Does the type of seizure influence heart rate variability changes?

OBJECTIVE: Heart rate variability (HRV), an index of the autonomic cardiac activity, is decreased in patients with epilepsy, and a low HRV is associated with a higher risk of sudden death. Generalized tonic-clonic seizures are one of the most consistent risk factors for SUDEP, but the influence (and relative risk) of each type of seizure on cardiac function is still unknown. Our objective was to assess the impact of the type of seizure (focal to bilateral tonic-clonic seizure - FBTCS - versus non-FBTCS) on periictal HRV, in a group of patients with refractory epilepsy and both types of seizures. METHODS: We performed a 48-hour Holter recording on 121 patients consecutively admitted to our Epilepsy Monitoring Unit. We only included patients with both FBTCS and non-FBTCS on the Holter recording and selected the first seizure of each type to analyze. To evaluate HRV parameters (AVNN, SDNN, RMSSD, pNN20, LF, HF, and LF/HF), we chose 5-min epochs pre- and postictally. RESULTS: We included 14 patients, with a median age of 36 (min-max, 16-55) years and 64% were female. Thirty-six percent had cardiovascular risk factors, but no previously known cardiac disease. In the preictal period, there were no statistically significant differences in HRV parameters, between FBTCS and non-FBTCS. In the postictal period, AVNN, RMSSD, pNN20, LF, and HF were significantly lower, and LF/HF and HR were significantly higher in FBTCS. From preictal to postictal periods, FBTCS elicited a statistically significant rise in HR and LF/HF, and a statistically significant fall in AVNN, RMSSD, pNN20, and HF. Non-FBTCS only caused statistically significant changes in HR (decrease) and AVNN (increase). SIGNIFICANCE/CONCLUSION: This work emphasizes the greater effect of FBTCS in autonomic cardiac function in patients with refractory epilepsy, compared to other types of seizures, with a significant reduction in vagal tonus, which may be associated with an increased risk of SUDEP.

Iron deficiency status irrespective of anemia: a predictor of unfavorable outcome in chronic heart failure patients.

OBJECTIVE: To assess the prognostic significance of iron deficiency (ID) in a chronic heart failure (CHF) outpatient population. METHODS AND RESULTS: We prospectively evaluated 127 patients with stable CHF and left ventricular ejection fraction ≤45%. Clinical and analytical data as well as information regarding the occurrence of the composite endpoint of overall mortality and nonfatal cardiovascular events were assessed. Among the 127 patients enrolled [81% men, median age: 62 years (25th-75th percentile: 53-68)], 46 (36%) patients had ID. Women, patients with higher plasma brain natriuretic peptide levels (>400 pg/ml) and with right ventricular systolic dysfunction presented ID more frequently (p < 0.05 for all). At 225 ± 139 days of follow-up, the composite endpoint occurred in 15 (12%) patients. It was more frequent in ID (24 vs. 5%, p = 0.001) and anemic patients (25 vs. 8%, p = 0.014). In a Cox regression analysis, ID was associated with a higher likelihood of composite endpoint occurrence (HR 5.00, 95% CI 1.59-15.78, p = 0.006). In a multivariable analysis adjusted for clinical variables, including the presence of anemia, ID remained a significant predictor of the composite endpoint (HR 5.38, 95% CI 1.54-18.87, p = 0.009). CONCLUSION: In a CHF outpatient population, ID carried a higher risk of unfavorable outcome, irrespectively of the presence of anemia.

Loop diuretic discontinuation in chronic heart failure patients: A retrospective study.

