Detection of impending reflex syncope by means of an integrated multisensor patch-type recorder.

We assessed the capability of an integrated multisensory patch-type monitor (RootiRx®) in detecting episodes of reflex (pre)syncope induced by tilt table test (TTT). Firstly, we performed an intrapatient comparison of cuffless systolic blood pressure (SBP), R-R interval (RRI) and variability (power spectrum analysis) obtained by means of the RootiRx® with those obtained with conventional methods (CONV) with validated finger pressure devices at baseline in supine position and repeatedly during TTT in 32 patients affected by likely reflex syncope. Secondly, the LF/HF values obtained with RootiRx® during TTT were analyzed in 50 syncope patients. Compared with baseline supine recordings, during TTT a decrement of median SBP was observed with CONV (-53.5 mmHg) but not with RootiRx® ®(-1 mmHg). Conversely, RRI reduction (CONV: 102 ms; RootiRx®: 127 ms) and RRI Low Frequency/High Frequency powers ratio (LF/HF) increase (CONV: 1.6; RootiRx®: 2.5) were similar. The concordance was good for RRI (0.97 [95% CI 0.96-0.98]) and fair for LF/HF ratio (0.69 [95% CI 0.46-0.83]). During the first 5 min of TTT the LF/HF ratio was higher in patients who later developed syncope than in no-syncope patients. This ratio was significantly different among patients with syncope, presyncope or without symptoms at the time of syncope (p value = 0.02). In conclusion, cuffless RootiRx® was unable to detect rapid drops of SBP occurring during impending reflex syncope and thus cannot be used as a diagnostic tool for hypotensive syncope. On the other hand, RRI mean values and LF/HF power ratios obtained with RootiRx® were consistent with those simultaneously obtained using conventional methods.

Feasibility of Blood Pressure Measurement With a Wearable (Watch-Type) Monitor During Impending Syncopal Episodes.

Background We assessed the reliability and feasibility of blood pressure (BP) measurements by means of a new wearable watch-type BP monitor (HeartGuide) in detecting episodes of hypotensive (pre)syncope induced by tilt table test. Methods and Results An intrapatient comparison between systolic BP (SBP) measured by means of the HeartGuide device and noninvasive finger beat-to-beat BP monitoring was undertaken both at baseline in supine position and repeatedly during tilt table test in patients evaluated for reflex syncope. Intrapatient fall of systolic BP from baseline was measured. Eighty-one patients (mean age, 61±19 years; 46 women) were included. Overall, HeartGuide was able to yield BP values at the time of BP nadir in 58 (72%) patients (average HeartGuide SBP 102±18 mm Hg, versus finger SBP 101±19 mm Hg). Compared with baseline, the maximum SBP decrease was on average -28.5±27.8 and -30.3±33.9 mm Hg respectively (Lin's concordance correlation coefficient=0.78, r=0.79, P=0.001). In the subgroup of 38 patients with tilt table test induced (pre)syncope, the average HeartGuide SBP during symptoms was 97±16 mm Hg, and the finger SBP was 94±18 mm Hg. Compared with baseline, the maximum SBP decrease was on average -35.2±29.3 and -43.3±31.8 mm Hg, respectively (Lin's concordance correlation coefficient=0.83, r=0.87, P=0.001). Conclusions Our data indicate that the HeartGuide BP monitor can detect low BP during presyncope and that its measure of SBP change is consistent with that simultaneously obtained through continuous BP monitoring, despite some intrapatient variability. Thus, this device might be useful in determining the hypotensive nature of spontaneous (pre)syncopal symptoms, a possibility that should be verified by field studies.

Underlying hemodynamic differences are associated with responses to tilt testing.

