake in patients with hypertrophic cardiomyopathy: a single-center study.

Most patients with hypertrophic cardiomyopathy (HCM) usually complain of a reduced exercise capacity, and several factors have been advocated as possible causes of this clinical feature. The present single-center study was designed to investigate exercise capacity and its main clinical determinants in HCM patients. One hundred ninety seven patients of 223 evaluated underwent a complete clinical assessment, including Doppler echocardiography, cardiopulmonary exercise test (CPET) and, in most cases, cardiac magnetic resonance. The HCM population (male 75 %; age 47 ± 16 years; NYHA class I or II 95 %; left ventricular ejection fraction 61 ± 3 %; resting left ventricular outflow tract gradient ≥30 mmHg 22 %; late gadolinium enhancement presence 58 %) showed slightly reduced mean peak oxygen uptake values (pVO2 75 ± 15 %, 23.2 ± 6.7 ml/kg/min) with a significant reduction of the achieved percentage of peak heart rate reserve (%pHRR 65 ± 20 %). Adopting a pVO2 <80 % cut-off value, 59 % of HCM patients showed a reduced exercise capacity. Age, male gender, left atrial size, chronotropic and systolic blood pressure response, ventilatory efficiency, late gadolinium enhancement presence and ß-blocker therapy were independently associated with pVO2 (R (2)-adjusted index 0.738). A %pHRR cut-off value of 74 % appeared to most accurately predict an impaired exercise capacity (area under curve 0.90). A great prevalence of reduced exercise capacity is present in NYHA class I-II HCM patients. Notwithstanding its multifactorial genesis, few parameters might be adopted in identifying this feature. In this context, %pHRR value might represent a reliable and easy-to-obtain tool for the clinical evaluation of HCM patients.

Rationale for cardiopulmonary exercise test in the assessment of surgical risk.

Although in the past years a reduced mortality in peri-operative care has been observed, cardiovascular mortality and morbidity still is a major burden in patients undergoing noncardiac surgery and its evaluation is still a difficult task. An accurate risk stratification can improve quality of peri-operative care and may improve survival, while reducing healthcare costs. In clinical practice, we make our assessment of a patient's cardiac status based on history, examination and investigations, together with risks related to the surgical procedure, to generate an 'individualized cardiac risk assessment'. At the present, risk stratification with clinical risk score and cardiac testing have been shown to be suboptimal in identifying high-risk patients. Surgery, like exercise, increases oxygen consumption. Indeed, one of the key elements in determining risk assessment is exercise intolerance, but future research in this field is needed to clarify this statement. Cardiopulmonary exercise testing (CPET) provides a global assessment of functional capacity involving and integrating the physiological measurement during incremental exercise. The pattern of CPET's variables identifies the abnormal exercise capacity, often providing an objective evaluation of cause and, moreover, predicting outcomes in both apparently healthy and chronic disease populations. An anaerobic threshold VO2 above 11 ml/kg per min seems to identify individuals with a very low surgical risk even if undergoing major surgery. This review is focused on tools of risk assessment in patients undergoing noncardiac surgery and on the physiological basis for CPET in detecting patients 'at risk'.

Kinetics of plasma SPB and RAGE during mechanical ventilation in patients undergoing major vascular surgery.

Receptor-of-Advanced-Glycation-End-products (RAGE) and Surfactant-Protein-type-B (SPB) are reported as lung injury markers. Unlike SPB, RAGE is secreted by several tissues, so that RAGE specificity as lung injury marker is questionable. We measured SPB and RAGE in 19 patients undergoing major vascular abdominal surgery. SPB and RAGE were measured before mechanical ventilation (T0), at 1st (T1), 2nd (T2) and, when present, 3rd (T3) hour of mechanical ventilation, and 1h after extubation (T(POST)). Last data during mechanical ventilation, either T2 or T3, are reported as T(END). SPB and RAGE values were normalized for total protein (SPB(N) and RAGE(N)). SPB(N) and RAGE(N) increments from T0 to T(END) were 56.2 [39.1] ng/mg (mean [75-25 percentile]) and 10.6[7.1] pg/mg, respectively. SPB values increased progressively during mechanical ventilation, whereas RAGE values increased at T(1) but not thereafter. SPB(N) increase (T(END)-T0), but not RAGE(N), was related to ΔPaO(2)/FiO2 changes during mechanical ventilation (r=0.575, p=0.01). Plasma RAGE(N) and SPB(N) kinetics in patients undergoing major vascular surgery are different.

Cardiovascular and noncardiovascular comorbidities in patients with chronic heart failure.

