Clinical profile and outcomes of pediatric hypertrophic cardiomyopathy in a South Indian tertiary care cardiac center: a three decade experience.

INTRODUCTION: Although much research has been done on adult hypertrophic cardiomyopathy, data on pediatric hypertrophic cardiomyopathy is still limited. METHODS AND RESULTS: The study enrolled all patients with cardiomyopathy who presented to us between 1990 to 2020 and were younger than 18 yrs. During the thirty-year study period, we identified 233 cases of pediatric cardiomyopathy. Sixty-three cases (27%) had hypertrophic cardiomyopathy. Out of the 63 HCM cases, 12% presented in the neonatal period and 37% presented in the first year of life. The median age of presentation was 7 yrs (Range 0.1-18 yrs). Sixteen patients had proven syndromic, metabolic, or genetic disease (25%). LV outflow obstruction was present in 30 patients (47%). Noonan syndrome was present in 9 of the 63 patients (14%). Dyspnea on exertion was the most common mode of presentation. Cardiac MRI was done in 28 patients, out of which 17 had late gadolinium enhancement (LGE). Mid myocardial enhancement was the most common pattern. Four patients had LGE of more than 15%. Over a mean follow-up period of 5.6 years (0.1-30 years), twenty-one were lost to follow-up (33%). Among the patients whose outcome was known, eleven died (26%), and thirty-one (73%) were alive. The 5-year survival rate of HCM patients was 82%, and the 10-year survival rate was 78%. Seven died of sudden cardiac death, three from heart failure, and one from ventricular arrhythmias. Sustained ventricular arrhythmias were seen in three patients and atrial arrhythmias in two. First-degree AV block was seen in 10 patients (15%) and bundle branch blocks (BBB) in five (8%). Eight patients required ICD or transplant (12.7%). Two patients underwent ICD for primary prevention, and one underwent PPI for distal AV conduction disease. Among the various clinical, echocardiographic, and radiological risk factors studied, only consanguinity showed a trend towards higher events of death or ventricular arrhythmias (P-value 0.08). CONCLUSION: More than one-third of our HCM cohort presented in infancy. LV outflow tract obstruction is common (47%). Mid myocardial enhancement was the most common pattern of late gadolinium enhancement. SCD was the most common cause of death. The outcome in our HCM cohort is good and similar to other population cohorts. Only Consanguinity showed a trend towards higher events of death or ventricular arrhythmias.

To evaluate the feasibility of cadmium/tellurium (Cd/Te) quantum dots for developing N-terminal Natriuretic Peptide (NT-proBNP) in-vitro diagnostics.

Quantum dots have been widely used for biomedical applications like imaging, targeted drug delivery, and in-vitro diagnostics for better sensitivity. In-vitro diagnostic, lateral flow-based assay systems are gaining attention in the field of biomarker analysis mainly due to ease of test and quick availability of results. In the study, the potential of water-soluble carboxylic (-COOH) functionalized photoluminescent Cadmium Telluride Quantum Dots (CdTe) nanoparticles for lateral flow-based detection of N-terminal Natriuretic Peptide (NT-proBNP) biomarker (for heart failure) detection has been evaluated. Monoclonal antibodies were conjugated with COOH functionalized CdTe with EDC-NHS coupling chemistry, and conjugation was confirmed using FTIR. The CdTe nanoparticle exhibited an emission maximum at 715 nm when it is excited with 375 nm. The COOH functionalized CdTe showed an antigen concentration-dependent linearity in the lateral flow applications when the dye was prepared freshly and used. However, a relative reduction in CdTe quantum dot fluorescence intensity with time was observed. Factors such as low stability could be due to the quenching of the fluorescence of CdTe. This limits its commercial viability as an in-vitro diagnostic tool; thus, modifications of the quantum dots are required to have a stable preparation for its commercial potential for quantifications.

The Cardiology Society of India-Kerala Acute Heart Failure Registry: poor adherence to guideline-directed medical therapy.