INTRODUCTION AND OBJECTIVES: The use of loop diuretics is central in managing congestion in heart failure (HF), but their impact on prognosis remains unclear. In euvolemic patients, dose reduction is recommended, but there is no recommendation on their discontinuation. This study aims to assess the impact of loop diuretic discontinuation on the prognosis of outpatients with HF with reduced ejection fraction. METHODS: This retrospective cohort study collected data from medical records of patients followed in an outpatient HF clinic at a university hospital center. Patients were included if they had been on loop diuretics and these were discontinued. Demographic, clinical and laboratory data were collected, and number and type of congestive events during the one-year period after discontinuation were recorded. RESULTS: Among 265 patients on loop diuretics, almost half (129) discontinued them at some point. Patients had optimized medical therapy, low median age, low New York Heart Association class, low B-type natriuretic peptide values, normal blood pressure, controlled heart rate and kidney function within normal limits. Among 122 patients with one year of follow-up, 18 (14.8%) had a congestive event. Fifteen events (83.3%) were low-dose diuretic reinitiation at a scheduled visit. There were only three worsening heart failure events (2.5%) during the one-year period. A significant improvement in kidney function from discontinuation to the one-year follow-up appointment was also observed. CONCLUSIONS: In our cohort, loop diuretic discontinuation was possible and safe in a large proportion of patients. The results should be interpreted with caution and cannot be extrapolated to a broader population of HF patients.

[Hypocalcemia as a reversible cause of heart failure]. / Hipocalcemia como uma causa reversível de insuficiência cardíaca.

Calcium plays a key role in heart muscle contraction and relaxation. Hypocalcemic heart failure is a rare and potentially reversible disturbance, which reflects this intrinsic relationship. The authors present the case of a 35-year-old woman who developed acute heart failure during the early postoperative period following total thyroidectomy. The echocardiogram showed severe global left ventricular dysfunction. Laboratory tests showed severe hypocalcemia and new-onset hypoparathyroidism. Cardiac catheterization showed angiographically normal coronary arteries. After clinical, hemodynamic and metabolic stabilization, a repeat echocardiogram revealed recovery of left ventricular function. Subsequently, cardiac magnetic resonance imaging was performed, which also showed no alterations. The patient was discharged asymptomatic, medicated with calcium carbonate, calcitriol and levothyroxine. This case highlights the importance of considering hypocalcemia as a cause of reversible myocardial dysfunction.

Iatrogenic ventricular fibrillation in Wolff-Parkinson-White syndrome.

Wolff-Parkinson-White (WPW) syndrome is the most common manifestation of ventricular pre-excitation syndrome and is mostly found in individuals with no structural heart disease. Although the risk of malignant arrhythmias is low, sudden cardiac death (SCD) as the first clinical manifestation of WPW syndrome is well documented, and atrial fibrillation (AF) with a rapid ventricular response is the main mechanism involved. Unfortunately, the signs of pre-excitation and arrhythmias are sometimes under-diagnosed and under-treated. We describe the case of a 31-year-old man who was admitted with an irregular wide complex tachycardia consistent with pre-excited AF, which was not promptly diagnosed, and who developed ventricular fibrillation (VF) after administration of atrioventricular (AV) nodal blockers, as a primary manifestation of WPW syndrome. Blocking the AV node in patients with pre-excited AF may increase the ventricular rate and potentially result in hemodynamic instability. Among patients with WPW syndrome who survive an episode of SCD, catheter ablation of the accessory pathway is the treatment of choice.

Hyperkalemia as a limiting factor of neurohormonal blockade/modulation in everyday clinical practice.

INTRODUCTION AND OBJECTIVES: Neurohormonal blockade (NB)/modulation is the combination of two renin-angiotensin-aldosterone system inhibitors (RAASi) with a beta blocker. It is the core therapy for heart failure with reduced ejection fraction (HFrEF). While improving long term prognosis, it also induces hyperkalemia (serum K+ >5.0 mEq/L) due to RAASi effects. This may cause lethal arrhythmias and increase mortality in the short term. Thus, hyperkalemia frequently leads to withholding or reducing the intensity of neurohormonal blockade/modulation, which is associated with worsening long term prognosis. We assessed the relevance of hyperkalemia as a limiting factor of neurohormonal blockade/modulation in real life clinical conditions. METHODS: We reviewed the medical records of HFrEF patients attending a HF clinic at a tertiary Portuguese hospital during 2018 (n=240). The number of patients not tolerating maximal neurohormonal blockade/modulation due to hyperkalemia was determined. The incidence and characteristics of hyperkalemia episodes were also assessed. RESULTS: Only six patients (3%) achieved maximal doses of neurohormonal blockade/modulation. Hyperkalemia was the limiting factor in 48 (20%) patients. A total of 185 hyperkalemia episodes occurred in 100 (42%) patients. Forty-five (24%) episodes were moderate or severe (serum K+ >5.5 mEq/L). In these HFrEF patients, the co-existence of hypertension, diabetes or renal failure was associated with the occurrence of hyperkalemia. CONCLUSIONS: In daily clinical practice, hyperkalemia is frequent and limits neurohormonal blockade/modulation by leading to the withholding or reducing of the intensity of RAAS inhibition. Considering the negative prognostic impact associated with sub-optimal neurohormonal blockade/modulation, addressing hyperkalemia is an important issue when treating HFrEF patients.