A broad spectrum of concomitant disorders may complicate heart failure adding further morbidity and mortality risk. Comorbidities may be subdivided into cardiovascular and noncardiovascular. The first group includes hypertension, coronary artery disease, peripheral artery disease, cerebrovascular disease, arrhythmias and valvular heart disease. Noncardiovascular comorbidities include respiratory, endocrine, metabolic, nutritional, renal, hematopoietic, neurological as well as musculoskeletal conditions. In recent years, advances in the treatment of heart failure have not been attended by important changes in management of its comorbidities. They now seem to be major causes of the poor prognosis of heart failure patients. In this review we provide an updated summary of the epidemiological, pathophysiological and clinical characteristics of comorbidities as well as their potential impact for heart failure treatment.

Effects of pink grapefruit juice on QT variability in patients with dilated or hypertensive cardiomyopathy and in healthy subjects.

Recent evidence shows that pink grapefruit juice, which is a recommended dietary addition that contains high amounts of the antioxidant flavonoid naringenin, prolongs the corrected QT (QT(c)), a noninvasive electrophysiological marker of spatial myocardial repolarization, and does so by inhibiting the rapid component of the delayed rectifier K+ current (I(Kr)). Prompted by the observation that all class III antiarrhythmic drugs inhibit this current, thereby sometimes provoking torsades de pointes, we compared the effects of a liter of freshly squeezed pink grapefruit juice with those of 2 commonly used class III antiarrhythmics amiodarone and sotalol on the major noninvasive markers of temporal variability in myocardial repolarization used to stratify the risk of sudden death from malignant ventricular arrhythmias. In 32 subjects, 10 with postischemic dilated cardiomyopathy, 12 with hypertensive cardiomyopathy, and 10 healthy, we assessed QT(c) and QT variability index (QTVI) after administration of fresh pink grapefruit juice, placebo, amiodarone, or sotalol. After pink grapefruit juice and sotalol, all these indexes increased significantly from values observed after placebo (P<0.05) and from values after amiodarone (P<0.05). Conversely, after amiodarone, QT(c), but not QTVI, increased significantly from values after placebo (P<0.05). Presumably because of its high naringenin glycoside content, pink grapefruit juice prolongs cardiac repolarization and concurrently increases temporal cardiac repolarization dispersion. The potential proarrhythmic actions of pink grapefruit juice might be of concern in patients with major myocardial structural disorders.

Increased QT variability in young asymptomatic patients with beta-thalassemia major.

BACKGROUND: Despite recent progress in iron chelation therapy, sudden cardiac death due to malignant ventricular arrhythmias remains a vexing, clinical problem in patients with beta-thalassemia major (TM). In this study we assessed whether the major indices of QT variability, emerging tools for risk stratification of sudden cardiac death, differ in young asymptomatic patients with TM and healthy persons. METHODS: Thirty patients with TM and 30 healthy control subjects underwent a 5-min electrocardiography recording to calculate the following variables: QT variance (QT(v)), QT(v) normalized for mean QT (QTVN) and QT variability index (QTVI). All subjects also underwent a two-dimensional and Doppler echocardiography study and magnetic resonance imaging (MRI) to determine cardiac and hepatic T2* values. RESULTS: No differences were observed in clinical and conventional echo-Doppler findings in healthy control subjects and patients with TM whereas QT(v), QTVN and QTVI values were significantly higher in patients than those in controls (QT(v), P < 0.001; QTVN, P < 0.05 and QTVI, P < 0.001) and cardiac T2* and hepatic MRI T2* values were significantly lower in patients with TM (P < 0.001). The indices of temporal QT variability correlated significantly with MRI data. CONCLUSIONS: Young asymptomatic patients with TM have increased cardiac repolarization variability as assessed by QT variability indices, probably due to cardiac iron deposition. These easily assessed, non-invasive markers could be used to identify increased myocardial repolarization lability early in asymptomatic patients with TM.

Age and QT variability index during free breathing, controlled breathing and tilt in patients with chronic heart failure and healthy control subjects.

UNLABELLED: The QT variability index (QTVI) indicates temporal dispersion in myocardial repolarization, and a high QTVI is associated with a propensity for sudden death from malignant ventricular arrhythmias in subjects at high risk. In this study, the authors assessed the effects of free breathing, controlled breathing, and sympathetic stress (tilt) on the QTVI in patients with chronic heart failure (CHF) and healthy control subjects. The authors also examined the influence of age on the same variables. To obtain normative data, they calculated 95% confidence intervals for healthy subjects grouped according to age. Under all experimental conditions, the QTVI was larger in the CHF group overall and in the age subsets than in controls. In patients and controls, the QTVI increased significantly during tilt, although no differences were found between the QTVI measured during free and controlled breathing. In healthy controls, the following variables correlated significantly with the QTVI: age and baseline heart rate (P < 0.001). In patients with CHF, aging had no influence on the QTVI. CONCLUSION: Age, sympathetic stress, and CHF all tend to increase the QTVI and could potentially induce sudden death. Further studies should assess the usefulness of the QTVI as a marker predicting sudden cardiac death under the various conditions of risk.

Influence of cardiac-resynchronization therapy on heart rate and blood pressure variability: 1-year follow-up.