AIMS: Data on the burden of acute heart failure (AHF) admissions, practice patterns, and outcomes are rare from India and other low- and middle-income countries. We aimed to describe the baseline characteristics, guideline-directed medical therapy (GDMT) prescribing patterns and 90-day mortality rates in patients admitted with AHF in Kerala, India. METHODS AND RESULTS: The Cardiology Society of India-Kerala Acute Heart Failure Registry (CSI-KHFR) is an observational registry from 50 hospitals in Kerala, India, with prospective follow-up. Consecutive patients with AHF, who consented to participate, were enrolled. The 2016 European Society of Cardiology criteria were used for the diagnosis of AHF. Kaplan-Meier survival analysis and Cox-proportional hazard models were used for data analysis. The variables in the MAGGIC risk score were used in the multivariable model. A total of 7507 patients with AHF (37% female) participated in the CSI-KHFR. The mean age was 64.3 (12.9) years. More than two-third had reduced ejection fraction (EF) (67.5%). Nearly one-fourth (28%) of patients with heart failure (HF) with reduced EF received GDMT. Overall, in-hospital and 90-day mortality rates were 7% and 11.6%, respectively. Prescriptions of different components of GDMT were independently associated with 90-day mortality. CONCLUSION: The CSI-KHFR recorded an in-hospital and 90-day mortality of 7% and 11.6%, respectively. Only one of four patients received GDMT. AHF mortality was independently associated with GDMT initiation. Quality improvement initiatives that focus on increasing GDMT prescription may improve the survival of HF patients in India.

Clinical profile & long-term natural history of symptomatic coronary artery disease in young patients (<30 yr).

Background & objectives: Several studies have shown a high prevalence of cardiovascular risk factors in patients in the age group of 30-74 yr, but there is a paucity of data in young patients below 30 yr. We analyzed the clinical and coronary angiographic profile of patients <30 yr of age with symptomatic coronary artery disease (CAD) and also assessed their intermediate and long-term outcomes. Methods: All patients less than 30 yr of age who presented with symptomatic CAD from 1978 to 2017 in the department of Cardiology of a tertiary care hospital in south India, were studied for coronary risk factors and angiographic and treatment patterns, and the follow up data were collected. Results: The mean age of the 159 patients <30 yr of age was 26.7±3.29 yr. Male preponderance was observed (91.8%), 63.5 per cent patients were smokers and 88.3 per cent were dyslipidaemic. Acute myocardial infarction was the most common mode of presentation. Forty one per cent patients were non-adherent to medications. Risk factor control was inadequate with respect to smoking cessation, alcoholism, physical activity and dietary regulation. The predictors of long-term mortality were multivessel CAD [hazard ratio (HR): 1.927, 95% confidence interval (CI): 1.003-3.701] and reduction in ejection fraction (EF) (10% decrease in EF; HR: 1.349, 95% CI: 1.096-1.662). Overall mortality was 30 per cent at 10 yr and 48 per cent at 20 yr. Interpretation & conclusions: Decreasing EF and multivessel involvement were found to be the strong correlates for long-term mortality in young patients below 30 yr of age with CAD. High long-term mortality rates and poor risk factor control suggest the vast scope for the improvement of outcomes in these patients with aggressive risk factor control.

Enhanced P-selectin expression on platelet-a marker of platelet activation, in young patients with angiographically proven coronary artery disease.

P-selectin (CD62p) exposure is an established marker for platelet activation. P-selectin exposure can trigger variety of thrombotic and inflammatory reactions. In patients with coronary artery disease (CAD), platelets are activated, and hence, there is increased P-selectin exposure. The role of P-selectin exposure in patients on treatment with statins and anti-platelets is conflicting. A case-control study was performed to determine P-selectin exposure in consecutively recruited 142 patients (age ≤ 55 years) with angiographically proven CAD on treatment and 92 asymptomatic controls. P-selectin exposure was determined by flow cytometry. Data on conventional risk factors were obtained along with estimation of levels of thrombotic [fibrinogen, lipoprotein (a), tissue plasminogen activator, plasminogen activator inhibitor-1, homocysteine and von Willebrand factor] and anti-thrombotic factors (antithrombin III). The P-selectin exposure was compared among patient groups who had different modes of presentation of CAD and categories of CAD disease severity. The patients were followed up for a period of 26 months. The results indicate that P-selectin exposure was significantly elevated in patients (mean ± SD 9.24 ± 11.81) compared to controls (mean ± SD 1.48 ± 2.85) with p < 0.0001. Similarly, conventional risk factors were significantly elevated in patients. P-selectin exposure showed significant negative correlation with antithrombin III levels. P-selectin exposure was higher in patients who presented with acute coronary syndromes than those who presented with effort angina. Cardiovascular event rate was 6 % on follow-up. The study establishes that thrombotic-inflammatory pathways enhancing P-selectin exposure unrelated to treatment might be activated in patients, while the event rate remained lowered, and hence, treatment strategies should be inclusive to control these factors.