Sacubitril/valsartan in everyday clinical practice: an observational study based on the experience of a heart failure clinic.

BACKGROUND: Heart failure (HF) is a growing public health problem. Sacubitril/valsartan is now recommended to be used in persistently symptomatic patients with left ventricular ejection fraction (LVEF) <40%, replacing angiotensin-converting enzyme inhibitors (ACEis)/angiotensin receptor blockers (ARBs). In the present study, we aimed to characterise the challenges of sacubitril/valsartan use in everyday clinical practice. METHODS: We assessed the medical records of patients with HF and reduced ejection fraction eligible for sacubitril/valsartan attending a HF clinic at a Portuguese University Hospital during 2018 (n=152). The number of eligible patients receiving the drug and the reasons for not prescribing sacubitril/valsartan were evaluated. Additionally, we assessed the tolerability of maximal doses of sacubitril/valsartan. New York Heart Association functional class (NYHA class) and LVEF before and after up-titration to maximal tolerated sacubitril/valsartan dose were compared. Median follow-up was 41 months. RESULTS: Of the 152 included patients, 75 (49%) were prescribed the drug. The two main reasons for non-prescription were patient financial barriers (31%) and hypotension (27%). Only 33% of patients on sacubitril/valsartan did reach maximal dose. Hypotension was the main limiting factor for dose optimisation. Duration of sacubitril/valsartan treatment showed a positive association with LVEF improvement during follow-up (6.6% absolute LVEF increase/year). NYHA functional class improved significantly from baseline through the end of follow-up. CONCLUSIONS: In every-day clinical practice, although sacubitril/valsartan was associated with a marked improvement in NYHA class and in LVEF, important financial and clinical barriers to the implementation of this therapy were identified.

Temporal trends of lipid control in very high cardiovascular risk patients.

INTRODUCTION: Since 2011, the European guidelines have included a specific low-density lipoprotein cholesterol (LDL-C) target, <70 mg/dl, for very high cardiovascular risk (CVR) patients. However, registries have shown unsatisfactory results in obtaining this level of adequate lipid control. OBJECTIVES: To assess temporal trends in the use of lipid-lowering therapy (LLT) and attainment of adequate control in very high CVR patients since 2011. METHODS: We performed a retrospective observational study including very high CVR patients admitted in two periods: the first two years since the 2011 guidelines (2011/2012) and five years later (2016/2017). Lipid values, LLT, clinical variables and adequate lipid control rates were analyzed. RESULTS: A total of 1314 patients were reviewed (2011/2012: 638; 2016/2017: 676). Overall, 443 patients (33.7%) were not under LLT and only a slight improvement in drug prescription was observed from 2011/2012 to 2016/2017. In LLT users, the proportion of high-intensity LLT increased significantly in the later years (6.4% vs. 24.0%; p<0.001), but this was not associated with adequate lipid control. Overall, mean LDL-C was 95.4±37.2 mg/dl and adequate control was achieved in 320 patients (24.4%), without significant differences between 2011/2012 and 2016/2017 (p=0.282). Independent predictors of adequate control were male gender, older age, diabetes, chronic kidney disease, prior acute coronary syndrome, prior stroke and LLT, while stable coronary artery disease was associated with higher risk of failure. CONCLUSION: Even after the introduction of specific LDL-C targets, these are still not reached in most patients. Over a five-year period, LLT prescription only improved slightly, while adequate lipid control rates remained unchanged.