Aim of this study was to explore whether differences in resting hemodynamic parameters may be associated with tilt test results in unexplained syncope. We analyzed age, gender, systolic (SBP), diastolic blood pressure (DBP) and heart rate (HR) by merging three large databases of patients considered likely to be of vasovagal reflex etiology, comparing patients who had tilt-induced reflex response with those who did not. Tilt-induced reflex response was defined as spontaneous symptom reproduction with characteristic hypotension and bradycardia. Relationship of demographics and baseline supine BP to tilt-test were assessed using logistic regression models. Individual records of 5236 patients (45% males; mean age: 60 ± 22 years; 32% prescribed antihypertensive therapy) were analyzed. Tilt-positive (n = 3129, 60%) vs tilt-negative patients had lower SBP (127.2 ± 17.9 vs 129.7 ± 18.0 mmHg, p < 0.001), DBP (76.2 ± 11.5 vs 77.7 ± 11.7 mmHg, p < 0.001) and HR (68.0 ± 11.5 vs 70.5 ± 12.5 bpm, p < 0.001). In multivariable analyses, tilt-test positivity was independently associated with younger age (Odds ratio (OR) per 10 years:1.04; 95% confidence interval (CI), 1.01-1.07, p = 0.014), SBP ≤ 128 mmHg (OR:1.27; 95%CI, 1.11-1.44, p < 0.001), HR ≤ 69 bpm (OR:1.32; 95%CI, 1.17-1.50, p < 0.001), and absence of hypertension (OR:1.58; 95%CI, 1.38-1.81, p < 0.001). In conclusion, among patients with suspected reflex syncope, younger age, lower blood pressure and lower heart rate are associated with positive tilt-test result.

Low Creatinine Potentially Overestimates Glomerular Filtration Rate in Older Fracture Patients: A Plea for an Extensive Use of Cystatin C?

AIM: Muscle mass is frequently reduced in older patients experiencing injurious falls and may further reduce during hospitalization for bone fracture. In these patients, renal function may be overestimated, because it is usually calculated using serum creatinine, which is strictly related to muscle mass. We evaluated if creatinine levels change during hospitalization in older patients with fracture. We also assessed the role of cystatin C as a more appropriate marker of renal function, comparing estimated glomerular filtration rate (eGFR) according to different formulas based on creatinine and/or cystatin C levels. METHODS: Patients aged 65+ years, consecutively hospitalized for fracture, were enrolled in a prospective cohort study. Creatinine and cystatin C levels were measured at baseline and in the post-operative period; eGFR was calculated using six equations based on creatinine and/or cystatin C. RESULTS: 425 patients were enrolled (mean age 84 years, mean creatinine 0.97 mg/dL, mean cystatin C 1.53 mg/L). Creatinine levels significantly decreased after surgery (p<0.001), while cystatin C remained stable. According to creatinine-based formulas, eGFR was < 60 mL/min/1.73 m2 in 29-30% at baseline and only in 17% participants in the post-operative period. Conversely, according to equations including cystatin C, eGFR was < 60 mL/min/1.73 m2 in half to three-quarters of the sample at all assessments. CONCLUSIONS: In older fractured patients, creatinine levels decline during hospital stay and may possibly overestimate renal function, whereas cystatin C remains stable. Whether cystatin C is a more reliable marker of renal function in this specific population should be further investigated.

Plasma adenosine and neurally mediated syncope: ready for clinical use.

Either central or peripheral baroreceptor reflex abnormalities and/or alterations in neurohumoral mechanisms play a pivotal role in the genesis of neurally mediated syncope. Thus, improving our knowledge of the biochemical mechanisms underlying specific forms of neurally mediated syncope (more properly termed 'neurohumoral syncope') might allow the development of new therapies that are effective in this specific subgroup. A low-adenosine phenotype of neurohumoral syncope has recently been identified. Patients who suffer syncope without prodromes and have a normal heart display a purinergic profile which is the opposite of that observed in vasovagal syncope patients and is characterized by very low-adenosine plasma level values, low expression of A2A receptors and the predominance of the TC variant in the single nucleotide c.1364 C>T polymorphism of the A2A receptor gene. The typical mechanism of syncope is an idiopathic paroxysmal atrioventricular block or sinus bradycardia, most often followed by sinus arrest. Since patients with low plasma adenosine levels are highly susceptible to endogenous adenosine, chronic treatment of these patients with theophylline, a non-selective adenosine receptor antagonist, is expected to prevent syncopal recurrences. This hypothesis is supported by results from series of cases and from observational controlled studies.