Circulating Thrombotic Risk Factors in Young Patients with Coronary Artery Disease Who Are on Statins and Anti-platelet Drugs.

Thrombotic risk factors may contribute to premature coronary artery disease (CAD), in addition to the conventional risk factors. There is paucity of data on studies evaluating the role of thrombotic factors in premature CAD in Indian patients. Thus a case-control study was performed to evaluate the role of thrombotic and atherogenic factors in young patients with angiographically proven CAD who are on treatment with statins and anti-platelet drugs. 152 patients (≤55 years) with angiographically proven CAD and 102 asymptomatic controls were recruited. Clinical and biochemical data were obtained in both groups. Blood levels of thrombotic factors-fibrinogen, antithrombin-III, tissue-plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), von-Willebrand factor (v-WF), lipoprotein(a) [Lp(a)] and homocysteine were analyzed. Patients had high levels of conventional CAD risk factors (diabetes mellitus, smoking, hypertension, dyslipidemia and positive family history) compared to controls. Logistic regression analysis revealed that low antithrombin-III (odds ratio/OR 11.2; 95 % confidence interval/CI 2.29-54.01), high fibrinogen (OR 6.04; 95 % CI 1.09-33.21) and high Lp(a) (OR 4.54; 95 % CI 0.92-22.56), as important, independent risk factors in patients. PAI-1(OR 0.15; 95 % CI 0.03-0.69) levels were significantly lower in patients. But other thrombotic risk factors studied (t-PA, v-WF and homocysteine) were comparable among patients and controls. The treatment using statins and anti-platelet drugs might be contributing to the control of some of the thrombotic risk factors. The strategies aiming at lowering the levels of thrombotic risk factors along with conventional risk factors may be useful in primary and secondary prevention of CAD.

Culprit Lesion Morphology on Optical Coherence Tomography in ST-elevation Myocardial Infarction vs Non ST-elevation Myocardial Infarction - A Systematic Review of 7526 Patients.

Background: Patients with STEMI are postulated to have different culprit lesion morphology compared to NSTEMI. The use of OCT in ACS can help delineate lesion morphology. The aim of this systematic review was to analyze the available data on culprit plaque morphology in ACS patients. Methods: The available literature was systematically screened for studies on culprit lesion morphology in ACS patients. Data was extracted from the selected studies and analyzed for baseline characteristics as well as culprit lesion morphology on OCT. Lesion characteristics between STEMI and NSTEMI groups were compared. Results: A total of 32 studies were selected for the final analysis. The average age of the study population was 62.4 years. Majority of patients (66.6%) had STEMI on presentation. NSTEMI patients had a higher prevalence of diabetes compared to STEMI. Both STEMI and NSTEMI patients had similar prevalence of thin-cap fibroatheroma (44.9%). The mean fibrous cap thickness was 84.2 µm in the study. STEMI patients had higher prevalence of lipid plaques, macrophages and luminal thrombus as compared to NSTEMI patients. Plaque rupture was the predominant culprit lesion morphology in both STEMI and NSTEMI groups, with higher prevalence in STEMI patients. Plaque erosion was also more common in STEMI patients (34.4% vs 13.2%). Conclusion: Plaque rupture is the predominat culprit lesion morphology in both STEMI and NSTEMI patients, despite having differences in baseline characteristics. Use of OCT to determine plaque morphology in ACS patients can help guide management strategy in select cases. [PROSPERO CRD42021249742].

Percutaneous valvuloplasty for mitral valve restenosis: postballoon valvotomy patients fare better than postsurgical closed valvotomy patients.