Heart rate variability in patients with refractory epilepsy: The influence of generalized convulsive seizures.

OBJECTIVE: Patients with epilepsy, mainly drug-resistant, have reduced heart rate variability (HRV), linked to an increased risk of sudden death in various other diseases. In this context, it could play a role in SUDEP. Generalized convulsive seizures (GCS) are one of the most consensual risk factors for SUDEP. Our objective was to assess the influence of GCS in HRV parameters in patients with drug-resistant epilepsy. METHODS: We prospectively evaluated 121 patients with refractory epilepsy admitted to our Epilepsy Monitoring Unit. All patients underwent a 48-hour Holter recording. Only patients with GCS were included (n = 23), and we selected the first as the index seizure. We evaluated HRV (AVNN, SDNN, RMSSD, pNN50, LF, HF, and LF/HF) in 5-min epochs (diurnal and nocturnal baselines; preictal - 5 min before the seizure; ictal; postictal - 5 min after the seizure; and late postictal - >5 h after the seizure). These data were also compared with normative values from a healthy population (controlling for age and gender). RESULTS: We included 23 patients, with a median age of 36 (min-max, 16-55) years and 65% were female. Thirty percent had cardiovascular risk factors, but no previously known cardiac disease. HRV parameters AVNN, RMSSD, pNN50, and HF were significantly lower in the diurnal than in the nocturnal baseline, whereas the opposite occurred with LF/HF and HR. Diurnal baseline parameters were inferior to the normative population values (which includes only diurnal values). We found significant differences in HRV parameters between the analyzed periods, especially during the postictal period. All parameters but LF/HF suffered a reduction in that period. LF/HF increased in that period but did not reach statistical significance. Visually, there was a tendency for a global reduction in our patients' HRV parameters, namely AVNN, RMSSD, and pNN50, in each period, comparing with those from a normative healthy population. No significant differences were found in HRV between diurnal and nocturnal seizures, between temporal lobe and extra-temporal-lobe seizures, between seizures with and without postictal generalized EEG suppression, or between seizures of patients with and without cardiovascular risk factors. SIGNIFICANCE/CONCLUSION: Our work reinforces the evidence of autonomic cardiac dysfunction in patients with refractory epilepsy, at baseline and mainly in the postictal phase of a GCS. Those changes may have a role in some SUDEP cases. By identifying patients with worse autonomic cardiac function, HRV could fill the gap of a lacking SUDEP risk biomarker.

Survival of patients with familial dilated cardiomyopathy on optimal heart failure therapy.

BACKGROUND: Familial dilated cardiomyopathy (FDCM) is characterized by clinical and genetic heterogeneity. There are still few survival studies concerning this subgroup of patients. AIM: To determine the prognosis of patients with FDCM on optimal medical therapy and attending a heart failure clinic. METHODS: This is a prospective study including patients with FDCM, defined according to the guidelines of the European Society of Cardiology. Cardiovascular morbidity and all-cause mortality were evaluated. RESULTS: Thirty-six patients, 23 (64%) men, were followed for 3.8 +/- 2.5 years. Age at baseline was 42 +/- 14 years and 67% were in NYHA class II. In 22% heart failure symptoms first occurred after a respiratory infection, and in 6%, after pregnancy/delivery. Most patients were in sinus rhythm (89%) and 33% had left bundle branch block (LBBB). Baseline left ventricular (LV) ejection fraction was 28 +/- 9%, LV end-diastolic diameter was 68 +/- 8 mm and left atrial dimension was 46 +/- 9 mm. Baseline serum sodium was 140 +/- 3 mEq/l. All patients were taking angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin-II receptor blockers (ARBs), 81% beta-blockers and 47% spironolactone. During follow-up, 5 patients died, 4 underwent heart transplantation and one received an implantable cardioverter-defibrillator. Five-year survival was 68%. CONCLUSIONS: Five-year survival of our patients with FDCM, under optimal medical therapy, was similar to that of other forms of nonischemic DCM reported in the literature.