Renal function and delirium in older fracture patients: different information from different formulas?

OBJECTIVES: the association between renal function and delirium has not been investigated in older fracture patients. Creatinine is frequently low in these subjects, which may influence the association between delirium and renal function as estimated with creatinine-based formulas. Cystatin C could be a more reliable filtration marker in these patients. AIM: to confirm the association between renal function and delirium in older fracture patients comparing creatinine- and cystatin-based estimated glomerular filtration rate (eGFR) METHODS: patients aged 65+ requiring surgery for traumatic bone fractures were included. Six equations were used to calculate eGFR, based on serum creatinine and/or cystatin C obtained within 24 h of admission: Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology (CKD-EPIcr, CKD-EPIcys, CKD-EPIcr-cys) and Berlin Initiative Study equations (BIS-1, BIS-2). Delirium was identified with a chart-based method. RESULTS: 571 patients (mean age 83) were enrolled. Delirium occurred in the 34% and was associated with a lower eGFR regardless of the equation used. In a multivariable model, the association between moderate renal impairment (eGFR 30-60 ml/min/1.73 m2) and delirium remained significant in patients aged 75-84 and only when estimated with cystatin-based or BIS-1 equations. Only dementia was significantly associated with delirium in subjects 85+. CONCLUSIONS: in older fracture patients, moderate renal impairment was independently associated with delirium only among subjects aged 75-84, when eGFR was estimated with cystatin-based or BIS 1 equations, and not with the most commonly used equations (MDRD, CKD-EPIcr).

Autonomic dysfunction: Diagnosis and management.

The autonomic nervous system is designed to maintain physiologic homeostasis. Its widespread connections make it vulnerable to disruption by many disease processes including primary etiologies such as Parkinson's disease, multiple system atrophy, dementia with Lewy bodies, and pure autonomic failure and secondary etiologies such as diabetes mellitus, amyloidosis, and immune-mediated illnesses. The result is numerous symptoms involving the cardiovascular, gastrointestinal, and urogenital systems. Patients with autonomic dysfunction (AUD) often have peripheral and/or cardiac denervation leading to impairment of the baroreflex, which is known to play a major role in determining hemodynamic outcome during orthostatic stress and low cardiac output states. Heart rate and plasma norepinephrine responses to orthostatic stress are helpful in diagnosing impairment of the baroreflex in patients with orthostatic hypotension (OH) and suspected AUD. Similarly, cardiac sympathetic denervation diagnosed with MIBG scintigraphy or 18F-DA PET scanning has also been shown to be helpful in distinguishing preganglionic from postganglionic involvement and in diagnosing early stages of neurodegenerative diseases. In this chapter, we review the causes of AUD, the pathophysiology and resulting cardiovascular manifestations with emphasis on the diagnosis and treatment of OH.

Usefulness of Tilt Testing and Carotid Sinus Massage for Evaluating Reflex Syncope.

Thirty years ago Tilt Testing (TT) was described as a tool in the diagnostic work-up of vasovagal syncope; after its initial success, some flaws have become evident. The concept of hypotensive susceptibility has provided the test a new relevance, shifting from diagnosis only, to therapeutic management. Carotid Sinus Massage (CSM) was introduced at the beginning of the XX century; the technique has evolved over years, whereas the concept of carotid sinus syndrome (CSS) has remained unchanged and uncontested for more than half a century. Nowadays, CSS is a matter of debate, with new classifications and criteria coming on the scene. Recently, a common central etiological mechanism has been hypothesized for reflex syncope, manifesting as CSS, vasovagal syncope or both. In this context, TT and CSM acquire an important role in clinical practice, being essential for a complete diagnosis and treatment. Recalling their historical background, the present paper illustrates an actual interpretation of TT and CSM.