BACKGROUND: Several studies have shown that cardiac-resynchronization therapy (CRT) improves haemodynamic function, cardiac symptoms, and heart rate variability (HRV) and reduces the risk of mortality and sudden death in subjects with chronic heart failure (CHF). In subjects with CHF, power spectral values for the low-frequency (LF) component of RR variability < or =13 ms2, are associated with an increased risk of sudden death. AIMS AND METHODS: To assess whether spectral indexes obtained by power spectral analysis of HRV and systolic blood pressure (SBP) variability could predict malignant ventricular arrhythmias in patients with severe CHF treated with an implantable cardioverter-defibrillator (ICD) alone or with ICD+CRT. In addition, changes in non-invasive spectral indices using short-term power spectral analysis of HRV and SBP variability during controlled breathing in 15 patients with CHF treated with an ICD alone and 16 patients receiving ICD+CRT, were assessed pre-treatment and at 1 year. RESULTS: Arrhythmias necessitating an appropriate ICD shock were more frequent in subjects who had low LF power. CRT improved all spectral components, including LF power. CONCLUSIONS: Low LF power values predict an increased risk of malignant ventricular arrhythmias; after 1 year of CRT most non-spectral and spectral data, including LF power, improved. Whether these improvements lead to better long-term survival in patients with CHF remains unclear.

Power spectral analysis of heart rate variability as a predictive test in choosing the most effective length for tilt-training.

BACKGROUND: In patients with refractory neurally mediated syncope, tilt training--standing motionless against a wall for increased periods of time per day over one month--can often eliminate recurrent episodes and reduce presyncopal symptoms. We designed dual retrospective and prospective studies to assess cardiovascular autonomic function in subjects with recurrent syncope and identify the most effective length of tilt training between one and three months. METHODS AND RESULTS: In the retrospective study, before tilt training, and in the prospective study, before and after training, all subjects underwent a recording for short-term spectral analysis of heart rate and systolic blood pressure variability. Before tilt-training, autonomic nervous system function differs in patients with recurrent neurally mediated syncope who respond to tilt training for one month and those who do not. "Responders", patients experiencing no episodes of syncope during the 12-month follow-up, had higher low-frequency power of RR (LF(RR)) (p < 0.05) and LF(RR) in normalized units (NU) (p < 0.001) and lower high-frequency power (HF(RR)) (p < 0.05) and HF(RR)NU (p < 0.001) than "non-responders", patients reporting at least one syncopal episode during the 12-month follow-up. In the retrospective study, no difference was found between spectral data for "non-responders" with positive responses to tilt test with and without nitro derivatives. Prolonging tilt-training to three months increased the number of responders (late-responders) by 80% (p < 0.001) and power spectral analysis of heart rate variability (HRV) before tilt training can identify late-responders by their low LF(RR)NUs (<40) and high HF(RR)Nus (>60). Furthermore in late-responders, tilt training brings about a change in cardiovascular autonomic function: at 3 months, LF(RR)NUs increase and HF(RR)NU diminish. CONCLUSION: Power spectral analysis of HRV seems to be a useful tool to preselect patients who are most likely to benefit from prolonged therapy, thus increasing compliance.

Heart rate and blood pressure variability in subjects with vasovagal syncope.

Autonomic nervous system control in subjects with vasovagal syncope is controversial. In the present study, we used short-term spectral analysis to evaluate autonomic control in subjects with recurrent vasovagal syncope. We assessed the ability of spectral indices of HR (heart rate) variability to predict tilt-test responses. A series of 47 outpatients with recurrent vasovagal syncope and with positive responses to head-up tilt testing underwent a further study of RR variability during controlled breathing at rest and during tilt testing. During controlled breathing, RR interval variability of total power (TP(RR); P<0.001), low-frequency power (LF(RR); P<0.05), high-frequency power (HF(RR); P<0.001) and HF expressed in normalized units (HFnu(RR); P<0.001) were all higher, and LF expressed in normalized units (LFnu(RR)) and LF/HF ratio were lower in subjects with vasovagal syncope than in controls (P<0.001). To assess the ability of spectral components of RR variability to predict tilt-test responses, we prospectively studied 109 subjects with recurrent vasovagal syncope. The two normalized measures, HFnu(RR) and LFnu(RR), determined during controlled breathing alone predicted a positive tilt-test response (sensitivity, 76%; specificity, 99%; positive predictive value, 96%; and negative predictive value, 90%). During tilting, subjects with vasovagal syncope had lower SBP (systolic blood pressure; P<0.05), LF component of peak SBP variability (LF(SBP)) and LFnu(RR) than controls, and higher TP(RR), HF(RR), HFnu(RR) and alpha HF (P<0.001). These spectral data indicate that vagal sinus modulation is increased at rest in subjects with vasovagal syncope. Spectral analysis of RR variability during controlled breathing, a procedure that predicts tilt-test responses, could be a useful guide in choosing the method of tilt testing.