I-123-MIBG cardiac uptake imaging, in familial dilated cardiomyopathy.

UNLABELLED: The pathological significance of myocardial adrenergic activity in patients with heart failure is well documented. No previous study has assessed the usefulness of I123-metaiodobenzylguanidine (123I-MIBG) cardiac uptake imaging for the evaluation of familial dilated cardiomyopathy (DCM). OBJECTIVE: To evaluate cardiac adrenergic activity, using 123I-MIBG cardiac uptake imaging, in members of a genotyped family with DCM. METHODS: Clinical evaluation, 12-lead ECG, 2D echocardiogram, heart rate variability analysis by 24h Holter, plasma B-type natriuretic peptide (BNP) measurements and 123I-MIBG cardiac imaging were performed in all participants. Anterior projection planar images and single photon emission computed tomographies of the thorax were obtained 20 min and 4 hours after the intravenous administration of 370 MBq of 123I-MIBG (early and late images). Heart/mediastinal (H/M) ratio and myocardial washout (MW) rate were obtained based on the anterior planar images. In polar maps, segmental uptake of 123I-MIBG was evaluated using a 4-grade visual score: grade 1 - uptake > 75% of maximum myocardial uptake (MMU); grade 2 - uptake 51-75% of MMU; grade 3 - uptake 26-50% of MMU; grade 4 - uptake < or = 25% of MMU. RESULTS: Eleven adults were included: 4 with DCM, 4 with isolated left ventricular enlargement (LVE), and 3 with normal echocardiogram. Patients with DCM and LVE presented higher MW rates, lower H/M ratios and higher visual score grades than those with normal 2D echocardiograms. One patient with a normal echocardiogram but carrying the disease locus also presented an abnormal MIBG cardiac scintigram. CONCLUSION: Patients with the phenotypic expression of the disease (DCM and LVE) and even carriers of the DCM gene with normal echocardiograms may present an abnormal MIBG cardiac scintigram, probably reflecting cardiac adrenergic hyperactivity. If confirmed in larger numbers, this method may be useful for the evaluation of DCM families.

Genetic variants identified by target next-generation sequencing in heart transplant patients with dilated cardiomyopathy.

INTRODUCTION AND OBJECTIVES: Dilated cardiomyopathy (DCM) is a myocardial disease that can progress to a terminal stage, requiring heart transplantation. In this work we aim to contribute to knowledge of genetic variants in adult patients undergoing heart transplantation due to end-stage DCM, reporting the results obtained in our single-center tertiary hospital series using target next-generation sequencing (NGS). METHODS AND RESULTS: Genetic variants were screened in 15 genes, preselected based on variants previously identified in DCM patients. Thirteen unrelated patients were included, nine (69%) male, mean age at diagnosis 33±13 years, eight (62%) with familial DCM. Nine genetic variants were identified in six (46%) patients: five in LMNA, two in LBD3, one in TNNT2 and one in TCAP. These variants were new in most patients. The majority were classified as of uncertain significance. Two patients were double and triple heterozygotes in the LBD3 and LMNA genes, respectively. CONCLUSION: Our results highlight the potential of NGS in the genetic characterization of DCM patients. LMNA is one of the most frequently mutated genes and should be included in all target gene assessments of end-stage DCM patients until more data are available.

Genetic Variants Are Not Rare in ICD Candidates with Dilated Cardiomyopathy: Time for Next-Generation Sequencing?