In Hospital and 3-Month Mortality and Functional Recovery Rate in Patients Treated for Hip Fracture by a Multidisciplinary Team.

OBJECTIVES: Medical comorbidities affect outcome in elderly patients with hip fracture. This study was designed to preliminarily evaluate the usefulness of a hip-fracture unit led by an internal medicine specialist. METHODS: In-hospital and 3-month outcomes in patients with hip fracture were prospectively evaluated in 121 consecutive patients assessed before and followed after surgery by a multidisciplinary team led by internal medicine specialist; 337 consecutive patients were recalled from ICD-9 discharge records and considered for comparison regarding in-hospital mortality. RESULTS: In the intervention period, patients treated within 48 hours were 54% vs. 26% in the historical cohort (P<0.0001). In-hospital mortality remained stable at about 2.3 per 1000 person-days. At 3 months, 10.3% of discharged patients had died, though less than 8% of patients developed postoperative complications (mainly pneumonia and respiratory failure). The presence of more than 2 major comorbidities and the loss of 3 or more BADL were independent predictors of death. 50/105 patients recovered previous functional capacity, but no independent predictor of functional recovery could be identified. Mean length of hospital stay significantly decreased in comparison to the historical cohort (13.6± 4.7 vs 17 ± 5 days, p = 0.0001). Combined end-point of mortality and length of hospitalization < 12 days was significantly lower in study period (27 vs 34%, p <0.0132). CONCLUSIONS: Identification and stabilization of concomitant clinical problems by internal medicine specialists may safely decrease time to surgery in frail subjects with hip fracture. Moreover, integrated perioperative clinical management may shorten hospital stay with no apparent increase in in-hospital mortality and ultimately improve the outcome. These results are to be confirmed by a larger study presently ongoing at our institution.

The pathophysiologic mechanisms associated with hypotensive susceptibility.

INTRODUCTION: Patients with vasovagal syncope (VVS) and positive tilt table test (TTT) were not found to benefit from pacing in the ISSUE-3 trial despite the presence of spontaneous asystole during monitoring. "Hypotensive susceptibility" unmasked by TTT was reported as a possible explanation. The purpose of this study was to assess the pathophysiologic mechanisms associated with hypotensive susceptibility. METHODS: 366 consecutive patients with the diagnosis of VVS who also had TTT were identified. Baroreflex gain (BRG) in addition to blood pressure (BP) and heart rate (HR) responses during the first 20 min of TTT were analyzed and compared between patients with positive TTT (n = 275, 75 %) and negative TTT (n = 91, 25 %). RESULTS: The mean BRG was similar between the groups (12.5 ± 6.3 versus 12.4 ± 6.3 ms/mmHg, p = 0.72); however, an age-dependent decrease was noted (17.6 ± 4.8, 15.0 ± 6.0, 10.6 ± 4.2, 10.3 ± 6.4 and 9.9 ± 8.5 ms/mmHg for patients <21, 21-40, 41-60, 61-80 and >80 years old, respectively; p < 0.001). In addition, we saw a main effect of age on the type of response with a greater prevalence of a vasodepressor response in older subjects (p < 0.001). During the first 20 min of TTT, BP was similar in patients with tilt-positive VVS when compared with patients with tilt-negative VVS; however, HR was significantly lower. CONCLUSION: BRG is similar in tilt-positive VVS patients when compared with tilt-negative VVS patients. An age-dependent decrease in BRG was noted with a higher prevalence of a vasodepressor response seen in older patients. The clinical significance of the blunted HR response in tilt-positive VVS remains to be determined.

Standardized algorithm for cardiac pacing in older patients affected by severe unpredictable reflex syncope: 3-year insights from the Syncope Unit Project 2 (SUP 2) study.