AIM: To compare the results of percutaneous mitral valvuloplasty (BMV) for mitral restenosis in post-BMV versus postclosed mitral valvotomy (CMV) patients. METHODS AND RESULTS: Ninety-two patients who underwent BMV for mitral restenosis were followed up prospectively. Of these, 28 patients had undergone previous percutaneous mitral valvuloplasty (PRIOR BMV) and 64 patients had undergone previous closed mitral valvotomy (PRIOR CMV). BMV for mitral restenosis was a success in 59% patients (57.1% PRIOR BMV, 59.3% PRIOR CMV, P = 1.0). Incidence of severe mitral regurgitation was 3.25%, all in the PRIOR CMV group. In univariate analysis, the major predictor of successful BMV for mitral restenosis was Wilkins score (P = 0.004). At a follow up of 3.47 + 2.07 years, mitral valve area was similar between groups (1.45 +/- 0.22, 1.46 +/- 0.26, P = 0.35). The combined end points of mitral valve replacement (MVR), need for re-repeat BMV for mitral restenosis or death was higher in the PRIOR CMV group (31.2% PRIOR CMV, 7.1% PRIOR BMV, P = 0.027). Event-free survival at follow up was lower in the PRIOR CMV group (69% PRIOR CMV, 92.8% PRIOR BMV) mainly due to the higher need for MVR (11 vs. 0 patients, P = 0.03). CONCLUSIONS: In conclusion, following BMV for mitral restenosis, patients with PRIOR BMV are found to have lesser event rates on follow-up compared to patients with PRIOR CMV, though procedural success rates are similar.

Immediate, early and mid-term outcomes following balloon mitral valvotomy in patients having severe rheumatic mitral stenosis with significant tricuspid regurgitation.

BACKGROUND: The study examined the influence of significant tricuspid regurgitation (TR) on the immediate, early and mid-term outcomes of patients with severe mitral stenosis (MS) undergoing balloon mitral valvotomy (BMV). METHODS: Among the 818 consecutive patients who underwent elective BMV in this institute from 1997 to 2003, 114 had significant TR. After propensity score-matched analysis, the data of 93 patients with significant TR were compared with the data of 93 patients who had no significant TR at the baseline. Outcomes were assessed immediately, at 1 year (early) and at 5 years (mid-term) after BMV. RESULTS: Patients with significant TR presented more frequently with NYHA class III-IV status, atrial fibrillation (AF), severe pulmonary hypertension (PH), advanced mitral valve disease as assessed by echocardiographic score > 8, and with history of previous BMV. After propensity score-matched analysis, it was found that the immediate procedural success (54.8% vs. 58.1%, P = 0.650), immediate in-hospital events and prevalence of AF and heart failure at 1 year of follow-up were comparable between the two groups. At 5 years after BMV, the significant TR group had higher prevalence of heart failure and AF, greater attrition in mitral valve area (MVA) and higher pulmonary artery (PA) pressure. CONCLUSIONS: Significant TR identifies a sicker patient population with MS. Even though patients with significant TR have comparable immediate and early outcomes after BMV, they have poor outcomes on mid-term follow-up. Longer follow-up with more patients is needed to assess survival aspect of TR on patients undergoing BMV and also to look at the need for interventions to address the significant TR, apart from the mitral valve interventions.

Implication of d-dimer in rheumatic severe mitral stenosis - A tertiary centre study.

BACKGROUND: In rheumatic mitral stenosis (MS), left atrial (LA) thrombus and LA spontaneous echo contrast (LA SEC) reflect hypercoagulability. The study focuses on whether D-dimer levels predict the existence of LA thrombus and SEC in patients with severe MS. METHODS: 95 consecutive patients with severe MS referred for transesophageal echocardiogram (TEE) between July 2011 and March 2012 to evaluate LA thrombus prior to balloon mitral valvotomy (BMV) were included in the study. D-Dimer levels in these patients were observed. RESULTS: Out of the 95 patients, 15 (15.8%) had LA thrombus and 52 patients had LA SEC (54.7%). Any correlation between D-Dimer levels and existence (or non-existence) of LA thrombus was not noticed from the receiver operating characteristics (ROC) curve with an area of .535. For patients with LA SEC, the D-Dimer levels were found to be considerably higher (776 ± 866 µg/L vs. 294 ± 331 µg/L, p = .001). An ideal cut-off level of 393 µg/L for diagnosing LA SEC was illustrated by the ROC curve with a sensitivity of 63.4%, specificity of 83.72%, positive predictive value of 82.5% and a negative predictive value of 65.45%. CONCLUSIONS: D-dimer levels were not representative of the presence or absence of LA thrombus in patients with severe MS. Nonetheless, this study demonstrated the substantial link between D-Dimer level and LA SEC. If a D-Dimer level of 400 µg/L or higher is taken as positive, it has high specificity and positive predictive value for diagnosing LA SEC.