BACKGROUND: Sudden cardiac death (SCD) risk stratification in dilated cardiomyopathy (DCM) has been based on left ventricular ejection fraction (LVEF), even though SCD may occur with LVEF > 35%. Family history of unexplained SCD, especially in the young, raises concern about potential inheritable risk factors. It remains largely unknown how genetic tests can be integrated into clinical practice, particularly in the selection of implantable cardioverter defibrillator (ICD) candidates. We aimed to assess the diagnostic yield of genetic testing in DCM patients with a class I recommendation for ICD implantation, based on current guidelines. METHODS: We included ambulatory stable adult patients with idiopathic or familial DCM with previously implanted ICD. Molecular analysis included 15 genes (LMNA, MYH7, MYBPC3, TNNT2, ACTC1, TPM1, CSRP3, TCAP, SGCD, PLN, MYL2, MYL3, TNNI3, TAZ, and LDB3) using next-generation sequencing. RESULTS: We evaluated 21 patients, 12 (57%) males and 9 (43%) with familial DCM, including 3 (14%) with a family history of premature unexplained SCD. Mean age at DCM diagnosis was 40 ± 2 years, and mean age at ICD implantation was 50 ± 12 years. LVEF was 27 ± 9%, and LV end-diastolic diameter was 65 ± 7 mm. Genetic variants were found in six (29%) patients, occurring in 5 genes: TPM1, TNNT2, MYH7, PLN, and MYBPC3. The majority were classified as variants of uncertain significance. Family history of SCD was present in both patients with PLN variants. CONCLUSION: In patients with DCM and ICD, genetic variants could be identified in a significant proportion of patients in several genes, highlighting the potential role of genetics in DCM SCD risk stratification.

Spontaneous acquired left descending coronary artery to left ventricle fistula in a patient with an apical saddle thrombus.

Coronary artery fistulas are a rare anomaly. The majority are congenital in origin, although they may be acquired due to invasive cardiac procedures or trauma. The most common course is between the right coronary artery and the right ventricle. The authors describe the case of an acquired left anterior descending coronary artery to left ventricle fistula, associated with a saddle thrombus, in a patient with a previously normal coronary angiogram and none of the predisposing factors mentioned above. Spontaneous formation of acquired coronary fistulas is reported as a very rare event in the literature.

Cardiac papillary fibroelastoma: Report of a surgical series.

INTRODUCTION: Papillary fibroelastoma (PFE) is a rare primary benign tumor of cardiac origin that predominantly affects the cardiac valves. Although most patients are asymptomatic, serious complications may result given their propensity for embolization. Advances in imaging technology have enabled earlier detection and more accurate characterization of these tumors. We report a case series, describing clinical presentation, treatment and outcome. METHODS: Institutional records of a tertiary center between 1997 and 2015 were reviewed for all patients diagnosed with PFE treated surgically and confirmed histologically. Demographic and clinical characteristics, echocardiography findings and treatment modalities were analyzed and recurrence at follow-up was studied. RESULTS: A total of 26 patients (69% male), aged 54±18 years, had a PFE. Clinically, PFE presented with neurologic deficits in eight cases and was asymptomatic in 65.4%. The mitral valve surface was the predominant tumor location (53.8%), followed by the aortic valve (34.6%). Tumor size ranged between 3 mm and 22 mm, 26.9% had a pedicle and 42.4% were mobile. All patients were treated successfully by complete resection, isolated in 88.5% and with valve repair in three cases. No other cardiac procedure was performed concomitantly and there were no major postoperative complications. Median follow-up was 61±49 months and no tumor recurrence or embolic events were documented. CONCLUSIONS: Fibroelastomas are generally small, single and detected by chance during routine imaging exams. Complete surgical resection of the tumor has an excellent prognosis and appears to be a good strategy.

Cardiac pauses during sleep in a patient with sleep obstructive apnea and atrial fibrillation.

Cardiac rhythm disturbances are common in sleep apnea patients. The authors report on a 74-year-old female patient with atrial fibrillation, with a background history of arterial hypertension, obesity, and obstructive sleep apnea. Holter monitoring was performed, on 5 different occasions. Pauses were seen in every Holter monitoring, the number of which varied between 10 and 72. All pauses occurred during the sleeping period and adjacent hours (23:00-8:59 hours) with a single exception. In this patient, we can speculate that parasympathetic may predominate over sympathetic activity during sleep.

Left ventricular reverse remodeling in dilated cardiomyopathy- maintained subclinical myocardial systolic and diastolic dysfunction.