AIMS: The aim of this study was to determine the long-term effects and determinants of success of cardiac pacing in patients affected by reflex syncope enrolled in the Syncope Unit Project 2 (SUP 2) study. Initial results have validated the effectiveness of a standardized guideline-based algorithm which can be used in clinical practice in order to select suitable candidates for cardiac pacing. METHODS AND RESULTS: In this prospective, multicentre, observational study, patients aged >40 years, affected by severe unpredictable recurrent reflex syncope, underwent carotid sinus massage (CSM), followed by tilt testing (TT) if CSM was negative, followed by implantation of an implantable loop recorder (ILR) if TT was negative. Those who had an asystolic response to one of these tests received a dual-chamber pacemaker. Of 281 patients who met the inclusion criteria, 137 (49%) received a pacemaker and were followed up for a mean of 26 ± 11 months: syncope recurred in 25 (18%) of them. At 3 years, the actuarial syncope recurrence rate was 20% [95% confidence interval (CI) 12-30] and was significantly lower than in 142 patients who did not receive a pacemaker and were observed by means of an ILR [43% (95% CI 29-57), P = 0.01]. The 3-year recurrence rate was not different among 78 CSM+, 38 TT+, and 21 ILR+ patients, whereas it was lower in 20 patients with negative TT [5% (95% CI 0-15)] than in 61 patients with positive TT [24% (95% CI 10-38)]. CONCLUSION: The benefit of cardiac pacing is maintained at 3 years, irrespective of the index diagnostic test, and is maximum in patients with negative TT. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01509534.

My older patient with cancer reports falls: What should I do?

Falling is one of the major geriatric syndromes, with a multi-factorial pathogenesis due to age-related changes, pathological conditions and environmental hazards. Such a multi-factorial syndrome needs a standardized approach aimed at identifying risk factors. A comprehensive loco-motor, gait and standing balance, cardiovascular and neurological assessment, as well as a drugs regimens review, should be part of the routinely approach. Modification of environmental hazards, exercise training, behavioral and pharmacological treatment of specific diseases which can be the leading cause of falls, should all be part of an individualized intervention. Particular attention should be paid in the evaluation of unexplained falls, which can mask hypotensive or arrhythmic syncope.

Neuroautonomic evaluation of patients with unexplained syncope: incidence of complex neurally mediated diagnoses in the elderly.

BACKGROUND: The incidence of syncope increases in individuals over the age of 70 years, but data about this condition in the elderly are limited. Little is known about tilt testing (TT), carotid sinus massage (CSM), or supine and upright blood pressure measurement related to age or about patients with complex diagnoses, for example, those with a double diagnosis, ie, positivity in two of these three tests. METHODS: A total of 873 consecutive patients of mean age 66.5±18 years underwent TT, CSM, and blood pressure measurement in the supine and upright positions according to the European Society of Cardiology guidelines on syncope.1 Neuroautonomic evaluation was performed if the first-line evaluation (clinical history, physical examination, electrocardiogram) was suggestive of neurally mediated syncope, or if the first-line evaluation was suggestive of cardiac syncope but this diagnosis was excluded after specific diagnostic tests according to European Society of Cardiology guidelines on syncope, or if certain or suspected diagnostic criteria were not present after the first-line evaluation. RESULTS: A diagnosis was reached in 64.3% of cases. TT was diagnostic in 50.4% of cases, CSM was diagnostic in 11.8% of cases, and orthostatic hypotension was present in 19.9% of cases. Predictors of a positive tilt test were prodromal symptoms and typical situational syncope. Increased age and a pathologic electrocardiogram were predictors of carotid sinus syndrome. Varicose veins and alpha-receptor blockers, nitrates, and benzodiazepines were associated with orthostatic hypotension. Twenty-three percent of the patients had a complex diagnosis. The most frequent association was between vasovagal syncope and orthostatic hypotension (15.8%); 42.9% of patients aged 80 years or older had a complex diagnosis, for which age was the strongest predictor. CONCLUSION: Neuroautonomic evaluation is useful in older patients with unexplained syncope after the initial evaluation. A complex neurally mediated diagnosis is frequent in older people. Our results suggest that complete neuroautonomic evaluation should be done particularly in older patients.