Immediate and late clinical outcomes of balloon mitral valvotomy based on immediate postballoon mitral valvotomy mitral valve area & percentage gain in mitral valve area-A tertiary centre study.

AIM: The aim of the study was to compare the immediate and late clinical outcomes of balloon mitral valvotomy (BMV), based on the immediate post-BMV valve area and percentage gain in mitral valve area (MVA). METHODS: Clinical data of 818 consecutive patients who underwent BMV in our institute from 2000 to 2008 were analyzed retrospectively. They were categorized into three groups based on the postprocedural MVA and percentage gain in valve area-(1) 50% gain with final MVA <1.5 cm2, group 1 (fair result); (2) final MVA of ≥1.5 cm2, group 2 (good result); and (3) <50% gain with final MVA <1.5 cm2, group 3 (suboptimal result). RESULTS: The baseline characteristics of the three patient groups were clearly distinct. Those who had <50% gain with final MVA <1.5 cm2 were older and had higher incidence of atrial fibrillation (17 [22.4%]), heart failure (32 [42.1%]), pulmonary artery hypertension (45 [59.2%]), and significantly deformed valves (39 [51.3%]) at baseline. At a mean follow-up period of 5.64 ± 3.84 years, incidence of redo BMV (23 [4.6%]) and mitral valve replacement (17 [3.4%]) was higher in them than those with immediate MVA ≥1.5 cm2. Among those with MVA <1.5 cm2, events on follow-up were similar irrespective of the percentage gain in MVA. CONCLUSIONS: Immediate postprocedural MVA of ≥1.5 cm2, and not percentage gain, predicts better long-term clinical outcomes after BMV. Patients who had less than 50% gain with final MVA <1.5 cm2 represent high-risk population with advanced mitral valve disease and comorbidities.

Long-term outcome of patients undergoing balloon mitral valvotomy in pregnancy.

The outcome of 36 patients (mean age 25.8 +/- 4.3 years) who underwent balloon mitral valvuloplasty during pregnancy is described in this report. The procedure was successful in 35 patients (97.2%), with no maternal mortality, and all patients subsequently had symptomatic improvement and uneventful deliveries. The children had normal growth and development at a follow up of 2.8 +/- 3.3 years. Thus, in patients with symptomatic severe mitral stenosis, balloon mitral valvuloplasty is feasible, safe, and effective with good long-term outcomes for both the mother and the fetus.

Emergency surgery after percutaneous transmitral commissurotomy: operative versus echocardiographic findings, mechanisms of complications, and outcomes.

OBJECTIVE: This study was undertaken to determine the clinical profile of patients undergoing emergency surgery after balloon mitral valvotomy, to note operative findings and compare them with those of transthoracic echocardiography, to describe the mechanisms of complications, and to describe outcomes. METHODS: A retrospective study was undertaken of patients requiring emergency surgery after percutaneous mitral valvotomy with an Inoue balloon from January 1990 to December 2003. The data analyzed included demographic variables, causes and clinical presentations of complications, and outcome. In 14 consecutive cases of mitral regurgitation, an observational study comparing the operative findings with echocardiography was also undertaken. RESULTS: In 1388 cases of valvotomy, complications necessitating urgent surgery occurred in 31 cases (2.2%). Acute mitral regurgitation occurred in 23 cases (74.2%), and cardiac tamponade occurred in 8 cases (25.8%). Mitral regurgitation was due to leaflet tearing in all cases: anterior leaflet in 20 cases and posterior leaflet in 3 cases. Hypotension, orthopnea, and pulmonary edema were the clinical presentation for mitral regurgitation. Transthoracic echocardiography underestimated the severity of mitral valve pathology. Bilateral severe commissural fusion and pliable leaflet with paracommissural calcium was seen in anterior leaflet tearing. Cardiac tamponade with hemodynamic compromise occurred as a result of left atrial perforation in 6 cases, right atrial perforation in 1 case, and left ventricular perforation in 1 case. High septal puncture led to atrial perforation. Operative mortality was 9.6%, and low cardiac output developed in 29%. CONCLUSION: Acute mitral regurgitation and cardiac tamponade were the causes of emergency surgery after balloon valvotomy. Transthoracic echocardiography underestimated the severity of valve pathology.