In idiopathic dilated cardiomyopathy (DCM), myocardial deformational parameters and their relationships remain incompletely characterized. We measured those parameters in patients with DCM, during left ventricular reverse remodeling (LVRR). Prospective study of 50 DCM patients (in sinus rhythm), with left ventricular ejection fraction (EF) <40%. LVRR was defined as an increase of ten units of EF and decrease of diastolic left ventricular diameter (LVDD) in the absence of resynchronization therapy. Performed morphological analysis, myocardial performance quantification (LV and RV Tei indexes) and LV averaged peak systolic longitudinal strain (SSR long) and circumferential strain (SSR circ). At baseline, mean EF was 25.4 ± 9.8%, LVDD was 62.4 ± 7.4 mm, LVDD/BSA of 34.2 ± 4.5 mm/m2 and 34% had MR grade >II/IV. LVRR occurred in 34% of patients within 17.6 ± 15.6 months and was associated with a reduced rate of death or heart failure hospitalization (5.9% vs. 33.3; p = 0.03). Patients with LVRR had a final EF of 48.9 ± 7.9% (Δ LV EF of 22.4%) and there was a significant decrease (p < 0.05) in: LVDD/BSA, LV systolic diameter/BSA, LV diastolic volume, LV systolic volume, LV mass; an increase (p < 0.05) in sphericity index. However, measures of diastolic function (LA volume/BSA, e'velocity and' E/e'ratio), final LV and RV Tei indexes were not significantly different from baseline. Additionally, final SSR circ and SSR long values were not different from basal. Patients who recovered EF >50% (n = 10), SSR circ and SSR long were inferior to normal. Improvement in EF occurred in one-third of DCM pts and was associated with a decrease of major cardiac events. There was an improvement of diastolic and systolic volumes and in sphericity index, confirming truly LV reverse reshaping. However, myocardial performance indexes, SSR long and SSR circ in reverse-remodeled DCM were still abnormal, suggesting a maintained myocardial systolic and diastolic dysfunction.

The role of biomarkers in dilated cardiomyopathy: Assessment of clinical severity and reverse remodeling.

INTRODUCTION: Biomarkers in dilated cardiomyopathy (DCM) reflect various pathobiological processes, including neurohormonal activation, oxidative stress, matrix remodeling, myocyte injury and myocyte stretch. We assessed the role of biomarkers in clinical and echocardiographic parameters and in left ventricular (LV) reverse remodeling (LVRR). METHODS: In this prospective study of 50 DCM patients (28 men, aged 59±10 years) with LV ejection fraction (LVEF) <40%, LVRR was defined as an increase of >10 U in LVEF after optimal medical therapy. RESULTS: Baseline LVEF was 25.4±9.8% and LV end-diastolic diameter (LVEDD)/body surface area (BSA) was 34.2±4.5 mm/m2. LVRR occurred in 34% of patients within 17.6±15.6 months. No correlation was found between B-type natriuretic peptide (BNP), 25-hydroxyvitamin D (25(OH)D), CA-125, high-sensitivity C-reactive protein (hs-CRP), lipoprotein(a) [Lp(a)], noradrenaline, adrenaline, renin or aldosterone and LVRR. Patients in NYHA class III or IV, with pulmonary congestion or ankle edema, had higher CA-125, cystatin C, BNP and hs-CRP levels (p<0.05). CA-125 was correlated with BNP (r=0.61), hs-CRP (r=0.56) and uric acid (r=0.52) (all p=0.01). BNP correlated directly with LVEDD (r=0.49), LV volumes (r=0.51), pulmonary artery systolic pressure (PASP) (r=0.43) and E/e' (r=0.31), and was inversely correlated with LVEF (r=-0.50) and e' velocity (r=-0.32) (p<0.05). CA-125 was positively correlated with left atrial volume/BSA (r=0.46), E/A ratio (r=0.60) and PASP (r=0.49) (p<0.05). CONCLUSIONS: No correlation was found between biomarkers and LVRR, but CA-125, BNP and hs-CRP were predictors of clinical severity and congestion. BNP correlated with parameters of systolic and diastolic dysfunction, while CA-125 correlated with measures of diastolic dysfunction.